Silver catalysis in organic synthesis 9783527342822, 3527342826, 9783527807697, 3527807691, 9783527342815, 9783527807680

Table of contents :
Content: Volume 1: 1. Introduction to Silver Chemistry 2. Silver-Catalyzed Cycloaddition Reactions 3. Silver-Catalyzed Cyclizations 4. Silver-Mediated Radical Reactions 5. Silver-Mediated Fluorination, Perfluoroalkylation and Trifluoromethylthiolation Reactions 6. Coupling Reactions and C-H Functionalization Volume 2: 7. Silver-Catalyzed CO2 Incorporation 8. Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions 9. Asymmetric Silver-Catalyzed Reactions 10. Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives 11. Silver Complexes in Organic Transformations 12. Silver Nanoparticles in Organic Transformations

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Silver Catalysis in Organic Synthesis

Silver Catalysis in Organic Synthesis

Edited by Chao-Jun Li and Xihe Bi

Volume 1

Silver Catalysis in Organic Synthesis

Edited by Chao-Jun Li and Xihe Bi

Volume 2

Editors Chao-Jun Li

McGill University Department of Chemistry 801 Sherbrooke Street West Montreal, QC H3A 0B4 Canada

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Xihe Bi

Northeast Normal University Department of Chemistry 5268 Renmin Street Changchun 130024 China

Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Cover

Cover image kindly provided by Dr. Dingyi Tong (Ningbo Institute of Industrial Technology (CNITECH), Chinese Academy of Sciences (CAS))

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at . © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Print ISBN: 978-3-527-34281-5 ePDF ISBN: 978-3-527-80769-7 ePub ISBN: 978-3-527-80768-0 oBook ISBN: 978-3-527-34282-2 Typesetting SPi Global, Chennai, India Printing and Binding

Printed on acid-free paper 10 9 8 7 6 5 4 3 2 1

v

Contents to Volume I Preface xi 1

Introduction to Silver Chemistry 1 Paramasivam Sivaguru and Xihe Bi

1.1 1.1.1 1.1.2 1.1.3 1.2 1.2.1 1.2.2 1.2.3 1.2.4 1.2.4.1 1.2.4.2 1.3

History and Features of Silver 1 Chemistry of Silver 1 Silver Nanoparticles 3 Silver Applications 3 Silver Catalysis 4 Alkynophilicity/Carbophilic Nature of Silver 4 Oxo- and Azaphilic Character of Silver 7 Halogenophilicity of Silver 7 Redox Chemistry of Silver 8 One-electron Ag(I)/Ag(II) Redox Cycles 8 Two-electron Ag(I)/Ag(III) Redox Cycle 8 Representative Examples of Silver Catalysis in the Organic Transformations 9 Protodecarboxylation of Carboxylic Acids 9 A3 Coupling Reaction 10 Incorporation of CO2 11 Enantioselective Nitroso-aldol Reaction 12 Chemoselective Cyclopropanation Using Donor–Acceptor Diazo Compounds 13 Homocoupling of Alkyl Grignard Reagents 14 Oxidative Arene Cross-coupling 15 Hydroazidation of Alkynes 16 Isocyanide–alkyne Cycloaddition 17 Nitrogenation of Terminal Alkynes 18 Decarboxylative Alkynylation 19 Nitrene Transfer Reactions 20 Fluorination Reactions 22 Summary 23 References 23

1.3.1 1.3.2 1.3.3 1.3.4 1.3.5 1.3.6 1.3.7 1.3.8 1.3.9 1.3.10 1.3.11 1.3.12 1.3.13 1.4

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2

Silver-catalyzed Cycloaddition Reactions 33 Daesung Lee and Sourav Ghorai

2.1 2.2 2.2.1 2.2.2 2.2.3 2.3 2.4 2.5 2.5.1 2.5.2 2.5.3 2.6 2.7 2.7.1 2.7.2 2.7.3 2.8

Introduction 33 [3+2] Cycloadditions 34 Cycloaddition of Azomethine Ylides Cycloaddition of 2-Isocyanoacetates Cycloaddition of Azides 53 [2+2] Cycloadditions 59 [3+3] Cycloadditions 60 [4+2] Cycloadditions 63 Diels–Alder Reactions 63 Oxa- and Aza-Diels–Alder Reactions Hexadehydro Diels–Alder Reactions [2+2+1] Cycloadditions 73 Miscellaneous Reactions 74 [2+1] Cycloaddition 74 [4+1] Cycloaddition 77 [4+2] Cycloaddition 77 Conclusion 78 References 79

3

Silver-Catalyzed Cyclizations 85 Valerie H. L. Wong and King Kuok (Mimi) Hii

3.1 3.2

Introduction 85 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions) 86 Conia-ene Reaction 86 Cycloisomerization 89 Cycloisomerization of Enynes 90 Cycloisomerization of 1,n-Allenynes 94 Cycloisomerization of 1,n-Diyne Compounds 95 Cycloisomerization Reactions of Propargyl Compounds 96 Electrocyclic Reactions 99 Miscellaneous Reactions 100 Formation of C—N Bonds 102 Intramolecular Hydroamination 102 Alkynes 102 Allenes 116 Alkenes 122 Cycloisomerization Reactions of Alkynes 122 Imines as Nucleophiles 123 Oximes 129 Hydrazones 134 Aromatic N-Heterocycles 141 Other Nucleophiles 143 Formation of C—O Bonds 144 Hydroalkoxylation 144

3.2.1 3.2.2 3.2.2.1 3.2.2.2 3.2.2.3 3.2.2.4 3.2.3 3.2.4 3.3 3.3.1 3.3.1.1 3.3.1.2 3.3.1.3 3.3.2 3.3.2.1 3.3.2.2 3.3.2.3 3.3.2.4 3.3.2.5 3.4 3.4.1

34 47

67 72

Contents

3.4.1.1 3.4.1.2 3.4.1.3 3.4.2 3.4.2.1 3.4.2.2 3.4.2.3 3.4.3 3.4.3.1 3.4.3.2 3.4.4

Alkynes 144 Allenes 149 Alkenes 154 Hydrocarboxylation 155 Alkynes 155 Allenes 157 Alkenes 158 Cycloisomerization of C=O 159 Alkynes as Partners 159 Allenes as Partners 168 Miscellaneous Reactions 169 References 173

4

Silver-Mediated Radical Reactions Lin Zhu and Chaozhong Li

4.1 4.2 4.3 4.3.1 4.3.2 4.3.3 4.3.4 4.4 4.4.1 4.4.2 4.5 4.5.1 4.5.2 4.5.3 4.6 4.6.1 4.6.2 4.7

Introduction 183 Protodecarboxylation 184 Radical Coupling 187 Formation of C—C Bonds 187 Formation of C—O/S/Se Bonds 202 Formation of C—N/P Bonds 209 Formation of C—Halogen Bonds 216 Radical Addition 222 Formation of C—C Bonds 222 Formation of C–Heteroatom Bonds 228 Cascade Radical Cyclizations 233 Formation of C—C Bonds 233 Formation of C—O/S/Se Bonds 241 Formation of C—N/P Bonds 244 Rearrangement/Migration/C—C Bond Cleavage 249 Aryl Migration 249 Radical C—C Bond Cleavage of Cycloalkanols 255 Conclusion and Perspective 259 Acknowledgment 260 References 261

5

Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions 271 Vanessa Koch, Andreas Hafner, and Stefan Bräse

5.1 5.2 5.2.1 5.2.2 5.2.3 5.2.3.1 5.2.3.2 5.2.3.3

Introduction 271 Silver-Mediated Fluorinations 273 Nucleophilic Silver-Catalyzed Fluorination 274 Electrophilic Silver-Catalyzed Fluorination 279 Radical Silver-Catalyzed Fluorination 287 Fluorination via Addition to Alkenes 287 Decarboxylative Fluorination 294 C—C Bond Activation 296

183

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5.2.3.4 5.3 5.3.1 5.3.2 5.3.2.1 5.3.2.2 5.3.2.3 5.3.3 5.4 5.5

C—H Bond Activation 297 Silver-Mediated Trifluoromethylations and Perfluoroalkylations 298 Syntheses and Properties of Perfluoroorgano Silver Compounds 300 Silver-Mediated Perfluoroalkylations 301 Perfluoroorgano Silver Compounds in Copper-Mediated Perfluoroalkylations 301 Perfluoroorgano Silver Compounds as Precursors for Radicals 304 Perfluoroorgano Silver Compounds as Nucleophilic Reagents 309 Silver-Catalyzed Perfluoroalkylations 313 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations 314 Conclusion and Outlook 324 References 324 331

6

Coupling Reactions and C—H Functionalization Qing-Zhong Zheng and Ning Jiao

6.1 6.2 6.2.1 6.2.2 6.2.3

Introduction 331 Formation of Carbon–Carbon Bonds 332 Glaser Coupling 332 A3 Coupling 332 Oxidative Cross-coupling and Oxidative-Induced C—H Functionalization 335 Oxidative-Induced C—H Functionalization 335 Oxidative Cross-coupling 340 Oxidative Coupling/Cyclization Reactions 344 Synthesis of Biaryls 356 Miscellaneous Reactions 362 Isocyanide-Involved Reactions 362 Diazo-compound-Involved Reactions 364 Synthesis of Perfluoroalkylated Compounds 367 C—H Carboxylation 368 Arylation and Alkylation Reactions 370 Formation of C–Heteroatom Bonds 371 Formation of C–Halogen Bonds 371 C—F Bond Formation 371 C—Cl Bond Formation 374 C—Br Bond Formation 377 Formation of C—N/P Bonds 378 C—N Bond Formation 378 C—P Bond Formation 387 Formation of C—O/S Bonds 392 C—O Bond Formation 392 C—S Bond Formation 392 Formation of C—B Bonds 397 Miscellaneous Reactions 397 Conclusion 398 References 399

6.2.3.1 6.2.3.2 6.2.4 6.2.5 6.2.6 6.2.6.1 6.2.6.2 6.2.6.3 6.2.6.4 6.2.6.5 6.3 6.3.1 6.3.1.1 6.3.1.2 6.3.1.3 6.3.2 6.3.2.1 6.3.2.2 6.3.3 6.3.3.1 6.3.3.2 6.3.4 6.3.5 6.4

Contents

Contents to Volume II Preface xi 7

Silver-Catalyzed CO2 Incorporation 407 Tohru Yamada, Kohei Sekine, Yuta Sadamitsu, and Kodai Saito

8

Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions 439 Mahzad Dehghany, Josephine Eshon, Jessica M. Roberts, and Jennifer M. Schomaker

9

Asymmetric Silver-Catalyzed Reactions Hélène Pellissier

10

Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives 645 Zhenhua Jia, Mingxin Liu, and Chao-Jun Li

11

Silver Complexes in Organic Transformations 661 Guichun Fang and Xihe Bi

12

Silver Nanoparticles in Organic Transformations 723 Alain Y. Li, Alexandra Gellé, Andreanne Segalla, and Audrey Moores Index 795

533

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v

Contents to Volume I Preface xi 1

Introduction to Silver Chemistry 1 Paramasivam Sivaguru and Xihe Bi

2

Silver-catalyzed Cycloaddition Reactions 33 Daesung Lee and Sourav Ghorai

3

Silver-Catalyzed Cyclizations 85 Valerie H. L. Wong and King Kuok (Mimi) Hii

4

Silver-Mediated Radical Reactions Lin Zhu and Chaozhong Li

5

Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions 271 Vanessa Koch, Andreas Hafner, and Stefan Bräse

6

Coupling Reactions and C—H Functionalization Qing-Zhong Zheng and Ning Jiao

183

331

Contents to Volume II Preface xi 7

Silver-Catalyzed CO2 Incorporation 407 Tohru Yamada, Kohei Sekine, Yuta Sadamitsu, and Kodai Saito

7.1 7.2 7.3 7.4 7.5 7.5.1

Introduction 407 Carboxylation of Terminal Alkynes 408 Carboxylation of Aryl Boronic Esters 413 Functionalization of Terminal Epoxides 414 Cascade Carboxylation and Cyclization 416 Silver-Catalyzed Sequential Carboxylation and Cyclization of Propargyl Alcohols 417

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Contents

7.5.1.1 7.5.1.2 7.5.1.3

Synthesis of Cyclic Carbonate 417 Catalytic Asymmetric Synthesis of Cyclic Carbonate 420 Three-Component Reaction of Propargyl Alcohols, Carbon Dioxide, and Nucleophiles 421 7.5.1.4 CO2 -Mediated Transformation of Propargyl Alcohols 422 7.5.1.5 Transformation of Amine Derivatives 424 7.5.1.6 Cascade Carboxylation and Cyclization of Unsaturated Amine Derivatives 424 7.5.1.7 Benzoxazine-2-one from o-Alkynylaniline and Carbon Dioxide 426 7.5.1.8 Allenylamine 427 7.5.1.9 Domino Carboxylation–Cyclization–Migration of Unsaturated Amines 428 7.5.1.10 Carboxylation Involving C—C Bond Formation: Sequential Cyclization 431 7.5.1.11 Carboxylation of Enolate: Sequential Cyclization 431 7.5.1.12 Carbon Dioxide Incorporation Reaction Using Other Carbanions 435 7.6 Conclusion 435 References 436 8

Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions 439 Mahzad Dehghany, Josephine Eshon, Jessica M. Roberts, and Jennifer M. Schomaker

8.1 8.2 8.2.1 8.2.2 8.2.3 8.3 8.3.1

Introduction to Silver-Mediated Carbene Transfer Reactions 439 Introduction to Cyclopropanation 440 General Catalysts for Cyclopropanation 440 Recent Advances in Silver-Catalyzed Cyclopropanation 441 Recent Advances in Silver-Catalyzed Cyclopropenation 441 Introduction to C–H Insertion 443 General Mechanism of C–H Functionalization via Transition Metal-catalyzed Carbene Transfer 443 General Catalysts for C–H Functionalization via Carbene Transfer 447 Recent Advances in Silver-Catalyzed Alkane C–H Functionalization via Carbene Transfer 450 Advances in Silver-Catalyzed Carbene Insertion into Alkene or Aromatic C(sp2 )—H Bonds 450 Silver-Catalyzed Carbene Insertion into N—H Bonds 452 Silver-Catalyzed Carbene Insertion into O—H Bonds 458 Silver-Catalyzed Functionalization of Esters 458 Silver-Catalyzed Si–H Functionalization 461 Summary 461 Introduction to Transition Metal-Catalyzed Nitrene Transfer 464 General Catalysts for Silver-Catalyzed Nitrene Transfer 468 Typical Nitrogen Sources for Silver-Catalyzed Nitrene Transfer 470 General Mechanistic Features of Metal-Catalyzed Nitrene Transfer 470

8.3.2 8.3.3 8.3.4 8.4 8.5 8.6 8.7 8.8 8.9 8.9.1 8.9.2 8.9.3

Contents

8.10 8.10.1 8.10.2 8.10.3 8.11 8.11.1 8.11.2 8.11.3 8.12 8.13 8.14 8.15 8.15.1 8.15.2 8.15.3 8.15.4 8.15.5 8.15.6 8.16

Aziridination 471 Intramolecular Aziridination 471 Intermolecular Aziridination 474 Mechanistic Insights into Silver-Catalyzed Aziridination 477 C—H Bond Amidation 484 Intramolecular C—H Bond Amidations 484 Intermolecular C—H Bond Amidation 494 Mechanistic Aspects of Site-selective C—H Bond Amidation 498 Silver-Catalyzed N—N Bond Formation 502 Summary 503 Introduction to Transition Metal-Catalyzed Silylene Transfer 504 Silver-Mediated Silylene Transfer Reactions 508 Olefins 508 Carbonyl Compounds 513 C—O Bonds 518 Allenes 522 Allylic Silanes 522 Allylic Sulfides 522 Summary 525 References 525

9

Asymmetric Silver-Catalyzed Reactions Hélène Pellissier

9.1 9.2 9.2.1 9.2.1.1 9.2.1.2 9.2.2 9.3 9.3.1

Introduction 533 Silver-Catalyzed Mannich Reactions 534 Vinylogous Mukaiyama–Mannich Reactions 534 With Hoveyda–Snapper Catalysts 534 With Other Catalysts 541 Other Mannich-Type Reactions 546 Silver-Catalyzed 1,3-Dipolar Cycloadditions 554 Formal 1,3-Dipolar Cycloadditions of Glycine Imino Esters and α,β-Unsaturated Carbonyl Compounds 555 Formal 1,3-Dipolar Cycloadditions of Glycine Imino Esters and Nitroalkenes 564 Formal 1,3-Dipolar Cycloadditions of Isocyanoacetates and α,β-Unsaturated Carbonyl Compounds 568 Other 1,3-Dipolar Cycloadditions 573 Silver-Catalyzed Domino and Tandem Reactions 574 Domino and Tandem Reactions Initiated by a Michael Addition 574 Domino Reactions Initiated by an Aldol Reaction 579 Domino Reactions Initiated by a Cyclization 583 Domino Reactions Initiated by a Mannich Reaction 589 Miscellaneous Domino Reactions 592 Silver-Catalyzed Michael Reactions 595 α,β-Unsaturated Carbonyl Compounds as Acceptors 595 Nitroalkenes as Acceptors 598 Other Acceptors 599

9.3.2 9.3.3 9.3.4 9.4 9.4.1 9.4.2 9.4.3 9.4.4 9.4.5 9.5 9.5.1 9.5.2 9.5.3

533

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Contents

9.6 9.6.1 9.6.2 9.7 9.8 9.9 9.10 9.11 9.12

Silver-Catalyzed Aldol-Type Reactions 601 Aldol Reactions 601 Nitroso-aldol Reactions 606 Silver-Catalyzed Alkynylations 610 Silver-Catalyzed Allylations 616 Silver-Catalyzed Cyclizations of Allenes 619 Silver-Catalyzed Aminations 623 Silver-Catalyzed Miscellaneous Reactions 624 Conclusions 633 References 634

10

Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives 645 Zhenhua Jia, Mingxin Liu, and Chao-Jun Li

10.1 10.1.1 10.1.2 10.1.3 10.2

Homogeneous Silver-Catalyzed Reduction of Aldehyde 645 Silver-Catalyzed Hydrosilylation of Aldehyde 647 Silver-Catalyzed Hydrogenation of Aldehyde 649 Silver-Catalyzed Transfer Hydrogenation of Aldehyde 651 Silver-Catalyzed Oxidation of Alcohol, Aldehyde, and Their Derivatives 652 Conclusion 657 Acknowledgment 658 References 658

10.3

11

Silver Complexes in Organic Transformations 661 Guichun Fang and Xihe Bi

11.1 11.2 11.2.1 11.2.2 11.2.3 11.2.4 11.2.5 11.2.6 11.2.7 11.2.8 11.2.9 11.3 11.3.1 11.3.2 11.3.3 11.3.4 11.3.5 11.3.6 11.3.7

Introduction 661 NHC–Silver(I) Complexes 662 A3 Coupling Reaction 663 CO2 Insertions 665 Borylation Reactions 667 Hydroborylation 668 Carbene Transfer with Diazo Compounds 668 Cyclization Reactions 670 Oxidation of Alcohols 672 Semi-hydrogenation of Alkynes 672 Synthesis and Application of Organosilver Complexes 673 Chiral Silver Phosphates 674 Alkynylation 675 Mannich Reaction 675 Intramolecular Annulation 677 Cycloisomerization 678 Enantioselective Semipinacol Rearrangement 683 Asymmetric Hetero-Diels–Alder Reaction 685 Miscellaneous Reaction 686

Contents

11.4 11.5 11.5.1 11.5.2 11.6 11.6.1 11.6.2 11.6.3 11.6.4 11.6.5 11.6.6 11.7

P,O-type Silver Complexes 688 Tpx -silver Complexes (Trispyrazolylborate Ligands) 690 Carbene Transfer Reactions 690 Nitrene Transfer Reactions 694 Silver Complexes with Pyridine-Containing Ligands 696 Silver-Catalyzed Nitrene Transfer (Aziridination vs C–H Amination) 698 Carbene Insertion 706 Hydrofunctionalization 707 Hunsdiecker Reaction 709 Twelve-membered Pyridine-containing Ligands (Pc-Ls) 710 Miscellaneous Reactions 711 Summary 713 References 714

12

Silver Nanoparticles in Organic Transformations 723 Alain Y. Li, Alexandra Gellé, Andreanne Segalla, and Audrey Moores

12.1 12.2 12.2.1 12.2.2 12.2.3 12.3 12.3.1 12.3.2 12.3.3 12.3.4 12.3.5 12.4 12.4.1 12.4.2 12.4.3 12.4.4 12.5 12.5.1 12.5.2 12.5.3 12.5.4 12.6 12.6.1

Introduction 723 Epoxidation of Alkenes 724 Epoxidation of Ethylene 724 Epoxidation of Propylene 727 Epoxidation of Styrene and Other Alkenes 729 Alcohol Oxidation 733 Aerobic Alcohol Oxidation 735 Alcohol Dehydrogenation 737 Silver Alloys in Alcohol Oxidation 739 Alcohol–Amine Coupling 742 Alcohol–Alcohol Coupling 748 Reduction 750 Carbonyl Reduction 750 Reduction of Alkynes 754 Reduction of Epoxides 755 Nitro Compound Reduction 757 Alkynylations 759 Cyclizations 759 A3 Coupling 761 Alkyne Coupling to Carbon Dioxide 765 Alkyne Cross-coupling 767 Plasmon-Mediated Ag NP Catalysis 768 Localized Surface Plasmon Resonance (LSPR) in Coinage Metal Nanoparticles 768 Plasmon-Mediated Oxidations Using Ag NPs 770 Reduction Catalyzed by Ag PNPs 771 Silver Halides for Photocatalysis 772

12.6.2 12.6.3 12.6.4

ix

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Contents

12.7 12.7.1 12.7.2 12.8 12.8.1 12.8.2 12.8.3 12.9

Oxidative Coupling 772 C–H Oxidation 772 Azo Coupling 775 Miscellaneous Applications 776 Nitrile Hydrolysis 776 Silanol Chemistry 778 Silver as a Lewis Acid 780 Conclusion 781 References 782 Index 795

xi

Preface Recently, coinage metal (copper, silver, and gold) salts and complexes are being increasingly used as homogeneous catalysts in organic synthesis. Among them, an important methodology is catalysis by silver, owing to its relatively lower cost than other expensive transition metals, excellent selectivity, and stability. However, in comparison with other transition metals, silver catalysts have long been believed to have low catalytic efficiency, and the rapid development of silver chemistry was achieved only in the past few decades. Generally, silver salts are mostly utilized as either σ-Lewis acid or π-Lewis acid, with preference to σ-coordination over π-coordination due to the ready availability of empty f orbitals and relativistic contraction of the electron cloud. Apart from the Lewis acid character, silver salts are also employed as cocatalysts, halophiles, general oxidants, SET oxidants (single electron transfer), weak bases, and radical initiators in numerous transformations. In addition, the distinctive d10 electronic configuration of silver allows to easily coordinate with most unsaturated bonds such as C=C, C≡C, C=X, and C≡X bonds (X = heteroatom), which facilitates the formation of new C—C or C—X bonds. Because of these aforementioned advantages, silver catalysis has provided a distinctive opportunity in organic synthesis. The first silver-catalyzed reaction was reported in 1933, in which ethylene was oxidized into ethylene oxide, and has been used on preparative and industrial scales for decades. Since then, a number of silver-catalyzed reactions have been developed and even applied in the synthesis of complex natural products and functional materials. As a record of these early developments, a topical book entitled Silver in Organic Chemistry edited by M. Harmata was published in 2010, which covered the literature up to 2008. Thereafter, there has been no book devoted to the catalysis by silver in the chemistry literature, although such a collection would be of great interest to the chemical community. Therefore, we have been privileged to invite our colleagues, who are leading scientists in this field, to contribute to this new book that emphasizes on the importance of silver catalysis in various organic transformations, covering the literature up to 2017. The present book consists of 12 chapters. It begins with a brief history

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Preface

and applications of silver and mainly emphasizes the fundamental reactions involved in silver catalysis by Prof. X. Bi, which laid the foundation for further discovery of catalytic reactions. The following chapter from Prof. D. Lee focuses on the silver-catalyzed/silver-mediated different types of cycloaddition reactions {[3+2], [2+2], [3+3], [4+2], [2+2+1], [2+1], [4+1]}. Major developments in the silver-catalyzed cyclization reactions are described in Chapter 3 by Prof. K. K. M. Hii. These reactions are particularly important for the production of either carbocyclic or heterocyclic rings, through the formation of C—C, C—N, and C—O bonds. Chapter 4 by Prof. C. Li provides critical and comprehensive insights into the roles of silver in radical transformations, including the protodecarboxylation, radical coupling, addition, cascade cyclization, and rearrangement reactions. Chapter 5 from Prof. S. Bräse highlights the recent progress in the silver-catalyzed various fluorination, perfluoroalkylation, and perfluorothiolation reactions. In Chapter 6, Prof. N. Jiao discusses the important advances in the silvercatalyzed/silver-mediated coupling reactions and C−H functionalization reactions. Prof. T. Yamada in Chapter 7 describes the recent developments in the silver-catalyzed utilization of carbon dioxide in organic synthesis, for instance, the carboxylation reactions of terminal alkynes, boronic esters, and terminal epoxides, as well as tandem cyclization reactions involving nucleophilic additions into carbon dioxide. The focus of Chapter 8 by Prof. J. M. Schomaker is devoted to carbene transfer (cyclopropanation, cyclopropenation, and C(sp3 )—H and X—H [X = heteroatom] bond insertion), nitrene transfer (aziridination, C—H amidation, and N—N bond formations), and silylene transfer (C—Si and Si—O bond formation) reactions. Chapter 9 by Prof. H. Pellissier exemplifies the major progresses in the silver-catalyzed enantioselective reactions. The silver-mediated oxidation and reduction of aldehydes are deliberated in Chapter 10 by Prof. C.-J. Li. Particularly, hydrogenation, transfer hydrogenation, and aerobic oxidation of aldehydes are discussed. Chapter 11 summarizes the catalysis of silver complexes by Prof. X. Bi. Special attention is given to the use of NHC–silver(I) complexes, chiral silver phosphates, P,O-type ligand silver(I) complexes, trispyrazolylborate–silver(I) complex, and silver complexes with pyridine-containing ligands as the catalysts. The last chapter of this book showcases the applications of silver nanoparticles in catalytic organic transformations by Prof. A. Moores. Especially, the epoxidation of alkenes, oxidation of alcohols, reduction reactions, and alkynylation reactions are deliberated. As the editors, we believe that this book will be very useful to those who are working (such as chemistry researchers, graduate students, and university/college professors) or will work in either the fundamental or applied sectors of this field, as a source of basic knowledge and convenient reference, and it will also inspire new ideas for the reader’s own research endeavors.

Preface

Finally, we wish to express our sincere thanks to all the contributors for their cooperation. We also wish to express our sincere gratitude to all the people who gave valuable help in different ways during the process of gathering materials, writing, and publishing this book. We also appreciate the staff of the editorial team of Wiley-VCH for their continuous help. September 2018

Chao-Jun Li Department of Chemistry and FQRNT Center for Green Chemistry and Catalysis McGill University, 801 Sherbrooke Street West Montreal, QC H3A 0B8, Canada Xihe Bi Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis Department of Chemistry Northeast Normal University Changchun 130024, China

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1

1 Introduction to Silver Chemistry Paramasivam Sivaguru and Xihe Bi Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun 130024, China

1.1 History and Features of Silver Silver is a malleable, ductile, and precious metal that has been known since ancient times (its first debut around 5000 BCE) and is located in group 11 (Ib) and period 5 of the periodic table, between the coinage metal copper (period 4) and gold (period 6). Silver is widely distributed in nature. But its abundance in the earth’s crust is very low (0.05 ppm) than other metals [1]. It occurs both naturally in its pure form and in ores, particularly derived from all the sulfur bearing lead, copper, gold, tellurides, and zinc, which is extracted through refining [2]. Silver has the atomic number 47 and atomic weight of 107.880, and its ground state electronic configuration is [Kr] 4d10 5s1 , just like copper and gold. Mostly, silver can exist in a mixture of isotopes, 107 Ag and 109 Ag, approximately occurring in the equal proportions. The most common oxidation states of silver are 0 and +1, although some other oxidation states (+2 and +3) are also known [3]. Among these Ag(II) salts/complexes are less stable than that of Ag(I) and Ag(III) salts/complexes. Silver is noticeably diamagnetic, and its magnetic susceptibility is almost independent of temperature from room temperature to just below the melting point. The elemental silver has the highest electrical conductivity (1⋅59 μΩ cm at 20 ∘ C) [4], thermal conductivity (429 W m−1 K−1 ) [5], and optical reflectivity than any other metal, but it has the lowest electrical contact resistance, and its specific heat capacity is 0.23 J kg−1 K−1 at 25 ∘ C. The melting and boiling point of silver is 961.9 and 2212 ∘ C, respectively [6]. The heat of fusion of silver is 11.28 kJ mol−1 , and its hardness is 2.7 on the Mohs scale. 1.1.1

Chemistry of Silver

It has been recognized that the outer orbital 5s1 electronic configuration of silver allowed to form numerous silver(I) salts/complexes with a wide variety of counterions (halide, sulfide, nitrate, oxide, acetylide compounds, cyano-derivatives, and olefin complexes). Silver dissolves readily in nitric acid to form silver nitrate Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

2

1 Introduction to Silver Chemistry

(Eq. (1.1)), which is a transparent crystalline solid that is readily soluble in water, and is a photosensitive. In addition, it is a precursor for the preparation of various other silver compounds. Silver could also dissolve rapidly with hot concentrated sulfuric acid (Eq. (1.2)). However, in the presence of ethanol, silver reacts with nitric acid to give the silver fulminate (AgCNO), which is a powerful touch-sensitive explosive used in percussion caps [7]. Also, silver nitrate reacts with sodium azide (NaN3 ) to form silver azide (AgN3 ), which is also used as an explosive [8]. Silver or silver nitrates simply precipitate as silver chloride in the presence of chlorides, which are used in the photographic emulsion: 3Ag + 4HNO3 → 3AgNO3 + 2H2 O + NO3

(1.1)

2Ag + 3H2 SO4 → 2AgHSO4 + SO2 + 2H2 O

(1.2)

Furthermore, silver nitrate could easily react with copper to produce the silver crystals (Eq. (1.3)). The alkaline solution of copper also reduces the silver nitrate into silver in the presence of reducing sugars. Tollens’ test/silver mirror test is a qualitative test to distinguish between an aldehyde and ketone. The Tollens’ reagent [Ag(NH3 )2 ]+ is prepared from silver nitrate by two-step process. In the first step, under basic conditions silver nitrate forms an insoluble silver oxide (Eq. (1.4)), and it dissolves readily with the addition of sufficient aqueous ammonia (Eq. (1.5)), which oxidizes an aldehyde into corresponding carboxylic acid (Eq. (1.6)) [9]: Cu(s) + 2AgNO3 → Cu(NO3 )2 + 2Ag(↓)

(1.3)

2AgNO3 + 2OH− → Ag2 O + 2NO3 − + H2 O

(1.4)

2Ag2 O + 4NH3 + H2 O → 2Ag(NH3 )2 + 2OH +

−

(1.5)

R − CHO + 2Ag + 2OH → R − COOH + 2Ag + H2 O +

−

(1.6)

Silver is stable in oxygen and water, but it is tarnishing in the presence of ozone or hydrogen sulfide or sulfur in air/water owing to the formation of a black silver sulfide layer. Besides, silver readily forms soluble silver complexes such as Ag(NH3 )2 + , Ag(S2 O3 )2 3− , and Ag(CN)2 − with excess of respective ions. The silver thiosulfate complex is used to dissolve undeveloped AgBr and fix the photography [10]. The silver cyanide complex is frequently used in electroplating [11]. A systematic sequence of reactions outlined in Figure 1.1 illustrated the chemistry of silver.

Ag Metal

HNO3

Ag+ Colorless solution

CO3–

Ag2CO3

OH–

Cream colored solid

Cl–

Ag2O Dark brown solid

AgCl

NH3

Ag(NH3)2+

White solid

Colorless solution Br–

Ag Lustrous metal

Al/hot Na2CO3

Ag2S Black solid

S–

Ag(CN)2– Colorless solution

Figure 1.1 Reactions in the silver series.

CN–

AgI Yellow solid

I–

Ag(S2O3)23– Colorless solution

S2O32–

AgBr

Pale yellow solid

1.1 History and Features of Silver

1.1.2

Silver Nanoparticles

Nanoparticulates (colloidal) of silver are fine particles of metallic silver that has been known for about 120 years [12]. Usually, these are synthesized by the reduction of soluble silver with reducing agents such as citrate, glucose, ethyl alcohol, and sodium borohydride as well as an appropriate stabilizing agent. The added stabilizing agent plays a crucial role to prevent the growth and aggregation of the formed silver nanoparticles. The reduction process can be carried out in both aqueous and organic solvents. However, a practical and reproducible synthesis of silver nanoparticle is very difficult than that of expected [13]. This might be due to its different morphologies and crystal sizes when changing reaction conditions such as concentrations, reducing agents, temperature, and additives [13, 14]. Depending on the reaction conditions, there are numerous kinds of silver nanoparticles that have been documented in the literature, including spherical [15], bipyramids [16], discs [17], rods [14, 18], cubes [19], prisms [20], rings [21], platelets [22], triangular prisms [23], and octahedral particles [19c]. Because of the different sizes and morphologies, nanosilver possesses the unique chemical, physical, and optical properties compared with the parent metallic silver. The unique properties of nanosilver are mainly attributed to the high surface area to volume ratio, leading many industrial sectors to incorporate silver nanoparticles into their products. Two main factors such as surface effects and quantum effects to cause nanomaterial behave significantly different than bulk materials [24]. These factors affect the chemical reactivity of materials as well as their mechanical, optical, electrical, and magnetic properties. Due to the unique chemical and biological properties of nanosilver, which are appealing to the consumer products, food technology, textiles/fabrics, catalysis, and medical industries. 1.1.3

Silver Applications

In the earlier years, silver has been used as a precious commodity in currencies, ornaments, jewelry, food decoration, solar cells, and photography [25]. Silver and its compounds have extensive applications in the twentieth century including electrical conductors, electrical contacts, catalysis, electronics, mirrors, assembly of chemical equipment and brazing alloys, drinking water filtration system, swimming pool filtration systems, healthcare products, and medical tools [26]. Silver paints are used for making printed circuits. Silver threads are woven into the fingertips of gloves so that it can be used with touch screen phones. Most importantly, silver/silver nanoparticles have long been used as an effective antibacterial agent against a broad spectrum of gram-negative (Acinetobacter, Escherichia, Pseudomonas, Salmonella, and Vibrio) and gram-positive (Bacillus, Clostridium, Enterococcus, Listeria, Staphylococcus, and Streptococcus) bacteria, which means silver is toxic to bacteria [27]. In addition to this, silver/silver nanoparticles are also found to have antifungal, antiviral, anti-inflammatory, antibiofilm, antiglycoprotein film, surface plasmon resonance, plasmonic heating, and metal-enhanced fluorescence properties [28]. Silver and silver nanoparticles are broadly used in urinary catheters and endotracheal breathing tubes [29]. The silver diammine

3

4

1 Introduction to Silver Chemistry

fluoride complex is a topical drug used to treat and prevent dental caries and relieve dentinal hypersensitivity [30]. One of the most beneficial uses of silver has been as a disinfectant, perhaps, which is routinely used in treating wounds and burns owing to its broad spectrum of toxicity to bacteria as well as its reputation of limited toxicity to humans [31]. Moreover, silver can easily bind with human body proteins (albumins and metallothioneins) and also interact with trace metals in metabolic process [32].

1.2 Silver Catalysis Recently, catalysis by silver is an important methodology in organic synthesis owing to its more economical than other expensive transition metals (TM), excellent selectivity and stability, and environmentally benign nature. But, in comparison with other TM, silver catalysts have long been believed to have low catalytic efficiency, and the rapid development of silver chemistry was achieved only in the past few decades [33]. Generally, silver salts are mostly utilized as either σ-Lewis acid or π-Lewis acid, with preference to σ-coordination over π-coordination due to the ready availability of empty f orbitals and relativistic contraction of the electron cloud [34]. In addition to the Lewis acid character, which are also employed as cocatalysts, halophiles, general oxidants, SET oxidants (SET = single electron transfer), weak bases, and radical precursors. In addition, the typical d10 electronic configuration of silver salts could easily coordinate with most of the unsaturated bonds (π-donors) like C=C, C≡C, C=X, and C≡X bonds (X = heteroatom) and n-donors such as (thio)ethers, amines, and phosphine than other metals [35]. Because of these aforementioned advantages, silver catalysis has provided a unique opportunity in organic synthesis. In the earlier year, the utilization of silver in organic chemistry can be classified into two prime distinct areas: (i) heterogeneous oxidation processes and (ii) homogeneous silver-mediated or silver-catalyzed reactions. The first silver-catalyzed reaction appeared in 1933, in which silver oxidizes the ethylene into ethylene oxide, and has been used on preparative and industrial scales for decades [36]. Further advancement of this protocol was also extended to other substrate, butadiene [37]. In addition to the olefin and alcohol oxidation, other examples of catalytic oxidation of CO to CO2 [38] and reduction of NOx [39] by silver-based heterogeneous catalysts have also been reported. Besides, a number of silver-catalyzed transformations have been developed and even applied to the synthesis of complex natural products and functional materials, which include cycloadditions, allylations of carbonyl and imine groups, and aldol reactions along with their asymmetric versions using chiral ligands, Michael and Mannich reactions, intramolecular heterocyclizations, silver-catalyzed functionalization of C—H/C—C bonds, and C—H bond activations of terminal or silylated alkynes applied to C—C and/or C—X bond constructions [33, 35]. 1.2.1

Alkynophilicity/Carbophilic Nature of Silver

Generally, the bonding of TM complexes with alkyne or alkene as π-ligands is explained on the basis of the Dewar–Chatt–Duncanson (DCD) model [40],

1.2 Silver Catalysis

which reflects the bond as a donor–acceptor interaction between two closedshell fragments [41]. The reason for the reputation of the donor–acceptor bonding model in TM chemistry is partly due to the fact that coordination chemistry plays a much bigger role for the TM than for main-group elements. Another reason is the success of ligand field theory (LFT) in explaining chemical bonding even in TM compounds that are not coordination compounds. According to the DCD model, a σ-bond is formed by the overlap of the π-system of the ligand with an empty metal orbital of suitable symmetry. A π-interaction then results through a back-donation of electron density from filled metal d orbital into an antibonding π* orbital of alkyne or alkene. A TM can contribute four principal components to the bonding with alkynes as ligands (Figure 1.2) in which the in-plane π|| orbitals are responsible for a σ-symmetric M ← L donation and M → L back-donation. The orthogonal out-of-plane π⟂ orbitals can participate in M ← L π-donation, while mixing an occupied d orbital of the metal with the empty π⟂ * orbital of alkyne can result in the addition of M → L back-donation. However, which has the δ symmetry and provide a weak overlap that leads to the minute contribution to the bonding. Thus, alkynes may be considered as 2- or 4-electron donor. As a result of DCD model, an elongation of triple (bending) or double (pyramidalization) bond observed as a magnitude of the net shift of electron density from bonding π orbital into the antibonding π* orbitals. Therefore, the degree of distortion from the geometry of the unbound ligand may be reserved for the indication of the degree of back-bonding [42]. It was observed from the literature that the silver(I) salts act as a σ-Lewis acid or π-Lewis acid in homogeneous catalysis [34]. The d10 electronic configuration makes silver(I) cation favoring to interact with most of the unsaturated system, particularly carbon–carbon π-bond of alkynes 1, so-called alkynophilicity. Upon coordination with silver(I) salts, alkyne moiety 2 is more prone to nucleophilic attack by a relatively weak nucleophile, i.e. during coordination more electron density is lost than is gained through back-donation, rendering the alkyne becomes electrophilic. But, in the case of terminal alkyne 3, silver acetylide 4 can be formed in the presence of a suitable base and then react with carbon nucleophile (Figure 1.2). On the basis of the above characteristics features of silver(I) salts, which can be considered as one of the effective catalyst for alkyne activation [33c, 43]. The resulting silver intermediate 5 undergoes various pathways. The first potential pathway is the trapping of such a silver intermediate by an electrophile Metal R1

R Ag+

R Alkynophilicity

H Ag+ 3

R Ag+ 2

1 R

1

R H

Ag

Alkyne δ

dxy

π⊥*

Ag

dyz

π⊥

Ag

π⊥

L

dxz

π|| *

Ag

π||

L

dz2

π||

Ag

4

Figure 1.2 Orbital diagram. Activation of alkyne by silver catalyst.

σ

L

L

5

6

1 Introduction to Silver Chemistry

where the deargentation process takes place and the carbon–silver bond is replaced by carbon–electrophile bond 6 (Scheme 1.1). If the electrophile is a simple proton, this step is termed as protodeargentation. R1

R Ag+

Ag

Nu– Nucleophilic addition

R

2

R1

E+

E

Nu

Electrophilic deargentation

R

5

R1

Ag+

+ Nu 6

Regeneration of the catalyst

Scheme 1.1 Trapping of silver intermediate by an electrophile.

Due to the delocalization ability of 4d electron of silver to the nonbonding electron of a carbocation, the silver intermediate 5 undergoes another kind of trapping reaction with external electrophile, where the electrophilic trapping occurs at the β-position to silver to generate the new silver intermediate via back-donation silver, which exists as two mesomeric forms, namely, silver-stabilized carbocation 7 and carbenes 8 (Scheme 1.2). Then, depending on its nature, the new silver intermediate can be trapped following a carbocation or carbene reactivity. Ag+

Ag

Ag

R1

E+

R

Nu

Back-donation of silver

E R1

5

E R1

R Nu 7

Carbocation reactivity

R Nu 8

Carbene reactivity

Scheme 1.2 Trapping of silver intermediate by back-donation of silver.

On the other hand, the nucleophilic addition of a nucleophile bearing a leaving group to a silver-activated alkyne results in a silver intermediate 9, where, upon back-donation, extrusion of leaving group occurs to form the new silver intermediate that also exists in two limited mesomeric forms like silver-stabilized carbocation 10 and carbene 11 (Scheme 1.3). These silver intermediates can also be trapped following the carbocation and carbene reactivity, according to its nature. These three kinds of silver-catalyzed/silver-mediated alkyne activation reactions are completely described in the forthcoming chapters of this book.

Ag R

Nu LG+

Ag+

Ag

R1

1

R Back-donation of silver

9 Carbocation reactivity

R

R1

R Nu 11

Nu 10 Carbene reactivity

Scheme 1.3 Reaction with nucleophile bearing a leaving group via back-donation of silver.

1.2 Silver Catalysis

1.2.2

Oxo- and Azaphilic Character of Silver

Apart from the carbophilic character of silver, silver(I) can also form strong bonds with oxo groups, so-called oxophilicity (Scheme 1.4). This may be due to the donation of lone pairs on O into an empty orbital of silver, which might be in dπ , σ*, or π* character. However, the oxophilic Lewis acid character of Ag(I) has been poorly investigated [44]; such an oxophilic character of Ag(I) has been ascribed on the basis of analogous gold(I)-catalyzed reactions [45]. However, the donation of lone pair electrons on N into an empty orbital of silver form a new strong bond, which inhibited the N-nucleophilicity; this process can be termed as azaphilicity (Scheme 1.5) [46]. Generally, the oxo- and azaphilic character of silver(I) salts has been exploited in reactions such as various cycloaddition reactions, allylation of carbonyl compounds, aldol-type reactions, Michael and Mannich reactions, and others. O R

H

+ CNCH2COOMe

[Ag] cat.

P

O Ag

P

H

R

CO2Me

R O

CNCH2CO2Me

N

Oxophilic activation

Scheme 1.4 Oxophilic activation of silver. R3 O

R1

O

[Ag] cat.

R1

R4

N

N

R2

R4

O

O

R2

Ag

R3

R1 N

Azaphilic activation

COOH R2

Scheme 1.5 Azaphilic activation of silver.

1.2.3

Halogenophilicity of Silver

Another important characteristic feature of silver(I) chemistry is the insolubility of its corresponding halogen salts (halogenophilicity). Generally, several TM-catalyzed transformations are led in the presence of Ag(I) salts to elicit the precipitation of AgX salts (X = Cl, Br, I) from coordinatively saturated metal centers, for example, in the palladium-catalyzed cross-coupling reactions involving aryl or alkyl halides (Scheme 1.6) [47]. R3 R1 R2

L2Pd0 X

R1 R2

AgI PdIIL2X

R1 R2

AgX

R4 PdIIL2

Base

R1 + Pd0

R2 R3

Halogenophilicity

Scheme 1.6 Halogenophilicity of silver in the Pd-catalyzed cross-coupling reaction.

R4

7

8

1 Introduction to Silver Chemistry

1.2.4 1.2.4.1

Redox Chemistry of Silver One-electron Ag(I)/Ag(II) Redox Cycles

It is well known that the silver(I) salts are extensively employed as one-electron oxidant as compared with other group 11 metals, copper, and gold that are involved in the two-electron redox chemistry [48], for instance, in the oxidation of alcohols into the corresponding carbonyl compounds under mild conditions [33e, 49]. Subsequently, an increasing number of oxidative C—C bond-forming and C—C bond cleavage reactions have been well documented by the use of the Ag(I) as a sacrificial outer-sphere one-electron oxidant [50]. For example, silver(I) is involved as an efficient catalyst in the oxidative decarboxylation of acids by peroxydisulfate ion in aqueous solutions [51]. Mechanistically, the in situ formed metastable intermediate Ag(II) species, from the rate-limiting oxidation of silver(I) by peroxydisulfate, played a crucial role in the specific and efficient decarboxylation process. The direct and facile oxidation of the carboxylic acid group by Ag(II) proceeds very fast and generates an acyloxy radical, which subsequently fragments into an alkyl radical and carbon dioxide. The final products are obtained by oxidation of the alkyl radical by silver species as well as by hydrogen transfer to solvent (Scheme 1.7). R COOH + S2O82– Ag(I) + S2O82– Ag(I) + SO4 Ag(II) + R COOH R COO R

+ HY

Ag(I)

R H + CO2 + 2SO42– Ag(II) + SO42– + SO4 Ag(II) + SO42– Ag(I) + R COO + H+ R

+ CO2

R H + Y

Scheme 1.7 One-electron Ag(I)/Ag(II) redox cycle in Ag(I)-catalyzed oxidative cross-coupling reaction.

1.2.4.2

Two-electron Ag(I)/Ag(III) Redox Cycle

The investigation of two-electron Ag(I)/Ag(III) redox chemistry of silver is very rare, although Li and coworkers proposed in their studies on Ag(I)-catalyzed radical aminofluorinations that electrophilic fluoride sources are capable of generating monometallic Ag(III)—F intermediate species, but the C—F bond formation is proposed to occur through a one-electron redox reaction of Ag(II)—F with carbon-centered radical species [52]. Recently, the research group of Ribas studied the two-electron redox chemistry of silver in the C—O and C—C cross-coupling reactions [53], where silver can engage in two-electron oxidative addition and reductive elimination processes. More importantly, an aryl–Ag(III) 12-1 was evidently identified as a key intermediate in the catalytic cycle (Scheme 1.8) and also provided the appropriate evidence of aryl halide oxidative addition and C—N, C—O, C—S, C—C, and C—halide bond-forming

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

R N

N

X

AgI

R

R N

AgIII N

X–

N 12

R N

Y

N Nuc

Nuc

R N

N

12-1

13

R AgI

R N

+

R +

Nuc N

N

N 13

R

N

X

AgI

R

N Oxidative 12 addition

Reductive elimination

+

2+

Y-Nuc R

N

AgIII N

R

R N

AgIII N

N

N

12-2

12-1

+

R

X–

HX HY-Nuc Nucleophile coordination

Scheme 1.8 Two-electron Ag(I)/Ag(III) redox cycle in Ag(I)-catalyzed cross-coupling reaction.

reductive elimination steps. These results exemplify a new revolution in the fundamental sympathetic of silver’s redox chemistry and opens budding new opportunities for designing Ag-catalyzed synthetic tools in organic synthesis, parallel to the well-known Pd(0)/Pd(II) and Cu(I)/Cu(III) catalysis [54].

1.3 Representative Examples of Silver Catalysis in the Organic Transformations 1.3.1

Protodecarboxylation of Carboxylic Acids

Decarboxylation reactions are important transformations in synthetic organic chemistry [55], especially for the removal of carboxylate group that are employed as one of the directing groups in other transformations [56] including decarboxylative coupling reactions [57]. Consequently, significant attention has also been paid to study the protodecarboxylation of carboxylic acids. Generally, this protodecarboxylation reaction proceeds in the presence of TM such as Cu, Ag, Au, Hg, Pd, and Rh (Scheme 1.9) [58]. Among the coinage metal catalysts, silver

9

10

1 Introduction to Silver Chemistry

[Au]

[M] R H

M = Cu, Ag, Pd, Rh

R [Au]

R COOH

Scheme 1.9 Transition metal-catalyzed protodecarboxylation reaction of carboxylic acid.

catalysts have been efficiently activating the decarboxylation of the variety of carboxylic acids under mild conditions [58g] as compared with their Cu(I)-catalyzed counterparts [58c]. Notably, silver catalysts exhibited the excellent selectivity toward the monoprotodecarboxylation of dicarboxylic acids, owing to the remarkable activating effect of α-heteroatoms and ortho-electron-withdrawing groups [58g]. Mechanistically, the reaction was proposed to proceed via silver arene intermediate 14-2, followed by protodemetalation with an aryl carboxylic acid molecule to regenerate the starting complex (Scheme 1.10). But, in the case of gold catalysis, the obtained products are not pronated because the reaction stops at the metalation (Scheme 1.9). This might be due to the high stability of C—Au bond [58k,l]. EWG

COOH or N

COOH

COOH

Ag2CO3 (10 mol%) AcOH (5 mol%) DMSO, 120 °C

COOH

EWG

COOH

H

or N

H

COOH

Possible reaction mechanism CO2 AgX Ar COOH

Ar COOAg

Ar Ag

14

14-1

14-2

HX

Ar H 15

Scheme 1.10 Ag(I)-catalyzed protodecarboxylation of aromatic carboxylic acids.

1.3.2

A3 Coupling Reaction

A3 coupling or aldehyde–alkyne–amine reaction [59] is a significant reaction as the resulting propargylamines [60] are the key building block in the synthesis of nitrogen-containing biologically active pharmaceuticals, agrochemicals, and natural products [61]. It was evident from the literature database that the silver-catalyzed A3 reaction is especially effective even with aliphatic aldehydes and more challenging coupling partners such as aniline and ketones [62]. Moreover, these silver-catalyzed approaches provided an attractive platform for developing tandem reactions, particularly for the synthesis of N-/O-containing heterocyclic compounds [63]. Besides, Li et al. observed that the phosphine ligand served as a remarkable chemo-switch in this silver-catalyzed A3 reaction in water. In the absence of phosphine ligand, exclusive aldehyde–alkyne–amine coupling product 19 was observed, whereas, in the presence of phosphine (Cy3 P) ligand, reaction provided the exclusive aldehyde–alkyne coupling product 20 (Scheme 1.11) [64]. It is well known that the simple alkynyl silver reagents are typically too reactive and involved in the nucleophilic addition reaction to carbonyl compounds.

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

Cat. AgCl 5 mol% Water, 100 °C O + H

R 16

N H

R 19

R1

+ H

17

N

Cat. AgCl/L 5 mol%

18

Water, 100 °C

R1

OH R

L = phosphine ligand

20

R1

Scheme 1.11 Ligand-controlled A3 coupling reaction in water.

Mechanistically, the authors postulated that the coordination of the electrondonating P-ligand increases the electron density of silver, which results to weaken the Ag—C bond of silver acetylide A (Scheme 1.12). OH R1 + i-Pr2NEt

H R R1

20

18 Cy3PAgCl

H2O, Cl–

i-Pr2NEtH+Cl–

O

AgPCy3 Cy3PAg 18-1

R 18-3

R1

Cy3PAg

R1

R1

O R

H 18-2

Scheme 1.12 Catalytic cycle involved in the ligand-controlled A3 coupling reaction in water.

1.3.3

Incorporation of CO2

The incorporation of CO2 into propargyl alcohol is one of the frequently employed methods for the synthesis of functionalized cyclic carbonates by means of TM catalysts (Cu, Pd, Pt, Rh, Hg, and Ru). However, these reported approaches required harsh reaction conditions (high CO2 pressure and high reaction temperature) and are only applicable to terminal alkynes, and the internal alkynes had sluggish under these catalytic conditions [65]. But, Yamada et al. discovered that, under the catalysis of silver, the CO2 incorporation into propargyl alcohol 21 is more effective even with internal propargyl alcohols [66]. Their study revealed that the combined use of Ag(I) with DBU (1,8-Diazabicyclo(5.4.0)undec-7-ene) was found to be optimum to produce the

11

12

1 Introduction to Silver Chemistry

sole exo-alkenyl cyclic carbonates 22 in high to excellent yields, although other TM catalysts such as copper, gold, rhodium, mercury, platinum, and palladium were not effective at room temperature. Mechanistically, the DBU induced the deprotonation, and the silver catalyst activated the C≡C bond from the opposite side of the carbonate anion to promote anti-addition via 5-exo-dig cyclization as supported by DFT (density functional theory) calculations (Scheme 1.13) [67]. The backside attack is analogous to the typical reactivity of the related gold(I) catalysts [68], but only the silver catalyst is able to induce cyclization, and gold catalysis fails under these conditions [69].

O

AgOAc (10 mol%) DBU (0.1–1.0 equiv.) CO2 (0.1–1.0 MPa)

H

1 2R

3

R

R 21

O

R3

R1

2 22 R

DBU + Ag+

H-DBU+ O R1 R2 21-1

O

Toluene, rt

DBU

R3

O

H-DBU+

O

CO2

O

O O R1 R2

AgOAc R3 CO2-fixation

O

Ag+ 21-2

O

R3 2

Intramolecular cyclization

Ag R 21-3

R1

Scheme 1.13 Ag(I)-catalyzed tandem carboxylation and cyclization reaction.

1.3.4

Enantioselective Nitroso-aldol Reaction

The asymmetric nitroso-aldol-type reaction is one of the important transformations in organic synthesis that can introduce a hydroxyl group at the α-position of carbonyl compounds [70]. However, a key challenge arising in the exploitation of nitroso-aldol synthesis is controlling selectivity between O- and N-adduct owing to the high reactivity of nitroso derivatives toward nucleophiles. Generally, an organocatalyst like l-proline exclusively promotes the O-nitroso-aldol reaction of aldehyde and ketone [71]. In sharp contrast, the selective N-nitroso-aldol reaction is very difficult task to achieve [72]. However, Yamamoto and coworkers selectively achieved the N-adduct 28 in the nitroso-aldol reaction of tributyltin enolate 26 with nitrosobenzene 27 using 10 mol% of AgOTf and (R)-BINAP system (Scheme 1.14) [73]. During their studies, the authors isolated the three different BINAP-silver complexes 23–25 via the systematic survey of metal-to-ligand ratio; the complex either 23 or 25 was selectively generated from 2 equiv. of (R)-BINAP with 1 equiv. of AgOTf or 2 equiv. of AgOTf with 1 equiv. of (R)-BINAP, respectively, and the complex 24 was generated from 1 : 1 ratio of (R)-BINAP and AgOTf. But each of the three complexes plays a different role in regio- and enantioselectivity of this nitroso-aldol reaction. Among the three complexes, the monometallic complex

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

P

P

P AgOTf

P

Ag

P

–

P OTf P

P AgOTf

P

23 (2 : 1)

24 (1:1)

PPh2 PPh2

=

AgOTf P

25 (1:2)

N-Nitroso aldol synthesis OSnBu3

(R)-BINAP/AgOTf (complex 25)

O N

+

Ethyleneglycol diethyl ether –78 °C, 2 h

Ph 26

27

O N

+ Ph 30

27

OH N Ph or

28, N-adduct (96%, >99% ee)

O-Nitroso aldol synthesis OSnMe3

O

O O

O O

THF, –78 °C, 2 h complex 23 24 25

N H

Ph

Ph

29, O-adduct (4%)

O (R)-TolBINAP/AgOTf

N H

or

OH N Ph

29

28

O-Adduct/N-adduct >99 N-adduct >99:1 95:5

ee (%) 99 9

Scheme 1.14 Enantioselective N- and O-nitroso-aldol synthesis.

23 resulted the complete N-selectivity 29 in THF without any enantioselectivity (O-/N- = 1 : >99, 2% ee). And the enantioselectivity of N-adduct 29 was also very low when using the monometallic complex 24 derived from AgOAc (∼20% ee). However, by using bimetallic complex 25 in ethylene glycol diethyl ether, excellent levels of enantio- and regioselectivities were observed (O-/N- = 4 : 96, >99% ee). But, in the presence of complex 24 derived from (R)-TolBINAP and AgOTf, the reaction of trimethyltin enolate 30 with nitrosobenzene 27 exclusively provided the O-adduct 28 with excellent regio- and stereoselectivity (O-/N- = >99 : 1, >99% ee) [73]. 1.3.5 Chemoselective Cyclopropanation Using Donor–Acceptor Diazo Compounds TM catalysts played a critical role on modulating the decomposition chemistry of diazo compounds. Traditional carbenoids functionalized with one- or twoelectron acceptor groups (ester, ketone, phosphonate, etc.) are highly electrophilic. On the other hand, carbenoids with a donor (aryl, vinyl, alkynyl) and an acceptor group are much more chemoselective than traditional carbenoids [74] as witnessed from the myriad of reported organic transformations [75]. For instance, Davies and Thompson demonstrate that the AgSbF6 -catalyzed reaction of trans-β-methylstyrene 31 with donor–acceptor diazo compounds 32 provides a very different reactivity profile than the reaction in the presence of Rh2 (OAc)4 catalyst where the silver-catalyzed reaction resulted the cyclopropane 33 in excellent yields (80%) and diastereoselectivity (>94% de) and also retained the

13

14

1 Introduction to Silver Chemistry

orientation between phenyl and methyl groups in the product. While rhodium catalysts selectively produced the C—H insertion product 34 (4%), carbene dimerization was a dominant product when using large excess of substrates (Scheme 1.15). Moreover, the silver-catalyzed cyclopropanation of a variety of alkenes including more hindered substrates can also be achieved, despite that these substrates failed to afford the cyclopropane derivatives with rhodium catalysts [76]. One the other hand, the silver-catalyzed reaction of the vinyldiazoacetate 35 with 1,3-cyclohexadiene 36 also has a major effect, in which the AgSbF6 resulted in the tandem cyclopropanation and cope rearrangement to give formal [4+3] cycloadduct 37 in 67% yield. However, rhodium acetate-catalyzed reaction proceeds through the tandem C—H activation/cope rearrangement to afford 1.4 : 1 ratio of products 37 and 38 in 36% yield (Scheme 1.16). N2

+

Ph

Ph 31

Catalyst COOMe CH2Cl2, reflux Ph

32

Ph

COOMe + Ph

COOMe

Ph 33

Catalyst AgSbF6 Rh2(OAc)4

34 Yield 80% 4%

33 : 34 > 20 : 1 1: > 20

>94% de

Scheme 1.15 Chemoselective reaction of styrene with donor–acceptor diazo compounds.

COOMe + 35

N2

COOMe

Catalyst CH2Cl2, reflux Ph 36

+ Ph

Ph 37 Catalyst

Yield

38 COOMe 37 : 38

AgSbF6 Rh2(OAc)4

67% 36%

5.4 : 1 1.4 : 1

Scheme 1.16 Reaction of vinyldiazoacetate with 1,3-cyclohexadiene.

1.3.6

Homocoupling of Alkyl Grignard Reagents

TM-mediated/TM-catalyzed oxidative homocoupling of organometallic reagents is an important transformation in organic synthesis, and significant progress has been made on the several catalytic homocoupling of aryl–metal reagents [77]. However, the homocoupling of alkyl–metal reagents, especially those bearing β-hydrogens, has not been developed well, because of the difficulty in the alkyl–alkyl coupling by TM catalysis [78]. In this connection, Hayashi et al. developed a silver-catalyzed protocol to achieve the oxidative alkyl–alkyl homocoupling, where the silver tosylate (AgOTs) selectively catalyzes the homocoupling of alkylmagnesium reagents 39 in the presence of 1,2-dibromoethane as an oxidant in THF at RT to give the corresponding symmetrical alkanes 40 in excellent yields (Scheme 1.17). However, the effective aryl–aryl coupling catalyst FeCl3 and other TM catalysts such as CoCl2 , NiCl2 , and CuCl2 produced very

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

BrCH2CH2Br (1.2 equiv.) AgOTs (1 mol%)

Ralkyl MgX

Ralkyl Ralkyl

THF, rt, 30 min

39

40

½R R 40 AgOTs

RMgX

Ag 39-2

Ag R 39-1

Ag Br 39-3

RMgX

½ BrCH2CH2Br

½ C2H4

Scheme 1.17 Silver-catalyzed homocoupling of alkyl Grignard reagents.

poor yields of homocoupling products along with alkene as a by-product. This may be due to the as-formed alkyl–metal intermediate more prone to undergo β-elimination to give alkene, but the alkyl silver intermediate failed to undergo β-elimination [79]. Mechanistically, the alkyl silver 39-1 species was proposed as a key intermediate in this reaction, which undergoes disproportionation to give homocoupling product 40 and silver(0) species 39-2. Then the formed Ag(0) species 39-2 undergoes oxidation with 1,2-dibromoethane followed by transmetalation with Grignard reagents to regenerate alkyl silver species 39-1 to carry the catalytic cycle. This proposed mechanism is completely different than that of the reported one, where the alkyl bromide 41 was proposed as a crucial intermediate (Scheme 1.18) [80]. Step I

R MgBr 39

Step II

R MgBr 39

+

Br

Br +

R Br 41

R Br 41 [Ag] cat

+

+

C2H4

R R 40

+

MgBr2 MgBr2

Scheme 1.18 Alternative mechanism.

1.3.7

Oxidative Arene Cross-coupling

Biaryl molecules are considered as abundant building blocks in light-emitting diodes, electron transport devices, liquid crystals, and medicinal compounds [81]. Because of the structural simplicity of biaryl compounds belies its preparative complexity, although the palladium-catalyzed cross-coupling reactions (Suzuki and Stille couplings) of alkyl halides and organometallics are the most accepted and widely used methods for the synthesis of biaryls. But these approaches required the preactivation of both aromatic coupling substrates and provided the unwanted homocoupling products that hampered the applicability of these reactions [82]. In the past few decades, some important advances have been made in the biaryl synthesis by direct cross-coupling that are devoid of any substrate preactivation [83]. For example, Fagnou group realized that the

15

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1 Introduction to Silver Chemistry

palladium can catalyze the cross-coupling of N-substituted indoles 42 and benzenes 43 to give the C3 and C2 aryl indoles 44 and 45 in high yield over a range of indoles without recourse to any activating groups (Scheme 1.19). In this reaction, the authors found that the oxidant plays a critical role to control the product selectivity. In the presence of stoichiometric Cu(OAc)2 oxidant (10 mol%), the Pd-catalyzed reaction of N-acetyl indoles and benzenes selectively afforded the C3 aryl indoles 44 in high yields (C3/C2 = 8.9 : 1) [84]. However, the Pd-catalyzed reaction was carried out with stoichiometric AgOAc oxidant, which delivers the C2 aryl indoles 45. Changing the N-acetyl to N-pivalyl indole resulted in excellent C3/C2 selectivity (1 : 25) [85]. Furthermore, these standard conditions did not afford any by-products resulting from the homocoupling of arene substrates. The reason for the inversion in C2/C3 selectivity is explained as follows: in the presence of AgOAc, the acetate behaves as a base not counterion that instructs the increased C2 selectivity to Pd catalyst, where the carboxylate-induced cleavage of higher-order Pd clusters and the formation of monomeric Pd species were occurring. While excess of Cu(OAc)2 is added into the catalytic quantity of Pd(TFA)2 , mixed Pd—Cu clusters may be formed that exhibit pronounced C3 selectivity [86]. H

Ph H

H +

+

Additive, benzene PivOH,110 °C

N R 42

Pd(TFA)2, oxidant

Pd(TFA)2

Ac

10 mol%

Ac

10 mol%

AgOAc (2.2 equiv.)

Piv

5 mol%

AgOAc (3 equiv.)

Additive 3-Nitropyridine (10 mol%) Cu(OAc)2 (3 equiv.) CsOPiv (40 mol%

Ar

Ar

3-Nitropyridine (10 mol%) CsOPiv (40 mol%) None

44/45/46 8.9 : 1 : 0.26 1:4:0 1 : 2 5 : 0.7

H

PdX2 XH

Step 1

A complete inversion of selectivity is required Ar

Pd(0)

Ar

46

Oxidant

But Ar H not...

Ph N R

45

R

Oxidant Ag(I)/Cu(II) “X2”

N R

N 44 R

43

+

PdX Ar

Step 2

Ar

H But Ar not...

H

Pd Ar

XH

Scheme 1.19 Oxidative arene cross-coupling.

1.3.8

Hydroazidation of Alkynes

The hydroazidation of alkynes is one of the most straightforward pathways to access synthetically useful vinyl azides, which are versatile synthetic intermediates in numerous organic transformations, particularly in the TM-catalyzed azaheterocyclization reactions [87]. However, the synthetic potency of vinyl

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

azides from unactivated alkynes remains largely unexplored [88]. In 2014, Bi’s group established a silver(I)-catalyzed protocol for the chemo- and regioselective hydroazidation of ethynyl carbinols 47 with TMSN3 , affording diverse 2-azidoallyl alcohols 48 in high yields, where the hydroxyl group that is close to the alkyne unit plays a critical role in directing the regio- and chemoselectivity, and a trace amount of water in DMSO (dimethyl sulfoxide) was necessary for the reaction. But other TM catalysts such as Cu(I) and Pd(II) salts failed to yield the hydroazidation product. Mechanistically, silver acetylide 47-1 and vinyl silver 47-2 were proposed as a key intermediate in this reaction (Scheme 1.20) [89]. Later, they found that the stoichiometric amount of water has avoided the dependence of the hydroxyl group in the hydroazidation reaction. Accordingly, the numerous unactivated terminal alkynes 49 underwent the hydroazidation using TMSN3 in H2 O with the assistance of Ag2 CO3 to give the excellent yields of corresponding vinyl azides 50 in shorter reaction times (Scheme 1.20) [90]. HO R1

+ R2

TMS N3

Ag2CO3 (10 mol%)

R1

OH

R2 48 N3

DMSO, 80 °C, 1-2 h

47 TMS N3

Ag2CO3

H2O

Ag2CO3 H2O R1 R1

OH HN3 47-1

R1 R2 R3

Ag

+ 49

R1 R2

Ag

OH

H N3

TMS N3

Ag2CO3 (10 mol%) H2O (2.0 equiv) DMSO, 80 °C, 20–90 min

R2 R3

47-2

R1

N3 50

Scheme 1.20 Hydroazidation of unactivated alkynes.

1.3.9

Isocyanide–alkyne Cycloaddition

The [3+2] cycloaddition of isocyanides and alkynes is an atom-economic and straightforward method for the synthesis of pyrroles, which are important motifs in numerous natural products, pharmaceuticals, agrochemicals, and functional materials. However, most of the reported reactions are highly limited to electron-deficient alkynes under base or copper catalysis [91]. In 2013, Bi’s group [92] and Lei group [93] have addressed these challenges through a silver-catalyzed cycloaddition reaction of unactivated terminal alkynes and isocyanides (Scheme 1.21). Remarkably, Ag2 CO3 exhibited the unique catalytic activity toward the pyrrole 51 synthesis than other silver salts such as AgNO3 , AgBF4 , AgClO4 , AgOAc, AgOTf, Ag2 O, AgF, and AgNO2 . In contrast, Cu(OAc)2 and CuI catalysts were found to be ineffective. Also, the standard conditions did not produce any by-products derived from the homocoupling of terminal

17

18

1 Introduction to Silver Chemistry

R1

H 51 +

R2

Lei’s work

52

H 51 +

Ag2CO3 (10 mol%) 1,4-dioxane, 80 °C

R2 N H 53

NMP, 80 °C

NC

R1

R1

Ag2CO3 (10 mol%)

R2

Bi’swork

NC 52

Scheme 1.21 [3+2] cycloaddition of isocyanides with terminal alkynes.

alkynes. But the reaction mechanism of this reaction proposed by both Lei’s and Bi’s groups remains unclear. Later, Bi’s group collaborates with Zhang group to study the precise reaction mechanism of this Ag2 CO3 -catalyzed cycloaddition of isocyanides with terminal alkynes. The combined DFT and experimental results clearly revealed that the reaction underwent through an unexpected multicatalyzed radical process, where the Ag2 CO3 served a dual role as a base for deprotonating isocyanide and an oxidant to initiate the initial isocyanide radical formation. After the cycloaddition of isocyanide radical with silver acetylide, the substrate (isocyanide) and solvent (1,4-dioxane) replaced the role of Ag2 CO3 and acted as a radical shuttle to regenerate the isocyanide radical for the next cycle, completing the protonation (Scheme 1.22) [94]. Step I

N C

Ag2CO3

EtO2C

AgHCO3 + Ag(s) N

EtO2C Ph O

H Radical transfer

H

EtO2C Step III

Step II

Step IV

O

Ph

N C

Ag

NC EtO2C

H N

EtO2C Ph

H H

EtO2C

N

H

EtO2C Ph

Ph Ag2CO3

N Ag

AgHCO3

Scheme 1.22 Favorable radical catalytic cycle for the isocyanide–alkyne cycloaddition.

1.3.10

Nitrogenation of Terminal Alkynes

The transformation of alkynes is a fundamental method that has been widely utilized in organic synthesis. Recently, the catalytic selective cleavage of carbon– carbon triple bond has attracted significant attention, and several TM-catalyzed C≡C bond cleavage reactions have been reported for the construction of new C—C and C—heteratom bonds, especially silver catalyst remarkable catalytic activity [95]. For example, Jiao et al. reported a novel and direct method for the nitrogenation of alkynes 54 into nitriles 55 through the selective cleavage of C≡C bonds. A range of aryl/alkyl terminal alkynes smoothly underwent this selective

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

nitrogenation using 10 mol% of Ag2 CO3 as catalyst to afford the desired nitriles in high yields. However, the reaction catalyzed by other TM, such as AuCl3 , NiCl2 , FeCl2 , Cu(OAc)2 , and Pd(OAc)2 , either did not proceed or gave only poor yields, indicating the amazing catalytic reactivity of silver in this nitrogenation process [96]. Mechanistically, the formation of vinyl azide 54-3 is a crucial intermediate in this nitrogenation reaction, which could directly transform into corresponding nitriles 55 under standard conditions. But, in the absence of another equivalent of TMSN3 , corresponding nitriles obtained in very poor yields imply the pivotal role of TMSN3 in C≡C bond cleavage. From these, the author concluded that the conversion of vinyl azides into nitriles does not require the silver catalyst. Then the as-formed vinyl azide 54-3 cyclizes with azide to form the unstable intermediate 54-4, which undergoes fast rearrangement to give nitrile with the release of HN3 and CH2 N2 (Scheme 1.23) [96]. +

R

Ag2CO3 (10 mol%)

TMS N3

DMSO, 100 °C, air, 12 h R = aryl or alkyl

(2 equiv)

54

N3

R [Ag] 54-2

HN3 CH2N2

N 55

H2O

–

N3

R

55

H R

R H

N

[Ag]+ 54-1 [Ag]+ R

H

N3

H

R

H 54-3

N

R

N–

N+ N NH N 54-4

HN3

54

Scheme 1.23 Silver-catalyzed nitrogenation of terminal alkynes via C≡C bond cleavage.

1.3.11

Decarboxylative Alkynylation

Introduction of an alkynyl group into a molecule has drawn considerable attention not only because of its applications in materials science and chemical biology but also because of its versatile building blocks in organic synthesis [97]. Rapid progress has been made in the TM-catalyzed alkynylation via the Sonogashira reaction, which results in expedient route to C(sp2 )—C(sp) and C(sp3 )—C(sp) bond formations. However, these approaches are highly restricted to primary or secondary alky–alkynyl coupling, while tertiary alkyl–alkynyl coupling reaction remains a difficult task [98]. In this connection, Li group described a silver-catalyzed decarboxylative alkynylation of aliphatic carboxylic acids 56 in aqueous conditions (Scheme 1.24). Especially, in the presence of AgNO3 as catalyst and K2 S2 O8 as oxidant, various primary/secondary/tertiary alkyl carboxylic acids smoothly underwent the decarboxylative C(sp)—C(sp3 )

19

20

1 Introduction to Silver Chemistry

I

O R CO2H + O 56 R = 1°, 2°, 3° alkyl G = Ph, p-Cl-C6H4, TIPS

AgNO3 (30 mol%) K2S2O8 (30 equiv.)

G

R

G 58 33 examples upto 94%

DMF/H2O (1 : 1), rt, 10 h (or) CH3CN/H2O (1 : 1), 50 °C, 10 h

57

S2O82– O

O Ag2+

O

Ag+

I

TIPS

O

R

R CO2H

I R TIPS

I HO2C

O

+e, +H+ or H-abstraction

I

O

R

TIPS

Scheme 1.24 Silver-catalyzed decarboxylative alkynylation.

coupling with various ethynylbenziodoxolones 57, leading to the corresponding alkylated compounds 58 in high yields under mild conditions. Notably, this catalytic process exhibited the good functional group tolerance, including the more complex molecules such as N-protected amino acids or dehydrolithocholic acids. Based on their control experiments, the authors proposed a radical mechanism as shown in Scheme 1.24. Oxidation of Ag(I) by persulfate generates Ag(II), which then induces decarboxylation of aliphatic carboxylic acid into alkyl radical. The addition of alkyl radical to the C≡C triple bond of alkynyliodine(III) compound and subsequent β-elimination to afford the final product along with the benziodoxolonyl radical. The latter is transformed into 2-iodobenzoic acid either by H-abstraction or by reduction [99]. 1.3.12

Nitrene Transfer Reactions

N-containing organic compounds are principal components of many biologically and pharmaceutically important molecules. Therefore, the selective introduction of N-atom into molecules is of great interest of research. The TM-catalyzed nitrene transfer into C—H or C=C bond of unsaturated substrates represents a straightforward strategy for the construction of new C—N bonds, and significant progress has been achieved in the past decades [100]. However, the chemoselective C—N bond formation via the nitrene transfer into a substrate bearing both C—H and C=C bonds is challenging task, because these substrates give rise to multiple products or exhibit substrate or catalyst controlled selectivity [101]. Thus, a novel method that can achieve both the product by means of same metal and same ligands is highly needed. In 2013, the Schomaker group has solved this problem by employing this nitrene transfer reaction of homoallenic carbamates 59 with silver catalysis. Particularly, a silver complex derived from AgOTf and

1.3 Representative Examples of Silver Catalysis in the Organic Transformations

1,10-phenanthroline (phen) showed significant chemoselectivity by tuning the metal ligand ratio [102]. In the absence of an allenic C—H bond, the selective aziridination took place, and no competitive C—H amination was observed. But, in the presence of allenic C—H bonds, aziridination 60 is preferred over C—H amination 61 with a monomeric (phen)AgOTf complex derived from an equimolar ratio AgOTf and Phen, and the chemoselectivity for aziridination over C—H amination varied from 3.7 : 1 to >20 : 1. In sharp contrast, when the AgOTf/Phen ratio was increased to 1 : 3, the aziridination process was suppressed, and reactivity favored to the C—H insertion, leading to C—H aminated products 61 with excellent chemoselectivities (Scheme 1.25). Notably, trisubstituted allenes exhibited excellent selectivity under both conditions, while less substituted allenes usually gave better selectivity in C—H insertion. This result shows that Ag has the unique ability to change coordination geometry in response to changes in the metal/ligand ratio. The control experiment results support that a concerted pathway involves singlet nitrene for the C—H insertion (Scheme 1.26, Path B). But the aziridination pathway could involve either singlet R2

R •

R1

R2

2 equiv. PhIO, 4 Å MS CH2Cl2, rt

R1

O R3

NH2 R3

R •

R2 R1

H N

AgOTf/phen (1 : 3) O

O 61

2 equiv. PhIO, 4 Å MS CH2Cl2, rt

N

O

R1

N

+ R2

H

E

R≠H

59

O

O

20 mol% AgOTf 25 mol% phen

O

R3 R3

H

O

3 R3 R Z

Aziridination (A) O

R2

H •

R1

O O

R3

Insertion (I)

NH2 R3 59

AgOTf/phen (1 : 1.25)

R2

2 equiv. PhIO, 4 Å MS CH2Cl2, rt

R1

A:I = 1 : 13 to 1 : 76

N

O

H 3 3 60 R R Aziridination (A)

A:I = 3.7 : 1 to 20 : 1

Scheme 1.25 Silver-catalyzed nitrene transfer reaction. H

O PhI

PhI Singlet or triplet nitrene

Et

O

PhI

H Path B

Path A

Singlet nitrene Et H H

O O

Phen Ag Et

N

Ag OTf

Less steric congestion favors aziridination

N

N Ag

N

O

O H H

Et

H HN

O

N

OTf N N

O

O

N Ag

N

Steric congestion favors insertion

O

Et

Scheme 1.26 Proposed mechanisms for Ag-catalyzed divergent chemoselective amination.

21

22

1 Introduction to Silver Chemistry

or triplet nitrene intermediate or perhaps both (Scheme 1.26, Path B) because of the energy difference between these two states are very small. 1.3.13

Fluorination Reactions

The replacement of a hydrogen by fluorine in organic molecules leads to dramatic changes in their properties such as solubility, metabolic stability, and bioavailability [103]. Thus, the efficient strategies toward fluorinated compounds have attracted significant attention. It was observed from the literature database that the silver-catalyzed/silver-mediated approaches occupied a prime position for the synthesis of fluorine-containing molecules [104]. For instance, Liu and coworkers established a novel silver-catalyzed intramolecular aminofluorination of allenes 62 for the synthesis of 4-fluoro-2,5-dihydropyrroles 63 [105]. Particularly, AgNO3 resulted in remarkable catalytic reactivity in the aminofluorination of allenes using NFSI (N-Fluorobenzenesulfonimide) as a fluorine source. Moreover, the reaction was tolerant to various functional groups and substitution pattern. It should be noted that under the catalysis of palladium, no conversion was observed, indicating the critical role of silver(I) in the reaction outcome. The preliminary mechanistic study revealed that the reaction proposed to proceed via a vinyl silver intermediate 62-1, which reacts with NFSI, to afford the product with the regeneration of silver catalyst (Scheme 1.27). R2

R3 •

R1 NHTs

62

R2

NFSI (1.5 equiv.) AgNO3 (20 mol%)

R1

K2CO3 (2 equiv.), Et2O, rt

F R3 N Ts 63 Ag(I)

Ag(I)

R2

Ag(I) [Ag(I)]n

R2

Ag(II)F [Ag(II)]n

NFSI R1

R3 N Ts 62-1

R1

N Ts

R3 62-2

Scheme 1.27 Silver-catalyzed aminofluorination of allenes with NFSI.

In another example, Li and coworkers introduced a fluorine atom into the C(sp3 ) carbon via a silver-catalyzed decarboxylative fluorination of aliphatic carboxylic acids 56 using Selectfluor 64 as a fluorine source in aqueous conditions [106]. With 20 mol% of AgNO3 as catalyst, various aliphatic carboxylic acids smoothly underwent the decarboxylative fluorination to afford the corresponding fluoroalkanes 65 in high yields and excellent chemoselectivity. The reactivity of carboxylic acids decreases in the order of tertiary > secondary > primary ≫ aromatics. Based on their control experiment results, the authors proposed a radical mechanism as shown in Scheme 1.28. Formation of Ag(III)—F intermediate 64-1 via the oxidation of Ag(I) by Selectfluor was proposed as

References

R COOH 56

AgNO3 (20 mol%) Selectfluor (2 equiv.)

R F 65

Acetone/water (1 : 1) reflux or 45 °C, 10 h (or) H2O, 55 °C, 1–10 h

R F 65

Ag(I)

Cl

N N F

F Ag(II) R 64-2

CO2

64

F Ag(III) 64-1

R COOH 56

Scheme 1.28 Ag(I)-catalyzed decarboxylative fluorination of aliphatic carboxylic acids.

critical step, which then undergoes SET with carboxylate anion to produce Ag(II)—F 64-2 and carboxyl radical. The fast decarboxylation provides alkyl radical, which then abstracts fluorine atom from the Ag(II)—F to afford alkyl fluorides and regenerate the Ag(I) catalyst.

1.4 Summary This chapter provides a collective information concerning the history, features, chemistry, and applications of silver salts/silver nanoparticles. More importantly, the fundamental reaction involved in the catalysis of silver is described on the basis of key prominent mechanistic aspects. Knowledge of these fundamental reactions would be useful to understand and develop the catalytic new multistep transformations. As the purpose of this book is the catalysis of silver in organic transformations, the remaining chapters provide an overview of various silver salts/silver complexes/silver nanoparticle-catalyzed/mediated organic transformations with the scope of reactivity, selectivity, and also reaction mechanism.

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26 27

28

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33

2 Silver-catalyzed Cycloaddition Reactions Daesung Lee and Sourav Ghorai University of Illinois at Chicago, Department of Chemistry, 845 West Taylor Street, Chicago, IL 60607, USA

2.1 Introduction Cycloaddition reactions are one of the most powerful reactions in synthetic chemistry, and transition metal catalysts have played a crucial role to significantly broaden their scope. It is well documented that the thermally allowed cycloaddition reactions are significantly accelerated by transition metal-based Lewis acid. More importantly, numerous cycloaddition reactions that are not feasible under thermal conditions have been made possible by the use of transition metal complexes. Silver-catalyzed reactions constitute a subset of these metal-catalyzed cycloaddition reactions, which are invaluable tools in synthetic chemistry. Especially, the oxo- and azaphilic character of silver ion allows for the formation of robust chiral bidentate complexes, which could be reliably engaged in a variety of asymmetric transformations including cycloadditions [1]. The cycloaddition reactions wherein silver is used as a secondary catalyst along with other transition metals such as copper, rhodium, and gold are not included. Typical cycloaddition reactions involve total number of [4] or [6] electrons allocated in two reacting counterparts, which form a new ring through either an inter- or an intramolecular process. The traditional definition of cycloaddition is mainly mechanism based with the implication of concerted electron movement between the reacting counterparts following the Woodward–Hoffmann rules. However, the silver-catalyzed cycloaddition reactions delineated in this chapter are more broadly defined wherein [m+n] cycloaddition stands for any process that forms [m+n]-membered cyclic structures from two reacting counterparts with each [m] and [n] number of atoms, regardless of the reaction mechanisms. Thus, the reactions of tropone and fulvenes with azomethine ylides are classified as [3+3] rather than [6+3] cycloaddition, and ring-forming reactions that occur through multistep processes are also included. The classification of reaction types follows the [m+n] definition in the order of [3+2], [2+2], [3+3], [4+2], [2+2+1]. Other ring-forming reactions outside of these categories such as [2+1] and [4+1] are categorized miscellaneous, which are summarized at the end.

Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

34

2 Silver-catalyzed Cycloaddition Reactions

2.2 [3+2] Cycloadditions 2.2.1

Cycloaddition of Azomethine Ylides

Azomethine ylides are nitrogen-based 1,3-dipoles, which are represented as the most common resonance form with an iminium ion and a carbon-centered anion next to it [2]. Structurally, azomethine ylides can assume four different forms (W shape, U shape, and two different S shapes), which are directly related to the stereochemistry of the cycloaddition products. Azomethine ylides are generated in situ from various precursors in the presence of dipolarophiles such that immediate reaction occurs upon their formation. The dipolar cycloaddition of azomethine ylides involves 6-π-electrons; thus the addition process is suprafacial following the Woodward–Hoffmann rules. Considering the frontier molecular orbital theory, the dominant interaction in the dipolar cycloaddition will involve the HOMO of electron-rich azomethine ylides with the LUMO of the π-system of the reacting dipolarophiles. Thus, most examples of the silver-catalyzed cycloadditions described in this section involve electron-deficient alkenes reacting with silver-complexed azomethine ylides in situ generated from imine precursors [3]. An early example of silver-promoted [3+2] cycloaddition of azomethine ylides was reported by Grigg and Gunaratne in 1982. The thermal reaction between methyl propiolate and arylidene imine 1 was slow (t 1/2 = 38 h) albeit cycloadduct 2 was obtained in high yield (Scheme 2.1) [4, 5]. On the other hand, the same reaction in the presence of AgOAc (1.5 equiv.) proceeded with a remarkably increased rate, which is presumably the consequence of facile formation of a putative silver ion-chelated dipole 3 under the conditions. MeO2C

AgOAc (1.5 equiv.)

MeO2C Ph

Ph Ph

N 1

Toluene, 80 °C CO2Me t1/2 = 3.3 h 95%

Ph

N H 2

CO2Me

Ph

OMe

N O

Ag 3

Scheme 2.1 An early example of a silver-promoted azomethine ylide cycloaddition.

Subsequently, it was found that a catalytic amount of a silver additive was sufficient for 1,3-dipolar cycloadditions of azomethine ylides. As an example, in the presence of AgOAc, arylidene imines 4 smoothly reacted with chiral α,β-unsaturated ketones to afford fully substituted pyrrolidines 5a and 5b with excellent diastereoselectivity (Scheme 2.2) [6, 7]. Although LiBr promoted this transformation, better selectivity was observed with AgOAc/DBU. The highest selectivity was observed with α,β-unsaturated ketones containing a bulky dibenzylamino, benzyloxy, or free hydroxyl substituent at the γ-position. Lowering the reaction temperature (−78 ∘ C) further improved the selectivity. In 2001, Subramaniyan and Raghunathan demonstrated the effectiveness of Pätzel’s catalytic protocol for the preparation of highly substituted spiropyrrolidines (Scheme 2.3) [8]. Employing AgOAc (15 mol%) and Et3 N at ambient temperature, spiropyrrolidines 8 were generated efficiently from glycine-derived azomethine ylides 6 and (E)-3-arylidene-chroman-4-ones 7. The observed

2.2 [3+2] Cycloadditions

O R*

CH3 N

EtO2C

R*

AgOAc (15 mol%) DBU, THF, rt, 2–8 h

EtO2C

78–96%

Ph

4 O

O

O

R* = 5a:5b

HO

O

R*

COCH3 Ph

N 5a H

COCH3

EtO2C 5b

NBn2

OBn

Ph

N H

NBn2 Bn

95 : 5

92 : 8

>95 : 5

>95 : 5

>95 : 5

Scheme 2.2 Diastereoselectivity in azomethine ylide cycloadditions. R2

O

O

6

O

69–85% N

R1

AgOAc (15 mol%) Et3N, CH3CN, rt, 2–4 h

7

N H

CO2Me R1

R1 = H, Cl, OMe R2 = H, Cl, OMe, Me, NO2

R2

O

CO2Me

8

Scheme 2.3 Substituted spiropyrrolidines from azomethine ylide cycloadditions.

syn–endo stereochemistry of cycloadduct 8 is the consequence of well-defined geometry of both the putative silver ion-chelated azomethine ylides and the enone substrates. The synthesis of spirooxindoles through a cascade Pd(OAc)2 /PPh3 -catalyzed intramolecular Heck reaction followed by a Ag2 O-promoted cycloaddition of azomethine ylides was reported by Grigg et al. (Scheme 2.4) [9]. The in situ generated α-methylene oxyindole 9 reacted with azomethine ylides derived from the corresponding aldimine precursors in the presence of Ag2 O/DBU at ambient temperature, delivering spiropyrrolidines 10 in 59–68% yield. Although it is expected that the silver ion-chelated syn-dipole 11a is more favorable than anti-dipole 11b, the X-ray structure of the major diastereomer corroborates the stereochemistry derived from anti-dipole 11b. Me N I

R1

Me N

O Pd(OAc) 2

O

PPh3, K2CO3

OMe O

N R

Ag

11a syn-Dipole

MeO2C

R1

N Ag 11b anti-Dipole

R

N

Me N

CO2Me

Ag2O (10 mol%) DBU, CH2Cl2, rt 59–68%

9 R1

R

O R1 10 R

N H

CO2Me

R = 3-Py, Ph R1 = CH2OH, CH2Ph, Bn-4-OH, Me

Scheme 2.4 Cascade Heck and Ag2 O-promoted azomethine ylide cycloadditions.

35

36

2 Silver-catalyzed Cycloaddition Reactions

Alternatively, spiropyrrolidines could be generated from cyclic 1,3-dipoles and acyclic dipolarophiles (Scheme 2.5) [10]. Adimines 12 derived from homoserine lactone or homocysteine thiolactone reacted with methyl acrylate in the presence of Ag2 O (10 mol%) and base (Et3 N or DBU) to afford spiropyrrolidines 14 in moderate to good yields. The stereochemistry of 14 suggests the involvement of a silver ion-chelated azomethine ylide 13 as a putative 1,3-dipole. For the reaction of arylidene imines, stoichiometric AgOAc (1.5 equiv.) was more effective than catalytic Ag2 O (10 mol%). O N

X

R

12

Toluene, 25 °C

Ag

O

X = O, S R = Aryl, Alkyl

Ag2O (10 mol%) Et3N (1.1 equiv.)

CO2Me

X

R

N

X

CO2Me

O

R

N H 14

X = O (26–89%) X = S (34–64%)

13

Scheme 2.5 Spiropyrrolidines from Ag-chelated azomethine ylide cycloadditions.

In 2002, Zhang and coworkers demonstrated highly enantioselective 1,3dipolar cycloadditions of azomethine ylides catalyzed by AgOAc and a chiral ligand 15 (Scheme 2.6) [11]. By employing this catalytic system, a variety of tetrasubstituted pyrrolidines 16 were generated in good yield and excellent enantioselectivity. Also, a fused bicyclic pyrrolidine 17 was generated in 87% yield and 99% ee employing N-methylmaleimide as a dipolarophile.

O

Me N

MeO2C R

O

O

CO2Me N

CO2Me

Fe

H N PAr2

HN

O

15 Ar2P Ar = 3,5-Me2Ph

AgOAc, i-Pr2NEt Toluene, rt

R = i-Pr, Ph, c-Hex, 2-Naph, 4-F-Ph

Fe

MeO2C

CO2Me

O

Me N

H

O H

R CO2Me R CO2Me N N 16 H 17 H 73–98% 87% (70–97% ee) (99% ee)

Scheme 2.6 Enantioselective azomethine ylide cycloadditions for tetrasubstituted pyrrolidines.

Relying on (S)-BINAP-based catalyst 18, significantly improved enantioselectivity was realized for bicyclic pyrrolidine 19 (Scheme 2.7) [12]. Other catalysts generated in situ by mixing BINAP and silver salts such as AgOAc, AgOTf, and AgF were also found to be effective. In silver-catalyzed cycloaddition reactions of azomethine ylides, (S)-QUINAP (20a) has shown a high degree of control over both diastereo- and enantioselectivity to generate trisubstituted pyrrolidines 21 (Scheme 2.8) [13]. A notable feature of this catalytic system is that the cycloaddition reaction could be performed at relatively low temperature (−45 ∘ C) with low catalyst loading (1 mol%). Similar yield and enantioselectivity were obtained with slightly different ligand (S)-PINAP (20b) [14].

2.2 [3+2] Cycloadditions

Me N

O

Ar

Ph P Ph Ag ClO4 P Ph Ph 18 (5 mol%)

O

N

Me N

O H

H

Ar

CO2Me

N H

Et3N (5 mol%) Toluene, rt, 16 h

CO2Me

O

19

Ar = Ph, 2-Naph, 2-Cl-Ph, 4-MeO-Ph

endo/exo >98 : 2 82–90% (64–99% ee)

Scheme 2.7 Enantioselective azomethine ylide cycloadditions with Ag-BINAP.

t-BuO2C + MeO C 2 N

i-Pr2NEt, THF –45 °C, 20 h X

X X = MeO, Br, CN

Ph

O

t-BuO2C

AgOAc (3 mol%) 20a (3 mol%)

CO2Me N H 21 89–95% (89–96% ee)

N N

N

PPh2

PPh2 20a (S)-QUINAP

20b (S)-PINAP

Scheme 2.8 Enantioselective azomethine ylide cycloadditions with Ag-QUINAP.

In 2010, Kobayashi and coworkers demonstrated an exo-selective [3+2] cycloaddition of azomethine ylides derived from α-aminophosphonates 22 by employing (R)-DTBM-SEGPHOS 23 (Scheme 2.9) [15]. This unprecedented chiral silver amide-catalyzed reaction could generate a wide range of optically active proline derivatives 24 containing a phosphonate moiety. Electron-deficient dipolarophiles provided the cycloadduct in excellent yield with high diastereoand enantioselectivity. R2

R1

R2

AgOTf (3 mol%) KHMDS (3 mol%), Toluene, 25 °C, 2 h N 22

P O

OEt OEt

23 (3 mol%) (R)-DTBM-SEGPHOS Ar = 3,5-t-Bu2-4-MeO-C6H2

R1 = Ph, 4-Me-Ph, 4-MeO-Ph, 4-F-Ph R2 = CO2t-Bu, CO2Me, COMe, CN

O O

PAr2

O

PAr2

R1

P(OEt)2 O exo/endo >99 : 1 56–99% (82–99% ee) N 24 H

O

Scheme 2.9 Enantioselective azomethine ylide cycloadditions with Ag-DTBM-SEGPHOS.

Wang and coworkers also observed exo-selectivity in the [3+2] cycloaddition of alkylidene malonates 25 under silver-catalyzed condition in the presence of a P,N-bidentate ligand (S)-TF-BiphamPhos 26 (Scheme 2.10) [16, 17]. High

37

R1

t-BuO2C t-BuO2C 25 R2

AgOAc (3 mol%) K2CO3 (2 equiv.), CH2Cl2, rt, 3–5 h 26 (3 mol%) CF3 Br

R3 N

CO2Me

R1 = Ph, p-MeO-Ph, p-Br-Ph Et, Bu, i-Bu R2 = Ph, Cy, Ar, Naph R3 = H, Me

R2 MeO2C

N

R1 = Aryl, Cinnamyl, n-Bu R2 = Me, Et, n-Bu, i-Bu, Bn

N R3 H 27 exo-Adduct 18–98% (72–99% ee)

CF3 E (CO2tBu) 2 R3 Br R N R1 H E N Ag O OMe F3C H F3C N P H Br TS-27 CF3

(S)-TF-BiphamPhos Br CF3 O

R1

Crucial hydrogen bonding

CO2Me

R2

NH2 NHPPh2

F3C F3C

R1

t-BuO2C t-BuO2C

t-Bu

AgOAc (3 mol%) 26 (3 mol%)

N O

28

CH2Cl2, rt, 3–5 h 86–99% (90–99% ee)

Scheme 2.10 Enantioselective azomethine ylide cycloadditions with Ag-TF-BiphamPhos.

MeO2C H R2 HN R1 H

O t-Bu N O

29

2.2 [3+2] Cycloadditions

conversion and regioselectivity was observed irrespective of the electronic character of the substituents on azomethine ylides and alkylidene malonates. The observed exo-selectivity can be justified a putative transition state TS-27. This protocol has been extended to atroposelective desymmetrization of prochiral N-(2-t-butylphenyl) maleimide 28. Under standard condition, highly enantioselective 1,3-dipolar cycloaddition between maleimide and azomethine ylide occurred to afford octahydropyrrolo[3,4-c]pyrroles 29 with four adjacent stereogenic centers and a N–C chiral axis. Because of the geometrical requirement of hydrogen bonding shown in the transition state TS-27, cyclic dipolarophiles such as maleimide generate endo-product 29. A catalytic system involving AgClO4 complexed with Feringa’s phosphoramidites 30 was found to be effective for enantioselective [3+2] cycloaddition of azomethine ylides (Scheme 2.11) [18, 19]. Azomethine ylides derived from glycine, alanine, leucine, and phenylalanine provided cycloadducts, including 31 in good yields with excellent enantioselectivity (>99 : 1 er), which can be justified by a putative transition state TS-31. Pyrrolidine 31 served as an intermediate for the synthesis of prolinamide 32, an inhibitor of hepatitis C virus polymerase.

t-BuO2C CO2Me N

AgClO4 (5 mol%) Et3N, toluene, –20 °C, 17 h 30 (5 mol%)

t-BuO2C

O O

CO2Me N H 31

S

i-Bu

S

Ph

i-Bu

70% (82% ee)

Ph P N

HO2C

Ph OMe O Ar P Ag O N H O O H TS-31 OMe N

i-Bu

Ph

CO2H

N S Prolinamide O

Ph-4-CF3 32

Scheme 2.11 Enantioselective azomethine ylide cycloadditions with Ag-Feringa phosphoramidite.

In 2005, Pfaltz and coworkers reported a silver-based catalytic system for intramolecular azomethine ylide-mediated [3+2] cycloaddition reactions (Scheme 2.12) [20]. From an activity-guided screening process, phosphinooxazoline (PHOX) 34 was identified as the most effective ligand to generate a product with high yield and enantioselectivity. Under optimized condition, Ag(I)-PHOX complex (3 mol%) promoted intramolecular cyclization of imine 33 to generate tricyclic products 35 containing four contiguous stereogenic centers with excellent enantioselectivity (up to 99% ee). O

33 R1 = CO2Me, H R2 = Me, H

O

Ag(OAc) (1–3 mol%) Toluene, 0 °C, 6 h 34 (1–3 mol%)

N

CO2Me

R2

R1

O Ph

(o-Tol)2P

N

PHOX

Ph

H H

CO2Me NH

61–74% (83–99% ee)

R2

R1 35

i-Pr

Scheme 2.12 Enantioselective azomethine ylide cycloadditions with Ag-PHOX

39

40

2 Silver-catalyzed Cycloaddition Reactions

Zhou and coworker employed ferrocenyloxazoline-based N,P-ligand 36 to achieve the highly stereoselective 1,3-dipolar cycloaddition of azomethine ylides (Scheme 2.13) [21]. With this catalytic system, external base was not required for the formation of a silver ion-ligated azomethine ylide, presumably because acetate was involved in the deprotonation step. With this protocol, various optically active fully substituted pyrrolidines 37 were obtained. MeO2C

CO2Me

R

CO2Me

N

AgOAc (3 mol%) Et2O, –25 °C, 3–20 h 36 (3.3 mol%) O

R

Bn N P(4-F CC Fe 3 6H4)2

R = 4-Cl-Ph, 4-CN-Ph 1-Napthyl, i-Pr

MeO2C

CO2Me N H 37

CO2Me

56–99% (88–98% ee)

Scheme 2.13 Enantioselective azomethine ylide cycloadditions with Ag-ferrocenyloxazoline.

It was found that silver-complexed ferrocenyl N,P-ligands 38a (R = Me) and 38b (R = H) containing the common chirality source but differing by the steric factors and hydrogen bonding capability could generate the opposite enantiomers of pyrrolidine 39 (Scheme 2.14) [22]. While the steric hindrance of dimethylamino group directs the approach of dimethyl maleate from the α-face at the transition state (TS-39a) leading to product 39a, the hydrogen bonding interaction between NH2 moiety with the two carbonyl groups of dimethyl maleate favors the β-face approach (TS-39b), providing the opposite enantiomer 39b. These transition state models were further supported by theoretical calculations. MeO2C

CO2Me +

p-ClC6H4

N

CO2Me

Me N Me Ar2P Ag N O MeO O TS-39a O

AgOAc (3 mol%) MeO2C CO2Me L* (3.3 mol%) Et2O, –25 °C PAr2 CO2Me p-ClC6H4 N NR2 H 39a,b L* = Fe 38a, R = Me 95% (–92% ee) 38b, R = H 90% (92% ee)

(Ar = 3,5-Me2C6H3) Ar OMe

OMe

39a

H O OMe N H O Ar Ar2P Ag N OMe O TS-39b OMe

39b

Scheme 2.14 Enantioselective azomethine ylide cycloadditions with Ag-ferrocenyl N,P-ligands.

Fukuzawa and coworkers introduced ThioClickFerrophos (TCF) 40, a ferrocene-based bidentate P,S-ligand, for asymmetric [3+2] cycloaddition between alkyl or arylidene malonate and azomethine ylides derived from glycine imino ester (Scheme 2.15) [23]. This catalytic system, which does not require

2.2 [3+2] Cycloadditions

E Ar

E

E

AgOAc (5 mol%) Et2O, rt, 15 h

Ar

E

R1 CO2Me 40 (5.5 mol%) N 41 H R1 N CO2Me Me N N E = CO2Et 60–99% N R1 = Aryl or c-Hex Ph PPh (87–99% ee) 2 Ar = Ph, Tol, 2-MeO-Ph Fe St-Bu 4-CF3-Ph, 4-Cl-Ph t-Bu-TCF

N N

N

Ph t-Bu

S Ph Ag Fe P Ph O TS-41 MeO

Ar

E

N E Ar

Scheme 2.15 Enantioselective azomethine ylide cycloadditions with Ag-ThioClickFerrophos.

external base, generated highly functionalized pyrrolidine derivatives 41 with high levels of regio- (only exo-cycloadduct) and enantioselectivity (87–99% ee), via the transition state TS-41. This protocol was further extended to the reactions of nitroalkenes with the same levels of efficiency and selectivity [24]. Relying on a ferrocene-based ligand Taniaphos 43, Adrio and Carretero developed efficient 1,3-dipolar cycloaddition reactions of α-iminonitriles 42 with dimethyl fumarate or N-methylmaleimide, providing 2-cyanopyrrolidinines 44 (Scheme 2.16) [25]. Under optimized condition, endo-cycloadducts were obtained as the major product, and highest endo-selectivity was achieved when ketimines were employed as azomethine ylide precursors. The stereochemical outcome can be explained by the transition state TS-44 where the front face of the silver-coordinated azomethine ylide is more exposed to interact with the incoming dipolarophile. MeO2C R R1

2

CO2Me AgOAc (10 mol%) Et2O, rt, 24 h

N CN 42 R1 = Ar, CH=CH-Ph R2 = H, Ph, 4-F-Ph

MeO2C

43 (11 mol%) PPh2 Taniaphos

Me2N

Fe

PPh2

R2

CO2Me

CN N H 44 endo/exo 75 : 25 to 93 : 7 (68–99% ee) R1

Ph PPh2 P Ag Ar Ph N Fe NMe2NC TS-44

E

E

Scheme 2.16 Enantioselective azomethine ylide cycloadditions with Ag-Taniaphos.

In 2005, Jørgensen and coworkers reported that cinchona alkaloids could mediate the asymmetric 1,3-dipolar cycloaddition of azomethine ylide with alkyl acrylate to afford chiral pyrrolidines 46 (Scheme 2.17) [26]. The combination of AgF with hydrocinchonine 45 was the choice of catalyst whereby cycloadducts 46 were generated with moderate enantioselectivity. In terms of mechanism, upon forming silver complex the substrate imine would be deprotonated by hydrocinchonine to generate azomethine ylide, which exists in chiral ion-pair environment, leading to stereoinduction. Recently, new cinchonidine-based pseudo-enantiomeric amidophosphine ligands 47 were developed for 1,3-dipolar cycloaddition of azomethine ylide (Scheme 2.18) [27]. As expected, silver-complexed pseudo-enantiomeric ligands 47-S and 47-R afforded pyrrolidines 48 in high yield with opposite chirality. A cooperative mechanism is suggested for the reaction with ligands 47-S and

41

42

2 Silver-catalyzed Cycloaddition Reactions

R1

R1

45 (5 mol%)

CO2R2

N

R3O2C

AgF (5 mol%) CH2Cl2, –24 °C, 4 d

R3O2C

HO

R1 = 4-Me-Ph, 4-Br-Ph 2-Naph, 2-Furyl R2, R3 = Me, t-Bu

46 N

63–97% (41–73% ee)

H

N

CO2R2

N H

Hydrocinchonine

Scheme 2.17 Enantioselective azomethine ylide cycloadditions with Ag-hydrocinchonine. R1O2C

CO2R1 R3

R2

N

R1O2C

Ag2CO3 (2 mol%) 47-S or 47-R (4 mol%)

R3 R2

Toluene, rt, 2–4 h CO2Me

R1 = Me, Et R2 = Ph, 4-MeO-Ph, 4-Cl-Ph R3 = H, Me, 3-Indolylmethyl O 47-S

CO2Me

N 48 H

47–99% (86–96% ee)

N N

CO2R1

N H HN N

NH H N O

Ph2P

PPh2

O

N

O 47-R

Scheme 2.18 Enantioselective azomethine ylide cycloadditions with Ag-cinchona alkaloid derivatives.

47-R wherein the tertiary amine accelerates the reaction by deprotonating the azomethine ylide precursor and the two amides serve as H-bond donors interacting with substrates while the amidophosphane forms a chelate with silver ion. In 2016, Xu and coworkers employed chiral sulfinylimine-containing nonbiaryl atropisomers of tertiary amide in endo-selective silver-catalyzed 1,3-dipolar cycloaddition of azomethine ylide (Scheme 2.19) [28]. In the presence of axially chiral ligand syn-(R,RS )-49 (Xing-Phos), highly enantioselective reaction was achieved with N-aryl maleimide as dipolarophile. Ar2 N

O

O

AgF (2.5 mol%) H2O, Toluene, –20 °C, 10 h

O

49 (5.5 mol%) t-Bu Ar1

N

CO2Me

Ar1 = Ph, 2-MeO-Ph, 3-Br-Ph 4-Me-Ph, 4-F-Ph Ar2 = Ph, 3-Cl-Ph, 3-Me-Ph 3-Br-Ph, 4-MeO-Ph

Ph

O

H

Ar2 N

O H

1

Ar

S NH O Ni-Pr2 PPh2

CO2Me N H endo:exo >98 : 2 3–99% (65–98% ee)

Scheme 2.19 Enantioselective azomethine ylide cycloadditions with Ag-sulfinylimine.

2.2 [3+2] Cycloadditions

As a surrogate of oxygen-substituted dipolarophile, boron-containing alkene such as (E)-β-B(dam)acrylates 50 was employed in the cycloaddition of azomethine (Scheme 2.20) [29]. Under optimized conditions, 1,8-diaminonaphtalene (dam) derivative 50 afforded boron-containing pyrrolidine 51 in moderate to good yield. This protocol with DTBM-SEGPHOS as a chiral ligand afforded pyrrolines with 60% ee. 3-Borylpyrrolidine 51 could be easily transformed into 3-hydroxy pyrrolidine 52 through transesterification with pinacol followed by oxidation. MeO2C

B(dam)

50 R2 R1

N

CO2Me

AgOAc (10 mol%) dppe (10 mol%) LiHMDS (30 mol%) Toluene, rt, 10 min–3 h 27–98%

MeO2C R1

B(dam) R2

N 51 H

CO2Me 1. CbzCl, Et3N MeO2C 2. pinacol, 2 M H2SO4

R1 = Ph, 2-MeO-Ph, Thienyl R2 = H, Me HN B(dam) = B HN

R1

3. H2O2/NaOH 68–83%

OH

R2 N CO2Me 52 Cbz

Scheme 2.20 Azomethine ylide cycloadditions with a boron-containing alkene.

The efficient synthesis of trifluoromethylated pyrrolidines by silver-catalyzed 1,3-dipolar cycloaddition was reported by employing N-(2,2,2-trifluoroethyl) imines 53 and electron-deficient dipolarophiles including N-methylmaleimide, generating pyrrolidines 54 (Scheme 2.21) [30]. The chelating ability of an ester or pyridyl group in imine with silver ion expedites the formation of the corresponding azomethine ylides. High conversion rate and excellent diastereoselectivity was observed with AgOAc/PPh3 in tert-butyl methyl ether at ambient temperature. Using ferrocenyl bisphosphine ligand Taniaphos 43, trifluoromethylated pyrrolidine 54a was obtained in 91% ee. Me F3C

N 53a

F3C

N 53b

CO2Me Me N

AgOAc/PPh3 (10 mol%)

(Ph)3P Ag N F3C

O OMe

Me Cs2CO3 (20 mol%) (Ph)3P Ag N t-BuOMe, rt, 23 h N F3C Me

O

Me N

O

O

Me N

Me

O H

CF3 N R 54a, R = CO2Me H 83% (>20 : 1 dr) 91% ee of 54a 54b, R = Pyridyl 88% (20 : 1 dr) with Taniaphos (43)

Scheme 2.21 Azomethine ylide cycloadditions for trifluoromethylated pyrrolidines.

Three-component coupling of aldehydes, amines, and electron-deficient alkenes is a common protocol for pyrrolidine synthesis. Garner and Kaniskan developed effective cascade reactions catalyzed by AgOAc/PPh3 , generating regioisomers of endo-cycloadducts 55a and 55b (Scheme 2.22) [31]. This silver-catalyzed cascade reaction was further extended to a highly diastereo- and enantioselective [3+2] cycloaddition of azomethine ylides by employing the Oppolzer’s sultam as a chiral auxiliary (Scheme 2.23) [32, 33]. The in situ generated azomethine ylide derived from glycyl sultam 56 provided fully substituted pyrrolidines 57 with excellent diastereoselectivity via the transition

43

44

2 Silver-catalyzed Cycloaddition Reactions

CO2Me

AgOAc (10 mol %) PPh3 (20 mol%)

CO2Me H2N

RCHO

MeO2C

CO2Me

R

THF, rt, 1–12 h

CO2Me R = Ph, Cinnamyl, Ph(CH2)2, n-Bu, BocNHCH2

CO2Me CO2Me

N H

R

CO2Me CO2Me

N H

55a

55b

48–95%

0–17%

Scheme 2.22 Cascade protocol for azomethine ylide cycloadditions. MeO2C

O N

H2N RCH2OH R = n-Bu, i-Pr, BnOCH2, Ph(CH2)2

BocHN

O S O

(Gly–Xc)

H MeO2C

58 +

OMe OBn

ent-Gly–Xc (ent-56)

CO2Me AgOAc (5 mol%) 74%

H XcOC

N H

N H 57

H H N N Ag O O S H CO2MeO

R

Me H N O

MeO2C Boc Me

BocHN

R

CO2Me

XcOC

58–94% TS-57

56

OMe

OHC

MeO2C

AgOAc (5 mol%) THF, rt, 2 h–overnight

CO2Me

NH

N H

OMe Me

HN Boc 59

H

O

OMe

H O

MeO

OBn

H N

O

Me Bioxalomycin b2

Scheme 2.23 Dia- and enantioselective azomethine ylide cycloadditions employing Oppolzer’s sultam.

state TS-57. Exploiting this protocol, a formal total synthesis of bioxalomycin β2 was accomplished starting from aldehyde 58 and glycyl sultam ent-56 through pyrrolidine intermediate 59. Diastereoselective 1,3-dipolar cycloaddition of azomethine ylides was reported based on (S)- and (R)-lactate as a chiral auxiliary (Scheme 2.24) [34]. The reactions of (S)-lactate-derived acrylate 60 with arylidene imines in the presence of catalytic amounts of AgOAc/base afforded endo-isomer 61 as the major product with high diastereoselectivity. O

R1 Ar

N

O MeO2C CO2R2

Ar = Ph, 2-Naph R1 = H, Me, i-Bu, Bn R2 = Me, i-Pr, t-Bu

O

60

AgOAc (10 mol%) KOH/Et3N (10 mol%) Toluene, rt, 1 d

MeO2C

O 61

32–73% Ar (86–99% de)

R1 N H

CO2R2

Scheme 2.24 Diastereoselective azomethine ylide cycloadditions employing lactate.

A sulfinyl group was used as a chiral auxiliary for diastereoselective 1,3-dipolar cycloaddition of azomethine ylides (Scheme 2.25) [35, 36]. α-Sulfinylated acrylate 62 and cyclopentenone 63 could undergo cycloaddition at relatively low temperature in the presence of AgOAc/DBU, generating pairs of cycloadducts 64a/64b and 65a/65b, wherein the endo-isomer was major. The ratio of products was

2.2 [3+2] Cycloadditions AgOAc (15 mol%)

O S Tol CO2Me

62

MeO2C N

Naph

DBU (1.2 equiv.) MeO2C N THF,rt 64a H AgOAc (7.5 mol%)

O O S 63

Tol(O)S CO Me 2

DBU (0.6 equiv.) Tol CH3CN, 0 °C

S(O)Tol

MeO2C N 64b H 57% (90 : 10) O

Naph

O H

Tol(O)S

MeO2C

Naph

H

Tol(O)S Naph N 65b H 73% (58 : 42)

CO2Me

Naph N 65a H

CO2Me

Scheme 2.25 Sulfinyl chiral auxiliary-based diastereoselective cycloadditions of an azomethine ylide.

dependent on various factors, such as loading of catalyst, base, solvent, and temperature. Optically pure dihydro- and tetrahydropyrrole derivatives were generated via desulfurization under pyrolytic or hydrogenolytic conditions. Bioactive pyrrolidines 68, which perturb the integrin-mediated adhesion of melanoma cell to endothelium of metastasized organs, could be prepared by silver-catalyzed 1,3-dipolar cycloaddition (Scheme 2.26) [37]. It is proposed that the cycloaddition between nitroalkenes 66 and chiral imines 67 proceeds through a more favorable transition state TS-68a than the other diastereomeric TS-68b, providing the observed products 68 [38]. Grigg observed that the cycloaddition between nitroolefins and azomethine ylides catalyzed by Ag2 O generated a mixture of endo/exo-cycloadduct (2 : 1–5 : 1) with moderate to excellent yield. Me O2N

R1 OR2

66

R1 = Me, Et R2 = Ph, 2-F-Ph 3,5-F2-Ph

R1

R4 R3

N 67

CO2CH3

R3 = Ph, t-Bu, c-Hex R4 = H, Me R2O

AgOAc (10 mol%) Et3N, CH3CN, rt, 5 h 60–92%

H s R

OR2 R4

R3

R s H

Me O2N H N H 68

CO2CH3

OR2

N O vs O N O O R4 R4 3 N N R R3 OMe MeO Ag Ag O O TS-68a TS-68b (0.0 kcal mol−1) (1.2 kcal mol−1)

Scheme 2.26 Ag-catalyzed diastereoselective cycloaddition of nitroalkenes with azomethine ylides.

Wu and coworkers reported diastereoselective 1,3-dipolar cycloaddition reactions between azomethine ylides and fluorinated imines 69, generating fluorinated tetrahydroimidazole derivatives 70 (Scheme 2.27) [39]. In this reaction, AgOAc was found to be superior to AgOTf, Ag2 SO4 , AgNO3 , and Ag2 CO3 . The unusual 2,5-trans-stereochemical relationship in tetrahydroimidazole 70 is rationalized by the transition state TS-70 where the Ag+ -coordinated azomethine ylide assumes an S shape rather than a seemingly more favorable U shape.

45

46

2 Silver-catalyzed Cycloaddition Reactions

Ar

Rf

N

PMP

PMP AgOAc (5 mol%) THF, rt, 24 h

69 N

CO2Me

42–96% up to 20 : 1 dr

PMP

N

Rf N

Ar

Rf = CF3, CF2Br Ar = Aryl, 2-Furyl, 2-Thienyl, 2-Naph

CO2Me N TS-70 Ag Transition state with S-shaped ylide

CO2Me

N H

CF2Br

Ph

70

Scheme 2.27 Cycloadditions of azomethine ylides with fluorinated imines.

The enantioselective homodimerization of glycine-derived azomethine ylides was promoted by silver-complexed ligand 49 (Xing-Phos) (Scheme 2.28) [40]. The choice of base was crucial for high diastereo- and enantioselectivity. Under optimized conditions, tetrahydroimidazoles 71 were obtained in good yield with excellent diastereo- and enantioselectivity. A general trend of the selectivity depending on the R-substituent was observed. For example, products 71 with a 3-substituent were generated with relatively low diastereoselectivity, whereas products with a 4-substituent showed the opposite trend (>95 : 5 dr).

N

MeO2C

R N

CO2Me

AgOAc (2.5 mol%) MeO2C Xing-Phos 49 (5 mol%) Na2CO3 (10 mol%) EtOAc, –20 °C, 24 h

N H

R

R R = H, 3-F, 3-Cl, 3-Br, 3-Me, 3-OMe 4-F, 4-Cl, 4-Br, 4-OMe, 4-CF3, 4-Me, 4-SiMe3

R N CO2Me 71

61–96% Up to 20 : 1 dr and 98% ee

Scheme 2.28 Enantioselective homodimerization of azomethine ylides with Ag-Xing-Phos.

In 2004, Tepe and coworker reported a silver-catalyzed exo-selective [3+2] cycloaddition between azalactones 72 and electron-deficient olefins such as N-phenyl maleimide, diethyl fumarate, and diethyl malonate, producing Δ1 -pyrrolines 74 in moderate to good yield (Scheme 2.29) [41]. In the presence of AgOAc, an amino acid-derived azalactone is transformed into a münchnone intermediate 73, which participates in the cyclization. Unusual exo-selectivity was observed due to the anti-conformation of münchnones 73 as opposed to the syn-conformation of acyclic azomethine ylides, which produce endo-cycloadducts. O

O

AgOAc (10 mol%)

O R1

N

R2

THF, rt

72

R1 = Me, Ph, Bn R2 = Me, Ph, Bn, 3-Indolylmethyl R3 = CO2Me, CO2Et; R4 = H, CO2Et

O R1

R3

N

R2

Ag 73 Münchnone

R4

Then Me3SiCHN2

R3 R1

R4

CO2Me N R2 74 15–95%

Scheme 2.29 Exo-selective cycloaddition of azalactones with electron-deficient olefins.

2.2 [3+2] Cycloadditions

2.2.2

Cycloaddition of 2-Isocyanoacetates

Schörkopff and Porsch pioneered the cyclization reactions of 2-isocyanoacetate [42], and Ito et al. broaden the scope of the reaction by accommodating asymmetric transition metal-catalyzed protocols in 1986 [43]. Since then cyclization reactions involving 2-isocyanoacetate have become an important synthetic tool for nitrogen-containing heterocycles. However, the silver-catalyzed cycloaddition of 2-isocyanoacetates constitutes a minor subset of this class of reactions, and a relatively small number of examples are reported in the literature. In 1991, Ito and coworkers reported one of the earliest silver-catalyzed cyclization reactions of 2-isocyanoacetate and aldehydes to form chiral oxazoline derivatives 76 (Scheme 2.30) [44]. With the silver complex of chiral ligand 75, trans-oxazolines 76 were generated predominantly in good yield and enantioselectivity. AgClO4 (2 mol%) ClCH2CH2Cl, 30 °C, 1 h

R CHO C

75 (2 mol%)

CO2Me

N

NMe N Fe PPh2

CO2Me

R

trans/cis Yield (%) ee (%) R 90 80 96/4 Ph 91 90 99/1 i-Pr 90 88 99/1 t-Bu 90 87 CH2 CMe 97/3

N

O 76

PPh2

Scheme 2.30 Ag-catalyzed reactions of 2-isocyanoacetate and aldehydes.

Silver ion complexed with cinchona-derived phosphine ligand 78 was found to be an effective catalyst for asymmetric cyclization of isocyanoacetate with ketones (Scheme 2.31) [45]. Under optimized conditions, polysubstituted transoxazolines 77 were obtained as the major product via the transition state TS-77. In general, poor enantioselectivity was observed with aliphatic ketones. This catalytic system was further extended to the synthesis of pyrrolines from isocyanoacetate and α-thioacrylates [46].

CN

Ag2O (2.5 mol%), 78 (5 mol%) 4 Å MS, AcOEt, –20 °C, 72 h

O

O OR1

R2

R1 = Me, Et, t-Bu R2 = Me, Et, Pr, CH2iPr R3 = Ph, 4-Me-Ph, 4-Br-Ph 4-NO2-Ph, 4-CN-Ph Pyrazin-2-yl 5-Br-Thiophen-2-yl MeO2C

O CN

OMe

R3 R2 O H N OMe O Ag C N N PPh2

R3

t-BuS

Ar O

Ag2O (10 mol%) 78 (20 mol%) CHCl3, –20 °C 80%

R2

R3

CO2R1 N

O 77

55–84% 84 : 16–96 : 4 dr

N

(88 : 12–99 : 1 er)

TS-77

MeO2C

OMe

NH PPh2 N

St-Bu

O 78

CO2Me N 86 : 14 dr (99 : 1 er for trans)

Scheme 2.31 Ag-catalyzed asymmetric cyclization of isocyanoacetate with ketones.

47

48

2 Silver-catalyzed Cycloaddition Reactions

Grigg et al. reported the silver-catalyzed reaction between 2-isocyanoacetate and electron-deficient olefins, which proceeded in stepwise manner to deliver either Δ1 - or Δ2 -pyrroline derivatives depending on the structure of alkenes (Scheme 2.32) [47]. In general, kinetically favorable Δ1 -pyrrolines were formed initially, which tautomerized into more stable Δ2 -pyrrolines 79a. Endo- and exo-cyclic olefins showed similar reactivity to provide the corresponding cycloadduct 79b and 79c with similar efficiency. In the absence of an alkene counterpart, cyclodimerization of 2-isocyanoacetates occurred to generate 1,4-disubstituted imidazoles 80. A strong counterion effect was observed; thus significant rate enhancement was observed when AgOTf was used in place of AgOAc. Δ2-Pyrroline R Electron-deficient AgOAc alkenes (0.2–2 mol%) C N N CO2Me CH3CN, rt 79a H 0.5–4 h

Ph N

O H

Δ1-Pyrroline O

MeN

O

H

Ph-2-Br O CO Me 79b N 2 CO2Me 79c N 67%, R = CO2Me 88% 85% 73%, R = CHO (64 : 36 dr) (83 : 17 dr)

O RO

N

C

CO2Me

AgOAc (2–5 mol%) CH3CN, rt, 2–20 h

RO2C

N N

80

CO2R

88%, R = Me 90%, R = Allyl

Scheme 2.32 Ag-catalyzed reaction of 2-isocyanoacetate to generate Δ1 - or Δ2 -pyrrolines.

Escolano and coworkers implemented a cooperative catalysis in [3+2] cycloaddition of isocyanoacetate with α,β-unsaturated ketones (Scheme 2.33) [48]. Suitable combination of a silver salt and a chiral organocatalyst promoted asymmetric cycloaddition between isocyanoacetate and α,β-unsaturated ketones, rendering 2,3-dihydropyrroles 84 in good yield and enantioselectivity. The combination of cupreine (CPN) and AgNO3 was found to be most effective. The reaction commences with coordination of a silver ion to the isocyanide followed by deprotonation by CPN to form a hydrogen-bonded ion pair 81. Additional hydrogen bonding interaction of CPN with methyl vinyl ketone promotes the formation of adduct 82, setting the chirality. The ring closure between the enol and the silver-coordinated isocyanide moiety of 82 delivers the 1,2-dihydropyrrole 83, which then isomerizes to the more stable 2,3-dihydropyrrole 84. Gong and coworkers reported the silver-catalyzed asymmetric [3+2] cycloaddition of isocyanoacetate with 2-oxobutenoate (Scheme 2.34) [49]. Among chiral ligands examined, a phenolic hydroxyl group-containing binaphthyl phosphine ligand 85 was most effective, generating 4,5-dihydropyrrols 86 with up to 94% ee. Other silver salts such as AgO2 CCF3 , Ag2 CO3 , and AgO2 CPh also showed high catalytic activity except AgOTf. The relative and absolute stereochemistry of the products can be rationalized by the transition state TS-86 where the hydrogen bonding interaction between the ligand and the isocyanoacetate substrate is crucial.

2.2 [3+2] Cycloadditions

CO2R1 N C

R2

R1 = Me, Et, t-Bu R2 = Me, Et

Et

N

AgCPN C N N H O OH OR1

H HO

84

N H

AgCPN OH

COR2 H

H

R1O2C

83

N

AgCPN Cupreine (CPN) H

OH

Stereochemistry-determining

81 OH

R1O2C

N

N C AgCPN

Et

H

CH2Cl2, rt, 14 h up to 85% (89% ee)

AgCPN

CO2R1

COR2

AgNO3, (5 mol%) cupreine (10 mol%)

O

82 H R1O2C

1,4-Addition R2

O

R2 N C Ag-CPN

Scheme 2.33 Asymmetric cycloadditions of isocyanoacetate with α,β-unsaturated ketones. Ar CN

Crucial hydrogen bonding

O AgOAc (10 mol%) CO2Me CHCl3, –10 °C‚ Ar, 2 h

MeO2C 85 (12 mol%) Ar

O R

MeO2C

R

Ar = Ph, 3-Cl-Ph, 4-Cl-Ph 4-MeO-Ph, 4-F-Ph R = Aryl, c-Hex

OH PPh2

CO2Me N H

86

Ph

2 : 1–5 : 1 dr 73–98% (90–94% ee)

O P

O

H

OMe

N Ag

O

O TS-86

Ar H Ph

OMe

Scheme 2.34 Ag-catalyzed asymmetric cycloaddition of isocyanoacetate with 2-oxobutenoate.

Zhao et al. developed a cooperative catalysis protocol for [3+2] cycloaddition α-aryl 2-isocyanoacetate and N-substituted maleimides relying on AgOAc and squaramide-linked cinchona alkaloid 87 (Scheme 2.35) [50]. High diastereoselectivity (>20 : 1) was observed for bicyclic oxazolines 88, but the yield and enantiomeric excess were dependent on the amount of catalyst loading. A cinchona alkaloid-derived squaramide 90 and AgOAc were employed as a cooperative catalyst for highly enantio- and regioselective reaction between

NC R1

CO2R2

R1 = H, i-Pr, Ph, Bn, Ar R2 = Me, Et, t-Bu, Bn R3 = Me, Bn, Ph, Ar

O NR3 O

AgSbF6 (10 mol%) CH2Cl2, 3 Å MS, rt, 0.5–96 h

CO2R2 O

R1

NR3

N

87 (5 mol%) CF3 N CF3

88 O >20 : 1 dr

N H

H N

50–98% (10–90% ee)

O

O

N

Scheme 2.35 Ag-catalyzed asymmetric cycloaddition of α-aryl 2-isocyanoacetate.

49

50

2 Silver-catalyzed Cycloaddition Reactions

CF3

NC R1

R4

N

CO2R2 89

N R3

R1 F3C

AgOAc (5 mol%), 90 (5 mol%) THF, 0 °C, 10 min R4 O

OMe

N N O R3 76–99% >15 : 1 dr (58–98% ee) 91

N

R1 = Ph, 4-F-Ph, 4-MeO-Ph R2 = Me, Bn, t-Bu R3 = H, PMB R4 = H, F, Me, Cl, MeO

CO2R2 N

Ph NH

HN Ph

N HO O

90 O

Scheme 2.36 Enantioselective reactions of isocyanoacetate with cyclic trifluoromethyl ketimines.

isocyanoacetate and cyclic trifluoromethyl ketimine 89 (Scheme 2.36) [51]. Metal chelation and hydrogen bonding of OH or NH group generate a chiral environment whereby tetrahydroimidazo-[1,5-c] 91 was generated with high diastereo- (>15 : 1) and enantioselectivity (up to 98%). An electron-withdrawing CF3 substituent on 89 was required for successful implementation of the reaction. Zhao and coworkers developed silver-promoted double [3+2] cyclization of α-iminoarylesters 92 with 2-isocyanoacetates, where relatively basic salts such as Ag2 O, Ag2 CO3 , AgOAc, Cu2 O, and Cu(OAc)2 catalyzed the reaction to provide products 95 containing both oxazole and imidazole moieties in high yield (Scheme 2.37) [52]. A catalyst generated from Ag2 O and quinine-based chiral phosphine ligand 93 was most effective to generate 95 with high enantioselectivity. At low temperature, the initially formed pyrazolines 94 could be isolated. Ag2O (10 mol%) THF, –20 °C, 24 h

CN R2

O 92

N R1

CO2R3

R2

93 (20 mol%)

O = H, Me 2 R = H, 6-Me,7-Br, 6-OMe, 6-Cl R3 = Me, Et, i-Pr, t-Bu, Ph MeO

R1

CN N O O

N

H N

H

O N

PPh2

R2 94

CO2R3

N CO2R3 R2 95 O 61–99% (37–98% ee) N

OH N

N 3 R2 CO2R

CO2R3

Scheme 2.37 Ag-promoted double cyclization of α-iminoarylesters with 2-isocyanoacetates.

Dixon and coworkers reported the diastereo- and enantioselective Mannich cyclization involving isocyanoacetates and phosphonylimines (Scheme 2.38) [53, 54]. Catalyzed by a binary catalytic system with phosphine ligand 96 and silver salt (Ag2 O or AgOAc), isocyanoacetates slowly reacted with a wide range of phosphonyl imines at low temperature (−20 ∘ C) to deliver polysubstituted imidazolines 97 with high enantioselectivity. Recently, silver-catalyzed diastereoselective [3+2] cycloaddition reactions of 2-isocyanoacetate with chiral N-phosphorylimine 98 were reported (Scheme 2.39) [55]. In the presence of a catalytic amount of AgF, a range of

2.2 [3+2] Cycloadditions

O O Ag2O (5 mol%), Ph P P Ph 96 (20 mol%) N N CN CO2R1 N Ph Ph Ar 4 Å MS, AcOEt 1 Ar R2 R2 97 CO2R –20 °C, 60 h R1 = t-Bu, CH(Ph)2 70–96%, 73 : 27–99 : 1 dr R2 = Me, Et (90–99% ee) Ar = Ph, 4-NO2-Ph, 4-Me-Ph 2-F-Ph, 3-Me-Ph

N NH PPh2 N

O 96

Scheme 2.38 Enantioselective Mannich cyclization of isocyanoacetates with phosphonylimines. i-Pr

AgF (5 mol%) CH2Cl2, rt, 16 h i-Pr N P 98

N

N

Ar

N O i-Pr

Ar = Ph, 4-Me-Ph, 4-F-Ph 4-MeO-Ph, 4-NO2-Ph naphthyl, pyridyl

O

N

(99a:99b = 96 : 4) CN

N

P

Up to 88%

1. KOH, H2O/MeOH reflux, 6 h

N CO2Me Ar

i-Pr 99a

CO2Me

3. (Boc)2O, DMAP

i-Pr

Cs2CO3 (2.2 equiv.) 4 Å MS THF, rt

N

Up to 92%

N

(99a:99b = 4 : 96)

CH3CN, 6 h

N N

P

O

2. MeOH, SOCl2 reflux, overnight

O

(36% overall) CO2Me

Boc N

Ar

i-Pr

Ph

99b

N Boc 100

CO2Me

Scheme 2.39 Ag-catalyzed diastereoselective cycloaddition of isocyanoacetate with chiral N-phosphorylimine.

2-imidazolines 99a were obtained in high yield with excellent diastereoselectivity. When alkali metal such as LiOH or Cs2 CO3 was used instead of silver salts, the opposite diastereomers 99b were generated. 2-Imidazolines 99a could be easily converted to Boc-protected imidazolidinone 100. A regioselective synthesis of 4-picolinoyl pyrroles 102 from 2-pyridyl alkynyl carbinol 101 and 2-isocyanoacetate was achieved by exploiting dual catalytic nature of silver carbonate (Scheme 2.40) [56]. The observed regioselectivity is the consequence of forming isocyanide-coordinated silver chelate 103. Under the conditions, the benzylic alcohol was oxidized by silver carbonate to the corresponding ketone. Ag2CO3 (10 mol%) 1,4-Dioxane, 80 °C R1 10–20 min

OH

R1 N 101

CN

CO2Et

65–87%

OH

O CO2Et

N

NH 102

N

Ag

103

N

CO2Et

R1 = H, Me, Br

Scheme 2.40 Dual catalytic nature of silver carbonate for the synthesis of 4-picolinoyl pyrroles.

In 2013, silver-catalyzed [3+2] cycloadditions between alkynes and isocyanides were independently reported by Lei and Bi (Scheme 2.41) [57–59]. Reaction with

51

52

2 Silver-catalyzed Cycloaddition Reactions

R3

R2 R3 Ag2CO3 (10 mol%)

R2 R1 N H 104

1,4-Dioxane, 80 °C, 0.5–2 h

R1

71–96% R1 = CO2Et, Ph, Ts 1 R2 = Pr, Ph, 4-CN-Ph, CH2OPh R 3 = H, CO Et, COPh R 2

R4 Ag2CO3 (10 mol%)

NC

R4

NMP, 80 °C, 1 h R1 N 40–99% 105 H Ag (I)

N C AgL 106 +

R4

AgL

R1 = CO2Et, CO2Me, PO(OEt)2 R4 = CH2OH, Ph, 4-Me-Ph Pr, COCH3, 4-MeO-Ph

AgL R4 R1

107

R4

AgL N

C

AgL

R1

108

N

AgL

109

Scheme 2.41 Ag-catalyzed cycloadditions of isocyanides with alkynes.

unactivated terminal alkyne or internal alkyne generated 2,3- or 2,3,4-substituted pyrroles 105/104, respectively, with excellent yield in absence of any external base. It was found that silver carbonate (Ag2 CO3 ) outperformed other silver salts such as AgNO3 , Ag2 O, AgOAc, AgOTf, AgF, AgBF4 , and AgClO4 . Control experiments and theoretical studies suggest that the reaction commenced with the anion of silver-coordinated isocyanide 106 and silver acetylide 107, which then merged to form adduct 108. The ring closure of 108 generates 109, which undergoes double bond migration and protonation to provide pyrrole 105. Recently, the silver-catalyzed cascade reaction of isocyanoacetate was extended to β-enaminones 110, which furnished functionalized pyrroles 115 in good yield (Scheme 2.42) [60]. The silver-promoted tautomerization of 110 generates imine 111, the cycloaddition of which with α-metalated isocyanide generates 2-imidazoline 112. Retro-hetero-Michael reaction of 112 to generate intermediate 113 followed by ring closure to form 114 and its dehydration and protonation leads to the final product 115. R1

O R1

R2 110

CN

HN R3 Ag2CO3 Tautomerization O R1

CO2R4

1,4-Dioxane, 80 °C 6–24 h Ag2CO3 (10 mol%)

R2 NR3

–H2O Ag CN

R1

CO2R4

R [3+2] cycloaddition

N 111 R3 1

CO2R4 N 115

R1

H

CO2R4 NR3

O

N

OH R2 Ag 114

2

R = CO2Me, CO2Et, COPh, CO2Bn R O H Nucleophilic addition R2 = Me, Et, Pr 3 R N R1 4 R2 CO2R R3 = Ph, 4-I-Ph, 4-CF3-Ph, 1-Naph N NH Ag R4 = Me,Et Ag 112 113 4 NR3 Retro-hetero-Michael R O2C

Scheme 2.42 Ag-catalyzed cascade reactions of isocyanoacetate with β-enaminones.

2.2 [3+2] Cycloadditions

The regioselective synthesis of 1,4,5-trisubstituted imidazoles was achieved by silver-catalyzed cross-dimerization of two isocyanides (Scheme 2.43) [61]. Because of the low reactivity of aryl isocyanides, relatively high loading of silver carbonate (30 mol%) was necessary for the reaction. In terms of mechanism, the initially formed adduct 116 undergoes 1,2-migration of either the ester (CO2 Et) or carbamoyl group (CONR2 ) to generate the penultimate intermediate 117, which then lead to imidazole 118 after the elimination of silver. FG

CN R +

Ar NC

Ag2CO3 (30 mol%)

1,4-Dioxane 80 °C, 1 h

FG N

Ag

R Ag

FG [3+2] R

Ag

Ag

N Ar

1,2Migration

N

116

R

R

N

FG Ag

N Ar 117

N Ar

N

Ag FG

N Ar

118 45–90%

FG = CO2Et, CONR2 R = H, Me, Ph, Bn, CH2F, Br Ar = 4-Br-Ph, 2,5-Me2-Ph, 1-Naph

Scheme 2.43 Ag-catalyzed cross-dimerization of two isocyanides.

Similar to isocyanoacetates, α-trifluoromethylated isocyanide participates in [3+2] cycloaddition with compounds of polarized double bonds, including imines, alkenes, and aldehydes, to generate trifluoromethylated imidazolines, pyrrolines, and oxazolines (Scheme 2.44) [62]. The reaction proceeds through the formation of silver-promoted and base-assisted generation of anionic silver complex 119 followed by subsequent cycloaddition. The prowess of this protocol was demonstrated in the gram-scale synthesis of β-trifluoromethyl β-amino alcohols via the formation oxazolines followed by hydrolysis. Moderate enantioselectivity was achieved with chiral ligand 78. Ts Ag N

R1

Toluene,15 °C 1–30 h

PMB

PMB N

95%, 4.2 : 1 dr

R1

Ag2CO3 (5 mol%) CF3 DBU (10 mol%)

CN

CF3

Ts N

N

Ag CF3 R1 119

OMe

CF3 R1

N

NC NC

CN

CF3 R1

60%

N H

R2 R2CHO 63–99% 1.4–5 : 1 dr

R1 = 4-Me-Ph, 4-F-Ph, 4-Cl-Ph, 3-Me-Ph, 2-MeO-Ph, 2-Naph R2 = 4-F-Ph, 4-NO2-Ph, 4-MeO-Ph, 2-Naph, 2-Py, CO2Et

O N

NH O 78

Ph2P

CF3 R1 6 N HCl, CH3CN R reflux, 0.5 h F3C Quantitive

R

NH2 OH

Scheme 2.44 Cycloadditions of α-trifluoromethylated isocyanides.

2.2.3

Cycloaddition of Azides

The Huisgen 1,3-dipolar cycloaddition of terminal alkynes with azides generally requires high temperature up to 100 ∘ C and produces a mixture of 1,4- and

53

54

2 Silver-catalyzed Cycloaddition Reactions

1,5-disubstituted triazole isomers. Sharpless and Medal independently discovered that this cycloaddition was remarkably accelerated in the presence of a catalytic amount of copper species, which generated only 1,4-disubstituted triazole isomers [63, 64]. Subsequently, Sharpless reported ruthenium-catalyzed reactions that afforded only 1,5-disubstituted triazoles [65], and recently Ni-catalyzed reaction was also reported [66]. Compared with the vast number of reports on copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with azides, only a small number of silver-catalyzed reactions are reported, which in many cases requires a copper cocatalyst to complete the cyclization step. In 2011, McNulty et al. reported the first successful silver-catalyzed azide– alkyne cycloaddition (AgAAC) (Scheme 2.45) [67, 68]. Although silver salts such as AgOAc, Ag2 O, AgNO3 , and AgOTf are not reactive catalyst, their complexes with hemilabile bidentate P,O- and P,N-type ligands become catalytically active. For example, AgOAc and 2-diphenylphosphino-N,N-diisopropylcarboxamide 120a effectively promote the cycloaddition between azides and terminal alkynes at ambient temperature, generating 1,4-disubstituted triazoles 121 in excellent yield. Carboxylic acid additive such as benzoic acid or caprylic acid further improved the reaction. In the catalytic mechanism, the hemilabile ligand plays a crucial role. It is believed that an electron-deficient 14e-silver species 122 reacts with acetylene to form silver acetylide 123. Association with azide on the metal center in 124 followed by cyclization generates strained cyclic intermediate 125, which undergoes shifting of the nitrogen to generate a triazole 121 after protonolysis of 126. The limitations of the catalytic system involving complex 120a are high catalyst loading (20 mol%) and excess alkyne (5 equiv.) D

N3

Caprylic acid (20 mol%) toluene, rt, 48 h

N

120a (20 mol%) or 120b (2 mol%) R1

2

Ni-Pr2

R R1 = Me, OMe, F, Cl, Br R2 = Cl, OMe, NO2, Br

Ni-Pr2 123

N N N Ar2

Ni-Pr2

H+

Ar1 O Ag

2

Ar1

124

(D)H 121 72–99% (55% loss of D)

i-Pr2N N P O O N N R R Ag H3C P Ar2 O 126 R R N–C 120a, R = Ph; 120b, R = t-Bu migration Ni-Pr2 Ni-Pr

P R R

N N

N

OAc

HOAc

O Ag

Ar1

R1

O Ag P 122 R R

N

O Ag N Ar2

P R R

O Ag

Ar1 N

N

P N R R 125 1 Ar

Scheme 2.45 Ag-catalyzed azide–alkyne cycloadditions.

R2

2.2 [3+2] Cycloadditions

to achieve high degree of conversation. Catalyst 120b significantly improved the catalytic efficiency by modulating the electronic and steric factors on the metal center, requiring only 2–2.5 mol% catalyst loading to achieve near-quantitative formation of triazoles even after multiple cycle of the reaction. Because of their unique electronic and steric properties, metal N-heterocyclic carbenes have emerged as efficient catalyst in numerous transformations. It was reported that the catalytic activity of AgCl in azide–alkyne cycloaddition was substantially increased by NHC ligation (Scheme 2.46) [69]. Cycloaddition between various alkyne and azide was accomplished with 3.5 mol% AgCl or 0.5 mol% Ag–NHC complex 127, providing 1,2,3-triazole in moderate to good yield. It was suggested that the bulky NHC ligand stabilizes silver ion and other intermediates to prevent side reactions.

2

1

R

R

N3

R1 = Ph, CH2OH, CH2O(4-Cl)C6H4 R2 = Bn, 4-NO2-Ph, 2-NO2-Ph

AgCl (3.5 mol%), THF, rt or i-Pr

Ph N

Ag

N

i-Pr

N

N

2 N R

R1 With AgCl : 28–77% With 127 : 54–77%

i-Pr i-Pr 127 (0.5 mol%)

Scheme 2.46 Ag–NHC-catalyzed azide–alkyne cycloaddition.

The scope of catalytic activity of silver salt was extended to the [3+2] cycloaddition of sodium azide and nitriles to form 5-substituted tetrazoles by using silver bis(trifluoromethanesulfonyl)imide (Ag(NTf )2 ) (Scheme 2.47). Other silver salts such as Ag2 CO3 , AgNO3 , AgOAc, Ag2 O, and AgOTf provided low to moderate yield [70]. Substitution at the 2-position of nitriles significantly affects the outcome of reaction due to steric hindrance. R1 CN

NaN3

AgNTf2 (5 mol%)

Toluene, 85 °C, 1–5 h 78–96% R1 = Ph, 4-Cl-Ph, 4-HO-Ph, 2-Furanyl

R

1

N N N N H

Scheme 2.47 Ag-catalyzed cycloaddition of azide with nitriles to form 5-substituted tetrazoles.

Silver dicyanamide/diisopropylethylamine also promoted the regioselective [3+2] cycloaddition of azide and terminal alkyne in H2 O/ethylene glycol (Scheme 2.48) [71]. Silver dicyanamide is a polymeric structure wherein metal ion are cross-linked via dicyanamide (–Ag–NC–N–CN–Ag–) in a spiral chain. With 10 mol% loading of AgN(CN)2 , 1,4-disubstituted-1,2,3-triazoles were obtained in moderate yield along with 1,5-disubstituted isomer. Selectivity and yield were improved by adding DIPEA (1 equiv.), which not only acts as base but also acts as a regiochemistry-controlling element via coordinating with silver ion.

55

56

2 Silver-catalyzed Cycloaddition Reactions

R1 N3

AgN(CN)2 (10 mol%)

R2

DIPEA (1 equiv.), H2O/(HOCH2)2, rt

R1 = Bn, Ph, Ar R2 = Ph, Ar, n-Alkyl, Ester, CH2OH

R1

N N N

R2

85–95%

Scheme 2.48 Ag-promoted azide–alkyne cycloaddition.

It was found that the cycloaddition between aryl nitrile and sodium azide could be promoted by AgNO3 [72]. Both electron-rich and electron-deficient aromatic nitriles provided 5-substituted 1H-tetrazole 128 in good yield. Most likely the in situ generated silver azide interacts with the π-system of nitriles to promote the [3+2] cycloaddition (Scheme 2.49) [73]. This protocol was also employed for the synthesis of tetrazoles 129 containing a pyrazole moiety [74]. Furthermore, the Lewis acidic character of silver nanoparticles (Ag NPs) was exploited in AgAAC reaction, and the advantage of using Ag NPs as catalyst is its easy recovery and reuse. N N NH N

CN NaN3

R

DMF, 120 °C

R = 4-Br, 4-OH, 4-OMe, 4-NHCOPh, 3-NO2

R

128 N N N NH

CN Ar

NaN3

N N

AgNO3 (10 mol%) DMF, 120 °C, 6–7 h

Ph

AgNO3 (10 mol%), 5 h: 76–87% AgNPs (20 mol%), 8 h: 82–93%

Ar 129

N N

Ar = 4-F-Ph, 4-Cl-Ph

Ph

Scheme 2.49 Ag NP-promoted cycloadditions between aryl nitriles and sodium azide.

Because of high surface area, graphene has emerged as an efficient 2D platform for various chemical reactions (Scheme 2.50) [75]. High activity of graphene derives from its ability to absorb reactants through π–π stacking interaction and reversible redox behavior. Relying on these advantages, one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles on silver–graphene nanocomposite (Ag–C) was realized using aniline as precursor. Only a small amount of Ag–C (0.5 mol%) was enough to catalyze the cycloaddition between terminal alkyne and in situ generated azide effectively, providing triazoles in good to excellent yield. Ag–graphene displayed superior catalytic activity to metallic nanoparticle, because of the large surface area.

R

1

N3 +

Ag-graphene (0.5 mol%) R2

Water, 8–10 h, rt 84–98%

R1

N N N

R1 = H, 4-OMe, 2-NO2, 3-OH, 2-I, 3-Cl R2 = H, 4-OMe, 4-F, 4-Ph, 4-CN

Scheme 2.50 Ag–graphene nanocomposite-promoted synthesis 1,2,3-triazoles.

R2

2.2 [3+2] Cycloadditions

Silver nanoparticles generated from oleic acid and Ag2 O can promote [3+2] cycloaddition between aryl azides and alkynes at room temperature (Scheme 2.51) [76]. Coating the nanoparticles with oleic acid improved the colloidal stability and dispersive properties of the nanoparticles in solution. Reaction in wet medium required shorter reaction time and resulted in higher product yield, which is assumed to be the consequence of coordinated water molecules with the nanoparticles. Cycloaddition involving phenyl azide and para-methoxy phenyl azide provided 1,4-disubstituted 1,2,3-trizole 130a irrespective of the alkyne substrate. On the other hand, 1,5-disubstituted isomer 130b started to grow when an electron-withdrawing group was introduced. N N N

N3 R

R

Ag2O-NPs

MeO2C

N N N

Toluene, 20 °C 3–16 h R

CO2Me 130a

130b

CO2Me

R 130a (%) 130b (%) H 0 90 0 OMe 95 25 Cl 70 44 NO2 50

Scheme 2.51 Ag nanoparticle-promoted cycloaddition between aryl azides and alkynes.

The superior catalytic activities of functionalized silver nanoparticles (FnAgNPs) over naked Ag NPs were demonstrated in the [3+2] cycloaddition of nitroolefins and azides (Scheme 2.52) [77]. FnAgNPs were synthesized through reduction of AgNO3 using aqueous seed extract of Protorhus longifolia as reducing agent. Imaging techniques (SEM, TEM) revealed that spherical Ag NPs were 23 ± 1 nm in size and capped with polyols (characteristic O–H and –C–O– signals in IR spectrum of extract). Capping agents influenced the catalytic activity of nanoparticles by modulating their size, shape, and solvent interaction. The catalyst loading and reaction time significantly influenced the outcome of the reaction. Higher yield of triazoles (65%) was achieved with FnAgNP compared with naked Ag NPs, which provided only 25% yield of the product. R1

R1 NO2 1

N3

R = H, Br, Me, CN, OH, OMe R2 = Ph, Bn

R2

Functionalized Ag NPs Toluene, 80 °C, 10–18 h 61–88%

R2 N N N

Scheme 2.52 Functionalized Ag NP-promoted cycloaddition between aryl azides and nitroalkenes.

FnAgNPs capped with polyallyamine-based resin was exploited in the azide–alkyne click reaction in aqueous medium (Scheme 2.53) [78]. FnAgNPs were synthesized from the reduction of AgNO3 with hydrazine followed by stabilizing the nanoparticles in polyallylamine gel. Catalyst loading as low as 1 mol% could provide high yield of tetrazole products at 80 ∘ C. The FnAgNPs could be reused more than 10 times without significant loss of catalytic activity.

57

58

2 Silver-catalyzed Cycloaddition Reactions

R1

R2

R1 Ag NPs (1 wt%)

N3

R2

N N N

Water, 80 °C, 7–15 h 92–96%

R1 = H, 3-Cl, 4-F; R2 = H, 4-OEt, 4-Me, 4-Cl

Scheme 2.53 Functionalized Ag NP-promoted azide–alkyne click reaction.

Porphyrin-supported mixed-valent Ag(I)/Ag(II) metal–organic frameworks were also catalyzed by the azide–alkyne click reaction (Scheme 2.54) [79]. With 1 mol% loading of the heterogeneous catalyst, phenyl acetylene, sodium azide, and benzyl chloride generated triazole products in moderate yield. This robust catalyst system could be recovered through filtration after the reaction and can be reused multiple times without substantial loss of catalytic activity. Copper analogue of this catalyst displayed better substrate scope and superior catalytic activities in azide–alkyne cycloaddition (AAC) reactions. Porphyrin-supported Ag(I)/Ag(II) catalyst

Ph

NaN3

Cl R R = 2-F, 3-Me

50 °C, 12 h

Ph

N N N R R = 2-F: 42% R = 3-Me: 40%

Scheme 2.54 Ag(I)/Ag(II) metal–organic frameworks for azide–alkyne click reactions.

Recently, 3D supramolecular coordination polymers (SCPs) of silver {[SnMe3 (bpe)] [Ag(CN)2 ]⋅2H2 O} were found to be an effective catalyst for the alkyne–azide click reaction. Loading of 15 mol% of the silver complex could promote quantitative conversion within 25–30 minutes compared with 25–28 hours with AgNO3 (Scheme 2.55) [80]. The high catalytic activity of SCPs can be justified by the characteristic metal ion environment with high surface areas, pores, and cavities. SCPs could be reused but the reused catalyst showed significantly lower catalytic activity.

Ph

N3

[SnMe3(bpe)] [Ag(CN)2] 2H2O R R = CH2Br, Ph

Acetonitrile/water (1 : 1) 25–30 min, rt bpe = 1,2-bis(4-pyridyl)ethane

Ph

N N N

R

100%

Scheme 2.55 Alkyne–azide click reaction catalyzed by Ag-SCP.

1,4-Disubstituted-1,2,3-triazoles could be synthesized by silver-catalyzed reactions between isocyanides and diazo compounds (Scheme 2.56) [81]. This approach is particularly effective for the preparation of trifluoromethylated triazoles under mild conditions; however, choosing a right solvent in anhydrous environment was found to be crucial.

2.3 [2+2] Cycloadditions

1

N2CHR2

R N C

Ag2CO3 (10 mol%) 4 Å MS 1

R

DMF, 40 °C, 6 h R = c-Hex, Ph, 4-F-Ph, 2-MeO-Ph R2 = CF3, CO2Et, CO2t-Bu, SiMe3 1

N N N

R2

21–95%

Scheme 2.56 Ag-catalyzed reactions between isocyanides and diazo compounds.

2.3 [2+2] Cycloadditions The silver-catalyzed [2+2] cycloaddition between electron-deficient alkenes and siloxyalkynes was reported by Kozmin where AgNTf2 (10 mol%) was superior to other Lewis acids such as BF3 ⋅OEt2 , TiCl4 , Sc(OTf )3 , AgSbF6 , and AgOTf (Scheme 2.57) [82]. Diverse α,β-unsaturated esters, ketones, and nitriles smoothly participated in the reaction to generate tri- or tetrasubstituted siloxycyclobutene derivatives 131 in good yield. A stepwise mechanism is involved in this reaction, because E- and Z-crotonates provide the same trans-substituted siloxycyclobutene, which was further confirmed by deuterium scrambling. It is proposed that the reaction commences with the interaction of AgNTf2 with siloxyalkyne to form a zwitterionic intermediate 132. OTIPS

O R2

R1

O

AgNTf2 (5 mol%) TIPSO CH2Cl2, 20 °C

R2

68–90%

R3

R1

AgNTf2

131

TIPSO

O C

AgNTf2 R1

TIPS

132 R1

R3

R1 = n-Bu, Bn, Ph R2 = Me, OMe, Ph R3 = H, -CH2-CH2-

TIPS O

R1 O C

R3 AgNTf2

R3

R2

Ag– NTf2 O

R2

Scheme 2.57 Ag-catalyzed [2+2] cycloaddition of siloxyalkynes.

Due to the ring strain, alkoxymethylidene cyclopropane 133 readily participates in the [2+2] cycloaddition with imines to generate azetidines 134 (Scheme 2.58) [83]. In the presence of Ag(fod) (10 mol%), the reaction proceeded smoothly at 30 ∘ C with a high cis/trans ratio of the product, while the corresponding thermal reaction occurred at 80 ∘ C with significantly lower cis/trans ratio. A stepwise mechanism involving a zwitterionic intermediate was proposed for this reaction. Hsung and coworkers reported silver-catalyzed inter- and intramolecular [2+2] cycloadditions of ynamides with α,β-unsaturated enones (Scheme 2.59)

59

60

2 Silver-catalyzed Cycloaddition Reactions

OR1

OR1 R1 = Bn, n-Bu CH3CN, 80 °C R2 = Ph, 4-MeO-Ph, or N N 4-CF3-Ph, t-Bu 10 mol% [Ag(fod)] R3 R3 = Ts, Ns, SO Ph R3 R2 2 EtOAc, 30 °C 134

R2

133

Catalytic 1

2

R3

Entry

R

R

1 2 3 4

Bn Bn Bn Bn

Ph CO2Et

Ts Ts Ph Ms 4-CF3Ph Ms

Thermal Yield(%) cis/trans

Yield (%) cis/trans 135 : 1 35 : 1 46 : 1 48 : 1

94 45 77 76

97 57 93 84

51 : 1 1.2 : 1 5:1 4:1

Scheme 2.58 Ag-catalyzed formation of azetidines from alkoxymethylidene cyclopropane. Mbs

N

Bn

O AgNTf2 (10 mol%) Mbs

N

H

O

CH2Cl2, rt, 3 h Me 88% H Mbs = 4-methoxybenzenesulfonyl

Me EWG

Bn N

R2 O

AgNTf2 (10 mol%) 1

R

EWG

CH2Cl2, rt, 3 h 15–60% EWG = Ts, Mbs, Bs, Ns

R2 N

H

135a

O R1 = Me, Ph R1 R2 = Bn, allyl, homoallyl 135b

Scheme 2.59 Ag-catalyzed [2+2] cycloadditions of ynamides with α,β-unsaturated enones.

[84]. AgNTf2 was identified as the most effective catalyst for both the inter- and intramolecular reaction to generate 135a and 135b, respectively. The formation of fused bicyclic products 135b failed with a shorter tether between the ynamide and enone moieties.

2.4 [3+3] Cycloadditions Silver-catalyzed [3+3] cycloaddition is underexplored area compared with other types of cycloadditions. Some of the examples are [6+3] cycloaddition in terms of involved π-systems, but based on the number of atoms in the incipient ring from each contributing component, they are classified as [3+3] cycloaddition. Guo and coworkers reported silver-promoted cycloaddition between tropone and homoserine lactone-derived azomethine ylide to generate tricyclic piperidines 136 under mild conditions (Scheme 2.60) [85]. AgOAc/DBU was found to be optimal, and other silver salts such as AgBF4 , AgSO3 CF3 , AgSO3 CH3 , and AgCO2 CF3 could catalyze the reaction but to a lesser degree. High diastereoselectivity (>20 : 1) was observed in all cases. The cycloaddition between 2-isocyanoacetates and fulvenes 137 was catalyzed by AgOAc/PPh3 (3 mol%) and Et3 N (15 mol%) to generate dihydropyridines

2.4 [3+3] Cycloadditions

O

O Ar

N

O

O

AgOAc (10 mol%), PPh3 (20 mol%) DBU (20 mol%), MeOH, rt, 12–16 h 51–76%, >20 : 1 dr

O O

N H

Ar

Ar = 2-Me-Ph, 3-Me-Ph, 3-MeO-Ph, 2-F-Ph 4-F-Ph, 4-Cl-Ph, 4-Br-Ph, 1-Naph

136

Scheme 2.60 Ag-promoted cycloaddition between tropone and azomethine ylide.

139 in 64–95% yield (Scheme 2.61) [86]. From unsymmetrical fulvenes, both cis- and trans-isomers were generated in a 1 : 1 ratio. Reactions with chiral ligand (S)-TF-BiphamPhos (26) provided only low enantioselectivity (28% ee). A stepwise mechanism involving the formation of zwitterionic intermediate 138 was proposed. R1 137

R2

CO2R4

CN

B R1 = Me, Et, Ph, 4-MeO-Ph, 4-Cl-Ph BH+ R2 = H, Me, Et R3 = H, Me, Pr, Bn Ag R4 = Me, Bn

64–95%

B

Ag+ R2 R1

R3

BH+ R

3

1

2

R R

CO2R4 N

CO2R4

137

R3 CO2R4 NH

139

Ag+

N +

R1 R2

AgOAc/PPh3 (3 mol%) Et3N (15 mol%), CH2Cl2, rt, 12 h

R3

R3 CO2R4

N 138

Ag

Ag

Scheme 2.61 Ag-catalyzed cycloaddition of 2-isocyanoacetates with fulvenes.

Sato explored the reaction between naphtho[b]cyclopropene 140 and iminotropones 141 in the presence of silver tetrafluoroborate to generate products 142 (Scheme 2.62) [87]. The reaction is believed to occur via a [2π+2σ] mechanism, which commenced with imine insertion on cyclopropane, and the spirocyclic intermediate undergoes a ring expansion via 1,2-shift bond shift. R N 140

R AgBF4 (3 mol%) benzene, 0 °C

141

R = Me (12% yield) R = OMe (5% yield)

N 142

Scheme 2.62 Ag-catalyzed reaction of naphtho[b]cyclopropane with iminotropones.

Doyle and coworkers developed a sequential binary catalytic protocol to generate cis- disubstituted 3,6-dihydro-1,2-oxazine derivatives 145 employing Rh2 (OAc)4 and AgSbF6 /(s)-t-BuBox as the catalysts (Scheme 2.63) [88]. Catalyzed by Rh2 (OAc)4 , γ-phenyl enol diazoacetate 143 was converted to a

61

62

2 Silver-catalyzed Cycloaddition Reactions Ph

OTBS CO2Me

Ph

71–95% (79–97% ee) (S)-t-BuBox

143 N2 Rh2(OAc)4 CH2Cl2, rt 0.5 h

144

O

Ar1

O N

t-BuO2C

Ph

O

Ar2

Ring closure Ph

Ar2

TBSO N

O t-BuO

Ar1

Ar2

TBSO

O CH2Cl2 N –78°C

1 CO2t-Bu Ar

O N

TBSO

TBAF, 0 °C

Ar1 = Ph, 2-MeO-Ph, 4-MeO-Ph Ar2 = Ph, 4-Cl-Ph, 4-Me-Ph

Me Me O

Ph

t-BuO2C 145 Ar2

N N t-Bu AgSbF6 t-Bu

Ph TBSO

HO

Rh(II)/Ag(I)

O

Ar1 N

Ar1

Ar2

Ag

N N *

t-BuO

Ag

N N *

O

Scheme 2.63 Ag-catalyzed [3+3] cycloaddition of nitrones with donor–acceptor cyclopropenes.

relatively stable donor–acceptor cyclopropenes 144, which then participated in the [3+3] cycloaddition with nitrones catalyzed by AgSbF6 /(s)-t-BuBox. Using chiral rhodium catalyst in first step followed by achiral silver catalyst provided low enantioselectivity of the final product 145, whereas the reaction sequence with achiral rhodium first followed by chiral silver complexes provided high level of enantioselectivity. A broad range of nitrones could be accommodated in the reaction with high enantioselectivity except for nitrones containing an electron-withdrawing group on the N-phenyl group, which slightly lowered the enantioselectivity. Fan and coworkers also reported sequential binary catalytic [3+3] cycloaddition with single catalyst starting from 2-alkynyl cyclohexadienimines 146 and 2-alkynylbenzaldoxims 147 (Scheme 2.64) [89]. The reaction commenced with the conversion of 146 into 148 and oxime 147 into 149 by the action of the silver catalyst followed by their [3+3] cycloaddition to generate 150. The structural reorganization of 150 generates oxocino[4,3,2-cd]indole derivative 151 upon heating. The overall reaction was found to be general in terms of substituents. An exception is for an alkyl substituent of R1 , which provides comparatively low yield. R3 R1

R2 MeO R4 146

MeO R2 4

R

N Ts

R3

147 N HO

5

R

AgOCOCF3 (10 mol%) ClCH2CH2Cl, rt

Ag R1 N 148 Ts

R6

R3

+ Ag

O

R2 MeO R4

R6 N

R5 149

O

R6 N

R5 1,4-Dioxane R1

N 150 Ts

90 °C, 2 h 97% Me

O Ph

[3 + 3] dipolar cycloaddition

151 N Ts

Scheme 2.64 Ag-promoted sequential binary catalytic [3+3] cycloadditions.

N

Ph

2.5 [4+2] Cycloadditions

The silver-catalyzed [3+3] cycloaddition was also demonstrated with azomethine imine (Scheme 2.65) [90]. At high temperature, the reaction between vinylpyrrole 152 and azomethine imine 153 in the presence of silver trifluoroacetate generated the [3+3] cycloadduct 154. It was found that the initially formed cis-diastereomer gradually isomerized into the trans-isomer during the reaction. Other transition metal salts such as ZrCl4 , In(SO3 Me)3 , and NiCl2 (Ph2 PCH2 )2 were capable of promoting the reaction but in low yield. R2

R2

Ar N

R1

AgOCOCF3 (10 mol%)

N O

N

N N

R

153 152

Ar

R1

C6H5Cl, 120 °C, 2–12 h

R = β-Me: 6–47% R = α-Me: 2–8%

R1 = Ph, alkyl; R2 = H, alkyl Ar = Ph, 4-Cl-Ph, 4-MeO-Ph

N

O

154

Scheme 2.65 Ag-catalyzed [3+3] cycloaddition with azomethine imine.

2.5 [4+2] Cycloadditions 2.5.1

Diels–Alder Reactions

trans-Cycloheptene readily isomerizes to its cis-isomer (t 1/2 = 23 minutes at −10 ∘ C). However, it was found that the silver-complexed trans-cycloheptene derivative 156, generated by treating nitroso compound 155 with AgClO4 , could be isolated as a thermally stable and moderately light-sensitive solid (Scheme 2.66) [91]. The Diels–Alder reaction of 156 with various 1,3-dienes such as furan, 2,3-dimethyl-1,3-butadiene, anthracene, and cyclohexadiene proceeded at room temperature to afford the corresponding cycloadducts 157 where the ring junction stereochemistry was always trans but the endo/exo diastereoselectivity was marginal (up to 4.4 : 1). H

NO N O 155

H

O NH2

CH3OH AgClO4

O

OMe AgClO4 156

25 °C

H 4.4 : 1 dr OMe

157

Scheme 2.66 Diels–Alder reaction of Ag-complexed trans-cycloheptene.

The catalytic activity of AgClO4 was also demonstrated for the Diels–Alder reaction between 1,3-dienes and α,β-unsaturated ketones (Scheme 2.67) [92]. In the presence of Lawesson’s reagent or Ph2 SN=S, AgClO4 (4–10%) could promote cycloaddition of various dienes, and high endo-selectivity was observed with cyclic dienes. Silver-promoted sequential 1,3-acyloxy migration to generate vinyl allene 158 followed by Diels–Alder reaction was exploited in the synthesis of hydroisoquinoline derivatives 159 (Scheme 2.68) [93]. The viability of this reaction highly

63

64

2 Silver-catalyzed Cycloaddition Reactions

O

O Ph

Catalyst (10 mol%) CH2Cl2, –78 °C

Ph

endo/exo = 99/1 [0.5 Lawesson′s reagent + AgClO4] [3 Ph2Sn = S + AgClO4]

87% yield 90% yield

Scheme 2.67 Ag-catalyzed Diels–Alder reaction of α,β-unsaturated ketones. 2 [Ag]+ R

OCOR1 R2 AgSbF6 (5 mol%) JohnPhos (5 mol%)

5

R

R3

TsN R6

4 Å MS, toluene 80 °C, 2–72 h

R4

R1OCO

R2

OCOR1 [4 + 2]

R5 R

TsN 158

R6

3

–[Ag]+

R4

TsN 5 R3 6R R4 159 R 34–99%

Scheme 2.68 Ag-promoted sequential 1,3-acyloxy migration and Diels–Alder reaction.

depends on the electronic nature of migrating group. Control experiment proved the silver ion dependence of both steps. Silver-catalyzed [4+2] cycloaddition reactions of 2-alkyl benzaldehyde 160 and various alkenes were exploited for the construction of tetrahydronaphthol 161 framework (Scheme 2.69) [94]. No product could be formed from 2-methyl benzaldehyde because of the low acidity of the benzylic proton; thus installation of a carbonyl on the methyl group is necessary. Counterion of the silver catalyst together with an external base such as 2,6-dibromopyridine or pyridine N-oxide has a vital role in this reaction. The stereochemical outcome can be justified by the [4+2] cycloaddition of a H-bonding-stabilized enol intermediate through endo transition state TS-161. R1

160 O

O

R

AgSbF6 (5 mol%) NPO (1.0 equiv.)

R1

R2

R3

R4

R5 ClCH2CH2Cl, rt, overnight 41–95% 161 O (up to 99 : 1 dr)

OH

R2 R3 R5 R4

R

R3 R1

R2

R5

R4 O H O Ph TS-161

Scheme 2.69 Ag-catalyzed Diels–Alder reaction of 2-alkyl benzaldehyde.

The silver-promoted Diels–Alder reaction was exploited in the total synthesis of pentamethyl derivative of kuwanon and dorsterone (Scheme 2.70) [95]. In the presence of a binary catalytic system AgOTf/Bu4 NBH4 , diene 162 chalcone 163 slowly underwent [4+2] cycloaddition to generate a mixture of pentamethylated kuwanon and dorsterone in a 60 : 40 ratio with 65% total yield. Silver nanoparticles (Ag NPs) are potential heterogeneous catalyst for many chemical transformations based on its size-related properties. In 2010, Porco reported the total synthesis of panduratin relying on [4+2] cycloaddition catalyzed by Ag NPs (Scheme 2.71) [96]. It was shown that the in situ generated

2.5 [4+2] Cycloadditions Ar

Ar Ar MeO

MeO MeO O OMe

162

Me O Ar

CH2Cl2, 60 °C, 18 h 65% (endo:exo = 60 : 40)

OH

163

O Me OMe

Me AgOTf (60 mol%) Bu4NBH4 (10 mol%)

O OMe

O Ar

O Ar

OH

OH

Me

Me

Me Me OMe OMe endo (Pentamthyl kuwanon) exo (Pentamthyl dorsterone)

OMe

Ar = 4-MeO-Ph

Scheme 2.70 Ag-promoted Diels–Alder reaction for kuwanon and dorsterone derivatives. Ph MeO

OH Me

Ph AcO

O 165

Me

2. aq. NaHCO3 MeOH (87%)

O Me

164 OH O

1. Silica-supported Ag NPs (85%)

Me

OH

MeO

OH

O

Panduratin

Me

AMe

OAc

OAc

OAc

Silica-supported Ag NPs (0.1 mol%) CH2Cl2, 50 °C, 48 h

O OAc

OMOM OH

HO O MOMO

OMOM 166

OMOM

O O

1. Na2CO3, MeOH/water 2. Pd(OAc)2, pyr, O2, 80 °C 3. 3 M HCl, MeOH, 80 °C

endo/exo = 2 : 1 90% OH

O HO

OH

Sorocenol B

Scheme 2.71 Synthesis of panduratin relying on Ag NP-catalyzed Diels–Alder reaction.

Ag NPs from AgBF4 and Bu4 NBH4 were able to catalyze the cycloaddition of 2-hydroxychalcone 164 with various dienes regioselectively at room temperature. Silver catalysts of different counterions such as − OTf, − ClO4 , or − OAc afforded poor yield and low endo-selectivity. Fixation of Ag NPs on silica gel generated highly active yet oxygen- and water-tolerant reusable heterogeneous catalyst systems, which could be reused multiple times without loss of the catalytic activity. The effectiveness of silica-supported Ag NPs for Diels–Alder reaction was further exploited in the synthesis of sorocenol B starting from chalcone 165 and 1,3-diene 166 [97]. In terms of the reaction mechanism, it is believed that Ag NPs behave as electron shuttles and/or redox catalyst although their role as a conventional

65

66

2 Silver-catalyzed Cycloaddition Reactions

Lewis acid cannot be ignored. In a putative catalytic cycle, single electron transfer (SET) from a deprotonated chalcone leads to phenoxy radical, which then participates in [4+2] cycloaddition (Scheme 2.72). After the cycloaddition, back electron transfer (BET) followed by protonation furnishes the observed cycloadduct. OH

OH

O

+ R2

CH2Cl2, 25–40 °C, 5–36 h

R1 R1 = H, OMe, OAc R2 = H, Ph R3 = H, Me

R2 85–98%

R3

SET

AgNP– δ– – –δ δ δ

O

O

H+

AgNP

Proposed catalytic cycle O

O Ph

Ph R1

R1

R1

AgNP

AgNP– δ– – δ– δ δ O

Ph

0.25 mol% AgNP

Ph

R3

O

AgNP– δ– – –δ δ δ O

Ph

O

R2

R1

R3 Ph

O

BET H+

R2

R1

R3

R2 R3

Scheme 2.72 A putative mechanism of Ag NP-catalyzed Diels–Alder reaction.

The synthesis of brosimone A and B was achieved through Ag NP-catalyzed dehydrogenative Diels–Alder (DHDA) reaction (Scheme 2.73) [98]. Using cyclopentene as hydrogen scavenger and Pt/C-AgNP as a catalyst, chalcones 167 were dimerized to form adduct 168. The exo-isomer 168 was converted to brosimone B through transfer hydrolysis with 1,4-cyclohexadiene as proton source. OH O

OBn

OH O

Cyclopentene RO OBn 64%

167

BnO

Pt/C (10 mol%) Ag NP (0.2 mol%)

O

OR

DDQ (1.5 equiv.) Ag NP (0.3 equiv.) OR

OH

130 °C, 72 h 62%

OR RO

OR exo-Cycloadduct (exo:endo = 1.2 : 1)

OH OR O

OR

O

168, R = Bn Brosimone B, R = H

RO HO

HO

OR 169, R = Bn

Brosimone A, R = H OR exo:endo = 20 : 1

Pd/C 1,4-Cyclohexadiene

Pd/C 1,4-Cyclohexadiene

Scheme 2.73 Ag NP-catalyzed dehydrogenative Diels–Alder (DHDA) reactions for brosimones.

2.5 [4+2] Cycloadditions

Although the second DHDA reaction of 168 failed under same conditions, employing a stronger oxidant DDQ resulted in the successful intramolecular DHDA to generate symmetrical cycloadduct 169, which upon hydrogenolysis afforded brosimone A. A unique Ag NP-based photocatalytic system was developed from AgNO3 and dialdehyde 170 (Scheme 2.74) [99]. These spherical Ag NPs of size in the range of 7 nm are capable of catalyzing Diels–Alder reaction under visible light. In the presence of Ag NPs, 2,3-dimethyl-1,3-butadiene underwent [4+2] cycloaddition with large array of alkynes and quinone derivatives in EtOH–H2 O (1 : 1) at room temperature. O H CHO

OHC 170 O CHO

OHC

THF–water (2 : 3) OHC OHC OHC

CHO AgNO3 Ag0 CHO CHO Ag NP Fluorescent aggregates

CO2H

Ph 75 min Visible light Ag NPs EtOH:water (1 : 1), rt O

83%

4h O

O

O

84%

Scheme 2.74 Ag NP-promoted photocatalytic Diels–Alder reaction.

2.5.2

Oxa- and Aza-Diels–Alder Reactions

It was found that [4+2] cycloadditions between 1,3-dienes and aldehydes could be promoted by silver salts (Scheme 2.75) [100]. In the presence of 5 mol% AgBF4 , various aromatic and aliphatic aldehydes reacted with 1,3-dienes to generate dihydropyran derivatives 172. Heteroatom substituent at the ortho-position increased the yield, which implies that the silver-chelated aldehyde 171 is involved in the cycloaddition. Other heteroaromatic aldehyde containing pyrrole, furan, indole, and thiophene moieties afforded the corresponding dihydropyrans in moderate to excellent yields. O H

AgBF4 (5 mol%) ClCH2CH2Cl, 80 °C, 24 h

O

Ag X

X

172

O

X = H, Me, OMe, Br

X 171

X Yield(%) H 81 Me 65 p-OMe 45 p-OMe 95 o-Br 98

Scheme 2.75 Ag-catalyzed oxa-Diels–Alder reaction.

The hetero-Diels–Alder reaction between α-ketoester and the Danishefsky’s diene catalyzed by AgF2 complex of a peptide-derived ligand 173 provided dihydropyranones (Scheme 2.76) [101]. This silver-catalyzed reaction engenders

67

68

2 Silver-catalyzed Cycloaddition Reactions

OEt

R

O

OSiMe3 AgF2 (10 mol%) THF, –30 °C, 24 h

O

t-Bu

O

OMe

H N

N N

O

Bn

R = i-Pr, 86% (90% ee) CO2Et R = c-Hex, 62% (90% ee) R

O

O NHn-Bu 173 (10 mol%)

Scheme 2.76 Ag-catalyzed asymmetric oxa-Diels–Alder reaction.

much higher enantioselectivity than previously reported with copper-Box/Pybox complexes [102]. Isochromenylium species is a well-known oxa-1,3-diene that readily undergoes [4+2] cycloaddition, and the isochromenylium derived from ortho-alkynyl salicylaldehydes 174 participates in the double [4+2] cycloaddition of two styrene molecules to generate product 178 (Scheme 2.77) [103]. The reaction starts with the silver-mediated cycloisomerization of ortho-alkynyl salicylaldehydes 174 to generate isochromenylium 175 followed by the first cycloaddition with styrene and subsequent ring opening to generate intermediate 176. The second [4+2] cycloaddition with another styrene approaching from the sterically less hindered face of 176 furnishes adduct 177, which undergoes protodemetalation to afford the final product 178. Diphenyl hydrogen phosphate (DPP) additive is believed to boost up the protodemetalation process. It was found that styrene derivatives with electron-withdrawing substituent did not participate in the reaction. Ar OH O

O

AgOTf/DPP (10 mol%) THF, 0 °C to RT

Ar

H

40–85% 174

R

Ar 178 O

Ag+L/ TfO– Putative catalytic cycle

OH O TfO–

OHTfO–

Ar H

TfO– O

R 175

+

Ag L

Ag O

TfO– HO R O

Ag+L

R

H

Ar Ar

177

R

L+AgO

H O TfO–

R

Ar Ar L+AgO

R

Ar

176

Scheme 2.77 Ag-mediated formation of isochromenylium followed by Diels–Alder reaction.

2.5 [4+2] Cycloadditions

It was reported that silver complexes could promote an inverse-electrondemand Diels–Alder reaction between 1,2-diazine and siloxyalkynes (Scheme 2.78) [104]. Cyclic 1,2-diazine 179, unreactive toward siloxyalkynes in the absence of catalyst even at high temp, readily participated in the Diels–Alder reaction promoted by a π-philic silver catalyst to generate silyl-protected 2-naphthols 180. The yield of the reaction was further improved by adding bidentate ligand because silver ions tend to form polymeric complex with phthalazine. A stepwise mechanism is proposed where simultaneous coordination of the silver catalyst to both phthalazine and siloxyalkyne substrates initiates the reaction. R1

OTIPS N

AgNTf2 (1 mol%) rt, CH2Cl2

R1

OTIPS

N R2

179

N

R1 = Cl, Me, NO2 R2 = alkyl or phenyl

N

67–94%

(1.1 mol%) N

N N

N Ag NTf2

Putative catalytic cycle Ag

N

N

N Ag

[4 + 2]

N

R

R2

180

N N

OTIPS

OTIPS N N R

R2 N Ag N OTIPS

Scheme 2.78 Ag-promoted Diels–Alder reaction of 1,2-diazine with siloxyalkynes.

The hetero-Diels–Alder reaction between the Danishefsky’s diene and N-benzylidene aniline was effectively promoted by silver phosphine complexes containing a carborane counteranion such as [Ag(PPh3 )(CB11 H12 )] and [Ag(PPh3 )(CB11 H6 Br6 )] (Scheme 2.79) [105, 106]. Because of the water- and air-stable carborane ligand, the catalytic activity of these complexes are superior to [Ag(PPh3 )(BF4 )] and [Ag(PPh3 )(OTf )] or comparable with [Ag(PPh3 )(ClO4 )]. Me3SiO

Ph

H N

OMe

Catalyst (1 mol%) O

Ph Water–CH2Cl2 (1:1)

Catalyst Yield (%) Ph Ag(PPh )(BF ) 35 3 4 70 Ag(PPh3)(OTf) N Ph Ag(PPh3)(ClO4) 90 98 Ag(PPh3)(CB11H12) 99 Ag(PPh3)2(CB11H12)

Scheme 2.79 Ag-promoted hetero-Diels–Alder reaction with a carborane counteranion.

69

70

2 Silver-catalyzed Cycloaddition Reactions

The catalytic activity of these silver complexes depends on the existence of external proton source; thus no conversion was observed in rigorously dry dichloromethane. DFT calculations on model system show the counterion effect and water dependence of the reaction. A one-pot three-component coupling protocol was implemented for aza-Diels–Alder reaction involving aldehydes, aromatic amines, and the Danishefsky’s diene promoted by a silver catalyst (Scheme 2.80) [107]. The reaction in water was found to be more effective than that in THF–water mixture, which is due to the slower hydrolysis of the Danishefsky’s diene in water. Me3SiO R1CHO

R2NH2

Water, rt, 2–3 h 51–90% R1 = Ph, c-Hex, Ph(CH2)2, (CH3)2CHCH2 R2 = Ph, 4-MeO-Ph, 4-Br-Ph

OMe

R1

O

AgOTf (10 mol%)

N

R2

Scheme 2.80 Ag-catalyzed one-pot protocol for aza-Diels–Alder reaction.

Jørgensen and coworkers reported the first silver-catalyzed asymmetric aza-Diels–Alder reaction to form 2,3-dihydropyridin-4(1H)-ones (Scheme 2.81) [108]. For the cycloaddition between the Danishefsky’s diene and electrondeficient imine, both Ag-BINAP complexes 181a and 181b were effective catalysts, but they generated the product with marginal enantioselectivity. Significantly higher enantioselectivity could be achieved with the corresponding Cu-BINAP complexes. OSiMe3

CO2Et

+ Ts

N

OMe 181a, Ar = Ph 181b, Ar = Tol

Ligand/Lewis acid (10 mol%)

N

THF, –78 °C PAr2 PAr2

CO2Et

O

Ts

Ligand Lewis acid Yield (%) ee (%) 181a 181b 181b

AgSbF6 AgOTf AgClO4

75 85 90

33 34 30

Scheme 2.81 Ag-catalyzed asymmetric aza-Diels–Alder reaction.

The catalytic activity of robust cationic and neutral silver-XPhos complexes 182a–182d for aza-Diels–Alder reactions was explored (Scheme 2.82) [109]. With 6 mol% loading of these catalysts, the Danishefsky’s diene and aldimines provided dihydropyridones in excellent yield. The bulky phosphine ligands are responsible for the stability of these complexes, which results in their good catalytic performance. Silver complexes ligated with amino acid-derived iminophosphine ligands 183a and 183b were found to be effective for asymmetric aza-Diels–Alder reactions between the Danishefsky’s diene and arylimines derived from o-anisidine (Scheme 2.83) [110]. High enantioselectivity (up to 95% ee) was achieved with a wide range of substrates. With 0.1 mol% loading of the catalyst, greater than

2.5 [4+2] Cycloadditions

Me3SiO

Ph N

Ag–L (6 mol%) Dioxane/water rt, 1 h

Ph

OMe

t-Bu t-Bu P Ag OTs i-Pr

t-Bu OTs t-Bu P Ag OH2

Ph

O N

Ph

t-Bu SbF 6 t-Bu P Ag NH Ph 2

Ag–L Yield (%) 182a 182b 182c 182d

91 94 80 96

t-Bu Ph t-Bu P Ag N SbF 6 Ph

Me i-Pr

182a

182b

182c

182d

Scheme 2.82 Ag-XPhos complexes for aza-Diels–Alder reactions.

+

Ar

AgOAc/183a,b (0.5–1 mol%) O i-PrOH (1 equiv.) THF, 4 °C, 12 h

Ar

OSiMe3

N

86–98% (89–95% ee)

OMe MeO Me

Et

PPh2

O 183a

Et H N

N OMe

Ar = Ph, 2-Br-Ph 3-NO2-Ph, 4-MeO-Ph 2-Furyl, 1-Naph, 2-Naph

MeO Me

H N

N

N

PPh2

O

183b

Scheme 2.83 Ag-iminophosphine-catalyzed aza-Diels–Alder reactions.

98% conversion of starting materials was accomplished with slightly reduced enantioselectivity (88% ee). In the absence of alcohol additive i-PrOH (t-BuOH, MeOH, and H2 O could also serve the purpose), the reaction was much slower. Yamamoto and coworker reported highly regio-, diastereo-, and enantioselective silver-catalyzed azo-Diels–Alder reaction between acyclic siloxydienes and 2-hydrazinopyridine 184 (Scheme 2.84) [111]. The efficiency of the reaction was sensitive to the ratio of a silver salt and the ligand. Siloxydienes bearing protected alcohols and amines provided cycloadducts 185 with good to excellent enantioselectivity. R1

N

TIPSO N R2

Troc

R1 = Me, Bn, 4-MOM-Bn R2 = Me, i-Pr, Ph, 2-Furyl

N 184

R1 AgOTf (10 mol%) (R)-BINAP (10 mol%) EtCN, –78 to 40 °C, 3 h 65–87% (55–99% ee)

TIPSO

N N

Py Troc

R2 185

Scheme 2.84 Diastereo- and enantioselective Ag-catalyzed azo-Diels–Alder reaction.

The azo-Diels–Alder reactions between dienes and urea-based diazene 186 were effectively promoted by BINOL-derived silver phosphate 187 (Scheme 2.85) [112]. The dienes containing a free hydroxyl group and its protected forms as a silyl ether provided products 188 and 189 with the opposite regioselectivity. This

71

72

2 Silver-catalyzed Cycloaddition Reactions

R

HO

O 1

+

Boc

N N

N H 186

CH2Cl2, –40°C

Ar

TBSO

O N N

Ar2 Boc 187 (10 mol%) 188 O O P 98% (88% ee) O OAg(OH)2

Ar1 = 4-Cl-Ph

N N

NHAr′

Boc NHAr′

189 O 96% (98% ee)

Ar2 Ar2 = 2,4,6-i-Pr3-Ph

Scheme 2.85 Asymmetric azo-Diels–Alder reactions with BINOL-derived Ag phosphate.

behavior is the consequence of the hydrogen bonding between the silver phosphate moiety and the hydroxyl group. It is evident from computational study that water molecules played a pivotal role in determining stereochemistry. 2.5.3

Hexadehydro Diels–Alder Reactions

It was reported that thermally generated arynes from tetraynes 190 could participate in C–H insertion process in the presence of π-philic metal complexes (Scheme 2.86) [113]. Although many π-philic metal including AgSbF6 , AgNO3 , AgOAc, AgO, Cu(OTf )2 , Zn(OTf )2 , Sm(OTf )3 , In(OTf )3 , Sc(OTf )3 , and Ru3 (CO)12 could promote the C–H insertion, AgOTf (10 mol%) was the catalyst of choice, which generated product 192 in the range of 62–96% yield. The Thorpe–Ingold effect induced by the propargylic gem-dimethyl group significantly improved the yield of the product. Although the mechanism for the formation of the aryne intermediate is not clear, one of the possible modes is the silver-promoted stepwise process, leading to the bis-carbenoid 191. Exploiting the reactivity of silver-activated aryne 193, a range of nucleophile addition products 195 could be generated employing − F, − CF3 , and − SCF3 as the R1

=R

R AgOTf (10 mol%) Toluene, 90 °C, 5 h 62–96%

TsN

190 1

R = Alkyl, aryl, silyl R2 = Alkyl

R2

N Ts

192

Ag+

R2

R R TsN

NTs

H Ag+

Ag+

R

N Ts

R2

R

+

Ag

N Ts

H Ag+

R2

191

Scheme 2.86 Ag-catalyzed C–H insertion in hexadehydro Diels–Alder reactions.

2.6 [2+2+1] Cycloadditions

nucleophiles (Scheme 2.87) [114]. For hydrofluorination, AgBF4 could be used not only as a stoichiometric reagent but also as the catalyst (10 mol%) in combination with pyridinium tetrafluoroborate as a HF source. Bis-halogenation products 196 could be generated by trapping the organosilver intermediate 194 with N-halosuccinimides. R R1 = R R2

TsN

n-Bu

[Ag–Nu]

Toluene, 90 °C, 4 h

R1, R2 = Alkyl, aryl, silyl

Ag+

R

R

2

R

N Ts

R

N Ts

Ag+ 193

N Ts

–

Nu

Ag

90 –F –CF3 75 –SCF3 85

195

Ag+ R 2

R

R

N Ts

H

H+

2

Nu Yield (%)

Nu

SiMe3

NXS N Ts X 196

Nu

Ag 194

X Yield (%) F

50 80 55

Cl Br I

Scheme 2.87 Ag-promoted addition reactions in hexadehydro Diels–Alder reactions.

2.6 [2+2+1] Cycloadditions Metal-catalyzed multicomponent coupling reactions (MCRs) have drawn significant attention because of their capacity to generate complex molecular structures with atom economy. While classical isocyanide-based MCRs such as Ugi, Passerini, and Gröbcke–Blackburn–Bienaymé reactions proceed without catalyst, a new isocyanide-based three-component reaction was realized with allenoate and electron-deficient alkenes in the presence of metal complexes (Scheme 2.88) [115]. AgSbF6 was found to be the catalyst of choice among various metal complexes examined including FeCl3 , RuCl3 ⋅xH2 O, HAuCl4 ⋅3H2 O, R1

R1

CO2Et +

•

Ar CN–R2

AgSbF6 (5 mol%)

CN

CO2Et

+

Toluene, 90–120 °C, 8–24 h CN Ar 49–95% NR2 R1 = H, Me 2 R = Bn, c-Hex, PMB, 2,4-Me2-Ph NC CN Ar = Ph, 3-MeO-Ph, 4-Br-Ph

Ag+

Ag+

OEt OEt R1

O •

1

R

OEt Ag

R1

O

O

Ag

Ag

C

CN–R2

Ar

N+ 2 R CN

NC

Scheme 2.88 Ag-catalyzed isocyanide-based three-component coupling reaction.

73

74

2 Silver-catalyzed Cycloaddition Reactions

AgOTf, Cu(TFA)2 , CuI, K2 PtCl4 , BiCl3 , and InCl3 . It is proposed that the reaction commences with the 1,4-addition of isocyanide onto the silver ion-coordinated allenoate ester followed by the second 1,4-addition of the resultant enolate and cyclization. The decomposition of methyl phenyl diazoacetate by silver complexes in the presence of arylaldehydes and electron-deficient alkenes or alkynes provided highly substituted tetrahydrofuran or dihydrofuran derivatives (Scheme 2.89) [116]. Although conventional silver complexes such as AgBF4 and AgSbF6 could promote the reaction, bulky N-heterocyclic carbene-ligated cationic silver species in combination with 4 Å molecular sieves provided most favorable results. High regioselectivity and diastereoselectivity can be rationalized by the [3+2] cycloaddition involving an asynchronous endo transition state. R1

CHO Ar

CO2Me +

+

N2 R3

R2

IPrAgCl (5 mol%) AgOTf (5 mol%)

MeO2C

O

Ar

4 Å MS, CHCl3, rt 20–96%

R3 2

R1

R

+

Ar = Ph, 2-Naph, 4-NO2-Ph

Ph

O

R1 = CO2Et, CO2Me, COCH3

CO2Me

–

Ph

R2 = H, CO2Et R3 = OH, Me, Br, F, NO2

Scheme 2.89 Ag-promoted synthesis of dihydrofuran derivatives via [3+2] cycloaddition.

2.7 Miscellaneous Reactions 2.7.1

[2+1] Cycloaddition

The silver-catalyzed reaction between N-substituted α-imino esters and diazo compound provided aziridines in moderate to good yield with excellent regioselectivity (Scheme 2.90) [117]. However, low enantioselectivity was observed even under optimized conditions employing (R)-Tol-BINAP (181b)–CuClO4 catalytic system. This reaction proceeds via the nucleophilic addition of diazo compound with silver ion complexed imine instead of generating metal carbenoid intermediate.

N EtO2C

Ts

N2

AgSbF6 (10 mol%) 181b (11 mol%)

LnAg

THF, –78°C

EtO2C

R

N

Ts

Ts –

N2 +

R

N

AgLn

Ts N

R

EtO2C

N2

EtO2C

R

+

R = SiMe3, 88%, 20 : 1 dr, 12% ee R = CO2Et, 32%, 1 : 1 dr, 20% ee

Scheme 2.90 Ag-catalyzed formation of aziridines diazo compounds and imines.

2.7 Miscellaneous Reactions

Davis and coworker demonstrated that the silver-catalyzed reaction of phenyl diazoacetate and vinyl diazoacetate with styrene generated highly substituted cyclopropanes with exceptional diastereoselectivity (Scheme 2.91) [118]. Analogous cyclopropanation reactions could be carried out under mechanochemical conditions in stainless steel and vial system using silver foil as the promoter [119]. R

CO2Me

R

AgSbF6 (10 mol%)

CO2Me

R = Ph, 96%

+ Ph

N2

CH2Cl2, reflux

R = Cinnamyl, 82%

Ph

Scheme 2.91 Ag-catalyzed [2+1] reaction for cyclopropanation.

He and coworker developed an efficient aziridination via silver-catalyzed nitrene transfer onto alkenes (Scheme 2.92) [120]. It was proposed that the electronic communication between the two silver moieties in the dimeric silver complex 197 plays an important role to react with PhI=NTs to form a transient silver nitrenoid Ag=NTs. O N R1

197 (2 mol%), 4 Å MS

+ PhI=NTs R2

CH3CN, rt, 8–20 h 66–91%

O

t-Bu

AgNO3 (2 mol%)

R3

R1 R2

Ts N

N Ag N

R3 t-Bu

t-Bu

+

O N

t-Bu N

Ag N N

t-Bu

197 t-Bu [Ag2(t-Bu3tpy)3(NO3)](NO3)

Scheme 2.92 Ag-catalyzed nitrene transfer for aziridination.

An effective aziridination was realized via nitrene transfer catalyzed by silver hydrotris(pyrazolyl)borate complex 198 (Scheme 2.93) [121]. Through experimental and computational studies, a two-electron transfer pathway was proposed for this aziridination reaction. By maintaining a minimum energy crossing point (MECP) between the triplet and closed-shell singlet surfaces, the direct formation of the aziridines occurs, and the stereochemistry of the olefin is retained. Relying on this catalytic system, regioselective aziridination was achieved to form a vinyl aziridine from dienes or 2,4-dien-1-ols [122, 123]. A silver-catalyzed aziridination reaction was also realized by using Chloramine-T as the nitrene precursor (Scheme 2.94) [124, 125]. A stoichiometric amount of silver nitrate was required, and the choice of solvent was crucial for this reaction. It was reported that di-tert-butylsilylene transfer from cyclohexene silacyclopropane 199 to alkenes could be promoted by silver complex (Scheme 2.95) [126–128]. Although silylene transfer could occur at high temperature (130 ∘ C) without catalyst after an extended reaction time (36 hours), using 10 mol%

75

76

2 Silver-catalyzed Cycloaddition Reactions

198 (1 mol%)

+ PhHI=NTs

CH2Cl2, rt overnight

H

Ts N

–

TS 198

+

R

HO

Ag

[(Ar)3BH]

–

[(Ar)3BH] Ag N Triplet Ts

PhI=NTs

Br

N N N N

N N

Ag+ Br 3

B

Br

Ts

N

198 (5 mol%)

NTs

HO

CH2Cl2, rt, 3 h >99%

R

Regioselectivity >85% Stereoselectivity >98%

Scheme 2.93 Nitrene transfer catalyzed by Ag-hydrotris(pyrazolyl)borate. AgNO3 (1 equiv.) R2

Na+ Cl

R3 R1 3 equiv.

N

Ts

CH2Cl2, rt or

–

+

Ts

N

Toluene, 60 °C 43–92%

1 equiv.

R1

R2 R3

Scheme 2.94 Ag-catalyzed aziridination using Chloramine-T.

t-Bu Si t-Bu

+

R1

199

R2

AgOTf (5–10 mol%) toluene-d8, 2 h, –27 °C TMEDA 61–99% (NMR) 89 : 11–95 : 5 dr

AgOTf

t-Bu

t-Bu R2

R1

ZnBr2 (20 mol%) HCO2CH3

Si 200

61–87% 74 : 26– >99 : 1 dr

t-Bu t-Bu Si O R1 201

OMe R2

R1 = Me, i-Pr, n-Bu, Bn

AgOTf

R2 = H, Me TfO

t-Bu Si t-Bu AgLn

t-Bu AgLn t-Bu Si OTf

t-Bu OTf AgLn t-Bu Si R1

R2

Scheme 2.95 Ag-catalyzed silylene transfer to alkenes to form silacyclopropanes.

AgOTf or AgOC(O)CF3 significantly reduced the reaction time (2 hours) even at −27 ∘ C. The silacyclopropanes 200 could be further reacted with methyl formate in the presence of 20 mol% ZnBr2 to provide oxasilacyclopentane acetals 201 in 61–92%. The silver-catalyzed silylene transfer could occur with terminal and internal alkynes (Scheme 2.96) [129]. Differently substituted silacyclopropenes 202 were generated from 199 and alkynes by employing Ag3 PO4 (10 mol%) as a catalyst, and without isolation they were treated with carbonyl compound in the presence of copper salt to generate oxasilacyclopentenes 203. In all cases, carbonyl insertion has occurred into the more substituted C—Si bond.

2.7 Miscellaneous Reactions

t-Bu Si t-Bu + R2 199

1

Ag3PO4 (10 mol%) Benzene-d6, 22 °C, 3 h

R

79–97% (NMR)

R3COR4, CuLn (15 mol%) Toluene, –20 °C, 3 h

t-Bu t-Bu Si R2 R1 202

t-Bu t-Bu Si O R3 R1 R4 203 R2

68–94% Regioselectivity 97 : 3–99 : 1

R1 = Et, Ph, n-Bu, CH2OTIPS, CH2OMe; R2 = H, Me, Et

CuLn = CuBr2, CuI, Cu(OTf)2

R3 = Ph, Et, n-Pr, OEt; R4 = H, Me, Et

Scheme 2.96 Ag-catalyzed silylene transfer to alkynes to form silacyclopropenes.

2.7.2

[4+1] Cycloaddition

The silver-promoted transfer of di-tert-butylsilylene from cyclohexene 199 to α,β-unsaturated ketones generated oxasilacyclopentenes (Scheme 2.97) [130]. The initial formation of silyloxy ylide 204 followed by its 6π-electrocyclic ring closure constitutes a formal [4+1] cycloaddition, which provides various oxasilacyclopentenes 205. t-Bu

O Si

t-Bu t-Bu

199

+ R1

AgOCOCF3 (1–5 mol%) CH2Cl2, rt, 3 h

R3 R2

+

O

71–99%

R1

R1 = OBn, OEt, Ph, Me

t-Bu

Si– t-Bu

O Si

R3

R1

R2 204

R2 = H, Me. R3 = H, Me, Ph

205

t-Bu R3

R2

Scheme 2.97 Ag-catalyzed silylene transfer to α,β-unsaturated ketones to form oxasilacyclopentenes.

The silylene transfer from 199 could be extended to imines derived from α,β-unsaturated aldehydes (Scheme 2.98) [131]. The initial cycloadduct 206 could not be isolated; rather it readily isomerized via iminium species 207 under the conditions, leading to dimerized tetracyclic compound 208. Ar t-Bu Si t-Bu 199

+

AgOTf (1 mol%) Toluene, 23 °C, 1 h

N Me

207

N

t-Bu t-Bu Si Me Ar N

Si– t-Bu Me

N

t-Bu

+ Si Ar N

+

Ar = 4-Me-Ph t-Bu

t-Bu

t-Bu Ar

Si

t-Bu Me

206 t-Bu N

Si

t-Bu Me

Me Ar +N t-Bu

40% Si

Me t-Bu

Ar N t-Bu

208 Si

Me t-Bu

Scheme 2.98 Ag-catalyzed silylene transfer to α,β-unsaturated imines.

2.7.3

[4+2] Cycloaddition

Azetidines were employed as the four-atom component in metal-catalyzed [4+2] cycloaddition reactions with ynamides (Scheme 2.99) [132]. The reaction of azetidine and ynamides was promoted by AgSbF6 at room temperature to

77

78

2 Silver-catalyzed Cycloaddition Reactions

R2

R3

2

R

1

R C N Me 209

Ar N

X = O, NTs

R2

CH2Cl2, rt, 0.25–4 h

Ar

45–90%

R1, R3 = Ms, Ts R2 = alkyl, aryl Ar = Ph, 4-Cl-Ph 4-MeO-Ph

Ag+

AgSbF6 (10 mol%)

N

N Me

Ag

R1

R3

R1

N

Me N

R3

Ar 211 Ag+

Plausible reaction mechanism

Me

N

Ag

R1 +

N

R

2

Ar

R

Me 3

N

Ag R2 Ar

R1 NR3

Me Ag R2

+

N

R1 NR3

Ar 210

Scheme 2.99 Ag-catalyzed formal [4+2] cycloadditions between azetidine and ynamides.

produce 2-amino-1,4,5,6-tetrahydropyridine derivatives 211 in moderate to high yield. Other catalytic systems like AgNTf2 , LAuCl/AgBF4 , LAuCl/AgSbF6 , and LAuCl/AgNTf2 could also promote the reaction. Mechanistically, the reaction commenced with the interaction of ynamide with a silver ion to generate organosilver keteniminium intermediate 209, which reacts with an azetidine to generate a carbocationic intermediate 210 followed by its cyclization and demetalation, leading to 211.

2.8 Conclusion The silver-promoted [2+2] cycloaddition was first reported 50 years ago, but the majority of experimental and theoretical studies were documented in the last decade. Summarized herein are representatives of various silver-catalyzed cycloadditions reactions. These examples clearly reflect not only the unique merits but also the limitation of silver-catalyzed cycloaddition reactions compared to those with other metal complexes. Although moderately Lewis acidic, the carbophilic, oxophilic, and azaphilic character of d10 silver ion has shown remarkable catalytic effectiveness in the synthesis of a large array of carbocycles and heterocycles. Silver-promoted dipolar cycloaddition is highly efficient to construct five-membered heterocycles such as pyrrolidines, imidazolines, oxazolines, pyrroles, and triazoles derivatives, and the asymmetric [3+2] cycloaddition of azomethine ylides with alkenes to form pyrrolidines is one of the most successful areas of silver-catalyzed cycloadditions. The unique merit and utility of silver-catalyzed [4+2] cycloaddition begins to emerge and was clearly demonstrated in the synthesis of core structures of several natural products including brosimones, panduratin A, and sorocenol B. Yet the construction of other rings via [2+2], [3+3], and [2+2+1] cycloadditions is still in infancy. The ready availability of diverse form of silver complexes, the easy handling mainly due to their relatively nonsensitive nature to moisture and

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3 Silver-Catalyzed Cyclizations Valerie H. L. Wong 1 and King Kuok (Mimi) Hii 2 1 School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371. 2 Imperial College London, Department of Chemistry, Exhibition Road, South Kensington, London SW7 2AZ, UK

3.1 Introduction This chapter provides an overview of the developments in silver-catalyzed cyclization reactions, i.e. the generation of either a carbocyclic or heterocyclic ring, through the formation of C—C, C—N, and C—O bonds. This may be achieved through cyclization reactions, such as the enyne reaction and related reactions of unsaturated systems containing heteroatoms (C=N and C=O) and alkynes/allenes, as well as the addition of N—H and O—H bonds to alkenes, allenes, and alkynes. All these reactions are made possible by the π-acidity/“carbophilicity” of the group 11 metals (copper, silver, and gold) that can activate unsaturated carbon–carbon multiple bonds, which has been exploited extensively in the last two decades in catalytic synthetic methodology development: the most famous examples include the use of Cu catalysts in Huisgen 1,3-dipolar cycloaddition reactions between alkynes and azides (CuAAC) [1] and the use of Au catalysts for a broad range of reactions involving transformation of alkenes and alkynes, including the addition of heteroatoms, cycloisomerization, rearrangement, and redox reactions [2]. In comparison, silver is often overlooked in these reactions, even though they may be expected to display intermediate behavior. This chapter will aim to provide an overview of the use of silver salts and complexes in cyclization reactions that involve the activation of an unsaturated carbon–carbon bond, with an emphasis on the role of silver in the reaction mechanism and the resulting regio- or chemoselectivity of the process. Note that cascade-type carboxylation and cyclization will not be included, as it will be covered elsewhere in the book (Section 7.5, “Silver-catalyzed CO2 Reactions”). It should be noted that some of the reactions listed in this chapter are also known to proceed under Brønsted acid catalysis (particularly at elevated temperatures). In the absence of control experiments, it is not always clear what the active catalyst is, particularly when silver salts of weak counteranions (e.g. OTf, BF4 , NTf2 ) were employed, which can generate strong Brønsted acids Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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3 Silver-Catalyzed Cyclizations

in situ. It is beyond the remit of this review to distinguish between Brønsted and Lewis acid-catalyzed reaction; we will simply include reactions that occurred in the presence of silver salts or complexes. Conversely, there are cases where silver catalysis is clearly evident, e.g. when the reaction proceeds with good enantioselectivity.

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions) Both silver and gold catalysts are frequently employed in cycloisomerization reactions where an allene or an alkyne undergoes carbon–carbon bond-forming reactions with carbonyl/carboxy groups, imines, amides, or alkenes [3]. The reactions are known to be sensitive to the counteranion. The reaction also often involves H-abstraction/transfer, where the balance between pK a of the reactants and X− becomes important. 3.2.1

Conia-ene Reaction

The Conia-ene reaction involves an intramolecular addition of an enol to an alkene or an alkyne, resulting in the formation of a carbocyclic ring containing a quaternary stereogenic carbon (Scheme 3.1). The cyclization generally proceeds with exo-dig regioselectivity to form the smaller ring, although endo-dig cyclization is favored in some cases. A number of catalysts with different modes of activation have been reported to be effective for the Conia-ene reaction [4]. Reactions that proceed with pure alkyne activation are best known to proceed with cationic Au(I) catalysts, in work pioneered by Toste and coworkers [5–7]. Interestingly, Ag(I) salts were initially reported to be inactive in these reactions. However, this was shown not to be the case by Miesch and coworkers [8], where alkynylsilyl enol ethers 1 undergo cyclization in the presence of 5 mol% of AgNTf2 to afford the spiro compounds 2 and 3 (Scheme 3.2), with yields that are comparable with that obtained using gold(I) catalysts: control reactions showed that neither silver(I) carbonate or the conjugate acid of the counteranion (triflimide, Tf2 NH) were catalytically active. The reactions produced five-membered carbocycles in all the examples shown, but the position of the C=C bond in the final product was found to be dictated by the choice of solvent: in CH2 Cl2 , the formation of the exo-regioisomers 3 was favored in most cases, while the endo-regioisomer 2 was obtained as the major product when the reaction was conducted in toluene. The proposed mechanism involves the π-activation of the alkyne by Ag, followed by an exo-dig cyclization with the most substituted R2

O

R1 n

R2 R1

O

n

Scheme 3.1 The Conia-ene reaction.

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

AgNTf2 (5 mol%)

O

Toluene, 23 °C (R = H) OTBS

2 O

AgNTf2 (5 mol%) R

CH2Cl2, 23 °C (R = H, CO2Et) 1 NIS (1.0 equiv.) AgNTf2 (5 mol%) DCE, 23 °C (R = H)

3 R 35–86% O

I 4 13–81%

Scheme 3.2 The first reported Ag-catalyzed Conia-ene reaction.

(thermodynamically more stable) silyl enol ether to afford a vinyl silver(I) organometallic species, which can undergo protonolysis reactions to afford either regioisomer 2 or 3, depending on the relative pK a of Tf2 NH in different solvents (Scheme 3.3). In the presence of N-iodosuccinimide (NIS), the vinyl silver(I) intermediate can be trapped to afford the (E)-alkenyl iodide derivatives 4 (Scheme 3.2). OTBS 2 or 3 OTBS

OTBS NTf2 +

[Ag] HNTf2 OTBS

OTBS

[Ag]

+

[Ag] +

OTBS H [Ag]

Scheme 3.3 Proposed mechanism for the Ag-catalyzed Conia-ene reaction.

Verma and coworkers exploited the inherent Lewis acidity of the silver salt in a Conia-ene reaction by using AgOTf to catalyze the electrophilic cyclization of 3-(2-alkynyl)aryl-β-ketoesters 5 to heterocyclic compounds 6, such as acridinol, quinolinol, naphthalenol, and benzothiophenol (Scheme 3.4) [9]. In this case, the

87

88

3 Silver-Catalyzed Cyclizations

O

OH CO2Et

CO2Et

AgOTf (10 mol%)

X

X

CH2Cl2, 25 °C

R

R

X = CH, N, S R = alkyl, aryl

5

6

Scheme 3.4 Cycloisomerization of alkynyl β-ketoesters.

1,3-ketoester can chelate to the silver salt to generate the active enolate for the Conia-ene reaction, in addition to the π-activation of the carbon–carbon triple bond. The presence of Ag(I) was essential for the success of the reaction, as CuOTf and triflic acid were not effective for the assembly of the aromatic ring. A similar strategy was employed for the synthesis of 3-pyrrolines 8 from N-sulfonyl-β-ketopropargylamines 7 (Scheme 3.5) [10]. Once again, only the silver salts with weakly coordinating counteranions (AgOTf, AgSbF6 , and AgNTf2 ) were effective as catalysts, while other Lewis acids such as Au(I), Cu(I), Cu(II), and Fe(III) did not induce any product formation. When the 3-pyrrolines 8 (R2 = Ts) were treated with a stoichiometric amount of K2 CO3 in methanol, desulfonylation of the nitrogen atom triggered an isomerization process to furnish the corresponding 2-substituted pyrroles 9 in good yields.

O R1

R3

R2 N

R3

AgOTf (10 mol%)

K2CO3 (1.0 equiv.)

R1

MeNO2, 80 °C

O

7 R1 = alkyl, aryl, heteroaryl R2 = Ts, Ns R3 = H, Me, Ph

8

N R2

R3 R1

MeOH, r.t. (R1 = aryl, R2 = Ts, R3 = H)

O 9

N H

Scheme 3.5 Ag-catalyzed Conia-ene cyclization of β-ketopropargylamines.

Cyclic 1,3-diketones 10 undergo silver-catalyzed 6-endo-dig cyclization to furnish bicyclo[3.2.1]alkenes 11 in good yields (Scheme 3.6) [11]. AgOTf was the best catalyst for the reaction, but good to excellent yields were also obtained using AgSbF6 , AgNTf2 , AgClO4 , and AgBF4 . In contrast, no product was formed in the presence of AgOAc, AgNO3 , AgCN, Ag2 CO3 , or PhCO2 Ag. Interestingly, [Au(PPh3 )Cl] is not an effective catalyst for the reaction, which was attributed to its inability to enolize the ketone. O

R1 n

AgOTf (5 mol%) O 10

R2

R2

O

DCE, 90 °C R1 = H, CO2Et, COMe R2 = aryl n = 0 to 2

R1 O

n

11

Scheme 3.6 6-endo-dig cyclization to furnish bicyclo[3.2.1]alkenes.

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

AgNTf2 is also able to catalyze the rare 7-exo-dig cyclization of silyl enol etherynesulfonamides 12 to form bridged bicyclic keto-enamides 13 (Scheme 3.7) [12]. The procedure tolerates a variety of ynesulfonamide substituents, such as aryl, alkyls, heteroaryls, protected alcohols, halogens, alkenes, and cycloalkanones. Ts N

OTBS

AgNTf2 (1 mol%)

n

R2

R3

1

R

R3

Ts N n

DCE, r.t. n = 0 to 3

O R1

12

R2 13

Scheme 3.7 Ag-catalyzed 7-endo-dig Conia-ene reaction.

In 2016, Enders and coworkers have shown that silver catalysts can be used successfully in combination with organocatalysts to achieve a one-pot stereoselective synthesis of spiropyrazolones 16 from alkyne-tethered nitroolefins 14 and pyrazolones 15 (Scheme 3.8). The reaction involves a sequential organocatalytic asymmetric Michael addition of the pyrazolone to the nitroolefin in the presence of 1 mol% of the dihydroquinine-derived squaramide 17, followed by a silver-catalyzed formal Conia-ene reaction [13]. The same approach was adopted to achieve an enantioselective Conia-ene reaction of alkyne-tethered β-ketoesters 18 to furnish cyclopentane products 19 in good yields and enantioselectivities [14]. In this case, enantioselectivity was achieved via the enamine activation of the ketone by the cinchona-derived primary amine 20 (in the presence of trifluoroacetic acid, TFA), which directs the stereochemistry of the electrophilic activation of the alkyne by AgNTf2 .

R

O

NO2

1

+ R

14

R3

2

O R

R2

1

18

17 (1 mol%) Ag2O (3 mol%)

R N R4 CHCl3, –40 °C N 15 R1 = Me, OMe, Cl, F R2, R3 = alkyl, aryl R4 = Me, aryl

O2N

O N N

1

R 16 R2

20 (20 mol%), O TFA (20 mol%), R1 R2 AgNTf2·MeCN (2.5 mol%)

R2

O

O

HN

N H

N

N

4

MeO

OMe

CF3

17

Et NH2 N

CH2Cl2, r.t. R1 = alkyl, aryl R2 = CO2R, CO2R, SO2R

CF3

19

H 20

Scheme 3.8 Asymmetric Conia-ene reaction achieved by using chiral amine-silver catalysts.

3.2.2

Cycloisomerization

This class of reaction includes the reaction between unsaturated carbon–carbon functional groups, e.g. ene–yne reactions between alkene and alkyne or between two alkenes – the latter requiring matching highest occupied molecular orbital– lowest unoccupied molecular orbital (HOMO–LUMO) combinations, which invariably involves alkenes with different electronic properties.

89

90

3 Silver-Catalyzed Cyclizations

3.2.2.1

Cycloisomerization of Enynes

Cycloisomerization reactions of 1,n-enynes (where n ≥ 6) are a highly effective strategy for the synthesis of carbo- and heterocycles. In the presence of “carbophilic” metal catalysts, the triple bond is activated towards the attack by the alkene to form metal carbenoid intermediates to afford diene products after a series of proton shifts (Scheme 3.9) [15, 16]. [M] [M]

X n

X

R

n

X = CH2, N, O, etc.

H

[M] X

+H

X n

n R

+

R

R +

–H

[M]

[M] X

X n

n R

R H

Scheme 3.9 Cycloisomerization of 1,n-enynes.

In 2012, Shin and coworkers explored the silver-catalyzed cycloisomerization of propiolamide-derived 1,6-enynes 21, resulting in the selective formation of 1,4-dienes 22 at room temperature (Scheme 3.10) [17]. In this case, AgNTf2 has been shown to be more efficient than gold or platinum salts. The reactions of cyclohexenyl amide substrates 23 can only be achieved using a higher catalyst loading of AgSbF6 under more forcing conditions; in this case, better yields were obtained using [Au(tBuXPhos)][SbF6 ]. The nature of the N-substituent and the terminal group on alkyne were key to the observed selectivity, as demonstrated by the cyclization of the N-tosyl-tethered 1,6-enyne substrate 25 and the ester-substituted 27. In the former case, the 6-endo-dig Alder-ene-type product 26 was obtained in a low yield, along with extensive decomposition of the starting material; in the latter case, an intramolecular [4+2] annulation product 28 was obtained following hydrolysis. For the cyclization of 1,6-enynes 29 substrates with allylstannane groups, the reaction afforded a mixture of the vinylstannanes 30 and the diene 31 using AgOTf (10 mol%) in the absence of any ligands (Scheme 3.11) [18]. The proposed mechanism involves a silver carbene intermediate 32 that isomerizes to the alkenyl silver complex 33, which then reacts with the tin electrophile Bu3 SnOTf generated in situ to give the stannane product 30. Using the chiral catalyst [(AgOTf )2 (Tol-BINAP)], the reaction furnished optically active 30 (where Z = SO2 Ph) with up to 78% enantiomeric excess (ee) (Scheme 3.12). Jiang and coworkers demonstrated that tri- or tetrasubstituted furans 36, 37, and 37′ can be constructed from electron-deficient alkynes 34 and propargyl alcohol derivatives 35 by a silver-catalyzed one-pot reaction (Scheme 3.13) [19]. The mechanism involves the nucleophilic addition of 35 to 34 to form the enyne adduct 38, which subsequently undergoes 6-endo-dig cyclization and rearrangement to form the allene intermediate 39: when R1 ≠ R2 , either of the carbonyl

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

O

O AgNTf2 (5 mol%)

R1 N

R3

R1 N

DCE, r.t.

R1 = H, aryl, Bn, allyl, n-Bu; R2, R3 = Me, H R1 = Ph; R2,R3 = (CH2)4

2

R

21

O Ph

R2

R3

22

O

N

AgSbF6 (15 mol%)

PhN

DCE, 80 °C n

n

23

24

O AgNTf2 (5 mol%)

Ts N

Ts

Ag

N

DCE, 60 °C

Ts N H-transfer

H

+

25

26, 21%

O

+

CO2Et

TsN

Ag

Ag

CO2Et

AgNTf2 (5 mol%) DCE, r.t.

CO2Et TsN

TsN H

27 C–O

O TsN

O

Then hydrolysis

28

Scheme 3.10 Cycloisomerization of 1.6-enynes derived from propiolamide.

Z Z

R1

SnBu3 [Ag]

R2

Toluene, 70 °C

Z = CO2Me, SO2Ph, CH2OAc, CH2OTBDPS +

R1

+

R2

R1

Z Z

R2

30 31 When Z = CO2Me, R1 = R2 = H [Ag] = AgOTf (10 mol%): 29% (24), 24% (25) [Ag] = [Ag(OTf)(PPh)3]3 (3 mol%): 90% (24 only)

29 SnBu3

[LAg] [LAg(OTf)] MeO C 2 29 MeO2C

Z Z

–

OTf

[Ag] –SnBu3OTfMeO2C SnBu3 MeO2C

H 32

SnBu3OTf –[LAg(OTf)]

33

Scheme 3.11 Intramolecular carbostannylation of alkynes catalyzed by Ag(I).

30

91

92

3 Silver-Catalyzed Cyclizations

SnBu3 [(AgOTf)2(R)-tol-BINAP] PhO2S * (5 mol%) PhO2S Toluene, 50 °C SnBu3 91% yield, 89 : 11 e.r.

PhO2S PhO2S

Scheme 3.12 Enantiomeric silver-catalyzed carbostannylation of alkynes. 1. DABCO (10 mol%), CH2Cl2, r.t.

R1

O 36 R2 = CO2Me, CO2Et R1 = OMe, OEt; R3 = H, alkyl, aryl

+ R2 34

HO 35

1. PBu3 (20 mol%), CH2Cl2, r.t.

R3

R2

2. AgOAc (5 mol%), PPh3 (10 mol%), toluene, 50 °C

R3

O

O

R1

O

O

R3

R1

R3

Ph +

2. AgOAc (5 mol%), Ph toluene, 50 °C

R1

O 37

O 37′

R2 = Ph R = aryl; R3 = H, Ph 1

R3

PPh3 or DABCO O 34 + 35 R1 R2

O

R2

R2

O 38

O

O

II O

Ag +

+

Ag

R1

R3

R1

R3

O

Ag(I)

R3

R1 R2

37 + 37′

• O 39

I

Scheme 3.13 Silver-catalyzed assembly of highly substituted furan rings from electron-deficient alkynes and propargyl alcohols.

groups could undergo cyclization (pathway I or II) to form the regioisomeric furans 37 and 37′ . In a very similar reaction, Martins et al. reported that a 6-endo-dig cyclization of N-propargylic β-enaminones 40 (where R3 = CF3 or CO2 Et) occurred to afford 1,2-dihydropyridines 41 in the presence of 10 mol% of AgNO3 (Scheme 3.14) [20]. The reaction was proposed to proceed via the intramolecular nucleophilic attack of the α-carbon of the carbonyl group on the activated alkyne. With one substrate (R1 = Pr, R2 = Me, R3 = CF3 ), however, 5-exo-dig cyclization occurred to afford a highly substituted pyrrole 42 in excellent yield (80%) (Scheme 3.15). The formation of this compound may occur via an allene intermediate, in a similar manner as described in Scheme 3.13.

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

O

R2

O R3

AgNO3 (10 mol%)

N R1

R3

CHCl3, 25 °C R1 = aryl R2 = alkyl R3 = CF3, CO2Et

40

R2

N R1

41

R3 O

AgNO3

R2

N R1

H

3

O

R H

Ag

R3 R2

O R2

+

N NO– 3 R1

N R1

Ag

H

NO3

Scheme 3.14 Ag-catalyzed 4-endo-dig cyclization of N-propargylic β-enaminone. O

CF3 O Me

AgNO3

F3C Me

N Pr

H

N Pr 42

Scheme 3.15 5-exo-dig cyclization of a N-propargylic β-enaminone.

6-endo-dig cyclizations are more common for conjugated systems that can form an aromatic ring in the process. For example, in the presence of silver salts such as AgSbF6 , AgPF6 , AgOTf, AgNO3 , and AgTFA, the 2-alkynyl-3-(silyl enol ether)quinoline derivatives 43 can undergo a benzannulation reaction, providing access to a large variety of polysubstituted acridines 44 (Scheme 3.16) [21]. However, the reaction fails when silver salts such as AgF, AgOAc, Ag2 CO3 , and Ag2 O are used. OTBS R2

OTBS AgOTf (5 mol%) DCE, 50 °C

N 43

R1

R2 N 44

R1

R1 = alkyl, aryl, pyridyl, ferrocenyl, TMS R2 = H, OMe

Scheme 3.16 Benzannulation of 2-alkynyl-3-(silyl enol ether)quinoline derivatives.

93

94

3 Silver-Catalyzed Cyclizations

AgOTf catalyzed the cascade reaction of acetylenic aldehydes 45 with indoles 46 to form highly substituted tetrahydrocarbazoles 48 (Scheme 3.17) [22]. In the proposed mechanism, the 3-alkylidene-3H-indolium cation intermediate 47 is formed via the aldol condensation between the aldehyde moiety and indoles. The further addition of two indole moieties during the cyclization process affords 48 as the final product. In the reaction, Ag(I) acts as both a σ- and a π-acid, simultaneously activating the carbonyl functionality of 45 during the aldol reaction, and later the alkyne functionality of 47, to trigger the intramolecular cycloisomerization reaction. N R1 R2

R3

R3

Me

R1 R2 AgOTf (10 mol%)

+ R3

OHC

N

45

CHCl3, 25 °C

41

R3 N+

46

R1 R2

N

47 N

R3 48

Scheme 3.17 Cascade reaction of acetylenic aldehydes with indoles.

3.2.2.2

Cycloisomerization of 1,n-Allenynes

Malacria and coworkers investigated the cycloisomerization reactions of allenylynamides 49 in the presence of AgOTf, resulting in the formation of N-heterocycles with non-conjugated trienes. Depending on the substitution on the ynamide (R1 ) or the allene (R2 and R3 ), Alder-ene-type cycloadducts 50, fused piperidines 51, or cross-conjugated trienes with an exocyclic 1,2-diene moiety 52 may be formed (Scheme 3.18) [23]. R2

R1 = aryl, SiMe3; R2 = Me; R3 = H

N Ts R1 50 R3

•

R3

R2

NTs 1 49 R

AgOTf (10 mol%) CH2Cl2, r.t.

•

R2

NTs

N Ts

+

Ag

R3

R1

+

R2

R2

R1 = CRR′OH, CO2Et; R2 = Me; R3 = H

R1

O N Ts

Ag

R1 = SiMe3; R2 = H, Me; R3 = Me

R R′ 51 R3

N Ts R1 52

Scheme 3.18 Cycloisomerization of allenylamides catalyzed by AgOTf.

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

1,6-Allenynes 53 can also undergo cycloisomerization reactions in the presence of gold, platinum, and silver catalysts. Gandon and coworkers reported a detailed study of the effect of ligand and counteranion on the reaction [24]. A weakly coordinating anion effect was observed with silver salts as catalysts. AgSbF6 and AgPF6 facilitated the formation of the unexpected vinyl chloride product 56, while the use of AgOTf directed the reaction toward the Alder-ene products 55. In contrast, AgBF4 promoted the formation of a mixture of both the hydrindiene-type product 54 and Alder-ene products 55, while no reaction occurred when AgClO4 , AgNO3 , AgCl, or AgI were used. Introduction of bulky ligands such as (biphenyl-2-yl)(t Bu)2 P led to exclusive formation of the hydrindiene-type products 54 (Scheme 3.19). Silver salt (5 mol%)

•

MeO

MeO

+

CH2Cl2, r.t. MeO

MeO 53

MeO

+

MeO

MeO 54

MeO

55

56

Cl

Scheme 3.19 Cycloisomerization of 1,6-allenynes.

3.2.2.3

Cycloisomerization of 1,n-Diyne Compounds

Electrocyclization reactions of 1,n-diynes can only proceed via the activation of one of the alkynes to create electronically compatible frontier orbitals. In 2006, Toste and coworkers reported a silver-catalyzed synthesis of aryl ketones 59 from propargyl esters 57 (Scheme 3.20) [25]. The reaction involves a [3,3]-sigmatropic rearrangement of the propargyl ester to the allenyl acetate intermediate 58, followed by 6-endo-dig cyclization. The presence of MgO is required as an acid scavenger to prevent the deactivation of the silver catalyst by the pivalic acid by-product. AgSbF6 (5 mol%), PPh3 (2 mol%) MgO (1.5 equiv.)

OPiv R2 57

R1

•

R2

R2 R1

CH2Cl2, r.t. R1 = H, alkyl R2 = H, alkyl, Ph

O

OPiv

58

1

R 59

Scheme 3.20 Cycloisomerization of 1,6-diynes.

Similarly, Chen et al. developed a silver-catalyzed cyclization reaction between 1,6-diyne-4-en-3-ol 60 and N-halosuccinimide (NXS, X = Br, I) to give halide-substituted benzo[a]fluorenols 61 (Scheme 3.21) [26]. It was proposed that the reaction initiates by an electrophilic activation of one of the alkyne group by X+ , which triggers a reaction cascade; the role of the silver catalyst is to liberate (and return) the OH− group. The methodology was subsequently extended for the synthesis of trisubstituted naphthalenes 63 by the cyclization of triynol substrates 62 (Scheme 3.22) [27].

95

96

3 Silver-Catalyzed Cyclizations

OH

R1 R

1

R

2

+ NXS Ar

OH 60

+

X

+

2

R

R1

6-Endo Electrophilic addition

+

O

61

OH

Friedel–Craft

X

1

R

Ar

+

2

–H

X

OH

R

Ar Ag

R2

Ar HO

CH2Cl2, 10 °C X = I, Br

60

X

X

AgBF4 (10 mol%)

+

H

R1

X

–

–OH

+

R1

X Tautomerism R1 2

R

R2

61

R2

+

Ar

Ar

–

Ar

Scheme 3.21 Cyclization reaction between 1,6-diyne-4-en-3-ol and NXS. OH

X

R1

+ NXS R2 62

Ar

AgOTf (10 mol%) DCE, 10 °C X = I, Br

R1 R2

O

Ar

63

Scheme 3.22 Silver-catalyzed cyclization of triynol substrates to trisubstituted naphthalenes.

3.2.2.4

Cycloisomerization Reactions of Propargyl Compounds

The chemoselectivity of the tandem cyclization of alkynylaziridines 64 is dictated by the choice of the catalyst (Scheme 3.23) [28]. The use of AgNTf2 triggered a SN 2′ -type Friedel–Crafts addition of the aromatic ring onto the alkyne to form aminoallenylidene-fused heterocycles 65 such as isochromans (X = O), isoquinolines (X = NTs), and tetrahydronaphthalenes (X = CH2 , C(CO2 Et)2 ). The use of a Au(I) catalyst, on the other hand, resulted in a further 5-endo-trig cyclization of 65 to 1-azaspiro[4.5]decanes 66. The propensity of propargyl acetates to undergo 1,3-acyloxy migration to form allenyl intermediates was exploited by Shi and coworker for the synthesis of nitrogen heterocycles. In the presence of AgSbF6 , the N-sulfonylhydrazone propargylic ester substrates 67 are transformed into an allenyl acetate intermediate 68, which can undergo a Mannich-type addition/elimination to furnish 5,6-dihydropyridazin-4-one derivatives 69 (Scheme 3.24) [29]. Similarly, the allenyl acetate intermediate generated from the N-activated aziridine propargylic esters 70 undergoes a rare 5-exo-tet cyclization to afford pyrrolidin-3-one derivatives 71 (Scheme 3.25) [30].

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

R5 R1

AgNTf2 (5 mol%) CH2Cl2, –20 °C to r.t. R1 R

X

5

R4 R3

R2

•

3 NH R R4 Z 65

X

[Au]

N Z 1

R

64 R1 (PPh3)AuNTf2 (5 mol%) X = O, NTs, CH2, C(CO2Et)2 CH2Cl2, 0 °C to r.t. R1 Z = Ts, Ns N Z 3 4X R R 66

R5

Scheme 3.23 Au- vs. Ag-catalyzed cyclization of alkynylaziridines 59. AcO R N N

OAc R1 R1 R2 67

AgSbF6 (10 mol%), H2O (1.0 equiv.) CH2Cl2, r.t. R = Ts, Ms, SO2Et R1 = alkyl; R2 = aryl

R1

•

R1

O

R1

N H

2

R1

N N R2 R Ag+ 68

N

R 69

Scheme 3.24 Tandem 1,3-acyloxy migration/Mannich-type addition/elimination. OAc R1 AgSbF6 (10 mol%), H2O (1.0 equiv.) R2

R N

R3 N R4 70

CH2Cl2 r.t. R = Ts, PhSO2, 4-BrC6H4SO2 R1, R2 = alkyl R3 = Ts, 4-O2NC6H4SO2 R4 = aryl

AcO N R

•

R1

O

R2 R3 N

R

N

R2 R1

+

R4 Ag

71

Scheme 3.25 Tandem 1,3-acyloxy migration/5-exo-tet cyclization.

Taylor, Unsworth, and coworkers demonstrated that alkyne-tethered indoles 72 can either undergo electrophilic cyclization via C3 or C2 of the indole ring to afford the spirocyclic product 73 or the carbazole product 74, respectively (Scheme 3.26), dependent upon the combination of silver catalyst(s) and solvent employed for the reaction [31]. The protocol was extended to construct spirocyclic scaffolds 79–82 by the dearomatization of indole-, anisole-, pyrrole-, and benzofuran-tethered ynone derivatives 75–78 (Scheme 3.27) using either 1 mol% of AgOTf, 10 mol% of AgNO3 [32], or silica-supported AgNO3 [33]. Using the silver salt of chiral phosphoric acids (CPAs), modest levels of enantioselectivity can be attained in the cyclization of indole derivatives (up to 89 : 11 e.r.).

97

98

3 Silver-Catalyzed Cyclizations

HO AgOTf (10 mol%) THF, r.t.

OH

Ph N 73

N H

Ph

AgNO3 (10 mol%), Ag2O (5 mol%)

72

CH2Cl2, r.t.

Ph

N H 74

Scheme 3.26 Silver-catalyzed dearomatization of alkyne-tethered indoles. O

O AgOTf (1 mol%) N H 75

N H

R

R

CH2Cl2, r.t. N 79

R = Ar, alkyl, TMS Ar

Ar AgNO3 (10 mol%) CH2Cl2, r.t.

O

N 80

76

O

O

O AgOTf (1 mol%) Ar

O 77

O 81 O

O R2 OH

R1 78

Ar

CH2Cl2, r.t.

O R2 +

AgNO3–SiO2 (10 mol%) CH2Cl2, r.t. R1 = alkyl, aryl R2 = H, OMe

R1

R2

O R1

O 82

82′

R′ O O P O OAg R′ CPA catalysts

Scheme 3.27 Construction of spirocyclic scaffolds by silver-catalyzed cyclization of tethered ynone derivatives.

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

3.2.3

Electrocyclic Reactions

In 2009, Malacria and coworkers reported that α-allenols 83, containing two germinal aryl groups at the α-position can undergo a Nazarov-type cyclization in the presence of AgOTf to form benzofulvenes 83 (Scheme 3.28) [34]. It was believed that the reaction proceeds via 4π-electrocyclization of the aryl prop-2-ene-1-yl cation intermediate 84, involving one of the aromatic rings and the allene. In some cases, competitive intramolecular hydroalkoxylation of 83 occurred to produce dihydrofurans 86 as side products. • AgOTf (1 mol%)

Ar

•

Ar

OH 83

Ar

+

Ar

+

CH2Cl2, r.t.

Ar Ar

O

R

R 84

85

86 (Side product)

Scheme 3.28 Formation of benzofulvenes from α-diaryl-α-allenols.

Liu and coworkers later reported the condensation reaction of the conjugate aldehyde 87 with the secondary anisidine 88. In the presence of a Lewis acidic AgClO4 catalyst, the cationic 1-aminopentadienyl intermediate 90 undergoes a 4π-conrotatory imino-Nazarov cyclization to form the oxyallyl cation intermediate 91, which was trapped by the nucleophilic pendant aryl group in a 5-exo cyclization reaction to afford the indoline-fused cyclopentanone 89 (Scheme 3.29) [35]. OMe MeO

CHO

OMe + Bn

MeO 87

N H

O AgClO4 (30 mol%) MeO

MeCN, 110 °C 88

N Bn 89

OMe 87 + 88

MeO MeO

Ag(I) –H2O

Isomerization

+

MeO

N Bn

MeO OMe

+

MeO Imino-Nazarov

N Bn 90

MeO

+ N Bn 91

OMe

OMe Ag(I)

MeO MeO

H2O N Bn

–MeOH –H+

89

Scheme 3.29 Synthesis of an indoline-fused cyclopentanone via Ag-catalyzed condensation between a conjugate aldehyde and a secondary arylamine.

99

100

3 Silver-Catalyzed Cyclizations

Treated with 0.1 equiv. of AgOTf, N-propargylic hydrazones 92 undergo a [3,3]-sigmatropic rearrangement/1,3-H shift/6π-aza-electrocyclization cascade to yield polysubstituted 1,6-dihydropyridazines 93 (Scheme 3.30) [36]. The proposed mechanism involved the activation of the C≡C bond by silver, triggering a 6-endo-dig cyclization to form intermediate 94, which decomposes to form the allenic intermediate 95. Subsequent 1,3-H shift and 6π-aza-electrocyclization ensue to furnish the 1,6-dihydropyridazine 93 as the final product. R3

N

N

R2

R4

R3 92

Ag(I)

N

N

R2

R3

R4 +

R3 1,3-H shift

N

R2

N

EtOAc, r.t. R4 R1 R1 = H, alkyl, aryl, OMe, CO2Me, F, Br 93 R2 = CO2Et, CF3, CHO, nPent, 4-BrC6H4 R3 = Ar; R4 = H, Me

R1

92

R3

AgOTf (10 mol%)

Ag

N

N

4

N

R4

R1

R2

R3

R1

H

Ag 94

N

R2

•

R1

N

R4

95

R2 Electrocyclization

R1

R

+

N

93

Scheme 3.30 Silver-catalyzed [3,3]-sigmatropic rearrangement/1,3-H shift/6π-aza-electrocyclization cascade.

3.2.4

Miscellaneous Reactions

Pati and Liu reported the silver-catalyzed cyclization of 1-(2,2-dimethylcyclopropyl)methyl ketones 96 to 1,2,4-trisubstituted benzenes 97 (Scheme 3.31) [37]. It was proposed that the Ag catalyst assisted the cleavage of the cyclopropane ring to form a tertiary cationic intermediate 98. Deprotonation occurs to give the 4-en-1-one 99, followed by an unusual intramolecular C—C bond formation between the ketone and an allylic C—H bond to give the 1,2,4-trisubstituted benzene product 97 after aromatization. The cycloisomerization of nitrogen or carbon-tethered indolylcyclopropenes 100 to spiro[indoline-3,4′ -piperidine] derivatives 101 was later reported by AgNTf2 (10 mol%) R1

O R

1

R

R1 = aryl R2 = alkyl, aryl

96

96

Ag

+

Ag(I)

Ag O R1

+

R2

R2

DCE, 80 °C

2

Me

97 +

O

O

R2

R1 H 98

Ag R2

R1

99

Scheme 3.31 Rearrangement of 1-(2,2-dimethylcyclopropyl)methyl ketones to 1,2,4-trisubstituted benzenes.

97

3.2 Cyclization by the Formation of C—C Bonds (Cycloisomerization Reactions)

Tang, Shi, and coworkers (Scheme 3.32). From deuterium labeling studies, two independent pathways were proposed for the reaction (Scheme 3.33): in the major pathway, the Ag catalyst attacks the C3 position of the indole to give [d]-102, where syn-addition on the double bond of the cyclopropene moiety occurs to afford intermediate [d]-103, which protodemetalates to form [d]-101. In the minor pathway, the silver coordinates simultaneously to both the ester and the electrophilic double bond, and nucleophilic attack takes place at the indole C3 position to give intermediate [d]-103′ that leads to [d]-101′ [38]. R2O2C n

CO2R2

R1 N H

X

AgOTf (10 mol%)

X

n

Toluene, 80 °C

R1

X = NTs, NBs, C(CO2Me)2 R1 = H, Me, OMe, Br, Cl, F R2 = Me, Et, Bn

100 (n = 1, 2)

N 101

Scheme 3.32 Cycloisomerization of tethered indolylcyclopropenes.

N Ts N H

CO2R2 D

[D]-100

Ag(I) Major

Minor O

CO2Et

D

+

Ag

NTs

D

NTs Ag +

N H

N H [D]-102′

CO2Et

O

N [D]-101′

CO2Et

OEt

Ag NTs –Ag(I) D

D

[D]-102

NTs +

N H [D]-103′

D Ag

NTs –Ag(I)

CO2Et NTs

D

+

N H [D]-103

N [D]-101

Scheme 3.33 Competitive pathways for the formation of spiro[indoline-3,4′ -piperidine] derivatives.

101

102

3 Silver-Catalyzed Cyclizations

3.3 Formation of C—N Bonds 3.3.1

Intramolecular Hydroamination

There is a substantial body of work where silver catalysts are employed to catalyze the intramolecular addition of N—H (and O—H; see Section 3.4.1) bonds to unsaturated C=C or C≡C bonds, activated by π-coordination to the metal to form N-heterocycles (Scheme 3.34). In the silver-catalyzed processes, the formation of five- and six-membered heterocyclic rings are most common, and both exo- and endo-modes of addition can be found; the level of selectivity appears to be largely dictated by the inherent geometric constraints of the acyclic precursor, defined by the pattern of substitution, as well as the Lewis acidity of cationic silver(I) to coordinate to Lewis basic sites on the substrates to direct the stereochemical course of these reactions. n exoH

X

n

Ag

H

X

n

+

Ag X = NR, O

n endo-

Ag

X H

Ag

+

X H

Scheme 3.34 Intramolecular hydroheterofunctionalization reactions (X = N, O).

3.3.1.1

Alkynes

5- and 6-exo-dig Cyclizations In 1990, Kimura et al. reported that O-propargylcar-

bamates 104 undergo intramolecular hydroamination reactions to form 4-methylene-2-oxazolidinones 105 and the 5-exo-dig cyclization occurred in the presence of 10 mol% of silver isocyanate and 10 mol% of potassium tert-butoxide (Scheme 3.35(1)) [39]. Likewise, Nagasaka and coworkers reported the cyclization of β-alkynylpropanamides 106 to form the alkylidene-γ-butyrolactams 107 as the (E)-isomer exclusively under similar conditions (Scheme 3.35(2)) [40]. The acyclic substrate can be prepared in situ by the nucleophilic addition of propargylic alcohol 108 to phenyl isocyanate, which furnished oxazolidine-2-ones 109 as the final product (Scheme 3.35(3)) [41]. With internal alkyne substrates, the addition proceeds with anti-addition of N—H across the triple bond exclusively to afford the Z-configured product. These observations support the hypothesis that Ag is activating the π-bond toward a nucleophilic attack, rather than the formation of an alkynyl silver intermediate. In this regard, the Ag(I) catalyst is more similar to gold(I) rather than Cu(I) catalysts. Reactions described in Scheme 3.35 required basic conditions for the deprotonation of the NH, prior to the cyclization reaction; this is not always necessary. In an interesting work by Van der Eycken and coworkers, propargylic urea derivatives 110 (generated in situ from the corresponding propargylamine and tosyl isocyanate) cyclize in the presence of AgOTf to give the N-cyclized imidazolidin2-one product 111 selectively (Scheme 3.36) [42]. This is in contrast with the

3.3 Formation of C—N Bonds

O

AgNCO (10 mol%), KOtBu (10 mol%)

O

R

N H

O 104

R2 106

+ PhN=C=O

2

R

R3

O N

[2]

R2

R1 = H, alkyl, aryl R2 = alkyl, Bn, ether

OH R1

R1

Toluene, 65−70 °C

[1]

O

105

AgOTf (15 mol%), LiHMDS (30 mol%)

N H

O N

THF, r.t. R = Ph, Me, CH=CH−Me

O R1

O R

107 O

AgOAc (10 mol%), DMAP (30 mol%)

O

N Ph

1,2-Cl2C6H4, 40 °C R1 2 R

108

[3]

R3 109

Scheme 3.35 Intramolecular 5-exo-dig cyclizations of O-propargylcarbamates and β-alkynylpropanamides under basic conditions.

R1

N Ts N

O

R2

R3

O

Au(PPh3)Cl (5 mol%), AgOTf (5 mol%)

R1

CH2Cl2, r.t. or 50 °C (O-Cyclization)

R2

N

110

112 NBoc R1

N

NHBoc

N H

Ts

R3

113

R3

R1

Toluene, 80 °C (N-Cyclization)

R2

O N

N Ts

111

NBoc AgNO3 (15 mol%)

R3

NH2

R1 N

N Boc

R2

3

MeCN, r.t.

R2

AgOTf (20 mol%)

R

TFA/CH2Cl2 (1: 2)

114

R1 N

N

r.t. R2

R3

115

Scheme 3.36 Cyclization of propargylic ureas and thioureas.

result obtained with cationic Au(I) catalysts, which favored O-cyclized oxazolidin-2-imine products 112. A similar approach was used to access 1,4,5-trisubstituted 2-aminoimidazoles 115 from propargylguanidine precursors 113, prepared from polysubstituted propargylamines and thioureas [43]. Deprotection of the Boc groups of the cyclized product 114, by the treatment with TFA/CH2 Cl2 (1 : 2), gave 115 in good yields. The reactions were re-examined by Looper and coworkers [44], who compared the catalytic activity and selectivity of AgOAc with [Rh2 (oct)4 ]; it was found that while Ag favors the 5-exo-dig cyclized product 114, the Rh catalyst favors the formation of the 6-endo-dig product. Subsequently, the authors developed a cascade sequence, consisting of a highly selective silver(I)-catalyzed 5-exo cyclization of guanidine 116. The resultant intermediate 117 undergoes an intramolecular Michael addition with the unsubstituted guanidine nitrogen to form the six-membered ring in the bicyclic guanidine products 118 and 118′ ; the mode of addition is dependent on the R3 -substituent on the five-membered ring (Scheme 3.37) [45].

103

104

3 Silver-Catalyzed Cyclizations R2 N

3

R2 R

NH2 O N

R1 AgNO3 (10 mol%) R3 MeCN, r.t.

N

3

R

R2 N

NH

R

116

R1 H

N

1

O

R4

N O R4 117

R4

N

R3

R2 N

N N

R4

118 syn-Selective (R3 = aryl)

R1 H

118′ anti-Selective (R3 = alkyl or α-branched)

O

Scheme 3.37 Synthesis of bicyclic guanidines by a tandem hydroamination/Michael addition sequence catalyzed by AgNO3 .

Silver(I) catalysts can also facilitate the addition of imidates to alkynes. Wong et al. reported that the silver(I) bis(pyridyl) complexes are a highly efficient class of catalysts for the cyclization of trichloroacetimidate derivatives of (homo)propargylic alcohols 119 to afford exo-dig products oxazoline (120, n = 0) and oxazine (120, n = 1) products (Scheme 3.38) [46]. For the more challenging substrates containing internal alkyne, the reaction was performed in acetone at reflux or MeCN at 60 ∘ C. The presence of pyridine in the system suppresses the competitive Brønsted acid catalysis, preventing competitive side reactions, such as the isomerization to the aromatic oxazoles. Cl3C

NH

R3

O 1

n

R R2 119 (n = 0, 1)

CCl3 [Ag(py)2][OTf](10 mol%) O N Acetone, 23 °C,6 h 1 n R 2 n = 0, 1 R 120 R1, R2 = H, alkyl, aryl R3 = Ph, TMS, Br

R3

Scheme 3.38 Silver-catalyzed intramolecular addition of imidates to alkynes.

Benzo-fused N-heterocycles can be similarly prepared: AgOAc-catalyzed hydroamination of 1-(2-(sulfonylamino)phenyl)prop-2-yn-1-ols 121 produced (Z)-2-methylene-1-sulfonylindolin-3-ols 122 exclusively (Scheme 3.39(1)) [47]. The reaction was later employed by Xue and coworkers to initiate a one-pot sequential hydroamination/[4+3] cycloaddition for the synthesis of indolecontaining 5,7,6-tricyclic skeletons 123 (Scheme 3.39(2)) [48]. Using a more elaborated substrate 124, Ramasastry and coworkers described a Ag(I)/Bi(III)/ Pd(II)-promoted relay catalytic system that integrates an intramolecular hydroamination and 1,3-allylic alcohol isomerization (1,3-AAI) in a one-pot synthesis of 1,3-disubstituted furo[3,4-b]indoles 125 via an isofuran annulation of δ,ε-unsaturated alcohols (Scheme 3.39(3)); similarly, cyclopenta[b]indoles 127 can be obtained from 126 by incorporating a Nazarov-type cyclization in the cascade (Scheme 3.39(4)) [49]. On the other hand, using 1-((2-tosylamino)aryl)but-2-yne-1,4-diols 128, a AgOTf-catalyzed tandem heterocyclization/alkynylation reaction can be achieved, with the liberation of two molecules of H2 O to afford 2-alkynylindoles 129, without the need to resort to cross-coupling reactions (Scheme 3.40) [50].

3.3 Formation of C—N Bonds R2 OH R

NH SO2R4 121

R3

R1 MeCN, r.t. 3 R –R = H, alkyl, aryl R4 = alkyl, aryl

121 (R2 = H; R3 = Tol) CH2Cl2, r.t.

HO

NH Ts 124

[1] N R3 SO2R4 122 R5

1

AgOTf (5 mol%)

R2

R2 OH

AgOAc (5 mol%)

1

R1

ZnCl2 (1.1 equiv.) R3

N Ts

R5

(5.0 equiv.)

H OH

[2]

R1 N R3 Ts 123

HO AgOAc (2 mol%) R1

DCE, 60 °C

N Ts

R2

R1

Bi(OTf)3 (5 mol%) (1,3-AAI) 0 °C, r.t. O

OH Pd(OAc)2 (10 mol%)

Ph HO R2

NH Ts 126

60 °C

R2 125

N Ts

R1

[3]

Ph HO

AgOAc (2 mol%) R1

R1

N Ts

R2

DCE, 60 °C N Ts

R2

R1

H+ (10 mol%) 0 °C Ph Ph

Nazarov-type cyclization

+ 2

R

N Ts

1

R

R2

N Ts 127

R1

[4]

Scheme 3.39 Ag-catalyzed 5-exo-dig cyclization of 2-aminobenzo-tethered alkynes and its use in tandem processes for fused indole derivatives.

The proposed mechanism involves the C—OH bond activation by coordination to the hydroxyl group of 142 and intermediate allene 130. Using a similar substrate 1-(2-allylamino)phenyl-4-hydroxy-but-2-yn-1-ones 131, the same authors extended the reaction to the synthesis of spirocyclic rings 132 by a tandem hydroamination/hydroarylation reaction (Scheme 3.41) [51]. Mechanistically, the reaction initiates with a 5-exo-dig hydroamination reaction, as described in Scheme 3.40, to produce the allenamide 134, which undergoes a 5-endo-trig intramolecular hydroarylation, followed by rearomatization and protodemetalation to afford the spirocyclic 132. Formation of six-membered N-heterocycles can also be accomplished using silver catalysis via 6-exo-dig cyclizations. Hu and coworkers reported the preparation of functionalized pyrido[2,3-d]pyrimidines 135 from N,N-di-Bocprotected 6-amino-5-iodo-2-methyl pyrimidin-4-ol 133: the acyclic substrate

105

106

3 Silver-Catalyzed Cyclizations

R2 OH

R2 AgOTf (5 mol%)

R1

OH NH 3H R Ts 128

R2 OH 128

Ag(I)

R3

R1

Toluene, 70 °C –2H2O

N Ts 129 R2 OH

Ag+

R1

•

OH –AgOH R1 H R3

NH Ts

R3

N Ts 130

Ag+ R2

Ag(I) R1

OH •

N Ts

H R3

129

–AgOH

Scheme 3.40 Synthesis of 2-alkynylindoles by tandem heterocyclization/alkynylation.

R3 O

R3

R2

O

AgOTf (10 mol%) R2

Toluene, r.t.

N R1 132

4

NH HO R R1 131

R4

R3

O Ag

Ag(I)

131

NH R1 HO R4 133

R2

R3

2

R

• N R1

O H •

N + R4 R1Ag 134

R4

R3

O

Ag(I)

O

–Ag(I) R –H2O R2 3

–Ag(I)

132

2

R

N R4 R1 Ag

Scheme 3.41 Silver-catalyzed tandem hydroamination/hydroarylation reactions.

134 was assembled using a Heck–Sonogashira reaction; the subsequent removal of the Boc protecting group and 6-exo-dig cyclization occurred in the presence of silver trifluoroacetate and TFA (Scheme 3.42) [52]. In some cases, the amine nucleophile required for the cyclization is formed in situ. For instance, Wu and coworkers described the synthesis of isoquinolines 138 via a base-promoted tandem reaction of (E)-2-alkynylbenzaldehyde 136 with 2-isocyanoacetate 136 (Scheme 3.43) [53]. In the mechanistic proposal, it was

3.3 Formation of C—N Bonds

Boc

N

N(nBu)3 (4 equiv.), Pd(PPh3)4 (5 mol%), CuI or ZnBr2 (10 mol%)

Boc I

N N

+

R

OH

Boc

Boc

N

R

N

MW (80 or 100 °C), DMF R = aryl,TMS

N

133

OH R

134

CF3CO2H (20% v/v), CF CO Ag (10 mol%) 3 2 CH2Cl2, reflux

OH R

N N

R

N

135

Scheme 3.42 Synthesis of pyrido[2,3-d]pyrimidines by Ag-catalyzed 6-exo-dig cyclization reactions. O R3

1

R

+ R 4

R

NC

R4 R1

MeCN, 80 °C

137

2

R3

DBU (1.0 equiv.), AgOTf (10 mol%)

2 138 R

136

136 + 137

N

R3

DBU

O

R1

R3

N

B = base

R1

R4 H

O

R2 140 R3

R3 R4 1

NHCHO

141

B

R4 H

R2 139

R

+

N HB

R2

Ag(I)

R4 1

R

N

CHO

–CO

138

R2

Scheme 3.43 Formation of isoquinoline from 2-alkynylphenylchalcones.

suggested that the reaction of 136 and 137 generates the isocyanate 139, which cyclizes to form oxazole 140. Rearrangement to the acyclic precursor 141, and silver-catalyzed 6-exo-dig cyclization, results in the isoquinoline product 138 after loss of CO. 5- and 6-endo-dig Cyclizations Formation of N-heterocycles by Ag-catalyzed

5-endo-dig addition of N—H to alkynes is fairly commonplace (Scheme 3.44): O-propargylic hydroxylamines 142 and their sulfonamide derivatives 143 undergo facile cyclization to 4,5-dihydroisoxazoles 144 in the presence of

107

108

3 Silver-Catalyzed Cyclizations

O

NH2

or

1

R

2

R 142 R1 = iBu, Ph; R2 = H, alkyl, aryl

O

H N

SO2R3

R1

AgNO3–SiO2 (5 mol%) CH2Cl2, 20 °C

R2 143 R1 = iBu; R2 = nBu; R3 = p-MeC6H4, p-O2NC6H4 OH NH

AgOTf (5 mol%)

R2 145

R1

O N

R2 [1]

R1 144

R2

DCE, r.t. R2 = CF3, n-C4F9 R1 = aryl, heteroaryl

N O

R1

[2]

146

Scheme 3.44 5-endo-dig cyclization of hydroxylamine derivatives.

AgNO3 adsorbed onto silica gel as catalyst (Scheme 3.44(1)) [54]. Conversely, N-(2-perfluoroalkyl-3-alkynyl) hydroxylamines 145 can also undergo a silvercatalyzed cyclization to afford the corresponding cyclic nitrones 146 in good to excellent yields (Scheme 3.44(2)) [55]. A general method for the synthesis of N-tosylpyrroles 149 from 3-alkynylhydroxyalkanamine derivatives 147 was reported, using AgNO3 supported on silica gel as catalyst (Scheme 3.45(1)) [56]. Mechanistic studies showed that the reaction proceeds via the hydroxylated dihydropyrrole intermediate 148, which dehydrates to give the aromatic product. On the other hand, Dovey and coworkers demonstrated a two-step synthesis of pyrroles 152 involving a C-propargylation of vinylogous amides 150, followed by a silver-catalyzed intramolecular hydroamination reaction (Scheme 3.45(2)) [57]: the C—N bond formation can be drastically facilitated by microwave irradiation, reducing the reaction time from overnight to just one minute. Likewise, 2,5-disubstituted pyrrolines 154 were obtained from aryl-substituted acetylene-containing amino acids 153 by Boc deprotonation followed by a silver-catalyzed 5-endo-dig cyclization reaction (Scheme 3.45(3)) [58]. The obtained pyrrolines can be efficiently converted to the corresponding 5-substituted proline derivatives by catalytic hydrogenation. Finally, pyrazoles 156 and 157 may be prepared by the Ag-catalyzed cyclization of propargylic hydrazines, prepared in situ by nucleophilic substitution of propargylic alcohol 155 with p-tolylsulfonohydrazide (Scheme 3.45(4)) [59]. A silver-catalyzed 5-endo-dig hydroamination reaction was adopted successfully by Knölker and coworkers in the total synthesis of a class of bioactive halogenated natural products – pentabromopseudilin, pentachloropseudilin, and their synthetic analogues – by a silver-catalyzed intramolecular 5-endo-dig cyclization of N-tosylhomopropargylamines 158 to construct the 2-arylpyrrole core structures 159 (Scheme 3.46) [60]. Similarly, a tandem intramolecular hydroamination/asymmetric semipinacol rearrangement process was reported by Zhang and coworkers in the formal synthesis of (−)-cephalotaxine: a chiral silver phosphate salt 159 (R′ = anthracenyl) was used to convert a cyclobutanol 160 to the key spiro intermediate 1-azaspirocycle 162 (Scheme 3.47) [61].

3.3 Formation of C—N Bonds

1

R

TsHN

R1

N Ts 148

147

N H

THF, r.t. R = alkyl, Ph, Bn

COMe

CO2Me HN Y

X

Boc

R1

COMe R

N H

COMe 151

r.t., overnight; or MW (700 W), 1 min

1. HCl, EtOAc, r.t., 3h 2. Et3N, CHCl3, r.t., 30 min

R1 155

[2]

N R 152

R [3]

CO2Me

N

3. AgOTf (10 mol%), MeCN, r.t. or reflux

Y X

153

OH

[1]

R3 N Ts 149

AgNO3 (20 mol%)

150

R

–H2O

R3

Br, nBuLi R

R2

OH 2 R

AgNO3–SiO2 OH (10% w/w) R2 R3 CH Cl , 20 °C 2 2

X = Y = CH, R = NH2, OMe, NO2, Me, F X = CH, Y = N, R = H X = N, Y = CH, R = H H N N or AgOTf (10 mol%) R2 + H2NNHTs 1 DCE, reflux R R2 156 R1 = aryl, heteroaryl R2 = Ph, nBu, cyclopropyl

154

Ts N N

[4]

R1 157 R1 =

aryl; R2 = H

Scheme 3.45 Synthesis of five-membered N-heterocycles by Ag-catalyzed 5-endo-dig cyclization reactions.

OMe

OMe R

X OMe

NHTs

R 158 R = H, Cl, F

AgOAc (10–15 mol%) Acetone, 56 °C; or CH2Cl2, 40 °C

R

X N Ts

R 159

X N Ts

X

X Pentabromopseudilin (X = Br) Pentachloropseudilin (X = Cl)

Scheme 3.46 Synthesis of halogenated 2-arylpyrrole natural products by silver-catalyzed 5-endo-dig cyclization of N-tosylhomopropargylamines.

Hamada and coworkers employed a silver-catalyzed 5-endo-dig cyclization to trigger a one-pot sequential AgOAc-catalyzed hydroamination/etherification and acid-promoted skeletal rearrangement of aryl group-substituted propargyl alcohol derivatives 163, via the 5-exo-dig intermediate 164, to afford fused tricyclic indole/benzofuran derivatives 165 in yields of 66–89% (Scheme 3.48) [62]. Access to 1,2,5- and 1,2,3,5-substituted pyrroles 167 and 168 may be attained by a one-pot two-step sequential reaction involving the ring opening of 1-(aziridin-2-yl)propargylic alcohol 166 by nucleophiles such as acetic acid and

109

110

3 Silver-Catalyzed Cyclizations

SO2R NH

159 (20 mol%)

SO2R N

CCl4, 5 Å MS, 25 °C

R′

HO

OH 160

161

O

O O P O OAg R′ 159

O

N O H HO

R′ = anthracenyl

N SO2R

OMe (–)-Cephalotaxine

162

Scheme 3.47 Synthesis of a key spiro intermediate for (−)-cephalotaxine using enantioselective silver catalysis. Ts

N

Ts XH

R1O

HO

N

AgOAc (10 mol%) MeCN, r.t. R2

X R1O

163 XH = NMsH, OH

HO

R2

164

CH2Cl2,0 °C

TFA (8 equiv.) Ts N

R1O

X R2 165

Scheme 3.48 Ag-catalyzed tandem hydroamination/etherification/skeletal rearrangement reactions.

trimethylsilyl azide in the first step, followed by a AgOAc-catalyzed 5-endo-dig cyclization and dehydration (Scheme 3.49) [63]. 5-endo-dig cyclization of 2-alkynyl-substituted aromatic amine derivatives can also be achieved using silver catalysts. In the presence of silver(I) nitrate, alkynesubstituted pyrimidines 169 cyclized to form 4,6-substituted pyrrolo[3,2-d] pyrimidines 170, a bioactive isosteric scaffold of purine (Scheme 3.50) [64]. Likewise, an efficient synthesis of pyrazolo[1,5-a]pyridines 172 can be achieved by the cyclization of 1-amino-2-triethyl-silanylethynyl-pyridinium salts 171 (Scheme 3.51) [64, 65]. In some cases, the desilylated side product 173 was also detected. Yang and coworkers demonstrated a two-step/one-pot protocol method for the synthesis of 4-acetonylindoles 175 from 2-alkynylanilines 174 and silyl enol

3.3 Formation of C—N Bonds

AcOH CH2Cl2, r.t.

1. AgOAc (5 mol%), CH2Cl2, r.t.

OH AcO R1

NH

Bn

2. KOH, EtOH HO

167 R1 = aryl, heteroaryl R2 = H

HO R2 N Bn

R1 166

TMSN3, TMEDA

AgOAc (5 mol%)

OH

CH2Cl2, r.t.

N3 Bn

Bn N R1

R1

NH

N3

MeCN, r.t.

Bn N R1

R2 168 R1 = aryl, heteroaryl R2 = alkyl, aryl

Scheme 3.49 Generation of nucleophilic N—H by ring opening of aziridines. R1

R1

NH

AgNO3 (20 mol%)

NH2

N

NH

DMF, 90 °C

N

N 169

H N

R2

N

R2

170

Scheme 3.50 Synthesis of 4,6-substituted pyrrolo[3,2-d]pyrimidines.

SO – 3 R

NH2 N + N 171

SiEt3 Ag2CO3 (4 mol%), DMF, r.t.; or AgOAc (4 mol%), tAmOH R t

R = F, Cl, Br, OMe, CO Bu

SiEt3 N N

N N

+ R

172

173

Scheme 3.51 Synthesis of pyrazolo[1,5-a]pyridines.

ethers, triggered by an iodosylbenzene-mediated oxidative dearomatization, followed by a silver-catalyzed domino reaction (Scheme 3.52) [66]. Using 2-alkynylaniline derivative precursors, C3-substituted indole rings can be constructed by incorporating an electrophilic reactant in the silver-catalyzed process. For example, (3-indolyl)stannanes 176 can be prepared in good yields by a tandem silver-catalyzed cyclization/stannylation reactions between N-protected 2-alkynylaniline derivatives 174 with 2-tributylstannylfuran (Scheme 3.53) [67]. By using electrophilic fluorinating reagents such as NFSI and Selectfluor, a series of fluorinated indole derivatives that can be derived from 2-alkynylaniline derivatives, including 3,3-difluoro-3H-indoles 177, 2-hydroxy-3,3-difluoroindolines 178, 2-alkoxy-3,3-difluoroindolines 179, and 3-fluoroindoles 180, may be obtained in good yields (Scheme 3.54) [68].

111

112

3 Silver-Catalyzed Cyclizations

4

4

R R1 R2

PhIO (1.1 equiv.) N H

MeOH, 25 °C

R3

R

R1 MeO R2

N

R3

AgOTf (10 mol%), OTMS 6 (2.0 equiv.) R R R5 1 R MeCN, 25 °C R2

R1, R2 = H, Me, OMe, Ph, nBu R3 = Ts or Bz R4 = H, alkyl, aryl, TMS R5, R6 = H, alkyl, aryl

174

O

6

R5 R4 N R3 175

Scheme 3.52 Synthesis of 4-acetonylindoles using a two-step/one-pot protocol involving an oxidative dearomatization and a silver-catalyzed domino reaction. R4 1

R

2

R

R3

+

N H 174

SnBu3 O

SnBu3

AgSbF6 (5 mol%),

R4

DCE, 80 °C R3 = Ts, Ms, acyl R4 = alkyl, aryl, heteroaryl

N R3 176

(R1 = R2 = H)

Scheme 3.53 Tandem 5-endo-dig cyclization/electrophilic trapping reactions using 2-alkynylaniline derivatives. Ag2CO3 (10 mol%), NFSI (2.0 equiv.)

F F

R1

Ar

1,4-dioxane, 60 °C (R2 = R3 = H)

N 177

(R1 = H, Me, Cl, Br; R2 = H; R4 = Ar) F F

1. AgNO3 (10 mol%), R1 MeCN, 80 °C 2. Selectfluor (2.0 equiv.), H2O (3.0 equiv.), 0 °C (R2 = H) 174 (R4 = Ar)

N R3 178

OH Ar

(R1 = H, Me, Br; R3 = Me, Bn; R4 = Ar) F F

1. AgNO3 (10 mol%), MeCN, 80 °C 2. Selectfluor (2.0 equiv.), R′OH (5.0 equiv.), 4 Å MS, 0 °C (R1 = R2 = H; R3 = Me; Ar = Ph)

N Me 179

OR′ Ph

(R′ = Me, Et, Bn, CH2CH = CHPh) 1. AgNO3 (10 mol%), MeCN, 80 °C 2. Selectfluor (1.2 equiv.), r.t. (R1 = R2 = H)

F Ar N R3 180 (R3 = H, Me, Bn)

Scheme 3.54 Electrophilic trapping with fluorinating reagents.

3.3 Formation of C—N Bonds

Using aryl aldehydes as an electrophile, tandem cyclization/deoxygenative addition reactions proceeded under silver catalysis to furnish symmetrical 3,3′ -bisindolylarylmethanes 181 (Scheme 3.55) [69]. The Ag(I) catalyst was proposed to activate both the alkyne and carbonyl groups simultaneously, allowing the 5-endo-dig indole annulation and addition to the carbonyl to occur in a facile manner. R2 R4

R1

R1 + ArCHO

R2

NH2 174

(R3 =

H)

AgOTf (5–10 mol%) R2

HN R1

R4

Toluene, 80 °C

HN R1 = Cl, H R4 2 = Cl, H R R4 = Ph, nBu, –(CH2)2OBz, –CH2CH2OH

Ar 181

Scheme 3.55 Synthesis of 2,2′ -disubstituted 3,3′ -bisindolylarylmethanes by tandem cyclization/deoxygenative addition reaction of o-alkynylanilines.

When the −NH nucleophile that attacks the activated alkyne is part of a N-heterocycle, N-fused heterocycles are obtained. Zhan et al. developed an efficient cascade methodology for the synthesis of 9H-pyrrolo[1,2-a]indole 183, 1H-pyrrolo[1,2-a]indole 184, and 3H-pyrrolo[1,2-a]indole 185, starting from propargyl alcohols 155 and 3-substituted 1H-indoles 182 (Scheme 3.56) [70]. The transformation proceeds via a AgOTf-catalyzed Friedel–Crafts reaction to provide the requisite 2-propargyl or 2-allenyl indole intermediates 186 and 187, respectively, that can undergo intramolecular C—N bond formation reactions to produce the fused rings. In 2007, Pal and coworkers reported that silver salts catalyze the intramolecular 6-endo-dig cyclization of 2-alkynyl benzensulfonamides 188 to 3-substituted benzothiazines 189 in good yields (Scheme 3.57) [49, 71]. The synthesis of 2-alkoxypyridine (191) and isoquinoline (193) derivatives was reported by Fürstner and coworkers to be attainable by a silver-catalyzed 6-endo-dig cyclization of imidates 190 and 192, respectively (Scheme 3.58) [66]. 6-endo-dig cyclization was also reported by Liu and coworkers, where tricyclic xanthines 196 were synthesized from 8-(but-3-ynyl)-xanthines 194 by treating with AgAsF6 under microwave irradiation in water (Scheme 3.59) [72]. The reaction involves a 1,3-H shift between N7 and N9 of the xanthine ring to form the isomeric intermediate 195, prior to the ring formation process. The isomerization process does not occur if AuCl(PPh3 ) was employed as the catalyst. Later, the protocol was extended to the synthesis of fused tricyclic benzimidazoles using 5 mol% of AgOTf as the catalyst (Scheme 3.60) [73]. In these cases, the cyclization of the alkyne-tethered benzimidazoles 197 is less predictable: either the 6-exo-dig (198) or 7-endo-dig (199) cyclization products, or a mixture of both, can be obtained, depending on the nature of the alkyne tether (X) and the substituent at the alkyne terminus (R2 ).

113

R4

R5

R1 N

OH +

R1

R4

R5

R2 182

155

N H

5 AgOTf (5 mol%) R

Toluene, 80 °C

R4

R2 183 (R1 = aryl, Nap, 2-thienyl; R2 = aryl; R4 = Me, Ph, CH2CO2Et; R5 = H, Cl)

R1

Me

N H 186

Ph

R2

N R2 184 (R2 = alkyl, TMS)

OH R1

R2

+ 182 R3

5 AgOTf (5 mol%) R

Toluene, 80 °C

R4 N H

R3 • R1

108

R5

R4 R3 N

R2

R1

187

R2

185 (R1, R2 = Me, aryl, 2-thienyl, (CH2)5; R3 = Ph, TMS, nBu; R4 = Me, Et, Ph, CH2CO2Et)

Scheme 3.56 Tandem Friedel–Crafts reaction/intramolecular hydroamination to form tricyclic scaffolds.

3.3 Formation of C—N Bonds

R

S

H N

O O 188

AgSbF6 (15 mol%), Et3N (3.0 equiv.)

R

EtOH, 80 °C R = aryl, alkyl

Me

O

S

N

Me

O

189

Scheme 3.57 Silver-catalyzed 6-endo-dig cyclization of 2-alkynyl benzensulfonamides.

OEt

AgOTs (5 mol%), DMEDA (5 mol%)

NH

CHCl3, 0 °C to r.t.

R2 R1 190 OR1

AgOTs (5 mol%), DMEDA (5 mol%)

NH

R3

R1 = Ph, nBu R2 = H, Me, Ph

CHCl3, 0 °C to r.t.

OEt N R

2

R1 191 OR1 N

R3

R2

R2

192

193

R1 = Me, Et R2 = alkyl, aryl R3 = F, Cl, OMe

Scheme 3.58 Silver-catalyzed 6-endo-dig cyclization of alkynyl imidates.

O R1 O

N N R2

O

H N

AgAsF6 (20 mol%)

N

H2O, MW 150 °C

194

R1, R2 = Me, Et, nPr, n Bu, CH2C6H11, Bn

R1 O

O

N N R2

N

R1

N H

O

N

N N N R2 196

195

Scheme 3.59 Intramolecular hydroamination of an alkyne by the isomerization/cyclization of 8-(but-3-ynyl)-xanthines.

X = C, O R2 = Ar R1

N

R1

N H 197

R1

N

R1

N

AgOTf (5 mol%)

X

H2O, MW 150 °C R2

X

R2 198 X = O, R2 = H, Me

R1

N

R1

N R2 199

Scheme 3.60 Cyclization of alkyne-tethered benzimidazoles.

X

115

116

3 Silver-Catalyzed Cyclizations

Larger Ring Cyclizations A very rare example of a 7-exo-dig cyclization was

reported for the preparation of the central ring of tricyclic benzo[f ]imidazo [1,2-d][1,4]oxazepine derivatives 201 from [4,5-diaryl-2-(2-(prop-2-yn-1-yloxy) aryl)-1H-imidazoles] 200, catalyzed by AgNO3 (Scheme 3.61) [74].

Ar

H N

Ar

N

O

AgNO3 (10 mol%)

O

Ar

N

Ar

N

DMF, 80 °C 200

R

R 201

Scheme 3.61 7-exo-dig cyclization reaction to form benzo[f ]imidazo[1,2-d][1,4]oxazepine.

3.3.1.2

Allenes

exo-trig Cyclizations The first example of the silver-catalyzed intramolecular

addition of amine nucleophiles to allenes was reported in 1979 by Claesson et al. [75], where the cyclization of different substituted primary and secondary α-aminoallenes 202 to 3-pyrrolines 203 occurred at ambient conditions in the presence of 5 mol% of AgBF4 (Scheme 3.62). R2

R3

•

NHR1

R2 AgBF4 (5 mol%)

R4

CHCl3, r.t.

202

R3 N R4 R1 203

Scheme 3.62 The first example of Ag-catalyzed addition of N—H to allenes.

The method was later reexamined by Gallagher and coworkers with 50 mol% of AgBF4 [76]. Using an optically active δ-aminoallene 204 (80% ee), the chirality could be transferred to the piperidine product 206 during the silver-catalyzed process; the method was subsequently employed in the formal synthesis of the alkaloid (−)-coniine (Scheme 3.63).

NH • Ph

Me H

204

Bn NH

AgBF4 (50 mol%) CH2Cl2, 20 °C

H

Me +

Ag 205

N

H Me

Ph 206

N H

H Me

(–)-Coniine

Scheme 3.63 6-exo-trig cyclization of an optically active δ-aminoallene.

As an extension of this work, the authors used 10 mol% to 1 equiv. of AgBF4 to induce the cyclization of secondary γ-aminoallenes 207 (Scheme 3.64) [77]. Very high stereoselectivity for cis-208 was observed (>50 : 1) for substituted amines (R = Ts, Bn, Boc). However, cyclization of the primary amine (R = H)

3.3 Formation of C—N Bonds

EtO2C

NH R

•

AgBF4 (0.1–1.0 equiv.) CH2Cl2, 20 °C

EtO2C

N R cis-208

R = H, Boc, Bn, Ts

207

+ EtO C 2

N R

trans-208

Scheme 3.64 Silver-catalyzed cyclization of secondary γ-aminoallenes.

was unselective, suggesting that the size, and not the electronic nature, of the substituent on the amine nitrogen is critical for observed stereoselectivity. The first enantioselective examples of the silver-catalyzed hydroamination reaction were reported by Hii and coworkers. Using a chiral silver phosphinic salt (β-CgPOOAg), the intramolecular cyclization of a series of N-protected γ-aminoallenes 217 can be achieved with up to 68% ee (Scheme 3.64) [78]. In this work, pyridine was added to accelerate the reaction (Scheme 3.65).

Z

H Ph Ph N 209

•

β-CgPOOAg (15 mol%), Pyridine (15 mol%) DCE, 24 h

Ph Ph

Z = Ts, 4-Ns, SO2Me, SO2Mes, SO21-Np, Cbz, Bn

N Z

210

β-CgPOOAg = O O O P OAg O

Scheme 3.65 First enantioselective hydroamination of allenes catalyzed by silver.

Carbamates are reactive nucleophiles in silver-catalyzed heterocyclization reaction of allenes. In the presence of an organic base, AgNCO or AgOTf catalyzes the stereoselective cyclization of O-2,3-butadienylcarbamates 211 to 4-vinyl-2-oxazolidinones 212 (Scheme 3.66) [79, 80]. The reaction yield was dependent upon the nature of the N-substituent, facilitated by electronwithdrawing groups such as tosyl. Moderate to high stereocontrol in favor of the trans-isomer was observed, and the selectivity increases with the size of the substituent R2 . These results were rationalized by comparing the steric H H R2

O

+

•

Ag 1 R1 AgNCO or AgOTf (10 mol%), R HH • Et3N (10 mol%) R2 R1 R1 NHTs Benzene, 50 °C O NTs O A

O 211

R2 O

O O H NTs R1 • 1 H R2 +R Ag B

R1 R1 N Ts

O trans-212 (major product)

Scheme 3.66 Silver-catalyzed cyclization of allenyl carbamates.

O O

N Ts R1

R2

R1 cis-212

117

118

3 Silver-Catalyzed Cyclizations

environment of the transition states: A is favored over the transition state B, as it is free from gauche repulsions between R2 and the allene. Employing the silver-catalyzed cyclization of allenic hydroxylamines 213 as a key step, Bates et al. achieved the total synthesis of alkaloids, including sedamine [81], porantheridine [82], and sedinine [83] (Scheme 3.67).

O

H N

Ph

Boc •

AgNO3 (20 mol%), TMG (10 mol%) Acetone–H2O (5 : 1), r.t.

N

O

Boc

OH Ph

Ph

TMG = 1,1,3,3-tetramethylguanidine

O R

H N

Boc •

AgBF4 (10 mol%) CH2Cl2, r.t.

O

N

Boc

N n

Pr

O

Me Porantheridine

R = nPr or Me 213

H

H

(R = nPr)

R

N Me Sedamine H

(R = Me)

OH Me

OH N H H Me Sedinine

Ph

Scheme 3.67 Total synthesis of alkaloids achieved using silver-catalyzed cyclization of allenic hydroxylamines.

Intramolecular cyclization of aminoallene intermediates may be embedded in cascade reactions. In a reported synthesis of functionalized pyrroles, Xin and coworkers reported a cyclization/sulfonyl group migration cascade process catalyzed by AgTFA, where 3-aza-1,5-enynes 214 are transformed into 2-trifluoromethyl-5-(arylsulfonyl)methyl pyrroles 215 (Scheme 3.68) [84]. The authors proposed that the reaction initiates with an aza-Claisen rearrangement of 3-aza-1,5-enyne, followed by an imine–enamine isomerization to generate intermediate 216. In the presence of Ag(I) catalyst, the C—N bond formation occurs, rather unusually, at the central sp-hybridized carbon; the reaction terminates with a migration of the sulfonyl group to yield the final product 220. 5- and 6-endo-trig Cyclizations Highly substituted Δ3 -pyrrolines can be accessed

efficiently by 5-endo-trig cyclization of α-aminoallenes; the use of silver catalysts was first reported by Dieter et al. [85, 86]. Using 20 mol% of AgNO3 , cyclization of a-aminoallenes 217 occurred in a facile manner at ambient conditions, affording the pyrrolines 218 with high levels of diastereoselectivity (c. 95%), in favor of the syn-product (Scheme 3.69(1)). In later work, the reaction between chiral propargyl mesylate/perfluorobenzoates with α-(N-carbamoyl)alkylcuprates was used to prepare enantioenriched α-aminoallenes 219. In the ensuing silver-catalyzed cyclization, it was shown that the N-alkyl-substituted Δ3 -pyrrolines 220 can be obtained in moderate yields with retention of the enantiopurity (Scheme 3.69(2)) [87]. The synthetic methodology was subsequently adopted by Werner et al. to create an 80-member library of 3,4-dehydroproline amide derivatives 221 for

3.3 Formation of C—N Bonds

R2 CO2Me R1

214

R1 = aryl R2, R3 = alkyl, aryl

•

CF3

N H

R O2S

215 R2

CO2Me

Isomerization

•

CF3 N SO2R3

R1

R2

R 3

R2

CO2Me

1

DMF, 80 °C

N CF3 SO2R3 214

aza-Claisen rearrangement

Ag(I)

R2

AgTFA (5 mol%)

CF3 HN SO2R3 216

R1

R2

CO2Me

CO2Me

CO2Me

1

R

CF3 Ag • HN R1 SO2R3

CF3 N H SO2R3

Ag

215

– Ag(I)

Scheme 3.68 Cyclization/sulfonyl group migration cascade of 3-aza-1,5-enynes to functionalized pyrroles.

•

N H

R2

R3

R1

R

H

R1

Acetone, r.t.

R2

1. s-BuLi,THF, –78 °C, TMEDA R1 2. CuCN.2LiCl • 3. R

R1

OX (X = Ms, C6F5CO) R2 • R1 MeO2C NH2

R3 R4

N

R3 H

R1

R anti-218

217

N Boc

R2

AgNO3 (20 mol%)

R2

1. TMSCl, MeOH

H 2. AgNO3 (20 mol%) NBoc Acetone, r.t. 219

H R3

N

[1]

R syn-218

R1 N

R2 H

[2]

220 R2

R2 AgNO3 (20 mol%) R1 Acetone, r.t. MeO2C

R3 N R4 R1

R1 R6HNOC

N

R3 [3] R4

R5 O 221

Scheme 3.69 Stereoselective 5-endo-trig cyclization of α-aminoallenes to Δ3 -pyrrolines.

biological evaluation (Scheme 3.69(3)). In this work, chiral α-aminoallenes were derived from amino acids [88]. In closely related work, chiral N-Boc glycinates 222 (derived from ynamidoalcohols) were subjected to a Claisen rearrangement to the allenylamides 223, which underwent stereoselective silver-catalyzed cyclization to 2,5-disubstituted 3-pyrrolines 224 in excellent yields (82–90%) and diastereoselectivities (dr ≥ 95 : 5) (Scheme 3.70) [89].

119

120

3 Silver-Catalyzed Cyclizations

NHBoc

O

Ts N R2

O 1

R

1. LiHMDS, ZnCl2, THF, –78 °C

H

2. K2CO3, MeI, DMF, r.t.

•

Boc HN CO2Me

R1

N Ts R2 223

222

Acetone, r.t.

R1

AgNO3 (5 mol%)

Boc N CO2Me N Ts R2 224

R1 = H, Me, CH2OBn, iPr, (CH2)2CH=CH2, –(CH2)2Ar, –(CH2)4OTBDPS R2 = Bn, CH2C3H5, CH2Ar, –(CH2)2Ar Scheme 3.70 Tandem Claisen/5-endo-trig cyclization to 2,5-disubstituted 3-pyrrolines.

The vinyl silver intermediate generated by the silver-catalyzed 5-endo-trig cyclization of α-aminoallenes may be trapped by an electrophilic halogen source, such as N-chlorosuccinimide (NCS), allowing the formation of chlorinated 3-pyrrolines 226 (Scheme 3.71) [90]. When the electrophilic fluorinating agent NFSI is employed, 4-fluoro-2,5-dihydropyrroles 227 are obtained, which can be converted into 4-fluoropyrroles 228 [91]. Good yields were obtained for substrates possessing an electron-withdrawing or aromatic group at R2 . A double hydroamination reaction of 2-trifluoromethyl-1,3-enynes 229 was reported by Xiao and coworkers [92]. In the presence of 10 mol% of AgNO3 the reaction with a range of alkyl, aryl, and allyl primary amines proceeded via the

R3 R2

[Ag(phen)OTf] (10 mol%) 2,6-lutidine (40 mol%) NCS (1.3 equiv.)

•

225

R2

•

R1 NHTs

R2

MeCN, 80 °C

NHR1

R3

R1 = Ph, PMB; R2 = aryl; R3 = Ph, Me

R3

AgNO3 (20 mol%), F-N(SO2Ph)2 (1.5 equiv.), R2 K2CO3 (2.0 equiv.) Et2O, r.t.

R1

R1 = H, alkyl, aryl R2 = CO2Et, CO2Bn, SO2Ph, aryl, alkyl R3 = H, Ph, iBu

Cl N R1 226

F 3 N R Ts 227

KOtBu; or DDQ/NaOEt

R2 R1

Scheme 3.71 5-endo-trig cyclization of α-aminoallenes trapped with NCS.

F 3 N R H 228

3.3 Formation of C—N Bonds

CF3 + R2NH2 R1

AgNO3 (10 mol%)

F3C

CF3 R

PhCl, r.t.

1

• HN

H 229

H 1 N R 2 R 231

2

R

230

Scheme 3.72 Ag-catalyzed double hydroamination of 2-trifluoromethyl-1,3-enynes.

•

OMe

1. tBuCN

Li

2. H2O

232

•

OMe

OMe

AgNO3 (20 mol%), K2CO3 (2.0 equiv.)

tBu

tBu N H 234

MeCN, r.t.

HN 233

Scheme 3.73 Ag-catalyzed 5-endo-trig cyclization of an α-iminoallene.

α-aminoallene intermediate 230 to furnish 4-trifluoromethyl-3-pyrrolines 231 in moderate to good yields (Scheme 3.72). In a separate example, the addition of lithiated methoxyallene 232 to pivalonitrile afforded the iminoallene 233, which, upon treatment with 20 mol% of AgNO3 , cyclized to the pyrrole derivative 234 (Scheme 3.73) [93]. In 1986, Grimaldi reported that the 6-endo-trig cyclization of β-allenic primary amides 235 occurred in the presence of 10 mol% of AgBF4 , with selective attack of the nitrogen atom to the allene, to afford the 3,6-dihydro2(1H)-pyridones 236. In all of the examples given, gem-dimethyl groups were present at the α-carbon, suggesting that the reaction is subjected to the Thorpe–Ingold effect (Scheme 3.74(1)) [94]. Subsequently, the silver-catalyzed cyclization of N-monosubstituted allenic carboxamides 237 was examined by Albanov and coworkers [95]. In this work, nucleophilic attack of oxygen or nitrogen are competitive, leading to dihydrofuran 238 or dihydropyrrole 239 derivatives, respectively (Scheme 3.74(2)). The chemoselectivity of the reaction is highly dependent upon the silver counterion as well as the substituents: when AgOAc was employed as the catalyst, a higher selectivity toward the formation of

•

R1 R2

O

R2

•

NH2

NH

R3

237

CHCl3, reflux

[1]

O 236

235 R1 R1

O

R1 2 NH R

AgBF4 (10 mol%)

AgOAc or AgNO3 (17 mol%) Acetone, r.t. R1 = H, Me R2 = H, OMe R3 = iPr, nPr

R2

R2 N R3

Scheme 3.74 Silver-catalyzed cyclization of amidoallenes.

O 238

R1 + O R1

R1 N R1 R3 239

[2]

121

122

3 Silver-Catalyzed Cyclizations

the dihydrofuran product 238 was observed for the allene substrate containing terminal gem-dimethyl groups (R1 = Me). 3.3.1.3

Alkenes

Compared with alkynes and allenes, silver-catalyzed hydroamination reactions of alkenes are rarely reported. The research group of Wolfe reported the only intramolecular example [96]: in the presence of a stoichiometric amount of base and a catalytic amount of AgNO3 , the cyclization of tosyl-protected N-allylguanidines 240 to cyclic guanidines 241 proceeded in high yields (Scheme 3.75). The presence of O2 was essential to allow a catalytic amount of AgNO3 to be employed, although its exact role in the reaction is not clear. N R1

N

Ts NH2

R2

AgNO3 (15 mol%), NaOtBu (1.0 equiv.) PhCl, O2, 80 °C R1 = alkyl, benzyl, ether R2 = H, Me

240

N 1

R N

Ts NH

R2 241

Scheme 3.75 Silver-catalyzed cyclization of N-allylguanidines to cyclic guanidines.

Recently, Chen and coworkers reported an efficient synthesis of 2-substituted 4H-pyrido[1,2-a]pyrimidin-4-ones 245 in good yields from 2-aminopyridines 242 and alkynoates 243, catalyzed by AgOTf (Scheme 3.76) [97]. The first step of the reaction involves the silver-catalyzed addition of the amino group of the 2-aminopyridine to the triple bond of the alkynoate to give the intermediate 244, which then cyclizes to give the product. It is likely that the Ag acts as a Lewis acid in this process.

R1

NH2 N 242

O

+ R2

OEt

H N

AgOTf (30 mol%) ClC6H5,120 °C

R

243

R1 = H, Me, Ph, F, Cl, Br, I, CO2Me, CF3 R2 = Me, tBu, COCH3, aryl, thienyl

R2

1

R1

N

O

244

OEt

N

R2

N O 245

Scheme 3.76 Silver-catalyzed reaction of 2-aminopyridines and alkynoates to form pyrido[1,2-a]pyrimidin-4-ones.

3.3.2

Cycloisomerization Reactions of Alkynes

Much like the Conia-ene reaction (Section 3.2.1), silver salts can catalyze the cycloisomerization reaction of alkynes with a wide range of C=O and C=N groups to furnish different heterocycles. Many of the examples below employ

3.3 Formation of C—N Bonds

2-alkynylaryl aldehydes, as well as its Schiff base, oxime, or hydrazone derivatives, as precursors [98]. In the presence of a silver catalyst, the C=O or C=N group adds to the alkyne to generate cationic fused rings (e.g. benzopyrylium salts) that can undergo further reactions with a wide range of nucleophiles (Scheme 3.77). H R

H Ag+

X

1

+

X+

R1

X

R1

R2

R2

R2

Ag

Ag

X = O, NR′

Scheme 3.77 Cycloisomerization reactions of alkynes with C=O and C=N moieties.

3.3.2.1

Imines as Nucleophiles

Larock and coworkers first reported the 6-endo-dig cyclization of 2-alkynylaryl aldimines bearing a tert-butyl imine group (246a) in the presence of AgNO3 to give the isoquinoline derivatives (247a); the tert-butyl group provided a nonacidic H+ source for the process, eliminating isobutene as a by-product (Scheme 3.78(1)). The reaction is also applicable to analogous pyridine carbaldehydes to afford naphthyridine products (247b) [99, 100]. The procedure was subsequently modified by Asao et al. for the preparation of 1,2-dihydroisoquinolines 248 by trapping the intermediate with carbon pronucleophiles (Scheme 3.78(2)) [101]. In a separate report, Zhang, Wu, and coworkers showed that the trifluoromethyl group can also be introduced into the isoquinoline scaffold using trimethyl(trifluoromethyl)silane as a nucleophilic reagent. The reaction can be performed at room temperature in the presence of acetic acid [102]. In the presence of the electrophilic fluorine reagent NFSI, silver-catalyzed cyclization of 246a afforded the fluorinated isoquinolines 249 (Scheme 3.79). AgNO3 (5 mol%)

N

CHCl3, 50 °C

X

246 R X = CH (a), N (b) R = aryl, alkenyl, alkyl N

R1

R2

N X

+

[1]

R 247

Nu AgX (cat.), Nu

N

R1 [2] R2

248

When Nu = CH2NO2, CH(CN)2, CH(CO2Me)2, C≡CR′ AgOTf (3 mol%), NuH (2 equiv), DCE, 80 °C When Nu = CF3: AgSbF6 (5 mol%), TMSCF3 (4 equiv.), AcOH (1.1 equiv.), MeCN, r.t.

Scheme 3.78 6-endo-dig cyclization of 2-alkynylaryl aldimines.

123

124

3 Silver-Catalyzed Cyclizations

NFSI (1.5 equiv.) AgNO3 (20 mol%), Li2CO3 (1 equiv.)

R2 1

R

DMA, 60 °C

N

F R2 R

1

N

246a

249

R1 = Cl, F, OMe, R2 = alkyl, aryl, ester, CH2N(Ts)(Boc) F

Ag 246a

Ag(I)

R2 R1

NFSI

N 250

R2 R1

249 +

N 251

Scheme 3.79 Oxidative aminofluorination of 2-alkynylaryl aldimines 246a.

In this case, oxidative fluorination of the sp2 C—Ag bond of the organosilver intermediate 250 occurs to form the intermediate isoquinolinium 251, which decomposes with the loss of isobutene to isoquinoline 249 [103]. Subsequent mechanistic studies revealed that the fluorination is the rate-determining step of the reaction [104]. The two methodologies can be coupled in a one-pot process for the synthesis of 1-(trifluoromethyl)-4-fluoro-1,2-dihydroisoquinoline 252 through the sequential addition of NFSI and TMSCF3 . By replacing the latter with sodium borohydride, the 4,4-difluoro-1,2,3,4-tetrahydroisoquinoline 253 can be obtained (Scheme 3.80) [105]. 2. Me4NF (2.0 equiv.), TMSCF3 (5.0 equiv.) R3 R1

N 246a

1. AgNO3/L (20 mol%), NFSI (3.0 equiv.), DMA, r.t., 4h

F R3 R1

R1 = H, OMe, F, Cl, R2 = alkyl, Ph, Bn R3 = nBu, Ph, cyclopropyl

N

F F

R2 L=

O

N N

2. NaBH4 (2.0 equiv.) R1 = H, OMe, F, Cl, R2 = alkyl, Bn R3 = nBu, cyclopropyl

R2

CF3 252

R1

N

R3 R2

253

Scheme 3.80 One-pot synthesis of 1,4-disubstituted 1,2-dihyroisoquinolines.

2-Alkynylaryl glycine imines 254 undergo cycloisomerization to generate a 1,3-dipolar species that can participate in [3+2] cycloaddition with alkynes in the presence of silver catalysts. The domino cycloisomerization/dipolar cycloaddition reaction was reported by Su and Porco [106]. The reaction was catalyzed by AgOTf (10 mol%) to generate a isoquinoline intermediate. In the presence of 2,6-di-tert-butyl-4-methylpyridine (DTMP), the azomethine ylide 255 is generated, which reacts with alkynes to furnish pyrrolo-isoquinolines 256 in moderate to good yields (Scheme 3.81). The tandem reaction was

R6 R1 CO2R5

N

R2 254

AgOTf (10 mol%), DTBMP (1.0 equiv.)

+

Toluene, 60 °C, air

R1 N

R2 R

R4

R3

R6

R1 CO2R5

R

R3

255

260

N

R2

4

3

R6 CO2R5 R4 256

R1, R2 = H, F, OMe, OCH2O R3, R4 = CO2Me, CO2Et, C4H9, CHO, COMe, Ph, TMS R5 = Me, tBu R6 = alkyl, phenyl, TMS F

R3

R3

1

R

N

CO2

R2

254 + MeO2C

R1 AgNO3 (20 mol%), (±)–L (20 mol%), NFSI (5.0 equiv.), Li2CO3 (3.0 equiv.) DMA, 60 °C

CO2Me

N MeO2C

(±)–L = CO2R2

CO2Me 257

Scheme 3.81 Silver-catalyzed [3+2] cycloaddition of 2-alkynylaryl glycine imines with alkynes.

O

N N

126

3 Silver-Catalyzed Cyclizations

subsequently further elaborated by Xu and Liu to incorporate a fluorination step (a tandem aminofluorination/[3+2] cycloaddition reaction) to afford the 4-fluoropyrrolo[α]isoquinolines 257 [103]. Using 2-alkynylaryl aldehydes 258, one of the reactants in a three-component coupling reaction with amines and diethyl phosphite, Wu and coworkers reported an efficient one-pot synthesis of 2,3-disubstituted-1,2-dihydroisoquinolin1-ylphosphonates 259 using AgOTf as a catalyst (Scheme 3.82) [107]. CHO

+ R2NH2

O + H P OEt OEt

R1

OEt EtO P O

AgOTf (5 mol%)

N

EtOH, 60 °C R1, R2 = alkyl, aryl

R2 R1

258

259

Scheme 3.82 Synthesis of 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonates using 2-alkynylaryl aldehyde precursors.

Using the same approach, a number of polycyclic heterocycles can be prepared (Scheme 3.83): benzothienopyridines 261a and benzofuropyridines 261b can be prepared by a one-pot tandem process by the reaction of tert-butylamine with alkylethynyl-benzothiophene-2-carbaldehydes 260a and alkylethynyl-benzofuran-3-carbaldehydes 260b, respectively, in the presence of AgNO3 under reflux in a protic solvent [108]. A very similar strategy was employed for the synthesis of substituted pyrroles 263 from β-alkynyl ketones 262 and primary amines (Scheme 3.84) [109]. R +

t

BuNH2

O X 260 X = S (a), O (b)

R

AgNO3 (10 mol%)

N

EtOH, 70 °C R = alkyl, aryl, SiMe3

X 261

Scheme 3.83 Synthesis of polycyclic compounds using 2-alkynyl aromatic aldehyde precursors. O +

R1 R2 262

R3

4

R NH2

AgOTf (5 mol%)

R4 N

1

R

R3

DCE, 50 °C 2

R R1, R2 = alkyl 263 3 R = H, SiMe3, CO2CH3 R4 = alkyl, allyl, benzyl, aryl, Ts

Scheme 3.84 Synthesis of pyrroles from β-alkynyl ketones and amines.

The use of diazoacetate as a reactant in the one-pot coupling reaction with 2-alkynylbenzaldehydes 258 and amines led to the formation of 3-benzazepines 264 (Scheme 3.85) [110]. The key step in the transformation involves a

3.3 Formation of C—N Bonds

CHO R

AgOAc (20 mol%)

+ R3NH2 + 4 R O N2

R2 258

O R4 R1

4 Å MS, DCE, 100 °C

R1

N R3 264

R1 = Cl, F, CF3, OMe R2 = alkyl, aryl, thiophenyl R3 = H, aryl R4 = (CH2)2Ph, (CH2)2Cl, CH2CH=CH

Ag(I)

H

R3 R2

Ag

1,2-Aryl migration –N2

R2

–Ag(I)

R4

N2 N

O

R4

O

1

R1

O N R3

Ag

R2

Scheme 3.85 Synthesis of 3-benzazepines by the coupling between a 2-alkynylbenzaldehyde, amine, and a diazo compound.

nucleophilic addition of the diazoacetate to form an isoquinolinium intermediate, followed by 1,2-aryl migration to form the expanded ring. Under microwave irradiation, treatment of 2-alkynylacetophenones (265a) or 3-acetyl-2-alkynylpyridines (265b) with ammonia in the presence of AgOTf resulted in the formation of the expected imino-cyclization products 266 and the carbocyclization products 267 (Scheme 3.86) [111]. In the proposed mechanism, Ag(I) activates the carbonyl group of 265 toward nucleophilic attack by ammonia, resulting in the formation of the imine 268, which exists in equilibrium with its enamine tautomer 268′ . Either imino- or carbocyclization with selective 6-endo-dig geometry can occur, via nucleophilic attack of the imine nitrogen or the enamine carbon, on the silver-activated alkyne, followed by protodemetalation to give the final products. By embedding nucleophilic components with the amine reactant, further ring formation can be achieved. This was described by Verma et al. (Scheme 3.87) [112] in the synthesis of oxazine/benzoxazine-fused isoquinolines and naphthyridines 271 by a silver-catalyzed domino process from 2-alkynyl aldehydes 269 and amino alcohols or diamines (270). The reactions were performed “on water” in the presence of AgNO3 at 80 ∘ C. Higher yields were obtained with aromatic amines compared with aliphatic amines. The final step of the proposed mechanism involves the silver-catalyzed intramolecular cyclization of the intermediate 272. A domino process for the synthesis of 2,3-substituted indoles 274 was described by Oh et al. [113] by a silver-catalyzed condensation of alkyne imino ethers 273 with active methylene compounds, such as dimethyl malonate. The cycloisomerization reaction was followed by a novel and unprecedented 1,3-alkenyl shift from the nitrogen to the silver-activated site, prior to the protodemetalation step (Scheme 3.88). 1,2,5-Trisubstituted 1H-imidazoles 278 can be constructed by a silvercatalyzed domino process starting from ketenimine 275 and propargylic amines

127

128

3 Silver-Catalyzed Cyclizations

R1

R1

AgOTf (10 mol%)

O

N

NH3/MeOH, MW 120 °C

X R2

265 X = CH (a), N (b)

R2

X

R1 = CH3O, F R2 = alkyl, aryl

NH2

1 + R

R2

X

266

267

266 + 267

265 Ag(I)

R1

NH R2

X Ag

R1

Ag

X

X +

Ag

R2

R2

268

R2

X

O

NH

+ NH2

+

R1

R1

NH3

Ag NH2

R1 X +

Ag

R2

268′

Scheme 3.86 Competitive imino- and carbocyclization of 2-alkynylacetophenones (265a) or 3-acetyl-2-alkynylpyridines (265b).

CHO

+

Y

269

R1

X

R1 X = CH, N R1 = alkyl, aryl

n

N

H2O, 80 °C

H2N

X

Y

AgNO3 (10 mol%)

n

270 n = 0,1 Y = OH, NH2, NHMe Y

271

n

Ag(I)

N H X R1 272

Scheme 3.87 Silver-catalyzed domino synthesis of benzoxazine/oxazine-fused isoquinolines and naphthyridines.

3.3 Formation of C—N Bonds

OEt N

+ X

R2

X

273 +

Ag(I)

H

X

N

–H+

R2 Ag

N R2

R1 X

Ag

X

N

R1

R2

R1

+

1,3–Alkenyl shift

X

274

X

–EtOH

X

X

R1 = alkyl or aryl R2 = H, OMe, NO2 X = CO2Me, CN X

R1

R2

Toluene, 80 °C

R1

273

H N

X AgOTf (5 mol%)

Ag

H+ –Ag(I)

274

X

Scheme 3.88 Synthesis of 2,3-substituted indoles via alkyne imino ethers and active methylene compounds.

276 (Scheme 3.89). The reaction involves a nucleophilic addition of propargylic amine to the ketenimine to form the intermediate 277, which then undergoes a silver-catalyzed 5-exo-dig cyclization and 1,3-H shift to generate the product [114]. Ph R1

C N R2 AgOTf (10 mol%), Et3N (1.0 equiv.)

275 +

THF, reflux

H2N

R3 276

R1

Ph

HN

R2 N

Ph

R1 R3

N

N

R2

Ag+ R3 277 278 R1 = Ph, Me; R2 = aryl, pyridyl; R3 = H, aryl

Scheme 3.89 Synthesis of trisubstituted 1H-imidazoles from ketenimines and propargylic amines.

3.3.2.2

Oximes

Shin and coworkers first reported the AgOTf-catalyzed cyclization of 2-alkynylbenzaldoximes 279, affording the isoquinoline-N-oxides 280 in good yields (Scheme 3.90) [115]. Subsequent Pd [116] or Cu [117] catalysis may be performed to introduce aryl and amine substituents at the C1 of the isoquinoline-N-oxides, respectively. In comparison, regioselectivity of the silver-catalyzed cyclization of o-alkynylaryl aldehyde oxime derivatives 281 is highly dependent on the substituent effects: at an elevated temperature, either the 1-acetoxyisoquinolines 282 or isoquinolines 283 can be obtained, depending on the O-substituent R3 (Scheme 3.91) [110].

129

130

3 Silver-Catalyzed Cyclizations Ar

ArX Pd catalysis

N

R1

O R2

N

R1

OH AgOTf (5 mol%)

N H

R2

CH2Cl2, r.t.

R2

279

N

R1

O

280

N

Cu catalysis

R1

N

O R2

Scheme 3.90 6-endo-dig cyclization of o-alkynylbenzaldoximes. R2 R1 N

R1 281

O

AgOTf (5 mol%)

R3 DMA, 110 °C

R2

R1 R1

NH O (R3 = Ac) 282

R2

R1 OR R1

N (R3 = Me) 283

Scheme 3.91 Regiodivergent cyclization of o-alkynylaryl aldehyde oxime derivatives.

A number of 1,3-disubstituted isoquinolines have been prepared from 2-alkynylbenzaldoximes 279 by tandem 6-endo cyclization/[3+2] cycloaddition/ rearrangement reactions (Table 3.1). In some cases, further rearrangement reactions resulted in the formation of bicyclic compounds or the 3,4-disubstituted isoquinolines. Conversely, isoquinoline-N-oxides can be activated toward nucleophilic attack in the presence of electrophilic activators. Wu and coworkers reported the reaction of 2-alkynylbenzaldoxime 279 with amines [125] and phenols [126] in the presence of 2 equiv. of PyBroP (bromotris(pyrrolidino)phosphonium hexafluorophosphate) to afford 1-aminoisoquinolines and 1-aroxyisoquinolines (Scheme 3.92). The proposed mechanism involves the reaction of the isoquinoline-N-oxide intermediate 280 with PyBroP to generate the adduct 292. Subsequent intermolecular nucleophilic addition of either amine or phenol then occurs to afford intermediate 293, which then undergoes deprotonation to produce the desired 1-aroxyisoquinoline product 291 with the release of tris(pyrrolidino)phosphine oxide by-product. The method was employed by Buron and Routier in the one-pot synthesis of 2,4-disubstituted γ-carbolines 295 from 2-alkynylindole-3-carbaldehyde oximes 294, where phenols, thiols, carboxylic acids, and amines can be used as nucleophiles for the reaction (Scheme 3.93) [127]. Using arylsulfonyl chlorides as activators, the reaction of 2-alkynylbenzaldoxime 279 and phenols or AgSCF3 generated the corresponding 1-aroxy- and 1-(trifluoromethyl)thio isoquinolines, 296 and 297, respectively (Scheme 3.94) [128, 129]. In the absence of nucleophile, 4-tosyloxyisoquinolines are formed. TsCl reacts with isoquinoline-N-oxide 280 to form the intermediate 299, which undergoes nucleophilic attack of chloride followed by a transfer of the tosyloxy group to

3.3 Formation of C—N Bonds

Table 3.1 Synthesis of 1,3-disubstituted isoquinolines by the tandem 6-endo cyclization/[3+2] cycloaddition/rearrangement reactions of o-alkynylbenzaldoximes.

N

R1

AgOTf (10 mol%)

Ag(I) catalyst, reagents

Product

R2

279 Ag(I) catalyst

OH

Reagents

Product

References O

R3 N C N

R3

R3

N

R3

N H

[118]

N

R1

R2 284

AgOTf (10 mol%)

R3 N C S

HN

[119]

R3 N

R1

R2 285

AgOTf (5 mol%)

OH R EWG

R3 EWG EWG = electron-withdrawing group (ester, ketone)

[120]

N

R1

R2 286

AgOTf (10 mol%)

[121]

R3

R3 R4

R4 O N

R1

R2 287

AgOTf (10 mol%)

OTf TMS

R1

O

N

TBAF (3.0 equiv.)

R2

288

AgOTf (10 mol%)

[122]

R3

R3

R3

[123]

R3 R1

O

N R2 289

AgOTf (10 mol%)

R3

C O

Et3N (1.5 equiv.)

[124]

N

R1

R2 O O 290

R3

131

132

3 Silver-Catalyzed Cyclizations

AgOTf (10 mol%), PyBroP (2.0 equiv.), iPr NEt (3.0 equiv.) 2

279 + NuH

N

R1

O

N PF 6 N P Br N

N

R1

1,4-Dioxane, 25 °C (NuH = R2NH, ArOH)

Ag(I)

279

Nu

R2 291

PyBroP

Nu-H

PyBroP R1

R2 280

Base R1

H Nu N N P O N N PF6 Br R2 293

291 +

N N P O N PF6 N Br R2 292

N N P O N

Scheme 3.92 Reaction of 2-alkynylbenzaldoxime with nucleophiles (amines and phenols) in the presence of PyBroP. OH N

Nu

R N Boc 294

N

1. AgOTf (10 mol%), CH2Cl2, r.t., 18 h 2. PyBroP, NuH, DIPEA, r.t., 18 h

R

N Boc 295

(NuH = ArOH, RSH, RCO2H, R2NH)

Scheme 3.93 Synthesis of 2,4-disubstituted γ-carbolines.

279 + Ar-OH

AgOTf (10 mol%), TsCl (1.5 equiv.), Ag2CO3 (0.75 equiv.), Et3N (3.0 equiv.)

O

N

R1

R2

1,4-Dioxane, 25 °C

279 + AgSCF3

AgOTf (10 mol%), p-MeOC6H4SO2Cl (1.5 equiv.), K3PO4 (4.5 equiv.) DMA, 25 °C

Ar

296 SCF3 N

R1

R2 297

Scheme 3.94 Reaction of 279 with O- and S-nucleophiles in the presence of arylsulfonyl chlorides.

3.3 Formation of C—N Bonds

AgOTf (10 mol%), ArSO2Cl (1.2 equiv.), KHCO3 (2.0 equiv.), 1 Ag2CO3 (2.0 equiv.) R

279

298 OSO2Ar Cl

279

R2

DCE, 25 °C –

Ag(I)

N

280

ArSO2Cl

O Ar S O N O

+

R1

R2 299 Cl

Cl N

R1 Base

O Ar S O N O

R1

–HCl

298

R2

H OSO2Ar

300

Scheme 3.95 Ag-catalyzed reaction of 2-alkynylbenzaldoxime with arylsulfonyl chloride.

the 4-position of isoquinoline to form the intermediate 300. Further cleavage of the N—O bond and elimination of HCl generates the 4-tosyloxyisoquinoline 298 (Scheme 3.95) [130]. An attempt was also made to utilize benzoyl chloride as an activator for the reaction. In this case, however, the silver-catalyzed reaction between 279 and benzoyl chloride and triethylamine afforded the unexpected product 2-(isoquinolin-1-yl)isoquinolin-1(2H)-ones 301 as a result of rearrangement reactions and nucleophilic attack on the isoquinoline-N-oxide intermediate (Scheme 3.96) [131]. R1

279

AgOTf (10 mol%), PhCOCl (1.5 equiv.), Et3N (1.5 equiv.) THF, 25 °C

R2

N

O N

R1

R2 301

Scheme 3.96 Ag-catalyzed reaction between 2-alkynylbenzaldoxime and benzoyl chloride and triethylamine.

In an analogous reaction to that was previously described in Scheme 3.82, 1-phosphorylated isoquinolines 302 can be prepared in moderate to good yields by the silver-catalyzed tandem reaction of 279 with H-phosphonates (Scheme 3.97) [132]. Using a bimetallic AgOTf/Cu(OTf )2 catalytic system, isoquinoline-N-oxides may undergo reductive N—O bond cleavage in (dimethylformamide/1,2dichloroethane (DMF/DCE) (5 : 1) (Scheme 3.98) [133]. In the proposed mechanism, DMF undergoes nucleophilic attack by the isoquinoline-N-oxide after

133

134

3 Silver-Catalyzed Cyclizations

R3 279 + R3 P O H

R3 O P R3

AgOTf (10 mol%) 4 Å MS, 1,4-Dioxane, 40 °C

N

R1

R2 308

Scheme 3.97 Synthesis of 1-phosphorylated isoquinolines. R3 N

R1 279

OH

AgOTf (5 mol%), CH2Cl2, r.t.

R3 +

N

R1

R2

R2

AgOTf (10 mol%), Cu(OTf)2 (10 mol%)

–

O

R3 N

1 DMF/DCE (5 : 1), 120 °C R

R2 304

O [M] H

O R3

N

N

(M = Ag or Cu) R1

N O

–CO2 –NHMe2

R2 303

Scheme 3.98 AgOTf/Cu(OTf )2 -catalyzed N—O cleavage for the synthesis of isoquinoline derivatives.

activation by Lewis acidic AgOTf or Cu(OTf )2 to form the intermediate 303. Fragmentation to CO2 and NHMe2 then gives the final product 304. 3.3.2.3

Hydrazones

Hydrazone derivatives of indole-3-carbonyl compounds 305 react with propargyl alcohols in the presence of AgOTf to afford annulated products N-iminoγ-carbolinium ylides 306 and 307 (Scheme 3.99) [134]. Two possible mechanisms were proposed by the authors, involving a propargylic cation species that can undergo substitution with 305 to form either an propargylic or allenic intermediate that can cyclize to form the pyridine ring. R3

NHTs N

R3 (R4 = aryl, R5 = H)

R1 N R2 305 +

AgOTf (20 mol%)

R5 108

6

R

N R2 306 R3

THF, 100 °C (sealed tube)

OH R4

R1

4=

NTs 6 R N

NTs 4 R N R5

R1

(R aryl, R5 = alkyl or aryl)

R4

N R2 307

R6

Scheme 3.99 Annulation between hydrazone derivatives of indole-3-carbonyl compounds and propargyl alcohols.

3.3 Formation of C—N Bonds

Liu and coworkers reported the silver-catalyzed tandem 6-exo-dig cyclization/ [3+2] cycloaddition cascade of 1-tosylhydrazon-4-oxy-5-ynes 308 with ethoxyethene to form the aza-cyclic products 310 via the key zwitterionic intermediate 309 (Scheme 3.100) [135]. OEt

AgOTf (5 mol%) R1

N

R2

NHTs OEt

(4.0 equiv.)

CH2Cl2, 25 °C OAc 308

R1 R1

N

NTs

R2 OAc 309

[3 + 2] cycloaddition

N

N

R2 OAc 310

Scheme 3.100 Ag-catalyzed annulation of 1-tosylhydrazon-4-oxy-5-ynes with ethoxyethene.

The isoquinolinium-2-yl amide intermediate 312 can be generated from the Ag-catalyzed cyclization of N ′ -(2-alkynylbenzylidene)hydrazide 311, which can undergo further [3+2] cycloaddition reactions with different reactive intermediates to furnish pyrazolo-isoquinolines. Several examples of these reactions have been provided, which are summarized in Table 3.2. In certain cases, rearrangement with radical cleavage of the N—N bond occurs to give bicyclic products 313–322. The isoquinolinium-2-yl amide 312 can also be further transformed into isoquinoline and pyrazolo[1,5-a]pyridine scaffolds by cooperative catalysis involving silver salts and transition metal catalysts such as copper, rhodium, and palladium. Wu and coworkers showed that copper(I) bromide promotes the formation of ketenimine from alkyne and sulfonyl azide, which can then undergo a [3+2] cycloaddition to afford the 2-amino-H-pyrazolo[5,1-a]isoquinolines 323 (Scheme 3.101) [138, 145]. Later, the same research group also demonstrated that cooperative catalysis with copper(II) acetate also allows the synthesis of 2-carbonyl H-pyrazolo[5,1-a]isoquinolines 324, where copper(II) plays a role in the intramolecular rearrangement after the cycloaddition step [139, 146]. Silver triflate and copper(I) iodide cocatalyze the tandem alkynylation and cyclization of 311 to furnish the H-pyrazolo[5,1-a]isoquinolines 325 [147]. Subsequently, Park and coworkers reported the synthesis of pyrazolopyrido[4,3-d]pyrimidines 327 by a silver-catalyzed 6-endo cyclization of 326, followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed nucleophilic addition of terminal alkynes (Scheme 3.102) [148]. Silver(I)–rhodium(I) cooperative catalysis also provides a novel route to the pyrazolo[5,1-a]isoquinolines 328, where rhodium(I) promotes the [3+2] cycloaddition of cycloprop-2-ene-1,1-dicarboxylate with 311 [149]. In the reaction with 2-vinyloxirane, oxidative addition of Rh(I) to 2-vinyloxirane generates an allylic rhodium complex, which undergoes cycloaddition with 311 and rearrangement to give 329 (Scheme 3.103) [150]. On the other hand, a combination of silver triflate and palladium(II) acetate catalyzed the reaction of 311 with N-allyl ynamide; the Pd(0) species formed in situ generates the reactive ketenimine intermediate from N-allyl ynamide, affording 2-amino-H-pyrazolo[5,1-a]isoquinolines 330 and 330′ (Scheme 3.104) [151].

135

136

3 Silver-Catalyzed Cyclizations

Table 3.2 Synthesis of aza-cyclic products by Ag-catalyzed tandem 6-exo-dig cyclization/[3+2] cycloaddition cascade of 1-tosylhydrazon-4-oxy-5-ynes 311.

N

R1

NHTs Ag(I) catalyst, reagents

R1

Ag(I) catalyst, reagents

[3 + 2] cycloaddition

312 + Intermediate

Intermediate

Product

References N

AgOTf (10 mol%)

[136]

N

TES N

N

N

R1

OTf (1.5 equiv.)

R2 313

CsF (3.0 equiv.) Et3 NBnCl (25 mol%) AgOTf (10 mol%) F

F

F

F

F

F

F

F F (2.5 equiv.)

F

AgOTf (10 mol%)

N

R1

N R2

314

Cs2 CO3 (3.0 equiv.) N.A.

[138]

N

R4

CO2

N

R3

N

R1

R2

(2.0 equiv.) 315

PPh3 (20 mol%) AgOTf (10 mol%)

[137] F

F

F

•

Product

R2

R2

311

NTs

N

N.A.

N

O CO2Me

N O

N

R1

CO2Me (1.5 equiv.)

[139]

N R2

316

Cs2 CO3 (3.0 equiv.) AgOTf (10 mol%) Bn N

Ts (1.5 equiv.)

K2 CO3 (1.0 equiv.)

NTsBn

• NTsBn N

R1 317

N R2

[140]

3.3 Formation of C—N Bonds

Table 3.2 (Continued) Ag(I) catalyst, reagents

Intermediate

AgOTf (5 mol%)

N.A.

EtO2C

Product CF3

EtO2C

CF3

N

R1

(2.0 equiv.)

CsF (1.5 equiv.) AgOTf (10 mol%) O

References

N R2

318 HO2C

N.A.

[141]

[142] R3

R3 N

R1

(2.0 equiv.)

319

H2 O (20 equiv.) 2,6-dimethylpyridine (2.0 equiv.) AgOTf (10 mol%) R3

R3

R2

[143]

R3

TsN N

N

R1

N NHTs (2.0 equiv.)

N

N R2

320

I2 (20 mol%) TBHP (2.0 equiv.) AgOTf (10 mol%) TMS

N N

N Ts Cl N

R1 Cl

N

[136]

OTf Cl (1.5 equiv.)

2 321 R

CsF (3.0 equiv.) Et3 NBnCl (25 mol%) AgOTf (10 mol%) O R3

Cl (1.5 equiv.)

NaH (1.5 equiv.) Et3 N (15 mol%)

R3

O

C O R1

R3 N Ts N

322 R2

[144]

137

138

3 Silver-Catalyzed Cyclizations

N

R1

+ N3-SO2R4

R2

311

NHSO2R4

R3

AgOTf (10 mol%), CuBr (10 mol%), K3PO4 (3.0 equiv.)

R3

NHTs

N

R1

Toluene, 25 °C

N R2

323

311

R3 • +

O2 AgOTf (10 mol%), Cu(OAc)2 (20 mol%), K2PO4 (10 mol%)

R3 R4O

DCE/DMF, r.t.

CO2R4

O

2C

N

R1

N R2

324

311

+ R3

Br

AgOTf (10 mol%), CuI (10 mol%), DBU (3.0 equiv.)

N

R1

DCE, 70 °C

R3 N R2

325

Scheme 3.101 Synthesis of H-pyrazolo[5,1-a]isoquinolines by the reaction of N′ -(2-alkynylbenzylidene)hydrazide 312.

R1

Ts NH N

N

R1 1. AgOTf (20 mol%), DCE, 80 °C 2.

N

R2

, DBU, r.t.

N N

N

N H 326

R2

N N H 327

Scheme 3.102 Synthesis of pyrazolopyrido[4,3-d]pyrimidines.

311 + R3

AgOTf (10 mol%), CO2Me RhCl(PPh3)3 (10 mol%) CO2Me Dioxane/THF, 60 °C

CO2Me MeO2C N

R1

N R2

328

311 + O

O

AgOTf (10 mol%), RhCl(PPh3)3 (10 mol%) DCE, 50 °C

Me

H N

R1

N R2

329

Scheme 3.103 Ag/Rh-catalyzed synthesis of H-pyrazolo[5,1-a]isoquinolines.

3.3 Formation of C—N Bonds

R5

N

311 +

R4

AgOTf (5 mol%), Pd(OAc)2 (10 mol%), PPh3 (20 mol%), Cs2CO3 (1.2 equiv.) DCE/toluene, r.t.

R3

Me Me R3 N

1

R

R3

NTs N

+

N

R1

R2 330

NTs

330′

N R2

Scheme 3.104 Ag/Pd-catalyzed synthesis of H-pyrazolo[5,1-a]isoquinolines.

In the presence of oxidant and base, amines and alcohols may be transformed into enamines and enolates, respectively, which are suitable nucleophiles for reaction with 311 to form a series of pyrazolo-isoquinolines 331 (Scheme 3.105) [152–155]. R3 NR2

R3

N

R1

R2

(a) or (b)

R4 (c)

311

R3

R4

R3

NR2

R3

N

N

R1

N R2

OH

R3

(d) or (e)

N

R1

N R2

331 Scheme 3.105 Synthesis of pyrazolo-isoquinolines via oxidized enamines and enolates. Reaction conditions: (a) AgOTf (5 mol%), Fe(acac)3 (5 mol%), TBHP (3.0 equiv.), DCE, N2 [152]; (b) AgOTf (5 mol%), PhI(OAc)2 (1.0 equiv.), DCE, air [152]; (c) AgOTf (10 mol%), PdBr2 (5 mol%), DMF, air, 65 ∘ C [153]; (d) AgOTf (10 mol%), DMP (2.0 equiv.), K3 PO4 (2 equiv.), DCE/CH2 Cl2 , 60 ∘ C [154]; (e) AgOTf (10 mol%), PdCl2 (5 mol%), K2 CO3 (3.0 equiv.), toluene, O2 [155].

The isoquinolinium-2-yl amide intermediate 312, generated from the cyclization of 311, can also react with nucleophiles. Homoenolates, derived from α,β-unsaturated aldehydes in the presence of N-heterocyclic carbene (NHC) catalyst 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr), can attack the 312 to generate intermediate 333 (Scheme 3.106). Methanol then acts as a proton source and regenerates the NHC catalyst, affording the 2-amino-1,2dihydroisoquinoline 332 in moderate to good yields [156]. Using 2-alkynylbenzaldehyde 258 as a precursor, Wu and coworkers showed that H-pyrazolo[5,1-a]isoquinolines 334 may be synthesized in one pot by a tandem reaction of 258, sulfonohydrazide, with a ketone or an aldehyde

139

140

3 Silver-Catalyzed Cyclizations

311

+

O R3

AgOTf (5 mol%), IPr·HCl (5 mol%), Cs2CO3 (25 mol%)

+ MeOH

THF/DCE, 50 °C

H

O

OMe

3

R

N

R1

NHTs R2

332 O R3

IPr

O

H

–IPr

N

R1

R3

IPr

IPr

O R3 332

O IPr

R3

H NTs

OMe

N

R1

NTs AgOTf

312

R2 312

R2 333

Scheme 3.106 Ag-catalyzed reaction of 1-tosylhydrazon-4-oxy-5-ynes 312 with α,β-unsaturated aldehydes. R4

R3 O

R1

AgOTf (10 mol%), K3PO4 (3.0 equiv.) R1

O

+ TsNNH2 + 3 R

R4

R2

N

N R2

EtOH, 60 °C 334

258

O

R3

R4 265a + TsNNH2 +

O

AgOTf (5 mol%) R4

R3

DCE/DMA, 60 °C

N

R1

N R2

335 OR

258 + TsNNH2 +

O 3

R

4

+ ROH

R

AgOTf (5 mol%), KOH (3.0 equiv.) DCE, r.t.

R4

R3 N

R1

N R2

336 NH2

R3 258 + TsNNH2 + R3

AgOTf (10 mol%), DABCO (2.0 equiv.) N

1,4-Dioxane, 70 °C

N

R1

N R2

337

Scheme 3.107 Synthesis of H-pyrazolo[5,1-a]isoquinolines from 2-alkynylbenzaldehydes.

3.3 Formation of C—N Bonds

(Scheme 3.107) [157]. As an interesting extension of this work, Wu later reported the a three-component reaction between 258, sulfonohydrazide, and α,β-unsaturated carbonyl compound to produce 335 via a [3+2] cycloaddition [157]; the incorporation of an alcohol gives the pyrazolo-isoquinolines 336 [158]. Nitriles are also suitable nucleophiles for the one-pot reaction, affording the pyrazolo-[5,1-a]isoquinolin-2-amines 337 [159]. 3.3.2.4

Aromatic N-Heterocycles

The cycloisomerization of aromatic N-heterocyclic compounds tethered with an alkyne moiety is a convenient method for the synthesis of nitrogen-fused heterocycles. In 1996, Lok et al. reported that 2-(propargylamino)benzoxazoles, benzothiazoles, and benzoselenazoles 338 cyclize in the presence of a catalytic amount of AgBF4 to give dihydropyrimidines 339 (Scheme 3.108) [160]. The reaction is accelerated by electron-donating groups on the benzene ring. R1

X

2

N

R

NH R4 R4

R1

X

R2

N

AgBF4 (cat.)

N

CD3CN, 40 °C

X = O, S, Se R1 = H, Cl R2 = Me, Cl, CN, OMe, CO2Me R3, R4 = H, Me

R3 338

R4 R4

R3 339

Scheme 3.108 Cycloisomerization of alkyne-tethered benzoxazoles, benzothiazoles, and benzoselenazoles.

Similar cyclization of propargyl-tethered pyridines 340 and to indolizines and pyrroloquinoxalines 341 was reported by Gevorgyan and coworkers (Scheme 3.109) [161]. Substrates with acetyloxy, diethylphosphatyloxy, and O-TBS-protected propargylic substituents and alkyl, aryl, and alkenyl substituents can be accommodated to offer products in good yields. R1

R1 AgBF4 (3 mol%)

X N

R2

CH2Cl2, r.t.

X N R2

340

341 X = CH, N R1 = OAc, OP(O)(OEt)2, OTBS R2 = H, alkyl, aryl, alkenyl

Scheme 3.109 Cycloisomerization of alkyne-tethered pyridines.

The cyclization of N-(prop-2-yn-1-yl)pyridin-2-amines 342 forms imidazo [1,2-a]pyridine derivatives 343 in the presence of 10 mol% of AgOTf as catalyst (Scheme 3.110) [162]. Dry deoxygenated solvent is required to prevent the competitive intramolecular dehydrogenative aminooxygenation reaction.

141

142

3 Silver-Catalyzed Cyclizations

N

H N N 342

N 343

R

Y

X

Deoxygenated MeCN, reflux

N NH2 344

O Sarpidem

R N

Y

AgOTf (10 mol%)

N

Cl

N

N

Deoxygenated MeCN, R reflux

R

X

N

AgOTf (10 mol%)

N NH 345

X = CH, N Y = CN, Ph, Me, Cl R = Me, Bn

Scheme 3.110 Cyclization of N-(prop-2-yn-1-yl)pyridin-2-amines 342 and 2-amino-6-propargylamine azines 344.

The usefulness of this synthetic method was further demonstrated in the total synthesis of the anxiolytic agent sarpidem. In a similar manner, iminoimidazoazines 345 have also been synthesized by the AgOTf-catalyzed cyclization of 2-amino-6-propargylamine azines 344 [157, 163]. With the aim of understanding the general reactivity of the pyridine motif toward alkynyl substrates, Gagosz studied the silver-catalyzed reaction of 2-propynyloxy-6-fluoropyridines 346 and arylamines under microwave irradiation. Interestingly, the oxazolopyridine imines 347 were obtained, proposed to be the result of a 3,3-rearrangement of 346 to form N-allenyl pyridone intermediate 348, which then undergoes a 5-endo cyclization at the central carbon of the allene to form the intermediate fluoropyridinium 349. Finally, 349 reacts with arylamine to furnish 347 after the loss of HF (Scheme 3.111) [164].

N

O R1

AgNTf2 (10 mol%), Na2CO3 (4 equiv.)

F + R3NH 2

R1 R1, R2 = alkyl R3 = aryl, benzyl, pyridyl

346

Ag(I)

O

N

[3,3]-

F

R+2 Ag

R1

R1

N Ag

R2 349

• R2

347

F

H Ag+

5-endo cyclization

348

H2NR3 O

R2

N

O

rearrangement

R1

N

CHCl3, MW 100 °C

R2

346

N

O

F

O R

N Ag

1

R2

NH2R3 F –Ag(I) –HF

347

Scheme 3.111 Reaction of 2-propynyloxy-6-fluoropyridines 346 and arylamines.

3.3 Formation of C—N Bonds

The silver(I)-catalyzed cycloisomerization reaction of ynone-tethered pyridine, isoquinoline, and pyrazine 350 was reported by Taylor and coworkers to afford quinolizinone products 351 in good yields under mild conditions (Scheme 3.112). The synthetic utility of the reaction was further demonstrated in the synthesis of the alkaloid (±)-lasubine II [165]. H R2 O

X

OH

2

N

R AgNO3 (2 mol%)

N

DCE/EtOH (1 : 1), r.t.

R1

N

O

X R1

R3 H, Me, CN, Br 351 R = H, Me R3 = H, alkyl, aryl, heteroaryl

R3

R1 =

OMe OMe

2

350

(±)-Lasubine II

Scheme 3.112 Cyclization of ynone-tethered pyridine-, isoquinoline-, and pyrazine 350.

The research group of Van der Eycken described a series of reactions involving a domino four-component Ugi reaction/Michael reaction of imidazole2-carbaldehyde, propargylamines, 2-alkynoic acids, and isonitriles to afford the imidazole-pyrrolone 352, which is subsequently subjected to a silver-catalyzed 6-exo-dig cyclization reaction to furnish the imidazole-based triheterocycles 353 in good to excellent yields (Scheme 3.113) [166]. R1 H N

O +

N

CO2H R1

MeOH, r.t.

O 352

O R2 NH R1

O NH N

N O [Ag]

Michael addition

N

N

R2NC

H2O, MW 120 °C

N

HO N

Ugi-4CR

R2 NH R1 AgSbF6 (5 mol%)

O NH N

NH2

50 °C

NH R2

R2 NH O R1 N N

N

O

353

Scheme 3.113 Four-component Ugi reaction/Michael reaction and silver-catalyzed 6-exo-dig cyclization to form imidazole-pyrrolones.

3.3.2.5

Other Nucleophiles

Liang and coworkers reported the silver-catalyzed cyclization of the 2-alkynylbenzyl azide system 353, where N2 acts as the leaving group, to give substituted isoquinolines 354 after treatment with base (Scheme 3.114) [167]. The method was further extended by Reddy et al. to the intramolecular cyclization of (E)-2-en-4-yn-1-azides 355 to furnish the corresponding substituted 3,6-disubstituted pyridines 356 in moderate to good yields [168].

143

144

3 Silver-Catalyzed Cyclizations

R2 N3

R1

R3

353

AgSbF6 (20 mol%), TFA (2.0 equiv.)

R1

N R3

3

R –

R1 = Cl, Me R2, R3 = alkyl, aryl

CF3CO2

AgSbF6 (30 mol%), TFA (2.0 equiv.)

DCE, 80 °C

R2

H NaHCO3 (aq.)

N

DCE, 80 °C –N2

N3

O

R2

R2

354

N

O R

1

R2

356

355 1

2

R = OMe, Me; R = alkyl, aryl, heteroaryl

Scheme 3.114 6-endo-dig cyclization of 2-alkynylbenzyl azides and 2-en-4-yn-1-azides.

Tandem 6-endo-dig cyclization/nucleophilic addition of alkyne-functionalized azomethine 357 with nucleophiles such as ketones, nitroalkanes, and terminal alkynes provided access to tricyclic amide products 358 (Scheme 3.115) [169]. The reactions proceeded under mild condition at 25 ∘ C, except for alkyne nucleophiles, which required heating at 60 ∘ C in acetonitrile.

N N

R1

R2 357

+ NuH O

AgOTf (20 mol%), L-proline (20 mol%)

Nu N N

R1

25 or 60 °C

NuH = ketone, nitroalkane, and terminal alkyne

358

R2

O

Scheme 3.115 6-endo-dig cyclization/nucleophilic addition of alkyne-functionalized azomethines.

3.4 Formation of C—O Bonds 3.4.1 3.4.1.1

Hydroalkoxylation Alkynes

The first examples of the silver-catalyzed cyclization of γ-acetylenic alcohols were reported by Pale and Chuche in 1987 [170, 171]. Employing silver salts with basic counterions (AgOAc, Ag2 O, and Ag2 CO3 ), a smooth 5-exo-dig cyclization of cis-2,3-epoxy-pent-4-yn-1-ols 358 to the 3,4-epoxy-2-methylene oxolanes 359 proceeded in good to excellent yields. In contrast, AgNO3 was ineffective, while AgBF4 led to competitive decomposition. Linear acetylenic alcohols, however, required stoichiometric amounts of Ag2 CO3 for the reaction to proceed. It was suggested that the epoxy group orientated the hydroxyl group and the acetylenic unit in a manner that favors the electrophilic addition. Propargylic substituents were found to be essential for the cyclization of linear acetylenic alcohols 360 [172]. It was thought that these propargylic substituents altered the adjacent π-system through hyperconjugation, leading to a dramatic acceleration of the

3.4 Formation of C—O Bonds

OH

R O 358 R = H, Me

R 360

O

Ag2CO3 (10 mol%) Benzene, 80 °C

R

O 359 O

OH Ag2CO3 (10 mol%) Benzene, 80 °C

R 361

R = OH, OMe, OMOM, OtBu, OtBDPS

F SiO2

F R1

F

F

AgNO3 (10 mol%) R2

THF, reflux

HO 362

R1

O

R

1

F

F

2 O R 363

R2

F Pd/H2

R1

2 O R 364

Scheme 3.116 Intramolecular hydroalkoxylation of γ-acetylenic alcohols.

reaction rate. Hammond and coworker later applied the strongly accelerating effect of propargylic substituent to the synthesis of fluorofuran derivatives 363 and 364 from β-acetylenic alcohols 362 (Scheme 3.116) [173]. Exposed to 10% w/w silver(I) nitrate absorbed on silica gel, 3-alkyne-1,2-diols 365 undergoes 5-endo-dig cyclization, followed by dehydration under mild reaction conditions, to give the corresponding furans 366 in essentially quantitative yields (Scheme 3.117) [174]. R2

OH R3

R1 OH 365

10% AgNO3–SiO2 CH2Cl2, 20 °C

R2 R1

3 O R R1, R2, R3 = alkyl, aryl, ether 366

Scheme 3.117 5-endo-dig cyclization of 3-alkyne-1,2-diols.

Substituted furans were also obtained from the silver-catalyzed cyclization reaction of allenyne-1,6-diols 367 (Scheme 3.118) [175]. The study revealed that Ag(I) tends to be more alkynophilic than allenophilic: with both an alkyne and allene moiety present in the substrate, nucleophilic attack of the homoallenyl alcohol occurs preferentially onto the activated alkyne instead of the allene to give the furans 368 as the final product. This contrasts with the reactivity compared with Au(III), which has a higher preference in the activation of the allene vs. the alkyne and gives dihydrofurans 369 as products. When the intramolecular nucleophile is a phenol, aurones 371 may be prepared by cyclization of 370 in the presence of 30 mol% of AgNO3 . Only traces of the isomeric flavones were detected (Scheme 3.119) [176]. This was extended in a tandem silver-catalyzed cyclization and azidation reaction of

145

146

3 Silver-Catalyzed Cyclizations

AgOTf (15 mol%) CH2Cl2, r.t. R OH

R

R

R

OH Ag

•

OH

OH

R

O

R

368

OH •

AuCl3 (15 mol%)

367 R = alkyl, aryl

CH2Cl2, r.t.

R

OH R

O

OH Au

•

OH

R

R 369

Scheme 3.118 Silver- and gold-catalyzed reaction of allenyne-1,6-diols. R2 R1

AgNO3 (30 mol%)

OH R2 O

O

R1

MeOH, r.t.

H

R1, R2 = H, OMe, OiPr

O 371

370 Ag2CO3 (5 mol%) TMSN3 (2.0 equiv.)

R1 OH

XH 372

R2

DMSO, 80 °C X = O, NTs R1 = H, Ph, Me, iPr R2 = aryl

[Ag] 5-exo-dig

R1 OH X 374

R1 N3 X 373

R2

TMSN3 R2

Scheme 3.119 Intramolecular 5-exo-dig hydroalkoxylation of alkynes by phenol nucleophiles.

hydroxyl/aminophenyl propargyl alcohols 372 for the synthesis of benzofuranyl and indolyl methyl azides 373 [177]. The azido group of the products can be used as a precursor for a variety of useful functionalities such as triazole, tetrazole, amide, amine, and pyrido derivatives. Although the formation of five-membered furan derivatives seems to be preferred in most of the silver-catalyzed cyclization reactions of alkynols, conveniently chosen substrates can lead to the formation of six-membered heterocycles. AgOTf catalyzes the oxacyclization of structurally diverse homopropargylic diols 375, leading to bridged bicyclic ketals bearing a functionalizable side chain 376 (Scheme 3.120) [178]. The research groups of Kanai and Shibasaki reported an asymmetric catalytic procedure for the synthesis of enantiomerically enriched dihydropyranones 379 from ynones 377 (Scheme 3.121) [173, 179]. The procedure involves

3.4 Formation of C—O Bonds

R1 HO HO

R1

AgOTf (5 mol%) Toluene, 25 °C R1 = allyl, alkynyl R2 = H, Ph

R2 375

O

O 2

R

376

Scheme 3.120 Double oxacyclization of homopropargylic diols. O R3 377 + R1CHO

O O O

R2

CuOCH2CF3/ O (R)-DTBM-SEGPHOS (3–5 mol%), R3 CF3CH2OH (40–200 mol%) * * R2 THF, –40 or –60 °C 1 R OH R1 = alkyl, aryl; R2 = Me, Et, Ph 378 R3 = H, Me AgOTf (10 mol%), CH2Cl2, r.t. or t Bu MW 100 °C PAr2 , Ar = OMe O t PAr2 R2 Bu

O (R)-DTBM-SEGPHOS

R1

2 O R 379

Scheme 3.121 Synthesis of enantiomerically enriched dihydropyranones from ynones.

two sequential steps where copper(I) catalyzes the asymmetric aldol reaction of ynone and aldehyde in the presence of a chiral diphosphine ligand, DTBM-Segphos. This affords the unstable aldol intermediate 378, which undergoes a silver(I)-catalyzed 6-endo-dig cyclization reaction to furnish the dihydropyranone product 379 with up to 93% ee. Enders and coworkers showed that silver catalysis can be combined effectively with a organocatalysts in one pot to achieve a sequential Michael addition/ hydroalkoxylation reaction enantioselectively. Using the cinchona alkaloid catalyst 383, the synthesis of annulated coumarins 380 and, depending on the substituents on the enynone, the six-membered ring fused 380′ [180]. Similarly, using the chiral squaramide 384, the synthesis of 4H-pyranonaphthoquinones 381 [181] and tetrahydrobenzofurans 382 was also achieved with high levels of enantioselectivity (Scheme 3.122) [181, 182]. Another example of cooperative catalysis was reported by Zhao and coworkers, where DBU and silver salt were combined to effect a nucleophilic addition/ cyclization reaction of propargylic alcohols 386 and trifluoromethyl ketones 385 to afford trifluoromethyl-substituted 5-alkylidene-1,3-dioxolane derivatives 388 in moderate to excellent yields (Scheme 3.123) [183]. DBU catalyzes the nucleophilic addition of 386 to 385, generating the intermediate 387, which then undergoes a silver-catalyzed 5-exo-dig cyclization to 388.

147

OH

O +

R1 O

1.383 (20 mol%), (S)-Boc-N-alanine (40 mol%), THF, 4 °C

O

Me R3

O 1

R

OH +

NO2 R3

R2

R2

O

O

R3

CH2Cl2, r.t.

N

380′

383

R3 F3C

O

NO2

381

O

NH2

O

O

R2

NO2

O

380

384 (0.5 mol%), R1 AgOTf (15 mol%)

384 (0.5 mol%), Ag2O (1 mol%)

OMe

O

N

O

CH2Cl2, r.t.

O

O + R1

R1

2. Ag2CO3 (10 mol%), toluene, r.t.

O

+

R2 O

O

O

NO2

F 3C

O

O

N H

N H

384 O

R

382

Scheme 3.122 Combining organocatalysis with silver catalysis for the asymmetric synthesis of O-heterocycles.

N

3.4 Formation of C—O Bonds

O R1

+ CF3

R2

385

R1 CF3 O O–

AgNO3 (10 mol%), DBU (10 mol%)

OH

Toluene, r.t., 24 h

+

Ag

386

R1 CF O

R2

387

3

O R2

388

Scheme 3.123 One-pot nucleophilic addition/cyclization reaction of propargylic alcohols and trifluoromethyl ketones.

3.4.1.2

Allenes

5-endo-trig In 1979, Olsson and Claesson reported that 2,5-dihydrofurans 390

can be prepared by 5-endo-trig cyclization of α-allenic alcohols 389 in the presence of silver salts (Scheme 3.124) [184]: a number of α-monoalkyl- and α,α-dialkyl-substituted α-allenols (R1 and/or R2 = alkyl) cyclized smoothly in the presence of 3 mol% of AgBF4 in CHCl3 . Unsubstituted α-allenols (R3 , R4 , R5 = H) required harsher conditions of 10 mol% of AgNO3 using water–acetone as solvents in the presence of CaCO3 to afford the corresponding products in moderate yields. R1 OH R2

•

R3

R5 R4

389

AgBF4 (3 mol%) CHCl3, r.t. R1–R5 = H, alkyl

R1 O R2

R5 R4

R3 390

Scheme 3.124 First reported 5-endo-trig cyclization of α-allenic alcohols.

Allenic alcohols bearing electron-withdrawing groups cyclize easily in the presence of silver salts: in the presence of 5 mol% of AgClO4 in CH2 Cl2 , α-allenols with electron-withdrawing phosphonate and phosphine oxide groups 391 afforded 2,5-dihydrofurans 392 in good yields at room temperature (Scheme 3.125) [184, 185]. Similarly, exposed to 10 mol% of AgF, the α-hydroxy allenic sulfones 393 yielded the corresponding 3-tosyl-2,5-dihydrofurans 394 in acetonitrile at room temperature (Scheme 3.154) [185, 186]. Notably, bis-allyl-substituted α-allenols 395 can be transformed to the corresponding 2,5-dihydrofuran derivatives 396 chemoselectively [187]. The reaction of lithiated methoxyallene and aldehydes generates α-allenols 397, which can cyclize under strongly basic conditions to the dihydrofurans 398 (Scheme 3.126) [188]. While the cyclization worked well with the alkoxyallene intermediate with alkyl substituents at R1 , cyclization of allenols with aryl substituents only proceeded in reproducible yields by using AgNO3 in acetonitrile. The alkoxyallene-based dihydrofuran derivatives can be further transformed into tetronic acid and pyridazine derivatives. Marshall and Wang reported that the diastereoisomers of the allenyl carbinols, 399 and 399′ , underwent smooth and stereospecific cyclization to the 2,5-dihydrofurans trans- and cis-400, respectively, upon treatment with AgNO3 –CaCO3 in an aqueous acetone solution (Scheme 3.127) [189, 190].

149

150

3 Silver-Catalyzed Cyclizations

OH Et

AgClO4 (5mol %)

Me

CH2Cl2, r.t.

•

R

P R O

R

P R O 392

390 HO R1 R2 Me • Ts Me 393 nBu

Bn OH

•

Et Me

O

R1 O R2

AgF (10 mol%) MeCN, r.t.

Me Me

Ts 394 Bn

AgNO3 (20 mol%) n

Bu

CH2Cl2, r.t.

O

395

396

Scheme 3.125 Ag-catalyzed 5-endo-trig cyclization of substituted α-allenic alcohols.

R1CHO

OR2

•

+

Li

•

OR2 HO 397

KOtBu, DMSO, 50 °C (R1 = alkyl); or

R1 AgNO (20 mol%), MeCN, r.t. (R1 = aryl) 3

OR2 O 399

R1

Scheme 3.126 Synthesis of alkoxyallene-based dihydrofurans by the cyclization of α-allenic alcohols. MeO2C

OH •

(S)

H C7H15 (R) 399 H (R)

OH •

MeO2C C7H15 (R)

H CH3

H CH3

AgNO3 (20 mol%), CaCO3 (0.8 equiv.) Acetone/H2O (3 : 2), r.t.

Me BnO

•

OH 401

H C7H15

H Me MeO2C O H trans-400

AgNO3 (20 mol%), CaCO3 (0.8 equiv.)

C7H15

Acetone/H2O (3 : 2), r.t.

399′

Me

C7H15

Me MeO2C H O H cis-400 Me Me

AgNO3 (20 mol%) Acetone, r.t.

BnO

H

O 402

C7H15 H

Scheme 3.127 Diastereoselective cyclization of α-allenic alcohols.

A similar procedure was also applied to the cyclization of the allene 401 to 402 [191]. Using chiral silver phosphate catalyst 159 (R′ = 4-diphenyl), kinetic resolution of racemic α-allenic alcohols (rac-403) can be achieved by an asymmetric silver-catalyzed hydroalkoxylation reaction (Scheme 3.128) [192]. The catalyst

3.4 Formation of C—O Bonds

OH • R (S)-403 R = alkyl, alkenyl, aryl

OH

159 (20 mol%)

•

R

O

+ R

CH2Cl2, –10 °C

rac-403

(R)-404

R′ O O O P OAg R′ 159 R′ = 4-diphenyl

Scheme 3.128 Kinetic resolution of racemic α-allenic alcohols.

preferentially promoted the cyclization of one enantiomer of the α-allenic alcohol to deliver 2,5-dihydrofurans 404 and enantiomerically enriched α-allenic alcohol 403 in ee of up to 99.8% (Scheme 3.151). 6-endo-trig Silver-catalyzed 6-endo-trig cyclization of β-allenols 405 to 5,6dihydro-2H-pyrans 406 was described along with 5-endo-trig cyclizations in the original report by Olsson and Claesson in 1979 (Scheme 3.129) [184]. Later, reaction of β,β- and β,γ-allenediols (407 and 410, respectively) was further investigated by Gore and coworkers, who reported a selective reaction of the β-hydroxy group vs. the γ-hydroxy group [193]. Reaction of unsubstituted β,β-allenediols 407 resulted in the preferential formation of the bicyclic acetals 408 rather than the dihydropyrans 409. A similar selectivity was also observed in the cyclization of the substituted β,γ-allenediols 410. Remarkably, the HO

R2

•

R1

R3 405 OH

AgNO3 (20 mol%), CaCO3 (0.8 equiv.)

2 O R 3 R

R1

Acetone/H2O (3 : 2), r.t. R1 = H, Me R2 = H, nPr R3 = H, Me, Et

406

OH

AgNO3 (10 mol%)

•

Acetone/H2O (1 : 1), r.t. 407 OH OH • 410

O 409

408

AgNO3 (10 mol%)

OH Acetone/H2O (1 : 1), r.t.

R

O

O

+

O R 411

O

OH

+

O R 412

When R = H, 411/412 = 9 : 1 R = Me, 411/412 = 0 : 1

Scheme 3.129 Silver-catalyzed 6-endo-trig cyclization of β-allenols.

151

152

3 Silver-Catalyzed Cyclizations

introduction of a methyl substituent at the terminal carbon of the allene in 410 resulted in a switch in selectivity toward the dihydropyran product 412. Silver-catalyzed cyclization of propargyl benzoates to form pyran ring systems was explored by Carter and coworkers [194]. The reaction involves a rearrangement of the propargyl benzoate 413 to the γ-allenol 415, followed by a silver-catalyzed hydroalkoxylation to afford the pyran ring products 414 (Scheme 3.130). The methodology was applied to the synthesis of the C1 —C12 subunit of madeirolide A. Ph O

R3

O

OH R3 R

AgBF4 (10 mol%)

R2

R1 Toluene or xylenes, reflux

O

R2

Ph

O

OH R3

OH O R1

OH O R2

R1 –Ag(I)

R

R2

Ag+ R3 O

O •

H R1

Ph

O

3

Ph

R3

O

Ph 414 Ph

Ag(I)

* O

2

413

413

R1

O * *

R2

R3

OH

O + Ag

•

Ag H O

R1

O

Ag –Ag(I) O

R2

H R1

414

Ph

415 EtO2C OPiv H

O

O

O H

H

H

O C1–C12 subunit of madeirolide A

Scheme 3.130 Formation of pyran ring systems via the cyclization of propargyl benzoates.

5-exo-trig The cyclization the γ-allenols 416 in the presence of a number of

Lewis acids was examined by Hii and coworkers [195]. Interestingly, the regioselectivity of the reaction is dictated by the Lewis acid catalyst: while AgOTf facilitated the formation of the 5-exo-trig vinyl-substituted tetrahydrofurans 417, Sn(OTf )2 or Zn(OTf )2 favored the 6-exo-dig tetrahydropyran ring products 418 and 419, respectively (Scheme 3.159). Density functional theory (DFT) calculations showed that in the silver-catalyzed reaction, the C—O bond formation occurred with concomitant deprotonation of the hydroxyl group by the counterion on the silver, followed by protonolysis of the vinyl silver intermediate

3.4 Formation of C—O Bonds

(Scheme 3.131). Replacing the counterion from TfO to TFA would reduce the activation energy by 1.5 kcal mol−1 . In accordance with the experimental results, the reaction with 15 mol% of AgOTf occurred in 16 h, while reaction with AgTFA gave a similar yield at room temperature in only 2 h. AgOTf (15 mol%)

•

HO

Ph Ph

DCE, r.t.

Ph Ph

O 417

416 Me

Ph Ph

•

O Ph 418 [Sn(OTf)2]

O O Ph Ph Me 419 [Zn(OTf)2]

F3C F3C X O X O 5-exo-trig H H O O O Ag O Ph Ag • Ph

Protonolysis

Ph

417

Ph

Scheme 3.131 Metal-directed regioselective cyclization of γ-allenols.

The observed counteranion effect led eventually to the development of the enantioselective version of the reaction. Using silver salts of chiral acids, derived from the oxophosphorus(V) acids, β-CgPOOH and TADDOL–POOH, γ-allenols and γ-allenic acids were transformed to tetrahydrofurans and lactones 421 with ee of up to 73% (Scheme 3.132) [78].

2

R

R2

X

•

OH n

420

1 1R

R

β-CgPOOAg or TADDOL-POOAg (15 mol%)

X R

DCE, r.t. n = 1, 2 X = H2, O

1

R1

O n

R2 421

R2

R1 = Ph; R2 = alkyl O O O O P Ag O β-CgPOOAg

O O

O O P O O Ag

TADDOL-POOAg

Scheme 3.132 Enantioselective cyclization of γ-allenols and γ-allenoic acids using chiral silver salts.

Subsequently, it was shown that enantioselective silver-catalyzed cyclization of γ-allenol 423 can also be achieved using a chiral atropisomeric diphosphine ligand 422, the reaction afforded the vinyltetrahydrofurans 424 with enantiomeric ratios up to 91.5 : 8.5 (Scheme 3.133) [196]. A one-pot intramolecular cyclization of epoxide-propargylic esters 425 to 1,4-oxazine derivatives was reported by Shi and coworkers [197]. The reaction

153

154

3 Silver-Catalyzed Cyclizations

•

HO

Br

AgSbF6 (15 mol%), 421 (7.5 mol%), Ph MeOH (3.0 equiv.) Ph DCE, 10 °C R = alkyl, aryl

R R

MeO MeO

O

423

PAr2 PAr2

Br 422 Ar = 4-CO2tBu-C6H4

424

Scheme 3.133 Enantioselective cyclization of γ-allenols using a chiral diphosphine ligand.

involves an epoxide ring opening by methanol, migration of the acyloxy group to form the allenyl intermediate 427 before cycloisomerization, and elimination of acetic acid to afford the 1,4-oxazine products 426 (Scheme 3.134) [191]. R1

R4 N

OAc R1 R2

O

AgNTf2 (10 mol%), TsOH (10 mol%)

R3 426

R 425

MeOH

O

MeOH/DCE (1 : 1), 60 °C

3

424

R2

R4 N

R4 N

OH

OAc R1 R2

Ag+ 1 R • R2

AcO Ag(I) N R4 R3

OMe

3

R

OMe

OH

OMe 427 OAc R4 N

R1

R1

O R2

–Ag(I)

–AcOH R3

R4 N

R2 O

OMe R3

OMe 426

Scheme 3.134 One-pot synthesis of 1,4-oxazine derivatives from epoxide-propargylic esters.

3.4.1.3

Alkenes

Intramolecular cyclization of alkenols (and alkenoic acids) can occur in the presence of silver salts. However, it must be noted that these reactions can also be catalyzed by Brønsted acids, which may be the active catalyst [198]. The silver-catalyzed hydroalkoxylation of unactivated alkenes was first reported in 2005 by He and coworkers (Scheme 3.135) [199]. In the presence of AgOTf, δ-alkenyl alcohols 428 afforded 5-exo-trig tetrahydrofuran products 429 exclusively, except with trisubstituted alkenes and terminal phenylalkenes, where the 6-endo-trig process dominates to afford substituted tetrahydropyrans 430.

3.4 Formation of C—O Bonds

R1

OH

AgOTf (5 mol%) R1 DCE, 83 °C

R2 428

R2 429

+

O

R1 R2 O 430

Scheme 3.135 Silver-catalyzed hydroalkoxylation of unactivated alkenes.

Dihydrobenzofurans (432, n = 1) or dihydrobenzopyrans (432, n = 2) can be prepared by the cyclization of phenol derivatives bearing an alkenyl side chain in the presence of silver salts (Scheme 3.136) [200]. A strong counteranion effect on catalytic efficiency was observed: while AgClO4 and AgOTf catalyzed the reaction efficiently, AgBF4 , AgTFA, and AgPF6 were ineffective.

n

OH 431

AgOTf or AgClO4 (5 mol%)

n

Toluene, reflux n = 1, 2

O 432

Scheme 3.136 Synthesis of dihydrobenzofurans and pyrans by intramolecular cyclization of phenol derivatives.

A similar counteranion effect was also observed in the silver-catalyzed sequential addition/cyclization of phenols to isoprene (Scheme 3.137). Only AgOTf, AgSbF6 , AgBF4 , and AgClO4 promoted the reaction, and other silver salts were ineffective. The reaction proceeds via the o-allylphenol intermediate 433 that undergoes a 6-endo-trig cyclization to give the dihydrobenzopyran 434. Interestingly, when the other dienes were used, 5-exo-trig cyclized dihydrobenzofuran products were also observed [201].

+

R

AgOTf (5 mol%)

OH

DCE, r.t.

R

R OH 433

O 434

R = H, 4-OMe, 4-Et, 4-Cl, 3,4-OCH2O

Scheme 3.137 Silver-catalyzed annulation of phenols with isoprene.

3.4.2 3.4.2.1

Hydrocarboxylation Alkynes

In the presence of AgI or Ag as catalyst, 2-alkynylbenzoic acids 435 can be converted to 5-exo-dig cyclized dihydrobenzofuranone derivatives 436 in high yields (Scheme 3.138) [202]. Complete selectivity toward 436 was obtained when the alkyne is substituted with a phenyl group (R2 = Ph). However, for substrates where R2 = alkyl group, cyclization resulted in the formation of the 6-endo-dig 3-alkylisocoumarins 437 as a side product. The ratio of 436 : 437 was found to increase with the bulkiness of the alkyl group. Conversely, Bellina et al. showed that AgNO3 in acetone at room temperature favored the formation of

155

156

3 Silver-Catalyzed Cyclizations

O OH

R1

R2

AgNO3 (20 mol%), acetone, r.t.; or

O R1

O

Ag (10 mol%), DMF, 60 °C

435 R1 =

H, OMe R2 = C3H7, C2H5CH(OMEM), (E)-C2H5-CH=CH

O +

O

R1

R2

R2

436 437 [Ag] = AgI or Ag (10 mol%), DMF, r.t. R1 = H; R2 = t-Bu, n-Hex, Cy, Ph [Ag] = AgNO3 (20 mol%), acetone, r.t.; or Ag (10 mol%), DMF, 60 °C R1 = H, OMe; R2 = C3H7, C2H5CH(OMEM), (E)-EtCH=CH

Scheme 3.138 Cyclization of 2-alkynylbenzoic acids: 5-exo-dig vs. 6-endo-dig.

the isocoumarins 437, while Ag powder in warm DMF favored benzofuranones 436 [203]. AgI, Ag, or Ag2 CO3 also catalyzed the cyclization of (Z)-2-alken-4-ynoic acids 438 to afford the (Z)-5-alkylidenefuran-2(5H)-ones 439 selectively in moderate yields, with a small amount of pyranone 440 formed as a competitive side product (Scheme 3.139) [202, 204]: the product distribution is dependent upon the substrate structure, the counteranion of the Ag catalyst, and the solvent. The strategy was later used in the synthesis of the naturally occurring ligustilide 442 (Scheme 3.140) [205].

O HO R

AgI or Ag (10 mol%); or Ag2CO3 (5 mol%) DMF, r.t. or 100 °C

438

R

O 439

R = nPr, iPr, tBu, nHex, Cy, Ph

O + R

O O 440

Scheme 3.139 Cyclization of (Z)-2-alken-4-ynoic acids. O

O OH

AgI or Ag (10 mol%)

O

DMF, r.t. 441

nPr

442

nPr

Scheme 3.140 Synthesis of ligustilide 442.

Synthesis of new 5-alkylidenebutenolide compounds can be achieved by a Ag2 CO3 -catalyzed regio- and stereoselective cyclization, and in situ dehydration, of the 2,5-diaryl-3-hydroxypent-4-ynoic acids 443, affording access to 3-aryl-5-(arylmethylidene)butenolides 444 in moderate yields (Scheme 3.141) [202, 206]. Highly E-selective olefination of alkynoates with ynolates provides tetrasubstituted alkenes 445, which can then undergo silver-catalyzed cyclization to give either the 5-exo tetronic acids 446 or 6-endo pyrones 447 (Scheme 3.142) [207]. The solvent and counteranion of the silver salts affected the product

3.4 Formation of C—O Bonds

R2 R2

OH

Ag2CO3 (1–20 mol%) DMF, r.t. HO R1

O

O

443

O

444 R1

Scheme 3.141 Cyclization and dehydration of 2,5-diaryl-3-hydroxypent-4-ynoic acids. Ag2CO3 (10 mol%) Me

OLi Me

+ O R1O

DMF, r.t.

THF, –78 °C to r.t. R2

CO2H

R1O R2 445

R1 = Et, iBu R2 = H, Bu, Ph, TES, TBS, MPMOCH2

Ag2CO3 (10 mol%), AcOH (0.5 equiv.) CH2Cl2, r.t.

Me

O O

R1O

R2 446 O

Me

O R2

R1O 447

Scheme 3.142 E-Selective synthesis of tetrasubstituted alkenes for silver-catalyzed cyclization.

distribution: in DMF, 5-exo cyclization is favored. On the other hand, Ag2 CO3 and Ag2 O favored the formation of 446, while AgSbF6 resulted in the pyrones 447. With AgOAc and AgClO4 , however, a poor selectivity toward either product was observed. Interestingly, the same reaction proceeded in the presence of a Brønsted acid and nonpolar solvent (acetic acid in CH2 Cl2 ) to afford 447 selectively. The synthesis of alkylidene seven-membered ring lactones by cycloisomerization of alkynoic acids 448 was investigated by Porcel and coworkers (Scheme 3.143) [208]. For terminal alkynoic acids, the preference for the 7-exodig cyclization product 449 over the 8-endo-dig product 450 was attributed to an unsymmetrical coordination of Ag(I) to the alkyne, leading to an enhanced electrophilicity at the more substituted carbon atom. Most nonterminal alkynoic acids required a stoichiometric amount of silver catalyst for the transformation, except in the case where R1 = H, R2 = Me, and X = O, where the reaction led to the formation of a 1 : 0.7 mixture of the seven- and eight-membered ring lactones. Similarly, 1,2,3-triazole-fused-1,5,-benzoxazocinones 452 can be prepared via a regioselective 8-endo-dig intramolecular cyclization of substituted ethynyl triazoyl benzoic acids 451 [209]. 3.4.2.2

Allenes

β-Allenic acids can be cyclized in the presence of Ag salts, as demonstrated in a short asymmetric total synthesis of (−)-malyngolide (Scheme 3.144) [210]: subjected to 10 mol% of AgNO3 and a sub-stoichiometric quantity of soluble amine,

157

158

3 Silver-Catalyzed Cyclizations

AgSbF6 (5 mol%), PPh3 (5 mol%), Et3N (2.0 equiv)

O OH

R1

R2

448

O

R3 OH

R1 N N

O

R1

DCE, 70 °C

X

R1 =

H, Me, Cl, OMe R2 = H, Me X = O, NTs

N

O

R2

+ R1

X

X

449

450

O R1

R3

N N 2 N R 452

R1 = Me, Cl R2, R3 = alkyl, phenyl, heteroaryl

451

R2

O

AgOTf (10 mol%), K2CO3 (2.0 equiv.) Toluene, MW 130 °C

R2

O

O

Scheme 3.143 Synthesis of seven- and eight-membered rings by intramolecular hydrocarboxylation reactions. H

nC

•

Me

9H19

OBn CO2H

AgNO3 (10 mol%), iPr NEt (5 mol%) Me 2 MeCN, 80 °C

O

453

nC

O 454

9H19

H2, Pd–C Me

OBn

O

nC H 9 19

O

OBn

(–)-Malyngolide

Scheme 3.144 Synthesis of malyngolide by silver-catalyzed cyclization of β-allenic acids.

the optically active allenic acid 453 is transformed via a 6-endo-trig cyclization to the δ-lactone 454. The chirality of the allenic moiety was preserved in this reaction, and the 6-endo-trig cyclization was preferred to the competitive 5-exo-dig pathway, possibly due to the enhanced stabilization provided by the developing positive charge at the disubstituted allene terminus in the transition state. When the carbinol allenoic acid 456 contains both hydroxy and carboxylic acid groups, nucleophilic addition of the carboxylic acid oxygen onto the allene occurred preferentially, resulting in the formation of the γ-lactone 457 (Scheme 3.145) [211]. OH

OH Ph

Me

•

C6H13

CO2Et 455

LiOH THF/EtOH/H2O

Ph

•

C6H13

Me CO2H

456

AgNO3 (10 mol%)

Me C6H13 Ph

O O OH 457

Scheme 3.145 Competitive nucleophilic cyclization of hydroxy and carboxylic acid groups.

3.4.2.3

Alkenes

Intramolecular cyclization of alkenoic acids can be effected by Brønsted acids, as well as metal salts containing weakly coordinating counterions [198]. The regioselectivity of AgOTf-catalyzed hydrocarboxylation of inert olefins 458 was reported by He and coworkers; selectivity toward the γ- or δ-lactones, 459 and 460, respectively, is dependent on the chain length and the substitution

3.4 Formation of C—O Bonds

pattern of the substrate (Scheme 3.146) [199]. Later, a very similar method was employed by Gooßen et al. for the isomerization and subsequent intermolecular hydrocarboxylation of unsaturated fatty acids 461 in the presence of AgOTf, leading to the formation of five-membered cyclic lactones 462. The reaction proceeds even for challenging substrates such as oleic and palmitoleic acid, where only one of the numerous possible double bond isomers could give rise to the desired γ-lactone [212]. R1

AgOTf (5 mol%) R1

O

R2

DCE, 83 °C

OH

R1, R2 = H, Me, Ph

458

O

O

R2

+

459

R1 R2 O 460

O

O n

OH

m

H

AgOTf (10–15 mol%)

O

ClC6H5, 130–160 °C

x

O

462 x = 5, 6,10,12

461

Scheme 3.146 Silver-catalyzed cyclization of alkenoic acids.

Cycloisomerization of C=O

3.4.3 3.4.3.1

Alkynes as Partners

The cycloisomerization of carbonyl groups onto alkynes results in the formation of fused furan or pyran ring systems. The research groups of Agrofoglio and Hudson demonstrated the use of AgNO3 as a catalyst for the preparation of substituted furanopyrimidine nucleosides 464 from 5-alkynyl uracil derivatives 463 (Scheme 3.147) [213]. The reaction involves a 5-endo-dig O-addition, followed by a H-transfer from the uracil to form the pyrimidine product. R2

R2

O NH N R1 463

O

AgNO3 (5 mol%)

O

Acetone, r.t.

N

R1 = H, alkyl, sugar R2 = alkyl, aryl

N O R1 464

Scheme 3.147 Synthesis of furanopyrimidine nucleosides.

The Belmont research group reported an efficient silver-catalyzed synthesis of a series of furoquinoline and pyranoquinoline cores from 1-alkynyl-2carbonylquinoline substrates 465 and alcohol nucleophiles (Scheme 3.148) [214]. The selectivity toward the 5-exo-dig furoquinoline product 466 or the 6-endo-dig pyranoquinoline product 466′ was dependent on the nature of the counteranion of the silver salt used: silver salts with counteranions with pK a > 10 (Ag2 CO3 , Ag2 O, AgO) favored the formation of 466, while those with counteranions with pK a < 0 (AgSbF6 , AgPF6 , AgOTf, AgNO3 ) favored the formation of 466′ . Subsequently, it was discovered that amine additives such as

159

160

3 Silver-Catalyzed Cyclizations

O 1

R N

R2

465

R1 OR′

R′OH (1.2 equiv.) Ag catalyst (5 mol%) DCE, r.t.

R1 OR′ O

+

O N

R1 = H, Me R2 = alkyl, aryl R′ = alkyl, benzyla

466

R2

N

R2

466′

Scheme 3.148 Synthesis of furoquinoline and pyranoquinoline rings.

pyridine, triethylamine, and DBU resulted in a switch in regioselectivity from the 6-endo-dig product to 5-exo-dig product when AgOTf was used as catalyst [215]. These results led them to explore the use of the silver imidazolate polymer ([Ag(Im)]n ) as a stable catalyst for the reaction. In addition, nucleophiles such as 1H-indoles, pyrroles, benzofuran, and 1,3,5-trimethoxybenzene are also compatible with the reaction conditions [216, 217]. In some cases, the counteranion of the silver salt and solvent play key roles in directing the regioselectivity of the reaction. Deng and coworkers observed that AgSbF6 -catalyzed cyclization of 2-diazo-3,5-dioxo-6-ynoates 467 in alcoholic solvents affords γ-pyrones 468, whereas the AgOAc-catalyzed cyclization in DCE yields 3(2H)-furanones 469 (Scheme 3.149) [217]. AgSbF6 catalyzed the 6-endo-dig cyclization of the alkynones 470 produces the benzopyrylium cation 471, which undergoes a further addition of an alcohol, leading to the formation of the 1-allenyl isochromenes 472 (Scheme 3.150) [218]. O

O

O

AgSbF6 (10 mol%) MeOH, 25 °C

R2 R1

N2 467

6-endo-dig

AgOAc (10 mol%), Et3N (1.0 equiv.) DCE, 25 °C 5-exo-dig

R1 = alkyl, aryl, SiMe3; R2 = Ph, OEt

O

O O

O R1

R2

O

R2

O

R1

N2 469

N2 468

Scheme 3.149 Regioselective cyclization of 2-diazo-3,5-dioxo-6-ynoates. R1 O

+ R3OH (2 equiv.)

[Ag] AgSbF6 (5 mol%)

+

470

Scheme 3.150 Synthesis of 1-allenyl isochromenes.

O

O

CH2Cl2, 35 °C R2

R1

R1

R2 471

R′ O H

• R2

OR′

472

3.4 Formation of C—O Bonds

The benzopyrilium ion intermediate 473 formed from 2-alkynylbenzaldehyde 258 can be arrested by a number of nucleophiles to form substituted isochromene derivatives 474 after protodemetalation (Scheme 3.151). Suitable nucleophiles for the reaction include “hard” nucleophiles such as alcohols [219] and “soft” carbon nucleophiles such as indoles [220], trimethoxybenzene [221], and even acetone [222]. NuH

O

NuH, Ag catalyst

H

R1

Nu

+

O

R1

258

R2

Ag 473

R2

O

R1

R2

H 474

NuH = OH 1

R

MeO

R

OMe O

R′

OH

N H

OMe

Scheme 3.151 Nucleophilic attack of the benzopyrilium ion intermediate to form substituted isochromene derivatives.

An enantioselective transformation of 2-(1-alkynyl)arylketones 136 into optically active 1H-isochromene derivatives 475 has been described by Terada et al., through a cyclization/enantioselective reduction sequence, catalyzed by the chiral silver phosphate catalyst 159 (R′ = C6 F5 ) and Hantzsch ester as the reducing agent (Scheme 3.152) [223]. R′O2C

O R3

R1

CO2R′

N H (1.1 equiv.) 159 (10 mol%) THF or EtOAc, r.t.

R2 136

R3 R1

O R2

R′ O O P Ag O O

475 (up to 92% ee)

R′ 159 (R′ = C6F5)

Scheme 3.152 Enantioselective synthesis of 1H-isochromene derivatives.

With a slight modification, isoquinolines 476 can also be prepared from o-(1-alkynyl)arylaldehydes (258) or ketones (136) and a suitable ammonia source such as ammonium acetate (Scheme 3.153) [224]. In this case, the isobenzopyrylium intermediate 477 undergoes protonation with acetic acid,

161

162

3 Silver-Catalyzed Cyclizations

O

AgNO3 (10 mol%), NH4OAc (1.5 equiv.)

R3

R1

tBuOH,

R2

r.t.

R3 N

R1

R2

R1 = H, Me, OMe, F etc. R2 = alkyl, aryl R3 = H (258), Me (136)

476

R3 136 or 258

Ag(I)

+

O

R1

R2

R3

NH4OAc –Ag(I) R1

+

R1

–

R2

Ag 477 H2N

NH3

O OAc 478

HO R3

R3 + OH

+

R2

NH2

R1

R2

476

–H2O

479

Scheme 3.153 Synthesis of isoquinolines from o-(1-alkynyl)arylaldehydes or ketones and an ammonia source.

produced from the decomposition of ammonium acetate, to give intermediate 478. Subsequent nucleophilic attack by ammonia and rearrangement produces the hemiaminal 479, which dehydrates to give the isoquinoline product. The isobenzopyrylium intermediate 516 can also undergo further cycloaddition reactions with olefins, as demonstrated by Zhu and coworkers, in the reaction of 2-alkynylaryl aldehydes 480, containing electron-deficient alkynes or terminal alkynes, to furnish the polycyclic compounds 481 [225], through a tandem 1,3-dipolar cycloaddition/cyclopropanation process (Scheme 3.154). O R1

H

480

+ CO2R2

R3

O

AgNTf2 (5 mol%) R1

R3 CO2R2

DCE, 28 °C 3

R1 = Me, OMe, F, CF3 R2 = Me, Et, Bn, (CH2)2Ph R3 = aryl

R

481

Scheme 3.154 Cycloaddition of isobenzopyrylium intermediate with olefins to produce polycyclic compounds.

Dihydronaphthofuran products can be obtained in good yields from orthocarbonylarylacetylenols by a silver-catalyzed annulation process (Scheme 3.155) [226]. The ortho-keto-formylarylacetylenols 482 led to the desired dihydronaphthofuran products 483 in a single step. The benzaldehyde substrate 482 (where R2 = H) required a one-pot two-step approach, where the bicyclic acetal intermediate 484 was treated with pyridinium p-toluenesulfonate (PPTS) to convert it to the corresponding dihydrofuran or dihydropyran 485.

3.4 Formation of C—O Bonds

R2 O

R1

n

R1

DCE, 85 °C, sealed tube (n = 3, 4)

OH

n−2

O 483

R1 = H, OH, F, Cl, Br, OMe, OBn R2 = aryl, Me, cyclohexyl

482

R1

DCE, r.t. (n = 3, 4)

PPTS, 85 °C, sealed tube

O O

AgTFA (2 mol%)

482 (R2 = H)

R2

AgTFA (2 mol%)

R1

n−2

484

R1 = H, F, OMe, OBn

n−2

O 485

Scheme 3.155 Synthesis of dihydronaphthofuran products from ortho-carbonylarylacetylenols.

With 1,3-dienes, 2-(1-alkynyl)arylaldehydes 486 undergoes a silver-catalyzed domino process to produce indanone-fused cyclohexene derivatives 487 (Scheme 3.156) [227]. In the proposed mechanism, 486 undergoes a silvercatalyzed 5-exo-dig cyclization to produce the oxonium ion 488, which is hydrolyzed into β-diketone 489 in the presence of adventitious water. The silver O

R1

R2

+ Diene

Dioxane,60 °C

487

Diene R2 O

R2 O O 487

486

Ag(I)

[4+2]

R1 491

R1

R1 = H, Me, OMe, F, Cl R2 = Me, Ph, OMe

O

486

R′

H

AgOTf (5 mol%)

O

R1

O Ag+

R2

+

Ag

O

Knoevenagel condensation

–H2O O

+

R1

R1

O

R2 O

O Ag

O + Ag

+Ag(I) +H+

490 +

H2O O

R1

R2

–H

O 489

R2

488

–Ag(I)

O

Scheme 3.156 Synthesis of indanone-fused cyclohexene derivatives by silver-catalyzed domino process.

163

164

3 Silver-Catalyzed Cyclizations

salt promotes the cyclization of 489 to 490, which subsequently undergoes Knoevenagel condensation to the indenone 491, which produced the final product via a [4+2] cycloaddition with diene. Silver-catalyzed cycloaddition of the electron-deficient enynone 492 produces the cationic intermediate 495, which can undergo a cycloaddition with 1,3diphenylisobenzofuran 493 to produce furan-containing polycyclic structures 494 in the presence of the phosphine ligand L (Scheme 3.157) [228]. Interestingly, the endo-product was favored, which contrasts with the exo-selectivity obtained with Au(I) catalysts. R1

Ph R2 +

O

AgOTf (5 mol%), L (5 mol%)

O

DCE, 30 °C

Ph

R3 492

O

R2

Ph

Ph

R1

O R endo-494 (major)

493 OMe PPh2

L=

Via:

R2 R1

+

O 495

Ph

+

R2

3

O

Ph

R1 O R3 exo-494 (minor)

R1 = H, Me, Ph R2 = nBu, Ph, 4-ClC6H4 R3 = alkyl, aryl

AgL R3

Scheme 3.157 Synthesis of polyheterocycles from 2-(1-alkynyl)-2-alken-1-ones 492 and 1,3-diphenylisobenzofuran.

Similarly, Yao and coworkers later reported the asymmetric annulation of 3-alkynylacrylaldehydes 496 and 2-hydroxystyrenes 497. The presence of AgOAc and a CPA (S)-TRIP triggered a cycloisomerization/oxa-[4+2] cycloaddition/SN 2 or SN 2′ substitution cascade to afford the polycyclic products 498 and 498′ with excellent enantioselectivities (Scheme 3.158) [229]. O H

+

OH

AgOAc (2.5 mol%), (S)-TRIP (3.75 mol%)

R1 O

DCE, r.t. 496

R1

R1

H + O

497

498

O

H H O 498′

R′ O O P O OH R′ (S)-TRIP (R′ = 2,4,6-(iPr)3C6H2)

Scheme 3.158 Asymmetric annulation of 3-alkynylacrylaldehydes 496 and 2-hydroxystyrenes.

3.4 Formation of C—O Bonds

Fan and coworker also demonstrated the synthesis of 4-substituted benzofurans 500 from 4-alkyl-2-ynylphenol 499 by an oxidative dearomatization/ cycloisomerization/Michael addition cascade (Scheme 3.159) [230]. It was proposed that the oxidative dearomatization of 4-alkyl-2-ynylphenol 499 by the iodobenzene diacetate in methanol to generate 4-alkyl-4-methoxy-2ynylcyclohexa-2,5-dienone intermediate 501. Silver-catalyzed cycloisomerization of the carbonyl oxygen and triple bond occurs to yield the oxonium ion 502, which undergoes an intermolecular nucleophilic attack by indole to form intermediate 503. Subsequent aromatization and protodemetalation afford the final product. R2 R2

OH

PhIOAc (1.1 equiv), AgOTf (10 mol%)

3 + R

R

N R4

1

MeOH, 0–25 °C alkyl, Ph R1 N R2 = H, alkyl, Ph, SiMe3 500 R4 R3 = H, F, Cl, Br, Me, OMe R4 = H, Me, Bn, alkenyl +

R2

O

Ag(I) R1 OCH3

O Ag

OCH3

R2

N R4

R3

H R1 OCH3 +

R3

488

O Ag

R1

Ag R1 OCH3 502

501

R2

R2

O

PhIOAc MeOH

+

R3

R1 =

499

499

O

–MeOH –Ag(I) N

500

4

503 R

Scheme 3.159 Silver-catalyzed oxidative dearomatization/cycloisomerization/Michael addition cascade.

Singh’s group later reported that the silver(I)-(R)-BINAP complex catalyzes an asymmetric aldol/cycloisomerization cascade reaction between ynones 34 and β-diketones, furnishing dihydrofuran derivatives 504, with an exocyclic double bond, in moderate to good yields (up to 95%) and good to excellent ee (up to 98% ee) (Scheme 3.160) [231]. The carboxyl group in amide derivatives can also participate in similar reactions: 5-exo-dig cyclization of propargylic amides 505 affords a series of 5-alkylidene oxazoline products 506 in the presence of bis(pyridyl)silver(I) complexes (Scheme 3.161) [232]. A direct correlation was established between the reaction rate and the electronic property of the pyridyl ligand:

165

166

3 Silver-Catalyzed Cyclizations

O

O 1

R

+

R2

R3 O

34

R4

AgOTf (10 mol%), (R)-BINAP (5 mol%)

R1 OH

4 Å MS,CH2Cl2, –60 °C

R2 R1 = alkyl, aryl R2 = CO2Me, CO2Et, CF3 R3, R4 = alkyl

O R3

O R4 504

PPh2 PPh2

(R)-BINAP

Scheme 3.160 Asymmetric aldol/cycloisomerization cascade reaction between ynones and β-diketones.

MeO R1 O

N

AgPF6 2 (1–15 mol%)

R4

HN R2

R4

O

CH2Cl2, r.t.

R3

R1 505

R1 = alkyl, alkenyl, Ph

N

R3 R2

506

R2, R3 = H, Me, 4-MeOC6H4 R4 = H, alkyl, Ph

Scheme 3.161 Ag-catalyzed cyclization of propargylic amides.

electron-rich pyridyl ligands had an accelerating effect on the reaction rate, with 4-methoxypyridine conferring the best catalytic efficiency. With internal alkyne substrates, a mixture of E- and Z-isomers was obtained. The silver-catalyzed heteroannulation of o-(1-alkynyl)benzamides 507 showed very high regio- and chemoselectivity, resulting in the exclusive formation of the 6-endo-dig 2-benzopyran derivatives 508 (Scheme 3.162) [233]. In contrast, the use of 1 equiv. of the strong base NaOt Bu results in the 5-exodig (Z)-3-aryl(alkyl)idene-isoindolone product 509, which can isomerize to the (E)-isomer under the strong basic conditions in certain cases. In comparison, the regioselectivity of the cycloisomerization reaction of o-alkynylbenzohydroxamic acids 510 is affected by the choice of silver salt and additive [234]: the use of silver(I) oxide allowed for the selective formation of the O-cyclized isobenzofuran-1-one oxime products 511, while the N-cyclized isoindolin-1-one products 512 was formed in the presence of a silver imidazolate polymer and triphenylphosphine. The silver-catalyzed cycloisomerization reaction of propargylic Meldrum’s acid 513 afforded the 5-exo-dig products, γ-alkylidene butyrolactones 514 in good yields (Scheme 3.163) [235]. For internal alkyne substrates (R = n Bu or Ph),

3.4 Formation of C—O Bonds

O

N N H

Ph

O

Ph

AgOTf (5 mol%)

N

O

DCE, r.t.

Ph R

R 507

R

508

509 (not formed) 1 N OR

Ag2O (5 mol%)

N H

R3

R3

EtOH, r.t.

O

O

OR1

R2

511 R2

O

[Ag(Im)n] (5 mol%), PPh3 (2.0 equiv.)

510

R3

EtOH, 70 °C

R1 = H, NO2

R2 = Ph, CH2OMe, nBu, CH2OH, CH(CH3)OH

N OR1

512

R2

R3 = Me, Bn, Piv

Scheme 3.162 Silver-catalyzed cyclization of o-(1-alkynyl)benzamide derivatives.

O O Ph

O

O O Me 513

Ag2CO3 (10 mol%) Solvent, r.t. R

R = H, nBu, Ph

O

O •

O Solvent R′ O O –Acetone Ph Ph R Ph Me R Me R Me Ag 514 Ag

O

Solvent Benzene:H2O (10 : 1) THF:H2O (10 : 1) Benzene:MeOH (10 : 1) THF:MeOH (4 : 1)

R′ CO2H CO2H CO2Me CO2Me

Scheme 3.163 Cyclization of propargylic derivatives of Meldrum’s acid.

mixtures of E- and Z-isomers were formed. The products contain a carboxylic acid or ester group at R′ , depending on whether water or methanol is used as the cosolvent for the reaction. At an elevated temperature (80 ∘ C), decarboxylation occurs to afford γ-alkylidene butyrolactones (R′ = H). A convenient route for the synthesis of α-naphthylamines 516 is the silver-catalyzed cycloisomerization of (o-alkynyl)phenyl enaminones 515 (Scheme 3.164) [236]. The reaction can be carried out in air, and the α-naphthylamine products can be obtained in up to 89% yields in 2 hours.

167

168

3 Silver-Catalyzed Cyclizations

HN

O R3

R1

HN

AgNO3 (10 mol%), R1NH2 (2.0 equiv.)

R1

R3

DMF, 80 °C, air R2 515

R1, R2 = aryl

R2

O 516

R3 = H, OMe, F, CF3

Scheme 3.164 Formation of naphthylamines by the cycloisomerization of (o-alkynyl)phenyl enaminones 515.

3.4.3.2

Allenes as Partners

Marshall and coworkers first demonstrated that the allenals and allenones 517 converted into furans 518 upon treatment with AgNO3 or AgBF4 in acetonitrile or acetone (Scheme 3.165) [237, 238]. In the proposed mechanism, the carbonyl group attacks the activated allene in a 5-endo-trig fashion, forming the cationic vinyl silver intermediate 519, which loses a proton to give 520. Protonolysis with loss of Ag(I) finally produces the furan derivatives. Conversely, the cycloisomerization reaction of amino acid-derived allenes 521 was reported by Brummond and coworker to proceed with 6-exo-trig selectivity in the presence of AgBF4 or AgNO3 to afford isomeric oxazines 522 and 523 (Scheme 3.166) [239]. The cycloisomerization of substituted propargyl acetates/pivaloates 524 and phosphatyloxy alkynyl ketones 526 to tetrasubstituted furans 525 and H

R2

•

R1

R3

R2

AgNO3 or AgBF4 (20 mol%)

O 517

MeCN or acetone, reflux

R3

R1, R2, R3 = H, alkyl

518

Ag(I)

H

R1

O

–Ag(I)

Ag+

R2

R2

Ag

R2

Ag

• R1

R3 O

H R3

O

R1

–H+

R3

519

R1

O 520

Scheme 3.165 Cyclization of allenals and allenones to furans.

R MeO2C

• NH

Ph O 521

AgNO3 (20 mol%), acetone, 70 °C; or AgBF4 (20 mol%), DCE, 65 °C R = Me, iBu

R

R MeO2C N

O

+

MeO2C

Ph 522

N

Ph 523

522/523 = 3 : 1–5 : 1

Scheme 3.166 Cyclization of amino acid-derived allenes to oxazines.

O

3.4 Formation of C—O Bonds

OR′ R2 R1 O

t

Bu

CH2Cl2, r.t.

tBu

OEt AgBF4 O P OEt (5 mol%) O Ph CH2Cl2, r.t. Ph 526 O

t

Bu

R′ = Ac, Piv R1, R2 = Ph, Me

524

OEt P O O •

R2

R′O

AgBF4 (5 mol%)

EtO

R1

O 525

AgBF4 (5 mol%)

Ph

O EtO

DCE, 60 °C

tBu

Ph

P O OEt t Bu

O 527

O

Ph Ph

Scheme 3.167 Cycloisomerization of substituted propargyl acetates/pivaloates and phosphatyloxy alkynyl ketones. O* t

Bu

O Ph Ph O 524′

O

AgBF4

O*

1,2-Migration

t

Ph

Bu

Cycloisomerization

O O* tBu

Ph Ag O

1,2-Migration

O 525′

Ph Ph

Cycloisomerization O O* t

•

Ph Ph

Bu O 528

Scheme 3.168 Possible mechanisms of cyclization of substituted propargyl acetates.

527, respectively, was described by Gevorgyan and coworkers to occur in the presence of AgBF4 in good to excellent yields (Scheme 3.167) [240]. By employing the 17 O-labeled substrate 524′ , it was shown that the reaction follows either a Rautenstrauch-type 1,2-migration of the acyloxy group followed by the cycloisomerization to the furan 525′ directly or, alternatively, two 1,2-migrations of the acyloxy group to form the postulated allenyl intermediate 528, which cycloisomerizes into the furan (Scheme 3.168) [241]. Under basic conditions, the alkyne moiety of the propargylamide 529 can be transformed to the allenylamide 530, which can cyclize in the presence of a silver catalyst, with elimination of both the sulfonyl and the acyloxy groups, to produce the 5-vinyloxazoles 531 (Scheme 3.169) [242]. 3.4.4

Miscellaneous Reactions

A triple cascade process was developed by Davies and coworkers for the rapid synthesis of polycyclic benzo-fused dihydrofurans 535 from α-aryldiazoketones 532 and alkenes (Scheme 3.170) [243]. The reaction

169

170

3 Silver-Catalyzed Cyclizations

Ph

O

O

O Ph 529

N Ts

Ph

Et3N

O

AgBF4 (10 mol%)

O •

Ph THF, r.t.

O

Ph

N 530 Ts

Ph

O Ph

Toluene, 80 °C

N

Ph

531

O Ph

Ph N PhCO2 Ts

Scheme 3.169 Formation of 5-vinyloxazoles by tandem cyclization/elimination reactions.

R

N2 R1

R3 (5.0 equiv.), Rh2(TFA)4 (2 mol%)

2

R3

R2

CH2Cl2, reflux

O

R1

532 O AgOTf (20 mol%)

O

533

Ag+

R2 O

R3

R

Toluene, 85 °C

2

R3

534

R1 Au (PPh3)AuCl (10 mol%)

R1

R2

R2

O

O

R

R3

R1

3

R1 535

Scheme 3.170 Synthesis of polycyclic benzo-fused dihydrofurans from α-aryldiazoketones and alkenes.

initiates with a rhodium-catalyzed cyclopropanation of 532 with alkenes to form 533, followed by a silver-catalyzed ring expansion to dihydrofurans 534. Finally, a gold-catalyzed cyclization forms the benzo-fused dihydrofurans 535. The intramolecular cyclization of phenoxyethynyl diols 536 proceeded in the presence of AgOTf catalyst to afford the multi-substituted α,β-unsaturated γ-lactones 537 (Scheme 3.171) [244]. The electron-rich phenoxyethynyl group of 536 readily coordinates to Ag(I) to form the electrophilic oxonium intermediate 538, which is susceptible to the intramolecular nucleophilic attack by the tertiary alcohol group. The loss of a molecule of water, generates the transient oxonium

3.4 Formation of C—O Bonds

R3

R3 OH AgOTf (0.5 mol%) n

R1 R2

OH

R1

n = 0,1

536

R1,

R 2,

R3

n

R1 R2

O H2O

O

Ag R1 R2

Ph

538

O

OPh

R3

Ag OPh

H+

n

•

R2 O H R3

R3 OH

n

R1

R2 537

Ag

Ag(I)

O

= alkyl

R3 OH 536

O

n

Toluene, r.t.

OPh

n

R1 R2

O

Ag OPh OH2

–PhOH –Ag(I)

537

539

Scheme 3.171 Intramolecular cyclization of phenoxyethynyl diols to multi-substituted α,β-unsaturated γ-lactones.

cation 539, which reacts with water to release a molecule of phenol, yielding the corresponding lactone product 537. Bi’s research group reported a silver-catalyzed heteroaromatization reaction of propargylic alcohols 540 with p-toluenesulfonylmethyl isocyanide (TosMIC) to furnish sulfonyl benzoheteroles 541 in moderate to excellent yields via a deoxysulfonylation/hydration/condensation reaction cascade (Scheme 3.172) [245]. Mechanistic studies revealed that deoxysulfonylation of propargylic alcohol 540 occurs in the presence of TosMIC to yield the intermediate 542 in the first step of the reaction. Subsequently, the regioselective hydration of 542 occurs to afford enol 543, which undergoes keto–enol tautomerism to give the α-tosyl ketone intermediate 544. A sequential addition/elimination cascade (i.e. condensation reaction) produces the benzofuran 541. AgSbF6 is an efficient catalyst for the cycloisomerization reactions of allenes 545 bearing cyclic acetal and thioacetal subunits to furnish trans-diastereomers of indeno-fused heterocyclic systems 546 (Scheme 3.173) [246]. The new indene ring system was constructed by the formation of a new bond between the acetalic carbon atom and the central allenic carbon atom, with the simultaneous migration of one of the alkoxy or alkylthio groups from its original position toward the external C1 of the propadiene fragment. Remarkably, only the alkoxy fragment migrates in substrates with thioacetal groups (X, Y = S, O). Cyclopropyl carbinol rearrangement of 2-[cyclopropyl(hydroxy)methyl] phenols 547 to the 2H-chromenes 548 and benzo[b]oxepines 549 occurs in the presence of AgOTf (Scheme 3.174) [247]. The selectivity of the reaction can be controlled by adjusting the reaction time.

171

172

3 Silver-Catalyzed Cyclizations

Ts

–

C N

(1.5 equiv.)

Ag3PO4 (10 mol%),

OH

Ts

H2O (2.0 equiv.) R1

R1

1,4-Dioxane, 100 °C

R2

XH 540

X

R1 = OMe, Cl, Br, tBu, NO2

R2

541

R2 = aryl, thienyl, naphthyl X = O, S, NTs Ts

–

Ag(I), C

Ts

Ts

N

Ag(I), H2O

540

R1 XH

OH R1

R2

XH 543

542 Ts

Ts R2

R1

R2

OH

R1

–H2O

X

O

XH 544

541

R2

Scheme 3.172 Heteroaromatization reaction of propargylic alcohols with p-toluenesulfonylmethyl isocyanide. n

X R1

AgSbF6 (10 mol%)

Y •

R2

H 545

R

1

Y

CH2Cl2, 25 °C

R2 546

X,Y = O, O; S, O n = 1, 2 R1 = H, OMe; R2 = Me, tBu, Ph

–Ag(I)

Ag(I)

n

X R1

Y • H

n

H X

X R1 2

R Ag+

n

Y R2 Ag

Scheme 3.173 Cycloisomerization reactions of allenes bearing cyclic acetal and thioacetal.

Samzadeh-Kermani demonstrated that 1,4-oxathian-3-imine derivatives 550 may be synthesized from terminal alkynes, isothiocyanates, and epoxides (Scheme 3.175) [248]. The reaction was proposed to proceed via a silver acetylide species generated in situ, which undergoes sequential reactions with the electrophiles.

References

R3 OH

AgOTf (10 mol%)

R1

Toluene, air, reflux, >1 h

R2

R4 OH 547

AgOTf (10 mol%) Toluene, air, reflux, 1–24 h

R3

R3 R1

1

R

R2

R4

O

R2

O

548

R4

549

Scheme 3.174 Cyclopropyl carbinol rearrangement.

R1

+

R2NCS

+

R5

Ag2CO3 (10 mol%)

O

R3

R4

3 Å MS, dioxane, 55 °C

R3 R5 R4

R1 O S

NR2

550

Scheme 3.175 Synthesis of 1,4-oxathian-3-imine derivatives from alkynes, isothiocyanates, and epoxides.

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183

4 Silver-Mediated Radical Reactions Lin Zhu and Chaozhong Li Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, PR China

4.1 Introduction The discipline of organic free radical chemistry dates back over 110 years since the discovery of triphenylmethyl radical by Moses Gomberg in 1900. Organic radical reactions became a thriving field in synthetic organic chemistry for a decade or so starting from the mid-1980s. Nevertheless, the significance of radicals in organic synthesis somehow remained hidden for a long period of time [1, 2]. However, the past few years have witnessed the renaissance of organic radical chemistry [3, 4]. It has now become an exciting area of research in organic chemistry, and new discoveries can be seen every day in various aspects of radical chemistry such as photoredox catalysis and transition metal-catalyzed radical reactions. In particular, the area of catalysis of radical reactions has flourished [5]. The combination of the versatility of transition metal catalysis with the unique reactivity of organic free radicals has infused new life and energy into radical chemistry and thus spurred a vigorous research in this area in the past few years. Silver-catalyzed radical reactions are no exception. Silver salts and complexes were often used as Lewis acids or halide ion scavengers in organic reactions. However, significant progresses have been achieved in the field of silver-mediated or silver-catalyzed radical reactions in the past decade. Ag(I) ion is a mild single-electron oxidant with E∘ (Ag+ /Ag0 ) = 0.80 V. It catalyzes a number of organic compounds such as thiols and carbanions to form the corresponding radicals under mild oxidative conditions. On the other hand, Ag(II) ion is a strong oxidant with E∘ (Ag2+ /Ag+ ) = 1.98 V. Moreover, the redox potentials of Ag(II) complexes can be tuned by the ligands coordinated to Ag(II). For example, the oxidation potential of Ag(Phen)2 + is about 1.39 V [6]. These unique properties make possible a wide range of radical reactions that are otherwise difficult to take place. In addition, Ag(II)-mediated radical reactions are generally easy to operate by using the combination of a readily available Ag(I) salt as the catalyst and an oxidant (e.g. K2 S2 O8 ) in stoichiometric or excess amount. In this context, silver-catalyzed decarboxylative functionalization of carboxylic acids [7] and deboronative functionalization of organoboronates have been Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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demonstrated to be an indispensible tool in organic synthesis. Silver-catalyzed 1,2-difunctionalization of olefins enables a variety of functional groups to be incorporated into organic molecules via radical addition. Silver-catalyzed radical fluorination has emerged as a powerful tool in C(sp3 )—F bond formations [8]. Silver catalysis has also shown its great potential in C—H/C—C bond functionalization reactions [9], radical cascade reactions, radical translocation reactions, etc. A nice comprehensive review on silver-mediated radical reactions was disclosed very recently by Bi and coworkers and classified according to the type of radicals generated [10]. This chapter focuses on the progress made in silvermediated radical reactions in the past decade, in which silver triggers the generation of radicals and/or promotes the radical processes. Those radical reactions in which silver salts (e.g. Ag2 CO3 ) simply act as a base or halide scavenger (to form AgX precipitate) are not included. The reactions in which silver serves as an oxidant only to quench radical species are also excluded. This review aims to provide a concise and critical rather than comprehensive insight into the roles of silver in radical transformations. It is organized based on the type of reactions, including protodecarboxylation, radical coupling, addition, cascade cyclization, and rearrangement.

4.2 Protodecarboxylation Carboxylate groups as traceless directing groups have drawn much attention in the past decade because of the abundance, easy preparation, and chemical versatility of carboxylates. However, traditional protodecarboxylation often requires harsh conditions such as the use of stoichiometric metal salts and high temperature. Therefore, more effective and economical protodecarboxylation protocols are highly desirable. In 2009, Larrosa and coworkers reported the silver-catalyzed protodecarboxylation of ortho-substituted benzoic acids (Scheme 4.1(1)) [11]. Various ortho-substituted benzoic acids were treated with catalytic Ag2 CO3 in DMSO at R1

R1 CO2H

R2

AgCO3 (cat.)

H R2

DMSO,120 °C

14 examples 71~100%

(a)

24 examples upto 95%

(b)

R1 = EWG, EDG; R2 = EWG, EDG, H R1 CO2H R2

AgOAc (cat.) K2CO3 (cat.) NMP, 120 °C

R1 H R2

R1 = EWG, EDG; R2 = EWG, EDG, H

Scheme 4.1 Silver(I)-catalyzed protodecarboxylation of benzoic acids.

4.2 Protodecarboxylation

R1 CO2H

AgX

2

R

R1

HX

R1

CO2Ag R2

CO2

H R2

R1

R1 Ag

R2

CO2H R2

Figure 4.1 Proposed mechanism of protodecarboxylation of benzoic acids.

120 ∘ C to afford the corresponding arenes in excellent yields. The relative basic counterion of Ag(I) proved crucial to achieve high efficiency, while the reaction failed to proceed when Pd or Cu salts were used as the catalyst. The presence of electron-withdrawing or electron-donating substituents ortho to the carboxylic acid was required for the reaction to proceed, and the reason remains unclear. The authors proposed the mechanism as follows. The silver carboxylate, whose formation is promoted by the basic counterion, undergoes decarboxylation to afford the silver arene intermediate. Protodemetalation of the silver arene with another carboxylic acid gives the final product and regenerates silver carboxylate (Figure 4.1). Almost at the same time, Gooßen et al. reported the same reaction under slightly altered conditions (Scheme 4.1(2)) [12]. The Gooßen group further conducted the comparative study on the protodecarboxylation, which showed that silver salts of ortho-substituted benzoates decarboxylate much more rapidly than the corresponding phenanthroline–copper(I) complexes [13]. While the silver-catalyzed protodecarboxylation took place at about 120 ∘ C, the phenanthroline–copper(I) system required a higher temperature of 170 ∘ C. Larrosa and coworkers carried out a combined experimental and computational investigation on the silver-catalyzed decarboxylation of benzoic acids, which revealed that the ortho-substituents lead to a much lower activation energy barrier for decarboxylation compared with their meta- and para-counterparts due to a combination of steric and electronic effects [14]. Larrosa and coworkers extended their protocol to the protodecarboxylation of a variety of heteroaromatic carboxylic acids catalyzed by Ag2 CO3 and AcOH in DMSO at 120 ∘ C [15]. Heteroaromatic acids with the carboxylate α to the heteroatom or having ortho-electron-withdrawing groups underwent efficient protodecarboxylation to produce the corresponding heteroarenes in excellent yields. The remarkable activating effect of ortho-substituents or α-heteroatoms allowed the regioselective monoprotodecarboxylation of aromatic and heteroaromatic dicarboxylic acids (Scheme 4.2(1)). In a similar fashion, Jafarpour et al. reported the silver-catalyzed protodecarboxylation of coumarin-3-carboxylic acids (Scheme 4.2(2)) [16]. Furthermore, with the use of D2 O as the cosolvent, the above protodecarboxylation reactions depicted in Schemes 4.1 and 4.2(1) were later extended to the deutero-decarboxylation of (hetero)aromatic acids by the groups of Gooßen and coworkers [17] and Larrosa and coworkers [18].

185

186

4 Silver-Mediated Radical Reactions

Ag2CO3 (10 mol%) AcOH (5 mol%)

CO2H X

CO2H

CO2H H

X

DMSO, 120 °C

18 examples 85–100%

(1)

7 examples 47–90%

(2)

X = O, N, S CO2H

Ag2CO3 (10 mol%)

O

H

AcOH (5 mol%)

R

R O

DMA, 100 °C, 16 h

O

O

Scheme 4.2 Ag(I)-catalyzed protodecarboxylation of heteroaromatic acids.

In 2012, Greaney and coworkers reported the protodecarboxylation of ordinary benzoic acids under oxidative radical conditions (Scheme 4.3) [19]. With AgOAc as the catalyst and K2 S2 O8 as the oxidant, a number of benzoic acids underwent protodecarboxylation in CH3 CN at 100 ∘ C to give the corresponding arenes smoothly. This protocol was applicable to all ortho-, meta-, or para-substituted benzoic acids. Benzoic acids with electron-withdrawing substituents were generally more effective substrates for protodecarboxylation than electron-rich benzoic acids (e.g. p-methoxybenzoic acid). The proposed mechanism involves the oxidation of carboxylate by the in situ formed Ag(II) to generate the carboxyl radical, which undergoes decarboxylation to give the corresponding aryl radical. The aryl radical then abstracts a hydrogen atom from the solvent (CH3 CN) to produce the final product. AgOAc (cat.) K2S2O8

CO2H R

H R

CH3CN, 100 °C

20 examples 34–84%

R = EWG, EDG, H K2S2O8 CO2–

R

Ag2+

Ag+

CO2

H CH3CN

R

CO2

R

R

Scheme 4.3 Silver(II)-catalyzed protodecarboxylation.

In another case, Jaenicke and coworkers reported the protodecarboxylation of carboxylic acids catalyzed by heterogeneous silver. Silver supported on alumina with 10 wt% Ag/Al2 O3 and about 40 nm size turned to be the most effective and exhibited much higher catalytic activity than AgOAc [20]. O’Hair and coworkers explored the gas-phase silver-mediated decarboxylation reactions with fixed-charge phosphine ligands in order to obtain detailed mechanistic information for reactive intermediates, and they found that the use of a phosphine ligand favors decarboxylation by dramatically reducing the availability of the fragmentation pathway for carboxylate anion loss [21].

4.3 Radical Coupling

4.3 Radical Coupling Cross-coupling reactions allow the assembly of two molecules in site-specific manner via carbon–carbon or carbon–heteroatom bond formation and have proven to be extremely useful in organic synthesis. While this area used to be dominated by transition metal-catalyzed non-radical processes, radical-based cross-coupling strategy has begun to invigorate this field, especially in the coupling reactions involving sp3 carbon centers. As expected, silver plays a crucial role in a large number of radical coupling reactions. Furthermore, unlike traditional cross-coupling reactions requiring strict anhydrous and oxygen-free conditions, many silver-mediated radical-based coupling reactions take place in aqueous solution in open flasks, thus rendering them more practical and sustainable. 4.3.1

Formation of C—C Bonds

The selective functionalization of (hetero)aromatic compounds is of paramount importance to the pharmaceutical and agrochemical industry. Silver salts have thus been demonstrated in recent years to play a key role in this type of transformations. Ag(I) salts, in combination with an oxidant (e.g. Na2 S2 O8 ) in many cases, effectively catalyze the generation of carbon-centered radicals from a wide range of substrates such as carboxylic acids, organoboronates, alkanesulfinic acids, and even hydrocarbons. The carbon-centered radicals then participate in subsequent radical reactions such as Minisci alkylation, acylation, and arylation, thus offering a unique strategy for C—C coupling. Significant advances have been achieved in Minisci alkylation and related reactions in recent years. In 2001, Hansen et al. reported the silver-catalyzed decarboxylative alkylation of N-alkyl 1,2,4-triazoles, leading to the synthesis of 5-alkylated triazoles in good regioselectivity (Scheme 4.4(1)) [22]. Secondary alkyl carboxylic acids gave the best performance in this protocol. An intramolecular version employing primary alkyl carboxylic acids was also developed. Two years after Hansen’s report, Cowden used N-protected amino acids as the source of 1-amidoalkyl radicals in the silver-catalyzed Minisci alkylation reaction of R1 N N

N

AgNO3 (10 mol%) + R2 – CO2H

(NH4)2S2O8 (1.5 equiv.) TFA/H2O, 70 °C

N

R1 N N

R1 = Me, Et; R2 = 2°, 3° alkyl Cl R2

R1 N

N N

CO2H + 3

R

(1)

R2 Cl

AgNO3 (10 mol%) (NH4)2S2O8 (1.8 equiv.) TFA (20 mol%), H2O

8 examples up to 60%

R1 R2

Cl

Scheme 4.4 Alkylation of 1,2,4-triazoles and pyridazines.

N N

N R3

Cl

14 examples (2) up to 88%

187

188

4 Silver-Mediated Radical Reactions

3,6-dichloropyridazines and obtained the 4-alkylated products in good yields (Scheme 4.4(2)) [23]. Minisci et al. treated quinolines with a combination of AgNO3 /(NH4 )2 S2 O8 / TFA in aqueous ethylene glycol, leading to an expedient synthesis of hydroxymethylated quinolines in satisfactory yields (Scheme 4.5(1)) [24]. The employment of ethylene glycol instead of MeOH as the hydroxymethyl radical precursor suppressed the further oxidation of the obtained products into aldehydes. Pratt and coworkers applied this method into the concise synthesis of analogs of biologically active α-tocopherol [25]. In another case, Miller and coworkers carried out the tridirectional Minisci reaction between cis-1,3,5-cyclohexanetricarboxylic acid and 4-cyanopyridine in a single step (Scheme 4.5(2)) [26]. The obtained product was shown to serve as a tripodal carbohydrate receptor. AgNO3 (10 mol%) (NH4)2S2O8 (4.0 equiv.) N

TFA (1.0 equiv.) H2O/ethylene glycol, reflux

(1)

OH

N 92% CN

CO2H

HO2C

4-Cyanopyridine AgNO3, (NH4)2S2O8

N N

CN (2)

10% H2SO4, 70–80 °C CO2H N

24%

NC

Scheme 4.5 Alkylation of quinolines and 4-cyanopyridine.

Regioselective C6-alkylation of purine nucleosides could also be achieved by silver-catalyzed Minisci reaction (Scheme 4.6(1)) [27]. Primary, secondary, and tertiary alkyl acids were all suitable partners in the C(sp2 )—C(sp3 ) coupling reaction. In a similar fashion, C4-alkylated pyrimidines could be conveniently synthesized via silver-catalyzed decarboxylative alkylation of pyrimidines in aqueous media (Scheme 4.6(2)) [28]. This method is also applicable to electron-deficient pyrimidines, albeit in a lower efficiency [29]. In 2014, Zhao et al. developed the direct C2-alkylation of benzothiazoles, thiazoles, and benzoxazoles with aliphatic carboxylic acids via silver-catalyzed decarboxylation (Scheme 4.7) [30]. The reaction proceeded at room temperature and was easily operational. A variety of secondary or tertiary alkyl carboxylic acids took part in the transformation in highly efficient and regioselective manner. Silver-mediated radical addition to quinones provides a convenient method for C—C bond formations and is extremely useful in organic synthesis. For example, various aminoalkylated naphthoquinones were readily prepared from

4.3 Radical Coupling

H N N

N

N

CH2Cl2/H2O, rt

N

+ R – CO2H R1

N

R

AgNO3 (5 mol%) K2S2O8 (2.0 equiv.)

N

(1) R1

N

R2

R2 R = 1°, 2°, 3° alkyl;

R1 =

H, F, Cl

R2 = ribosyl, deoxyribosyl, arabinosyl, benzyl

N

R1 N

R2

+ R – CO2H

21 examples 67–99% R

AgNO3 (20 mol%) K2S2O8 (1.0 equiv.)

N

R1 CH2Cl2/H2O, rt

R2 = H, Cl, Br, CN, OMe R3 = acyl or alkyl

N

(2) R2

24 examples 35–79%

Scheme 4.6 Alkylation of purine nucleosides and pyrimidines.

R1

N

+

AgNO3 (20 mol%) K2S2O8 (4.0 equiv.) R – CO2H

R

CH2Cl2/H2O, rt, 8 h

X X = O, S

N R1

R = 2°, 3° alkyl

X 30 examples 56–96%

Scheme 4.7 Alkylation of benzothiazoles, thiazoles, and benzoxazoles.

the decarboxylative alkylation of naphthoquinones with N-protected α-, β-, or γ-amino acids, as reported by Dessolin and coworkers (Scheme 4.8(1)) [31]. In an effort toward the total synthesis of natural product marmycin A, Zhang and coworkers developed the expedient synthesis of the key intermediate angucyclinone with the silver-catalyzed decarboxylative radical addition to bromoquinone as the key step (Scheme 4.8(2)) [32]. The same method was also applied into the facile construction of 3-hydroxyphenanthrene-1,4-diones as key intermediates to tanshinone I and its analogs [33]. The silver-mediated decarboxylative radical cyclization to quinone was employed by Kraus et al. as the key step in the expedient synthesis of bauhinoxepin J (Scheme 4.9(1)) [34]. The reaction of 11-hydroxyundecanoic acid with coenzyme Q0 (2,3-dimethyl-5methyl-1,4-benzoquinone) under silver catalysis provided the 6-alkylated product idebenone in one step (Scheme 4.9(2)) [35, 36]. In another case, the AgNO3 /K2 S2 O8 -mediated reaction of 2-methoxybenzoquinone with hexanoic acid in aqueous acetonitrile afforded the mixture of C6- and C5-pentyl-substituted products [37]. Organoborane compounds are among the most commonly employed intermediates in organic synthesis. In this regard, Baran and coworkers developed a general method for the alkylation of quinones with alkylboronic acids (Scheme 4.10) [38]. The reaction proceeded at room temperature under mild conditions, even without organic solvent when desired, thus providing a scalable, highly chemoselective, and practical access to diverse alkylquinones. The method

189

190

4 Silver-Mediated Radical Reactions

O R1

2 + R

O

AgNO3 (cat.) K2S2O8

NHPG

R1 (1)

n

H

n

CO2H

O R1 = Me, H

R2

O

R2 = H, CH3, Bn PG = Boc, Ac, TFA, Troc n = 0, 1, 2

NHPG

56 examples up to 73%

O

O Ar

AgNO3, (NH4)2S2O8

CO2H

H2O/CH3CN, 80 °C Ar = 3-Me-C6H4

Br

Br

+ O

(2)

O

Ar O

O

65%

O

O

Angucylinone

O

Scheme 4.8 Alkylation of naphthoquinones. O

O

O

AgNO3, (NH4)2S2O8

O

(1)

OH

(2)

O

O

HO2C

OMe

H2O/CH3CN, 70 °C, 6 h

OMe

40% O

AgNO3 (30 mol%)

O

MeO +

9

MeO

OH OH

O

K2S2O8 (2 equiv.) CH3CN/H2O, 70 °C

O MeO MeO

10

O Idebenone, 65%

Scheme 4.9 Alkylation of benzoquinones with carboxylic acids. O + R2B(OH)2

R1 O

O

AgNO3 (20–40 mol%) K2S2O8 (3.0–6.0 equiv.) CH2Cl2/H2O or PhCF3/H2O, rt

R1 R2 O

R2 = 1°, 2° alkyl or aryl

Scheme 4.10 Alkylation of benzoquinones with organoboronic acids.

50 examples up to 98%

4.3 Radical Coupling

could be extended to the arylation of quinones with arylboronic acids. Kinetic, spectroscopic, and computational studies were carried out to gain further understanding on these multiphase reactions, which showed that phase-transfer processes played an important role in these radical C—H arylation reactions [39]. Trifluoromethyl group is an important structural motif in pharmaceuticals and agrochemicals. The introduction of trifluoromethyl groups into organic molecules has received a considerable attention in recent years. The addition of trifluoromethyl radical onto (hetero)arenes, the Minisci trifluoromethylation, provides a facile access to trifluoromethylated compounds, and a number of novel methods have been developed in this area. For example, Sanford and coworkers reported the trifluoromethylation of (hetero)arenes using the combination of TMSCF3 , AgOTf, and KF (Scheme 4.11(1)) [40]. The trifluoromethylated products were obtained in good yields under mild conditions. Electron-rich arenes and heteroaromatics such as N-methyl pyrrole, thiophene, and caffeine were all suitable substrates in the reaction. The intermediacy of AgCF3 was proposed, and the involvement of caged and/or Ag-assisted trifluoromethyl radical rather than a pure CF3 radical was suggested by the authors. The protocol was later extended by Hao and coworkers to the ethoxycarbonyldifluoromethylation of arenes with TMSCF2 COOEt [41]. Greaney and coworkers then developed a catalytic version for the trifluoromethylation of electron-rich aromatic and heteroaromatic compounds at room temperature by using AgF as the catalyst, TMSCF3 as the CF3 source, and DIB (di(acetoxy)iodosobenzene) as the oxidant (Scheme 4.11(2)) [42]. Control experiments indicated that AgF or DIB alone was not sufficient in oxidizing TMSCF3 to •CF3 , whereas the combination of AgF and DIB proved to be highly effective. Shortly after Sanford’s report, Bräse and coworker described the ortho-trifluoromethylation of functionalized aromatic triazenes with AgF/TMSCF3 (Scheme 4.11(3)) [43]. For para-substituted triazenes, an excellent ortho-selectivity was observed. This protocol also tolerated AgOTf (4.0 equiv.) KF (4.0 equiv.)

H + TMSCF3

R

CF3 R

DCE, 50 °C

15 examples 42–88%

(1)

R = H, Me, OMe, I AgF (25 mol%) TMSCF3 (2.0 equiv.) CF3

PhI(OAc)2 (2.0 equiv.)

H

R

R DMSO, rt, 20 h iPr iPr

R

N N N

AgF (4.0 equiv.) TMSCF3 (4.0 equiv.)

i

Pr

i

Pr

28 examples 40–94%

(2)

F3C N N

R N

C6F12, 100 °C

Scheme 4.11 Trifluoromethylation of arenes with TMSCF3 .

11 examples (3) 39–74%

191

192

4 Silver-Mediated Radical Reactions

a wide range of functional groups. The Bräse group successfully extended the protocol to perfluoroalkylation and ethoxycarbonyldifluoromethylation of aromatic triazenes [44, 45]. Notably, the reaction was completely suppressed in Et3 N, indicating that the interaction between AgRF and the triazene moiety may play a key role in the reaction. In other cases, Hajra and coworkers reported the oxidative trifluoromethylation of imidazopyridines with CF3 SO2 Na as the CF3 source (Scheme 4.12(1)) [46]. The reaction was carried out in the presence of catalytic AgNO3 /TBHP in ambient air, leading to the regioselective synthesis of 3-(trifluoromethyl)imidazo[1,2-a]pyridine derivatives in satisfactory yields. Moreover, this protocol could be extended to other imidazoheterocycles as well. Zhang and coworkers also developed a silver-mediated oxidative C—H trifluoromethylation of arenes using cheap and commercially available trifluoroacetic acid as the •CF3 source, leading to an economical and efficient synthesis of various trifluoromethylated arenes (Scheme 4.12(2)) [47]. A variety of functional groups were tolerated well. Regioselectivity varied depending on the structure of the substrates, while products bearing ortho-CF3 to the cyano group were obtained preferentially in most cases. CF3SO2Na (2.0 equiv.) N N

R

Ar

N

AgNO3 (20 mol%) TBHP (20 mol%) DMSO, air, rt

Ag2CO3 (40 mol%) K2S2O8 (2.0 equiv.)

+ CF3CO2H

Ar 20 examples 63–78%

N

(1)

CF3

CF3 R

(2)

Na2CO3, H2SO4 CH3CN or CH2Cl2, 120 °C R = CN, CO2Et, I, Br, CF3, alkyl

21 examples up to 88%

Scheme 4.12 Trifluoromethylation of (hetero)arenes with CF3 SO2 Na or CF3 CO2 H.

Acyl radicals can also be effectively generated by silver-catalyzed decarboxylation of α-keto acids, which then participate in Minisci acylation reactions to provide C(sp2 )—C(sp2 ) coupling products. For example, the intramolecular decarboxylative Minisci acylation allowed the short synthesis of the 8-azaergoline ring system (Scheme 4.13(1)) [48]. Kraus and Melekhov reported the synthesis of acylhydroquinones from the reaction of quinones with monoamides of oxalic acid and applied this strategy in the synthesis of a tricyclic pyrrolobenzodiazepine skeleton (Scheme 4.13(2)) [49]. With Ag2 CO3 as the catalyst and K2 S2 O8 as the oxidant, the decarboxylative acylation of pyridine-N-oxides with α-oxocarboxylic acids proceeded smoothly in CH2 Cl2 /H2 O at 60 ∘ C, leading to the synthesis of various 2-acylated pyridine-N-oxides that are difficult to access by conventional

4.3 Radical Coupling

EtO2C

O

EtO2C

AgNO3 (cat.) (NH4)2S2O8

N CO2H

N O (1)

CH2Cl2/HOAc/TFA/H2O N H

N O

AgNO3 (cat.) (NH4)2S2O8

CO2Me CO2H

N H

46%

Benzoquinone CH3CN/H2O, 70 °C

O

O

O

CO2Me HN

N

N (2) O

O 62%

OH

Scheme 4.13 Synthesis of 8-azaergoline and pyrrolobenzodiazepine skeletons.

methods (Scheme 4.14(1)) [50]. The combination of Ag(I) and K2 S2 O8 also enabled the implementation of decarboxylative diacylation of coumarins with α-oxocarboxylic acids, leading to the synthesis of functionalized 3,4-diacylcoumarins under mild conditions (Scheme 4.14(2)) [51]. A mechanism involving double acyl radical addition was proposed. R1 O + O–

CO2H

R

+

N

Me, Cl, CN, OMe, H

N

R

+ O

O

Ar

Ar

K2S2O8 (3.0 equiv.) CO2H

(1)

R O– 20 examples, 43–81%

Ag2CO3 (10 mol%) O

O

+

CH2Cl2/H2O, 50 °C

R = Ar, alkyl R1 =

R1

Ag2CO3 (10 mol%) K2S2O8 (3.0 equiv.)

CH2Cl2/H2O, 50 °C

R

O

O Ar

(2)

O O 22 examples, up to 92%

Scheme 4.14 Acylation of pyridine-N-oxides and coumarins.

Li and coworkers reported the C3-acylation of 2-(pyridine-2-yl)-substituted benzofurans and benzothiophenes by reaction with α-oxocarboxylic acids in the presence of catalytic Pd(PPh3 )4 and excess Ag2 O/K2 S2 O8 at elevated temperature (Scheme 4.15) [52]. Control experiments indicated that both palladium and silver were required in order to achieve high yields of products. A mechanism involving the silver-mediated decarboxylation and palladium-catalyzed C(sp2 )—H bond activation was proposed by the authors. However, more mechanistic investigations are required to unveil the detailed mechanism because the possibility of direct acyl radical addition to indole cannot be excluded.

193

194

4 Silver-Mediated Radical Reactions

Pd(PPh)4 (10 mol%) Ag2O (2.0 equiv.) K2S2O8 (2.0 equiv.)

O

O

Ar

+ X

Ar

N

X = O, S

CO2H

Dioxane/HOAc/DMSO 120 °C, 21 h

X

N

26 examples, 64–96%

Scheme 4.15 Acylation of benzofurans and benzothiophenes.

Other than α-oxocarboxylic acids, aldehydes and even formamides can be employed as the acyl source in Minisci acylation reactions. For example, the silver-catalyzed intramolecular oxidative coupling of N-(2-formylaryl)indoles provided an atom-economical entry to indole–indolone scaffolds in satisfactory yields, as reported by Rao and coworkers (Scheme 4.16(1)) [53]. Han et al. introduced the silver-catalyzed cross-dehydrogenative coupling of pyridines with formamides in water, leading to the efficient synthesis of pyridine-2-carboxamides (Scheme 4.16(2)) [54]. In both cases, it was proposed that the interaction of Ag(I) with persulfate generates sulfate radical anion that abstracts a hydrogen atom from an aldehyde or formamide to generate the corresponding acyl radical. H H Ar1

O

O

AgOMs (cat.), oxone

N p-Dioxane/DCE 100 °C, N2

Ar2

N

Ar1

Ar2

(1)

24 examples, up to 90%

N R1

+

H

O

AgNO3 (20 mol%) HCOONa (2.0 equiv.)

O 2

NHR

R2 = H, Me

N R1

K2S2O8 (3.0 equiv.) O2, H2O, 80 °C

NHR2

(2)

20 examples, 29–95%

Scheme 4.16 Acylation of (hetero)arenes with aldehydes or formamides.

A long-standing challenge in Minisci reaction was the arylation of (hetero)arenes by oxidative decarboxylation of aromatic carboxylic acids, not only because it was hard to generate aryl radicals via oxidative decarboxylation but also because aryl radicals were too reactive to be effectively captured by arenes. On the other hand, the palladium/silver or palladium/copper-catalyzed decarboxylative cross-coupling to synthesize biaryl compounds was usually limited to ortho-substituted aromatic carboxylic acids. In 2012, Greaney and coworkers developed the Ag(I)-catalyzed intramolecular decarboxylative arylation of benzoic acids with microwave irradiation at 130 ∘ C for the synthesis of fluorenones in good yields (Scheme 4.17) [55]. As a comparison, the conventional Pd/Ag-mediated decarboxylative cyclization resulted in much lower yields of products. The employment of CD3 CN proved pivotal in achieving

4.3 Radical Coupling

O

AgOAc (20 mol%) K2S2O8 (3.0 equiv.)

R2

R1

O R2

R1 CD3CN MW, 130 °C

CO2H

13 examples 31–84%

Scheme 4.17 Intramolecular Minisci arylation.

good efficiency, presumably because the stronger C—D bond slowed down hydrogen abstraction from the solvent, thus enabling the intramolecular C—C bond formation to take place. In 2015, Su and coworkers made a breakthrough in this area by addressing a silver-catalyzed intermolecular Minisci reaction of aromatic carboxylic acids (Scheme 4.18(1)) [56]. With Ag2 SO4 as the catalyst and K2 S2 O8 as the oxidant, a variety of ortho-, meta-, para-substituted aromatic carboxylic acids as well as picolinic acid underwent decarboxylative coupling with electron-deficient benzenes or pyridines in good yields. The ortho-substituents were not a necessity in this transformation, yet their existence in the aromatic carboxylic acids increased the product yields. In the case of pyridines, C2-arylation occurred preferentially, and the addition of TFA proved essential, presumably by enhancing the reactivity of the pyridines toward aryl radical intermediates. Interestingly, strictly anhydrous conditions were required to guarantee the success of this protocol. Based on preliminary mechanistic studies, a radical mechanism similar to that of Minisci alkylation was proposed. The method was recently extended to the decarboxylative arylation of quinolines by Yuan et al. [57].

1

+ Ar – CO2H

R

X = CH, N

+ N

R1

Ar

TFA (if X = N) MeCN, 120 °C, 24 h

X

R1

Ag(I) (5 – 10 mol%) K2S2O8

R2 B(OH)2

AgNO3 (20 – 40 mol%) K2S2O8 (3.0 – 6.0 equiv.) TFA (1.0 equiv.) CH2Cl2/H2O, rt

X

50 examples (1) up to 85%

R2 N

37 examples (2) up to 96%

R1

Scheme 4.18 Intermolecular Minisci arylation.

Compared with aromatic acids, arylboronic acids are much easier to be oxidized. Aryl radicals can also be generated smoothly from the Ag(II)-mediated oxidation of arylboronic acids or esters under mild conditions. This led to the Minisci arylation of electron-deficient heterocycles with arylboronic acids under much milder conditions, as reported by Baran and coworkers [58]. With AgNO3 as the catalyst, K2 S2 O8 as the oxidant, and TFA as the additive, various heterocycles underwent the coupling reaction with functionalized boronic acids in CH2 Cl2 /H2 O (or PhCF3 /H2 O as an environmentally friendly alternative) at room temperature, leading the synthesis of the corresponding arylated

195

196

4 Silver-Mediated Radical Reactions

heterocycles in satisfactory yields (Scheme 4.18(2)). This protocol proved fairly general for both coupling partners with a satisfying functional group tolerance and was successfully utilized in the arylation of sensitive natural products such as quinine. Regioselectivity of arylation was controlled by the inherent reactivity of the substrates, and generally the C2 and C4 positions were favored. Mechanistic studies by Flowers and Patel revealed that pyridine coordinates to Ag(I) first and the oxidation of the resulting Ag(I)–pyridine complex to the corresponding Ag(II)–pyridine complex by persulfate serves as the rate-determining step in the overall process [59]. An intramolecular variant of the above C—H arylation was also reported by the Baran group [60]. In a similar fashion, Mahindra and Jain developed the C2-arylation of l-histidine with arylboronic acids [61]. Mai et al. also reported the silver-catalyzed C2-arylation of pyridine-N-oxides with arylboronic acids in highly regioselective manner under similar conditions [62]. Also, the silver-catalyzed direct arylation of N-iminopyridinium ylides with arylboronic acids was reported under almost the same conditions [63]. The same method was recently applied to the C6-arylation of purines and purine nucleosides by Du and coworkers [64]. Aromatic triazenes that are easily and rapidly prepared from bench-available anilines can also serve as the source of aryl radicals. In 2014, Wang and Falck developed the first example of silver-catalyzed C—H arylation of electron-deficient heteroarenes with triazenes as the coupling partners, leading to the synthesis of various heterobiaryls (Scheme 4.19(1)) [65]. Both electron-rich and electron-poor triazenes were suitable substrates in the coupling reactions. AgNO3 (20 mol%) K2S2O8 (3 equiv.)

1

N

N

R

+

N

Het R2

TFA, CH2Cl2/H2O, rt

R1 Het

(1) R2

41 examples up to 99% Cu(OAc)2 (0.3 equiv.) NH2

R1 + X X = NMe, O, S

R2

R2

AgONO (1.2 equiv.) LiBr (0.5 equiv.) CsOPiv (0.1 equiv.) 70 or 90 °C, 8 h

R1 X

(2)

43 examples 20–81%

Scheme 4.19 Arylation of heteroarenes with triazenes and amines.

Aryldiazonium salts are also well-known precursors of aryl radicals. In this regard, Seayad and coworker reported the copper-catalyzed arylation of pyrroles, furans, and thiophenes with anilines and AgONO under acid-free conditions (Scheme 4.19(2)) [66]. Replacement of AgONO by t-BuONO resulted in a dramatic drop in product yield, indicating the significance of AgONO for this C—H arylation. In this transformation, aryldiazonium salts were generated in situ from anilines and AgONO, which are then reduced by Cu(I) to aryl radicals

4.3 Radical Coupling

and Cu(II). Rapid addition of aryl radicals to heteroarenes followed by Cu(II) oxidation provides the arylation product along with the regeneration of Cu(I). A rare example for aryl–aryl cross-coupling is the use of phenols as the coupling partners due to the ease of homocoupling [67] of phenols. In the presence of AgNO3 and H2 O2 , the reaction of naphthols or phenols with aniline derivatives provided the corresponding 2′ -aminobiphenyl-2-ols as the cross-coupling products in satisfactory yields (Scheme 4.20) [68]. A mechanism involving the oxidation of phenols into electrophilic radical intermediate is proposed. R2

R2

AgNO3 (1.0 equiv.) H2O2 (3.0 equiv.)

OH +

Toluene, 0 °C to rt, 6 h

R1 R3

N

R4

R2 = OEt, Me

R3 N R4 OH R1 42 examples up to 70.2%

Scheme 4.20 Cross-coupling of phenols and anilines.

Taking advantage of the ease of silver-catalyzed radical decarboxylation of aliphatic carboxylic acids and α-oxocarboxylic acids, a number of new C—C coupling reactions other than the Minisci reaction were successfully developed in the past few years. In 2012, Li and coworkers introduced the silver-catalyzed decarboxylative alkynylation of aliphatic carboxylic acids in aqueous solution (Scheme 4.21(1)) [69]. With AgNO3 as the catalyst and K2 S2 O8 as the oxidant, primary/secondary/tertiary alkyl carboxylic acids underwent smooth decarboxylative C(sp)—C(sp3 ) coupling with various ethynylbenziodoxolones, leading to a convenient and efficient synthesis of alkynylated compounds under mild conditions. This protocol also exhibited an excellent functional group tolerance, thus allowing the alkynylation to proceed for complex molecules such as N-protected amino acids or dehydrolithocholic acids. Notably, the protocol represented the first example of alkynyliodine(III) compounds serving as radical acceptors. A radical mechanism was proposed based on related studies. As shown in Figure 4.2, the alkyl radical formed by Ag(II)-mediated decarboxylation of aliphatic carboxylic acid adds to the C≡C triple bond of alkynyliodine(III) compound, followed by subsequent β-elimination to afford the final product along with the benziodoxolonyl radical. The latter is transformed into 2-iodobenzoic acid either by H-abstraction or by reduction. Duan and coworkers then extended the above Li’s protocol to the decarboxylative alkynylation of α-keto acids and oxamic acids, providing an easy access to a variety of ynones and propiolamides (Scheme 4.21(2)) [70]. They also demonstrated that this radical process could also be applied to the C(sp2 )—H alkynylation of DMF. Furthermore, Chen and Hashmi directly applied Li’s protocol to the synthesis of difluoromethylated alkynes via silver-catalyzed decarboxylative alkynylation of α,α-difluoroarylacetic acids (Scheme 4.21(3)) [71].

197

198

4 Silver-Mediated Radical Reactions

I

O

AgNO3 (cat.) K2S2O8

G

R – CO2H + O

R

G

(1)

DMF/H2O or CH3CN/H2O 33 examples up to 94%

rt or 50 °C

R =1°, 2°, 3° alkyl G = Ph, p-Cl-C6H4, TIPS

R

I

O

O CO2H

+

G

O

R = aryl, alkyl, NR1R2

AgNO3 (cat.) K2S2O8

O

CH3CN/H2O

R

G

50 or 100 °C

36 examples up to 92%

AgNO3 (cat.) K2S2O8

F

G = TIPS, TBS, aryl, alkyl

I

O

CF2CO2H

G

+ O

(2)

F (3) G

CH3CN/H2O

R

R

50 °C

25 examples 37–97%

G = TIPS, aryl

Scheme 4.21 Decarboxylative alkynylation. S2O82–

O O

O Ag2+

Ag+

TIPS

I

O

R

R – CO2H

I R TIPS

I HO2C

O

+e, +H+ or H-abstraction

I

O

R

TIPS

Figure 4.2 Proposed mechanism of decarboxylative alkynylation.

In 2016, the Li group further developed the silver-catalyzed decarboxylative radical allylation of aliphatic carboxylic acids with allyl sulfones in aqueous solution (Scheme 4.22(1)) [72]. A wide range of primary/secondary/tertiary alkyl carboxylic acids underwent the C(sp3 )—C(sp3 ) coupling with various allyl sulfones in DCM/H2 O in satisfactory yields, while aromatic acids remained intact. The choice of biphasic solvent system gave more favorable results, presumably by inhibiting the decomposition of product alkenes. A radical mechanism was proposed, involving the addition of the alkyl radical onto an allyl sulfone followed by β-elimination to give the final product. Based on the similar strategy, Jiao

4.3 Radical Coupling

AgNO3 (20 mol%) E R – CO2H

+

E

K2S2O8 (2.0 equiv.) R

Ts

(1)

CH3CN/H2O, 50 °C 31 examples 44–89%

R = 1°, 2°, 3° alkyl E = H, Me, CN, CO2Et

NOBn R – CO2H

+

R1

PhO2S

R = 1°, 2°, 3° alkyl R1 =

AgNO3 (20 mol%) NOBn

K2S2O8 (1.5 equiv.) CH3CN/H2O 50°C, 12 h

H, CF3, C2F5, C4F9, CN, CO2Et, alkyl

R

R1

(2)

42 examples up to 93%

Scheme 4.22 Decarboxylative allylation and oximation.

and coworkers developed a silver-catalyzed decarboxylative cross-coupling of aliphatic carboxylic acids with sulfonyl oxime ethers, leading to the corresponding alkyl oxime ethers with good functional group tolerance and wide substrate scope (Scheme 4.22(2)) [73]. Ketoximes bearing electron-withdrawing groups (e.g. CN or CF3 ) exhibited a higher reactivity than alkyl-substituted ketoximes presumably because of the nucleophilic nature of alkyl radicals generated via oxidative decarboxylation. Silver-catalyzed decarboxylative alkenylation could also be implemented in a similar fashion. In this context, Mai et al. realized the Cu/Ag-catalyzed double decarboxylative cross-coupling reaction between aliphatic carboxylic acids and cinnamic acids in aqueous solution (Scheme 4.23(1)) [74]. Secondary and tertiary alkyl acids were good partners for the cross-coupling, whereas cinnamic acids bearing strong electron-donating groups (e.g. OMe) had a poor performance. Replacement of cinnamic acid by phenylpropiolic acid led to the corresponding decarboxylative alkynylation products. A plausible mechanism was proposed as follows. The Ag(II)-mediated decarboxylation of aliphatic carboxylic Cu (5 mol%) AgNO3 (20 mol%) Ar

CO2H

K2S2O8 (1.0 equiv.) + R – CO2H

CH3CN/H2O 90 °C, 12 h

Ar1

HO2C

Ar2

K2CO3 (1.0 equiv.) H2O, 100 °C

Scheme 4.23 Decarboxylative alkenylation.

R

(1)

30 examples 21–96%

AgNO3 (10 mol%) Na2S2O8 (0.5 equiv.)

O CO2H +

Ar

O Ar1 20 examples 54–92%

Ar2

(2)

199

200

4 Silver-Mediated Radical Reactions

acid generates the alkyl radical that adds to cinnamic acid regioselectively to give the corresponding benzyl radical. Further oxidation of the benzyl radical presumably promoted by copper affords the alkene product with the concomitant extrusion of CO2 . In a similar fashion, the silver-catalyzed double decarboxylative cross-coupling between α-keto acids and cinnamic acids provided an efficient strategy for the preparation of chalcone derivatives in water, as reported by Yang and coworkers (Scheme 4.23(2)) [75]. The double decarboxylative cross-coupling in Scheme 4.23 also pointed out an alternative route for the decarboxylation of cinnamic acids other than direct oxidative decarboxylation. Based on this strategy, Duan and coworkers developed a CuCl-catalyzed decarboxylative trifluoromethylation of cinnamic acids with CF3 SO2 Na as the CF3 source, tert-butyl hydrogen peroxide (TBHP) as the oxidant, and Ag2 CO3 as the additive (Scheme 4.24) [76]. Trifluoromethylated olefins were obtained in good yields with high E/Z selectivity. Ag2 CO3 was believed to play an important role in promoting the decarboxylation process.

R Ar

CO2H

+ CF3SO2Na

CuCl (20 mol%) Ag2CO3 (0.6 equiv.) TBHP (5.0 equiv.) DCE, 70 °C, 24 h

R CF3

Ar

13 examples 48–72% E/Z up to 99 : 1

Scheme 4.24 Decarboxylative trifluoromethylation of cinnamic acids.

Very recently, the silver-catalyzed decarboxylative trifluoromethylation of aliphatic carboxylic acids was successfully accomplished by Li and coworkers [77]. With AgNO3 as the catalyst and K2 S2 O8 as the oxidant, the reactions of various primary and secondary alkyl carboxylic acids with the mixture of (bpy)Cu(CF3 )3 and ZnMe2 in aqueous acetonitrile at 40 ∘ C produced the corresponding trifluoromethylated products in satisfactory yields (Scheme 4.25). This protocol exhibited a wide substrate scope and excellent functional group compatibility. Nevertheless, tertiary alkyl carboxylic acids failed to give the desired products presumably because of steric effect. Mechanistic studies revealed that the interaction of (bpy)Cu(CF3 )3 with ZnMe2 led to the MeCu(CF3 )3 anion, which was characterized by X-ray diffraction experiments. The authors then proposed a mechanism depicted in Figure 4.3. The MeCu(CF3 )3 anion undergoes reductive elimination to form MeCF3 and the − Cu(CF3 )2 anion. The latter is then oxidized to Cu(CF3 )2 . Finally, the CF3 group transfer from Cu(CF3 )2 to the alkyl radical generated by oxidative decarboxylation of carboxylic acid yields the trifluoromethylated product. AgNO3 (cat.), K2S2O8 R – CO2H R = 1°, 2° alkyl

(bpy)Cu(CF3)3, ZnMe2 CH3CN/H2O, 40 °C, 10 h

R – CF3

38 examples 52–88%

Scheme 4.25 Decarboxylative trifluoromethylation of aliphatic carboxylic acids.

4.3 Radical Coupling

S2O82– Ag2+ R – CO2H

Ag+

–H+, –CO2

R – CF3

R Cu(CF3)2

CuCF3

ZnMe2 + (bpy)Cu(CF3)3 [O] –Cu(CF ) Me 3 3

–Cu(CF

3)2 +

Me – CF3

Figure 4.3 Proposed mechanism of decarboxylative trifluoromethylation.

The use of tertiary alkyl halides in cross-coupling reactions was challenging due to the completing elimination processes. To address the challenge, Oshima and coworkers developed the AgNO3 -catalyzed benzylation and allylation reactions of tertiary and secondary alkyl halides with Grignard reagents (Scheme 4.26(1)) [78]. The reaction proceeded smoothly in ether under mild conditions, leading to the coupling products in high yields. The use of alkyl bromides gave more favorable results, and the reactivity of alkyl bromides decreased in the order tertiary > secondary ≫ primary. Replacement of Grignard reagents by organozinc reagents or organolithium reagents gave similar results [79, 80]. Dibenzylation and diallylation of gem-dibromoalkanes with Grignard reagents also proved to be successful (Scheme 4.26(2)) [81]. Mechanistic experiments supported the involvement of alkyl radicals in these cross-coupling reactions. The proposed mechanism is exemplified as follows with benzylmagnesium bromide as the nucleophile. The formation of electron-rich silver(0)–ate complex initially takes place through the reaction of Ag(I) with two equivalents of BnMgBr. The ate complex undergoes single electron transfer (SET) to alkyl halide to produce the corresponding alkyl radical and BnAg(I) intermediate. The alkyl radical is then trapped by BnAg(I) to give the cross-coupling product and regenerate Ag(0). AgNO3 (cat.) R

Br

+

BrMg

R2 Br R1

R

AgNO3 (cat.) +

Br

Et2O, 25 °C, 3 h

BrMg

Et2O, 25 °C, 3 h

R1 = alkyl; R2 = H, alkyl

14 examples 14–88%

(1)

18 examples 22–90%

(2)

R1 R2

Scheme 4.26 Benzylation and allylation of alkyl halides.

The above benzylsilver(I) chemistry was nicely extended by Hu and coworkers into homocoupling and cross-coupling of olefins [82, 83]. Taking advantage of the high electrophilicity of gem-difluoroalkenes, the Hu group successfully

201

202

4 Silver-Mediated Radical Reactions

developed the AgF-mediated fluorinative homocoupling of β,β-difluorostyrenes, leading to the synthesis of di(trifluoromethylation) products in good yields (Scheme 4.27(1)) [82]. On the basis of their mechanistic studies, the authors proposed that the nucleophilic addition of AgF to β,β-difluorostyrenes gives the benzylsilver(I) intermediates, which undergo homolytic cleavage of C—Ag bond followed by the dimerization of the resulting benzyl radicals to form the final product. Based on this proposal, the Hu group further developed the AgF-mediated fluorinative cross-coupling of β,β-difluorostyrenes and nonfluorinated styrene derivatives, providing a facile access to α-CF3 alkenes (Scheme 4.27(2)) and β-CF3 ketones (Scheme 4.27(3)) [83]. AgF (3.0 equiv.) F

Ar

Dark, 80 °C, 6 h

F +

Ar1

H

F

F +

Ar1

Ar

Ar F

F

CF3

pyridine/THF, 4A MS

H

R

NMP, 80 °C

CF3

OMe

NMP, 80 °C

R

Ar1

Ar2

CF3 O

AgF, AgBF4 Ar2

(1)

25 examples 21–83%

(2)

12 examples 64–85%

(3)

CF3

AgF, AgBF4 Ar2

11 examples 40–78%

Ar

1

Ar2

Scheme 4.27 AgF-mediated coupling of styrenes.

Closely related to the above benzylsilver(I) chemistry, the AgF-catalyzed homocoupling of α-aryl ketones was reported by Wang and coworkers [84]. In another case, the Ag2 O-mediated intramolecular oxidative coupling of acetoacetanilides for the synthesis of 3-acetyloxindoles was described by Yu et al. [85]. 4.3.2

Formation of C—O/S/Se Bonds

Wang and coworkers reported the AgSbF6 -catalyzed C4-sulfenylation of 1-methoxynaphthalene with diaryl disulfides, providing the corresponding aryl naphthyl sulfides in moderate to excellent yields (Scheme 4.28(1)) [86]. The addition of Cu(OAc)2 •H2 O significantly improved the efficiency of sulfenylation. The selenylation of 1-methoxynaphthalene with diaryl diselenides could also be achieved under similar conditions. In a similar fashion, Deng and coworkers reported the AgOAc-mediated vinylic C—H sulfenylation of enamides in DCE at elevated temperature (Scheme 4.28(2)) [87]. A mechanism involving the oxidation of enamides by Ag(I) to generate carbon-centered radicals was proposed. Ma et al. extended the method to the sulfenylation and selenylation of pyrazolones (Scheme 4.28(3)) [88]. The incorporation of trifluoromethylthio groups into new drugs and agrochemicals has attracted much attention owing to its strongly electron-

4.3 Radical Coupling

AgSbF6 (cat.) Cu(OAc) .H O

OMe

2

+

ArXXAr DCE 100–120 °C, 12 h

X = S, Se

NHAc H

OMe

2

AgOAc +

R2

SAr

ASSAr

R2

Ar1

+ O

(2)

n

n = 0, 1, 2

XAr

AgOTf, AgOAc R N N

15 examples 18–88%

NHAc

H

3

(1)

XAr

DCE, 125 °C, 24 h n

18 examples 21–95%

ArXXAr PhMe, 100 °C, 16 h

R

3

N

O

N

14 examples (3) 51–90%

1

Ar

ArX = TolS, PhSe

Scheme 4.28 Sulfenylation and selenylation.

withdrawing nature and high lipophilicity. In 2015, Tang and coworkers developed the silver-mediated aliphatic C—H trifluoromethylthiolation [89]. Various hydrocarbons with multiple unactivated C(sp3 )—H bonds were transformed into the corresponding trifluoromethylthiolation products in satisfactory yields by reaction with AgSCF3 and Na2 S2 O8 in aqueous solution under mild conditions (Scheme 4.29(1)). The reaction is site selective in that trifluoromethylthiolation occurred preferentially at methine or methylene positions remote from electron-withdrawing groups. The protocol showed a good functional group tolerance and wide substrate scope. A plausible mechanism was proposed by the authors as follows. The interaction between AgSCF3 and Na2 S2 O8 produces Ag(II)—SCF3 and a sulfate radical anion; the latter abstracts a hydrogen atom from a C(sp3 )—H bond in the substrate to generate the corresponding alkyl radical, which then reacts with Ag(II)—SCF3 or CF3 SSCF3 to afford the final product. Almost at the same time, Liu and coworkers reported the same aliphatic C—H trifluoromethylthiolation under slightly altered conditions (Scheme 4.29(2)) [90]. AgSCF3 (2.5 equiv.) Na2S2O8 (4.0 equiv.) R– H

R – SCF3

29 examples up to 94%

(1)

R – SCF3

34 examples up to 83%

(2)

MeCN/H2O/DCE, 35 °C AgSCF3 (1.0 equiv.) K2S2O8 (2.0 equiv.) R– H MeCN, 60 °C, Ar, 12 h

Scheme 4.29 Aliphatic C—H trifluoromethylthiolation.

203

204

4 Silver-Mediated Radical Reactions

Site-specific C(sp3 )—S bond formation could be achieved by decarboxylative thiolation of aliphatic carboxylic acids. In this context, Shen and coworkers demonstrated that, with the use of K2 S2 O8 as the oxidant, AgNO3 and sodium dodecyl sulfate (SDS) as the catalysts, and ((2-(2-iodophenyl) propan-2-yl)oxy)(trifluoromethyl)sulfane as the trifluoromethylthiolating agent, aliphatic carboxylic acids underwent decarboxylative trifluoromethylthiolation in water at 50 ∘ C to give the corresponding products in satisfactory yields (Scheme 4.30) [91]. The aqueous emulsion formed by the addition of SDS in water dramatically accelerated the reaction. This protocol proved to be quite general for tertiary and secondary alkyl carboxylic acids, while low yields of products were obtained for primary alkyl carboxylic acids. The method also exhibited a wide range of functional group tolerance. Mechanistic investigations supported the proposed mechanism in which the alkyl radical generated from the decarboxylation of Ag(II) carboxylate reacts with the trifluoromethylthiolating reagent to afford the final product. AgNO3 (30 mol%)

Me R – CO2H +

O – SCF3

Ar

n-C12H25SO3Na (20 mol%) K2S2O8 (1.0 equiv.)

Me R = 1°, 2°, 3° alkyl; Ar = 2-iodophenyl

H2O, 50 °C

R – SCF3 24 examples 20–91%

Scheme 4.30 Decarboxylative trifluoromethylthiolation of carboxylic acids.

Similarly, Xu and coworkers reported the synthesis of alkyl aryl sulfides via AgNO3 -mediated decarboxylative C—S coupling of aliphatic carboxylic acids using K2 S2 O8 as the oxidant and diaryl disulfide as the sulfur source (Scheme 4.31) [92]. The use of a stoichiometric amount of AgNO3 accelerated the decarboxylation and thus helped to keep the unwanted oxidation of product diaryl disulfides in a minimum level. AgNO3 (1.0 equiv.) R – CO2H + Ar R = alkyl

S

S

Ar

K2S2O8 (3.0 equiv.) CH3CN/H2O 60 °C, 24 h

R

S

Ar

24 examples 28–85%

Scheme 4.31 Decarboxylative arylthiolation of aliphatic carboxylic acids.

In another case, Hoover and coworkers reported the oxidative decarboxylative trifluoromethylthiolation of coumarin-3-acids with AgSCF3 and K2 S2 O8 under basic conditions (Scheme 4.32) [93]. The method is also applicable to thiocoumarin and quinolin-2(1H)-one carboxylic acids. Mechanistic studies suggested that an aryl–Ag species is generated by the silver-mediated decarboxylation, which undergoes trifluoromethylthiolation to afford the final product. In 2016, Shen and coworkers introduced a new shelf-stable and easily scalable difluoromethylthiolating reagent, S-(difluoromethyl) benzenesulfonothioate

4.3 Radical Coupling

R2

K2S2O8, K2CO3

R1 X

R2

AgSCF3 COOH O

CH3CN/H2O, 110 °C

SCF3

R1 X

22 examples 22–95%

O

X = O, S, NMe

Scheme 4.32 Decarboxylative trifluoromethylthiolation of coumarin-3-acids.

(PhSO2 SCF2 H), for radical difluoromethylthiolation [94]. Thus with AgNO3 as the catalyst and K2 S2 O8 as the oxidant, aryl and alkyl boronic acids underwent difluoromethylthiolation in aqueous emulsion at 50 ∘ C to afford the corresponding products in good yields (Scheme 4.33(1)). Under similar conditions, a variety of aliphatic carboxylic acids underwent decarboxylative difluoromethylthiolation smoothly (Scheme 4.33(2)). AgNO3 (cat.) n-C12H25SO3Na (cat.) R – B(OH)2 + PhSO2SCF2H R = 1°, 2° alkyl or aryl

K2S2O8 H2O, 50 °C, 3 h

R – SCF2H

(1)

28 examples up to 80%

AgNO3 (cat.) R – CO2H + PhSO2SCF2H R = 1°, 2°, 3° alkyl

n-C12H25SO3Na (cat.) K2S2O8 H2O, 50 °C, 6 h

R – SCF2H

(2)

25 examples 41–90%

Scheme 4.33 Difluoromethylthiolation of boronic acids.

An alternative strategy for the synthesis of SRf -containing compounds is the fluoroalkylation of thiols. In this regard, Yi and coworkers reported the silver-catalyzed fluoroalkylation of thiols with fluoroalkanesulfinates [95]. With AgNO3 as the catalyst and K2 S2 O8 as the oxidant, the reactions of aryl-, heteroaryl-, and alkylthiols with fluoroalkanesulfinates afforded the corresponding S-fluoroalkylation products in good yields (Scheme 4.34). The mechanism is likely to involve the generation of fluoroalkyl radicals via Ag(II)-mediated oxidation of fluoroalkanesulfinates followed by the attack of fluoroalkyl radicals onto disulfides formed from the oxidation of thiols. AgNO3 (10 mol%) K2S2O8 (2.0 equiv.) R – SH

R – SRf

+ RfSO2Na CH3CN/H2O, 80 °C

R = aryl, heteroaryl, alkyl Rf = CF3, CF2H, C2F5, C4F9, C6F13, C8F17

Scheme 4.34 Fluoroalkylation of thiols.

39 examples up to 91%

205

206

4 Silver-Mediated Radical Reactions

Silver-mediated decarboxylation reactions could also be utilized for C—O bond formations. In 2008, Huang et al. showed that N-acyl amino acids could be converted into imides in water at room temperature by oxidative decarboxylation induced by Ag+ /Cu2+ /S2 O8 2− (Scheme 4.35) [96]. The proposed mechanism involves the oxidative generation of 1-amidoalkyl radicals that are further oxidized to iminium ions followed by hydrolysis and subsequent oxidation. In a similar fashion, the biobased glutamic acid could be converted to succinimide in excellent yield, as reported by Fu and coworkers [97].

R1

AgNO3 (20 mol%) CuSO4.5H2O (20 mol%)

R2

O N

COOH

R1

(NH4)2S2O8 (3.0 equiv.)

R3

R2

O N

O

8 examples up to 89%

R3

H2O, rt

Scheme 4.35 Decarboxylation of N-acyl amino acids.

In 2012, Goossen and coworkers developed the silver-catalyzed decarboxylative Chan–Evans–Lam-type couplings of aromatic carboxylatic acids [98]. In the presence of Ag2 CO3 /Cu(OAc)2 , a variety of ortho-substituted aromatic carboxylic acids underwent decarboxylative etherification with alkyl orthosilicates or aryl borates in DMF at 145 ∘ C under aerobic conditions, leading to the regiospecific construction of diaryl and alkyl aryl ethers in satisfactory yields (Scheme 4.36). Based on their mechanistic studies, the authors proposed the mechanism consisting of three consecutive processes: silver-catalyzed decarboxylation, transmetalation, and Cu-mediated Chan–Evans–Lam-type cross-coupling, as shown in Figure 4.4. Ag2CO3 (25 mol%) Cu(OAc)2 (1.0 equiv.) Ar – COOK + Si(OR)4

Ar – OR O2, DMF, 145 °C, 18 h

20 examples 29–85%

R = alkyl, aryl

Scheme 4.36 Decarboxylative etherification of aromatic acids. 2X– + [CuI]X

[CuII]X2 [O] CO2

Ar-[Ag]

[CuII]X2

[CuI]X Ar

Decarboxylation cycle ArCOO[Ag]

Chan–Evans–Lam cycle Ar-[CuIII]X

KX

OR + M+ + X–

MOR

Ar-[CuIII]X2

[Ag]X ArCOOK

[CuII]X2

[CuI]X

Figure 4.4 Proposed mechanism of decarboxylative etherification.

4.3 Radical Coupling

The Goossen group went on to investigate the reactivity of benzoates without ortho-substitution and developed the synthesis of aryl ethers from benzoates through carboxylate-directed C—H alkoxylation with concomitant protodecarboxylation (Scheme 4.37) [99]. Meta-substituted aryl ethers were prepared from the corresponding para- or ortho-substituted benzoates and para-substituted aryl ethers from meta-substituted benzoates. A wide range of available aromatic carboxylic acids as well as heteroaromatic carboxylic acids were suitable reaction partners with primary or secondary alkoxides to form the products. The isotope labeling experiment indicated the breaking of the C—H bond as the rate-determining step, while control experiments confirmed that the C—O bond was formed between the alkoxide and a metalated arene and not through an attack of (per)oxo–copper species on to the arene ring. Thus, this protocol could be regarded as the silver/copper-mediated oxidative ortho-alkoxylation cycle of the benzoate linked with the silver-mediated decarboxylation cycle.

COOK

X

+ B(OR)3

R,R′

Ag2CO3 (1.0 equiv.) Cu(OAc)2 (25 mol%)

X

1 atm. O2, DMF, 140 °C

H

H

R,R′

X = C, N

OR 28 examples 37–84%

Scheme 4.37 C—H alkoxylation with concomitant protodecarboxylation.

The same research group went one step further to develop the bimetallic copper/silver-mediated dehydrogenative cross-coupling of arenes with alcohols (Scheme 4.38) [100]. Various arenes or heteroarenes with N-chelating directing groups were suitable coupling partners with linear or branch alkyl alcohols to give the corresponding aryl ethers in good yields. The presence of AgOTf proved crucial presumably by transferring the alkoxyl group to the copper catalyst. The isotope labeling experiment indicated the breaking of the C—H bond as the rate-determining step, while radical trapping experiments confirmed the involvement of alkoxyl radical. Thus, a plausible mechanism was proposed as illustrated in Figure 4.5. The arene undergoes chelation-assisted C—H activation with Cu(OAc)2 to form the Cu(II)–arene species, while alkoxyl radical is generated through the decomposition of the in situ formed silver alkoxide species. Then the alkoxyl radical is transferred to the Cu(II)–arene species to give the Cu(III) intermediate along with metallic silver, and finally reductive elimination of the Cu(III) intermediate affords the product with the release of the Cu(I) species to enter the next catalytic circle. Ag2CO3 (1.0 equiv.) X FG H

N

+ HOR

X

Cu(OAc)2 (25 mol%) FG 1 atm. O2, DMF, 140 °C

N

OR

Scheme 4.38 Dehydrogenative cross-coupling of arenes with alcohols.

24 examples 32–82%

207

208

4 Silver-Mediated Radical Reactions

HX N

FG

N

FG

HX

CuII

H CuIIX2

[AgIOR] ROH

X

1/2 H2O

AgIX

Ag0

1/4 O2 + HX CuIX

N

FG

CuIII X OR

N

FG

OR

Figure 4.5 Proposed mechanism of cross-coupling of arenes with alcohols.

Another approach to aryl C—O bond formations was silver-promoted intramolecular O-arylation of carboxylic acids or phenols (Scheme 4.39). Xu and coworkers demonstrated that, with AgNO3 as the catalyst and (NH4 )2 S2 O8 as the oxidant, 2-arylbenzoic acids underwent efficient cyclization to provide the corresponding six-membered lactones (Scheme 4.39(1)) [101]. A kinetic isotope effect study suggested that the reaction may occur via a radical process. This method was later applied by Basak and coworkers into the efficient synthesis of 6H-benzo[c]chromen-6-ones as potential DNA intercalating agents [102]. With regard to O-arylation of phenols, Lawson and coworkers reported the Ag2 CO3 -promoted synthesis of 5,6-O-annulated pyridones via C6-aryloxylation (Scheme 4.39(2)) [103]. The proposed mechanism involves the oxidation of phenoxide by Ag2 CO3 to phenoxyl radical that adds to the pyridone ring in a 6-endo mode. R2 R1 H

AgNO3 (20 mol%)

KOAc (3.0 equiv.) CH2Cl2/H2O, rt

CO2H

R2

(NH4)2S2O8 (3.0 equiv.)

(1)

R1 O

O

26 examples, 33–93%

R1

R1 R

N

OH

O

O

Ag2CO3 (2.1 equiv.)

E

K2CO3 (2.5 equiv.) PhMe, 90–120 °C

R

O

N

O (2) E

O 13 examples, 42–94%

Scheme 4.39 Intramolecular O-arylation of carboxylic acids and phenols.

4.3 Radical Coupling

In other case, Bi and coworkers reported the Ag2 O-mediated radical coupling of isocyanides with alkanols or phenols in the presence of water under aerobic conditions, leading to the formation of the corresponding carbamates [104]. Silver was also found to catalyze the cumene peroxidation and selective side-chain oxidation of alkyl aromatic compounds [105, 106]. 4.3.3

Formation of C—N/P Bonds

Dialkyl phosphites, dialkylphosphine oxides, or alkylphosphinates can be oxidized by silver(II) or silver(I) salts to generate the corresponding phosphorus-centered radicals, which add to C=C bonds or (hetero)arene rings to give the coupling products via C—P bond formations. A number of methods have been developed in recent years based on this strategy. In 2012, Huang and coworkers showed that, with AgNO3 as the catalyst and K2 S2 O8 as the oxidant, heteroarenes such as furan, thiophene, thiazole, and pyrrole underwent phosphonylation with dialkyl phosphites in CH2 Cl2 /H2 O at room temperature, affording the corresponding coupling products in satisfactory yields (Scheme 4.40(1)). Pyridines were also suitable substrates for the transformation, and 2-phosphonylated pyridines were obtained in acceptable yields after the addition of Na2 S2 O3 to prevent the products from over-oxidation (Scheme 4.40(2)) [107]. In a similar fashion, Wang and coworkers described the AgNO3 /K2 S2 O8 -mediated reaction of thiazolo[3,2-b]-1,2,4-trazoles with dialkyl phosphites in acetonitrile at reflux, leading to the formation of the corresponding C5-phosphonylated products [108]. Kim et al. also reported the synthesis of pyrrole-2-phosphonates in satisfactory yields by reaction of dialkyl phosphites with pyrroles in the presence of AgNO3 /K2 S2 O8 in DMF/H2 O at 50 ∘ C [109]. The same method also led to the preparations of dibenzo[b,f ][1,4]oxazepin-11-yl phosphonates, as reported by Sharma and coworkers [110]. AgNO3 (20 mol%) O

X

R1

+

K2S2O8 (4.0 equiv.) R1

H P OR2

Y

OR2

CH2Cl2/H2O, rt

O + H

N

P OR2 OR2

Y

O 2 P OR

(1)

OR2

8 examples, 51–89%

X = CH, N; Y = O, S, Me

R1

X

1. AgNO3 (20 mol%) K2S2O8 (4.0 equiv.) CH2Cl2/H2O, rt 2. Na2S2O3

R1 O N P OR2 R2O

(2)

10 examples, 53–81%

Scheme 4.40 Phosphonylation of heteroarenes with dialkyl phosphites.

In another case, Zou and coworkers reported the silver-catalyzed phosphonylation of substituted indoles [111]. With Ag2 CO3 as the catalyst and

209

210

4 Silver-Mediated Radical Reactions

Mg(NO3 )2 ⋅6H2 O and 4 Å MS as the additives, 2- or 3-substituted indoles underwent phosphonylation with dialkyl phosphites or diphenylphosphine oxide to provide 3- or 2-phosphorylated indoles in moderate to good yields (Scheme 4.41(1)). The use of Mg(NO3 )2 ⋅6H2 O rather than K2 S2 O8 presumably helps to avoid further oxidation of indoles. Under similar conditions, coumarins could be converted to coumarin-3-yl phosphonates [112]. As a comparison, Wan and coworkers showed that the reaction of dialkyl phosphites with 2,3-unsubstituted indoles and excess AgOAc at 90 ∘ C provided indolyl-2-phosphonates (Scheme 4.41(2)) [113]. P(O)R2 R1

R3

R1

N R2

O + H

or R3

N R2

or

P R R

R3

Ag2CO3 (cat.) Mg(NO3)2.6H2O 4 A MS, CH3CN

(1) R3

80 °C, 24 h R1

1

R

R2 25 examples, up to 84%

R2

O R1

+ N H

P(O)R2 N

N

OR2

O

AgOAc (3.0 equiv.) R1

H P OR2 DCE, 90 °C

P OR2 N H

(2)

OR2

16 examples, up to 71%

Scheme 4.41 Phosphonylation of indoles.

The silver-promoted phosphonylation of arenes were investigated by the groups of Cheng and coworkers [114–117]. Arenes bearing electron-withdrawing groups underwent regioselective phosphonylation with dialkyl phosphites in the presence of K2 S2 O8 and Ag2 SO4 to afford the corresponding 2-phosphonylated products (Scheme 4.42(1)) [114]. The ortho-regioselectivity presumably resulted from the stabilization of the cyclohexadienyl radical intermediates by the electron-withdrawing group through captodative effect. The same strategy was also employed in the ortho-phosphonylation reaction of ferrocenyl anilides with dialkyl phosphites mediated by Ag2 CO3 [115]. In contrast, the reaction of aromatic aldehydes or ketones with dialkyl phosphites showed excellent para-regioselectivity, affording p-formyl or p-acylphenylphosphonates in good yields (Scheme 4.42(2)) [116]. The para-regioselectivity was also observed in silver-promoted phosphonylation of 8-aminoquinoline amides (Scheme 4.42(3)) [117]. In 2015, Tan and coworkers nicely introduced the silver-catalyzed C—H phosphonylation of styrenes with dialkyl phosphites or diphenylphosphine oxide [118]. The reaction was promoted by the addition of TEMPO, providing

4.3 Radical Coupling

Ag2SO4 (10 mol%) O

EWG

+ H P OR2

1

R

EWG

K2S2O8 (3.0 equiv.) R

1

CH3CN/H2O, 90 °C

OR2

P R2O

EWG = CONR2, SO2NR2, NO2, NHCOR

O

O R + H P OR2

R1

OR2

OR2

Ag2O (10 mol%) K2S2O8 (2.0 equiv.)

O

CH3CN/H2O, 100 °C

R

O P OR2 R1

(2)

OR2

24 examples, 65–91%

R1 O +

H

R

K2S2O8 (2.0 equiv.) NaOH (2.0 equiv.) dioxane,120 °C

P

R1

R 2O

P OR2 OR2

O

R2O

Ag2CO3 (2.5 equiv.)

O

(1)

23 examples, 50–82%

R = H or Me

NH

O

NH

(3)

R O 23 examples, up to 76%

Scheme 4.42 Phosphonylation of arenes.

a highly regioselective and stereoselective approach toward the synthesis of (E)-vinylphosphonates and phosphine oxides (Scheme 4.43(1)). Unfortunately, unactivated alkenes proved to be incompatible with this protocol. The proposed mechanism involves the addition of phosphonyl radical addition to styrene to give the adduct radical, which is then trapped by TEMPO. Subsequent TEMPO-assisted elimination of TEMPOH yielded the final product, while TEMPOH is further oxidized back to TEMPO by K2 S2 O8 . Analogously, Qu and coworkers reported the silver-catalyzed, microwave-assisted radical phosphonylation of β-aryl-α,β-unsaturated carbonyl compounds with dialkyl phosphites, providing substituted (E)-alkenylphosphonates in good yields (Scheme 4.43(2)) AgNO3 (5 mol%) R2

O R1

Ar

+ H P X X X = Ph, OR

Ar + H R

O

P X

TEMPO (0.4 equiv.)

O PX2

Ar

Ar

(1)

22 examples 46–95%

(2)

O PX2

X THF, 100 °C, MW

Scheme 4.43 Phosphonylation of styrenes.

22 examples 51–81%

R1

PhMe, 100 °C

AgNO3 (10 mol%) Mg(NO3)2.6H2O (0.5 equiv.)

O

R2

K2S2O8 (2.0 equiv.)

R

O

211

212

4 Silver-Mediated Radical Reactions

[119]. In another case, Xu and coworkers developed the AgNO3 -mediated phosphonylation of ketene dithioacetals [120]. Site-specific C—P coupling can be achieved by decarboxylative phosphonylation of carboxylic acids. In this context, Gao and coworkers developed the nickel-catalyzed decarboxylative C—P cross-coupling of cinnamic acids with dialkyl phosphites, alkylphosphinates, or diphenylphosphine oxide, providing a facile route to the corresponding phosphorylated (E)-alkenes (Scheme 4.44(1)) [121]. The addition of 2 equiv. of Ag2 O proved to be crucial for the reaction. The method was also applicable to the decarboxylative phosphonylation of 3-arylpropiolic acids. While the detailed mechanism remains unclear, it was observed that the presence of radical scavengers such as BHT or TEMPO did not inhibit the reaction, suggesting that the C—P coupling might not be a radical process.

CO2H

Ar

Ni(dppf)Cl2 (5 mol%) Ag2O (2.0 equiv.)

O + H P X

2

R

CO2H NO2

O + H P X X

Pd(OAc) (cat.) Ag2CO3 LiNO3 DMF, 120 °C MW, 40 W

PX2

Ar

DMSO, 120 °C, 12 h

X

R

O 28 examples (1) 50–92%

R2

O PX2 R

29 examples up to 72%

(2)

NO2

Scheme 4.44 Decarboxylative phosphonylation of cinnamic acids and o-nitrobenzoic acids.

Another example of decarboxylative phosphonylation was reported by Xiao and coworkers using o-nitrobenzoic acids as the substrates [122]. With the use of Pd(OAc)2 as the catalyst and Ag2 CO3 and LiNO3 as the additives, the reaction of o-nitrobenzoic acids with dialkyl phosphites in DMF at 120 ∘ C under microwave irradiation afforded the corresponding 2-nitrophenylphosphonates (Scheme 4.44(2)). However, this protocol was not applicable to other benzoates. A tandem process consisting of Ag-mediated decarboxylation, transmetalation, and Pd-catalyzed C—P coupling might be the mechanism. Silver-mediated radical processes have also played a versatile role in C—N coupling reactions. In particular, the combination of a Ag(I) catalyst and a hypervalent iodine reagent has offered a facile route to C(sp3 )—H amination. An early example was reported by the He group in 2004 using AgNO3 as the catalyst, 4,4′ ,4′′ -tri-tert-butylterpyridine (tBu3 tpy) as the ligand, and PhI(OAc)2 as the oxidant [123]. A range of carbamates and sulfamates underwent stereospecific intramolecular C—H amidation to afford the five-membered and six-membered ring-insertion products, respectively (Scheme 4.45). The in situ formation of a disilver complex by reaction of AgNO3 with tBu3 tpy was identified. Preliminary mechanistic studies suggested the involvement of a silver nitrene intermediate, but the involvement of a short-lived radical as the reactive intermediate could not be ruled out. It is interesting to note that Shi and coworkers also reported a very similar strategy in 2014 [124].

4.3 Radical Coupling

O R

O

NH2

HN AgNO3 (4 mol%) tBu3tpy (4 mol%)

O

R

O

S

NH2

PhI(OAc)2 CH3CN, 82 °C

O O

13 examples 53–90%

or

or R

O

O HN

S

O O

R

Scheme 4.45 Intramolecular C—H amidation of carbamates and sulfamates.

The He group further developed the intermolecular C(sp3 )—H amination using PhI=NNs (Ns = p-nitrosulfonyl) as the nitrene source under the catalysis of a disilver complex generated in situ from the reaction of AgOTf with 4,7-diphenyl-1,10-phenanthroline (bp) [125]. Both benzylic C—H bonds and inert C—H bonds of cycloalkanes were compatible with this protocol, affording the corresponding amidated products in moderate to good yields (Scheme 4.46(1)). Similarly, Díaz-Requejo and coworkers also reported the intermolecular C—H amidation of unactivated alkanes with complexes Tpx Ag (Tpx = hydrotris(pyrazoyl)borate ligand) as catalysts and PhI=NTs as the nitrene source (Scheme 4.46(2)) [126]. A number of linear and branched alkanes were converted into amides in satisfactory yields with the reactivity decreased in the order tertiary > secondary ≫ primary. Radical trapping experiments confirmed the existence of a radical-based pathway. The authors proposed that the catalyst reacts with PhI=NTs to give silver nitrene intermediate [Ag]=NTs that may display both singlet and triplet configurations. The triplet configuration of this intermediate is responsible for the hydrogen abstraction from the alkane, resulting in the formation of alkyl radical and [Ag]–NHTs. Further interaction of alkyl radical with [Ag]–NHTs gives rise to the final product. NHNs [Ag2(OTf)2(bp)2] (2 mol%) PhI=NNs, CH2Cl2, 50 °C

Tp*,BrAg, PhI=NTs, 80 °C R– H

R – NHTs

10 examples 25–71%

(1)

6 examples 65–90%

(2)

R = 1°, 2°, 3° alkyl

Scheme 4.46 Intermolecular C(sp3 )—H amination.

In 2014, the Schomaker group disclosed the first example of ligand-controlled and site-selective silver-promoted C(sp3 )—H amination [127]. Two silver catalyst systems, namely, (t Bubipy)2 AgOTf and (tpa)AgOTf, were designed to promote tunable, regioselective amination of C—H bonds in different chemical environments: the former generally preferred amination of the most electron-rich C—H

213

214

4 Silver-Mediated Radical Reactions

bonds, while the latter was more sensitive to the steric environment around the reactive site as well as the bond dissociation energy (Scheme 4.47). Preliminary mechanistic studies excluded the presence of long-lived radical species in the reaction pathway; thus if radical intermediates are formed in either pathway, they undergo a rapid rebound, as no loss of stereochemical information is observed. The same group further designed a new silver complex, [(Py5 Me2 )AgOTf ]2 , that displayed much better selectivity for nitrene insertion into propargylic, benzylic, and allylic C—H bonds over tertiary alkyl C—H bonds [128]. The dimeric nature of the silver complex coupled with increased steric bulk around the metal center proved to be the key to the success of this design. Moreover, the Schomaker group also developed the tunable and ligand-controlled intermolecular allylic C—H amination employing sulfamates as the nitrogen source and (tpa)AgOTf as the catalyst [129]. O

AgOTf (10 mol%) (30 mol%)

tBubipy

O H

NH2 S O H

PhIO (3.5 equiv.) CH2Cl2, 4 A MS, rt R1

24 examples up to 20 : 1

R2

R

H

R1, R2 = alkyl

NH R1

R

AgOTf (10 mol%) tpa (12.5 mol%)

R2

O

O HN

R = aryl, alkenyl, alkynyl

O

O S

PhIO (3.5 equiv.) CH2Cl2, 4 A MS, rt

S

O

H

R1 R2

R

Scheme 4.47 Ligand-controlled site-selective intramolecular C(sp3 )—H amination.

Other than the C(sp3 )—N coupling reactions indicated above, C(sp2 )—N coupling reactions could also be implemented under silver catalysis. In 2013, Maiti and coworkers introduced the stereoselective nitration of mono- and disubstituted olefins with AgNO2 and TEMPO (Scheme 4.48) [130, 131]. A wide range of styrenes, heterocyclic olefins, and aliphatic olefins were nitrated smoothly in excellent regio- and stereoselectivity, providing (E)-nitroolefins exclusively. The reactivity of olefins decreased with the increase of substitution. Control experiments indicated that AgNO2 acted as both the nitro radical precursor and the oxidant. A plausible mechanism was proposed by the authors as follows. Thermal decomposition of AgNO2 generates the NO2 radical that adds to an olefin to give the adduct radical. Direct H-abstraction of the adduct radical by TEMPO gives the expected product. Alternatively, the adduct radical is trapped by TEMPO followed by TEMPO-assisted elimination of TEMPOH R2

R2

AgNO2 (3.0 equiv.), TEMPO (0.4 equiv.)

R1 R3

4 A MS, DCE, 70 °C

Scheme 4.48 Nitration of olefins with AgNO2 and TEMPO.

NO2

R1 R3

41 examples up to 97%

4.3 Radical Coupling

to afford the nitroolefin. In both cases, TEMPOH is oxidized back to TEMPO by excess AgNO2 . Interestingly, two silver-free variants for the stereoselective nitration of olefins were also reported by the groups of Maiti and Guo [132, 133]. Silver-mediated decarboxylative C—N coupling provided another convenient route to C—N bond formations. In 2015, Li and coworkers successfully developed the silver-catalyzed decarboxylative azidation of aliphatic carboxylic acids, leading to the convenient and efficient synthesis of various organic azides in aqueous solution under mild conditions (Scheme 4.49) [134]. In the presence of AgNO3 /K2 S2 O8 and with tosyl azide or pyridine-3-sulfonyl azide as the azide source, a wide range of alkyl azides were prepared accordingly. This protocol exhibited excellent functional group compatibility. Notably, the decarboxylation azidation method was then successfully employed as the key step in the asymmetric synthesis of natural alkaloids (−)-indolizidine 209D and 167B, enabling the general and straightforward design toward these indolizidines. On the basis of mechanistic experiments and their previous findings, the authors proposed the mechanism in that the alkyl radical generated via Ag(II)-mediated decarboxylation of carboxylic acid reacts with sulfonyl azide to give the alkyl azide with the concomitant release of the sulfonyl radical. Further oxidation of the sulfonyl radical leads to the formation of arenesulfonic acid. Shortly after Li’s publication, the Jiao group also reported the same reaction under slightly altered conditions [135].

R – CO2H

+

ArSO3N3

Ag2CO3 (cat.) K2S2O8

R – N3

CH3CN/H2O, 50 °C

33 examples 45–92%

R = 1°, 2°, 3° alkyl; Ar = Ts, 3-PySO2

Scheme 4.49 Decarboxylative azidation of aliphatic carboxylic acids.

As a comparison, Natarajan et al. reported the Ag2 CO3 -promoted ipsonitration of carboxylic acids by nitronium tetrafluoroborate [136]. In the presence of Ag2 CO3 and NO2 BF4 , various alkyl, aryl, and heteroaryl carboxylic acids underwent decarboxylative nitration in N, N-dimethylacetamide (DMA) at 90 ∘ C to give the corresponding nitro compounds in good yields (Scheme 4.50). Nevertheless, the detailed mechanism remains unclear. Ag2CO3 (50 mol%) NO2BF4 (1.5 equiv.) R – CO2H

DMA, N2, 90 °C

R – NO2

31 examples 79–93%

R = aryl, heteroaryl, 2°, 3° alkyl

Scheme 4.50 Decarboxylative nitration.

Other miscellaneous advances in silver-mediated C—N coupling reactions could also be found in the literature. For example, Wang and coworkers described the Ag2 CO3 /K2 S2 O8 -mediated amidation of benzoylformic acids

215

216

4 Silver-Mediated Radical Reactions

with tertiary amines via selective carbon–nitrogen bond cleavage [137]. Yao and coworkers synthesized the silver nanoparticle-loaded graphitic carbon nitride as visible light photocatalyst and investigated its application in oxidative amidation of aromatic aldehydes with secondary amines [138]. Liu and coworkers developed the AgNO2 /K2 S2 O8 -mediated oxidative nitration of tertiary benzylic C—H bonds of quinoxalines [139]. Teng et al. reported the Ag2 CO3 -mediated N-trifluoromethylation of sulfoximines with TMSCF3 under oxygen atmosphere [140]. 4.3.4

Formation of C—Halogen Bonds

In 2010, Wu and coworkers reported the silver-catalyzed decarboxylative halogenation of 2-nitrobenzoic acids [141]. With Ag2 CO3 as the catalyst and CuCl2 or CuBr2 as the halogen source, a number of 2-nitrobenzoic acids underwent decarboxylative halogenation in a mixed solvent of DMF and DMSO at elevated temperature under oxygen atmosphere, leading to the corresponding haloarenes in moderate to good yields (Scheme 4.51). The ortho-nitro substitution is crucial for the halodecarboxylation, while other benzoic acids were unreactive. COOH NO2

X

Ag2CO3 (10 mol%) +

R

CuX2 X = Cl, Br

R DMF/DMSO KOH, O2, 130–140 °C

NO2

11 examples 25–85%

Scheme 4.51 Decarboxylative halogenation of o-nitrobenzoic acids.

Hunsdiecker halodecarboxylation is one of the fundamental functional group transformations in organic chemistry. The conventional protocols suffered from many drawbacks such as overloading of metal salts or limited substrate scope. In 2012, Li and coworkers reported the first silver-catalyzed Hunsdiecker reaction of aliphatic carboxylic acids [142]. With Ag(Phen)2 OTf (Phen = 1,10-phenanthroline) as the catalyst and t-BuOCl as the chlorine source, primary, secondary, and tertiary alkyl carboxylic acids all underwent smooth chlorodecarboxylation at room temperature or 45 ∘ C to give the corresponding alkyl chlorides in good to excellent yields, while aromatic acids were inert (Scheme 4.52). This protocol exhibited a wide substrate scope and excellent functional group tolerance. The reactivity of carboxylic acids decreased in the order benzyl ≈ tertiary > secondary > primary ≫ aromatic. Chemoselective chlorodecarboxylation could thus be implemented based on the reactivity pattern. For example, the Ag(Phen)2 OTf-catalyzed reaction of Ag(Phen)2OTf (cat.) t-BuOCl

R – CO2H

R – Cl CH3CN, rt or 45 °C

37 examples 60–95%

R : 1°, 2°, 3° alkyl

Scheme 4.52 Decarboxylative chlorination of aliphatic carboxylic acids.

4.3 Radical Coupling

Figure 4.6 Proposed mechanism of decarboxylative chlorination.

tBuOCl

R – Cl

Ag(I)

Cl

Cl Ag(II)

Ag(I)

Ag(II) R

A

Ag(II) O t Bu RCO2H

CO2

t

Cl

Cl Ag(II) R

O

Ag(II)

Ag(I)

B SET

O

R

BuOH

Ag(II) O O

2,2-dimethylpentanedioic acid with t-BuOCl at room temperature afforded 4-chloro-4-methylpentanoic acid exclusively. The Li group conducted a series of mechanistic experiments, based on which an oxidative radical mechanism was proposed for the decarboxylative chlorination. As depicted in Figure 4.6, the interaction of Ag(I) complex with t-BuOCl generates the dinuclear Ag(II) complex A bridged by tert-butoxide and chloride, which undergoes the ligand exchange upon treatment with an aliphatic acid to give intermediate B. The carboxylate anion in B is then oxidized by an adjacent Ag(II) to give a carboxyl radical and the Ag(II)—Cl—Ag(I) complex. Fast decarboxylation of the carboxyl radical produces the corresponding alkyl radical. The alkyl radical then abstracts a chlorine atom from the Ag(II)—Cl—Ag(I) complex to afford the alkyl chloride, while the Ag(I) complex is regenerated to enter into the next catalytic circle. Interestingly, the above method of decarboxylative chlorination was directly applied into C(sp3 )—H chlorination by Ozawa and Kanai (Scheme 4.53) [143]. Benzylic, tertiary, and secondary C(sp3 )—H bonds were smoothly chlorinated with t-BuOCl in the presence of as low as 0.2 mol% catalyst under air atmosphere. The authors proposed that the homocleavage of the Ag—Ot Bu bond in complex A (in Figure 4.6) generates tert-butoxyl radical, which abstracts a hydrogen atom from a C(sp3 )—H bond of substrate to produce the corresponding carbon-centered radical. Further Cl-transfer from Ag(II)—Cl—Ag(I) complex to the alkyl radical affords the alkyl chloride. Ag(Phen)2OTf (0.2 mol%)

H R1

Cl

t-BuOCl (2.0 or 3.0 equiv.) R2

MeCN, rt, 48 h

R1

R2

22 examples 35–94% yields

Scheme 4.53 Aliphatic C—H chlorination.

The Li group later extended the above chlorodecarboxylation to the bromodecarboxylation of aliphatic carboxylic acids [144]. Thus the Ag(Phen)2 OTf-

217

218

4 Silver-Mediated Radical Reactions

catalyzed reactions of aliphatic carboxylic acids with dibromoisocyanuric acid in 1,2-dichloroethane (DCE) at room temperature provided the corresponding alkyl bromides in satisfactory yields (Scheme 4.54). The reaction exhibited a broad substrate scope and wide functional group compatibility. An oxidative radical mechanism similar to that of silver-catalyzed chlorodecarboxylation shown in Figure 4.6 was proposed. O

Ag(Phen)2OTf (cat.) Dibromoisocyanuric acid R – CO2H

R – Br DCE, rt

29 examples 52 – 93%

R : 1°, 2°, 3° alkyl

HN O

N N

Br O

Br Dibromoisocyanuric acid

Scheme 4.54 Decarboxylative bromination of aliphatic carboxylic acids.

In 2012, Li and coworkers developed a novel decarboxylative fluorination of aliphatic carboxylic acids that used AgNO3 as the catalyst and Selectfluor (1-chloromethyl-4-fluoro-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)) as the fluorine source [145]. The reaction proceeded smoothly in aqueous acetone solution, affording the corresponding alkyl fluorides in good to excellent yields, while aromatic acids were inert (Scheme 4.55). Replacement of Selectfluor by NFSI (N-fluorobis(benzenesulfonyl)imide) resulted in no reaction. This protocol exhibited an excellent functional group tolerance and a wide range of substrate scope. Moreover, chemoselective monofluorination could be successfully implemented for substrates with multiple carboxyl groups based on the observation that the reactivity of carboxylic acids decreased in the order tertiary > secondary > primary ≫ aromatic. AgNO3 (cat.) Selectfluor R – CO2H

R– F Acetone/H2O rt to reflux

29 examples 47–95%

R = 1°, 2°, 3° alkyl

Scheme 4.55 Decarboxylative fluorination of aliphatic carboxylic acids.

Based on their preliminary mechanistic studies, the authors proposed the following mechanism shown in Figure 4.7. The interaction of Ag(I) with Selectfluor generates the trivalent silver intermediate Ag(III)—F presumably via oxidative addition, which then undergoes SET with a carboxylate to give a carboxyl radical and Ag(II)—F. Fast decarboxylation of the carboxyl radical produces the corresponding alkyl radical, which in turn abstracts a fluorine atom from Ag(II)—F to afford the alkyl fluoride and regenerate the Ag(I) catalyst. It is noteworthy that the electrophilic fluorinating agent Selectfluor plays a dual role as both the oxidant and the fluorine source. Moreover, the new concept “silver-assisted fluorine atom

4.3 Radical Coupling

Figure 4.7 Proposed mechanism of decarboxylative fluorination.

Cl N N R–F

2BF4–

F

Ag(I)

Cl N N

2BF4–

F – Ag(III)

F – Ag(II) R

R – CO2H

CO2

transfer” involved in this protocol sets a wide platform for the prosperous development of radical fluorination reactions. Nevertheless, more mechanistic investigations are certainly required to reveal the nature of the fluorodecarboxylation. In this aspect, Flowers and Patel conducted spectroscopic and kinetic studies on the silver-catalyzed fluorodecarboxylation and suggested that Ag(II) generated from the interaction of Ag(I) with Selectfluor is the intermediate oxidant in the reaction [146]. Su and coworkers applied the above method of decarboxylative fluorination into the synthesis of fluticasone propionate, resulting in a much more efficient and eco-friendly synthesis of this corticosteroid (Scheme 4.56(1)) [147]. Goh and Adsool used Li’s protocol in the expedient synthesis of O F O

S O

HO

O

OH AgNO3 (cat.) Selectfluor O

HO

Acetone/H2O 45 °C, 3 h

F O

S O O

(1)

13 examples 25–88%

(2)

18 examples 17–91%

(3)

F 92.7%

O F

F

R1

CO2H R2

O

O

R3

R1

AgNO3 Selectfluor Benzene/H2O reflux,10 h

O

F O

R2 R3

R1 = H, Me; R2, R3 = H, alkyl, aryl

R F Ar

CO2H

R = H, F

AgNO3 (cat.) Selectfluor Acetone/H2O (1 : 1) 55 °C, 1 h

R F Ar

F

Scheme 4.56 Fluorodecarboxylation of α-thio, β-keto, and α-fluoro acids.

219

220

4 Silver-Mediated Radical Reactions

3-fluorobicyclo[1.1.1]pentan-1-amine [148]. Soorukram and coworkers applied the fluorodecarboxylation method in the synthesis of β-fluorinated γ-butyrolactones from paraconic acids and observed that the addition of a stoichiometric amount of AgNO3 considerably improved the efficiency of the reaction (Scheme 4.56(2)) [149]. Gouverneur and coworkers applied the protocol in the synthesis of di- and trifluoromethyl arenes from the corresponding α-fluoro- and α,α-difluoroarylacetic acids (Scheme 4.56(3)) [150]. Moreover, with [18 F]-labeled Selectfluor bis(triflate) as the fluorine source, a variety of 18 F-incorporated di- or trifluoromethylated arenes were successfully prepared. The Li group also successfully applied the protocol to the controlled decarboxylative fluorination of poly(meth)acrylic acids, leading to the novel synthesis of poly(vinyl fluoride-co-acrylic acid) and poly(2-fluoropropene-co-methacrylic acid) copolymers in high yields with well-defined molecular weights and polydispersities [151]. A linear correlation is observed between the extent of fluorination and the amount of Selectfluor, indicating that the copolymers of virtually any monomer ratios can be readily accessed by controlling the amount of Selectfluor. In a similar fashion, Hu and coworkers were able to prepare trifluoromethyl aryl ethers by treating the corresponding α,α-difluoroaryloxyacetic acids with Selectfluor II in the presence of catalytic Ag(I) salt in CH2 Cl2 /H2 O at 80 ∘ C (Scheme 4.57) [152]. Trifluoromethyl aryl sulfides could also be synthesized from the corresponding arylthiodifluoroacetic acids under similar experimental conditions. AgNO3 or AgI (cat.) Selectfluor II

F F

ArO C

ArO – CF2CO2H CH2Cl2/H2O, 80 °C

F

24 examples 26–83%

Scheme 4.57 Fluorodecarboxylation of α,α-difluoroaryloxyacetic acids.

As an extension of the above fluorodecarboxylation, Li et al. introduced the silver-catalyzed fluorination of alkylboronates [153]. Under the catalysis of AgNO3 , the reactions of various alkylboronic acids or their pinacol (pin) esters with Selectfluor in CH2 Cl2 /H2 O afforded the corresponding alkyl fluorides in good to excellent yields (Scheme 4.58(1)). The addition of TFA and/or H3 PO4 proved crucial to achieve satisfactory results as it may help to improve the solubility of boronates in aqueous solution. gem-Difluorides could also be prepared from the corresponding germinal bis(boronates) (Scheme 4.58(2)). A mechanism similar to that of fluorodecarboxylation (Figure 4.7) was proposed as follows: silver nitrate reacts with Selectfluor to give Ag(III)—F that undergoes SET with an alkylboronate to give the corresponding alkyl radical and Ag(II)—F. The subsequent fluorine atom transfer from Ag(II)—F to the alkyl radical affords alkyl fluoride and restores the Ag(I) catalyst. The silver-catalyzed radical fluorination was then extended to benzylic C—H fluorination by Tang and coworkers [154]. With AgNO3 as the catalyst, various arenes underwent C—H difluorination with Selectfluor to provide the

4.3 Radical Coupling

AgNO3 (cat.) Selectfluor R – B(OH)2 or R – Bpin

R–F CH2Cl2/H2O

R = 1°, 2°, 3° alkyl

31 examples 52–92%

(1)

TFA and/or H3PO4

Bpin PhthN Bpin

AgNO3 (cat.) Selectfluor

F PhthN

CH2Cl2/H2O

F

(2)

TFA/H3PO4

Scheme 4.58 Fluorination of alkylboronates.

corresponding difluoromethylated arenes in aqueous solution (Scheme 4.59). The addition of Na2 S2 O8 significantly improved the efficiency of the reaction. H H R

R1

AgNO3 (cat.)

F F

Selectfluor, Na2S2O8 MeCN/H2O, 80 °C

R

R1

31 examples 42–93%

Scheme 4.59 Benzylic C—H fluorination.

In 2017, Zhao and coworkers showed that the direct fluorination of 4,6-disubstituted 2-aminopyrimidines proceeded smoothly in the presence of Ag2 CO3 and Selectfluor in CH3 CN at 70 ∘ C to afford the 5-fluorinated 4,6-disubstituted 2-aminopyrimidines in satisfactory yields (Scheme 4.60) [155]. Based on their preliminary mechanistic studies, the authors proposed a tentative mechanism also shown in Scheme 4.60. The interaction between Ag(I) catalyst and 4,6-disubstituted 2-aminopyrimidines affords A, which is transformed into B upon treatment with Selectfluor. Homolysis of B gives radical species C along with Ag(II)—F. C tautomerizes into its resonance isomer D, which abstracts a fluorine atom from Ag(II)—F to afford the product and regenerate Ag(I) catalyst. Since fluoride salts are much cheaper than electrophilic fluorinating reagents, the development of synthetic methods to form C—F bonds using fluoride ions as the fluorine source is highly demanding. In this context, Hartwig and coworkers described their work on the AgF2 -mediated fluorodecarboxylation for the synthesis of trifluoromethyl aryl ethers (Scheme 4.61) [156]. Upon treating with a combination of AgF2 , AgF, and 2,6-difluoropyridine in CH3 CN, α,α-difluoroaryloxyacetic acids were smoothly transformed into the corresponding aryl trifluoromethyl ethers. This procedure could also be applied in the synthesis of mono- or difluoromethyl ethers from the corresponding aryloxyacetic acids or α-fluoroaryloxyacetic acids in moderate yields. The weak coordination of 2,6-difluoropyridine played an important role in increasing the solubility of AgF2 . The authors proposed a mechanism in which the alkyl radical generated by AgF2 -mediated decarboxylation is quenched by AgF or AgF2 to give the fluorination product.

221

222

4 Silver-Mediated Radical Reactions

NH2

NH2 N

Ag2CO3 (2.0 equiv.)

N

R1

R2

Selectfluor MeCN, 70 °C

F HN Ag(III)F

Selectfluor

N

R1

N

R2

Ag(II)F + R2

B

NH2

NH

NH N

N R2

R1

SET

N

R1

A

N

R2

R1

HN Ag(I) N

10 examples 44–72%

N

N

R1

R1

R2

+ Ag(I) R2

F

D

C

N

N

N

Scheme 4.60 Fluorination of 4,6-disubstituted 2-aminopyrimidines. AgF2, AgF 2,6-difluoropyridine ArO – CF2CO2H MeCN, rt or 35 °C

F ArO C F F

21 examples 41–98%

Scheme 4.61 Fluorodecarboxylation of α,α-difluoroaryloxyacetic acids with AgF2 .

4.4 Radical Addition Radical addition to unsaturated moieties such as C=C bonds has been firmly established as a versatile tool in organic synthesis. Atom transfer radical addition reactions represent a unique class of transformations that are highly atom economic. These radical chain processes can be effectively triggered or initiated by silver catalysts. On the other hand, radical addition to C=C bonds can be followed by the oxidation of the adduct alkyl radicals to the corresponding carbocations and subsequent trapping with nucleophiles, resulting in the difunctionalization of olefins. Silver catalysts have also proved to be extremely useful in these radical polar crossover reactions. 4.4.1

Formation of C—C Bonds

Fluorinated compounds have found widespread applications in pharmaceuticals, agrochemicals, and materials science. The incorporation of fluorine atoms or fluoroalkyl groups into organic molecules has thus attracted a considerable attention in recent years. In this regard, silver-catalyzed radical addition

4.4 Radical Addition

reactions have been demonstrated to be an indispensible tool in the fluorination and fluoroalkylation of unsaturated moieties. In 2013, Maiti and coworkers reported the silver-catalyzed oxidative trifluoromethylation of styrenes [157]. Under the catalysis of AgNO3 and K2 S2 O8 , the reaction of styrenes with Langlois reagent (CF3 SO2 Na) in open flask at room temperature afforded the corresponding α-CF3 -substituted ketones in good yields (Scheme 4.62(1)). An excellent functional group tolerance was observed. The method was also applicable to vinyl cycloalkanes but not aliphatic alkenes with long chains (e.g. dodecene). 18 O labeling experiment revealed that both air and K2 S2 O8 may serve as the source of the oxygen atom in the ketone, while the existence of Ag(0) in the reaction mixture was confirmed X-ray photoelectron spectroscopy (XPS). Thus, a catalytic cycle that involves Ag(I)/Ag(0) is proposed. It is likely that the oxidative decomposition of CF3 SO2 Na gives the CF3 radical, which adds to the C=C double bond followed by subsequent trapping by air or K2 S2 O8 to yield the final product. AgNO3 (20 mol%) K2S2O8 (20 mol%)

O

+ CF3SO2Na

Ar

Ar

Open flask (air) DMF, rt AgNO3 (20 mol%) CF3SO2Na (1.2 equiv.) Ar NMP, O2 , 24 h

CF3

O Ar

CF3

33 examples 42–92%

(1)

29 examples 43–88%

(2)

Scheme 4.62 Synthesis of α-CF3 -substituted ketones using CF3 SO2 Na.

The Maiti group also developed an alternative route toward the synthesis of α-CF3 -substituted ketones under similar conditions using (hetero)arylacetylenes in placement of styrenes (Scheme 4.62(2)) [158]. The cocatalyst K2 S2 O8 was not required in this case. It is likely that the reaction proceeds via the CF3 radical addition to the alkyne. The resulting α-styrenyl radical is trapped by oxygen followed by H-abstraction from the solvent NMP to give the corresponding hydroperoxide intermediate. Subsequent reduction of the peroxide by Ag(0) generates the enol, which tautomerizes to ketone as the final product. The choice of NMP as the solvent proved essential as it can also serve as the hydrogen atom donor. Cai and coworkers later reported the AgF-mediated oxidative trifluoromethylation of styrenes with Ruppert–Prakash reagent (TMSCF3 ) for the synthesis of α-CF3 -substituted ketones (Scheme 4.63(1)) [159]. They also expanded the method to difluoromethylation using TMSCF2 CO2 Et or TMSCF2 CF3 and obtained α-fluoroolefinated ketones as the final product (Scheme 4.63(2)) [159]. Apparently dehydrofluorination occurred in the last step of the difluoromethylation reaction. In another case, Deng and coworkers reported the copper/silver-cocatalyzed oxidative fluoroalkylation of vinylarenes with ICH2 CF3 or ICH2 CHF2 , providing the corresponding β-CF3 - or β-CHF2 -substituted ketones efficiently

223

224

4 Silver-Mediated Radical Reactions

R

Ar

AgF (1.5 equiv.) TMSCF3 (2.0 equiv.)

O CF3

Ar DMF, O2 atmosphere, rt

23 examples 60–90%

(1)

12 examples 25–85%

(2)

R

AgF (1.5 equiv.) F

O

TMSCF2R (2.0 equiv.) Ar

R

Ar

DMF, O2 atmosphere, rt

3

R = CF3 or CO2Et

Scheme 4.63 AgF-mediated di- and trifluoromethylation of styrenes.

+

Ar

Cu(acac)2 (20 mol%) Ag2SO4 (20 mol%) ICH2R

R = CF3 or CHF2

Et3N (1.0 equiv.) TBHP (3.0 equiv.) CH3CN, 80 °C

O Ar

R

27 examples 25–72%

Scheme 4.64 Synthesis of β-CF3 - and β-CHF2 -substituted ketones.

(Scheme 4.64) [160]. TBHP rather than O2 was used as the oxygen source. Nevertheless, the catalytic role of Ag2 SO4 remains unclear. Hydrotrifluoromethylation of unactivated alkenes could also be achieved via silver catalysis. Radical hydrotrifluoromethylation of alkenes had remained challenging for a long time due to the competitive radical atom transfer processes and deprotonative trifluoromethylation. In 2013, the Qing group addressed this problem by using a hydrogen donor to inhibit the annoying side reactions (Scheme 4.65(1)) [161]. With AgNO3 as the catalyst, PhI(OAc)2 as the oxidant, and 1,4-cyclohexadiene (1,4-CHD) as the H-donor, the reaction of unactivated alkenes with TMSCF3 proceeded smoothly in NMP at room AgNO3 (10 mol%) TMSCF3 (8.0 equiv.) PhI(OAc)2 (4.0 equiv.) R

NaOAc (4.0 equiv.) 1,4-CHD (1.0 equiv.) NMP, rt, 24 h AgOTf (2.5 equiv.) PhI(OAc)2 (2.0 equiv.) TMSCF2CO2Et (5 equiv.)

R1 R2

NaOAc (1 equiv.) Hanztsch ester (1.0 equiv.) NMP, rt

H R

CF3

24 examples 45–87%

(1)

O R1

OEt R2 F F

23 examples 47–82%

(2)

Scheme 4.65 Hydrotrifluoromethylation and hydrodifluoromethylation of alkenes.

4.4 Radical Addition

temperature providing the corresponding trifluoromethylated alkanes in satisfactory yields. Monosubstituted alkenes and disubstituted terminal and internal alkenes all proved to be suitable substrates, and a wide range of functional groups were also tolerated. The involvement of CF3 radical was evidenced by mechanistic experiments with radical probes. This method was then extended by Wan and coworkers to the hydrodifluoromethylation of unactivated alkenes with TMSCF2 CO2 Et and Hantzsch ester in place of TMSCF3 and 1,4-CHD (Scheme 4.65(2)) [162]. Very recently, an interesting and novel oxidative fragmentation and reconstruction of enol triflates was reported by Li and coworkers [163]. Upon treatment with (NH4 )2 S2 O8 and a catalytic amount of AgNO3 , a wide range of enol triflates underwent desulfonylation in aqueous solution providing a novel access to α-trifluoromethyl ketones in good to excellent yields (Scheme 4.66). In addition, starting from cyclic enol nonaflates and aromatic enol nonaflates, the corresponding α-perfluoroalkyl ketones were also produced in satisfactory yields. Mechanistic investigations confirmed that the CF3 group in the triflyl group acted as the source of CF3 radical. Thus, it is likely that the CF3 radical addition to an enol triflate followed by β-scission gives the α-trifluoromethylated ketone and a CF3 SO2 radical. The latter expels SO2 to regenerate a CF3 radical that propagates the chain. The combination of Ag(I) and persulfate might serve as the initiator for the radical chain process.

O

O2 S

R1 R2

CF3

AgNO3 (1 mol%) (NH4)2S2O8 (20 mol%) t-BuOH/H2O, 30 °C, 12 h

O CF3

R1 R

2

43 examples up to 99%

R1 = alkyl, aryl; R2 = H, alkyl

Scheme 4.66 Synthesis of α-CF3 ketones from enol triflates.

Silver catalysis also allowed the introduction of fluorine atoms into olefins via carbofluorination. In 2014, Li and coworkers reported the first example of intermolecular carbofluorination of unactivated alkenes [164]. With AgNO3 as the catalyst and Selectfluor as both the oxidant and the fluorine source, the reaction of unactivated alkenes with active methylene compounds occurred in CH2 Cl2 /H2 O/HOAc, leading to the corresponding three-component condensation products under mild conditions (Scheme 4.67(1)). The reactivity of active methylene compounds increases in the order of malonate < malononitrile < cyanoacetate < acetylacetone < acetoacetate. Furthermore, with the promotion of NaOAc, the AgOAc-catalyzed carbofluorination of various unactivated alkenes with Selectfluor and acetone proceeded smoothly in aqueous solution at 50 ∘ C under almost neutral conditions (Scheme 4.67(2)). Mono-, di-, and even trisubstituted alkenes were compatible with this protocol. A variety of functional groups were well tolerated, including labile-free carboxylic acid, unprotected hydroxyl group, and primary alkyl bromide. The carbofluorination could also be extended to the use of ordinary ketones such as cycloalkanones

225

226

4 Silver-Mediated Radical Reactions

E1

AgNO3 (20 mol%) Selectfluor (2 equiv.)

R1

+

E2

R2 CH2Cl2/H2O/AcOH (1: 3 : 1) 50 °C, 12 h

E2

F

19 examples 30–95%

(1)

R3 R2

33 examples 46–97%

(2)

R1

16 examples 44–92%

(3)

R1

E1

2

R

E1, E2 = CN, CO2R, COR AgOAc (cat.) Selectfluor

R3

O

+

R1

R2

F O

NaOAc, H2O 50 °C, 12 h

R1

AgNO3 (cat.) Selectfluor

R1 R2

CH2Cl2/H2O/AcOH/H3PO4 50 °C, 24 h

F HO2C

R2

Scheme 4.67 Carbofluorination of unactivated alkenes.

and 3-pentanone, albeit in a lower efficiency. This radical carbofluorination method provided a convenient and efficient entry to structurally divergent, polyfunctional organofluorine compounds, which serves as valuable building blocks in the synthesis of more complex fluorinated molecules. Based on mechanistic studies, a plausible mechanism was proposed involving the oxidative generation of α-carbonyl radicals and silver-assisted fluorine atom transfer, in close similarity to that of decarboxylative fluorination (see Figure 4.7 in Section 4.3.4). Notably, the carbofluorination was elegantly controlled by radical polar effect. While the electrophilic α-carbonyl radical adds to electron-rich C—C double bond rather than abstracts an F atom from Ag(II)F intermediate, the adduct radical as a nucleophilic alkyl radical does the opposite. Using the combination of Ag(I) and Selectfluor, the Li group later extended the method into the silver-catalytic radical carbofluorination of unactivated alkenes with acetic acids, leading to an efficient and practical access to various γ-fluorinated aliphatic carboxylic acids (Scheme 4.67(3)) [165]. Acetic acids served as both the reagent and the cosolvent. Its sluggishness toward decarboxylation allowed the carbofluorination to occur under mild conditions. However, the extension of this protocol to propanoic acid or butanoic acid failed, probably because the decarboxylative fluorination became competitive. Based on the similar strategy, Duan and coworkers realized the silver-catalyzed decarboxylative acylfluorination of styrenes with α-oxocarboxylic acids and Selectfluor in aqueous solution (Scheme 4.68) [166]. The reaction was promoted by the addition of Na2 SO4 , leading to a novel and efficient synthesis of β-fluorinated ketones in satisfactory yields. However, aliphatic terminal alkenes failed to give expected products. In other cases, Qing and coworkers developed the silver-mediated trifluoromethylfluorination of unactivated alkenes (Scheme 4.69) [167]. The combination of Ag(I) and Selectfluor also enabled both intramolecular and intermolecular fluoroarylation of styrenes with aryldiazonium salts, as reported by Tang and coworkers (Scheme 4.70) [168].

4.4 Radical Addition

R1 Ar

AgNO3 (20 mol%) Selectfluor (1.5 equiv.)

O

+ R

CO2H

O

Na2SO4 (1 equiv.) acetone/H2O (1 : 1), rt

F

21 examples 35–73%

R1

R

Ar

Scheme 4.68 Acylfluorination of styrenes. AgOTf (2.0 equiv.) TMSCF3 (3.0 equiv.) PhI(OAc)2 (1.0 equiv.)

R2 R1 R3

F R2 R1

Selectfluor (3.0 equiv.) CsF (2.0 equiv.), DMF, –20 °C

R3

CF3 15 examples 31–73%

Scheme 4.69 Trifluoromethylfluorination of unactivated alkenes. N2BF4

F

R1

AgOTf, Selectfluor X

2

R

DMA, 25 °C

R2 R1

X = O, NTs

X

40 examples 22–85%

Scheme 4.70 Fluoroarylation of styrenes.

Silver-mediated radical addition reactions have also found applications in the synthesis of nonfluorinated organic compounds. For example, taking advantage of the ease of alkyl radical generation from alkylboronic acids or esters by reaction with Ag(I)/Selectfluor (see Section 4.3.4), Montgomery and Zhao developed the efficient assembly of indanone derivatives through a two-step protocol from vinyl arenes (Scheme 4.71) [169]. In the first step, the copper-catalyzed borylation/ortho-cyanation of styrenes led to the synthesis of o-cyanophenylethylboronates. The boronates were subjected to the treatment with AgNO3 and Selectfluor in the second step, providing the corresponding 1-indanones in satisfactory yields. A radical mechanism was proposed, which involves the alkyl radical addition to cyano group to generate the imine intermediate and subsequent hydrolysis to afford the ketone.

R

Cu(I) B2pin2

Bpin R

PhN(CN)Ts

CN

AgNO3 Selectfluor H2O/CH2Cl2 CF3CO2H, 50 °C

R O 10 examples 37–79%

Scheme 4.71 Synthesis of 1-indanones.

In another case, Li and coworkers introduced the silver-mediated 1,2alkylarylation of styrenes with α-carbonyl alkyl bromides and indoles (Scheme 4.72) [170]. The reaction was catalyzed by iron, providing 3-alkylated indoles in an efficient and highly regioselective manner. No reaction occurred when K2 CO3 or Cs2 CO3 was used in place of Ag2 CO3 . It is likely that the cleavage

227

228

4 Silver-Mediated Radical Reactions

1

R R2

+

Ar

EWG Br

Fe(acac)3 (5 mol%) Ag2CO3 (2.0 equiv.)

+ N R3

R3

R4

N

Dioxane, 120 °C R4

Ar 39 examples 45–97%

EWG = COPh, CO2Me, CO2Et, CN

EWG R1 R2

Scheme 4.72 1,2-Alkylarylation of styrenes.

of the alkyl C—Br bond generates the electrophilic radical, which adds selectively to styrene to form the corresponding benzyl radical. The benzyl radical is then oxidized to benzyl cation either by Fe(III) or by Ag(I), and subsequent trapping by indole gives rise to 3-alkylated indole. 4.4.2

Formation of C–Heteroatom Bonds

Radical fluorination has been demonstrated to be a versatile tool in C(sp3 )—F bond formations. For example, as an extension of silver-catalyzed decarboxylative fluorination of aliphatic carboxylic acids with Selectfluor (see Section 4.3.4), Li and coworkers introduced the intramolecular radical aminofluorination of unactivated alkenes (Scheme 4.73(1)) [171]. With AgNO3 as the catalyst and Selectfluor as both the fluorine source and the oxidant, N-aryl-4-enamides underwent aminofluorination in CH2 Cl2 /H2 O at reflux, leading to the synthesis of the corresponding 5-fluoromethyl-substituted γ-lactams in moderate to excellent yields. Substrates with various substitutions on the aromatic ring and the alkenyl chain were all compatible for the aminofluorination. N-Arylcarbamates and ureas also underwent the expected 5-exo cyclization smoothly. A mechanism similar to that of decarboxylative fluorination was proposed, which involves the silver-catalyzed oxidative generation of amidyl radicals, 5-exo amidyl radical cyclization, and silver-assisted fluorine atom transfer. The Li group went one step further to demonstrate the silver-catalyzed intermolecular radical phosphonofluorination of unactivated alkenes with diethyl phosphite and Selectfluor, O N H

X

Ar

O

AgNO3 (10 mol%) Selectfluor (2 equiv.)

R

N Ar

X

CH2Cl2/H2O (2 : 1) reflux

R

30 examples 50–91%

(1)

31 examples 40–93%

(2)

F

X = C, O, N AgNO3 (cat.) (EtO)2P(O)H (2 equiv.) Selectfluor (2 equiv.)

R3 R2 R1

CH2Cl2/H2O/AcOH 40 °C, 12–48 h

F R3 R2

O P(OEt)2 R1

Scheme 4.73 Aminofluorination and phosphonofluorination of alkenes.

4.4 Radical Addition

providing a convenient and efficient access to β-fluorinated alkylphosphonates in aqueous solution under mild conditions (Scheme 4.73(2)) [172]. The protocol exhibited a broad substrate scope, as not only mono- and disubstituted terminal alkenes but also di- and trisubstituted internal alkenes proved to be suitable substrates. Aside from diethyl phosphite, other phosphorus species such as diisopropylphosphite, ethyl butylphosphinate, and dibutylphosphine oxide all proved to be good reaction partners. Generally, good stereoselectivity was observed, presumably due to the steric effect of bulky phosphonyl groups. A radical mechanism similar to that of aminofluorination was proposed, involving the oxidative generation of phosphonyl radical by Ag(III)F species, addition of electrophilic phosphonyl radical to C=C double bond, and silver-assisted fluorine atom transfer from Ag(II)F species to the adduct radical. Under similar conditions, Li and coworkers were able to develop the silvercatalyzed intramolecular oxyfluorination of unactivated alkenes with oximes, leading to a practical synthesis of various 5-(fluoromethyl)-4,5-dihydroisoxazoles (Scheme 4.74(1)) [173]. A mechanism similar to that of aminofluorination indicated the above was proposed, involving the oxidative generation of oxygen-centered radicals from oximes. The intermolecular hydroxyfluorination of styrenes was later disclosed by Tang and coworkers (Scheme 4.74(2)) [174]. With AgOTf as the catalyst, Sm(OTf )3 as the additive, and Selectfluor as the fluorine source, a variety of styrenes underwent oxyfluorination in PhNO2 /H2 O/MeNO2 at 30 ∘ C, providing the corresponding products with anti-Markovnikov selectivity in good yields. Based on mechanistic investigations and DFT calculations, the authors proposed the mechanism that involves the SET oxidation of styrene followed by trapping with water to generate the benzyl radical. Subsequent fluorination of the benzyl radical with Selectfluor leads to the hydroxyfluorination product.

N

AgOAc (cat.) Selectfluor

OH

R1 R2

R

R3

HOAc (1 equiv.) toluene/H2O, 30 °C

N O

R3

R2

AgOTf (10 mol%) Sm(OTf)3, Selectfluor PhNO2/H2O/MeCN 30 °C

F

R1

17 examples 52 – 72%

(1)

F R

OH 21 examples 41–85%

(2)

Scheme 4.74 Oxyfluorination and hydroxyfluorination of alkenes.

On the other hand, Zhang et al. introduced the silver-catalyzed intermolecular aminofluorination of terminal allenes with NFSI rather than Selectfluor [175]. Thus under the catalysis of AgF, the reaction of allenes with NFSI in CH2 Cl2 at 50 ∘ C afforded the corresponding 2-fluorinated allylamines in good to excellent yields (Scheme 4.75). NFSI acted as both the fluorine source and the amine source. Both 1,1-disubstituted and monosubstituted allenes were compatible

229

230

4 Silver-Mediated Radical Reactions

R1

H + F N

R2

SO2Ar1

SO2Ar2

H

R1

AgF (10 mol%)

F SO2Ar1

R2

CH2Cl2, 50 °C

N

24 examples 43–93%

SO2Ar2

Scheme 4.75 Aminofluorination of allenes. R1

F

R2

NFSI

Ag(I) N(SO2Ph)2

R1 R2

FAg(II)Ag(I) or FAg(II)

FAg(II)Ag(II)N(SO2Ph)2 or FAg(III)N(SO2Ph)2

N(SO2Ph)2 R1 R2

Figure 4.8 Proposed mechanism of aminofluorination of allenes.

with this transformation, whereas electron-deficient allenes failed to react. The protocol also exhibited a wide functional group tolerance. A radical mechanism was proposed by the authors, as illustrated in Figure 4.8. The interaction of AgF and NFSI produces either a dinuclear Ag(II) intermediate such as FAg(II)Ag(II)N(SO2 Ph)2 or a Ag(III) intermediate such as FAg(III)N(SO2 Ph)2 . In either case (PhSO2 )2 N radical is generated along with Ag(II)F via SET. The aminyl radical adds to an allene to give the vinyl radical. Subsequent fluorine transfer from Ag(II)F to the vinyl radical provides the aminofluorination product and regenerates the Ag(I) as a catalyst. Sulfur-centered radicals could also be generated by silver oxidation. In 2014, Yadav and coworkers reported a novel oxysulfonylation of styrenes with thiophenols as the sulfonylation precursors. With a combination of air and K2 S2 O8 as the oxidant, the reaction of styrenes with thiophenols proceeded in DMF at room temperature to give the corresponding β-keto sulfones in good yields (Scheme 4.76(1)) [176]. Mechanistic investigations clearly demonstrated

R1

Ar

+ HS R2

DMF, rt, air

OH R

AgNO3 (20 mol%) K2S2O8 (3.0 equiv.)

+ ArSO2Na

O Ar

O

Ag2CO3 (20 mol%) PhMe, 100 °C

O S 2 R O R1

O

R1

R = Ar, Het, vinyl

Scheme 4.76 Sulfonylation of alkenes and alkynes.

S O

Ar

21 examples 75–94%

(1)

24 examples 30–93%

(2)

4.4 Radical Addition

that the thiyl radical oxidatively generated by Ag(I) adds to styrene followed by trapping with oxygen to afford β-hydroxy sulfide as the key intermediate, which is further oxidized by K2 S2 O8 to form the final product. In the same year, they also reported the oxysulfonylation of styrenes with cheap sodium arenesulfinate salts as the sulfonyl source under very similar conditions [177]. In another case, Bi and coworkers described the silver-catalyzed oxidative sulfonylation of allyl/propargyl alcohols with sodium sulfinates, providing a novel access to diverse γ-keto sulfones (Scheme 4.76(2)) [178]. The Bi group went one step further to develop the aminosulfonylation of alkynes with sodium sulfinates and TMSN3 , furnishing β-sulfonyl N-unprotected enamines in good yields (Scheme 4.77) [179]. The three-component condensation was highly stereoselective and enjoyed a wide substrate scope in that aryl-, heteroaryl-, and alkyl-substituted terminal alkynes as well as aryl and alkyl sulfinates all proved to be suitable coupling partners. Mechanistic investigations revealed the intermediacy of vinyl azides and the critical role of TMSN3 in generating the sulfonyl radical. A mechanism was then proposed by the authors that involves the rapid alkyne hydroazidation and the slow addition of sulfonyl radical to the resultant vinyl azide. The β-elimination of the adduct radical gives N2 and the imine that tautomerizes to enamine.

+ TMSN3 + R2SO2Na

R1

Ag3PO4 (20 mol%) H2O (2.0 equiv.) DMSO, 70 °C

R1 = (hetero)aryl, alkyl, alkenyl R2 = aryl, alkyl

NH2 O 2 R S R1 O 41 examples 45–87%

Scheme 4.77 Aminosulfonylation of alkynes.

The combination of AgSCF3 and K2 S2 O8 allowed the oxidative hydrotrifluoromethylthiolation of terminal alkynes, thus providing a facile synthesis of various vinyl trifluoromethyl sulfides (Scheme 4.78) [180]. Interestingly, Cao and coworkers demonstrated that both anti-Markovnikov and Markovnikov adducts could be obtained selectively by altering the reaction conditions. anti-Markovnikov products were obtained when the reaction was carried out in DMF in the presence of HMPA and 1,10-phenanthrolien (Phen). In contrast, Markovnikov addition products were obtained in DCE under the catalysis of CuCl. While the anti-Markovnikov reaction exhibited a broad substrate scope, the Markovnikov version was limited to phenylacetylenes with para-alkoxy substituents. Control experiments indicated silver(I) acetylide as the key

F3CS R 8 examples 50–81%

AgSCF3 (1.5 equiv.) K2S2O8 (3.0 equiv.) H2O (3.0 equiv.) CuCl (10 mol%) DCE, 100 °C, 17 h

AgSCF3 (1.5 equiv.) K2S2O8 (3.0 equiv.) R

HMPA (50 mol%) phen (10 mol%) DMF, 80 °C, 12 h

Scheme 4.78 Hydrotrifluoromethylthiolation of alkynes.

R

SCF3

23 examples 27–80%

231

232

4 Silver-Mediated Radical Reactions

intermediate, while deuterated experiments pointed out that the two vinylic hydrogens in the anti-Markovnikov products originated from water and DMF. A radical mechanism involving the addition of F3 CS• to silver acetylide was proposed for anti-Markovnikov hydrotrifluoromethylthiolation. However, the mechanism of the Markovnikov addition remains unclear. As indicated above (Scheme 4.73(2)), phosphorus-centered radicals could be readily generated by silver oxidation, which added to C—C double or triple bonds, resulting in C—P bond formations. In this regard, Liu and coworkers reported a simple silver-catalyzed intermolecular hydrophosphonylation of unactivated alkenes with diphenylphosphine oxide, providing a practical synthesis of alkyldiphenylphosphine oxides (Scheme 4.79(1)) [181]. The reaction is likely a radical chain process: diphenylphosphonyl radical initiated by Ag(I) oxidation adds to an alkene to give the adduct radical, which then abstracts an H-atom from Ph2 P(O)H to give the product and regenerate a phosphonyl radical. Phosphonyl radical addition to alkene can be followed by the oxidation of the adduct alkyl radical to give the corresponding carbocation, which is then trapped by a nucleophile to provide the difluonctionalization product of alkene. Zou and coworkers realized this radical polar crossover reaction in the aminophosphonylation of styrenes with diphenylphosphine oxide and anilines (Scheme 4.79(2)) [182]. The reaction was promoted by AgNO3 and catalyzed by CuBr2 . The latter probably helped in oxidizing the benzyl radical intermediate into benzyl cation.

R

Ar1

O + H P Ph Ph

AgF (20 mol%)

P

R

DMF, 110 °C

O + H P Ph + Ar2NH2 Ph

Ph

AgNO3 (2.0 equiv.) CuBr2 (20 mol%) CH3CN, 40 °C

O Ph

NHAr2 Ar

31 examples 30–96%

(1)

38 examples up to 79%

(2)

O PPh2

Scheme 4.79 Phosphonylation of alkenes.

Phosphonylation of alkynes could be designed analogously. For example, Zhao and coworkers reported the silver/copper-cocatalyzed oxyphosphonylation of alkynes with H phosphonates under aerobic conditions, providing a direct synthesis of β-keto phosphonates in high yields (Scheme 4.80(1)) [183]. Wang and coworkers offered an alternative route to β-keto phosphine oxides by silver-catalyzed oxidative decarboxylative coupling of arylpropiolic acids with H-phosphine oxides in air (Scheme 4.80(2)) [184]. Radical nitration reactions could also be mediated by silver. For example, Ma and coworkers reported the nitroaminoxylation of monosubstituted allenes with AgNO2 and TEMPO, providing a facile synthesis of functionalized nitroolefin derivatives in highly regio- and stereoselective manner (Scheme 4.81(1)) [185]. The •NO2 addition to allene followed by trapping by TEMPO is likely the mechanism. In another case, Mao and coworkers described the silver-catalyzed

4.5 Cascade Radical Cyclizations

R1

Ar

R2

AgNO3 (5 mol%) O CuSO4∙5H2O (10 mol%) + H P R4 K2S2O8 (4.0 equiv.) R3 CH2Cl2/H2O, rt, air

O Ag2CO3 (10 mol%) CO2H + H P R EtOH, air R –15 °C to rt R = aryl, alkyl

O R1 R2

O Ar

O P R3 27 examples 56–93% R4

O P R R

26 examples 24–74%

(1)

(2)

Scheme 4.80 Phosphonylation of alkynes. AgNO2 (2.0 equiv.) TEMPO (2.0 equiv.) R

R

NO2 R

O N

NaHCO3 (3.0 equiv.) 1,4-Dioxane, 60 °C

CO2H

t-BuONO Ag2O (5.0 mol%) TEMPO (1.0 equiv.) Benzene, 70 °C, 24 h

O

N

R

22 examples 29–91% E/Z up to 99/1

15 examples 31–83%

(1)

(2)

NO2

Scheme 4.81 Nitroaminoxylation of allenes and alkynes.

decarboxylative nitroaminoxylation of phenylpropiolic acids with t-BuONO and TEMPO, leading to the synthesis of (E)-β-nitroolefinic alkoxyamines in good yields (Scheme 4.81(2)) [186]. The authors proposed the mechanism involving the generation of silver acetylide from decarboxylation of silver propiolate, subsequent NO2 radical addition, and trapping with TEMPO.

4.5 Cascade Radical Cyclizations Radical cyclizations have been demonstrated to be a versatile tool for the synthesis of carbo- and heterocycles of various sizes. As one of the unique characteristics of radical chemistry, cascade radical cyclizations enable the rapid construction of a variety of polycyclic skeletons in one step and thus are extremely attractive in organic synthesis. Silver catalysts have played a vital role in many radical cascades by catalyzing the generation of radicals, by accelerating oxidative rearomatization, and by promoting the radical polar crossover processes. 4.5.1

Formation of C—C Bonds

A variety of carbon-centered radicals could be generated through silver oxidation and then participated in cascade radical reactions. In 2013, Duan and coworkers

233

234

4 Silver-Mediated Radical Reactions

reported the silver-catalyzed decarboxylative acylarylation of N-arylacrylamides with easily available α-oxocarboxylic acids, providing a practical synthesis of functionalized oxindoles (Scheme 4.82) [187]. The reaction proceeded in aqueous solution and exhibited a good functional group tolerance and broad substrate scope. The N-substitution (R2 ) is crucial to the success of the transformation as the NH analogs failed to give the cyclized products. This may be attributed to the fact that N-substitution makes the conformations required for radical cyclization more favorable. A plausible mechanism was proposed that consists of (i) Ag(II)-mediated oxidative decarboxylation of α-oxocarboxylic acids to generate acyl radicals, (ii) addition of acyl radicals to C=C double bond followed by cyclization onto aryl ring to give cyclohexadienyl radicals, and (iii) oxidative rearomatization of cyclohexadienyl radicals to provide the final product.

O

R1

+

N R2

R

CO2H

R3

O R3

AgNO3 (10 mol%) K2S2O8 (1.0 equiv.)

O

Acetone/H2O or H2O, 50 °C

R1

R

O

23 examples 44–92%

N R2

R = (hetero)aryl, Me

Scheme 4.82 Acylarylation of N-arylacrylamides.

Interestingly, the above protocol was extended to include a number of radical precursors other than α-oxocarboxylic acids, leading to the construction of 2-oxindoles bearing various functionalities. For example, α,α-difluoroarylacetic acids were used in place of α-oxycarboxylic acids to produce the corresponding difluoromethylated oxindoles [188]. 1,3-Dicarbonyl compounds and even simple ketones were adopted as α-keto radical precursors to react with N-arylacrylamides under almost identical conditions, affording the corresponding oxindoles in high efficiency [189]. Langlois reagent (CF3 SO2 Na) and zinc bis(difluoromethanesulfinate) were employed by Tan and coworkers as CF3 and HCF2 radical precursors and the corresponding tri- and difluoromethylated oxindoles were achieved, respectively [190]. As a comparison, Chen and coworkers described the AgF-mediated trifluormethylarylation of N-arylacrylamides with TMSCF3 in DMF at 100 ∘ C, providing an alternative route to trifluoromethylated oxindoles [191]. Wang et al. treated N-arylacrylamides with α,α-difluoro-α-(TMS)-acetamide in the presence of AgOAc as the catalyst and DIB as the oxidant, and the corresponding difluorinated oxindoles were obtained in satisfactory yields (Scheme 4.83) [192].

R1

N R2

+ TMS R3

F F

F

AgOAc (15 mol%) DIB (3.0 equiv.)

O

O

NR2

R3 O

CH3CN, 80 °C

Scheme 4.83 Difluoroamidation of N-arylacrylamides.

C(O)NR2 F

R1

N R2

22 examples 48–92%

4.5 Cascade Radical Cyclizations

The above strategy could also be extended to the construction of six-membered ring. Thus, Mai et al. developed the silver-catalyzed decarboxylative radical addition–cyclization of N-arylcinnamamides with aliphatic carboxylic acids, affording 3,4-disubstituted dihydroquinolin-2(1H)-ones in aqueous solution (Scheme 4.84) [193]. Meanwhile, with CF3 SO2 Na as the CF3 radical source, 3-trifluoromethylated 3,4-dihydroquinolin-2(1H)-ones could also be prepared in satisfactory yields under similar reaction conditions. In a similar fashion, α-oxycarboxylic acids were used as acyl radical precursors to participate in the reaction with N-arylcinnamamides to afford 3-acyl-4aryldihydroquinolin-2(1H)-ones. By increasing the amount of K2 S2 O8 , 3-acyl-4arylquinoline-2(1H)-ones could be achieved by further oxidative aromatization [194]. Coincidently, Duan and coworkers also reported the same transformation under very similar conditions at about the same time [195].

O

R1

Ar

N R2

+ R CO2H

R = 1°, 2°, 3° alkyl

Ar

AgNO3 (20 mol%) K2S2O8 CH3CN/H2O 100 °C, 12 h

R R1 N O R2 33 examples, 30–86%

Scheme 4.84 Synthesis of 3-alkyl-4-aryldihydroquinolin-2(1H)-ones.

The above protocol could also be extended to the synthesis of coumarins from aryl 3-arylpropiolates. Wang and coworkers offered a facile entry to 3-acylcoumarin derivatives by AgNO3 -mediated oxidative cyclization of 3-arylpropiolates with α-keto acids (Scheme 4.85(1)) at 60 ∘ C [196]. Interestingly, when the reaction was performed at 80 ∘ C with Ag2 CO3 as the catalyst, the rearrangement products were obtained, as reported by Ding and coworkers (Scheme 4.85(2)) [197]. While the normal product is formed by 6-endo cyclization of vinyl radicals, the rearrangement product may result from the 5-exo cyclization of vinyl radicals followed by oxidation and subsequent ester migration, as proposed by Ding et al. The relatively slow rate of acyl radical Ar1 O

R

+ O

Ar2

O + O

O Ar2

(1)

O O 28 examples, up to 78%

Ar1

O

Ar1 R

CO2H CH3CN/H2O, 60 °C

O

R

AgNO3 (1.0 equiv.) K2S2O8 (4.0 equiv.)

Ag2CO3 (20 mol%) K2S2O8 (2.0 equiv.)

R1

CO2H NaOAc (2.5 equiv.) CH3CN/H2O, 80 °C R1 = Ph, Me

Scheme 4.85 Synthesis of 3-acylcoumarins.

Ar1

O R1

R O O 20 examples, 45–78%

(2)

235

236

4 Silver-Mediated Radical Reactions

formation in the presence of catalytic Ag2 CO3 as well as the relatively high temperature might account for the unexpected 5-exo cyclization. The oxidative radical decarboxylation/addition/cyclization cascade was also employed for the construction of carbonyl-containing quinoline-2,4(1H,3H)diones [198]. In the presence of AgNO3 /(NH4 )2 S2 O8 , the reaction of o-cyanoarylacrylamides with α-keto acids in aqueous acetone at 120 ∘ C provided the corresponding products quinoline-2,4-diones in moderate to good yields (Scheme 4.86(1)). Apparently the α-carbamoyl radical intermediate attacks the C≡N bond rather than the aryl ring to give iminyl radical. Subsequent H-abstraction followed by hydrolysis gives rise to the ketone. In another case, Hao and coworkers reported the silver-catalyzed bicyclization of N-tethered 1,7-enynes for the diastereoselective synthesis of polycyclic 3,4-dihydroquinolin-2(1H)-ones (Scheme 4.86(2)) [199]. It is likely that the 6-exo cyclization of α-carbamoyl radical intermediate onto C≡C bond gives the vinyl radical, which undergoes 1,5-H-abstraction followed by 5-endo cyclization to generate the corresponding benzyl radical. Further oxidation of the benzyl radical by Ag(II) and subsequent deprotonation furnish the tricyclic alkene as the final product. This [2 + 2 + 1]-annulation strategy was also designed by Li and coworkers for the synthesis of 2,3-dihydro-1H-cyclopenta[b]benzofurans from O-tethered 1,7-enynes [200]. N O

R1 X

+ R

N R2

AgNO3 (5 mol%) (NH4)2S2O8 (1.0 equiv.)

O

R

N R2

O

O

(1)

38 examples, 34–87%

O N R2

X

R3

R4 R

R3

R1

CO2H Acetone/H2O, 120 °C

X = C, N

1

O

+ HO2C H R3

R5 R6

AgNO3 (10 mol%) K2S2O8 (4.0 equiv.) CH3CN/H2O 60 or 80 °C

R4

R1

R5 R2

R6

N

(2)

R3

O 41 examples, up to 75%

Scheme 4.86 Synthesis of functionalized quinolin-2(1H)-ones.

Very recently, Li et al. reported the silver-catalyzed oxidative intermolecular [3 + 2]/[5 + 2]-annulation of N-arylpropiolamides with 4-vinyl acids, leading to the synthesis of fused 2H-benzo[b]azepin-2-ones (Scheme 4.87) [201]. This radical cascade starts with the decarboxylation of vinyl acid to generate the corresponding alkyl radical, which adds intermolecularly to the C≡C bond of acrylamide. The resulting vinyl radical cyclizes to the C=C bond rather the aryl ring, and the adduct radical attacks the aryl ring in a 7-endo cyclization mode. Further oxidative aromatization leads to the final product. Radical polar effect and conformational effect nicely direct the reaction pathways as planned. Moreover, this strategy was applied to intermolecular [3 + 2]-annulation of 4-vinyl acids with

4.5 Cascade Radical Cyclizations

H R6

H R

R4

R3

R4

R O

n

R1

R3

AgNO3, K2S2O8 CH3CN/H2O 40 °C, 16 h

R2

HO

14 examples up to 87%

R

N R5

6

O

R5

N

R4 R3

n

R1

R2

n = 1, 2

AgNO3, K2S2O8 CH3CN/H2O 40 °C, 16 h

O

n

R1

R3

29 examples up to 90%

Scheme 4.87 Cascade reactions of vinyl acids with alkynes.

a wide range of terminal alkynes, providing a facile entry to multisubstituted cyclopentenes in good yields (Scheme 4.87). 2-Isocyanobiaryls represent another famous class of radical acceptors widely employed to testify radical mechanisms. The addition of a carbon-centered radical to the isonitrile generates the corresponding imidoyl radical, which then cyclizes to the arene to form cyclohexadienyl radical. Subsequent oxidative aromatization provides the phenanthridine product. Silver-mediated radical reactions have allowed the introduction of a variety of functionalities onto the phenanthridine skeleton. For example, Lei and coworkers reported the first silver-catalyzed radical decarboxylation/cyclization of α-oxocarboxylates with isocyanides, providing a novel synthetic approach to 6-acylated phenanthridines (Scheme 4.88(1)) [202]. Wan et al. used α,α-difluoroarylacetates in place of α-oxocarboxylates for the preparation of 6-difluoromethylated phenanthridines under similar conditions [203]. Li and coworkers employed alkanoic acids as alkyl radical precursors to synthesize 6-alkylphenanthridines. The Li group also extended the protocol to the reaction of vinyl isonitriles with carboxylic acids to produce 1-alkylisoquinolines (Scheme 4.88(2)) [204]. In another case, the Ag2 CO3 /K2 S2 O8 -mediated reaction of α-oxocarboxylates with 2-isocyanoacetates afforded the corresponding oxazoles [205].

R2

Ag2CO3 (10 mol%) Na2S2O8 (2.0 equiv.)

O +

R1

Ar

CO2K

Ar

N

(1)

O 18 examples, 39–85%

R1

R1

N

R1

DMSO, 100 °C, 6 h

NC

C

R2

CO2R2

RCO2H (2.0 equiv.) Ag2CO3 (20 mol%) K2S2O8 (2.0 equiv.) K3PO4 (1.0 equiv.) MeCN/H2O, 70 °C

R1

R1 (2) R

N

CO2R2

19 examples, 41–97%

Scheme 4.88 Synthesis of phenanthridines and isoquinolines.

237

238

4 Silver-Mediated Radical Reactions

Oxidative homodimerization of enamino ketones or esters for the synthesis of pyrroles has been extensively studied. However, this protocol suffered from limited substrate scope, and pure aldehyde enamines are rarely employed due to their instability. In 2010, Jia and coworkers demonstrated the first efficient and direct approach to polysubstituted pyrroles from the oxidative homodimerization of aldehyde enamines formed in situ by reaction of amines and aldehydes [206]. In the presence of stoichiometric AgOAc and NaOAc, various amines including anilines and aliphatic amines reacted with aldehydes to give the expected products in satisfactory yields (Scheme 4.89(1)). This method was then successfully applied in the rapid assembly of marine natural product purpurone, a potent ATP-citrate lyase inhibitor. A plausible mechanism was proposed as follows. The in situ generated imine tautomerizes to enamine, which is oxidized by Ag(I) to the α-imine radical cation. This transient species undergoes homocoupling to give the diimine. The aromatization of the diimine leads to the pyrrole product. It could be expected that the further oxidation of the α-imine radical cation would lead to the corresponding carbocation, which could be trapped by a carbon-centered nucleophile. Based on this idea, Li and coworkers developed the Ag2 CO3 -mediated cross-coupling between enamino esters and acetone at 110 ∘ C, furnishing the corresponding tetrasubstituted pyrroles in satisfactory yields [207]. Similarly, Lei described the cross-coupling of enamino esters with arylacetylenes in DMSO at 80 ∘ C, providing a novel entry to multisubstituted pyrroles [208]. Analogously, Liang and coworkers treated 2-pyridylacetate with arylacetylenes and Ag2 CO3 in DMF at 120 ∘ C and obtained the corresponding indolizine products [209]. However, it should be pointed out that the detailed mechanisms of the above pyrrole synthesis remains unclear, while purely ionic processes cannot be ruled out at this time.

R1 NH2

+

R2

O

AgOAc (2.0 equiv.) NaOAc (2.0 equiv.)

R2

R2 22 examples 25–80%

N R1

THF, 60 °C, 8 h

R1 = aryl, alkyl, H; R2 = aryl, alkyl

(1)

R1 R1

+ R2

N

Ag2CO3 (10 mol%) C

NMP or dioxane, 80 °C

R2

N H

34 examples 42–99%

(2)

Scheme 4.89 Synthesis of pyrroles.

Another method for pyrrole synthesis was the silver-catalyzed [3 + 2]cycloaddition between isocyanides and alkynes, as independently reported by the groups of Lei and Bi (Scheme 4.89(2)) [210, 211]. While non-radical mechanism involving the intermediacy of silver acetylides was initially proposed by both groups, a radical mechanism involving the oxidative generation of α-isocyanyl radical followed by addition to silver acetylide intermediate was later presented by Bi and coworkers based mainly on density functional calculations

4.5 Cascade Radical Cyclizations

[212]. However, it is somewhat suspectable that, according to the mechanism, the radical adds to silver acetylide to give β-arylvinyl radical rather than α-arylvinyl radical. Much as pyrroles, furans are also important structural motifs in many natural products and biologically active molecules, and thus their synthesis has attracted a considerable attention. In 2012, Lei and coworkers described the Ag2 CO3 -mediated oxidative coupling of terminal alkynes with 1,3-dicarbonyl compounds, leading to various polysubstituted furans in satisfactory yields (Scheme 4.90(1)) [213]. This protocol is efficient and operationally simple. In addition, the silver salts could be recycled conveniently by filtration and treating with nitric acid and Na2 CO3 . Based on their preliminary mechanistic studies, the authors suggested that silver acetylide might be the intermediate in the reaction and that the reaction might not process via oxidative radical cyclization. However, Novak and coworkers carried out the density functional calculations on the mechanism with ethyl acetoacetate and phenylacetylene as the model substrates and proposed that the deprotonation of acetoacetate followed by Ag(I) oxidation generates the α-carbonyl radical, which undergoes coupling with silver acetylide to give the propargyl ketone intermediate [214]. This analysis is highly questionable. In fact, Liu et al. reported the similar reaction with phenylpropiolate as an internal alkyne and obtained 3-phenyl-substituted furans (Scheme 4.90(2)) [215]. Radical addition to phenylpropiolate is more likely to give α-phenylvinyl radical, resulting in the formation of 2-phenyl-substituted furan rather than 3-phenyl-substituted one. It is possible that Ag(I) act simply as a Lewis acid in the above furan synthesis due to its alkynophilic nature.

O

O

R1

R2

O R1

+ Ar

DMF, 80 °C, 12 h

CO2Et

O R2

+

O

Ag2CO3 (2.0 equiv.) KOAc (2.0 equiv.) Ar

R1 26 examples 39–95% R2

O

(1)

O Ag2CO3 (1.2 equiv.) DMA, 120 °C, 3 h

R

R EtO2C

O

R1 13 examples 50–88% R2

(2)

R - Ph, CO2Et, H

Scheme 4.90 Synthesis of furans.

In sharp contrast, when the same two coupling partners in the above furan synthesis were subjected to a convincing oxidative radical condition, α-naphthols rather than furans were achieved, as reported by Narender and coworkers [216]. Thus with AgOAc as the catalyst, SDS as the surfactant, and Na2 S2 O8 as the oxidant, the reaction of benzoylacetate with alkynes in water at 60 ∘ C furnished the corresponding α-naphthols in high yields (Scheme 4.91). This protocol exhibited a wide substrate scope as not only terminal aryl- and alkylacetylenes but also internal alkynes such as arylpropiolates were all suitable coupling partners. It is

239

240

4 Silver-Mediated Radical Reactions

O R

R3

O OR2

1

OH

AgOAc (30 mol%) Na2S2O8 (1.0 equiv.)

+

OR2

R1

SDS (20 mol%) H2O, 60 °C, 3 h

R4

O

R3 4

R

49 examples, 41–75%

Scheme 4.91 Synthesis of α-naphthols.

worth mentioning that in the cases of arylpropiolates, 4-aryl-substituted naphthols rather than 3-aryl-substituted ones were isolated, a regioselectivity opposite to that in the above furan synthesis. The mechanism is likely that the Ag(II) oxidation of benzoylacetate generates the α-carbonyl radical, which adds to an alkyne followed by cyclization onto the arene. Further oxidative rearomatization gives rise to the α-naphthol. Silver-mediated oxidation of 1,3-dicarbonyls could be further utilized in the construction of polycyclic skeletons. For example, Lee et al. developed the synthesis of dihydrofuroquinolinones in moderate yields by Ag2 CO3 /Celite-promoted oxidative cycloaddition between 4-hydroxy-2-quinolones and olefins (Scheme 4.92(1)) [217]. Hong et al. reported the Ag2 CO3 -mediated sequential oxidative dimerization and cycloaddition of 1,3-cyclohexadiones to fulvenes, providing a facile synthesis of cyclopenta[b]chromenes (Scheme 4.92(2)) [218]. Silver-catalyzed decarboxylation could also be utilized in the synthesis of polycyclic compounds. For example, Zhang and coworkers reported a novel synthesis of naphtha[2,3-a]carbazole-5,13-diones from naphthoquinones and indol-3-ylpropanoic acids under the catalysis of AgOAc (Scheme 4.93(1)) [219]. The pentacyclic carbazoles were assembled via a tandem radical decarboxylation–alkylation–cyclization–aromatization sequence. In another example, Chuang and coworkers utilized α-keto acids to react with 2-(1-hydroxyalkyl)-1,4-naphthoquinones or 2-(1-amidoalkyl)-1,4naphthoquinones under typical radical decarboxylation conditions (AgNO3 / K2 S2 O8 ), providing a facile entry to naphtha[c]furan-4,7-diones and benzo[f ] isoindole-4,9-diones (Scheme 4.93(2)) [220]. R1

OH

O + R1

N R

O

R2

O + O

R3

Ag2CO3/celite R2

R2

CH3CN, reflux

Ag2CO3 CH3CN reflux

O

N R R2 O

O O

(1)

O 16 examples 30–78%

R3 5 examples 85–92%

Scheme 4.92 Synthesis of dihydrofuroquinolinones and cyclopenta[b]chromenes.

(2)

4.5 Cascade Radical Cyclizations

O

AgOAc (30 mol%) (NH4)2S2O8 CO2H

Br + N R2

OR1 O

O

R2 N (1)

CH3CN/H2O, 80 °C OR1 O 12 examples, 52–72%

O

X

O R1

O +

OH

R3 O

(2)

X

CH3CN/H2O, 70 °C R3 O 21 examples, up to 84%

O X = OH or

R1

AgNO3, K2S2O8

NHR2

Scheme 4.93 Synthesis of polycyclic carbazoles, pyrroles, and furans.

Polyphenols are another type of compounds easily undergoing oligomerization. As an example, Sako et al. developed the silver-mediated oxidative dimerization of 4-hydroxystilbenes, leading to a variety of dihydrobenzofurans of interesting biological activities (Scheme 4.94) [221]. A mechanism was proposed to involve the SET oxidation of the substrate by AgOAc to produce phenoxyl radical and subsequent regioselective homocoupling. A similar silver-mediated oxidative coupling of caffeic esters was also reported [222]. HO HO OH

AgOAc (1.0 equiv.) MeOH, 50 °C, 1 h

OH HO OH

OH

97%

OH

Scheme 4.94 Dimerization of resveratrol.

4.5.2

Formation of C—O/S/Se Bonds

Heteroatom-centered radicals such as thiyl radicals could be oxidatively generated under the catalysis of silver ion, which then took part in radical cascade reactions. A number of nice examples have been developed in this context in the past few years. For example, the silver-catalyzed radical addition–cyclization reaction of thiophenols with N-benzoylacrylamides under aerobic conditions provided sulfone-containing isoquinolinonediones, as reported by Xia et al. (Scheme 4.95(1)) [223]. Thiyl radicals obviously triggered the cascade process. The resulting sulfides were further oxidized to sulfones under the reaction conditions. The AgCl-catalyzed condensation of thiophenols with N-arylpropiolamides was also triggered by thiyl radicals, affording 3-thioazaspiro[4,5]trienones in good yields (Scheme 4.95(2)) [224]. In this reaction the radical addition–ipso-cyclization was followed by

241

242

4 Silver-Mediated Radical Reactions

O

O + Ar SH

N

R

O

AgNO3 (10 mol%) K2S2O8 (3.0 equiv.)

N O O R S Ar O 21 examples, 28–75%

1 atm O2 DMF, 80 °C

R1 + N R

R2

O

R1 O

Ar SH

AgCl (10 mol%) H2O (3.0 equiv.)

SAr R1

Dioxane, 80 °C, air

(1)

N

(2)

R

O 22 examples, 32–77%

Scheme 4.95 Thiolation of alkenes and alkynes.

oxidation, subsequent trapping with water, and further oxidation to ketone. The same cascade also prevailed in AgSCF3 /K2 S2 O8 /TBHP-mediated reaction of N-arylpropiolamides, leading to the preparation of 3-CF3 S-substituted azaspiro[4,5]trienones [225]. The increasing importance of trifluoromethylthiyl moiety in pharmaceuticals and agrochemicals has urged the development of new methods for its incorporation into organic molecules under mild conditions. In this regard, Wang and coworker developed the first silver-mediated radical aryltrifluoromethylthiolation of activated alkenes [226]. With K2 S2 O8 as the oxidant and HMPA as the additive, the reaction of N-arylacrylamides with AgSCF3 in acetonitrile provided the trifluoromethylthio-containing oxindoles efficiently (Scheme 4.96(1)) [226]. Under similar conditions, 3-trifluoromethylthiolated coumarins were

R2

AgSCF3 (1.5 equiv.) HMPA (0.5 equiv.)

O

K2S2O8 (3.0 equiv.) CH3CN, 75 °C, N2

R1 N R R2

AgSCF3 (2.0 equiv.) K2S2O8 (4.0 equiv.)

R1

DMSO, 30 °C, Ar O O

R1

R2 NaHCO3 (1.5 equiv.) DMSO, 80 °C, Ar

26 examples 30–91%

(1)

SCF3 25 examples up to 80% O

(2)

R1

O N R R2

R1 O

O AgSCF3 (1.5 equiv.) K2S2O8 (2.0 equiv.)

SCF3

R2

O R1

SCF3 R2

Scheme 4.96 Aryltrifluoromethylthiolation of alkenes and alkynes.

24 examples 31–92%

(3)

4.5 Cascade Radical Cyclizations

synthesized in good yields from aryl propiolates (Scheme 4.96(2)) [227], and 2-trifluoromethylthiolated indenones were prepared from arylpropynones (Scheme 4.96(3)) [228]. In a similar fashion, the reaction of 1,6-enynes with AgSCF3 furnished trifluoromethylthiolated polycyclic fluorene compounds in satisfactory yields (Scheme 4.97(1)) [229]. The use of a catalytic amount of 2,2′ :6′ ,2′′ -terpyridine helped to increase the product yield. The C≡C triple bond served as the primary acceptor of thiyl radicals, and the subsequent 6-exo cyclization onto C=C double bond was followed by the 5-exo cyclization onto the arene. Alternatively, the cyclization of 1,6-enynes could also be triggered by sulfonyl radicals. This was evidenced by AgNO3 -catalyzed condensation of allyl propiolates with sodium sulfinates using K2 S2 O8 and HNO3 as the oxidants, leading to the highly stereoselective synthesis of sulfonylated γ-lactones (Scheme 4.97(2)) [230]. In this transformation the sulfonyl radical attacks selectively the C=C double bond of 1,6-enyne. Apparently steric effects play a key role in directing the reaction pathways. AgSCF3 (1.5 equiv.) HMPA (0.5 equiv.) Terpyridine (10 mol%) X Y R

K2S2O8 (3.0 equiv.) CH3CN/DMF, 80 °C

R1 + R SO Na 2

O R2

(1) SCF3

R

37 examples up to 87%

X = NTs, C(CO2Me)2, Y = CH2 X = O, Y = C(O) O

X Y

H

AgNO3 (10 mol%) K2S2O8 (2.0 equiv.) HNO3 (1.0 equiv.) CH3CN, 90 °C

R1 R2

(2)

O O

SO2R

29 examples up to 92%

R = alkyl, aryl

Scheme 4.97 Cyclization of 1,6-enynes triggered by thiyl radicals.

Another example of trifluoromethylthiolation was recently reported by Shi and coworkers [231]. By taking advantage of the fast ring-opening of cyclopropylalkyl radicals, the AgSCF3 /Na2 S2 O8 -mediated reaction of benzylidenecyclopropanes in DMSO at 80 ∘ C afforded trifluoromethylthiolated 1,2-dihydronaphthalene derivatives (Scheme 4.98). Moreover, the obtained products could undergo further aromatization upon oxidation with Na2 S2 O8 , thus offering a facile access to trifluoromethylthiolated naphthalenes.

R1

+ AgSCF3

Na2S2O8 DMSO, HMPA 80 °C, 6 h

R1

18 examples SCF3 up to 65%

Scheme 4.98 Synthesis of trifluoromethylthiolated 1,2-dihydronaphthalenes.

243

244

4 Silver-Mediated Radical Reactions

Very recently, Bi and coworkers introduced a three-component condensation reaction of biphenyl acetylenes, TMSN3 , and sodium sulfinates under the catalysis of Ag3 PO4 , providing a novel synthesis of 6-sulfonylmethylated phenanthridines (Scheme 4.99) [232]. Mechanistic studies indicated the intermediacy of biphenyl vinyl azide (also see Section 4.4.2). Accordingly, a plausible mechanism was proposed involving the sulfonyl radical addition to vinyl azide to produce the iminyl radical with the release of N2 . The iminyl radical cyclization onto the aryl ring is followed by oxidative aromatization to give the phenanthridine. R1 + TMSN3 + R3SO2Na

R1

Ag3PO4 (20 mol%) H2O (2.0 equiv.)

N

DMSO, 70 °C 26 examples 43–74%

R2

O S O R3

R2

Scheme 4.99 Synthesis of 6-sulfonylmethylated phenanthridines.

4.5.3

Formation of C—N/P Bonds

In 2013, the Yang group reported the first silver-catalyzed phosphonoarylation of alkenes via a tandem radical process (Scheme 4.100(1)) [233]. With AgNO3 as the catalyst and Mg(NO3 )2 ⋅6H2 O as the additive, N-arylacrylamides reacted with diphenylphosphine oxide in CH3 CN at 100 ∘ C, leading to the R3 R1 N R2

O + H P R5 O R4

Ar R1 N R

N R2

CH3CN, 100 °C

AgNO3 (15 mol%) O Mg(NO3)2∙6H2O (0.3 equiv.) + H PPh2 CH3CN, 4A MS, 100 °C

Ar

O

R1

O

AgNO3 (5 mol%) Mg(NO3)2∙6H2O (0.8 equiv.)

O + H P R R

R2

O PR4R5

R1

O N R2 29 examples, up to 87% Ar

O PPh2

R1

(2)

N O R 22 examples, 52–75% O

AgOAc (10 mol%) Zn(NO3)2∙6H2O (0.5 equiv.)

N

O R P R Ar

CH3CN, 100 °C, Ar R1

R2

30 examples, up to 82%

Scheme 4.100 Phosphorylation of N-arylacrylamides.

(1)

(3)

4.5 Cascade Radical Cyclizations

corresponding phosphorylated oxindoles in moderate to excellent yields. Mechanistic experiments suggested the intermediacy of Ph2 P(O)Ag species, which adds to acrylamide to give the α-carbamoyl radical. Subsequent cyclization and aromatization produced the oxindole. It is likely that Mg(NO3 )2 ⋅6H2 O helped in oxidizing Ag(0) back to Ag(I). Under almost identical conditions, the reaction of N-arylcinnamamides with diphenylphosphine oxide proceeded in a mode of 6-endo cyclization, furnishing the synthesis of 3,4-disubstituted dihydroquinolin-2(1H)-ones in good yields (Scheme 4.100(2)) [234]. The regioselectivity of phosphonyl radical addition was nicely directed by the cinnamic aryl group. In a similar fashion, the silver-catalyzed reaction of indole-based cinnamamides with diarylphosphine oxides produced phosphonylated pyrrolo[1,2-a]indoles with high chemo- and diastereoselectivity under mild conditions (Scheme 4.100(3)) [235, 236]. Indole-based arylpropiolamides also underwent this radical cascade smoothly. Based on a similar strategy, Wu and coworkers developed the silver-catalyzed reaction of aryl alkynoates with dialkyl phosphites, thus providing a facile synthesis of 3-phosphonylated coumarins in satisfactory yields (Scheme 4.101(1)) [237]. Under similar conditions, the silver-catalyzed reaction of N-(p-methoxyaryl)propiolamides with dialkyl phosphites offered a facile access to various phosphonylated aza-decenones in satisfactory yields (Scheme 4.101(2)) [238]. Furthermore, phosphonylated indoloazepinone derivatives could be readily prepared from the oxidative cyclization of 2- or O

O O + H P R2 R2

R1

R

Ag2CO3 (10 mol%) Mg(NO3)2.6H2O 4 Å MS, CH3CN 100 °C, 12 h, air

R R1 O

O 2 R P 2 R

(1)

O

22 examples, 31–90% O R

R3

O

N R2

R1

O + H P R3 R3

AgNO3 (10 mol%) Mg(NO3)2.6H2O CH3CN 100 °C, air

P

O R N

R2

O

N

N R2

16 examples up to 92% R3

R3 O + H P Ar Ar

R1

(2)

R1

OMe

O

R3

O

AgOAc (10 mol%) Zn(NO3)2.6H2O THF, 60 °C, Ar

Ar

Scheme 4.101 Phosphorylation of alkynes.

1

R

N O P Ar2

N Ar1 R2 25 examples, up to 83%

(3)

245

246

4 Silver-Mediated Radical Reactions

3-propargylamide-substituted indoles with diarylphosphine oxides, as reported by Liang and coworkers (Scheme 4.101(3)) [239]. The silver-mediated dehydrogenative annulation reaction of diarylphosphine oxides with internal alkynes was reported independently by the groups of Duan and Satoh at about the same time [240, 241]. In the presence of stoichiometric Ag2 O or AgOAc, the reaction proceeded in DMF at 100 ∘ C to afford the corresponding benzo[b]phosphole oxides in satisfactory yields (Scheme 4.102). An excellent regioselectivity was observed when internal 1-phenylalkynes were used as the substrates, which should be attributed to the much greater radical-stabilizing effect of the phenyl group. Interestingly, a mixture of regioisomers was obtained when phosphine oxides bear a substituent on the aromatic ring. This result was analyzed based on the competitive 5-endo vs. 4-exo cyclization of the vinyl radical intermediate, as shown in Figure 4.9. A catalytic version of this transformation was also developed by the Duan group using Ag2 O as the catalyst and stoichiometric zinc nitrate as the oxidant [240]. Ackermann and Ma also described the same transformation a few months later [242]. R2 O P H

R1

R3 +

Ag2O (2.0 equiv.) or AgOAc (4.0 equiv.)

R4

H

O 2 P R R3

R1

DMF, 100 °C R4

Scheme 4.102 Synthesis of benzo[b]phosphole oxides.

Oxidative cyclization of 1,6-enynes could also be triggered by phosphonyl radicals. In this regard, Liang and coworkers reported the AgOAc-catalyzed reaction of 1,6-enynes with diarylphosphine oxides to give the corresponding phosphonylated fluorene derivatives in good yields (Scheme 4.103) [243]. Phosphonyl radical addition to alkynes could be followed by the cyclization of the resulting vinyl radicals onto nitriles to generate iminyl radicals. Subsequent H-abstraction and hydrolysis provide the corresponding ketones. Phosphonylated 1-indenones were successfully achieved in this manner by silver-mediated reaction of 2-alkynylbenzonitriles with diarylphosphoine R

Ph

R

Ph

4-exo Ph

P Ar

Ar

O

P

Ph

O 5-endo Ph R Ph P Ar

O

–e R –H+

H Ph

R

H Ar O P

Ph Ar

Ar Ph

–e R –H+

P

O Ph

P O

Ph

Figure 4.9 Proposed mechanism of the benzo[b]phosphole oxide formation.

Ph

4.5 Cascade Radical Cyclizations

R3 R1

MeO2C MeO2C

R2 R3

AgOAc (10 mol%) Zn(NO3)2.6H2O or AgOAc

R2

MeO2C

O + H P Ar CH3CN, 100 °C, Ar Ar

MeO2C 1 Ar R Ar P O 33 examples, up to 85%

Scheme 4.103 Synthesis of phosphonylated fluorenes.

oxides, as reported by Jiang and coworkers (Scheme 4.104(1)) [244]. Alternatively, the intermediate iminyl radicals could be trapped intramolecularly by an aromatic ring, leading to the construction of tricyclic skeletons. This was exemplified by the AgOAc-mediated synthesis of 4-quinazolinones from unsaturated N-cyanobenzamides and diphenylphosphine oxide, as reported by Cui and coworkers (Scheme 4.104(2)) [245]. R1

R O AgNO3 (2.0 equiv.) + H P R CH3CN/H2O R 80 °C, air

R2 CN

O P R

R2

R1

28 examples up to 76%

(1)

30 examples 43–91%

(2)

O O

Ph2P(O)H (2.0 equiv.) AgOAc (1.0 equiv.)

O N CN

Ar

CH3CN, 80 °C

O Ph2P

N

Ar N

Scheme 4.104 Synthesis of phosphonylated 1-indenones and 4-quinazolinones.

Phosphonyl radical addition to alkynes could also be followed intramolecular trapping with sulfonamides to give cyclized products. In this manner, Zhao and coworkers developed a novel and efficient synthesis of 3-phosphonylindoles from N-Ts-2-alkynylanilines and diarylphosphine oxides (Scheme 4.105) [246]. The reaction was mediated by AgOAc and proceeded smoothly in DMF at 100 ∘ C. The authors proposed a radical substitution mechanism involving the intramolecular attack of vinyl radical at the sulfonamide nitrogen to form the C—N bond with the release of tosyl radical. However, it remains unclear whether or not the reaction is a radical process. The phosphonyl radical addition to alkyl-substituted R2 R1 O + H P R3 NHTs

Ar

Ar

O P

AgOAc (3.0 equiv.)

R3

DMF, 100 °C, 6 h

R2

1

R

Scheme 4.105 Synthesis of 3-phosphonylated indoles.

N H

38 examples 28–74%

247

248

4 Silver-Mediated Radical Reactions

arylacetylenes (R2 = alkyl) should result in the formation of α-arylvinyl radicals, but the reversed regioselectivity was observed in the reaction. Another example of phosphonyl radical-triggered cascade was the AgOAc-mediated reaction of arylpropiolic acids with diarylphosphine oxides, providing a novel access to various 2-phosphinobenzo[b]phosphole oxide compounds in satisfactory yields (Scheme 4.106) [247]. Mechanistic studies revealed that the decarboxylative phosphonylation occurred first to give the alkynyldiarylphosphine oxide intermediate. The silver-mediated dehydrogenative annulation of the phosphonylated alkyne with another diarylphosphine oxide then takes place to give the final product (also see Scheme 4.102 and Figure 4.9). Ar

O

CO2H O + H P Ar Ar R1

Ar O P

AgOAc (4.4 equiv.)

P

Ar

22 examples up to 86%

DMF, 100 °C, Ar R1

R1

Scheme 4.106 Synthesis of 2-phosphinobenzo[b]phosphole oxides.

In another case, 2-isocyanobiphenyls were employed by Studer and coworkers for the efficient preparation of 6-phosphonylated phenanthridines by reaction with diphenylphosphine oxide (Scheme 4.107) [248]. The reaction was mediated by AgOAc under mild conditions, providing the expected products in moderate to excellent yields. Shortly after Studer’s report, Wang and coworkers reported a catalytic version of the protocol by using AgOAc as the catalyst and PhI(OAc)2 as the oxidant [249].

R2 R1 N

O AgOAc (3.0 equiv.) + H P Ph DMF, 100 °C R

R2 R1

C

N R

O P Ph

18 examples 40–85%

Scheme 4.107 Synthesis of 6-phosphonylated phenanthridines.

Other than phosphonyl radicals, nitrogen-centered radicals could also be generated to trigger radical cascades under silver catalysis. Based on their work on the silver-catalyzed difunctionalization of N-arylacrylamides for the synthesis of diphenylphosphoryl oxindoles (see Scheme 4.100(1)), Yang and coworkers developed the silver-catalyzed azidoarylation of alkenes [250]. With AgNO3 as the catalyst and Zr(NO3 )4 ⋅5H2 O as the oxidant, a number of arylacrylamides were treated with TMSN3 in CH3 CN at 100 ∘ C, leading to the synthesis of the corresponding azide-containing oxindoles (Scheme 4.108(1)). It is likely that the oxidation of TMSN3 by Ag(I) generates the azidyl radical that adds to the C=C bond of acrylamide. Subsequent cyclization onto aryl ring and rearomatization furnish the oxindole product. Almost simultaneously,

4.6 Rearrangement/Migration/C—C Bond Cleavage

R3 R1 N R2

O

+ TMSN3

AgNO3 (3.0 equiv.) HOAc (10 equiv.)

N R2

n

R3

n = 0,1

1.4-Dioxane, 120 °C

R2 R1

N3 O

(1)

N R2 34 examples, 39–89%

CH3CN, 110 °C

O

R1

AgNO3 (10 mol%) Zr(NO3)4.5H2O (0.8 equiv.)

R3 R1

NO2 n

(2)

N O R2 24 examples, up to 83%

Scheme 4.108 Azidoarylation and nitroarylation of alkenes.

Jiao and coworkers reported the same transformation with Ce(SO4 )2 in place of Zr(NO3 )4 ⋅5H2 O as the oxidant [251]. Similar to azidoarylation, radical nitroarylation of alkenes could also be promoted by silver. In this regard, the reaction of AgNO3 with N-arylacrylamides in 1,4-dioxane at 120 ∘ C produced the corresponding nitro-containing oxindoles (Scheme 4.108(2)) [252]. Further studies by the Yang group showed that the nitroarylation of N-arylacrylamides could also be accomplished by using AgNO3 as the catalyst and Mg(NO3 )2 ⋅6H2 O as both the nitrating reagent and the oxidant, thus rendering it more practical and economical [253].

4.6 Rearrangement/Migration/C—C Bond Cleavage Radical rearrangement reactions have drawn an increasing attention in the past few years. Through radical ipso-cyclization onto aromatic rings and the subsequent rearomatization, a number of aryl migration reactions can be successfully implemented, many of which are promoted by silver catalysts. By taking advantage of the intrinsic ring strains of cycloalkanols, silver-catalyzed oxidative ring-opening of cycloalkanols provides a convenient excess to a variety of distally functionalized ketones via C—C bond cleavage. 4.6.1

Aryl Migration

During their study on radical phosphonylation of alkenes, Xu and coworkers observed that the silver-mediated phosphonylation of α,α-diaryl allylic alcohols with diphenylphosphine oxide at 120 ∘ C under aerobic conditions led to the formation of β-phosphonylated α-aryl ketones in moderate to excellent yields (Scheme 4.1) [254]. A neophyl-type rearrangement was apparently involved in the reaction. For allylic alcohols with two different aryl groups, the electron-poor aryl group was found to migrate preferentially. In addition, ortho-substituted aryl groups were found to migrate less effectively. A plausible mechanism was then proposed by the authors, as also shown in Scheme 4.109. The oxidation of

249

250

4 Silver-Mediated Radical Reactions

O Ph P H Ph

OH + Ar1 Ar2

O

AgOAc (3.0 equiv.) 1,4-Dioxane, 120 °C, air

Ar

2

Ar1

21 examples up to 90%

O P Ph2

OH O Ph P H Ph

Ag(I)

HO Ph

Ag(0)

O P Ph2

Ph Ph

O Ph P Ph

OH O P Ph2

Ph Ph

OH

Ag(I)

Ph Ph

O

Ag(0)

O

P Ph2

Ph Ph

O P Ph2

Scheme 4.109 Synthesis of β-phosphonylated α-aryl ketones.

diphenylphosphine oxide by Ag(I) generates the phosphonyl radical that adds to the C=C bond of allylic alcohol to form the adduct radical. The nucleophilic alkyl radical then cyclizes to the electron-poor or less sterically congested aromatic ring in a 3-exo mode to give the corresponding cyclopentadienyl radical. Subsequent rearomatization produces the ketyl radical via C—C bond cleavage, resulting in the 1,2-phenyl migration. Further oxidation of the ketyl radical presumably by Ag(I) provides the ketone as the final product. The above reaction was extended by Wu and coworkers to dialkyl phosphites in place of Ph2 P(O)H by using AgNO3 as the catalyst and Mg(NO3 )⋅6H2 O as the additive, providing a convenient excess to dialkyl γ-ketophosphonates [255]. Furthermore, based on the 1,2-aryl migration strategy, Liu et al. were able to prepare various α-aryl-β-trifluoromethylthiolated ketones in moderate to good yields by treating α,α-diaryl allylic alcohols with AgSCF3 and pyridine in CH3 CN at 65 ∘ C [256]. It is worth mentioning that, when CuSCF3 was used in place of AgSCF3 , no expected product was observed, indicating that Ag(I) played a vital role in the formation of CF3 S radical. The 1,2-aryl migration was also observed by Li and coworkers in silverpromoted fluorocyclization of aryl-containing carbamates or acrylamides, providing a straightforward approach to the synthesis of various fluorinated oxazolidin-2-ones and oxazolidin-2,4-diones under mild conditions (Scheme 4.110) [257]. It is likely that the single-electron oxidation of the styrene moiety followed by intramolecular trapping by the Boc group gives the F R

N

X

Boc Ar X = CH2, C(O)

+

I O

AgSbF6 (10 mol%)

R

DCM, 55 °C

O

N

X F O

Ar

26 examples 28–83%

Scheme 4.110 Synthesis of fluorinated oxazolidin-2-ones and oxazolidin-2,4-diones.

4.6 Rearrangement/Migration/C—C Bond Cleavage

corresponding alkyl radical with concomitant ring closure. Subsequent 1,2-aryl migration and fluorination afford the final product. 1,4-Aryl migration has been firmly established as a unique characteristic of radical processes. Nevado and coworkers carried out an extensive study on the radical chemistry of N-(arenesulfonyl)acrylamides and developed several types of difunctionalization of activated alkenes based on 1,4-aryl migration from a sulfur to a carbon center. For example, under the catalysis of AgNO3 , the reaction of N-(arenesulfonyl)acrylamides with diphenylphosphine oxide at 100 ∘ C afforded β-phosphonylated α-arylamides in satisfactory yields (Scheme 4.111) [258]. The role of AgNO3 is likely the radical initiator; it oxidizes Ph2 P(O)H to Ph2 P(O) radical. The phosphonyl radical addition to the C=C bond of acrylamide gives the α-carbamoyl radical, which undergoes ipso-cyclization onto the aryl ring in a 5-exo mode to give the cyclohexadienyl radical. Subsequent rearomatization leads to the C—S bond cleavage. Further desulfonylation produces the corresponding amidyl radical, which abstracts a H-atom from Ph2 P(O)H to give the final product and regenerate a Ph2 P(O) radical (Scheme 4.111). The ipso-cyclization was suggested to be the rate-determining step in the overall process. This radical chain process provides a convenient entry to aryl-containing quaternary stereocenters, thus highlighting the great potential of 1,4-aryl migration in organic synthesis. Other than phosphonyl radicals, fluoroalkyl radical could also be employed to take part in the 1,4-aryl migration strategy [259]. The AgNO3 /K2 S2 O8 -mediated reaction of Rf SO2 Na with N-(arenesulfonyl)acrylamides afforded β-fluoroalkylated α-arylamides, as reported by Hu and coworkers [259]. In a similar fashion, the silver-catalyzed condensation of 1,3-dicarbonyls with N-(arenesulfonyl)-acrylamides gave the corresponding dihydropyridinones via further intramolecular ketone–amide condensation (Scheme 4.112(1)) [260]. Furthermore, with the use of aliphatic O R1

O

R2

N O S O

O + H P Ph Ph

R3

CH3CN, 100 °C

N O S O Ph

R1 HN Ph

R2 O Ph P Ph

N O S O Ph

1 Ph2P(O)H R N

O R2

R1

PPh2 O

Scheme 4.111 1,4-Aryl migration.

Ph

R2

PPh2 O

R3

HN

O

O R1

R2

AgNO3 (10 mol%)

5-exo

PPh2 O

O –SO2 PPh2 R2 O

11 examples 60–80%

R1

R1 N O2S

O R2

PPh2 O

O R1 N PPh2 O2S 2 Ph R O

251

252

4 Silver-Mediated Radical Reactions

carboxylic acids as alkyl radical precursors based on silver-catalyzed oxidative decarboxylation, the reaction of N-(arenesulfonyl)acrylamides with aliphatic carboxylic acids provided a convenient entry to various α-alkylated α-arylamides [261]. O O

O S

O

R3

N R1

+

O

R

R

R CH3CN/H2O, 50 °C

O O S

R2

N Ph

R1

O

AgSCF3 (2.0 equiv.) or K2S2O8 (1.5 equiv.)

R1

X

N

(2)

Ph2P(O)H (2.5 equiv.) AgNO3 (30 mol%)

R

(1)

N R R1 23 examples, up to 70% R2 O

R2

O

O

R3

AgNO3 (10 mol%) K2S2O8 (2.0 equiv.)

2

R

R

X = CF3S, Ph2P(O)

43 examples, up to 73%

Scheme 4.112 Synthesis of pyridinones and indolo[2,1-a]isoquinolinones.

The Nevado group further developed radical cascade reactions based on the 1,4-aryl migration chemistry. For example, the amidyl radical intermediate indicated in Scheme 4.111 could be intercepted intramolecularly by a C≡C bond, leading to the construction of cyclic skeletons. Indeed, the AgNO3 -catalyzed reaction of N-(2-alkynylbenzenesulfonyl)-N-arylacrylamides with Ph2 P(O)H in refluxing acetonitrile enabled the one-pot synthesis of indolo[2,1-a]isoquinolin-6(5H)-ones (Scheme 4.112(2)) [260]. Analogously, the use of AgSCF3 in place of AgNO3 /Ph2 P(O)H furnished the corresponding trifluoromethylthiolated tricyclic compounds [260]. Furthermore, the AgNO3 -catalyzed reaction of N-(2-vinylbenzenesulfonyl)arylamides with Ph2 P(O)H in acetonitrile at reflux produced functionalized indanes (Scheme 4.113) [262]. In this transformation the Ph2 P(O) radical attacks ArHN

O O

O S

N Ar

O R + Ph P H Ph

O Ar

N O S O

R 8-endo

X

Ar O N S O

AgNO3 (10 mol%)

R 19 examples 44–81%

O

CH3CN, 80 °C O

O R

O

R

ArHN –SO2

5-exo

X

X

PPh2

Ar N S O O

Scheme 4.113 Synthesis of indanes via 1,4-aryl migration.

R

O X

X = Ph2P(O)

4.6 Rearrangement/Migration/C—C Bond Cleavage

the styrenyl C=C bond rather than the acrylamide due to its electrophilic nature. The resulting benzylic radical then undergoes 8-endo cyclization to give the α-carbamoyl radical. Subsequent ipso-cyclization, desulfonylation, and H-abstraction from Ph2 P(O)H furnish the indane and complete the radical chain (Scheme 4.113). In a similar fashion, the tandem radical reaction of ortho-vinylbiphenyl-substituted acrylamides led to the efficient and highly stereoselective synthesis of functionalized dibenzocycloheptadienes (Scheme 4.114) [262]. An uncommon 10-endo cyclization of benzyl radicals was involved in the transformation. O

O O

O S

R

N Ar

O + Ph P H Ph

AgNO3 (10 mol%) CH3CN, 80 °C

Ar NH R

7 examples 65–78%

Ph2 P O

Scheme 4.114 Synthesis of dibenzocycloheptadienes.

1,4-Aryl migration could also take place from an oxygen to a carbon center. Qing and coworkers observed such a process in the trifluoromethylthiolation of aryl alkynoates [263]. In the presence of Na2 S2 O8 as the oxidant, the reaction of aryl alkynoates with AgSCF3 in acetonitrile at 100 ∘ C produced vinyl trifluoromethyl sulfides in moderate to good yields (Scheme 4.115). The proposed mechanism indicated that the 1,4-aryl migration results from ipso-cyclization of the intermediate vinyl radical followed by the rearomatization to form the carboxyl radical. The fast decarboxylation of the carboxyl radical and subsequent H-abstraction gives the vinyl sulfide. O O

Ar1

+ AgSCF3

SCF3

SCF3

Ar

O O

Ar1

CH3CN, 100 °C

Ar2 Ar

Ar 2

Na2S2O8 (2.5 equiv.)

O

Ar

SCF3

21 examples 21–68%

Ar SCF3

O

SCF3

COO

Scheme 4.115 Synthesis of vinyl trifluoromethyl sulfides.

Shi and coworkers described another type of 1,4-aryl migration, i.e. from a carbon to a nitrogen center rather than from a heteroatom (S or O) to a carbon center indicated above [264]. With AgOAc as the catalyst, PIFA as the oxidant, K2 CO3 as the base, and bipyridine as the ligand, 3,3-diaryl-substituted N-propyltrifluoro-methanesulfonamides underwent the C(sp2 )—C(sp3 ) bond cleavage to afford N-aryl-substituted products with concomitant C—O and

253

254

4 Silver-Mediated Radical Reactions

C—N bond formations (Scheme 4.116). Electron-rich arenes were more favorable to migrate than electron-poor ones. A plausible mechanism was proposed, which starts with the Ag(II)-mediated oxidative generation of sulfonamidyl radical. Ipso-cyclization of the N-radical in a 5-exo mode followed by C—C bond cleavage gives the corresponding benzyl radical. Subsequent oxidation and further trapping with trifluoroacetate anion led to the final product. The high stability of benzyl radical intermediates probably accounts for the success of this radical polar crossover process. Tf

R1

N

H

AgOAc (20 mol%) bipyridine (20 mol%) PIFA (2.0 equiv.)

Tf

R1

K2CO3 (2.0 equiv.) PhCl/DCE, 120 °C

N TFAO 21 examples, 44–74%

R2

R2

Scheme 4.116 1,4-Aryl migration from carbon to nitrogen.

1,5-Aryl migration could also be accomplished under silver-catalyzed oxidative conditions. Liang and coworkers carried out the AgNO3 /Zn(NO3 )2 -mediated reaction of N-(p-methoxybenzenesulfonyl)cinnamamides with dialkyl phosphites in refluxing acetonitrile and obtained phosphonylated azaspiro[4,5] decenones in highly regioselective manner (Scheme 4.117) [265]. This oxidative radical cascade involves successively phosphonylation, ipso-cyclization, rearomatization, desulfonylation, amidyl radical cyclization, and further oxidation. The 1,5-aryl migration from a sulfur to a carbon center results from the ipso-cyclization of vinyl radicals in a 6-exo mode. R1 O

O S O

N O

R2

O + H P OR OR

AgNO3 (50 mol%) Mg(NO3)2.6H2O CH3CN, 80 °C, Ar

O

R1

O P OR N R2 RO O 18 examples, 30–82%

Scheme 4.117 Synthesis of phosphonylated azaspiro[4,5]decenones.

1,5-Aryl migration via Smiles rearrangement was recently reported by Hossian and Jana [266]. With AgNO3 as the catalyst and K2 S2 O8 as the oxidant, 2-aryloxy- or 2-(arylthio)benzoic acids underwent rearrangement to give aryl-2-hydroxybenzoates or aryl-2-mercaptobenzoate dimers, respectively, via 1,5-aryl migration from oxygen or sulfur to carboxylate oxygen (Scheme 4.118). The authors proposed that the carboxyl radical is generated by Ag(II) oxidation, which undergoes an ipso-attack onto the aryl ether moiety intramolecularly. Subsequent rearomatization leads to the corresponding phenoxyl or thiyl radical via C—O or C—S bond cleavage. However, this mechanism is questionable

4.6 Rearrangement/Migration/C—C Bond Cleavage O R O

OH Ar

AgNO3 (5 mol%) K2S2O8 (1.5 equiv.) CH3CN, 130 °C, 36 h

O O

R

Ar 21 examples 34–64%

X

Scheme 4.118 Synthesis of aryl benzoates via 1,5-aryl migration.

due to the fast decarboxylation of carboxyl radical. It is more likely that the electron-rich arene is oxidized by Ag(II) intermediate to generate the arene radical cation, which is intercepted intramolecularly by the carboxylate as a nucleophile to give the cyclohexadienyl radical. Further C—O or C—S cleavage results in the 1,5-aryl migration. Other than aryl group migration, radical-based cyano group migration could also be designed under silver-mediated oxidative conditions. Zhu and coworkers described such a process in the trifluoromethylthiolation of unactivated alkenes [267]. With K2 S2 O8 as the oxidant, the reaction of unsaturated cyanohydrins with AgSCF3 in DMSO at room temperature afforded the cyanotrifluoromethylthiolation products in good yields (Scheme 4.119). It is likely that the CF3 S radical addition to C=C bond is followed by radical cyclization onto C≡N bond in a 5-exo or 6-exo mode. The resulting iminyl radical undergoes β-scission to give the ketyl radical. Further oxidation of the ketyl radical affords the ketone. The higher stability of ketyl radicals than ordinary alkyl radicals may play a crucial role in the 1,4- and 1,5-cyano group transfer processes.

HO R

AgSCF3 (1.5 or 2.0 equiv.) K2S2O8 (3.0 or 4.0 equiv.)

CN n

n = 1, 2

R2

DMSO, rt, N2

O R

CN n

SCF3 R2

26 examples 35–93%

Scheme 4.119 1,4- and 1,5-Cyano group migration.

4.6.2

Radical C—C Bond Cleavage of Cycloalkanols

Cycloalkanols are a class of organic compounds that are easily accessible. Because of their unique structures with intrinsic ring strains, cycloalkanols have long been established as an equivalent of homoenolates in the field of transition metal catalysis. However in recent years, silver-mediated radical-based ring-openings of cycloalkanols have emerged as a versatile tool for the synthesis of various distally functionalized ketones. In 2006, Narasaka and coworkers reported the silver-catalyzed condensation of cyclopropanols with silyl enol ethers [268]. With AgNO3 as the catalyst, (NH4 )2 S2 O8 as the oxidant, and pyridine as the additive, the reaction of cyclopropanols with silyl enol ethers in DMF at room temperature provided the corresponding 1,5-diketones (Scheme 4.120(1)). The addition of pyridine improved the product yield presumably by serving as a base and the ligand to Ag(I). The proposed mechanism involves the oxidative ring-opening of cyclopropanols to generate β-keto radicals, which add to C=C bonds of enol

255

256

4 Silver-Mediated Radical Reactions

R1

OH +

R1

AgNO3 (cat.) (NH4)2S2O8

OTBS R2

Pyridine, DMF, rt

OH

OTBS R2

+

+

R3

O

O

R1

R2

AgNO3 (cat.) (NH4)2S2O8

O

Pyridine, DMF, rt

R2 = CN, CO2Et

OH

OTBS

R2

R1

(1)

O R3

(2)

3 examples, 59–62%

AgNO3 (cat.) (NH4)2S2O8 1,4-CHD DMF, rt

12 examples 19–86%

O

H

O (3)

H TBSO

85%

H TBSO

Scheme 4.120 Ring-opening addition to alkenes.

ethers. Further oxidation leads to the formation of 1,5-diketones. The authors further developed an elegant three-component condensation reaction of cyclopropanols, electron-deficient alkenes, and silyl enol ethers, furnishing 1,7-diketones in moderate yields (Scheme 4.120(2)). Radical polar effects play a key role in this condensation as β-keto radicals are nucleophilic and preferentially add to electron-deficient alkenes. This radical ring-opening strategy was then successfully applied into the total synthesis of (−)-sordarin, a potent and selective inhibitor of fungal protein synthesis (Scheme 4.120(3)) [269]. In this case, the silver-catalyzed oxidative ring-opening of bicyclo[4.1.0]heptan-1-ol generated the cycloheptyl radical, which underwent fast 5-exo cyclization to furnish the desired bicyclo[5.3.0]decan-3-one in high stereoselective manner. 1,4-CHD was used as H-donor in the reaction. Cyclopropanols as β-keto alkyl radical precursors could also be utilized in the alkylation of quinones. Thus the treatment of cyclopropanols with quinones in the presence of K2 S2 O8 and catalytic AgNO3 in DCM/H2 O at room temperature furnished the corresponding γ-carbonyl quinones in satisfactory yields (Scheme 4.121(1)) [270]. This protocol showed a good functional group tolerance as well as a wide substrate scope, as exemplified by the efficient synthesis of biologically active natural products such as evelynin and taccabulin E [271]. Cyclobutanol and cyclopentanols could also undergo ring-opening under silver-mediated oxidative conditions to generate the corresponding γ-keto and δ-keto radicals, respectively, which could be trapped by aromatic rings either intermolecularly or intramolecularly. In this regard, Bao and coworkers reported the regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion of 1-arylcyclobutanols (Scheme 4.121(2)) [272]. Li and coworkers described the silver-catalyzed regioselective Minisci alkylation of heteroarenes (e.g. benzothiazole, benzoxazole, and thiazole) with tertiary cycloalkanols, providing a facile route to carbonyl-containing C2-alkylated heteroarenes (Scheme 4.121(3)) [273]. Alternatively, β-keto radicals generated from oxidative ring-opening

4.6 Rearrangement/Migration/C—C Bond Cleavage

O R1

OH

O

AgNO3 (cat.) K2S2O8

+ R2

R2

R1

DCM/H2O, rt O

O

2

R

N

+

R1

n

X

R1

R

OH

AgBF4 (20 mol%) K2S2O8 (4.0 equiv.)

R2

DCE/H2O, rt

O N R1

I O

R2

(3)

X

AgNO3 (cat.) K2S2O8

+

n

17 examples, up to 82%

OH R2

(2)

2

n = 1, 2, 3

X = O or S

15 examples 40–74%

O R1

DCM/H2O, rt

R1

(1)

O

AgNO3 (20 mol%) K2S2O8 (3.0 equiv.)

HO

17 examples 6–80%

R3

O

O

R2

R1

CH2Cl2, 30 °C

(4) R3

21 examples 50–81%

Scheme 4.121 Ring-opening addition to quinones, (hetero)arenes, and alkynes.

of cyclopropanols could be trapped by alkynes intermolecularly. Thus the silver-promoted reaction of cyclopropanols with ethynylbenziodoxolones in dichloromethane at 30 ∘ C provided a novel and convenient access to 4-yn-1-ones under mild conditions (Scheme 4.121(4)) [274]. The use of AgNO3 considerably improved the efficiency of the reaction presumably by accelerating the formation of β-keto radicals. Interestingly, a similar procedure without silver catalysis was also reported, but water was required as the cosolvent [275]. The oxidative ring-opening of cycloalkanols could be utilized for the preparations of various halogenated and chalcogenated ketones via carbon–heteroatom bond formations. In 2015, Zhu and coworkers successfully developed the oxidative ring-opening fluorination of cycloalkanols [276]. With AgNO3 as the catalyst, the reaction of various cyclopropanols and cyclobutanols with Selectfluor in aqueous solvents at room temperature led to the efficient synthesis of the corresponding β- and γ-fluorinated ketones, respectively (Scheme 4.122). Selectfluor served as both the fluorine source and the oxidant. A plausible

O R1

AgNO3 (cat.) 1 R Selectfluor

F R2

14 examples 50–83%

CHCl3/H2O, rt

OH

R1

OH R2

R2

R3

Scheme 4.122 Ring-opening fluorination of cycloalkanols.

AgBF4 (cat.) Selectfluor DCE/H2O, rt

O

R3 F

R1 2

R 19 examples 30–80%

257

258

4 Silver-Mediated Radical Reactions

mechanism involving fluorine atom transfer from Ag(II)F to alkyl radicals was proposed, consistent to Li’s proposal in decarboxylative fluorination of aliphatic carboxylic acids (see Section 4.3.4). The same method was also reported by the groups of Murakami and coworkers [277] and Loh and coworkers [278] at about the same time under slightly altered conditions. Very recently, Mohr and coworkers also reported the same transformation by using AgF2 as both the oxidant and the fluorine source [279]. Ring-opening chlorination of cycloalkanols could also be implemented in a similar fashion. With AgOTf as the catalyst, 1,10-phenanthroline as the ligand, and t-BuOCl as the chlorine source, a variety of cycloalkanols underwent ring-opening chlorination in CH3 CN at room temperature to furnish the corresponding distally chlorinated ketones in satisfactory yields (Scheme 4.123(1)) [280]. Not only cyclopropanols and cyclobutanols but also less-strained cyclopentanols, cyclohexanols, and cycloheptanols were all suitable substrates for the reaction. A plausible mechanism was proposed by the authors, involving the chlorine atom transfer from Ag(II)Cl to alkyl radicals, consistent to the proposal by Li et al. in silver-catalyzed decarboxylative chlorination of aliphatic carboxylic acids (see Section 4.3.4). At about the same time, Zhu and coworkers also reported the same transformation with NCS as the chlorine source [281]. In addition, they extended the method to include the silver-catalyzed ring-opening bromination of cyclobutanols with NBS (Scheme 4.123(2)) [281]. AgOTf (cat.) 1,10-phenanthroline

R2 OH + t-BuOCl R2 n n = 1, 2, 3, 4, 5

R

R1

CH3CN, rt

AgNO3 (cat.) K2S2O8

OH + NBS

DCE/H2O, 25 °C

R2

O

Cl

n

O Br

R

27 examples 20–93%

(1)

5 examples 58–70%

(2)

Scheme 4.123 Ring-opening chlorination and bromination of cycloalkanols.

Ring-opening trifluoromethylthiolation of cycloalkanols could also be accomplished by reaction with AgSCF3 in the presence of K2 S2 O8 and pyridine, thus offering a convenient entry to various trifluoromethylthiolated ketones, as reported by Zhang and coworkers (Scheme 4.124) [282]. R2 OH n

R2

+ AgSCF3

CH3CN, 60 °C

R2

O

K2S2O8, pyridine R1

n

SCF3

24 examples 31–76%

n = 1, 2, 3, 4, 5

Scheme 4.124 Ring-opening trifluoromethylthiolation of cycloalkanols.

In another case, the γ-keto radicals generated from ring-opening of cyclobutanols could be intercepted by a C≡C bond before radical halogenation, resulting

4.7 Conclusion and Perspective

in ring expansion of cyclobutanols. Zhang and coworkers described such a tandem radical process by using 1-ethynylcyclobutanols as the substrates [283]. Under the catalysis of AgNO3 , the treatment of 1-ethynylcyclobutanols with Selectfluor, NBS, or NCS in DCE/H2 O at room temperature afforded the corresponding halogenated 2-methylenecyclopentanones in good yields (Scheme 4.125). R

AgNO3 (cat.) Selectfluor or NBS or NCS

HO

O R

DCE/H2O, rt

16 examples 40–85%

X X = F or Br or Cl

Scheme 4.125 Ring expansion of 1-alkynylcyclobutanols.

While cycloalkanoxyl radicals are generated directly from cycloalkanols in the above transformations, they can also be generated via cleavage of weak N—O bonds. In this regard, Wu and coworkers reported the silver-catalyzed tandem reaction of 2-alkynylbenzaldoximes with alkylidenecyclopropanes, leading to formation of the unexpected benzo-7-azabicyclo[4.2.2]dec-7-en-4-ones in moderate to good yields (Scheme 4.126) [284]. Mechanistic studies revealed that the silver-catalyzed 6-endo cyclization of 2-alkynylbenzaldoxime occurs first to give isoquinoline-N-oxide, which undergoes [3 + 2]-cycloaddition with alkylidenecyclopropane to produce the isoxazolidine derivative. Subsequent N—O bond cleavage followed by ring-opening and recombination provides the final product. However, it should be point out that the Claisen rearrangement as an alternative mechanism for the last step cannot be excluded.

1

R

N

R3

OH + R3 R2

AgOTf (10 mol%) R1

DMF, 75 °C

R2

R3 R1

N

O R2

R3

R3 R1

O 15 examples 32–84%

N

N

O

O R1 R2

N R2

Scheme 4.126 Synthesis of benzo-7-azabicyclo[4.2.2]dec-7-en-4-ones.

4.7 Conclusion and Perspective The past decade has witnessed a significant progress in silver-mediated or silver-catalyzed radical reactions. The property of silver as a single-electron oxidant not only triggers the generation of a wide range of carbon- and heteroatom-centered radicals from stable, readily available substrates but also

259

260

4 Silver-Mediated Radical Reactions

enables a variety of radical polar crossover processes to take place under mild conditions. This has resulted in the successful implementation of a number of new reactions that are otherwise difficult or sluggish to proceed. In particular, the vast development in silver-catalyzed decarboxylative functionalization reactions not only have significantly expanded the scope of Hunsdiecker halogenation but also have infused new vitality to Minisci alkylation, arylation, acylation, and related reactions. The silver catalysis has also significantly broadened the radical-based difunctionalization of olefins, aryl migration, and oxidative C—C bond cleavage. Fruitful results have also been achieved in the area of silver-catalyzed cascade radical cyclizations. In the meantime, silver-mediated radical processes play an increasingly important role in the synthesis of organofluorine compounds that are crucial in pharmaceuticals, agrochemicals, and materials science. In particular, the AgSCF3 -mediated radical trifluoromethylthiolation has been demonstrated to be a powerful tool to incorporate the CF3 S motif into organic molecules. Silver-catalyzed radical fluorination has emerged as a versatile tool in C(sp3 )—F bond formations. In addition, many silver-catalyzed radical reactions proceed in aqueous solution in open flasks under mild conditions, rendering them highly practical and sustainable. These advances have also changed the role of silver from a Lewis acid or halide scavenger to a key player at the center stage of radical chemistry. The progresses in the past decade have also set up the platform for the future development of silver-catalyzed radical-based methodologies. For example, it is conceivable that more new cross-coupling methodologies based on silver-catalyzed decarboxylative functionalization will be developed. More studies are certainly expected to gain a detailed understanding on the mechanism of Ag(II)-assisted fluorine atom transfer processes, based on which more practical silver-catalyzed radical fluorination methods will be developed, especially with the use of fluoride ion, the cheapest fluorinating reagent, as the fluorine source. In the meantime, the choice of appropriate ligands may deserve more attention, which may allow not only the precise execution of new chemoselective radical transformations by adjusting the oxidation potentials of Ag(I) complexes but also the exquisite design of enantioselective radical reactions. Furthermore, while substantial achievements have been made in Ag(I)- and Ag(II)-mediated radical reactions, the chemistry of Ag(III) complexes remains largely unexplored and certainly deserves more attention.

Acknowledgment This project was supported by the National Natural Science Foundation of China (Grants 21421002, 21472220, 21532008, and 21602239) and by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant XDB20020000).

References

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359: 859–865. Cui, H., Wei, W., Yang, D. et al. (2015). RSC Adv. 5: 84657–84661. Jin, D.-P., Gao, P., Chen, D.-Q. et al. (2016). Org. Lett. 18: 3486–3489. Yin, F. and Wang, X.-S. (2014). Org. Lett. 16: 1128–1131. Zeng, Y.-F., Tan, D.-H., Chen, Y. et al. (2015). Org. Chem. Front. 2: 1511–1515. Song, Y.-K., Qian, P.-C., Chen, F. et al. (2016). Tetrahedron 72: 7589–7593. Qiu, Y.-F., Zhu, X.-Y., Li, Y.-X. et al. (2015). Org. Lett. 17: 3694–3697. Wu, W., Yi, S., Yu, Y. et al. (2017). J. Org. Chem. 82: 1224–1230. Chen, M.-T., Tang, X.-Y., and Shi, M. (2017). Org. Chem. Front. 4: 86–90. Tang, J., Sivaguru, P., Ning, Y. et al. (2017). Org. Lett. 19: 4026–4029. Li, Y.-M., Sun, M., Wang, H.-L. et al. (2013). Angew. Chem. Int. Ed. 52: 3972–3976. Zhang, H., Gu, Z., Li, Z. et al. (2016). J. Org. Chem. 81: 2122–2127. Xu, J., Yu, X., and Song, Q. (2017). Org. Lett. 19: 980–983. Liu, J., Zhao, S., Song, W. et al. (2017). Adv. Synth. Catal. 359: 609–615. Mi, X., Wang, C., Huang, M. et al. (2014). Org. Lett. 16: 3356–3359. Wang, L.-J., Wang, A.-Q., Xia, Y. et al. (2014). Chem. Commun. 50: 13998–14001. Hua, H.-L., Zhang, B.-S., He, Y.-T. et al. (2016). Org. Lett. 18: 216–219. Chen, Y.-R. and Duan, W.-L. (2013). J. Am. Chem. Soc. 135: 16754–16757. Unoh, Y., Hirano, K., Satoh, T., and Miura, M. (2013). Angew. Chem. Int. Ed. 52: 12975–12979. Ma, W. and Ackermann, L. (2014). Synthesis 46: 2297–2304. Zhou, Z.-Z., Jin, D.-P., Li, L.-H. et al. (2014). Org. Lett. 16: 5616–5619. Zhu, X.-T., Zhao, Q., Liu, F. et al. (2017). Chem. Commun. 53: 6828–6831. Zheng, J., Zhang, Y., Wang, D., and Cui, S. (2016). Org. Lett. 18: 1768–1771. Gao, Y., Lu, G., Zhang, P. et al. (2016). Org. Lett. 18: 1242–1245. Hu, G., Zhang, Y., Su, J. et al. (2015). Org. Biomol. Chem. 13: 8221–8231. Zhang, B., Daniliuc, C.G., and Studer, A. (2014). Org. Lett. 16: 250–253. Cao, J.-J., Zhu, T.-H., Gu, Z.-Y. et al. (2014). Tetrahedron 70: 6985–6990. Wei, X.-H., Li, Y.-M., Zhou, A.-X. et al. (2013). Org. Lett. 15: 4158–4161. Yuan, Y., Shen, T., Wang, K., and Jiao, N. (2013). Chem. Asian J. 8: 2932–2935. Li, Y.-M., Shen, Y., Chang, K.-J., and Yang, S.-D. (2014). Tetrahedron Lett. 55: 2119–2122. Wei, X.-H., Wu, Q.-X., and Yang, S.-D. (2015). Synlett 26: 1417–1421. Chu, X.-Q., Zi, Y., Meng, H. et al. (2014). Chem. Commun. 50: 7642–7645. Mi, X., Wang, C., Huang, M. et al. (2014). Org. Biomol. Chem. 12: 8394–8397. Liu, K., Jin, Q., Chen, S., and Liu, P.N. (2017). RSC Adv. 7: 1546–1552. Yang, B., Chansaenpak, K., Wu, H. et al. (2017). Chem. Commun. 53: 3497–3500.

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5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions Vanessa Koch 1 , Andreas Hafner 1,3 , and Stefan Bräse 1,2 1 Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany 2 Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics (ITG), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany 3 Bayer CropScience Schweiz AG, Development, Rothausstrasse 61, 4132 Muttenz, Switzerland

5.1 Introduction The modern drug and agrochemical research as well as materials science cannot be imagined without compounds containing fluorine [1]. For illustration, around 30% of the agrochemicals and 20% of the pharmaceuticals on the market are estimated to contain fluorine [2]. The exchange of hydrogen for fluorine can trigger significant changes in their physical, chemical, and biological properties [3]. C—F bonds offer special properties including high stability, a high electron-withdrawing effect, and low polarizability [1c, 3b,c, 4]. These characteristics, in combination with a low steric demand resembling that of hydrogen, make them a unique structural motif in organic and medicinal chemistry. Besides the modulation of acidity and basicity by the introduction of fluorine into a medicinal target, also the deceleration of oxidative metabolic processes by cytochrome P450 monooxygenases can be observed in case of the replacement of hydrogen for fluorine on aromatic rings. Moreover, fluorine atoms can serve as biochemical tag for magnetic resonance imaging (MRI) or for 18 F-positron-emitting tomography in order to diagnose various diseases such as cancer [5]. Motivated by the demand for fluorinated compounds in combination with the synthetic advent of the Balz–Schiemann reaction [6], the synthesis of fluorinated organic molecules has attracted major interest in organic synthesis, and a plethora of synthetic methods have been developed to get a suitable and extensive toolbox for biological but also materials sciences, including also asymmetric variants [7]. Besides monofluorination of organic compounds, e.g. by the Balz–Schiemann reaction [6], also trifluoromethylation has gained special importance in different fields, ranging from medicinal and biological applications to materials or polymer sciences. This enormous interest made trifluoromethylation reactions to one of Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

272

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

AgF AgNO3 Ag2CO3

AgOAc AgOTf Ag2O

AgSbF6 AgBF4 AgOP(O)Ph2

Figure 5.1 Commonly used silver(I) catalysts.

the most intensively investigated topics, resulting in the development of various methods for their introduction over the last years [8]. While copper-mediated perfluoroalkylation reactions are well documented [9], silver(I)-mediated perfluoroalkylations are relatively new and therefore less explored. This chapter will focus on the recent progress using perfluoroorgano silver(I) compounds and will not address the limited application of perfluoroorgano silver(III) compounds [10]. For the silver-catalyzed or silver-mediated reactions, an appropriate silver source is required, whereby in general inorganic and mostly commercially available silver salts have been used. A small selection is shown in Figure 5.1. Unlike other silver halides, silver(I) fluoride [11] is less sensitive to light and is highly soluble in water and slightly soluble in methanol or acetonitrile, which allows its use as catalyst for trifluoromethylation reactions. Silver(I) fluoride finds application in organofluorine chemistry for addition of fluoride across multiple bonds. For example, AgF adds to perfluoroalkenes in acetonitrile to give perfluoroalkyl silver(I) derivatives (see Section 5.3.1). It can also be used as a desulfurization–fluorination reagent on thiourea-derived substrates. Silver(I) nitrate [12] is often used in radical silver-catalyzed fluorination reactions (see Section 5.2.3), which is not only due to the fact that silver nitrate is the least expensive silver salt. Moreover, silver(I) nitrate bears many useful properties such as a relatively high photostability and a high solubility in water and other organic solvents including acetonitrile, alcohols, and DMF. On the other hand, silver(I) carbonate [13] and silver acetate [14] are both only poorly soluble in water and are sensitive to light. Nevertheless, both find application as silver(I) catalyst, though it is rarer than usage of more convenient silver sources. Silver(I) triflate [15] shows solubility in water and in all typical organic solvents that makes this silver(I) salt an interesting and relatively common applied silver catalyst. Even if silver(I) hexafluoroantimonate [16] is sensitive to light, hygroscopic, and very corrosive, it finds some application in silver-mediated fluorination reactions that is probably due to its good solubility and the non-coordinating properties of the counterion. Silver(I) trifluoroborate [17] is, like most of the silver salts, light sensitive and also hygroscopic, but shows good solubility in water and some organic solvents like benzene and diethyl ether. Although in general less used than the other silver salts, the bench-stable AgOP(O)Ph2 shows interesting activity as silver catalyst, for example, in the late-stage fluorination of complex alkenyl stannanes (Scheme 5.10). In summary, the present chapter provides a non-comprehensive overview over recently reported silver(I)-mediated and silver(I)-catalyzed fluorination, perfluoroalkylation, and perfluorothiolation procedures, whereby it does not cover reactions that provide trifluoromethyl groups by modification of exiting halomethyl groups [18].

5.2 Silver-Mediated Fluorinations

5.2 Silver-Mediated Fluorinations Without question, fluorinated arenes, alkenes, and alkanes play a pivotal role in modern organic chemistry. Selected examples of important drugs and crop protection agents are shown in Figure 5.2, which demonstrate the importance of fluorine in medicinal and herbicide chemistry. A recently published review about fluorination methods in drug discovery gives a broad overview of fluorination reactions on drugs and prodrugs [19]. One approach for the introduction of fluorine is the application of transition metal catalysis. Silver(I)-mediated fluorination has emerged as a frontier area in organic chemistry since the first direct silver-catalyzed fluorination about 70 years ago [20]. Today many different approaches for the derivatization of aryls, alkenes, alkynes, and alkanes are known, which can in principle be assigned to nucleophilic, electrophilic, or radical silver-catalyzed fluorination [21]. Besides an appropriate silver source like those previously described (see Section 5.1), a fluorinating reagent is required. Fluorinating agents can be classified by their ability to provide fluoride ions (F− ), fluorine radicals (F⋅ ), or electrophilic fluorine (F+ ). Typical nucleophilic fluoride sources are inorganic salts such as silver(I) fluoride (AgF), cesium fluoride (CsF), calcium fluoride (CaF2 ), or potassium fluoride (KF), which show poor solubility in organic solvents and have dual reactivity as a nucleophile and base. Additionally, organic OH NH

OH

O O–

N

HN

O

N

Ca2+

N

F

F

CO2H O

2

Atorvastatin

Ciprofloxacin (broad-spectrum antibiotic for the treatment of bacterial infections)

(prevention of cardiovascular disease, treatment of dyslipidemia)

(a) F

HO

F

O N

N N F

N

Flutriafol

(broad-spectrum fungicide) (b)

F

O

Etoxazole

(narrow-spectrum systemic acaricide to combat spider mites)

Figure 5.2 A selection of fluorinated biologically active compounds for medicinal applications (a) or crop protection (b).

273

274

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

Cl N N

−

2X

OTf N F

F

Selectfluor F-TEBA-BF4 F-TEBA-PF6

NFPy’s

−

F

O OO O S S Ph N Ph F

I O

NFSI

Figure 5.3 Commonly used electrophilic fluorination reagents.

nucleophilic fluorinating reagents such as tetrabutylammonium fluoride (TBAF), diethylaminosulfur trifluoride (DAST), or Deoxo-Fluor were broadly used. In combination with silver catalysis, inorganic salts, as well as tetraalkylammonium fluoride/tetrafluoroborate, are used. Not only are a broad number of nucleophilic fluoride sources known, but also there are numerous reagents that deliver electrophilic fluorine. Although reagents like xenon difluoride (XeF2 ), perchloryl fluoride (FClO3 ), or trifluoromethyl hypofluorite (CF3 OF) are more selective than fluorine gas (F2 ), there are still limitations and drawbacks for each of them. This led to the discovery of alternative reagents from which the most prominent ones are depicted in Figure 5.3. N—F reagents such as Selectfluor (in this chapter the designation F-TEBA is used), N-fluoropyridinium salts (NFPy’s), or N-fluorobenzenesulfonimide (NFSI) play a crucial role in electrophilic and radical fluorination because of their stability and easy handling. Likewise, hypervalent iodides can serve also as a source for electrophilic fluorination reactions [22].

®

®

5.2.1

Nucleophilic Silver-Catalyzed Fluorination

Since fluoride ions are very hard and relatively nucleophilic, it is not surprising that a larger number of nucleophilic fluorination reactions are known. Nevertheless, the high kinetic barriers for the formation of C—F bonds as well as the exclusion of hydrogen donors in order to maintain the good nucleophilicity of F− have to be considered for the design of new fluorination reactions. Nucleophilic fluorination reactions in general can be used for the synthesis of sp, sp2 , and sp3 fluorides and require different fluoride-containing reagents, whereby tetrafluoroborate and boron trifluoride are most commonly used [23]. Based on the mechanism of the Chichibabin reaction, the Hartwig group [24] developed a site-selective C—H fluorination of pyridines, quinolines, and diazines using commercially available silver(II) fluoride. Compared with the direct fluorination with F2 gas or the strong acidic and oxidizing reaction conditions of the classical Balz–Schiemann reaction, the silver-mediated C—H fluorination does not require harsh reaction conditions and is therefore broadly applicable (Scheme 5.1). Electron-donating and electron-withdrawing groups are tolerated as well as carbonyl-containing functional groups. Most of the reactions were completed within one hour at ambient temperature with high selectivity for fluorination adjacent to nitrogen. By including computational studies, Hartwig proposed the reaction mechanism that is initiated by the

5.2 Silver-Mediated Fluorinations

AgF2,MeCN, rt,1 h

R

R

N

N

N

H F

N

N

AgF2

AgF

F– AgF

F

– 2 AgF – HF

N

F

(a) N R

N

F

R

N

F

N

F

F

N

R

R R = Ph, 88% R = Et, 94% (b)

R = OMe, 57% R = Br, 43% R = CO2Et, 73%

R = H, 83%* R = Br, 65%

R = Me, 64% R = Ph, 64% R = NHBocPr, 78%

Scheme 5.1 Silver-catalyzed fluorination of pyridines, quinolines, and diazines. (a) Proposed reaction mechanism. (b) Selected substrate scope. *Reactions were performed at 50 ∘ C [24].

coordination of AgF2 to pyridine. After the addition of F− to pyridine to form an amido-silver(II) fluoride complex, the hydrogen atom is abstracted by a second equivalent of AgF2 to give the product along with 2 equiv. of AgF and 1 equiv. HF. Wang et al. described a silver-mediated fluorination of 5-iodotriazoles with AgF as fluoride source and N 1 ,N 1 ,N 2 ,N 2 -tetramethylethane-1,2-diamine (TMEDA) as ligand in boiling toluene [25]. Different 1,4-substituted 5iodotriazoles, which are readily available by click reaction of iodoalkynes and azides, were converted to the corresponding 5-fluorotriazoles [25]. It was shown that different substituted aryls carrying electron-donating and electronwithdrawing groups as well as thiophene and alkyl residues were tolerated at C4 (first row, Scheme 5.2). Moreover, the variation of the substituent R2 at N1 was also possible, resulting in mostly good yields of the products (second row, Scheme 5.2). The first example of a silver-mediated fluorination of primary and secondary alkyl iodides with the Ruppert–Prakash reagent (TMSCF3 ) as the source of fluorine was conducted in the presence of ionic liquid and CaF2 (Scheme 5.3). Due to the mild reaction conditions, a variety of functional groups is tolerated, which was showcased for the synthesis of complex natural products without significant loss of yields. Moreover, it has been demonstrated that a large surface area of CaF2 sizably increases the reaction yield [27]. Besides nucleophilic replacement reactions, a fluorine can be introduced by treating strained compounds such as cyclopropanes with a suitable fluoride source under silver catalysis. For example, trichloromethylcyclopropane carboxylates undergo regiodivergent electrophilic ring opening depending on the used silver salt. While the reaction with AgOAc leads to a selective C1—C2

275

276

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions N N

N N

AgF, TMEDA, PhMe, 20 h, 120 °C

N R2

R1 I

N N

N R2

R1 F

N N

N Bn

N N

N Bn

N N N Bn

N N

N Bn

O

S F

F

F

F

OMe

83%

N N

79%

66%

80% N N

N

Ph

R N

N

Ph

F

N

F N

R R = Me, 64% R = CN, 79%

10%

N

N N

Ph

70% N N

Ph N

F

F 95%

R = Me, 91% R = Cl, 85%

N

Ph

Ph F

F

O

Br

N Bn

65%

Scheme 5.2 Synthesis of 5-fluorotriazoles by silver-mediated fluorination of 5-iodotriazoles [26]. TMS-CF3, Ag2O, CaF2, [bmim][NTf2]

R I

N

R F

–

N+ Me

NTf2

MeCN, PhMe, 90 °C [bmim][NTf2] O R

O N

F

O

O

R = 4-fluorophenyl, 88% R = 2-thiophenyl, 57% O

F

F

8

81%

76%

AcO

F

O OAc

O R R = CN, 85% R = COMe,76%

F R = i-Pr, 63% R = OMe,71%

H O

O OH OBz OAc 43%

Scheme 5.3 Fluorination of primary and secondary alkyl iodides with the Ruppert–Prakash reagent [26].

cleavage to form a γ,δ-unsaturated ester, treatment with AgBF4 introduces a fluorine atom at C3 via C2—C3 bond cleavage. The proposed mechanism is based on the coordination of the silver(I) salt of a chlorine atom from the trichloromethyl group followed by fluoride transfer from AgBF4 to C3 that leads to the C2—C3 bond cleavage and the elimination of the silver-activated chlorine atom. Due to the regiospecifity of the reaction, 2,3-cis-substituted cyclopropanes predominately react to the syn-product, while 2,3-trans-substituted cyclopropanes generally favor the formation of the anti-product (Scheme 5.4) [28].

5.2 Silver-Mediated Fluorinations

CO2Et R

AgBF4, Bu4NBF4, CH2Cl2, –10 °C,10 h

H R

CO2Et CCl2

R

F3B– F

H H

H

H

F

CCl3

CO2Et

Cl

Cl Cl

Ag

Scheme 5.4 Ring-opening reaction of trichloromethylcyclopropane carboxylates with AgBF4 [28].

Functionalizing C—C triple bonds is an alternative approach for the construction of new C—F bonds. In 2012 Jiang and his coworkers developed a silver-assisted regio- and stereoselective bromofluorination of terminal alkynes using N-bromosuccinimide (NBS) and AgF as halogen sources [29]. The methodology was extended to internal electron-deficient alkynes to afford the corresponding products in high yields (Scheme 5.5a). Hydrofluorination of ynamides with anhydrous HF as fluorination reagent generally gives access to the cis-α-fluoroenamides. However, β-trans-hydrofluorination of N-sulfonyl ynamides can be promoted by AgF by which (Z)-α-fluoroenamides were provided in good yields and high regio- as well as stereoselectivity (Scheme 5.5b) [30]. A few years later, Zhu and coworkers showed that stoichiometric amounts of AgF can be replaced by Et3 N⋅3HF as fluorinating agent and catalytic amounts of AgNTf2 (Scheme 5.5c). It is noteworthy that regioselectivity can be inverted by using a copper(I) source [31]. (a) R1

R2

AgF, NBS, MeCN, H2O, 80 °C, 10 h

R1

H

F

R2

R2 = H, EWG

R1

N

SO2R2

(b) AgF, MeCN, H2O, 80 °C, 5 h

R1

F

R3

(c) Et3N·3HF, AgNTf2 (cat),

H

N SO2R2 R3

DMF, 70 °C, 12–17 h

Scheme 5.5 Fluorination of terminal and internal alkynes (a) and hydrofluorination of N-sulfonyl ynamides with over-stoichiometric amounts of AgF (b) and catalytic amounts of AgNTf2 and Et3 N⋅3HF as fluoride sources (c).

For the synthesis of fluorinated aryls, Lee and coworkers came up with an alternative idea. They intended to construct the aryl ring de novo via a silver-promoted thermal hexadehydro Diels–Alder reaction in which the formed silver aryne is trapped by fluoride. By using catalytic amounts of AgBF4 and pyridinium tetrafluoroborate as fluoride source, a number of different fluorinated aryls were synthesized (Scheme 5.6). It is worth to note that it was possible to trap the silver aryne with other nucleophiles such as CF3 − and SCF3 − to get the corresponding aryls (see Section 5.3.2) [33].

277

278

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

AgBF4 or AgBF4 (cat.) NH BF4–

R1 X R2

Y

R1

R1

R2

R2 X

X

C7H8, 90 °C

Y

Y

Ag

R1 = TMS,n-alkyl,aryl R2 = H,TMS,alkyl X = CH2,NTs,O Y = CH2,NTs

F

10 examples (75–93 %)

Scheme 5.6 Silver-mediated fluorination of arynes for the synthesis of fluorinated aryls starting from nonaromatic building blocks [32].

Davies and coworkers demonstrated in 2013 that silver-stabilized carbenes (obtained from vinyl diazoacetates) with adjacent carbonyl groups can serve as electrophiles for a nucleophilic fluorination to provide secondary and tertiary γ-fluoro-α,β-unsaturated carbonyls (Scheme 5.7). The reaction works for both aryl- and alkyl-substituted vinyl diazoacetates in good yields and tolerates different functional groups at the aryl ring. Moreover, no dependency of the size of the ester group was observed, and more surprisingly, even an amide can be used as acceptor group affording the product still in satisfying yield of 60%. It is to accentuate that the reaction was also successfully with disubstituted vinyl diazoacetates forming the quaternary fluorinated carbon center in good to excellent yields. The potential of the reaction was showcased for the fluorination of farnesol and also a cholesterol derivative at a late stage [34]. R2

N2

R1

F R2

AgOAc (cat.), Et3N 3 HF, CH2Cl2, reflux

OR

OR

R1 O

O

2

R1

= alkyl, aryl R2 = H, alkyl

18 examples (R = H, 60–96%) 7 examples (R2 ≠ H, 75–91%)

F

F

F CO2Me

Ph

F CO2Me

COR

R

Ph

85%

R = OMe, 96% R = Br, 89%

R = OiPr, 92% R = NMeOMe, 60% CO2Me F

CO2Me 91%

H H

85%

H

H

56% (dr > 20 : 1)

O F

Scheme 5.7 Synthesis of secondary and tertiary allylic fluorides by a silver-catalyzed vinylogous fluorination of vinyl diazoacetates with Et3 N⋅3HF as fluoride source [34].

5.2 Silver-Mediated Fluorinations

5.2.2

Electrophilic Silver-Catalyzed Fluorination

In contrast to nucleophilic fluorination reactions, their electrophilic counterparts are more challenging and, until recently, were less established [33, 35]. To overcome this imbalance, the development of crystalline and benchtop-stable reagents was as important as the use of transition metal organometallic compounds. The combination of those reagents with transition metal catalysis enables a wider spectrum of mechanisms, leading to the development of fluorination reactions of aryls starting from Ar—M such as aryl stannanes, boronic acids, or silanes. In this context the potential of silver-mediated fluorination reactions was discovered starting with initial studies by Tius and Kawakami on fluorination of trialkylstannanes with XeF2 [36]. Further investigations by the Ritter group led to silver-mediated fluorinations of functionalized aryl stannanes [37], boronic acids [38], and silanes [39], which were the first examples of the use of the transition metal silver to form carbon–heteroatom bonds by a cross-coupling reaction. The general proposal for silver-mediated and silver-catalyzed arene fluorinations proceeds over three steps comprising transmetalation, oxidation, and reductive elimination (Scheme 5.8). After transmetalation, presumably an intermediate of a high-valent and multinuclear aryl silver complex is formed, which undergoes a one-electron oxidation. The redox synergy of the multiple silver center lowers the high kinetic barrier to C—F reduction, enabling the reductive elimination to give the fluorinated product and the silver(I) [21e, 37b, 38].

Ar

Bimetallic redox chemistry

[M]

Ar F + 2 AgI

AgX Transmetalation

[M]X Oxidation

(ArAgI) (AgIX) F

+

F

Reductive elimination

Ar AgIILn [AgII]

Scheme 5.8 Proposed mechanism for silver-mediated and silver-catalyzed electrophilic fluorination ([M] = SnBu3 , B(OH)2 , Si(OEt)3 ) [21e, 37b, 38].

The fluorination of differently substituted tributylarylstannanes with 2 equiv. of AgOTf and F-TEDA-BF4 in acetone at ambient temperatures gives the corresponding products in good yields (63–83%) within 20 minutes (Scheme 5.9). The presented “late-stage fluorination” was applied to selected pharmaceutically active molecules in order to synthesize fluoro derivatives of estrone, δ-tocopherol, camptothecin, or quinine [38]. By changing the reaction conditions to Ag2 O, NaOTf, NaHCO3 , MeOH, and F-TEDA-PF6 in acetone, improvements in reaction yields (76–89%) were gained. This enabled the late-stage fluorination of other complex molecules including polypeptides, polyketides, and alkaloids [37b]. The proposed catalytic cycle includes an aryl transmetalation from Sn to Ag(I) producing the corresponding aryl Ag(I) species that is prone to aggregate with additional Ag(I). This is followed by Ag-based oxidative

279

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5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

fluorination, leading to the formation of a high-valent aryl silver fluoride complex. The latter should facilitate the reductive elimination of aryl fluoride and the regeneration of the Ag(I) catalyst. In the same year, the Gouverneur group presented a AgOTf-catalyzed 18 F-fluorination of electron-rich aryl stannanes by radiolabeled Selectfluor bis(triflate) through a simple “shake-and-mix” protocol at room temperature based on a similar strategy [40]. (a) AgOTf, F-TEDA-PF6, acetone, rt, 20 min SnBu3

(b)

18/19F

Ag2O, F-TEDA-PF6, NaHCO3, NaOTf, MeOH, acetone, rt, 20 min

N N

R

R

(c) AgOTf, F-TEDA-(OTf)2, acetone, rt, 20 min

O

F

H H

H

F

F

F

O

H N

OH O 73% (a)

–

2 PF6

F-TEDA-PF6 N

N N

N

85% (a)

CH3

F

18

H H

O

75% (b)

O 90% (b)

Scheme 5.9 Silver-mediated fluorination of aryl stannanes [37, 40].

In general, most of the procedures for the conversion of alkenyl stannanes into the corresponding fluoroalkenes suffer from largely variable yields and a limited compatibility with functional groups; most notably, protiodestannylation becomes a serious issue whenever protic sites are present in the substrate. The Fürstner group presented a convenient alternative with an improved application profile, which is largely unperturbed by free alcohol and amides of all sorts (Scheme 5.10). Key to success is the use of F-TEDA-PF6 in combination with nonhygroscopic and benchtop-stable silver phosphinate (AgOP(O)Ph2 ) that acts not only as an essentially neutral non-nucleophilic promotor but also as effective tin scavenger. This new method opens many opportunities for late-stage fluorination of complex molecules far beyond the scope of the comparable methods, as witnessed by the preparation of a fluorinated macrolide antibiotic, a fluorinated prostaglandin derivative, and a set of fluorinated amino acid surrogates and peptide isosteres [41]. Similar to the protocols for stannanes, functionalized allylsilanes can be converted to their fluorides. A regiospecific silver-mediated fluorination of arylsilanes with F-TEDA-BF4 as fluoride source has been reported by Ritter and coworkers (Scheme 5.11). The reaction is operationally simple and employs over-stoichiometric Ag2 O as readily available, inexpensive silver source, which can be recovered in high yields [39]. Consequently, this reaction was also extended to aryl and alkenyl boronic acids and esters by the group of Ritter (Scheme 5.12) and became since 2009 the first transformation of aryl boronic acids to aryl fluorides [37a]. The presented silver-mediated fluorination reaction uses commercially available boronic acids,

5.2 Silver-Mediated Fluorinations

F-TEDA-PF6, SnBu3

F

AgOP(O)Ph2, acetone, rt

R1

R1 R2

R2

OH

O

F

N H

F O

76%

Ph

OH

54%

O

F

OH

O

84% O O

O F 60%

O

Scheme 5.10 Late-stage fluorination by using alkenyl stannanes [41].

Si(OEt)3

R

N

F-TBAF-BF4, Ag2O, BaO, acetone, 90 °C, 2 h

CH3

N

F

F

R

–

2 PF6

F-TEDA-PF6 F

F MeOC

Cl

86%

AcHN

MeO

82%

79%

F

F

F

76%

F N

70%

60%

Scheme 5.11 Silver-mediated fluorination of arylsilanes [39].

does not require the addition of exogenous ligands, and can be performed on a multigram scale. The substrate scope contains electron-rich, electron-poor, sterically demanding ortho-substitution patterns as well as a variety of heterocyclic boronic acids (Scheme 5.12a). Moreover, it was shown that a one-pot hydrofluorination of an alkyne gives access to β-trans-fluorostyrenes via hydroboration of phenylacetylene followed by fluorination of the intermediate alkenyl boronate ester (Scheme 5.12b). A few years later, Li et al. were able to extend the deboronofluorination method to primary, secondary, and tertiary alkyl boronates with a broad substrate scope and wide functional group compatibility under modified reaction conditions (Scheme 5.13). Although the role of TFA as cosolvent remains unsolved, the authors suggest that TFA could help to increase the solubility of the borates in the aqueous phase and is therefore crucial for the success of the reaction. Interestingly, for primary alkyl borates, higher amounts of TFA and the addition of H3 PO4 were necessary in order to accelerate reaction times and to increase

281

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5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions B(OH)2 R

(1) NaOH, AgOTf, MeOH, 0 °C

F R

(2) F-TEDA-BF4, 3 Å MS, acetone, rt F F

F

F

F

HO 85%

MeO2C 70% F

Boc N N

F

N

AcHN 77%

72%

OHC 76%

73%

F

F

F

71% F

75%

N

N

N

75%

71%

(a)

HBPin

BPin

NaOH, AgOTf, F-TEDA-BF4

(b)

F

76%

Scheme 5.12 Silver-mediated fluorination of aryl boronic acids (a) and alkenyl boronic esters (b) [38].

yields. The mild conditions allowed further the synthesis of gem-difluorides from the corresponding gem-bis(borates) and the application to natural products such as steroids (not shown). Based on mechanistic experiments, the authors showed no doubt about the generation of alkyl radicals. Therefore, they proposed a Ag(III)—F intermediate that is presumably formed by oxidative addition and is followed by a single-electron oxidation of the alkyl boronate to give the alkyl radical. A subsequent fluorine atom transfer from the Ag(II)—F intermediate to the alkyl radical afforded the product and regenerated the Ag(I) catalyst [42]. AgNO3, F-TEDA-BF4, TFA, (H3PO4), CH2Cl2, H2O, 50 °C, 8 h

O R B O

R F

22 examples (55–93%) MeO

F NC

Ph

Ph

O

F

PhthN

F CO2Et

F F

92%

71%

55%

Scheme 5.13 Silver-mediated fluorination of alkyl boronates [42].

75%

5.2 Silver-Mediated Fluorinations

Besides boronic acids and esters, stable and easily accessible aryl- and heteroaryl trifluoroborates can be fluorinated under silver-mediated conditions. The application of trifluoroboronates allows a more simple experimental setup and includes a high tolerance toward several functional groups. While the reaction conditions for boronic esters were not suitable for trifluoroboronates and do not afford any product at all, overall good yields were obtained using F-TEDA-BF4 as fluoride source and AgOTf and LiOH⋅H2 O as activator in ethyl acetate. On the other hand, these reaction conditions do not work well for the corresponding boronic acids, pinacol, or MIDA esters. However, on the other hand, the method tolerates a wide range of electronically and structurally diverse substrates (Scheme 5.14) [43]. AgOTf, F-TEDA-BF4, LiOH H2O, EtOAc, 55 °C, 5–15h

BF3K R

F

F R R = OMe, 65% R = F, 65% R = CF3, 68% R = CO2Me, 82%

R R = OMe, 42% R = CF3, 45% R = CO2Me, 67%

F R

F R R = OMe, 40% R = F, 70%

F N

F N Boc

OMe

40%

42%

Scheme 5.14 Silver-mediated fluorination of aryl trifluoroborates [43].

An interesting building block for medicinal chemistry is α-fluoroketones, which are traditionally prepared by direct fluorination of α-haloketones or hydroxyl-substituted ketones. But also silver-catalyzed fluorination of carbonyldirected alkynes in the presence of NFSI can provide α-fluoroketones in moderate to good yields under simple and mild reaction conditions (Scheme 5.15a). Both aldehydes and ketones can be applied equally as directing carbonyl groups ortho to the alkyne to induce the reaction. The postulated mechanism involves a silver-mediated formation of a benzopyrylium ring that is opened by a nucleophilic attack of water to build a silver enolate. Next, silver is replaced by a fluorine atom from NFSI that, after an enol–keto tautomerism, forms the α-fluoroketones. In order to demonstrate the synthetic value of the α-fluoroketones, one of them was converted to fluorine-containing indanone via a N-heterocyclic carbene (NHC)-catalyzed intramolecular crossed-benzoin reaction (Scheme 5.15b) [44]. Electrophilic silver-catalyzed fluorinations are also reported for heterocycles. For example, 4,6-disubstituted 2-aminopyridines can be selectively fluorinated with F-TEDA-BF4 in the presence of Ag2 CO3 . In general, aminopyridines represent a ubiquitous structure found in many pharmaceutical intermediates, making them interesting target structures. One example is Ibrance – a drug designed by Pfizer for the treatment of breast cancer. With the presented silver-assisted fluorination, various aryl-substituted substrates were

®

283

284

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions H/R

O

H/R

R2

O

F R2

NFSI, AgF, DMA, 50 °C, 12 h R1

R1

CHO F

R

CHO F

Ph

O

R

CHO F

O

F R2

O O

O

R1 R1 = H, 83% R1 = Me, 59% R1 = Cl, 66%

O

88%

R = Me, 87% R = F, 77% R = CF3, 57%

R = Me, R2 = Ph, 70% R = Me, R2 = Hex, 68% R = Ph, R2 = Ph, 74%

CHO F

O 47%

(a)

N

CHO F N O

O N C6F5 BF4–

OH

DBU, toluene, rt

F

(b)

89%

Scheme 5.15 (a, b) Silver-catalyzed fluorination of carbonyl alkynes gives α-fluoroketones. DMA, N,N-dimethylacetamide [44]. NH2 N

NH2

F-TEDA-BF4, Ag2CO3, MeCN, 70 °C

N

N

R2

R1

N R2

R1 F

(a)

N

N Ph

Ph

NH2

NH2

NH2

NH2 N

N

N

N

N S

Ph

Ph

F

F

60%

72%

R

N

S

F

F

R

R = Me, 55% R = F, 52%

51%

(b) HN N R1

Ag

HN Ag(III)F F-TEDA-BF4

N R2

N R1

R2

NH

NH N

N R1

N

N R2

R1

N

+ Ag(II)F R2

Scheme 5.16 Silver-mediated fluorination of 2-aminopyrimidines using F-TEDA-BF4 . (a) Substrate scope of (b) proposed reaction mechanism [45].

5.2 Silver-Mediated Fluorinations

tolerated (Scheme 5.16a), and unlike the previously presented silver-catalyzed fluorinations, the unprotected amino groups are resistant to the treatment with Ag(I). Instead, the aminopyridine group allows the coordination of Ag(I). By the addition of F-TEDA-BF4 , the highly reactive aminopyridino-Ag(III)—F intermediate can be formed, which gives after N—Ag homolysis and tautomerization of the resulting radical the 5-fluorinated aminopyridine by reacting with Ag(II)—F species (Scheme 5.16) [46]. So far, only methods for electrophilic fluorination of aromatic compounds have been presented. However, also molecules with double and triple bonds or allenes can serve as starting materials for fluorination. The synthesis of fluorinated benzyl-substituted γ-lactones, for instance, proceeds from appropriately substituted double bonds that contain at their “side chain” a carboxylic acid function with an air- and moisture-stable hypervalent iodine(III) reagent and AgBF4 . In contrast to fluoraza reagents, the reaction with hypervalent iodine reagent delivers tertiary alkyl fluorides, while the same reaction with fluoraza regents provides the analogical primary alkyl fluorides. The mechanism is based on the combination of an intramolecular fluorocyclization and an aryl migration. Under these mild reaction conditions, a diversity of fluorinated lactones became accessible, whereby many functional groups attached to the aryl substituent were tolerated (Scheme 5.17). OH n R

O

O F

I

n

R

n = 1, 2

O

F

O

n = 1, R = H (81%), OMe (65%), F (77%) n = 2, R = H (38%)

O

OH

AgBF4, 4 Å MS, CH2Cl2, 40 °C, 1 h

O O

R

R

F R = H (86%), OMe (48%), F (69%)

Scheme 5.17 Intramolecular silver-mediated fluorocyclizations of unsaturated carboxylic acids with a stable hypervalent fluoroiodane reagent [47].

Under silver(I) catalysis, an intramolecular aminofluorination of allenes with NFSI, conducted by Xu et al. in 2011, gave access to tosyl-protected 4-fluoropyrrole derivatives (Scheme 5.18). The reaction tolerates various functional groups and substitution patterns. By screening the optimal reaction conditions, it became obvious that silver(I) plays a crucial role for the mechanism, since with palladium acetate, for example, no conversion was observed. Preliminary mechanistic studies imply that a vinyl silver intermediate is formed by silver-catalyzed amination of the allene, which reacts either with a proton to build the undesired hydroamination by-product or with NFSI to give the product in combination with a recycling of the silver(I) source. Since typical radical scavengers such as butylated hydroxytoluene (BHT) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) did not influence the fluorination, a radical pathway was excluded [48]. Based on the same concept, the synthesis of 4-fluoroisoquinolines via silvercatalyzed intramolecular oxidative aminofluorination of alkynes with NFSI as

285

286

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions R3

R2

R2

NFSI, AgNO3 (cat.), K2CO3, Et2O, rt

R1

R1

19 examples (28–92%)

NHTs

R2 R1

F N Ts

R2 R1

R3

R1 Ag(I)

NHTs

R2

Ag(II)F [Ag(II)]n N Ts

R3

N Ts

R2 R3

F

R3

R1

Ag(I) [Ag(I)]n N Ts

R2

H+

R3

R1

H R3

N Ts

NFSI

Scheme 5.18 Silver-catalyzed intramolecular aminofluorination of activated allenes with NSFI [48].

fluorinating reagent and silver(I) nitrate as catalyst in N,N-dimethylacetamide (DMA) was realized (Scheme 5.19). The use of Li2 CO3 as base turned out to be crucial for the reaction because it prevents the formation of the hydroamination product while favoring the formation of the 4-fluroisoquinoline derivative. A variety of functional groups on the aliphatic or aromatic substituted alkyne and the aromatic system were tolerated and afforded the corresponding fluorinated isoquinolines in good yield. The method offers the possibility to be followed by a [3+2] dipolar cycloaddition with dimethyl acetylenedicarboxylate to give 4-fluoropyrrolo-[α]-isoquinolines as tandem reaction under slightly modified reaction conditions [49]. R2 R1

NFSI, AgNO3 (cat.), Li2CO3, DMA, 60 °C, 5–10 h

N

H

F R1

R1

N

F

R

F

N

F

F

F C4H9

R N R = H, 87% R = OMe, 81% R = F, 68%

N

< 2% Without ≈ 27% Li2CO3

R2 R1

R2

R2

N R = NTsBoc, 71% R = CH2OAc, 85% R = C2H4CO2Me, 83%

R

N R = H, 87% R = OMe, 82% R = F, 84%

Ph N

S 79%

Scheme 5.19 Silver-catalyzed intramolecular aminofluorination of alkynes with NSFI [49]. Mechanistic studies were conducted by Liu’s working group and were not depicted [50].

5.2 Silver-Mediated Fluorinations

In a similar manner, the synthesis of a fluorinated indole derivative was shown by replacing the phenylmethanimine moiety by an aniline derivative. Dependent on the silver(I) catalyst and the amount and sort of the fluorine source, the silver-catalyzed one-pot cyclization/fluorination of 2-alkynylanilines gave either 3-fluoroindoles or 3,3-difluoro-3H-indoles in good yields. The reaction was found to have a broad tolerance toward different functional groups (Scheme 5.20) [51].

F F R1

Ar N

Ag2CO3, NFSI, 1,4-dioxane, 60 °C

Ar R1 NHR2

(1) AgNO3 (cat.), MeCN, 80 °C (2) F-TEBA-BF4, rt

F R1

Ar N R2

Scheme 5.20 Silver-catalyzed one-pot cyclization/fluorination of 2-alkynylanilines to give 3,3-difluoro-3H-indoles with 2.0 equiv. of NFSI and silver(I) carbonate or 3-fluoroindoles with 1.2 equiv. of silver(I) nitrate and Selectfluor [51].

5.2.3

Radical Silver-Catalyzed Fluorination

Over the recent years, radical fluorinations experienced a renaissance, probably due to the rediscovery of nitrogen-based electrophilic reagents such as Selectfluor (F-TEBA-BF4 ) in combination with transition metal catalysis, whereby one of the most commonly used metals is silver(I). In general, methodologies rely on five types of radical generation: addition to alkenes, radical decarboxylation, C—C bond activation, C—H bond activation, and fluorination of boronic acid derivatives (although going through a radical mechanism, the fluorination of boronic acid derivatives is shown for better comparison in Section 5.2.2). A comprehensive overview of these approaches is given in recent reviews [52]. 5.2.3.1

Fluorination via Addition to Alkenes

Recently, Li et al. showed a convenient approach for the synthesis of vicinal fluorohydrin starting from styrenes and providing therefore the first hydroxyfluorination method of styrenes with anti-Markovnikov-type regioselectivity (Scheme 5.21). The reaction proceeds under mild reaction conditions with F-TEBA-BF4 as fluorinating agent, AgOTf as catalyst, and Sm(OTf )3 as additive in a ternary solvent mixture of PhNO2 , H2 O, and CH3 NO2 . The reaction showed a good functional group tolerance including halides, esters, ethers, nitro, and cyano groups. In order to showcase the practicability of method, also more complex molecules bearing a coumarine or a steroidal moiety were subjected to the reaction conditions to afford the corresponding vicinal fluorohydrins in moderate yields. Mechanistic investigations and density functional theory (DFT) calculations demonstrated the radical character of the mechanism, which is supposed to proceed via a styrene radical cation. The latter reacts with H2 O to form a β-hydroxyl-substituted benzylic radical that is then trapped by the fluoride agent [53].

287

288

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions F

AgOTf, F-TEBA-BF4, Sm(OTf)3, PhNO2, H2O, MeNO2, 30 °C, 4–18 h

R

OH R

21 examples (41–85%) F

F OH R

R = CN, 75% R = NO2, 53% R = CO2Me, 61% R = OMs, 79%

F

R = o-Br, 66% R = m-Br, 67% R = p-Br, 77%

OH R

62%

O O

O F

F Boc

OH

NH

O

O

45% (dr = 1 : 1) OH

H H

MeO2C

H

HO 64% (dr = 1 : 1)

64% (dr = 1 : 1)

F

Scheme 5.21 Silver-catalyzed anti-Markovnikov hydroxyfluorination of styrenes [53].

An interesting approach for fluoroarylation of styrenes was given in 2015 by Tang and his coworkers by using AgOTf and F-TEDA-BF4 as fluorinating reagent in DMA at ambient temperature (Scheme 5.22). Under these conditions, diazonium salts, bearing electron-withdrawing and electron-donating substituents, were reacted with a broad number of different substituted styrenes to afford the corresponding fluorinated compounds with moderate to high yields. Lower yields were obtained for sterically hindered aryl- or heteroaryldiazonium salts. The practicality and effectiveness of the method was showcased for a few more complex styrenes incorporated in natural products such as the estrone and by a successful upscale to gram scale. F-TEDA-BF4,

N2BF4 R1

R2

+

R2

R1

F

R2

AgOTf, DMA, rt

R1 = H, R2 = H, R1 = H, R2 = F, R1 = F, R2 = H, R1 = F, R2 = Me, R1 = F, R2 = F,

R1

F O

66% 58% 74% 85% 80%

H H

F

F

H

43%

Scheme 5.22 Silver-catalyzed intermolecular fluoroarylation of styrenes [54].

With the analogous intramolecular fluoroarylation, fluorinated dihydrobenzofuranes and N-protected indolines were accessible, whereby again different substituents in ortho-, meta-, and para-position on both aromatic systems were compatible with the reaction conditions. While the trans-fluorinated dihydrobenzofuranes were formed with high diastereoselectivity, the fluorinated indolines were constructed with lower diastereoselectivity (Scheme 5.23). The authors proposed a radical chain mechanism or a single electron transfer (SET)

5.2 Silver-Mediated Fluorinations

N2BF4

F-TEDA-BF4,

R1 X

AgOTf, DMA, rt

R2

R1 X

X = O, N

F

F

R2

R1 = F, 71% (dr = 7 : 1) R1 = Me, 61% (dr = 14 : 1)

R2 = CF3, 56% (dr = 13 : 1) R2 = t-Bu, 64% (dr = 14 : 1)

Me

F

N Ts

O

O

R1

R2

F

ortho: 65% (dr = 4 : 1) meta: 61% (dr = 4 : 1) para: 75% (dr = 3.7 : 1)

Scheme 5.23 Silver-catalyzed intramolecular fluoroarylation of styrenes [54].

to be involved, since radical inhibitors such as BHT or TEMPO shut down the fluoroarylation. In the presence of over-stoichiometric amounts, the addition of TEMPO was found after the 5-exo cyclization instead of the fluorine consisting with a free radical mechanism. Not only styrenes can serve as targets for radical fluorinations, but also alkenes can be modified. The first carbofluorination of unactivated alkenes was described by Zhu et al. in the year 2014 (Scheme 5.24). By treating unactivated alkenes with active methylene compounds (E1 CH2 E2 ) such as 1,3-dicarbonyls or acetoacetates in the presence of AgNO3 and F-TEBA-BF4 , an access to γ-fluorinated compounds was provided in moderate to excellent yields depending on the chosen residues R1 and R2 [55].

E1

E2

+

AgNO3, F-TEBA-BF4, CH2Cl2, H2O, HOAc, 50 °C, 12 h

R1 R2

E = COMe, COPh, CO2Me, CN

E2 E1

F R2 R1

30–95%

Scheme 5.24 Silver-catalyzed radical carbofluorination of unactivated alkenes [55].

Further investigations showed that the active methylene compounds could be replaced by acetone to give γ-fluorinated ketones [55] or by acidic acid to afford γ-fluorinated aliphatic carboxylic acids [56]. Because of the mild reaction conditions, a number of functional groups at the alkyl chains including amides, tosylates, halogens, esters, nitriles, and ketones were tolerated. Unfortunately, the extension to activated alkenes as well as to other acids such as propionic acid failed due to decarboxylative fluorination that becomes competitive for longer chains. It is worth to mention that all reactions are highly efficient and can be accomplished stereoselectively depending on the chosen substrate. This was exemplary demonstrated for an estrone derivative that gives stereoselectively the 17α-fluoro derivative (Scheme 5.25) [55, 56].

289

290

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

R1

O

+

AgOAc (cat.), F-TEBA-BF4, NaOAc, H2O, 50 °C, 12 h

R2

F R3

R3

48–93%

Selected examples: CO2Me

O F

F

CO2Me H

50%

AgNO3 (cat.), F-TEBA-BF4, CH2Cl2, H2O, H3PO4, 50 °C, 12 h

R2

OH

H

AcO

R1 +

O

H

76% (93 : 7)

O

R2 R1

O

F O OH

R2 R1

44–92%

Scheme 5.25 Silver-catalyzed radical carbofluorination of unactivated alkenes [55, 56]. Cl

O R′

N N

R F

F Ag

O R′

Cl N N

R

R′

F–Ag(II)

F–Ag(III)

O R O

O R

R

R = OH,CH3

Scheme 5.26 Reaction mechanism of the silver(I)-catalyzed carbofluorination of unactivated alkenes with carbonyl compounds like ketones (acetone) or acidic acids [55, 56].

A plausible mechanism is shown in Scheme 5.26 and reminds strongly to the transition metal-assisted atom transfer radical addition (ATRA) mechanism. Presumably by oxidative addition of F-TEBA-BF4 , the Ag(III)—F intermediate is formed, which allows a SET from the substrate to the silver species. Deprotonation of the acetonyl radical cation affords an electrophilic α-carbonyl radical that adds to the alkene, resulting in the formation of the nucleophilic alkyl radical and allowing then the fluorine atom transfer from Ag(II)—F intermediate to the alkyl

5.2 Silver-Mediated Fluorinations

radical. In final steps, the carbofluorination product is built, the Ag(I) catalyst is regenerated, and the latter is able to enter into the next catalytic cycle [55, 56]. By transferring the methodology to styrenes, Duan and his coworkers presented an interesting approach for the synthesis of β-fluorinated 3-aryl ketones by a decarboxylative acylfluorination of styrenes with F-TEBA-BF4 under silver(I) catalysis (Scheme 5.27) [57]. A set of electronically different aryl α-oxocarboxylic acids afforded the product in moderate to high yields, whereby no conversion was observed when σ-methylphenylglyoxylic acid was used, probably due to steric hindrance. Moreover, styrene derivatives with electron-donating and electronwithdrawing groups at either 2-, 3-, or 4-position were compatible with the reaction conditions and gave the corresponding products in good yields. However, with aliphatic terminal alkenes, only traces of the product were obtained that indicate a limitation of the method to styrenes. R1

O R2

+ HO

R

F-TEBA-BF4, AgNO3, Na2SO4, acetone, H2O, rt

O

R1

O R2

R

R1 = H, Me R2 = Ar

35–73% (19 examples)

Scheme 5.27 Silver-catalyzed decarboxylative acylfluorination of styrenes with α-oxocarboxylic acids [58].

By using a similar approach, Li et al. were able to develop the first example of a catalytic phosphonofluorination of unactivated alkenes (Scheme 5.28). With diethyl phosphite, F-TEBA-BF4 as fluorine source, and AgNO3 as catalyst, a diverse set of β-fluorinated alkylphosphates with a wide compatibility toward functional groups and different alkenes became accessible in a ternary mixture of dichloromethane, water, and acidic acid [59]. Noteworthy, also azidofluorination with TMS azide of unactivated alkenes is known, but does not require any transition metal [60]. O H P OEt OEt

R1 +

R2 R3

AgNO3 (cat.), F-TEBA-BF4, CH2Cl2, H2O, HOAc, 40 °C,12– 48 h

O EtO P EtO

F R3

R2 R1

44–93% (33 examples)

Scheme 5.28 Silver-catalyzed phosphonofluorination of unactivated alkenes [59].

Another interesting application of Li’s methodology is the intramolecular silver(I)-catalyzed aminofluorination of unactivated alkenes that led to the synthesis of 5-fluoromethyl-substituted γ-lactams starting from N-arylpent4-enamides (Scheme 5.24). Best results were obtained with AgNO3 as silver(I) source and F-TEBA-BF4 in a biphasic solvent system of dichloromethane and water at 40 ∘ C that protects the products from undesired further oxidations. The proposed mechanism is based on the silver-catalyzed oxidative generation

291

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5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

of an amidyl radical analogously to the formation of the acetonyl radical in Scheme 5.26. This enables a 5-exo-mode cyclization to give a new carbon radical that is followed by a subsequent silver-assisted fluorine atom transfer (Scheme 5.29) [59].

O X

R

O

AgNO3 (cat.), F-TEBA-BF4, CH2Cl2, H2O, reflux

X

R N

N H

F 50–91% (18 examples)

X = C, N, O O X

Cl

NAr

N N

F F Ag(I)

O X

Cl N N

NAr

F–Ag(II)

F–Ag(III)

O X

NAr O –H+

X

O NHAr

X

NHAr

Scheme 5.29 Silver-catalyzed radical aminofluorination of unactivated alkenes and its proposed mechanism [59]. A detailed mechanistic study based on DFT calculations was given by Zhang [26] (not incorporated to the shown catalytic cycle).

A little later, Liu et al. also succeeded to establish a silver-catalyzed radical oxyfluorination of unactivated alkenes for the synthesis of 5-(fluoromethyl)-4,5dihydroisoxazoles by using an approach analogous to the just presented aminofluorination (Scheme 5.30). By treating 3-enal oximes with AgOAc and F-TEBA-BF4 as fluorine source and oxidant, an easy access to Δ2 -isoxazolines was given. This method overcomes several drawbacks of conventional methods such as a limited substrate scope, unsatisfying regioselectivity, and harsh reaction conditions. The reaction was compatible with both aryl and alkyl oximes and afforded their corresponding products in similar yields. Several functional groups on the aryl ring were tolerated including groups that enable further functionalization such as cyano, ethinyl, or halide residues. Therefore, the location of the substituent showed no significant effect on the yields. The diastereoselectivity of the reactions depends mostly on steric properties of the R2 group, which presumably controls the addition of the oxygen radical to

5.2 Silver-Mediated Fluorinations

N

OH

C7H8, H2O, HOAc, 30 °C

R1 R2

R3

R

R3

R1

R2

52–72% (18 examples) F

N O

F R = ortho-OMe, 61% R = meta-OMe, 70% R = para-OMe, 67% R = para-CN, 68%

N O

F

N O

AgOAc (cat.), F-TEBA-BF4,

H Me

Ph 58%

H F N O

H F N O Ph

65% (dr = 4 : 1)

H Ph

52% (dr = 17 : 1)

Scheme 5.30 Silver-catalyzed oxyfluorination of unactivated alkenes for the synthesis of 5-(fluoromethyl)-4,5-dihydroisoxazoles [61].

the double bond. Unfortunately, the reaction was limited to the synthesis of Δ2 -isoxazolines and could not be extended to the synthesis of Δ2 -oxazines [62]. An intramolecular fluorocyclization of unsaturated carbamates was described by the group of Lu in 2017 (Scheme 5.31). Various fluorinated or radiofluorinated oxazolidin-2-ones, oxazolidin-2,4-diones, and 1,3-oxazinan-2-ones were described to show options to tune their biological properties. In the presence of hypervalent iodine reagent and AgSbF6 , different (hetero)aryl-substituted olefins were successfully reacted to oxazolidin-2-ones or 1,3-oxazinan-2-ones. The reaction shows a broad tolerance to functional groups and different substitution patterns. Phenyl groups attached to the nitrogen or to the double bond can carry both electron-donating and electron-withdrawing groups at all positions of the aryl ring. While internal olefins can be used as substrate to afford the desired product, the usage of alkyl olefins gave fluorinated oxazolidin-2-one in 44% yield, and no migration was observed. The method could be successfully extended to the synthesis of biologically important six-membered 1,3-oxazinan-2-one ring systems. By using the analogous 18 F-labeled reagent and adjusting the reaction conditions, 18 F-labeled oxazolidin-2-ones were synthesized that may find application as radiotracers for positron emission tomography (PET) in diagnostic medicine [63].

R1

N Boc R2

R

AgSbF6(cat.),CH2Cl2, 55 °C, 3.5 h

F

O

O

R O

1,3-Oxazinan-2-one Ph

Ph O

R = p-OMe, 66% R = p-F, 65% R = m-Me, 83% R = o-OMe, 70%

PMP

N

78%

O R = p-OMe, 79% R = p-Cl, 76% R = m-Br, 59%

O

R2

N O

Ph

I

O

N

N O

F

F N O

28–83% (21 examples) PMP

F

R1

N

58% O

O

O

F 44%

Scheme 5.31 Silver-promoted fluorination of (hetero)aryl-substituted olefins [63].

F C6H5

293

294

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

Moreover, the authors demonstrated that phenyl-substituted acrylamides were also suitable substrates, resulting in oxazolidin-2,4-diones as product. Under slightly modified reaction conditions, a few examples were given comprising electronically different aryls as migrating groups (Scheme 5.32) [63]. O

O R1

N Boc R2

R1

AgBF4(cat.), CH2Cl2, 60 °C, 4 h

F

F I

N O

O

R2

O 43–56% (6 examples)

R1 ≠ R2 = aryl

Scheme 5.32 Silver-promoted fluorination of acrylamides leads to the synthesis of oxazolidin-2,4-diones [63].

5.2.3.2

Decarboxylative Fluorination

Inspired by fluorodecarboxylation with F2 and XeF2 , the Li group found an alternative approach for a decarboxylative fluorination of aliphatic carboxylic acids using F-TEBA-BF4 as fluorine source and AgNO3 as catalyst (Scheme 5.33). This comparatively mild method not only overcomes practical drawbacks based on the high toxicity and low stability of the fluorine sources but also is compatible with a wide range of functional groups such as esters, ketones, amides, and halides. Due to the differences in reactivity of the carboxylic acids following the expected order tertiary > secondary > primary ≫ aromatic, chemoselective decarboxylative fluorinations are possible. Therefore, elevated reaction temperatures and/or higher amounts of the fluorine source have to be applied for secondary or primary carboxylic acids, while aromatic carboxylic acids remain untouched. However, AgNO3 can be replaced by other silver(I) salts like AgBF4 or AgOAc exhibiting nearly the same catalytic activity, whereby no reaction took place without a silver(I) source [64]. Based on a systematic theoretical study, the mechanism includes the formation of H2 O-ligated silver carboxylate and its oxidation by F-TEBA-BF4 , which is followed by the cleavage of the Ag(II)—O bond, by the release of CO2 , and finally by fluorine abstraction [35f, 65]. An impressive example for the power of this reaction was the silver-catalyzed decarboxylative radical fluorination of poly(acrylic acid) and poly(methacrylic acid) releasing the corresponding fluorinated copolymers. The extent of fluorination could be controlled by the amount of the fluorinating reagent due to F-TEBA-BF4, AgNO3 (cat.), acetone, H2O

R CO2H O n-C10H21

F

F

N

76%

78%

F N

Ph F

O 82%

O

O

F

R F

77%

Br

8

F

O 73%

47%

Scheme 5.33 Silver-catalyzed decarboxylative fluorination of aliphatic carboxylic acids [64].

5.2 Silver-Mediated Fluorinations

the linear correlation between the fluorination and the amount of reagent. The reaction gave not only high yields but also well-defined molecular weights and polydispersities [66]. The same methodology was also transferred for the decarboxylative fluorination of nanodiamonds in order to modulate their optical and electromagnetic properties and to increase the hydrophobicity of their surface. Compared with traditional methods, the silver(I)-catalyzed radical substitution of carboxyls for fluorine atoms on the surface was accomplished best with F-TEBA-BF4 under mild reaction conditions of two days at 95 ∘ C (Scheme 5.34). Because of the mild reaction conditions, diamond carbons are not etched, allowing an application as nanosensors for quantum optical and magnetometry measurements [67]. R CO2H

F-TEBA-BF4, AgNO3, H2O, rt

R CO2H

n

1–X

F

X n

R = H, Me

Scheme 5.34 Controlled silver-catalyzed decarboxylative fluorination of poly(acrylic acid) (R = H) and poly(methacrylic acid) (R = Me) [66].

Similar reaction conditions were applied to paraconic acids to synthesize β-fluorinated γ-butyrolactones that have importance for organic synthesis and pharmaceutical science. In order to suppress the formation of the corresponding decarboxylated γ-butyrolactone and the butenolide, reaction conditions were optimized for paraconic acids by changing, for example, the solvent system. The generality of the reaction was shown for different substitution degrees at the γ-position bearing both mono- and disubstitution. Unsymmetrically γ-substituted paranoiac acids gave the corresponding β-fluorinated γ-butyrolactones as a mixture of diastereomers. In general, the fluorine atom of the major isomer is located on the opposite side to the larger substituent to build the thermodynamically more stable trans-isomer (Scheme 5.35) [68].

R1 R2 O

O 83%

O

F O 75%

O

R3

F R1 R2 O

O

F

F Me Me

F-TEBA-BF4, AgNO3, C6H6/H2O, reflux, 10 h

R3

HO2C

Ph

O

trans: 33%

Ph

F

F

F O

O

O

cis: 32%

Ph O Me

O

O

Me Ph

O

O

trans/cis (3 : 1), 86%

Scheme 5.35 Silver-mediated decarboxylative fluorination of paraconic acids [68].

Another example for an application of decarboxylative fluorination was given by Goh and Adsool. Under similar conditions, the mono-decarboxylative fluorination of bicyclo[1.1.1]dicarboxylate was performed in good yield in gram scale without the need of chromatographic purification to demonstrate the potential for its application in medicinal chemistry and industry (Scheme 5.36) [69].

295

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5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

CO2H

HO2C

F-TEBA-BF4, AgNO3, H2O, 65 °C CO2H

F

Scheme 5.36 Decarboxylative fluorination of a dicarboxylate [69].

5.2.3.3

C—C Bond Activation

While the synthesis of α-fluoroketones via a silver-mediated fluorination method is described in Section 5.2.2, β- or γ-fluoroketones can be obtained by a silver-catalyzed ring-opening fluorination of cyclopropanol or cyclobutanol and subsequent fluorination with F-TEBA-BF4 for which some recent examples were given in the following paragraphs [70]. While Ishida et al. applied stoichiometric amounts of the silver salts [71], Zhu and his coworkers were able to reduce the amount of silver to catalytic amounts of 20 mol% (Scheme 5.37) [70b]. The reaction proceeds with good regioselectivity and exhibits a good tolerance toward functional groups. However, electron-rich aryl cyclobutanol gave higher yields than electron-deficient ones, whereby no dependency of the location of the substituent on the aryl was determined. This dependency on electronic properties of the starting material was not observed for the aryl cyclopropanes. By a rational design of the cyclic substrate, also ring expansion could be achieved to give the ring-expanded secondary fluorides with good yields [70b]. In addition, Loh and his coworkers showed also the differences in using Fe(III) in contrast to R1 OH

O

F-TEBA-BF4,

R2

AgBF4, CHCl3, H2O, rt

R2

R1

O F

F

Ph

Et 50% (24 h)

O R1 OH

As above

F

R

R = H (71%, 4 h), p-OMe (76%, 7 h), o-Br (60%, 4 h), p-Br (72%, 4 h)

R2 O

O

R2

41% (24 h) O

R = H (78%, 5 h), o-OMe or m-OMe (75%, 5 h), p-OMe (80%, 6 h), R p-Br (51%, 32 h)

O F

Ph

OH

Ph F

Ph 73% (72 h)

Ring expansion F

F

n-C6H13

F

R1

O

O

OH

9

Ph

63%, dr = 2.3 : 1 (7 h)

55% (10 h)

F

Scheme 5.37 Cyclobutanol and cyclopropanol ring opening catalyzed by silver salts [70].

5.2 Silver-Mediated Fluorinations

Ag(I). While alkyl-substituted cyclopropanols exhibited just low reactivity with Fe(acac)3 , with AgNO3 as catalyst, the desired products were isolated in high yields under similar, but not identical reaction conditions [72]. Fluoroalkenes represent interesting structural motifs in many pharmaceuticals and have attracted special attention within recent years although the synthesis is challenging. In this context, Zhang and coworkers found a synthetic approach to β-halogenated 2-methylenecyclopentanones by a silver-catalyzed formal ring expansion of 1-alkynyl-substituted cyclobutanols (Scheme 5.38). Ag(I) initiates the ring opening of the cyclobutanol, and the resulting radical can be trapped by the alkyne to construct the five-membered cycle and a new alkenyl radical that is then fluorinated in the presence of an appropriate fluoride source (Scheme 5.38b). Reaction optimization led to AgNO3 as silver(I) catalyst and F-TEBA-BF4 as fluorine source in 1,2-dichloroethane and water at ambient temperature. As shown in Scheme 5.38b, both electron-donating and electron-withdrawing substituents on the aryl were well tolerated and gave the products in good yield and high stereoselectivity. Also, heteroaromatic substituted 1-ethinylcyclobutanols as well as aliphatic alkynes were suitable substrates for the developed reaction. Unfortunately, the method could be extended neither to cyclopropanols nor to cyclopentanols, but it is worth to note that the ring expansion could be also followed by chlorination or bromination under similar reaction conditions [73]. R O

F-TEBA-BF4, AgNO3, DCE, H2O, rt, 16–24 h

HO

R F

Br O

R (b)

F

F

60%

58%

F

80%

HO

Cl

S

F (a)

O

O

O

60%

O + Ag(I) + F-TEBA-BF4

O

O R

R

+Ag(II)–F

–Ag(I)

Ag(III)–F

R F

Scheme 5.38 Silver-catalyzed ring expansion/fluorination of ethinyl cyclobutanols for the synthesis of monofluoroethenyl cyclopentanones. (a) Selected examples to demonstrate the substrate scope. (b) Proposed reaction mechanism [73].

5.2.3.4

C—H Bond Activation

An interesting strategy for benzylic C—H fluorination is based on the idea that α-aminoalkyl radicals that are accessible from amino acids should be able to abstract a hydrogen atom from a benzylic sp3 C—H bond. The Baxter group demonstrated that α-aminoalkyl radicals of glycine can be generated by oxidative decarboxylation with AgNO3 as silver(I) catalyst and F-TEBA-BF4 that serves

297

298

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

as both a mild oxidant and source of fluorine (Scheme 5.39). The α-aminoalkyl radicals are further capable to abstract a benzylic hydrogen atom that allows the introduction of a fluorine atom. Mechanistic studies indicated that unprotected amino acids play a crucial role by binding to the silver catalyst and lowering its oxidation potential. Electron-rich and electron-poor substrates were functionalized, although higher conversion was observed for electron-rich substrates. By adjusting the stoichiometry of the amino acid and fluoride-containing reagent, difluorination was obtained for the electron-rich substrates. Unfortunately, the method remains limited to secondary and primary benzylic sites of which primary benzylic positions work best [35b].

H

+

H 2N

CO2H

F-TEBA-BF4, AgNO3, MeCN, H2O, 35 °C

F F Ph 76%

Ph 64%

F

F F

F Ph

F

BPin 76%

31%

N 57%

Scheme 5.39 Radical benzylic sp3 C—H fluorination using glycine as radical precursor. Selected examples were shown in order to demonstrate the tolerance toward different functional groups and systems [35b].

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations In this chapter we address the current status of silver-mediated trifluoromethylations including the development of syntheses to perfluoroalkyl compounds mediated by silver reagents (for reviews, see [8d, 74]). The access to those higher fluorinated compounds is needed for drug development and crop protection as they offer in many cases enhanced lipophilicity and metabolic stability in comparison with their non-fluorinated derivatives (Figure 5.4). This chapter covers both silver-mediated and silver-catalyzed conversion of arenes, alkynes, and alkenes to their respective trifluoromethyl or perfluoroalkyl counterparts (Scheme 5.40). Many of these transformations apply commercially available fluorinated reagents and salts that are listed in Table 5.1. One of the most widely used reagents for nucleophilic trifluoromethylation is (trifluoromethyl)trimethylsilane (TMS-CF3 ) that is also called Ruppert–Prakash reagent. Being discovered in 1984 by Ruppert et al. [75], its applications were further developed by Prakash et al. [76]. A number of analogous linear and branched alkyl derivatives are also commercially available and therefore commonly used not only in silver-mediated reactions.

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

NH

F O N N

F3C

S

CF3

H

N

O

H N

H

O

N H

O

Flufenacet

H N

O F 3C

N

F 3C

H

CF3

Dutasteride

Fluoxetine

Mefloxacin F

Me N N Me

O OH

N

O

F3C

OH Me

F3C F3C

SO2Me

O N

F

HN O O

N H N

Pyrifluquinazon

Pyrasulfotole

CF3 CF3

I

Flubendiamide

HN

SO2CH3

Figure 5.4 A selection of biologically active trifluoroarenes and perfluoroalkyl arenes. X

X

X

X

Electrophilic (“CF3+”) Nucleophilic (“CF3–”) Radical (“CF3 ”)

Silver catalyzed Silver mediated Rf

Rf

Rf

Rf

Scheme 5.40 Reactions covered in Section 5.3. Table 5.1 Overview about typically applied perfluorinated reagents and salts applied in silver-mediated and silver-catalyzed trifluoromethylation and perfluoroalkylation reactions. Reagent

Availability

Me3 Si—CF3

Commercial

Me3 Si—(CF2 )n F

Commercial for n = 1, 2, 3, 4, 5, 6, 7, 8, 10

Me3 Si—(C(CF3 )2 )F

Commercial

Me3 Si—(CF2 )n CO2 R

Commercial for n = 1, 2

Me3 Si—CF2 Ar

Commercial for Ph

Me3 Si—(CF2 )SPh

Commercial

CF3 SO2 Na

Commercial

CF3

299

300

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

5.3.1

Syntheses and Properties of Perfluoroorgano Silver Compounds

The syntheses of perfluoroorgano silver(I) compounds as well as their structure and use in transmetalation reactions were recently reviewed [77, 78]. Perfluoroorgano silver(I) compounds were generally prepared in one step by commercially available silver(I) fluoride and either perfluoroalkyl silyl sources [79] or perfluorinated olefins or alkynes (Scheme 5.41) [80]. Alternatively, these reagents can be obtained by transmetalation starting from other perfluoroalkylated metal organyls such as perfluoroalkyl cadmium compounds and silver(I) salts. However, these routes suffer from the simultaneous generation of a silver(III) species by in situ oxidation of the previously generated perfluoroorgano silver(I) species and were therefore less applied [81]. AgF – (or Ag(I) salt + F ) Me3Si Rf

Rf = CF3, C6F5, ...

AgF – (or Ag(I) salt + F )

F R

AgRf

F R

F3C

(a)

Rf = CF3, C6F5, ...

CF3

AgF MeCN

Ag

R R CF3 F

Ag

(b)

CF3 CF3

Scheme 5.41 Synthesis of perfluoroorgano silver compounds. (a) Synthesis from perfluoroalkylsilyl reagent. (b) Synthesis from fluorinated olefins/alkynes.

Most perfluoroorgano silver compounds were synthesized in polar and coordinating solvents like acetonitrile or propionitrile, allowing their rapid synthesis in very good yields at room temperature. Under these conditions, the silver species is sufficiently stabilized against decomposition by coordination of the silver atom to the N-donor group of the solvent [79b]. Csp2 -Ag-perfluoroorgano silver compounds profit from higher stability than their non-fluorinated counterparts, allowing harsher reaction conditions like thermally heating or exposure to light. [80a,e] Nevertheless, only few neutral [79b, 82] and anionic perfluoroorgano silver complexes [82, 83] have been isolated and characterized by X-ray analysis so far. In solution, perfluoroorgano silver compounds exist in a dynamic equilibrium of their neutral and anionic form comparable with the well-known equilibria of silver halides (Scheme 5.42), which is of course influenced by different parameters like the solvent, the silver concentration, and the temperature [82]. While in solvents like acetonitrile or DMF, the ionic species predominates over the neutral form; in stronger N-donating solvents such as triethylamine, only the neutral form was observed via 19 F NMR analysis [81]. +

2 AgRf S

–

Ag(S)2 + Ag(Rf)2 S = solvent

Scheme 5.42 Equilibrium of ionic and neutral perfluoroorganyl silver species.

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

5.3.2

Silver-Mediated Perfluoroalkylations

Although the first perfluoroorganyl silver compounds were already synthesized in 1950 [84], their application in organic synthesis as perfluoroalkylating reagents has been barely investigated over the following decades [8a, 21f, 49, 52a, 61, 72, 85]. However, perfluoroorganyl silver compounds were used in some C—C coupling reaction from which the most important examples were summarized in Scheme 5.43 [77b]. For example, they were applied as nucleophiles in the reaction with alkyl iodides [80b,d,e, 86], benzyl/allyl bromides [80b, 87], carbon dioxide [87], and acyl chlorides [80b] (selected examples in Scheme 5.43). Further examples demonstrated the use of perfluoroorgano silver compounds as precursors for the syntheses of sulfides [80c, 88], halides [80c,d,e, 88, 89], or nitroso compounds [90]. However, the real scope of these reactions was not explored, and only single examples have been raised in literature. Ag F

F3C

MeI

F

F3C

95%

F

F

(1) CO2 (2) BnBr (CF3)2CFAg

60%

O F3C F3C

OBn F

Br (CF3)2CFAg

50%

F

CF3 CF3

Scheme 5.43 Reported C—C coupling reactions using perfluoroorgano silver compounds prior to the year 2000.

5.3.2.1 Perfluoroorgano Silver Compounds in Copper-Mediated Perfluoroalkylations

Without any doubts, perfluoroalkyl copper compounds are powerful perfluoroalkylating reagents for the syntheses of various perfluoroalkylated substrates [8, 91]. These copper compounds can either be generated in situ or directly used as stable copper complexes (e.g. (phen)CuCF3 ). Nevertheless, many reports underline the positive effect of silver salts in these transformations. For example, Huang and coworkers described in 2011 a cooperative effect of silver in the copper-catalyzed trifluoromethylation of aryl iodides (Scheme 5.44) [83c]. They were able to demonstrate that the addition of silver(I) fluoride significantly increased the yield of the Cu-catalyzed reaction when (trifluoromethyl)trimethylsilane was used as CF3 source when compared with a silverfree protocol under otherwise similar reaction conditions. Furthermore, this is a rare example for a copper-catalyzed trifluoromethylation reaction in which

301

302

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

TMS-CF3, CuI (cat.), dmeda (cat.), NaOtBu (cat.), AgF, NMP, 90 °C, 6 h

I R

CF3 R

R = NO2, CN, CF3, Me, OMe

47−98%

Scheme 5.44 Ag-supported Cu-catalyzed trifluoromethylation of aryl iodides. dmeda, dimethylethylenediamine; NMP, N-methyl-2-pyrrolidone.

TMS-CF3 is applied as CF3 source instead of the more commonly used but also more expensive (trifluoromethyl)triethylsilane. In order to prove the cooperative effect of silver, both the (bathophenanthroline)AgCF3 and the (bathophenanthroline)CuCF3 complex were synthesized and tested under the developed reaction conditions. While the silver complex does not react with the aryl iodide in the absence of copper salts (Scheme 5.45a), the copper complex works also without the addition of a silver salt. This led to the suggestion that the trifluoromethyl silver acts as a transmetalation reagent for the generation of trifluoromethyl copper that then reacts with the aryl iodide to afford the desired trifluoromethylated product in a second step (Scheme 5.45b). I

N Ag CF3

CF3

N

NMP, 90 °C, 3 h

(a)

N AgI N TMS-CF3

(b)

CF3 ArI

+ AgF

N

Ag CF3 N

Ar-CF3

N

N TMS-F

Cu N

Cu

I

N

Scheme 5.45 (a) The trifluoromethyl silver complex without additives showed no reactivity toward aryl iodides. (b) Postulated cooperative effect of silver in the copper-catalyzed trifluoromethylation of aryl iodides.

A similar effect was observed in the selective copper-mediated trifluoromethylation of 5-iodotriazoles by the same working group (Scheme 5.46). By the addition of silver carbonate to the reaction, not only the obtained yields were significantly increased, but also side reactions like the protodehalogenation reaction were suppressed [92]. Based on a similar idea, Duan and coworkers developed a Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation of arylpropiolic acids with (trifluoromethyl) trimethylsilane, enabling the construction of Csp—CF3 bonds (Scheme 5.47). The presented methodology benefits of a broad tolerance toward functional

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

R1

N N

I

N

TMS-CF3, CuI, KF, phen, Ag2CO3, DMF, 100 °C, 2–3 h

R1 F 3C

R2

N N

N

R2

52−90%

Scheme 5.46 Trifluoromethylation of different 5-iodo-1,4-substituted triazoles.

CO2H

TMS-CF3, CuI, phen, Ag2CO3, KF, DMF, RT, 6.5 h

R

CF3 R

15 examples (31−87%)

Scheme 5.47 Synthesis of CF3 -containing alkynes by a Cu(I)/Ag(I)-mediated decarboxylative trifluoromethylation [93].

groups on the aryl moiety and mild reaction conditions, making it applicable to many substrates and affording the corresponding products in moderate to good yields. Probably, the [(phen)Cu(CF3 )alkyne] complex is generated in situ by the transmetalation between the [(phen)Cu(CF3 )] intermediate and the alkynyl silver complex Ag—≡—Ar that is formed by the decarboxylation of the arylpropiolic acid in the presence of silver(I) carbonate. Finally, the reductive elimination of the [(phen)Cu(CF3 )alkyne] complex delivers the corresponding products [93]. In 2002, a new reagent combination for the trifluoromethylation of various halides was introduced by Kremlev et al. that enables besides the substitution of aromatic and heteroaromatic bromines or iodides and also one of the sp3 -hybridized iodides (Scheme 5.48). Most likely the reactive species is trifluoromethyl copper (CuCF3 ) that is prepared in situ from the conveniently accessible silver(I) fluoride, trimethyl(trifluoromethyl)silane, and elemental copper by oxidative transmetalation. Mechanistic investigations based on various spectroscopic methods indicate that an interplay of copper in different oxidation states such as I, II, and III with elemental copper and silver as halide interceptors explains the reactivity of the reagent. Notably, this example is one of the few reactions that is demonstrated to work with aryl bromides [94]. An alternative trifluoromethylation method for arenes and heteroarenes was presented by Wan and coworkers and applies trimethylsilyl chlorodifluoroacetate

R Hal

TMSCF3, AgF, Cu, DMF, 90 °C, 5 h

R CF3

R = aryl, heteroaryl, alkyl Hal = Br, I

Scheme 5.48 Trifluoromethylation of various bromides and iodides including differently substituted aryls and various heteroaryls, as well as alkyl iodides.

303

304

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

(TCDA) as new reagent along with CuI, AgF, and TMEDA in DMF (Scheme 5.49). The addition of stoichiometric amounts of CuI was crucial for the reaction, since no reaction was observed without a copper(I) source. The authors assumed that the reaction proceeds in a stepwise manner whereby difluorocarbene is formed along with CO2 and AgCl by the reaction of TCDA with AgF. The difluorocarbene can then react with a second equivalent of AgF furnishing AgCF3 that exchanges a ligand with copper iodide to afford AgI and the reactive CuCF3 complex. In comparison with other established reagents, TCDA shows a good functional group tolerance including ester, amide, aldehyde, hydroxyl, and carboxylic acids and can be applied to many substrates varying from electron-deficient to electron-rich (hetero)aryl iodides [96]. I

CF3

ClF2CCO2TMS, AgF, CuI, TMEDA, DMF, 2–6 h, 100 °C

R

R

31 examples (17−98%)

R = CO2R, CHO, COMe, CN, NO2, Hal, OH, OR CONH2

CO2Me

88%

CF3 28%

N

N

N

CF3

CF3 70%

CO2Et CF3

83%

N

N CF3

69%

CF3 91%

Scheme 5.49 Trifluoromethylation of aryl iodides. TCDA, trimethylsilyl chlorodifluoroacetate [95].

The first method for trifluoromethylation of arylsilanes was reported by the Hartwig group and proceeds under mild oxidative reaction conditions with [(phen)CuCF3 ] as CF3 source and air as oxidant (Scheme 5.50). The optimization studies revealed that all reactions with additional AgF under air gave higher yields than those with other fluoride sources such as KF, KHF2 , or TBAF. In a couple cases, the addition of benzoquinone improved the yield when compared with air as only oxidant. With these reaction conditions, many arylsilanes including also heteroarylsilanes were trifluoromethylated in moderate to good yields [97]. 5.3.2.2

Perfluoroorgano Silver Compounds as Precursors for Radicals

In 1968, Miller and Burnard [80a] observed the dimerization of different perfluoroalkyl silver compounds after thermally heating and concluded that free radical chemistry led to the formation of these compounds. However, due to the rapid dimerization, the idea of using perfluoroorgano silver compounds as precursors for perfluoroalkyl radicals in perfluoroalkylation reactions was not further investigated until recently. In 2011, Sanford and coworkers reported the silver-mediated trifluoromethylation of different electron-rich arenes using TMS-CF3 as trifluoromethyl source

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

(phen)CuCF3 (cat.), AgF, benzoquinone, O2, DMF, 50 °C, 16 h

[Si] R

CF3 R

18 examples 34–96%

[Si] = SiMe(OSiMe3)2 O

F3C

OMe F3C

MeO

NEt2 NC

CF3

CF3

88%

81%

CF3

CF3

N

75%

Boc N

CF3

73%

96%

Scheme 5.50 Trifluoromethylation of aryl- and heteroarylsilanes. All yields were determined by 19 F NMR spectroscopy. More examples also for late-stage trifluoromethylation of pharmaceutically active molecules were given in the publication. phen, phenanthroline [97].

R

Me3Si CF3 AgOTf, KF, DCE, 85 °C, 24 h

CF3 R

15 examples (42–88%) Me

OMe CF3

CF3

S

CF3

O Me

81% (o/m/p = 1.4 : 1 : 2.7)

87% (o/m/p = 2.7 : 1 : 1.2.)

72% (C1/C2, 8 : 1)

Me N

N

O

N Me

N

CF3

42%

Scheme 5.51 Silver-mediated trifluoromethylation of arenes. DCE, 1,2-dichloroethane [98].

and AgOTf as silver source (Scheme 5.51). The optimization of the reaction revealed that AgOTf worked best for all tested silver salts and that no reaction was observed in the presence of copper salts such as CuI or [CuOTf2 ]⋅C6 H6 . In general, the reaction showed a modest preference for trifluoromethylation at C—H sites ortho and para to the electron-donating group for arenes. Besides arene, also heteroaromatics like thiophene, caffeine, or N-methylated pyrrole were trifluoromethylated in good yields with moderate to excellent site selectivity [98]. Initially, the authors believed that the reaction proceeded via a silver-promoted generation of a free trifluoromethyl radical that undergoes a radical aromatic substitution reaction. This would be followed by a SET from the radical intermediate to a second equivalent of Ag(I) and releases the trifluoromethylated product along with Ag(0) and HOTf (Scheme 5.52). In order to study the mechanism of the reaction, a radical inhibitor was added to the reaction, causing a dramatic drop in yields under otherwise analogous conditions supporting the assumption of radicals being involved in the mechanism. However, the observed selectivity

305

306

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

TMS−CF3

AgOTf

–TMSOTf

AgCF3

–Ag0

CF3

F3C H

R

R

CF3

AgOTf

–Ag0 –HOTf

R

Scheme 5.52 Proposed reaction mechanism for silver-mediated trifluoromethylation reactions [98].

in the reaction with anisole differs from the selectivity obtained by other established radical trifluoromethylation protocols, which suggests against a purely free radical pathway [98]. In 2012, Hafner and Bräse demonstrated that easy accessible aromatic triazenes are suitable substrates for silver-mediated aromatic C—H trifluoromethylation reactions, whereby AgF as silver source and TMS-CF3 as trifluoromethyl source were used in perfluorohexane (Scheme 5.53) [91, 100]. The trifluoromethylated products were obtained in good yields and high ortho-selectivity, especially when the para-position of the aromatic triazenes is blocked by another functional group. The reaction showed in general a broad tolerance toward functional groups including iodides or bromides that allow further functionalization. Moreover, the used triazenes are useful equivalents of protected diazonium salts and can be converted into different functional groups such as halides, azide, or nitrile or back to the starting amine [99].

N

N N

R

R = I, Br, Cl, F, CN, OMe, CO2Et

TMS-CF3, AgF, C6F12, 100 °C, 4 h

N

N N CF3

R

11 examples 39−74%

Scheme 5.53 ortho-Trifluoromethylation of functionalized aromatic triazenes [99a].

Because of the tolerance toward halides, in particular, iodides and bromides that are typically addressed by common copper- or palladium-mediated reactions, the presented silver-mediated trifluoromethylation reactions are completely orthogonal to other metal-mediated perfluoroalkylation reactions [8]. Further investigation by the group of Bräse allowed the transfer of the developed protocol to other silylated perfluoroalkyl sources such as (pentafluoroethyl) trimethylsilane, (heptafluoropropyl)trimethylsilane, and (ethoxycarbonyldifluoromethyl)trimethylsilane, enabling the synthesis of further perfluoroalkylated and ethoxycarbonyldifluoromethylated arenes in mostly good yields. Similar to the corresponding trifluoromethylation reaction, these perfluoroalkylations formed the corresponding products with high ortho-selectivity, leading to mono-ortho-substituted and di-ortho-substituted aromatic triazenes when para-substituted triazenes have been used (Scheme 5.54). Most likely the high

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

N

N N

TMS-Rf, AgF, C6F12, 100 °C, 4−16 h

R

R = I, Br, Cl, F, CN CO2Et

N

N N

Rf = C2F5, C3F7, CF2CO2Et

Rf R

41−79%

Scheme 5.54 ortho-Perfluoroalkylation and ethoxycarbonyldifluoromethylation of aromatic triazenes [101].

yields as well as the high regioselectivity can be explained by the coordination of the neutral trifluoromethyl species to the triazene moiety. This leads to the generation of a trifluoromethyl radical next to the ortho-position of the aromatic core structure [102]. Not only trimethyl(perfluoroorgano)silanes act as suitable precursors for perfluoroalkyl silver compounds, but also highly fluorinated olefins can be reacted with differently substituted arenes under solvent-free conditions to give methoxycarbonyltetrafluoroethylated arenes (Scheme 5.55).

D R

AgF, CF2=CFCO2Me, 100 °C, 16 h

D = −(N=N)−N(iPr)2 R = I, Br, Cl, F, CN, OMe, CO2Et

N N N F CF3 R

CO2Me

MeO or

16 examples 18−57%

F CF3

R

CO2Me

4 examples 25−42%

Scheme 5.55 Silver-mediated addition of fluoroolefins to arenes [101].

The fluoroalkylating reagent was prepared in situ via regioselective addition of silver(I) fluoride to the double bond of the fluorinated olefin, affording a secondary perfluoroalkyl silver species [102]. The regioselectivity of the nucleophilic addition of the fluoride ion was attributed to the repulsive interactions between the π-bond and the nonbonding electron pairs of the fluorine substituents (Scheme 5.56) [80a,c, 82, 101, 103]. However, fluoride abstraction also enables dimerization and oligomerization of fluorinated olefins, limiting the synthetic potential and the application of these fluorinated olefins in synthesis [104]. With the developed methodology the introduction of a methoxycarbonyltetrafluoroethyl group was accomplished in the presence of silver(I) fluoride and with 2,3,3-trifluoroacrylate as fluorinated olefin for various aromatic triazenes, as well as anisole derivatives (Scheme 5.56). The reaction proceeds best under neat reaction conditions, since the dimerization/oligomerization of the olefin was herein

307

308

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions F F

F F

AgF

R

Regioselective addition

F

F

F

R

F F

Ag

Repulsive interaction

Scheme 5.56 Regioselective addition of silver(I) fluoride to highly fluorinated olefins [101].

suppressed. In contrast, if other solvents like acetonitrile or 1,2-dichloroethane were applied, reduced yield or no conversion was observed, probably due to competing, and this case favored dimerization and oligomerization reactions. A similar concept was also used by Hu and coworkers in the silver(I)-mediated fluorinative homocoupling reaction of β,β-difluorostyrene derivatives. Like previously shown silver(I) fluoride adds regioselectively to the double bond of gem-difluoroalkenes and generates a (α-trifluoromethyl)benzyl silver compound that readily dimerizes to the corresponding homocoupled product that is depicted in Scheme 5.57. Both generality of the reaction of substrate scope and functional group tolerances were shown, enabling the synthesis of various homocoupled products [105]. Recently, Li et al. developed a silver-catalyzed decarboxylative radical addition–cyclization reaction between differently substituted α,α-difluoroarylacetic acids and acrylamides (Scheme 5.58). In the presence of silver(I) nitrate and K2 S2 O8 as oxidant, a number of difluorinated oxindoles have been synthesized under mild reaction conditions in moderate to good yields. The mechanism of the reaction is believed to proceed via a free radical mechanism where the in situ formed Ag(II) complex initiates a SET to the α,α-difluoroarylacetic acid under the release of CO2 and the formation of

R

CF3

AgF, 4 Å MS, pyridine, THF, dark, 80 °C, 6 h

F

R

F

R

CF3 11 examples 40−78% (syn/anti, c. 1 : 1)

R = I, Br, NPh2, OMe SMe, CO2Et

Scheme 5.57 AgF-mediated homocoupling of gem-difluoroalkenes [105].

F F

Ar

CO2H

AgNO3, K2S2O8, DMSO, H2O, 55 °C

+

Ar = anisole, naphthalene, thiophene

N Me

O

Ar

Me

F F O

N Me

7 examples (25−60%)

Scheme 5.58 Silver-catalyzed decarboxylative radical addition–cyclization of α,α-difluoroarylacetic acids with acrylamides for the synthesis of difluorinated oxindoles [53].

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

the corresponding α,α-aryl radical. The latter attacks the acrylamide at the terminal position, furnishing the more stable tertiary radical that reacts via an intramolecular radical cyclization. The resulting aryl radical is then oxidized and gives after deprotonation the desired products [53]. 5.3.2.3

Perfluoroorgano Silver Compounds as Nucleophilic Reagents

Due to the high affinity of silver(I) salts to halides, it is intriguing that only a few examples of silver-mediated perfluoroalkylation reaction with organic halides are reported so far. One of these silver-mediated perfluoroalkylation reactions was developed by Tyrra and coworkers in 2007 (Scheme 5.59). By using trifluoromethyl silver in combination with stoichiometric amounts of silver fluoride, the selective synthesis of trifluoromethyl ketones starting from their corresponding acyl chlorides was accomplished [106]. Until now, no further progress has been made in the development of silver-mediated nucleophilic perfluoroalkylation reactions with organic halides. O R

O

TMS-CF3, AgF Cl

R

EtCN, –30 °C→rt, 12 h or DMAP, CH2Cl2, 30 °C→rt, 48 h O

CF3

50–77%

O CF3

O CF3

CF3 O

Br 61%

50%

61%

Scheme 5.59 Synthesis of trifluoromethyl ketones using AgCF3 [106].

Hu and coworkers showed that trifluoromethyl silver is suitable for the silvermediated vicinal trifluoromethylation–iodination of different substituted arynes, while no reaction was observed between benzynes and a trifluoromethyl zinc or a trifluoromethyl copper species (Scheme 5.60). However, in situ generated trifluoromethyl silver is able to add readily to the triple bond of benzyne. In the presence of 1-iodophenylacetylene as electrophile, the corresponding ortho-trifluoromethylated iodoarenes are formed in moderate to excellent yield [107]. Ph TMS R OTf

R = Me, Ph, OMe, Br, allyl

I

AgCF3, TMP, CsF, MeCN, 50 °C, 5 h

CF3 R I

35−94%

Scheme 5.60 Silver-mediated trifluoromethylation–iodination of arynes [107].

309

310

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

Based on NMR studies, the reaction mechanism has been proposed, demonstrating that the addition of 2,2,6,6-tetramethylpiperidine (TMP) is crucial for the reaction in order to suppress side reactions during the iodination step (Scheme 5.61). After the addition of TMP to the reaction mixture, a trifluoromethyl silver–TMP complex is formed that interacts with 1-iodophenylacetylene followed by the expulsion of silver phenylacetylene to afford the corresponding trifluoromethylated phenyl iodides. Ag

AgCF3, TMP

R

TMP

R CF3 Ph

I Ph

I

Ag species

R

−Ph

CF3

I R

Ag

CF3

Scheme 5.61 Proposed mechanism of the trifluoromethylation–iodination of arynes.

The reactivity of perfluoroalkyl silver compounds toward arynes was also examined by Lee and coworkers in the silver-mediated trifluoromethylation of arynes [33]. This approach allows the synthesis of different trifluoromethylated arenes including indoline and isoindoline derivatives from bis-1,3-diynes as nonaromatic building blocks (Scheme 5.62). Mechanistically, the silver salt is proposed to induce the cyclization of these substrates to form an aryne that reacts after addition of the trifluoromethylating reagent similar to the mechanism presented by Hu et al. Noteworthy, this concept could be expanded to silver-mediated fluorination and trifluoromethylthiolation. R′

R′ Y Z

R

R = alkyl; R′ = Ph, alkyl Y, Z = CH2, NTs, O

TMS-CF3, AgF, MeCN, 90 °C, 4 h

R Y Z

o m CF3 10–78%

Scheme 5.62 Silver-mediated trifluoromethylation of bis-1,3-diynes.

Another usage of trifluoromethyl silver was recently reported by Wang and coworkers who showed its application for the silver-mediated trifluoromethylation of aryldiazonium salts (Scheme 5.63). After diazotization of commercially available anilines, the addition of trifluoromethyl silver enabled the direct trifluoromethylation of the corresponding diazonium salts. The reaction showed a

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

NH2 R

N2 Cl

Aq. HCl, tBuONO, EtCN, 0 °C, 15 min

CF3

AgCF3, EtCN, −78 °C, 3 h → rt, 1 h

R

R

R = CO2Et, COPh, CO2H, OBn, OMe, OH, NHAc, I, Br, Cl, F, NO2, SO3Et, Bpin, SiMe3

43−97%

O F3C

CF3

N

CO2Et

N Ts

N

Ph

H

O

H

F3C

72%

55%

58%

F3C

H

57%

Scheme 5.63 Silver-mediated trifluoromethylation of aryldiazonium salts [33, 108].

broad substrate scope and good functional group tolerance, allowing the conversion of various anilines into the trifluoromethyl arenes. Remarkably, the conversion of the amine group to the corresponding trifluoromethyl group was also feasible in good yields even when embedded in complex molecules such as an estrone and tocopherol framework showing the potential of this transformation [33, 108]. As expected, mechanistically studies could not prove the involvement of any radical intermediates. Instead an oxidative addition–reductive elimination mechanism seems likely as it is depicted in Scheme 5.64, whereby a high-valent aryl silver species is formed, enabling the elimination of AgCl [57]. Cl R

N2

AgCF3

Oxidative addition

R

CF3 Ag Cl

CF3

–AgCl

Reductive elimination

R

Scheme 5.64 Proposed mechanism for the silver-mediated trifluoromethylation of aryldiazonium salts.

Recently, this chemistry has been extended to hexafluoropropylene (HFP) as accepting olefins. Wang et al. were able to develop a copper-promoted perfluoroisopropylation of different aryldiazonium salts under mild conditions using commercially available HFP as the starting material, AgF as fluorine source, and CuI as copper source. Remarkably, the diazotization and perfluoroisopropylation can be conducted as a one-pot direct protocol converting various arylamines into their corresponding perfluoroisopropylarenes with good functional group compatibility (Scheme 5.65) [85f ]. The preparation of the thermally stable 1,3-bis(2,6-diisopropylphenyl)imidazol (idin)ylidene NHC-ligated difluoromethylated silver complexes [(NHC)AgCF2 H] led to the development of new difluoromethylation reactions with different electrophiles such as diaryliodonium salts, vinyl(phenyl)iodonium salts, aryldiazonium salts, and acyl chlorides (Scheme 5.66). All reactions proceed at room

311

312

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

F

CF3

(1) AgF, MeCN, rt, 2 h

F

F

(2) CuI,

F3C

CF3

R N2 Cl

, rt, overnight R

NH2

F

23 examples (34−89%)

tBuONO,

p-TSA, ACN, rt, 2 h

R

R = Br, F, NO2, NHAc, OBn, CN, COMe

Scheme 5.65 Silver-catalyzed regioselective perfluoroalkylation of hexafluoropropylene [85f ].

N2 BF4 R

N2CF2H

[(SIPr)Ag(CF2H)], MeCN, rt, 30 min

R

N

8 examples (74−90%) O

Cl

O

[(SIPr)Ag(CF2H)], CuI (cat.), phen (cat.), MeCN, rt, 2 h

R

Ag CF2H

N

CHF2

R

[(SIPr)Ag(CF2H)]

10 examples (55−92)% OTf I

R [(SIPr)Ag(CF2H)], CuI, MeCN, rt, 30 min

CHF2 R

[(SIPr)Ag(CF2H)], CuI, MeCN, rt, 30 min

OTf Ar

I

Ph

Ar

CHF2

R

13 examples (61−83%)

6 examples (71−94%)

Scheme 5.66 Silver-catalyzed difluoromethylation of diazonium salts, iodonium salts, and acid chlorides [109].

temperature affording the products in good to excellent yields with a broad tolerance toward functional groups such as halides, cyano, or ester. It is worth to note that alternative methods for the synthesis of difluoromethylated alkenes like the copper-mediated difluoromethylation of aryl iodides with TMSCF2 H or n-Bu3 SnCF2 H typically require high temperature, while this method works also under relatively mild conditions. Interestingly, the Sandmeyer-type trifluoromethylation of aryldiazonium salts gave even higher yields in the absence of copper salt than in the presence of copper salts. Most likely this is due to the faster

5.3 Silver-Mediated Trifluoromethylations and Perfluoroalkylations

direct nucleophilic substitution reaction compared with the dinitrogenative Sandmeyer reaction under the developed reaction conditions [109]. 5.3.3

Silver-Catalyzed Perfluoroalkylations

While all the previously presented examples cover procedures with stoichiometric amounts of perfluoroorgano silver compounds as perfluoroalkylating reagents, there are only a few silver-catalyzed trifluoromethylation reactions known. In 2013, Qing and coworkers reported a silver-catalyzed radical hydrotrifluoromethylation of unactivated alkenes using TMS-CF3 , catalytic amounts of a silver(I) salt, and PhI(OAc)2 as an oxidant [85v]. The desired hydrotrifluoromethylated products were first found in combination with the corresponding trifluoromethylated olefin. However, after addition of an H-donor like 1,4-cyclohexadiene (1,4-CHD), the desired products were obtained in good yields and selectivity, allowing the synthesis of various hydrotrifluoromethylated compounds with high compatibility of functional groups (Scheme 5.67). TMS-CF3, AgNO3 (cat.), PhI(OAc)2, NaOAc, 1,4-CHD, NMP, rt, 10 h

H

R

CF3

R

50–82% O S O O

H

CF3

H

O H

CF3

50%

77%, (dr = 6 : 1)

CF3

HO

82% O

O Cl

S O

H H

H CF3

60%

F 3C

H

O H

72%

Scheme 5.67 Silver-catalyzed regioselective hydrotrifluoromethylation of alkenes [85v].

In order to discover the mechanism of the reaction, experiments showed that most likely trifluoromethyl radicals are involved as the addition of radical scavengers suppressed the reaction under generation of the TEMPO-CF3 adduct. The proposed mechanism is depicted in Scheme 5.68. After the formation of the trifluoromethyl radical, it attacks the unactivated terminal alkene and forms the more stable radical that abstracts a hydrogen atom from 1,4-CHD to afford the anti-Markovnikov-type hydrotrifluoromethylation product. A similar concept was also applied for the trifluoromethylation of (hetero) arenes by Greaney and coworkers [110] whereby catalytic amounts of AgF are used in combination with TMS-CF3 and PhI(OAc)2 as reagents (Scheme 5.69).

313

314

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

TMS-CF3

Cat. AgNO3 PhI(OAc)2

CF3 R

H R

CF3

1,4-CHD R

CF3

Hydrogen abstraction

Scheme 5.68 Proposed mechanism for the silver-catalyzed hydrotrifluoromethylation of alkenes.

(Het)Ar H

TMS-CF3,PhI(OAc)2, AgF (cat. ), DMSO, rt, 20 h (Het)Ar CF3

40–94%

CHO

NMe2 CF3

MeO

N

S

O

OMe

MeO OMe

75%, (o/p = 2 : 1)

O CF3

63%

N

F3C

OMe

42%

Scheme 5.69 Silver-catalyzed trifluoromethylation of arenes [110].

It has been demonstrated that the combination of AgF/PhI(OAc)2 is crucial for the effective generation of trifluoromethyl radicals as both reagents alone gave only traces, respectively, and decreased yields of reactive trifluoromethyl radicals, when scavenged by TEMPO.

5.4 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations Since many pharmaceutically and agrochemically relevant molecules possess trifluoroalkylthio groups in particular trifluoromethylthiol groups (for a selection, see Figure 5.5), the introduction methods of these functional groups attracted much attention in the recent years. The trifluoromethylthio group has a significant influence on the chemical and physical behaviors compared with the non-fluorinated analog, as well as on the biological properties of the compound because of its high lipophilicity and strong electronegativity. Moreover, compounds bearing trifluoromethylthio groups can be easily converted to the corresponding sulfoxy derivatives that make those compounds even more valuable. Recent accounts [85k] and comprehensive reviews [111]

5.4 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations

Et

H N

SCF3

Tiflorex H N

O

N N N N S H 3C

CO2H O N S

O N H

H

Cefazaflur

CN

O Cl

H 3C

N

SCF3

N O

SCF3 O

F3C

Toltrazuril

CF3 S O

N N Cl

NH2

Fipronil

Figure 5.5 Pharmaceutically and agrochemically relevant molecules with trifluorothiomethyl and trifluorosulfoxyl groups.

summarize the current state of the art. Many copper-catalyzed reactions are known in combination with AgSCF3 as SCF3 -providing reagent, but only a few silver-mediated or even silver-catalyzed reactions are reported. In general, trifluoromethylthiolation proceeds via different pathways in which AgSCF3 can act as a nucleophile (− SCF3 ), electrophile (+ SCF3 ), or radical (⋅SCF3 ) precursor. For radical processes, the radical is often produced by mixing AgSFC3 with M2 S2 O8 (M = Na, K) in polar solvents such as MeCN, DMF, or DMSO. This chapter gives a non-comprehensive overview about the three processes. Some of the examples below are actually not real silver-mediated processes, since in these cases AgSCF3 reacts, strictly spoken, only as source of SCF3 , and silver itself has to the best of our knowledge no influence on the reaction mechanism. Nevertheless those examples help to understand the role of AgSCF3 in different reaction modes and are therefore cited. One of the simplest methods for the introduction of trifluoromethylthio group is the nucleophilic replacement of a leaving group by a SCF3 − ion. Xu et al. described a nucleophilic trifluoromethylthiolation of alkyl chlorides, bromides, and tosylates with AgSCF3 and nBu4 NI as additive (Scheme 5.70). Without additive, no conversion was observed, indicating that more ionic nBu4 N-SCF3 is formed in situ. The role of silver during this reaction is not discussed; nevertheless this approach is included for the sake of completeness [112]. R X

AgSCF3 Conditions

R SCF3

X = Br: 18 examples (65–99%) X = Cl: 11 examples (68–95%) X = OTs: 10 examples (41–95%)

Scheme 5.70 Nucleophilic trifluoromethylthiolation of alkyl chlorides (X = Cl, Bu4 NI, acetone, 80 ∘ C, 3–24 hours), bromides (X = Br, Bu4 NI, Bu4 NBr, THF, 80 ∘ C, 15 hours), and tosylates (X = OTs, Bu4 NI, MeCN, 100 ∘ C, 6 hours) [112].

AgSCF3 was also used as nucleophilic reagent in the synthesis of trifluoromethylthio-substituted 2H-chromenes and 1,2-dihydroquinoline derivatives starting from different substituted tertiary and secondary propargyl alcohols

315

316

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

(Scheme 5.71). From various experiments involving tertiary propargyl alcohols bearing two electron-rich or two electron-withdrawing or two electron-neutral aryls in all positions of the aryl moiety (ortho, meta, and para), it became clear that slightly lower yields were obtained with electron-rich substitution patterns than with their analogous electron-deficient ones. Moreover, one aryl ring was successfully replaced by an alkyl chain with only a small decrease in yield. By replacing the hydroxyl group at the aryl ring directly attached to propargyl alcohol by a protected amine, 1,2-dihydroquinolines were obtained in excellent yields under the same reaction conditions. Furthermore, the method was extended to secondary propargyl alcohols showing similar behavior with respect to steric and electronic effects compared with tertiary ones [113]. R1

OH

X

R3

X = O, NTs

R1

R2

AgSCF3, BF3OEt2, MeCN, rt, 0.5 h

R2

X R3

X = O: 32 examples (48–97%) X = NTs : 5 examples (76–82%)

SCF3

BF3 OEt2 –OH– +H+

Proposed reaction mechanism

R XH

R

R 6-Endo-trig

R XH

R

XH

R R

–H+

R Ag

X R

[Ag]

SCF3

SCF3

Scheme 5.71 Silver-mediated synthesis of trifluoromethylthio-substituted 2H-chromenes [113].

With AgSCF3 and trichloroisocyanuric acid (TCCA), the synthesis of various 3-((trifluoromethyl)thio)-4H-chromen-4-ones was accomplished (Scheme 5.72). Although no real catalysis happens, the reaction is an interesting application of an electrophilic trifluoromethylthio species and is therefore part of this chapter. Various functional groups such as nitro, halides, ethers, and esters were tolerated, giving the corresponding products with good yields of up to 95% [114]. O N

R OH

AgSCF3, TCCA, THF, rt

O SCF3 R O 23 examples (51–95%)

Scheme 5.72 Electrophilic trifluoromethylthiolation with AgSCF3 and TCCA for the synthesis of 3-((trifluoromethyl)thio)-substituted chromones [114].

5.4 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations

As shown in the previous chapters, arynes can serve as starting point for the introduction of fluorine or trifluoromethyl groups, as well as for the synthesis of aryl trifluoromethylthioethers (Scheme 5.73). With AgSCF3 , the o-SCF3 aryl silver intermediate is successfully formed in situ, but unfortunately did not undergo a clean protonation process. Rather, aryne multiple-insertion compounds were found, indicating that the generated aryl silver intermediate possesses a long lifetime and therefore is able to undergo (multiple) aryne insertion. In order to prevent this side reaction, a quenching step with 1-iodophenylacetylene was introduced to afford o-trifluoromethylthiolated iodoarenes. Against this background, Hu and coworkers established a versatile one-pot trifluoromethylthiolation–iodination protocol that provides the o-trifluoromethylthiolated iodoarenes in moderate yields and shows a satisfying tolerance toward functional groups such as acetals and bromides. Nevertheless, electron-withdrawing groups lower the obtained yields compared with electron-donating or electron-neutral functional groups, possibly because unproductive pathways were favored in this case. The o-trifluoromethylthiolated products can be used for the synthesis of Yagupolskii–Umemoto-type electrophilic trifluoromethylation reagents by a Sonogashira coupling with phenylacetylene followed by an acid-mediated intramolecular cyclization reaction [115].

TMS

I

R

OTf

Ph

AgSCF3, CsF, MeCN, rt, 8–24 h

SCF3 R I

(1) Phenylacetylene, CuI, (PPh3)2PdCl2, Et3N,rt

Ph S OTf – CF3

(2) Work up (3) TfOH, CH2Cl2, rt, 5min

Scheme 5.73 Silver-mediated trifluoromethylthiolation of arynes. Sonogashira coupling reaction, followed by a simple workup (evaporation and filtration), and an acid-mediated cyclization reaction give a Yagupolskii–Umemoto-type reagent in 80% yield [115].

In many reactions, AgSCF3 is used as precursor for the production of ⋅SCF3 and allows therefore silver-mediated radical trifluoromethylthiolations of different substrates from which a few examples are shown in the following paragraph. For example, Wang’s group realized a silver-mediated radical aryltrifluoromethylthiolation reaction of activated alkenes with AgSCF3 and K2 S2 O8 in order to synthesize trifluoromethylthio-containing oxindoles (Scheme 5.74) [116].

R2 R1 N R3

O

AgSCF3, K2S2O8, HMPA, MeCN, 75 °C,12 h

R2 R1

SCF3 O

N R3 25 examples (30–90%)

Scheme 5.74 Silver-mediated radical trifluoromethylthiolation reaction for the synthesis of trifluoromethylthio-containing oxindoles [116].

317

318

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

A little later, the same concept led to the development of a silver-mediated oxidative aromatic cyclization reaction of 1,6-enynes to afford different trifluoromethylthio-substituted fluorene derivatives (Scheme 5.75). Mechanistic investigations revealed that the reactions proceed via a radical process triggered by a C—C triple bond. The initial step is the formation of a styrene radical that is followed by a 6-exo-trig cyclization to form a tertiary alkyl radical. The latter initiates an intramolecular addition onto the aromatic ring generating an aryl radical intermediate that affords by a SET and a subsequent deprotonation of the desired product [117].

X

AgSCF3, K2S2O8, HMPA, 2,2′, 6′, 2″ -terpyridine, MeCN/DMF, 80 °C,12 h

R Y

X Y SCF3 37 examples (up to 87%)

X = NTs, C(CO2Me)2; Y = CH2 X = O; Y = CO SCF3

SET

SO42 SO4

X

AgCF3

–H+

S2O82

H SET Ag(I)

Y S2O8

SCF3 6-exotrig

2

SO42 X Y SCF3

SET

Ag(II)

X Y SCF3

SO4

H X Y SCF3

Scheme 5.75 Silver-mediated radical trifluoromethylthiolation/cyclization reaction of 1,6-enynes [117].

The same concept can also be found in the silver-mediated radical reaction cascade for the synthesis of 3,3-disubstituted-2-dihydropyridinones from N-(arylsulfonyl)acrylamides (Scheme 5.76) that involves the formation of four new bonds (one C—SCF3 , two C—C, and one C—N). Summarizing the mechanism, this was realized by the radical addition of ⋅SCF3 to the acrylic moiety of the molecule. The resulting carbonyl radical undergoes an ispo-cyclization in order to build up the first C—C bond. This is followed by the release of SO2 and the formation of an amidyl radical that furnishes the C—N bond by attacking the triple bound. Then, the second C—C bond is formed, affording the corresponding product in good selectivity and yield [85m]. Silver-mediated radical cyclization reactions like those presented before can also be used for the synthesis of 3-trifluoromethylthiolated coumarins that became accessible from aryl alkynoate esters with AgSCF3 and K2 S2 O8 in DMSO

5.4 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations

R1

O O

R3

AgSCF3, K2S2O8, HMPA, MeCN, 80° C, 20 h

R2

O N S O

R2

SCF3

N

R4

R3

R4 R1 12 examples (56–73%)

Scheme 5.76 Silver-mediated radical cascade reaction for the synthesis of trifluoromethylthiolated 3,3-disubstituted-dihydropyridinones [85m]. O

O

R1

AgSCF3, K2S2O8, DMSO, 30 °C, 15 h

O

O

R1 SCF3

R2

R2 24 examples (25–80%)

Scheme 5.77 Radical trifluoromethylthiolation of aryl alkynoates for the synthesis of 3-trifluoromethylthiolated coumarins. [118]

(Scheme 5.77). After regioselective addition of the ⋅SCF3 radical, a vinyl radical is formed that attacks the aryl. As a result, a radical-containing cyclic intermediate is formed. Further oxidation by Ag(II) and deprotonation yields the target coumarin. With this method many different substituted coumarin derivatives were synthesized in generally good yields [118]. The synthesis of trifluoromethylthiolated alkenes was recently achieved by oxidative trifluoromethylthiolation of aryl alkynoates with stoichiometric amounts of AgSCF3 and K2 S2 O8 as oxidant in MeCN (Scheme 5.78). The solvent had a crucial role in this reaction, since the exchange for DMSO gave the corresponding coumarine as major product and only traces of the desired trifluoromethylthiolated alkene were observed. Primary investigations of the mechanism showed that the reaction passes through a radical trifluoromethylthiolationinitiated aryl migration. After the silver-mediated formation of the SCF3 radical, the latter adds to the aryl alkynoate to form a styrene radical that subsequently undergoes ipso-cyclization to give a spiro intermediate. After 1,4-aryl migration, decarboxylation of the formed carboxyl radical occurred to give a vinyl radical that is then protonated by MeCN explaining the importance of the MeCN as solvent. The reaction is compatible with various aryl alkynoates containing different electron-donating and electron-withdrawing groups at different positions on both aryl rings and tolerates many functional groups such as halogens, nitriles, esters, and nitro group [119]. By a silver-mediated trifluoromethylthiolation of α,α-diaryl allylic alcohols with AgSCF3 , K2 S2 O8 as oxidant, and pyridine in MeCN, the synthesis of α-aryl-βtrifluoromethylthiolated ketones was accomplished in good yields (Scheme 5.79). The method tolerates symmetrical and nonsymmetrical α,α-diaryl allylic alcohols with electron-withdrawing, electron-donating, or electron-neutral substituents

319

320

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions Ar1 AgSCF3,K2S2O8, MeCN, 100 °C

O Ar2

O

SH

Ar1 SCF3 + R

Ar2

Ar1

O

O Ar2

21 examples (21–68%)

Major product in DMSO (80 °C)

O

Ar OAr

+

Ag(I)SCF3

CH3CN

SCF3

Ph

H SCF3

Ar

Ag(II)SCF3

SCF3 Ar

SCF3

Ar

Ar

SCF3

O O

O

–CO2

SCF3

O

O2C

Scheme 5.78 Silver-catalyzed tandem trifluoromethylthiolation/aryl migration of aryl alkynoates to trifluoromethylthiolated alkenes [119]. R1

AgSCF3, K2S2O8, pyridine, MeCN, 50 °C

R2

R1

HO R3

R1 = R2 = Ph R3 = H

Liu et al. [123]

O

21 examples (31–88%)

SCF3 R2 R3

OH

–H+

SCF3

Ph HO Ph Ph OH

SCF3

OH

Ph SCF3

Ph

SCF3 Ph

SCF3 Ph Ag(II)

Ag(I)

Scheme 5.79 Silver-mediated trifluoromethylthiolation of α,α-diaryl allylic alcohols for the synthesis of α-aryl-β-trifluoromethylthiolated ketones [120].

attached to one aryl or both of the aryl rings, respectively. On the basis of the substrate scope and mechanistic studies, the reaction proceeds via a radical mechanism that is initiated by the addition of a SCF3 radical to the double bond of the allylic alcohol. In order to stabilize the formed benzylic radical, the aryl group undergoes a neophyl rearrangement via a spiro [2,5]octadienyl radical. After migration, the carbon-centered hydroxyl radical is oxidized by Ag(II) and after deprotonation generates the desired ketone [120]. In analogy to the radical fluorinations presented in Section 5.2.3, a convenient approach for the introduction of a SCF3 group is the treatment of strained compounds such as cyclopropanes or arenes with AgSCF3 .

5.4 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations

Shi and coworkers applied this methodology to methylenecyclopropanes for the synthesis of trifluoromethylthiolated 1,2-dihydronaphthalene by radical trifluoromethylthiolation with AgSCF3 and Na2 S2 O8 as oxidant in hexamethylphosphoramide (HMPA) and DMSO (Scheme 5.80). In general, the reaction works better for substrates with electron-donating groups than for those bearing electron-withdrawing substituents with yields ranging from 25% to 65%. The obtained products were easily converted to their corresponding trifluoromethylthiolated naphthalene derivatives by dehydrogenation with Na2 S2 O8 as oxidant, offering an alternative method for trifluoromethylthiolated naphthalenes [56]. AgSCF3, Na2S2O8

R

SCF3

Na2S2O8

R

HMPA, DMSO, 80 °C, 8 h

SCF3 R

DMSO, 80 °C, 4–6 h

17 examples (25–65%)

8 examples (40–80%)

SCF3 R

Scheme 5.80 Radical trifluoromethylthiolation of methylenecyclopropanes for the synthesis of trifluoromethylthiolated 1,2-dihydronaphthalenes, whereby the reaction of AgSCF3 and Na2 S2 O8 provides the SCF3 radicals [56].

In 2016, Huang et al. established a silver-mediated oxidative trifluoromethylthiolation of cycloalkanols by C—C bond cleavage for the synthesis of β-, γ-, δ-, and ε-trifluoromethylthiolated ketones, whereby a brief reaction optimization revealed that the reaction proceeds best with AgSCF3 /K2 S2 O8 as oxidant and pyridine as additive in MeCN (Scheme 5.81). The elaborated method was not limited to strained cyclopropanols and cyclobutanols, allowing the synthesis of β- and γ-trifluoromethylthiolated ketones but could be also extended to cyclopentanols and cyclohexanols to afford the corresponding δ- and ε-trifluoromethylthiolated ketones. For 1-arylcycloalkanols, no significant influence of the functional groups itself or its position on the aryl ring was observed, giving the products with overall good yields. Besides aryl and heteroaryl substitution, also alkyl side chains were tolerated although the corresponding products were obtained in lower yields. Based on mechanistic studies, the reaction is assumed to proceed through a radical mechanism. R

OH R

AgSCF3, K2S2O8, pyridine, MeCN, 60 °C

O 1

n

n = 3, 4, 5, 6

R

R2 m

Zhang and coworkers [124] SCF3

24 examples (31–76%)

m = 1, 2, 3, 4

Scheme 5.81 Silver-mediated trifluoromethylthiolation of cycloalkanols for the synthesis of β-, γ-, δ-, and ε-trifluoromethylthiolated ketones [121].

321

322

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

Therefore, the proton of the hydroxyl group of the cycloalkanol is abstracted by the in situ formed sulfate radical anion and gives an oxygen-centered radical. This undergoes rearrangement by which the C—C bond is cleaved and the keto group is formed. The resulting alkyl radical is trapped with Ag(II)SCF3 to give the C—SCF3 bond and to recover Ag(I) [121]. In 2014 Shen and coworkers reported a silver-catalyzed decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids (Scheme 5.82). The major challenge of this method was to find an oxidant to reoxidize the silver(I) salt without oxidizing the alkyltrifluoromethylthioether. This was achieved by using K2 S2 O8 as oxidant and ArC(Me)2 OSCF3 as electrophilic trifluoromethylthiolation reagent that was developed by the same working group. As silver(I) source the group of silver(I) nitrate was used. In order to facilitate the formation of the product and to prevent side reactions, the product was physically separated from the oxidant by an aqueous emulsion that was formed by sodium dodecyl sulfate (SDS) in water. A wide range of tertiary and secondary alkyl carboxylic acids was converted to the corresponding trifluoromethylthiolated product in good to high yields with different functional groups such as halides and esters, but also alkene and alkyne groups were tolerated. In particular the good tolerance of the latter functional groups illustrates the differences to classical electrophilic addition reactions. However, reactions of primary alkyl carboxylic acids proceed much slower and in low yield (20–30%), whereas with aromatic carboxylic acids no reaction occurred at all. Most likely, the mechanism undergoes a free radical process that was demonstrated by radical clock and radical cyclization experiments [85k]. AgNO3 (cat.), SDS, K2S2O8, H2O, 50 °C, 12–48 h

Me R CO2H

+

Ar

OSCF3

R SCF3

Me 21 examples (20–91%)

Ar = 2-iodophenyl

SCF3 SCF3 R = H, 71% (2.0 mmol scale) R = Cl, 80% (dr = 9 : 1) R = OH, 86% (dr = 3.5 : 1)

TosN 45%

O O 90%

SCF3

SCF3

SCF3

Bn

9

65%

20%

Scheme 5.82 Silver-catalyzed decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids in aqueous emulsion [85k].

Almost simultaneously, Tang and Chen’s working group have reported on a direct silver-mediated oxidative aliphatic C—H trifluoromethylthiolation of unactivated tertiary and secondary C(sp3 )—H bonds (Scheme 5.83). Both methods are mild, efficient, and operationally simple, affording their corresponding products in good yields with a broad tolerance of functional groups. In general trifluoromethylthiolation occurred at the most remote position from the electron-withdrawing group (esters, bromine) with good site selectivity. By comparing the reactivity of secondary C—H bonds with that of tertiary ones, the

5.4 Silver-Mediated and Silver-Catalyzed Trifluoromethylthiolations

AgSCF3,Na2S2O8, MeCN, H2O, DCE, 35 °C Tang and coworkers [125a] R SCF3

R H Chen and coworkers [125b] AgSCF3, K2S2O8, MeCN, 60 °C, 12 h

Chen and coworkers [125b]: 34 examples (up to 83%)

Tang and coworkers [125a]: 34 examples (up to 83%)

Ph

O

SCF3

O

γ

β

O

Ph

32% (γ : β = 3 : 1)

β

O

γ

β

O

SCF3

O

SCF3 γ

H O

F3CS

δ

2 3

71% (δ : γ = 1.9 : 1)

53% H

O

H

γ

H

N O

H

AcO

Br 60%

75% (3°: 2° = 10 : 1)

CO2Me

NPht 77% (γ : β = 10 : 1)

SCF3

2°

83%

72% (γ : β = 15 : 1) O

F3CS γ

SCF3

SCF3

SCF3

H 48% + SCF3 at C-3 (16%, α / β = 1 : 1)

SCF3

β

71% (γ : β = 1.9 : 1)

O

Scheme 5.83 Silver-mediated oxidative aliphatic C(sp3 )—H trifluoromethylthiolation [122].

N2 OR

Ar

Ar

O

O

AgF, CF3SO2OCF3, MeCN, 30–10→°C, overnight

R = alkyl, allyl, benzyl

27 examples (27–90%)

OCF3

N2 R2

R1

R

O CO2Et

R

R = H, 62% R = p-Br, 79% R = o-Me, 83% R = m-Me, 53% R = p-Me, 60%

CO2Et

CO2Et

Et O

CO2Et

55%

89%

OCF3

Ph 70%

H H

Ph

CO2Et OCF3

S 90%

F3CO

OCF3

OCF3

TsN

R2

1

O 6 examples (48–94%)

O

OCF3

OCF3 OR

91%

H

H

O OCF3 48%

Scheme 5.84 Silver-mediated oxidative aliphatic C(sp3 )—H trifluoromethylthiolation [122].

323

324

5 Silver-Mediated Fluorination, Perfluoroalkylation, and Trifluoromethylthiolation Reactions

latter react preferably over the secondary C—H bonds in comparable electronic surroundings. Moreover, this method enabled the trifluoromethylthiolation of various substrates including natural products such as terpenes (+-sclareolide), steroids (androsterone derivative), and amino acid derivatives [122]. Besides silver-mediated trifluoromethylthiolation, it is worth to note that also attempts for silver-mediated trifluoromethoxylations occur in literature. One interesting approach represents the silver-mediated direct trifluoromethoxylation of α-diazoesters with AgF and CF3 SO2 OCF3 . While the reaction with alkyl α-diazoarylacetates gives the corresponding α-trifluoromethoxyl esters in good yields, the same reaction with various alkyl α-diazovinylacetates provided α-trifluoromethoxyl (E)-α,β-unsaturated esters in excellent yields and good regio- and stereoselectivity (Scheme 5.84).

5.5 Conclusion and Outlook Over the last decade, developments in the field of silver-mediated/catalyzed perfluoroalkylation reactions have revealed new insights into the mechanism of fluoroalkylations and offer new possibilities for the syntheses of fluorinated compounds. While at the beginning of 2010 only rare examples of reactions with participation of perfluoroorgano silver species were known, different approaches have been reported over the last years, allowing the perfluoroalkylation of, e.g. arenes and terminal alkenes. These transformations tolerate various functional groups, most interestingly halides that are commonly addressed by other metal-mediated perfluoroalkylating reactions. Furthermore, the different synthetic routes to perfluoroorgano silver compounds, especially the addition to highly fluorinated double bonds resulting in the synthesis of rare secondary perfluoroorgano metal compounds, should be useful for the direct introduction of new fluorinated groups to organic compounds. However, silver-mediated perfluoroalkylation reactions are just at the beginning, and there is still plenty of room for improvements.

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6 Coupling Reactions and C—H Functionalization Qing-Zhong Zheng 1,2 and Ning Jiao 2 1 State Key Laboratory of High-Efficiency Coal Utilization and Green Chemical Engineering, School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021, China 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, China

6.1 Introduction Silver, as a less expensive noble metal, is widely used for various organic transformations in the past decades. Nowadays, the silver-catalyzed reaction is one of the frontier areas in organic chemistry, and the progress of research on it is very rapid. However, compared with other transition metals, silver has long been believed to have low catalytic efficiency, and most commonly, they are used as either cocatalysts or Lewis acids. Only recently, Ag, especially Ag(I), has been demonstrated as important and versatile catalyst for a variety of organic transformations [1]. As is well known to all, transition metal-catalyzed versatile coupling reactions have emerged as a powerful method in organic synthesis [2]. Meanwhile transition metal-catalyzed C—H functionalization could offer green and sustainable methodologies to construct diverse organic molecules starting from simple compounds. The activation of C—H bonds [3] and their applications are also hot research areas in organic synthesis. Among the aforementioned transition metal-catalyzed organic transformations, Ag-catalyzed coupling reactions/C—H functionalization has emerged as a powerful method. According to the concept of this book, the recent developments of Ag-catalyzed coupling reactions/C—H functionalization are summarized in this chapter. In contrast, some Cu-, Au-, Pd-, and Rh-catalyzed reactions assisted or participated by silver salts are not covered in this chapter. A brief mechanistic discussion is given to provide information about a possible reaction pathway when necessary. Moreover, silver-mediated coupling reactions/C—H functionalization are also covered in this chapter.

Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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6.2 Formation of Carbon–Carbon Bonds 6.2.1

Glaser Coupling

The Glaser coupling, a well-known named reaction, is considered as the most convenient method for obtaining 1,3-diyne products from alkynes in transition metal-catalyzed coupling reactions. The homocoupling reactions have been widely used for the synthesis of various symmetric structures by using Cu, Pd, Fe/Cu, Ni, and Au catalysts. However, the development of the synthesis of 1,3-diynes with other catalytic systems is still necessary. In particular, novel synthetic routes and approaches to 1,3-diynes employing greener protocols are well appreciable. Very recently, Gao et al. demonstrated the light-induced homocoupling of aryl-alkynes (Glaser coupling) at metal surfaces [4]. Notably is that at the Ag(III) surface, the light-induced on-surface Glaser coupling proceeded rather efficiently. Such photochemical approaches are of particular importance as potentially orthogonal processes to thermal on-surface reactions. Sooner after this report, a [Ru(dppp)2 (CH3 CN)Cl][BPh4 ]-catalyzed homocoupling of alkynes in the presence of silver salts was also demonstrated by Bhattacharjee and coworkers [5]. 6.2.2

A3 Coupling

A3 coupling (also known as A3 coupling reaction or the aldehyde–alkyne–amine reaction) [6] is of current interest as it results in the formation of propargylamines [7], which are important as building blocks in the synthesis of nitrogencontaining biologically active pharmaceuticals, agrochemicals, and natural products [8–10]. In 2003, Li and coworkers reported the first silver-catalyzed A3 coupling reaction to generate propargylic amines 1 with high efficiency in water, without using any other cocatalyst or additives (Scheme 6.1) [11]. The silver-catalyzed reaction is especially effective for reactions involving aliphatic aldehyde. Mechanistically, n

R1 CHO +

AgI (1.5–3 mol%)

+ R2

N

H2O, 100 °C, N2

N H

R1

R1 = aryl, alkyl n = 0, 1, 2

N

n

1 R2 12 examples 47–99% yields

N

N Cl

Me 96%

91%

47%

Scheme 6.1 Silver-catalyzed three-component coupling of aldehyde, alkyne, and amine.

6.2 Formation of Carbon–Carbon Bonds

the addition of silver acetylide to the iminium ion was proposed to be the key step. After Li’s pioneering work, silver-catalyzed A3 coupling reaction was extensively studied, which mainly demonstrated the effects of other silver salts as catalysts [12]. Among them, effective catalyst [silver(I)(pyridine-containing ligand)] complexes 2 were recently discovered by Caselli and coworkers. The new catalytic system were compatible with a much broader scope of substrates, even the challenging coupling partners such as aniline and ketones (Scheme 6.2) [13].

O 1

R

+

+

R4

R3

2

R

N H

R5

R4

2 (3 mol%)

1

Toluene 150 °C, mW

R1 = Ar, Alk; R2 = H, Alk; R3 = Ar, Alk; R4 = Alk, c-Alk, Ar; R5 = Alk, c-Alk, H X = BF4, OTf

R

N

R5

R2

X– N + Ts N Ag N Ts N

R3

17 examples up to 98% yield 2

Scheme 6.2 [Silver(I)(pyridine-containing ligand)] complexes as unusual catalysts for A3 coupling.

The silver-catalyzed A3 coupling reaction provided an attractive platform for developing tandem reactions, particularly for the synthesis of N-/O-containing heterocycles, which was demonstrated by the successful synthesis of dihydrobenzofurans [14], aminoindolizines [15], chromeno[3,4-c]pyridin-5-ones [16], and quinolines [17]. Propargylamines have attracted considerable attention over the past few decades due to their wide applications in medical and synthetic chemistry. In 2014, an efficient method for the synthesis of propargylamines from terminal alkynes, dichloromethane, and tertiary amines using silver catalysts has been demonstrated by Zhou and coworkers [18] (Scheme 6.3). The reaction shows + CH2Cl2 + R1 NR2R3

R 3

AgOAc (5 mol%)

R NR2R3

Dioxane N2,120 °C

4

5

NR2R3 CH2Cl

CH2Cl2 4

R1

–R1Cl

Cl

NR2R3

NR2R3 Cl

Cl 4-1

4-2 Ag 3

R

Ag

5

H

Scheme 6.3 Synthesis of propargylamines from terminal alkynes, dichloromethane, and tertiary amines.

333

334

6 Coupling Reactions and C—H Functionalization

high functional group tolerance and can be conducted without the use of an exotic base, a cocatalyst, or an additive. The discovery not only provides a new strategy for the preparation of propargylamines but also suggests a powerful method for C—N bond cleavage. The catalytic reaction pathways for the three-component coupling reaction are proposed as shown in Scheme 6.3. First, methaniminium chloride 4–1 is formed by the reaction of R1 R2 R3 N with CH2 Cl2 and then decomposes via R1 Cl dissociation to afford methyleneammonium chloride 4–2 and the final reaction with silver acetylide to give the corresponding propargylamine 5, with the Ag(I) catalyst being regenerated. In 2005, Li and coworker discovered that a phosphine ligand could serve as a remarkable chemo-switch for the silver-catalyzed A3 reaction in water. Exclusive aldehyde–alkyne–amine coupling product was observed in the absence of phosphine, whereas in the presence of a phosphine ligand (Cy3 P), exclusive aldehyde–alkyne coupling product was obtained (Scheme 6.4) [19]. As we know alkynyl silver reagents are typically too stable to participate in nucleophilic addition to carbonyl compounds. Thus, the author proposed that the coordination of the electron-donating P-ligand increased the electron density on silver to weaken the Ag—C bond of silver acetylide 7–1. In this protocol, a variety of aldehydes 6 with aryl, alkyl, and styryl substituents were well tolerated. The Li group later expanded this silver-catalyzed nucleophilic addition. Later, the first silver-catalyzed fluorinated quinoline synthesis via a cascade O R

+

R′

H

H

Cy3PAgCl (0.5 mol%) i-Pr2NEt (20 mol%)

OH R

Water (2 ml), rt to 100 °C

7

6

R′

20 examples 35–98% yields OH R 7

R′

H

Cy3PAgCl

i-Pr2NEtH+Cl–

H2O, Cl O

R′ + i-Pr2NEt

AgPCy3

R′

Cy3PAg 7-1

R R′

O R′

Cy3PAg O R

H

Scheme 6.4 Silver-catalyzed A3 reaction in water.

R

H

6.2 Formation of Carbon–Carbon Bonds

alkyne–ketone–amino coupling/addition/condensation process in water was reported [20]. It provides new approaches for important quinoline intermediates bearing CF3 group. 6.2.3 Oxidative Cross-coupling and Oxidative-Induced C—H Functionalization 6.2.3.1

Oxidative-Induced C—H Functionalization

Csp —H bond functionalization is difficult due to the rapid homodimerization, leading to the formation of bis-alkynes. Meanwhile, alkynes are easily oxidized, and special conditions are required to prevent both dimerization and oxidation. Among the strategies for activation of the Csp —H bond of terminal alkynes, before 2010, there are few reports of using silver for in situ generation of acetylides. In 2010, Li and coworker reported the first silver-catalyzed oxidative coupling of terminal alkynes and benzylic ethers 8 by using 2.5 mol% of silver triflate as the catalyst and 1.5 equiv. of 2,3-dichloro-5,6-dicyanoquinone (DDQ) as the oxidant. They successfully accessed functionalized benzylic ether derivatives 9 (Scheme 6.5) [21]. Acyclic methyl benzyl ethers could be activated, but the desired coupling product was obtained in a poor yield.

+ O

AgOTf (2.5 mol%) DDQ (1.5 equiv.)

O

Ar Ar

120 °C, Ar, 16 h

8

9

Scheme 6.5 Cross-dehydrogenative coupling of a terminal alkyne and an ether.

Lei group realized a novel multimetallic radical oxidative cross-coupling between unactivated alkanes and terminal alkynes (Scheme 6.6) [22]. This method employs Cu, Ni, and Ag salts in catalytic amounts (Scheme 6.48). This method has been used to synthesize several unsymmetrical alkynes that are otherwise difficult to obtain. Preliminary mechanistic studies suggest that this reaction proceeds through a radical process and the Csp3 —H bond cleavage is the rate-limiting step. This study may have significant implications for controlling selective C—C bond formation of reactive radical intermediates by using multimetallic catalytic systems. H

[Cu], [Ni], [Ag]

[O]

H Unactivated alkanes

Radical intermediate

R [O]

R

Scheme 6.6 Cross-coupling between unactivated alkanes and terminal alkynes.

A silver-catalyzed double Csp3 —H cross-coupling to form 1,4-diketones has been developed by Wang and coworkers [23] (Scheme 6.7). The resulting ketones then undergo cyclization to yield tetrasubstituted furans, thiophenes, and pyrroles from benzyl ketone derivatives in a one-pot reaction process (Scheme 6.7).

335

336

6 Coupling Reactions and C—H Functionalization

O Ar1

R1

+

Ar 2

10

R1

AgF (10 mol%) Xylene, air, 140 °C

O R2

Ar1

Then TsOH (1.5 equiv.)

11

R2

O

Ar2 12

H3CO

F

O

O

H3C

CH3

Br

CH3

89%

OCH3

O

70%

69%

Scheme 6.7 Synthesis of tetrasubstituted furans by cross-coupling reactions.

Trifluoromethylated aromatic compounds are widely prevalent in pharmaceuticals, agrochemicals, and organic materials. Some trifluoromethylation methods have significant limitations, such as utilizing expensive trifluoromethylating reagents, needing high temperature, requiring inconvenient electrochemical or photochemical activation procedures, or utilizing potentially explosive reagents like peroxides at elevated temperatures. Sanford and coworkers were interested in the possibility of addressing some of these limitations by identifying metals other than Cu or Pd that could promote the formation of benzotrifluorides. This group developed the silver-mediated Csp2 —H trifluoromethylation of aromatic substrates with (trifluoromethyl)trimethylsilane (TMSCF3 ) (Scheme 6.8) [24]. The reaction was proposed to proceed via a AgCF3 intermediate (Scheme 6.9), and preliminary studies suggested against free trifluoromethyl radical as an intermediate.

R

+

CF3

AgOTf (4.0 equiv.) KF (4.0 equiv.) TMSCF3

DCE, N2 85 °C, 24 h c

b

CF3 R

a

13 c

CF3 MeO

87% S

CF3 a

81% (a:b:c = 2.7 : 1.4 : 1) CF3 a

b 72% (a:b = 8 : 1)

N N

Scheme 6.8 Silver-mediated trifluoromethylation.

N N

O 70% (4.8 : 1)

OMe

b

85% (a:b:c = 13 : 7.3 : 1) O

b

CF3 a

42%

CF3

6.2 Formation of Carbon–Carbon Bonds

TMSCF3

AgX

AgCF3

–TMSX

–Ag(0)

PhH

CF3

F 3C

CF3

H

AgX –Ag(0) –HX

Scheme 6.9 Proposed mechanism of silver-mediated trifluoromethylation.

Greaney and coworkers reported a silver-catalyzed Csp2 —H trifluoromethylation of electron-rich aromatic and heteroaromatic substrates (Scheme 6.10) [25]. The reaction can proceed at room temperature under air, and does not require excessive stoichiometries of substrate or reagent. A radical mechanism is implicated for the transformation.

Ar H

AgF (25 mol%) TMSCF3 (2.0 equiv.) Phl(OAc) (2.0 equiv.) DMSO, rt, 20 h

Ar CF3 14 Br

OMe b

a

CF3

MeO

MeO

MeO

MeO 77% (a:b = 2 : 1)

CF3

CF3

OMe OMe 55%

55% CF3

MeO

S

CF3

76%

CF3

Me N

MeO

Me 45%

N

OMe

72%

Scheme 6.10 Ag-catalyzed trifluoromethylation.

Recently, Zhang and coworkers developed a silver-catalyzed Csp2 —H C—H trifluoromethylation reaction of arenes using cheap and readily available trifluoroacetic acid (TFA) as the trifluoromethylating reagent (Scheme 6.11) [26]. A radical mechanism for this reaction is proposed (Scheme 6.12). [Ag+ ] is oxidized by K2 S2 O8 to generate [Ag2+ ]. The resulting [Ag2+ ] species undergoes electron transfer with TFA to yield radical intermediate 15, which decarboxylates

R

H + CF3COOH

R = CN, CO2Et, l, alkyl, etc.

Ag2CO3 (40 mol%) K2S2O8 (2.0 equiv.) Na2CO3 (1.5 or 2.5 equiv.) H2SO4 (0.5 or 0.2 equiv.) MeCN or DCM, 120 °C, 10 h

R CF3 20 examples 44–88% yields

Scheme 6.11 C—H trifluoromethylation of arenes using TFA as the trifluoromethylating reagent.

337

338

6 Coupling Reactions and C—H Functionalization

CO2 +

–H

CF3COOH

CF3

CF3COO

[Ag2+]

15

[Ag+]

SO42–

S2O82–

CF3

CF3

–e–, –H+

H

Scheme 6.12 Proposed mechanism of C—H trifluoromethylation of arenes using TFA as the trifluoromethylating reagent.

to release trifluoromethyl radical. Finally, reaction of trifluoromethyl radical with the arene substrate results in the desired trifluoromethylated product via radical substitution. Hajra group reported a direct and regioselective method for trifluoromethylation of imidazopyridines using sodium trifluoromethanesulfonate (Langlois reagent) in the presence of catalytic amount of AgNO3 and TBHP (tert-butyl hydroperoxide) at room temperature in ambient air (Scheme 6.13) [27]. N

N R

R

Ar

N H

16

N 18 H

N

N Ar

Ar

F3C

N

N

19 NO2

Me

N

N CF3

63% F3C

CF3 N

N

68%

CF3

71%

CF3 N

N CF3

74%

S

S

N

Me

N

17 CF3

CF3SO2Na (2 equiv.) DMSO, air, rt

S

Ar

N

AgNO3 (20 mol%) TBHP (20 mol%)

S

O N

N N S

71%

69%

Scheme 6.13 Trifluoromethylation of imidazoheterocycles via Csp2 —H bond functionalization.

6.2 Formation of Carbon–Carbon Bonds

Mechanistic studies indicate that the CF3 radical is involved in this transformation as a key intermediate. Doi and coworkers demonstrated a silver trifluoromethanesulfonate (AgOTf)-promoted direct and mild Csp2 —H formylation of benzenes (Scheme 6.14) [28]. A formylating species generated from Cl2 CHOMe–AgOTf is highly reactive, and the formylation of benzenes smoothly proceeded under temperature conditions as low as −78 ∘ C to provide the corresponding aldehydes without losing the protecting groups on the phenolic hydroxyl group. R

R′

R

AgOTf (3.0 equiv.) Cl2CHOMe (3.0 equiv.) CH2Cl2

O

R′

20

21

R = OBn, OMe, OAllyl, etc.; R′ = allyl, alkoxyl, halogen

22 examples up to 83% yield

Scheme 6.14 A direct formylation of substituted benzenes.

Cyclopropanols are versatile compounds that can be a repertoire for various classes of synthetic molecules such as azaheterocycles, β-substituted ketones, allyl chlorides, and other products by virtue of the strain energy associated with the three-membered ring. In 2013, Ilangovan et al. developed a AgNO3 -catalyzed oxidative ring opening of cyclopropanols at room temperature; resulting β-keto radicals were successfully added to quinones to furnish γ-carbonyl quinones 23 (Scheme 6.15) [29]. This protocol has also been successful for the synthesis of O

O AgNO3 (20 mol%) K2S2O8 (3 equiv.)

+ R1 R

DCM-H2O (1 : 1) 25 °C,1 h

OH O

22

R1

R 23

Cl

O

O

O

O

O

O

O

65%

62%

60% O

O

O

O

O

O

O

O

O O

O O

O 58%

O 78%

O

O

O

32%

Scheme 6.15 The preparation of γ-carbonyl quinones by C—H activation of quinones.

339

340

6 Coupling Reactions and C—H Functionalization

SO42– S2O82–

HO

R O

SO4 Ag(I)

R

O R

Ag(II)

HSO4 O

O

O

O Ag(II) Ag(I) O O

R

H SO4

HSO4

O

O R

Scheme 6.16 Plausible mechanism of the synthesis of γ-carbonyl quinines via C—H.

cytotoxic natural products, 4,6-dimethoxy-2,5-quinodihydrochalcone and evelynin. The mechanistic pathway is outlined in Scheme 6.16, which is in consistent with the general method of oxidative ring opening of cyclopropanols and a radical addition to quinones. 6.2.3.2

Oxidative Cross-coupling

Oxidative cross-coupling for the construction of C—C bond has been extensively investigated. And Ag catalysis [30] or Cu/Ag cocatalysis [31] also has been used to oxidative coupling reactions. The ready availability, high stability, and low cost of carboxylic acids make them extremely promising raw materials for chemical synthesis via oxidative cross-coupling reaction. In 2012, Li group reported a silver-catalyzed decarboxylative alkynylation (Scheme 6.17) [32]. This site-specific alkynylation is not only general and efficient but also functional group compatible. Moreover, it exhibits remarkable chemo- and stereoselectivity. The alkynylation reaction is believed to follow a radical process (Scheme 6.18). Oxidation of [Ag+ ] by the persulfate generated a [Ag2+ ] species, which oxidized the carboxylic acid to the corresponding acyloxyl radical with subsequent decarboxylation affording the carbon-centered radical. Addition of the carbon radical to the alkyne followed by β-fragmentation formed the new C—C bond (Scheme 6.18). Very recently, Li and coworkers developed a silver-catalyzed decarboxylative allylation of aliphatic carboxylic acids in aqueous solution (Scheme 6.19) [33]. With K2 S2 O8 as the oxidant, the reactions of aliphatic carboxylic acids with allyl sulfones afforded the corresponding alkenes in satisfactory yields. In addition, a novel Cu/Ag bimetallic tandem catalysis for selective alkenylation or alkynylation of alkanes via double-decarboxylative cross-couplings of cinnamic acids or phenylpropiolic acid and aliphatic acids also has been developed [34].

6.2 Formation of Carbon–Carbon Bonds

I

O R CO2H + 24

AgNO3 (30 mol%) K2S2O8 (3 equiv.)

TIPS

O

R

TIPS

CH3CN/H2O 50 °C, 10 h

26

25 iPr3Si (TIPS) TIPS

TIPS

TIPS

TIPS OMe CO2Et

n-Bu

Me Me

Et

94%

91%

60%

64%

TIPS Me H

O Ph

N

H O

O 63%

H

TIPS

H 61%

Scheme 6.17 Silver-catalyzed decarboxylative alkynylation.

O O

S2O82–

O O

I

I

[Ag2+] [Ag+]

R TIPS

R

R-CO2H RCO2

CO2

I

+ e–, + H+

HO2C

O

or H-abstraction

TIPS

I

O R

TIPS

Scheme 6.18 Proposed mechanism of decarboxylative alkynylation.

E R CO2H +

Ts

E

AgNO3 (cat.)/K2S2O8 CH3CN/H2O, 50 °C

R

Scheme 6.19 Silver-catalyzed decarboxylative allylation of aliphatic carboxylic acids in aqueous solution.

341

342

6 Coupling Reactions and C—H Functionalization

The Minisci reaction can realize the C—H alkylation of electron-deficient (hetero)arenes by silver-catalyzed oxidative decarboxylation of alkyl carboxylic acids to generate alkyl radicals. Minisci alkylations of electron-deficient pyrimidines with alkyl carboxylic acids were recently reported by Shore et al. [35]. Very recently, a silver-catalyzed decarboxylative direct C2-alkylation of benzothiazoles, thiazoles, and benzoxazoles was developed by Chen and coworkers [36] (Scheme 6.20). In comparison with Minisci reaction, this decarboxylative alkylation of heterocycles [37] was carried out at room temperature and under acid-free conditions. By using similar method, a decarboxylative alkylation or acylation reactions of simple pyrimidines in aqueous media were developed by Mai et al. [38]. In addition, alkyl radicals generated from the oxidative decarboxylation of aliphatic carboxylic acids can be used for the synthesis of five- or six-membered ring, such as succinimide and quinoline derivatives [39].

H + HOOC

R1 N

AgNO3 (20 mol%) K2S2O8 (4.0 equiv.)

R2

X

R3 R4

CH2CI2/H2O, rt, 8 h

N R1 X

R2 R3 R4

28

27 N

N

N

S

S

S

91%

93%

83%

N

N

N

O

O

O

83%

80%

83%

Scheme 6.20 Decarboxylative direct C2-alkylation of benzothiazoles with carboxylic acids.

Recently, Muthusubramanian group developed a silver-catalyzed decarboxylative acylation of pyridine-N-oxides 29 using α-oxocarboxylic acid 30 (Scheme 6.21) [40]. Acylated heteroarene N-oxides 31, which are difficult to access by the conventional methods, can be synthesized successfully in high yield by this protocol. The reaction was found to follow a radical mechanism. More recently, Duan and coworkers expanded the scope of decarboxylative acylation to coumarin substrates with α-oxocarboxylic acids as the acyl sources, as well as quinolinone and naphthoquinone substrates [41]. Aryl ketones are valuable building blocks of natural products endowed with a variety of biological properties in the synthesis of pharmacological compounds. Transition metal-catalyzed decarboxylative coupling has emerged as a promising concept for C—C bond formation for the synthesis of aryl ketones. However, all the efforts had been made with Pd-catalyzed or Pd/Cu cocatalyzed system, and the aryl ketone synthesis with arylglyoxylic acids by other much cheaper and easily available transition metal catalyst is highly appealing. In 2014,

6.2 Formation of Carbon–Carbon Bonds

R

O

+ N – O

R′

DCM/H2O 50 °C, 12 h

R′

29

R

Ag2CO3 (10 mol%) K2S2O8 (3.0 equiv.)

CO2H

N – O

30

O

31 R

R

R

Cl N – O O R = Me, 81% R = Cl, 78% R = OMe, 72%

N – O

N – O

O

R = Cl, 65% R = CN, 61%

O

R = H, 64% R = Cl, 73%

Scheme 6.21 Decarboxylative acylation of various aryl-N-oxides.

the silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with arylboronic acids for the synthesis of unsymmetrical diaryl ketones was demonstrated by Qi and coworkers [42] (Scheme 6.22). It is believed that the reaction is initiated by free radicals. O

O Ar1-B(OH)2

+

HOOC

Ag2CO3 (10 mol%)

Ar2

O

O

32

CH3

CN

95%

88% O

O

S

Ar2

O

OBn 93%

92%

Ar1

CH3CN, 60 °C,1 h

O

HO

BnO 94%

72%

Scheme 6.22 Silver-catalyzed coupling of arylboronic acids with arylglyoxylic acids.

Chalcones are ubiquitous in natural products and widely used as the important building blocks in the organic synthesis. However, the synthetic methods for the construction of chalcone skeletons are rare. Recently, palladium-catalyzed decarboxylative coupling has been developed for the preparation of chalcones. The development of more practical and environmentally benign approaches for the synthesis of chalcone derivatives is still a challenging, but

343

344

6 Coupling Reactions and C—H Functionalization

attractive, task. Very recently, Wang and coworkers described a silver-catalyzed double-decarboxylative strategy for the synthesis of chalcone derivatives 162 via cascade coupling of substituted α-keto acids with cinnamic acids under mild aqueous conditions (Scheme 6.23) [43]. A decarboxylative radical mechanism is involved in the reaction (Scheme 6.23). O R1 +

O

COOH AgNO3 (10 mol%) Na2S2O8 (0.5 equiv.)

R2

R1

K2CO3 (1.0 equiv.), H2O COOH

33

R2

20 examples 54–92% yield Na2S2O8 Ag(II)

O Ar1

Na2S2O8 2 O Ar

Ag(I) Ar1

COO CO2

COO Ag(II)

O Ar2

Ag(I) Ar1

O Ar1

O

O Ar2

CO2

Scheme 6.23 Double-decarboxylative cross-coupling of α-keto acids with cinnamic acids.

6.2.4

Oxidative Coupling/Cyclization Reactions

Recently, Baran group reported AgNO3 -catalyzed intramolecular radical cyclizations with trifluoroborates for the generation of tricyclic scaffolds via Csp2 —H functionalization (Scheme 6.24) [44]. A variety of functional groups are tolerated, such as nitriles, esters, and Lewis basic heteroatoms. This open-air radical chemistry does not involve high temperatures and avoids the use of toxic and/or expensive metals. This method circumvents recourse to potentially hazardous reagents (e.g. arenediazonium salts) and can be safely conducted on gram scale. BF3K X 34

AgNO3 (20 mol%) Na2S2O8 (3.0 equiv.) PhCF3/H2O (1 : 1) 60 °C, 1 h R

R X 35

X = O, C(O) R = H, OMe, F, CF3, CO2Me, etc.

Scheme 6.24 Pschorr-type cyclization using organotrifluoroborates as radical precursors.

In 2013, Yang group developed a highly efficient protocol for the preparation of various diphenylphosphoryl oxindoles by silver-catalyzed difunctionalization of alkenes through a carbon phosphorylation and C—H functionalization cascade process [45]. A variety of phosphorylated oxindoles were synthesized by using a catalytic system composed of silver nitrate (AgNO3 ) and magnesium nitrate

6.2 Formation of Carbon–Carbon Bonds

R3 R1

+ O N R2

H

O

HPR4R5

36 O PPh2

O

O PPh2

O

N Me

O

N Bn

82% O PPh2

R

58%

52%

N Me

O P(OEt)Ph

O N Me

O

N R2 37

MeCN, 100 °C

O PPh2

O PR4R5

R3

AgNO3 (5 or 20 mol%) Mg(NO3)2⋅6H20 (0.5 equiv.) R1

R = Me, 51% R = MeO, 64% R = F, 45% R = Cl, 48% R = Br, 37% R = I, 40% H

O N Me 43%

O PPh2 O

N Me 0%

Scheme 6.25 Silver-catalyzed carbon phosphorylation of alkenes.

hexahydrate (Mg(NO3 )2 ⋅6H2 O) to trigger the radical carbophosphorylation of N-arylacrylamides with phosphine oxides (Scheme 6.25). The proposed mechanism is shown in Scheme 6.26. Firstly, the Ph2 P(O)Ag intermediate A, which is generated from the reaction of silver(I) with diphenylphosphine oxide, is proposed to play a crucial role in the reaction. It may take place through two paths: one proceeds by the formation of diphenylphosphinoyl radical from A and its addition across the alkene to produce II (path A), and the other involves the addition of I itself to the carbon–carbon double bond, affording intermediate III, which is then oxidized to II. The resulting alkyl radical II participates in an intramolecular radical substitution reaction. Addition of the radical to the aromatic ring to generate the intermediate IV with a subsequent single electron transfer (SET) from IV to silver(I) would yield the product along with HNO3 and silver(0). In the presence of HNO3 , the Ag(0) was oxidized to Ag(I). Applying a similar strategy, some other heterocycles were also constructed successfully [46]. Almost simultaneously, the Yang [47] and Jiao [48] groups independently reported a similar silver-catalyzed carboazidation of N-arylacrylamides 85 with trimethylsilyl azide (Scheme 6.27). Using their methods, various azide-containing oxindoles were prepared smoothly in moderate to good yields. Both strategies are also proposed to proceed through a radical cascade process (Scheme 6.27). By using similar method, oxidative coupling/cyclization of acrylamides with 1,3-dicarbonyl compounds [50a], trifluoromethyl reagent [50b, c], trifluoromethylthiolation reagent [50d], and nitro-containing compounds [50e, f ] has been successfully applied to the synthesis biologically important oxindole skeletons containing various functional groups.

345

346

6 Coupling Reactions and C—H Functionalization

Ag(0) O AgNO3 + HPPh2

HNO3

O Ph2P Ag I

O PPh2

Path A

Path B

N

O

H Ag N

O P Ph2

O P Ph2

O

N

III

O II

HNO3

Ag(0) AgNO3

O P Ph2 O

O P Ph2 O

H N

N HNO3 + Ag(0)

IV

Scheme 6.26 Proposed mechanism of AgNO3 -catalyzed carbon phosphorylation of arylacrylamide.

R4 R3

R3

R4

R1

+ N R2

H

O

Conditions

TMSN3

R1

N3 O

N R2

38

39 Yang′ condition: AgNO3 (10 mol%) Zr(NO3)4⋅5H2O (0.8 equiv.) MeCN, 110 °C, 28 h, Ar

Jiao′s condition: AgNO3 (10 mol%) Ce(SO4)2 (2.5 mol%) MeCN, 80 °C, 24 h, Ar

R1, R3 = alkyl, aryl; R2 = alkyl

TMSN3 R4 +

R1 H

N R2

O

N3

4 R3 R

R4

O

R3

R3

N3 cat.

R1 H

N R2

O

Scheme 6.27 Silver-catalyzed carboazidation of arylacrylamides.

N3

R1 N R2

O

6.2 Formation of Carbon–Carbon Bonds

In 2014, Nevado and coworkers disclosed a mild and efficient protocol for the Ag-catalyzed and P-centered radical-mediated tandem addition/cyclization of acryl sulfonamides 40 to produce P-containing oxindoles 42, following by a desulfonylation process (Scheme 6.28) [50]. O Me

N SO2

O P(R2)2

O H P(R2)2

+ H

R1

AgNO3 (50 mol%) MeCN, 100 °C, 14 h –SO2

41

40

O N Me 42

R1

5 examples 52–59% yields

R1 = H, Me, tBu, Cl; R2 = OMe or R1 = F; R2 = OEt AgNO3

O H P(R2)2

O P(R2)2 41-1

Ag(0) + HNO3

41

Scheme 6.28 Ag-catalyzed and P-centered radical-mediated tandem reactions.

Very recently, Studer group reported a new reaction of AgOAc-promoted diphenylphosphinyl radical addition to arylisonitriles [51] 87 followed by cyclization of imidoyl radical and deprotonation for the synthesis of 6-phosphinoylated phenanthridines 88 (Scheme 6.29) [52]. The proposed reaction mechanism involved in radical pathway is outlined in Scheme 6.30. Similar reactions have also been reported by the Wang and group [53] as well as the Yang group [54]. R2

R2 O H P R4 R3

+

R1 N

C

AgOAc (3.0 equiv.) DMF, 100 °C, Ar, 4 h

R1

O N

43

44

P R3

R4 F

tBu Me

Me

Me O P

N Ph 63%

Ph

Ph

Me O P Ph 71%

Ph

P

N Ph

Ph

Ph

73%

80% O

Ph

N

O

O P

N

Me

O Me

Me O N 40%

P Ph

Scheme 6.29 Radical phosphorylation of isonitrile.

N

Ph 85%

O P Ph EtO

347

348

6 Coupling Reactions and C—H Functionalization

O H P Ph Ph

Ag(I)

Ag(0) O P Ph Ph

H N

N

P Ph

C

O

O

N

Ph

P Ph

Ph

Ag(I) –H+ H N

Ag(0)

O

O

N

P Ph

P Ph

Ph

Ph

Scheme 6.30 Proposed reaction mechanism.

Recently, Zhang and coworkers developed a silver-catalyzed tandem reaction of trifluoromethylation and cyclization of aryl isonitriles with the Langlois reagent (sodium triflinate) (Scheme 6.31) [55]. A series of trifluoromethylated phenanthridines is prepared from a cheap and stable trifluoromethyl source. A simple and practical protocol for the synthesis of gem-difluoromethylenated phenanthridine through the Ag(I)-catalyzed oxidative decarboxylation of aryl difluoroacetates was also developed recently [56]. R2 + CF SO Na 3 2

R1 NC 45

AgNO3 (1 mol%) TBHP (2.0 equiv.) Na2CO3 (1.0 equiv.) DMSO, 40 °C, 6 h

R2 R1 N

CF3

46 18 examples 32–85% yield

Scheme 6.31 Silver-catalyzed tandem trifluoromethylation and cyclization of aryl isonitriles.

Li group reported a silver-mediated synthesis of tetrasubstituted pyrroles via the cross-dehydrogenative coupling between enamino esters and acetone [57]. Soon after this report, Lei group successfully developed a silver-mediated oxidative tandem cross-coupling and intramolecular cyclization for the synthesis of pyrroles 49 (Scheme 6.32) [58]. This work also demonstrates that silver can act as a “key mediator” for the highly selective oxidative alkynylation, which will be quite important for designing new reactions. Liang and coworkers developed a silver-mediated sequential oxidative C—H functionalization [59] and 5-endo-dig cyclization of 2-alkylazaarenes with terminal and internal alkynes [60]. This process represents a simple, efficient, and

6.2 Formation of Carbon–Carbon Bonds

O Ar2 1

Ar

+

NH

Ag2CO3 (2.0 equiv.) DBU (2.0 equiv.)

O

R1

OR2

47

N Ar2

DMSO, 80 °C, N2, 12 h

48

R1 49

Br

OMe O

iPr

OR2

Ar1

N

N OMe

OMe

iPr

O

O

iPr

iPr

N

iPr

iPr

72%

84%

OMe

77% OMe

OMe O

O N

O

N

OMe

N OEt

OMe iPr

70%

70%

73%

Scheme 6.32 Oxidative cyclization of terminal alkynes and β-enamino esters.

atom-economic way to access biologically important indolizines (Scheme 6.33). Two different pathways were proposed. When the terminal alkynes were used, (R3 = H) 2-alkylazaarenes underwent deprotonation and nucleophilic attack on a silver acetylide intermediate, whereas the internal alkynes (R3 = Aryl, alkyl) involved a successive radical and ionic pathway. Agrawal and coworkers reported a similar reaction, which focused on terminal alkynes (Scheme 6.33) [61]. In these two reports Ag2 CO3 could be recycled and reused. R1

R2 Conditions + 1

R

N

R3

50

R2

N 51

R3

Liang and Pan’s condition: Ag2CO3 (2 equiv.) KOAc (2 equiv.) DMF, 120 °C, 12–18 h

Agrawal’s condition: Ag2CO3 (2 equiv.) KOAc (2 equiv.) DMF, 110 °C, 12 h

R1 = CO2Et, CO2Me, CN, etc. R2 = H, Me, n-Pr, Ph; R3 = Ar, Het, TMS

R1 = CO2Et, CO2Me, CN R2 = H; R3 = Ar, Het

19 examples; 55–86% yield

15 examples; 45–89% yield

Scheme 6.33 Silver-mediated C—H bond functionalization to construct substituted indolizines.

349

350

6 Coupling Reactions and C—H Functionalization

Benzo[b]phospholes, as phosphorus-containing heterocycles, have received considerable attention because of their inherent physical and optical properties, which allow the development of new classes of optoelectrochemical materials. However, methods for the synthesis of benzo[b]phospholes are lacking. Thus, the development of efficient methods for the synthesis of benzo[b]phosphole oxides would be highly appealing and significant. Recently, the groups of Duan [62], Satoh and coworkers [63] simultaneously demonstrated the silver-mediated C—H functionalization and cyclization of arylphosphine oxides with internal alkynes affording benzo[b]phosphole oxides 53 (Scheme 6.34). The reaction proceeded smoothly by either AgOAc or Ag2 O in DMF, providing a step-efficient route to produce benzo[b]phosphole oxides. Notably, the asymmetrical alkynes with diphenylphosphine oxide regioselectively resulted in single regioisomers, whereas diarylphosphine oxides with different aryl substituents or one aryl group with two annulated sites generally produced a mixture of regioisomers. The mechanism of radical process was proposed in two reports involving two possible 4-exo-trig and 5-exo-trig annulation pathways (Scheme 6.35). A similar reaction was also reported by Ackermann and coworker [64].

R1

R2 O R3 P Conditions H + H

R2 O P

R1

R3

R4

52

53

R4

Duan’s condition: Ag2O (5 or 200 mol%) Zn(NO3)2·6H2O (1.0 equiv.) DMF, 100 °C, N2

Satoh and Miura’s condition: AgOAc (4.0 equiv.) DMF, 100 °C, N2

R1 = H, OMe, F, etc. R2 = aryl, alkyl, OEt R3 = aryl, alkyl, CO2Et, CN R4 = aryl, alkyl

R1 = H, Me, OMe R2 = aryl, alkyl, OEt, etc. R3 = aryl, alkyl, Ac, etc. R4 = aryl, alkyl

19 examples; 11–94%

26 examples; 35–96%

Scheme 6.34 Silver-mediated C—H functionalization and cyclization of arylphosphine oxides with alkynes.

Huang and coworkers [65] successfully applied similar strategy for the regioselective synthesis of 3-phosphonated coumarin derivatives 55 via the generation and cyclization of a phosphonated vinyl radical intermediate (Scheme 6.36). Furan not only represents an important class of five-membered heterocycles prevalent in natural products, pharmaceuticals, and agrochemicals but also represents a valuable intermediate in organic synthesis. In 2012, Lei group reported an efficient silver-mediated route, leading to various polysubstituted furans from terminal alkynes and β-ketoesters via oxidative C—H/C—H functionalization (Scheme 6.37) [66]. Notably, Ag2 CO3 used in this reaction could be recycled and reused several times without a significant loss of catalytic efficiency. Preliminary

6.2 Formation of Carbon–Carbon Bonds

H

Ph

Ph Alkyne

Ph

P O

P Ph

Ph

Ph

P

O

H Ph O Ag(I)

Ag(0)

–H+

Ag(0) Ag(I)

O Ph P Ph

Ph H

Ph P O

H P

Ph

O

Ph

Ph

Ag(I) Ag(0)

–H+

Ph Ph

P Ph

Ph

H P Ph O

O

Ph

Scheme 6.35 Proposed mechanism of C—H functionalization and cyclization of arylphosphine oxides with alkynes. H O

O

R1

O + H

P

R3 R3

4 Å MS, CH3CN 100 °C, 12 h, air

2

54

R2

Ag2CO3 (10 mol%) Mg(NO3)2·6H2O (0.3 equiv.)

R

P R1 O 55

1=

R H, Me, F, etc. R2 = aryl, alkyl R3 = Me, Et, iBu, Ph

Scheme 6.36 Silver-catalyzed phosphorus carbocyclization of alkynoate. O O R

H + R2

1

R3

Ag2CO3 (2.0 equiv.)

O

R3 KOAc (2.0 equiv.) DMF, 80 °C, N2, 12 h R1

CO2Et

R2

O 56

O

CO2Bn

Ph

Ph O

Ph

O

O

75%

89%

40% CO2Et

CO2Et

CO2Et F

Ph O

OEt

Trace

O

O S 84%

O

65%

Scheme 6.37 Silver-mediated oxidative C—H/C—H functionalization route to polysubstituted furans.

O

R3 R3

351

352

6 Coupling Reactions and C—H Functionalization

mechanistic investigations indicated that silver acetylide might be the key intermediate and the additional silver oxidant must be needed to achieve this transformation. A silver(I)-promoted C—H bond functionalization/cyclization reaction starting from 1,3-dicarbonyl compounds and alkynoates was reported by Zhang and coworkers, which also produced polysubstituted furans [67]. Motivated by the undeniable significance of this silver-mediated synthesis of furan through oxidative coupling, Novák and coworkers conducted DFT and experimental investigations to elucidate the reaction mechanism [68]. The most favorable pathways have been identified on the basis of the calculated solvent-corrected Gibbs free energy profiles. The mechanism consists of successive radical and ionic pathways. The calculations clearly confirmed the dual role of silver as both an oxidant and a catalyst, as previously proposed in Lei’s report. Mai et al. described tandem decarboxylative radical addition/cyclization [69] of N-arylcinnamamides with aliphatic carboxylic acids (Scheme 6.38) [70]. This method represents one of the most straightforward routes to the synthesis of alkylated or trifluoromethylated biologically interesting 3,4-dihydroquinolin-2(1H)-ones 58. R2 N R1 H

Ar O

+ HOOC-R

AgNO3 (20 mol%) K2S2O8 (2.0 equiv.) CH3CN/H2O 100 °C, 12 h

57

Ar R R1 N R2 58

O

R2

N

O

R2 = H, 69% R2 = Br, 62%

N 70%

O

N

O

75%

Scheme 6.38 Radical tandem cyclization for the synthesis of 3,4-disubstituted dihydroquinolin-2(1H)-ones.

In addition, acyl radicals generated from the oxidative decarboxylation of α-oxocarboxylic acids can be used to construct nitrogen heterocycles, such as indoles and phenanthridines. Guo and coworkers demonstrated a mild and efficient silver-catalyzed acylarylation of activated alkenes with easily available α-oxocarboxylic acids (Scheme 6.39) [71]. This protocol provides a rapid access to a variety of functionalized oxindoles via a tandem decarboxylative radical cyclization strategy. Similar strategy was later applied in the synthesis of valuable substituted dihydroquinolinones through regioselective acylarylation of cinnamamides using readily available α-oxocarboxylic acids as acyl sources by the same group [72].

6.2 Formation of Carbon–Carbon Bonds

AgNO3 (10 mol%) K2S2O8 (1 equiv.)

O

R3 +

R1 N R2

OH

R4

O

H2O or acetone/H2O 50 °C, 24 h

O

O

N 2

O

O

O

Me

Br N

O

N

O 79%

82% O

O

R

O

O 67%

Ph N

R4

59

R

O

N

R3

R1

N

O

O

62%

R = Me, 87% R = OMe, 78% R = CF3, 71% R = CN, 86% R = CO2Et, 73%

Scheme 6.39 Silver-catalyzed decarboxylative acylarylation of acrylamides with α-oxocarboxylic acids.

Lei group reported a silver-catalyzed reaction for the synthesis of 6-aroylated phenanthridines 61 by using α-oxocarboxylates as acyl radical precursors in combination with Na2 S2 O8 as an oxidant (Scheme 6.40) [73]. Oxidative radical decarboxylation involves a Ag(I)/Ag(II) catalytic cycle via initial SET process. Yang and coworkers demonstrated the synthesis of biologically important 3-acylcoumarins via radical silver-promoted decarboxylative annulation of R2 R1

O COOK

+ R3

Ag2CO3 (10 mol%) Na2S2O8 (2 equiv.) DMSO, 100 °C, 6 h

NC

R2 R3

R1 N

60

N

N

71% O

O

61

S

N

O 74%

53%

O

CF3

Cl

OMe

37%

N

N

N O

O 41%

Scheme 6.40 Synthesis of 6-acyl phenanthridines by oxidative radical decarboxylation–cyclization.

O 39%

353

354

6 Coupling Reactions and C—H Functionalization

alkynoates with 2-oxoacetic acids with high yields [74]. Applying similar strategy, Ding and coworkers also reported a Ag2 CO3 -catalyzed radical tandem cyclization of alkynoates with aryl- and alkyl-substituted 2-oxoacetic acids, which involved sequential radical acylation, 5-exo-cyclization, ester migration, and aromatization, affording a series of 3-acylcoumarins with high efficiency and good functional group tolerance [75]. Lei group developed a silver-catalyzed synthesis of oxazoles 64 by the oxidative decarboxylation–cyclization of α-oxocarboxylates and isocyanides (Scheme 6.41) [76]. This method provided a novel strategy to the construction of oxazole rings compared with traditional methods. O R

COOK

OR′

+ CN O 63

62

R

O

R′OOC

N

Ag2CO3 (10 mol%) 1,10-phen (50 mol%) K2S2O8 (3 equiv.) DCM, 80 °C, 12 h

64 Cl

O EtOOC

O EtOOC

N

O EtOOC

N

76%

88%

N

68%

Br O N O EtOOC 71%

O

MeOOC EtOOC

N 84%

N

64%

Scheme 6.41 Oxidative decarboxylation–cyclization of α-oxocarboxylates and isocyanides.

Greaney group developed an intramolecular decarboxylative C—H arylation of benzoic acids (Scheme 6.42) [77]. By using catalytic silver to promote a radical pathway, this protocol can access a class of aroic acids that are not productive in mixed Pd/Cu or Ag catalytic decarboxylative arylations, and it also shows that aroic acids can be used as radical precursors for C—C bond formation, a transformation previously confined to alkanoic acids. The decarboxylation was O

CO2H 65

AgOAc (20 mol%) K2S2O8 (3 equiv.) d3-MeCN, 130 °C Microwave, 1 h 76%

O

66

Scheme 6.42 Decarboxylative C—H arylation of benzoic acids.

6.2 Formation of Carbon–Carbon Bonds

specific to acetonitrile, especially, deuterated acetonitrile (d3 -MeCN). Although this reaction needed expensive d3 -MeCN as a reaction solvent, it demonstrated the interesting concept of controlling product distribution through a solvent isotope effect. C—H functionalization/C—O cyclization reactions have been successfully applied for rapid access to oxygen-containing heterocycles (e.g. lactones) with atom economy. Despite palladium- or copper-catalyzed C—H functionalization/ C—O cyclization reactions for the synthesis of lactones have been realized, developing milder and more efficient transition metal-catalyzed radical-based C—H functionalization/C—O cyclization reactions remains an important challenging task. Xu and coworkers reported a silver-catalyzed Csp2 —H functionalization/C—O cyclization of 2-aryl carboxylic acids 67 to form lactones 68 under mild conditions at room temperature (Scheme 6.43) [78]. A kinetic isotope effect (KIE) study indicates that the reaction may occur via a radical process. R2

R1

COOH

H

AgNO3 (20 mol%) (NH4)2S2O8 (3 equiv.) KOAc (3 equiv.) CH2Cl2/H2O, rt

R2

R1

67

O

O

68

MeO R

O

O

R = H, 93%, 24 h R = Me, 71%, 24 h R = F, 72%, 16 h R = Cl, 75%, 16 h R = Br, 88%, 16 h

O

O

O 74%, 24 h

64%, 24 h F F

O

O

42%, 48 h

O

S O

O 63%, 24 h

O

O 40%, 12 h

Scheme 6.43 Silver-catalyzed Csp2 —H functionalization/C—O cyclization.

Early studies revealed the relative ease of Csp—H bond functionalizations by using silver species to form direct C—C or C—N bonds, while silver(I)-induced Csp3 —H bond functionalization to form a new C—C or C—N bond is still very challenging. Mukhopadhyay and coworker reported a new silver(I)-mediated Csp3 —H functionalization of primary amines and subsequent oxidative C—N cross-coupling reaction (Schemes 6.44 and 6.45) [79]. This protocol provided a highly efficient and straightforward approach to form significantly diverse

355

356

6 Coupling Reactions and C—H Functionalization

O

Ar

+ NH -CH -R1 2 2 O

Ar

Ar

N

Ar

N

Ag2CO3 (2 equiv.) 1,4-Dioxane, 80 °C, 10 h

70

69

N

N

N

N

R1 R1

N N

O O

74%

88%

60%

Scheme 6.44 Synthesis of 1,2,4,5-tetrasubstituted imidazoles.

O H Ag2CO3 (2 equiv.) + NH C H + R2-NH 2 2 1,4-Dioxane, 80 °C, 10 h O R1

Ar Ar 71

N

Ar

N

R1

R2 72

CH3 N

Ar

N N

CH3

N

N

N H3C 74%

CH3

OMe

78%

NO2 68%

Scheme 6.45 Synthesis of 1,2,4,5-tetrasubstituted imidazoles.

1,2,4,5-tetrasubstituted imidazoles (70 and 72). An efficient protocol for the synthesis of structurally diverse imidazoles by Ag2 CO3 -mediated coupling of vinyl azides with secondary amines was also developed recently [80]. Gao and coworker developed a Ag-mediated cascade decarboxylative coupling and annulation reaction, providing a general, one-step approach to structurally sophisticated 2-phosphinobenzo[b]phosphole oxide frameworks 74 of importance in materials science via sequential decarboxylative C—P cross-coupling and C—H/P—H functionalization (Scheme 6.46) [81]. The cascade reaction is completely suppressed by TEMPO, indicating that the reaction follows a radical pathway. 6.2.5

Synthesis of Biaryls

Methods for the cross-coupling of heterocycles with aryl groups are of fundamental importance in nearly all areas of chemical science. Baran group

6.2 Formation of Carbon–Carbon Bonds

O AgOAc (4.4 equiv.) COOH + H P R2 DMF, 100 °C, Ar R2 18 h

R1 73

R2 O O P P(R2)2 R3 74

Ph O P

O

Ph O P

P(Ph)2

O P(Ph)2

Ph O P

R1

O P(Ph)2

COOEt 79%

74%

68%

O O Ph P

P(Ph)2

Cl

Cl

69%

Ar O O P P Ar Ar Ph

Ar O O P P Ar Ar Ph

Ar = 2-MeC6H4 86% (4.2 : 1)

Scheme 6.46 Ag-mediated cascade reaction of arylpropiolic acids with diarylphosphine oxides.

demonstrated the direct Csp2 —H arylation of electron-deficient heteroarenes using aryl radicals delivered from arylboronic acids by means of inexpensive reagents AgNO3 /K2 S2 O8 (Scheme 6.47) [82]. This method allows for rapid access to a variety of arylated heterocycles 76 and 77 that would be more difficult to access with traditional methods. Recently, Flowers and coworker investigated the detailed mechanism of this reaction using kinetic and spectroscopic methods, in order to improve the catalytic system and broaden the substrate scope of the reaction. On the basis of the observed kinetic and spectroscopic data, they proposed a mechanism for the reaction (Scheme 6.48) [83]. The coordination of pyridine with Ag+ yields complex 78. Then, complex 78 can be oxidized by persulfate to give [Ag2+ ]–pyridine complex 79, which is the rate-determining step. Finally, the resulting complex 79 can oxidize arylboronic acid, providing an aryl radical 80, which can add to the pyridinium ion 81, affording the desired product. An off-cycle step is also involved outside of the desired pathway, in which the arylboronic acid is protodeboronated, resulting in the formation of unwanted side products. Despite the prevalence of quinones in several fields of science and technology, universal access to several quinone derivatives has been hampered by a lack of general methodologies relating to their synthesis. Baran group reported inexpensive reagents AgNO3 /K2 S2 O8 -catalyzed Csp2 —H arylation and alkylation of quinones with organoboronic acids (Scheme 6.49) [84]. A broader scope with respect to both quinones and alkyl- and arylboronic acids efficiently undergoes

357

358

6 Coupling Reactions and C—H Functionalization

AgNO3 (0.2 equiv.) B(OH)2 K2S2O8 (3 equiv.) TFA (1 equiv.)

+ Me

N

Me

1 : 1 DCM:H2O rt. 3–12 h

75

N 76 tBu

AgNO3 (0.2–0.4 equiv.) K2S2O8 (3–6 equiv.) R TFA (1 equiv.)

tBu + (HO)2B

N

N

1 : 1 DCM:H2O,rt 3–24 h

R

77

CF3 N Me b

N N

N a

Cl

Cl

Me

N

N

Me

68% + 5% bis (a:b = 2 : 1)

Me 51%

81%

tBu

20 : 1)[a]

65% (>20 : 1)[a]

BzO

Me SCF3

86% (>20 : 1)[a]

[a] The ratios of the shown products to other regioisomers were determined by 19F NMR spectroscopy and are given in parentheses.

Scheme 6.111 Silver-mediated Csp3 —H trifluoromethylthiolation.

A plausible mechanism is proposed in Scheme 6.112. K2 S2 O8 is reduced by Ag(I)SCF3 to generate sulfate radical anion, which abstracts the hydrogen atom from the substrate to produce the alkyl radical. The oxidation of Ag(I)SCF3 by K2 S2 O8 affords Ag(II)SCF3 and CF3 SSCF3 species; both of them might be trapped by the alkyl radical to give the corresponding trifluoromethylthiolated product. Ag(I)SCF3 + S2O82–

Ag(II)SCF3 + SO42– + SO4– 2 Ag(I) + CF SSCF

2 Ag(II)SCF3 R–H SO4–

3

R HSO4–

Ag(II)SCF3 or CF3SSCF3

3

R–SCF3 Ag(I) or SCF3

Scheme 6.112 Proposed mechanism of Csp3 —H trifluoromethylthiolation.

Almost simultaneously, Chen and coworkers reported the trifluoromethylthiolation of unactivated Csp3 —H bond by the similar protocol (Scheme 6.113) [188]. The reaction also has a good functional group tolerance and good selectivity. A similar reaction mechanism is involved as the above reaction. Arylvinyl sulfides are potential scaffolds found in biologically important natural products and natural product-inspired pharmaceutical compounds. Many transition metal-catalyzed/mediated C—H sulfenylations have been developed for the synthesis of diaryl sulfides, but very few of them can be applied to the

393

394

6 Coupling Reactions and C—H Functionalization

Alkyl

AgSCF3 (1.0 equiv.) K2S2O8 (2.0 equiv.)

H

Alkyl

CH3CN, 60 °C, 12 h

SCF3 176 O

SCF3

SCF3

β

γ

SCF3 21% (γ : β = 2.0 : 1)

72%

82% O

β

O

γ

N

SCF3

O

60% (γ : β = 4.9 : 1)

63%

SCF3

O

O

SCF3

56%

Scheme 6.113 Direct trifluoromethylthiolation of various unactivated Csp3 —H bonds.

vinylic C—H bond. There is no silver-promoted vinylic C—H bond sulfenylation that has been reported. Yang et al. developed a Ag-mediated oxidative vinylic C—H sulfenylation of enamides 177 with diaryl disulfides, affording biologically important arylvinyl sulfides 178 in a simple, efficient way (Scheme 6.114) [189]. NHAc

NHAc H

SR′

AgOAc (1.2 equiv.)

+

R′SSR′ DCE, 125 °C, 24 h

n

n

177

178

R′ = C6H5, 4-Cl-C6H4, 4-Me-C6H4, etc.

HN

NHAc H

AgOAc

O AgOAc –HOAc

20 examples 18–82% yield

HN

O Ag(I)

–Ag(0) NHAc

NHAc ArS

ArS

+

Ar

Ag(0)

S

ArSAg

ArS SAr

ArS –Ag(0)

ArS SAr

Scheme 6.114 Silver-mediated oxidative vinylic C—H bond sulfenylation of enamides.

6.3 Formation of C–Heteroatom Bonds

This strategy can also be applied to vinylic C—H selenation of enamides. On the basis of preliminary mechanistic studies, a plausible non-chain radical mechanism was proposed for this novel vinylic C—H sulfenylation (Scheme 6.114). Zhang et al. described a silver-catalyzed Csp2 —H coupling reaction of quinones 179 with aryl disulfides for the synthesis of quinonyl aryl thioethers 180 (Scheme 6.115) [190]. The reaction requires (NH4 )2 S2 O8 as the indispensable oxidant to be effective under mild reaction conditions. Preliminary mechanism studies indicate that the reaction is initiated by active disulfide–silver intermediates. O R

+

Ar

O 179 R = H, Me, Ar, etc.

S

S

Ar

AgOAc (20 mol%) dppp (24 mol%) (NH4)2S2O8 (3.0 equiv.) Bu4NBF4 (1.0 equiv.) DMSO, rt, 48 h

O R S

Ar

O 180 22 examples up to 88% yield

Scheme 6.115 Silver-catalyzed direct thiolation of quinones by activation of aryl disulfides.

The trifluoromethylthio group (CF3 S-) has been well recognized as an important structural motif in the design of lead compounds for new drug discovery because of its high lipophilicity and strong electron-withdrawing properties, which could improve the drug molecule’s cell-membrane permeability and enhance its chemical and metabolic stability. With the rapid development of C—H activation, an attractive strategy is direct C—H trifluoromethylthiolation of the substrate by employing an electrophilic trifluoromethylthiolating reagent. Shen group discovered a highly reactive trifluoromethylthiolating reagent 181 (Scheme 6.105). By using this trifluoromethylthiolating reagent, this group developed a silver-catalyzed decarboxylative trifluoromethylthiolation of secondary and tertiary carboxylic acids under mild conditions (Scheme 6.116) [191]. The reaction tolerated a wide range of functional groups. Radical clock and radical cyclization experiments suggested that the reaction proceeded through a free radical process (Scheme 6.117). Feng and coworkers reported a silver-mediated decarboxylative C—S cross-coupling reaction of aliphatic carboxylic acids using diaryl disulfides as the sulfur source (Scheme 6.118) [192]. This reaction proceeds smoothly under mild conditions and shows good tolerance of functional groups. The proposed reaction mechanism is shown in Scheme 6.119. Firstly, [Ag+ ] is oxidized to [Ag2+ ] in the presence of persulfate, and subsequently, [Ag2+ ] combines with aliphatic carboxylic acid to produce the alkyl radical via decarboxylation pathway. Finally, the alkyl radical attacks diaryl disulfide to afford the final product 183. Additionally, Alves and coworkers described an alternative method for the synthesis of diaryl selenides through the silver-catalyzed cross-coupling reaction of diaryl diselenides with aryl boronic acids (Scheme 6.120) [193]. This methodology is tolerant to electron donor and electron-withdrawing groups at the substrates, and the desired products were obtained in good to excellent yields.

395

396

6 Coupling Reactions and C—H Functionalization

I

SCF3

O

R–CO2H +

AgNO3 (30 mol%) n-C12H25SO3Na (20 mol%)

R–SCF3

K2S2O8 (1.0 equiv.) H2O, 50 °C, 12 h 181 Cl

SCF3 MeO

SCF3

SCF3

91%

Me

80% dr = 9 : 1

55%

SCF3

SCF3 7

Bn X = H, 86% X = F, 78% X = CF3, 82%

X

20%[a,b]

[a] The reaction was conducted in CH3CN/H2O (1 : 2). [b] 24 h.

Scheme 6.116 Decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids. I

Ag(I)

S2O82–

RCO2Ag(II)

O

SCF3

R

R–SCF3

CO2 RCO2H

Scheme 6.117 Proposed mechanism of decarboxylative trifluoromethylthiolation of aliphatic carboxylic acids. AgNO3 (1.0 equiv.) K2S2O8 (3.0 equiv.)

Ar S R COOH + Ar S 182

S

S

R

CH3CN/H2O (1 : 1) Ar, 60 °C, 24 h

O

S

S 183

S

O 70%

42%

Ar

Cl 60% Me

S

R O

S

R = p-Cl, 70% R = o-OMe, 41%

77%

Scheme 6.118 Decarboxylative C—S cross-coupling of aliphatic carboxylic acids.

6.3 Formation of C–Heteroatom Bonds

S2O82–

[Ag2+]

[Ag+] R

R COOH

Ar

S

S

Ar R

S

Ar

CO2

Scheme 6.119 Proposed mechanism of decarboxylative C—S cross-coupling.

RSeSeR

ArB(OH)2

184

Silver catalysis 21 examples up to 96% yield

RSeAr 185

Scheme 6.120 Silver-catalyzed cross-coupling of diaryl diselenides with aryl boronic acids

6.3.4

Formation of C—B Bonds

Transition metal-catalyzed Csp—H borylation is an ideal synthetic route for producing synthetically useful borylated alkynes 186; however, most borylated alkynes were synthesized using an equivalent amount of a strong base, such as n-BuLi [194]. Recently, Hu et al. realized a mild Ag(I)-catalyzed Csp—H borylation of various functionalized terminal alkynes with B(OiPr)pin (Scheme 6.121) [195]. Notably, the Ag(I) catalyst could be recycled by a cooperative PPh3 and BF3 system.

R

AgCl/Ligand/PPh3 (1/1/1 mol%) Cs2CO3 (1.1 equiv.), DMF, 50 °C

+

N R

1 M HCl, 0 °C

B(OiPr)pin

Bpin

Ligand

186 Cl

Bpin 92%

Bpin 84%

N

Bpin

Bpin Bpin

79%

N

N

3 73%

75%

Scheme 6.121 Ag(I)-catalyzed C—H borylation of terminal alkynes.

6.3.5

Miscellaneous Reactions

In 2008, Oshima and coworkers reported a silver-catalyzed transmetalation between chlorosilanes and aryl and alkenyl Grignard reagents for the synthesis of tetraorganosilanes (Scheme 6.122) [196]. This protocol will be applicable to the synthesis of organosilicon reagents and organosilicon-based advanced materials.

397

398

6 Coupling Reactions and C—H Functionalization

R3Si Cl + ArMgBr

AgNO3 (5 mol%) THF, 25 °C or below

R3Si

Ar

187

Scheme 6.122 Silver-catalyzed transmetalation between chlorosilanes and Grignard reagents.

α-Aminophosphonates and their derivatives have received considerable interests in organic and medicinal chemistry over the past several decades because they are functional surrogates for both natural and unnatural α-amino carboxylic acids. Gao and coworkers developed the first Ag-catalyzed three-component reaction of readily available THIQs, aldehydes, and H-phosphonates, providing a new approach to α-aminophosphonate derivatives. This reaction could proceed without the need of an oxidant, and various valuable endo-products can be conveniently obtained in a one-pot process (Scheme 6.123) [197]. In addition, the synthesis of peptides by silver-promoted coupling of carboxylates and thioamides was recently reported by Hutton et al. [198].

R1

O + RCHO + R2 P H NH R2 R1 = H, MeO, Br; R = aryl, alkyl R2 = MeO, EtO, BnO, iPrO, etc.

AgOAc (10 mol%)

R1

N

DCE, 90 °C, Ar, 3 h

R

R2 P R2 O 188 25 examples 46–93% yields

Scheme 6.123 Ag-catalyzed C1-phosphonylation of N-unprotected THIQs.

6.4 Conclusion In the past few years, silver has exhibited interesting catalytic activities in organic synthesis. The results summarized in this chapter highlight numerous important advances that have been made in the development of silver-catalyzed coupling reactions/C—H functionalization. Many of these catalytic systems were developed based upon information garnered from detailed mechanistic studies, which illustrate the complexity of silver-catalyzed coupling reactions/C—H functionalization. Despite all of these advances in the past few years in this area, there are still many challenges. For instance, the development of new catalytic systems with increased reactivity and selectivity under mild conditions and with a wide substrate scope will have important implications for the practical application of these reactions. On the other hand, mechanistic investigations of the reported reactions and future development of novel reactions are expected to be conducted. A better understanding of the mechanism can provide more inspiration on new reaction design.

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4464–4474. (b) Lepitre, T., Pintiala, C., Muru, K. et al. (2016). Org. Biomol. Chem. 14: 3564–3573. (c) Carrill-Arcos, U.A., Rojas-Ocampo, J., and Porcel, S. (2016). Dalton Trans. 45: 479–483. (d) Asahara, H., Kataoka, A., Hirao, S., and Nishiwaki, N. (2015). Eur. J. Org. Chem. 18: 3994–3999. Lundquist, J.T., Satterfield, A.D., and Pelletier, J.C. (2006). Org. Lett. 8: 3915–3918. Huang, C., Liang, T., Harada, S. et al. (2011). J. Am. Chem. Soc. 133: 13308–13310. Guo, S., Zhang, X., and Tang, P. (2015). Angew. Chem. Int. Ed. 54: 4065–4069. Wu, H., Xiao, Z., Wu, J. et al. (2015). Angew. Chem. Int. Ed. 54: 4070–4074. Yang, L., Wen, Q., Xiao, F., and Deng, G.-J. (2014). Org. Biomol. Chem. 12: 9519–9523. Zhang, C., McClure, J., and Chou, C.J. (2015). J. Org. Chem. 80: 4919–4927. Hu, F., Shao, X., Zhu, D. et al. (2014). Angew. Chem. Int. Ed. 53: 6105–6109. Wang, P.-F., Wang, X.-Q., Dai, J.-J. et al. (2014). Org. Lett. 16: 4586–4589. Goldani, B., Ricordi, V.G., Seus, N. et al. (2016). J. Org. Chem. 81: 11472–11476. Brown, H.C., Bhat, N.G., and Srebnik, M. (1988). Tetrahedron Lett. 29: 2631–2634. Hu, J.-R., Liu, L.-H., Hu, X., and Ye, H.-D. (2014). Tetrahedron 70: 5815–5819. Murakami, K., Hirano, K., Yorimitsu, H., and Oshima, K. (2008). Angew. Chem. Int. Ed. 47: 5833–5835. Hu, G., Chen, W., Ma, D. et al. (2016). J. Org. Chem. 81: 1704–1711. Hutton, C.A., Shang, J., and Wille, U. (2016). Chem. Eur. J. 22: 3163–3169.

407

7 Silver-Catalyzed CO2 Incorporation Tohru Yamada, Kohei Sekine, Yuta Sadamitsu, and Kodai Saito Department of Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan

7.1 Introduction The development of efficient catalytic processes for the chemical fixation of carbon dioxide into organic compounds to synthesize industrial, high-value products is of great interest and has been one of the long-standing goals for chemists since carbon dioxide is an abundant, inexpensive, nontoxic, and renewable source of carbon [1]. However, carbon dioxide is thermodynamically stable and much less reactive than other carbon derivatives due to its high oxidation state. Therefore, strong nucleophiles, such as organolithium and Grignard reagents, or harsh reaction conditions are generally required to utilize carbon dioxide in organic syntheses. For example, the Kolbe–Schmitt reaction, which is one of the classical carboxylation reactions using carbon dioxide and considered as a textbook organic reaction, requires high pressure carbon dioxide and a high temperature, though the reaction has been employed for the commercial production of salicylic acid. One of the major issues for the fixation of carbon dioxide into organic molecules is to control the equilibrium between the substrate and its carboxylated intermediate. Considering the carboxylation of simple alcohols or amines with carbon dioxide, these two reactions are in equilibrium. Therefore, the problem is that the corresponding carbonate and produced carbamate are easily converted back to the starting material and carbon dioxide. The transformation of the unstable intermediates into a stable product is one of the reliable solutions of the problem. Silver catalysts are widely utilized in organic reactions as Lewis acids. This feature is strongly reflected in the easy formation of silver acetylides and silver–π complexes, which are well known as highly reactive species. As representative examples, the reactions of silver acetylides with various carbon electrophiles are frequently used for the homologation of acetylene units, and the silver-catalyzed cyclization reactions of alkyne or allene derivatives are promising synthetic methods of heterocyclic compounds. The silver-catalyzed or silver-mediated reactions have been reviewed [2] and summarized in a book [3]. It has since been revealed that silver catalysts still have the additional potential to show a unique reactivity in several carboxylation reactions using carbon dioxide [4] (Scheme 7.1). Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

408

7 Silver-Catalyzed CO2 Incorporation

Nu–

CO2

O O–

Nu

–CO2

R

O

E+ Nu

H

E

O

R′–X

Propiolic acid derivative

R

R

O

OR″

Ag O

Ar

B O Ar

CO2

Ar

O Ag+

COOH

Aryl carboxylic acid

Ag O

R

O + O Ag

O

Cyclic carbonate

R

R O

H–Nu R

Nu

O Alkylidene cyclic carbonate and carbamate

H–Nu R Ag

R

+

Scheme 7.1 Representative silver-catalyzed utilization of carbon dioxide.

In this section, the recent progress of the silver-catalyzed utilization reactions of carbon dioxide in organic syntheses, including the carboxylation reactions of terminal alkynes, boronic esters, and terminal epoxides and tandem cyclization reactions involving nucleophilic additions into carbon dioxide, is described.

7.2 Carboxylation of Terminal Alkynes Carboxylation of terminal alkynes involving the formation of metal acetylide intermediates has been widely developed using various transition metal catalysts. The preliminary reaction for the synthesis of the propiolic acid derivatives based on the insertion reaction of carbon dioxide into silver acetylide was reported by Saegusa’s group in 1974 (Scheme 7.2) [5]. In this study, they discovered that the addition of the trialkylphosphine or isonitrile ligands having a high σ-donor strength is quite important for the efficient carbon dioxide insertion to the silver acetylide 1, prepared by the metalation of a terminal alkyne with t-BuOAg. They also reported in the same paper that copper acetylide has a similar reactivity to the carbon dioxide insertion reaction. A catalytic method of the corresponding reaction catalyzed by silver iodide was developed by Lu and coworkers who reported using Cs2 CO3 under

7.2 Carboxylation of Terminal Alkynes

R1

+

Ag

Ligand

CO2

O

MeI

R1

THF, 80 °C

1

OMe 2 n-Bu3P t-BuNC (MeO)3P Trace 70 65

Ligand Yield (%)

Scheme 7.2 Preliminary report for silver-catalyzed carboxylation of terminal alkynes. AgI (1 mol%) CO2 (0.2 MPa) Cs2CO3 (1.5 equiv.) R

HCl

H

R

COOH

DMF, 50 °C

3

4

3

CsHCO3

– –

CsCO3

AgI

I Ag O

–

Cs

O O

R

5

Ag –

O R

COO–

CsCO3–

R I

MeO

I

CO2

O Ag

COOH

COOH

88% F

HO

64%

COOH F3C

81%

COOH 83%

Br

COOH COOH 78%

O2N

COOH

Cl 76%

74%

Scheme 7.3 Silver-catalyzed ligand-free carboxylation of terminal alkynes.

0.2 MPa of carbon dioxide in dimethylformamide (DMF) (Scheme 7.3) [6]. Features of this method are that the use of expensive or complex ligands is not needed (ligand-free) and various functional groups containing aryl–OMe, –OH, –F, –CF3 , –Br, –Cl, and –NO2 are compatible. This same research group subsequently reported DFT studies of the catalytically active species in this

409

410

7 Silver-Catalyzed CO2 Incorporation

silver-catalyzed ligand-free carboxylation reaction. They found that a silver compound 5 bearing a CsCO3 − anionic ligand rather than the conventionally considered silver propiolate is the active catalyst in this reaction [6b]. In addition, Gooßen and coworkers found that the same reaction proceeded at the lower catalyst loading of AgBF4 (0.05–0.25 mol%) in DMSO(Scheme 7.4) [7]. Zhang’s group developed a highly efficient and reusable N-heterocyclic carbene polymer-supported silver nanoparticle catalyst (Ag–NHC nanoparticle) (Scheme 7.5) [8]. They found that the carboxylation of terminal alkynes was effectively promoted at room temperature using 0.3 mol% Ag–NHC nanoparticle and 1.2 equiv. of Cs2 CO3 in DMSO even under 0.1 MPa of carbon dioxide. AgBF4 (0.05–0.25 mol%) CO2 (0.1 MPa) Cs2CO3 (1.2 equiv.) R

H

HCl

R

COOH

DMSO, 50 °C

Scheme 7.4 Silver-catalyzed carboxylation under atmospheric pressure of carbon dioxide.

R

H

Ag–NHC nanoparticle (0.3 mol%) CO2 (0.1 MPa) Cs2CO3 (1.2 equiv.)

HCl

DMF, room temperature

R

COOH

Scheme 7.5 Silver nanoparticle-catalyzed carboxylation.

A ligand-free Ag(I)-based bifunctional catalytic system based on the use of silver tungstate was developed by He and coworkers (Scheme 7.6) [9]. In this reaction, they proposed that silver tungstate could activate both carbon dioxide and a carbon–carbon triple bond for the direct carboxylation of terminal alkynes with atmospheric carbon dioxide at room temperature. The proposed catalytic cycle starts with the formation of silver acetylide 6 based on the coordination of silver to the carbon–carbon triple bond in the presence of a base, and carbon dioxide is simultaneously activated by tungstate to give the WO4 2− –CO2 adduct. The silver acetylide nucleophilically attacks the tungstate–CO2 adduct 7, resulting in the formation of the silver carboxylate 8 with the release of WO4 2− . N-Butyl iodide alkylated the silver carboxylate to afford the corresponding ester 9. The interactions of WO4 2− with carbon dioxide were confirmed by NMR measurement. When carbon dioxide was absorbed by a suspension of Ag2 WO4 in DMSO-d6 , the 13 C NMR spectrum showed the appearance of a new signal at 𝛿 = 157.8 ppm (the 13 C signal of carbon dioxide is at 𝛿 = 124.2 in the same measurement conditions). It could strongly support the existence of the interaction of the tungstate anion with carbon dioxide in this reaction system. One of the most attractive and practicable approaches to suppress the use of petroleum feedstock is to recycle carbon dioxide as a renewable and environment-friendly carbon source. In fact, amine scrubbing technology is used for the purification of gases by capturing carbon dioxide using alkanolamines as a scavenger. The carbon dioxide fixation reaction into terminal alkynes based

7.2 Carboxylation of Terminal Alkynes

R

Ag2WO4 (2.5 mol%) CO2 (balloon) Cs2CO3 (1.2 equiv.) n-BuI (1.2 equiv.)

H

R

DMF, room temperature COO-n-Bu

R

COO-n-Bu 9

[Ag]

n-BuI

R

[Ag]

CO2Ag

R

8

WO42– CO2 (124.2 ppm)*

R O O W O O 7

O 2– C O

[Ag]

H

Cs2CO3

6

(157.8 ppm)*

*13C NMR chemical shift in DMSO-d6 under carbon dioxide (1 atm) at 25 °C Scheme 7.6 Bifunctional silver complex-catalyzed carboxylation of terminal alkynes.

on this process was developed by Hong and coworkers [10]. Their strategy is as follows: (i) exhaust gases containing carbon dioxide are generated from the combustion of fossil fuels, and carbon dioxide is selectively captured by an alkanolamine solution, resulting in the formation of the amine adduct, and (ii) the carbon dioxide fixation reaction into a terminal alkyne catalyzed by the silver complex is performed using pure carbon dioxide, generated by heating the adduct. This concept was elegantly demonstrated using exhaust gasses generated from the combustion of a candle and 2-aminoethanol 10 as the carbon dioxide scavenger. The pure carbon dioxide derived from the adduct 11 smoothly reacted with aryl- and alkyl-group-substituted terminal alkynes to give propiolic acid derivatives 12 in the presence of silver iodide and Cs2 CO3 in DMF (Scheme 7.7). Anastas’s group achieved the three-component reaction between an aryl-group-substituted terminal alkyne 13, carbon dioxide, and propargyl bromide derivative 14 in the presence of a catalytic amount of silver iodide and potassium carbonate in dimethylacetamide (DMA) to furnish arylnaphthalene lactones 15 and 16 (Scheme 7.8) [11]. During the first stage of the reaction, the carboxylation of the terminal alkyne proceeded to give the alkynyl carboxylate, followed by the alkylation reaction with 3-bromo-1-phenyl-propyne to afford the corresponding 1,6-diyne compound 17. Finally, the [2+2+2] cyclization of the 1,6-diyne occurred to provide two isomers of the arylnaphthalene lactones 15 and 16. The selectivity depended on the electronic properties of the aromatics on the terminal alkyne. Interestingly, in

411

412

7 Silver-Catalyzed CO2 Incorporation

R

AgI (2.5 mol%) Cs2CO3 (1.5 equiv.)

H

R

COOH

CO2, DMF, 25 °C

12

125 °C H N

HO

OH

NH2

HO 11

10

O 25 °C

CO2 from combustion

Scheme 7.7 Silver-catalyzed carboxylation using carbon dioxide generated from combustion.

R1

AgI (20 mol%) CO2 (0.1 MPa) K2CO3 (2.3 equiv.)

Br

R2 +

DMA, 100 °C

R5

R3 R4

R6

H

13

14

R5

R1

O

R2

O R3 R4

R6 O +

R

R3

R6 R2 = OMe, R4 = Me, R1 = R3 = H R2 = R4 = CF3, R1 = R3 = H

13 + 14

cat. Ag CO2 Base

O

R4

5

R1 2

R

15

16

20%

14%

Trace

39% O

R4

O O

R3

R4

O

R3 + R2

R2 R

1

R1 R5 17

R6

Scheme 7.8 Silver-catalyzed one-pot synthesis of arylnaphthalene lactones.

R5 17

R6

7.3 Carboxylation of Aryl Boronic Esters

the case of gold iodide, no arylnaphthalene lactone was detected, but a 1,6-diyne compound was obtained in the presence of the alkyl-group-substituted propargyl bromide instead of the aryl-group-substituted one. Copper iodide was ineffective in this reaction, though the 1,4-diyne compound was obtained from the direct coupling reaction of phenyl acetylene with 3-bromo-1-phenyl-propyne.

7.3 Carboxylation of Aryl Boronic Esters As already mentioned, the insertion reaction of carbon dioxide into the sp-hybridized carbon–silver bond has classically been known and investigated. On the other hand, the corresponding carbon dioxide insertion reaction into the sp2 -hybridized carbon–silver bond is a comparatively challenging issue because a reliable method for generation of the sp2 -hybridized carbon–silver bond is being developed even now. An innovative method for the generation of the sp2 -hybridized carbon–silver bond has been developed by Ritter and Furuya in 2009 by the transmetalation reaction from aryl boronic acid 18 to silver (Scheme 7.9) [12]. The resulting sp2 -hybridized carbon–silver bond 19 was successfully used for the fluorination reaction with Selectfluor as the fluorinating reagent, followed by the formation of fluorinated product 20.

®

B(OH)2

(1) NaOH (1 equiv.), MeOH; AgOTf (2 equiv.), 0 °C

Ag

Transmetalation

Ph

Ph 19 sp2-hybridized carbon–Ag bond

18

(2) 1.05 equiv Selectfluor® 3 Å MS, acetone, 23 °C Fluorination

F Ph 20 82%

Scheme 7.9 Transmetalation and fluorination of boronic acids using silver triflate.

Furthermore, the catalytic carboxylation reaction of aryl–metal bonds, generated by the transmetalation reaction from aryl boronic ester derivatives 21, has been achieved using rhodium and copper catalysts (Scheme 7.10) [13]. Inspired by these precedent reports, Zhang et al. developed a silver-catalyzed carbon dioxide incorporation reaction into the sp2 -hybridized carbon–silver bond, generated from the transmetalation reaction of an aryl boronic ester 22 with a silver catalyst in 2012 (Scheme 7.11) [14]. After their detailed examination of the reaction conditions, it was found that the addition of PPh3 as a ligand for the silver catalyst and potassium tert-butoxide as a base is essential for increasing the efficiency of the carboxylation reaction. In particular, various functional groups, such as bromo-, iodo-, nitro-, vinyl-, and alkynyl-substituted

413

414

7 Silver-Catalyzed CO2 Incorporation

Rh, or Cu cat. CO2

O Ar B

HCl aq

Ar COOH

O 21 Reaction conditions; Rh cat.: [Rh(OH)(cod)]2 (3 mol%) dppp or (p-MeO)dppp (7 mol%) CsF (3 equiv.) 1,4-Dioxane, 60 °C

Cu cat.: [(IPr)CuCl] (1 mol%) t-BuOK (1.05 equiv.) THF, reflux

Scheme 7.10 Transition metal-catalyzed carboxylation of aryl boronic esters. AgOAc (10 mol%) PPh3 (15 mol%) O

Me Me

Ar B O 22

t-BuOK (2 equiv.) CO2 (2 MPa)

H3O+

Ar COOH

THF (70 °C) or 1,4-dioxane (100 °C)

26

AgOAc t-BuOK Ar COOK 25

Ar Ag 23

CO2

Ar COOAg 24

t-BuOK

Scheme 7.11 Silver-catalyzed carboxylation of aryl boronic esters.

organoboronic esters, which are inactive toward rhodium catalytic systems, are compatible with the reaction conditions. In addition to the reaction mechanisms in the cases of the rhodium and copper catalytic systems, the proposed reaction mechanism starts with the transmetalation reaction of the aryl boronic ester 22 by the silver catalyst in the presence of t-BuOK. The carbon dioxide fixation reaction into the resulting sp2 -hybridized carbon–silver bond 23 proceeded to give the silver carboxylate complex 24. Subsequently, the transmetalation reaction of the silver carboxylate with t-BuOK occurs to regenerate the silver catalyst with the release of the potassium benzoate derivative 25. Hydrolysis of the potassium salt produces a benzoic acid derivative 26.

7.4 Functionalization of Terminal Epoxides The synthesis of cyclic carbonates via the cycloaddition of carbon dioxide with terminal epoxides is one of the most representative and efficient routes. Cyclic carbonates are industrially utilized as polar aprotic solvents in organic and polymer synthesis, intermediates for organic synthesis, precursor for producing fine

7.4 Functionalization of Terminal Epoxides

chemicals, and raw materials for engineering plastics. Various homogeneous and heterogeneous catalysts have been employed for the epoxide formation reaction, including alkali metal salts, metal oxides, ammonium salts, Schiff bases, and transition metal complexes [15]. In general, the use of a catalyst containing both Lewis acidic and Lewis basic sites is needed in the cycloaddition reaction of carbon dioxide with terminal epoxides, because the Lewis acidic site (A+ ) electrophilically activates the oxygen atom of the epoxide 27, and the Lewis basic (X− ) site would open the epoxide ring via a nucleophilic attack, leading to an oxy-anion intermediate 28 coordinating to the Lewis acidic site. The oxy-anion intermediate 28 captures carbon dioxide to afford the intermediate 29, and an intramolecular nucleophilic attack of the resulting oxy-anion occurs to furnish the cyclic five-membered carbonate 30 (Scheme 7.12). One of the strategies for enhancement of the catalytic activities is the use of a strong Lewis acidic cation for increasing the electrophilicity and a bulkier cation to weaken the electrostatic attraction between the anion and cation. Additionally, a Lewis base is also required to have the appropriate nucleophilicity and leaving ability.

O

A+

A+X–

O O–

Ph

CO2

X

A+

O– X

O

Ph

27

28

29

Ph

O –A+X–

O

O 30

Ph

Scheme 7.12 Cycloaddition reaction of terminal epoxide with carbon dioxide.

The first example of the silver–NHC-catalyzed reaction of carbon dioxide with terminal epoxides 31 was reported by Çetinkaya and coworkers (Scheme 7.13) [16]. Although they had already developed the same reaction catalyzed by the cationic diimine ruthenium complex in the presence of 4-dimethylaminopyridine (DMAP) as a cocatalyst [17], a more efficient conversion was successfully achieved by using silver–NHC catalyst [Cn min]2 Ag]2 [Ag2 Br4 ] (Cn min; 1-(Cn H2n+1 )-3-methylimidazol-2-ylidene, n = 4–14). All the isolated silver complexes are air and moisture stable, and the solid-state structure of the optimized silver complex (n = 14) was definitely determined by an X-ray single crystal diffraction analysis. In this crystal structure, two (C14 min)2 Ag+ cations are bridged by the divalent [Ag2 Br4 ]2− anion with a weak Ag(cation)–Ag(anion) interaction. They proposed that the [Ag2 Br4 ]2− anion could function as a Lewis basic site and [(C14 min)2 Ag]+ could work as a Lewis acidic site in the catalytic cycloaddition reaction. The benefits of the new catalyst are that various silver–NHC complexes are rapidly synthesized from easily accessible starting materials and a stable in the presence of air and moisture.

415

416

7 Silver-Catalyzed CO2 Incorporation

Cat. (0.1 mol%) DMAP (0.2 mol%) CO2 (1.5 MPa)

O Ph

O O

O

100 °C, 2 h

31

Ph 32

cat.: Ru(diimine)(p-cymene)

73% conversion, TOF 365 /h

[(C14min)2Ag]2[Ag2Br4]

80% conversion, TOF 800 /h

N Ph

C14H29 NH Br– + N

N

+ Ru

BF4–

Ph Cl

Ag2O

Lewis acidic site Lewis basic site

[C14mim-H]Br

Ru(diimine)(p-cymene)

[(C14min)2Ag]2[Ag2Br4]

Scheme 7.13 Ruthenium- or silver-catalyzed cycloaddition reaction of terminal epoxide with carbon dioxide.

7.5 Cascade Carboxylation and Cyclization The Lewis acidic transition metal-catalyzed cyclization reaction based on the electrophilic activation of unsaturated carbon–carbon bonds – sequential intramolecular nucleophilic attack – is one of the most reliable methods for the construction of carbocycles and heterocycles [2e, 18]. Carbon dioxide could be introduced into this reaction system as another component, resulting in the formation of various heterocycles. The general concept of the cascade carboxylation and cyclization using an alkyne substrate is shown in Scheme 7.14. Cat. M+X– CO2 Base

Nu–H R3

R1 R2

O O

Nu–

H-base+ O

O

M+X– CO2

–

O

R1 R2 34

R1

R2 37

33 Base

R3

Nu

R3

R3 CO2 fixation

O

Nu R

1 2R

Nu

R3

M+X– 35 Intramolecular cyclization

M

R2

R1

36

Scheme 7.14 Concept for cascade carboxylation and cyclization of alkyne derivatives.

7.5 Cascade Carboxylation and Cyclization

Usually, any base can be used for the deprotonation of the nucleophilic part of the substrate 33 to form the anionic intermediate 34. The anionic part captures carbon dioxide, resulting in the formation of the carboxylate intermediate 35. The intermediate nucleophilically attacks the alkyne part, activated by a Lewis acidic transition metal catalyst, to afford the vinyl metal intermediate (alkenyl metal intermediate) 36. Finally, the metal–carbon bond was protonated to furnish the cyclic compound 37. In this section, the cascade carboxylation and sequential cyclization reactions using various alkyne substrates, including propargyl alcohols, propargylamines, and alkynes containing other nucleophilic parts, are described.

7.5.1 Silver-Catalyzed Sequential Carboxylation and Cyclization of Propargyl Alcohols Propargyl alcohols could be regarded as amphoteric molecules in the presence of Lewis acidic transition metal catalysts with bases [19]. Under these reaction conditions, the hydroxy group could be deprotonated by a base to give an oxy-anion intermediate having the appropriate nucleophilicity. On the other hand, the alkyne part functions as an electrophile when the Lewis acidic transition metal coordinates. Carbon dioxide could react with the intermediate generated from the propargyl alcohol under the abovementioned conditions to give an alkylidene cyclic carbonate. The features of this strategy are that the reaction proceeds under mild reaction conditions and is an atom-economical method. Thus, it is frequently used for the synthesis of functionalized cyclic carbonates. 7.5.1.1

Synthesis of Cyclic Carbonate

The carbon dioxide incorporation reaction into a propargyl alcohol 38 was first reported by Dimroth and Pasedach in 1961 using copper(I) iodide as a catalyst in the presence of triethylamine as a base, and they successfully demonstrated the efficient synthesis of an alkylidene cyclic carbonate 39 (Scheme 7.15) [20]. This catalytic system was revisited by Laas’s group in 1981, and they synthesized various heterocycles using alkylidene cyclic carbonates as the starting materials [21]. After this report, although various transition metals such as ruthenium [22], palladium [23], and cobalt [24] were employed for this alkylidene cyclic carbonate

OH 2

H

R

R1

Cat. CuI NEt3 CO2

O O

O R1

38

R2

Propargyl alcohols (terminal alkynes)

Alkylidene cyclic carbonate

39

Scheme 7.15 Preliminary report for cascade carboxylation and cyclization of propargyl alcohols with carbon dioxide.

417

418

7 Silver-Catalyzed CO2 Incorporation

synthesis, the application for the reaction of propargyl alcohols containing an internal alkyne part had been highly limited using these catalytic systems. In 2007, Yamada et al. discovered that a silver catalyst is quite effective for the carbon dioxide incorporation reaction into propargyl alcohols 40 including an internal alkyne part (Scheme 7.16(1)) [25]. They demonstrated that the combined use of silver acetate and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was an efficient catalyst system for this reaction to afford the corresponding cyclic carbonates 41 in high to excellent yields, and it was also elucidated that other transition metals such as copper, gold, rhodium, mercury, platinum, and palladium were not effective at room temperature. The exo-alkenyl cyclic carbonates 41 were obtained as the sole isomers, and the geometry of the carbon–carbon double bond was confirmed to be the Z isomer by an X-ray single crystal structure analysis and NOE measurements. These results indicated that the silver catalyst activates the carbon–carbon triple bond from the opposite side of the carbonate anion to promote anti-addition by 5-exo-dig cyclization. This stereoselectivity was also supported by DFT calculations [26]. The outer-sphere attack is similar to the typical reactivity of the related gold(I) catalysts [27], but only the silver catalyst was able to induce cyclization, while gold catalysis fails under these conditions [28]. AgOAc (10 mol%) DBU (0.1–1.0 equiv.) CO2 (0.1–1.0 MPa)

OH R3

R2

Toluene, r.t.

R1

R1, R2 = alkyl, Ar O

40 –O

R3

O R2 Ag+

R1

O R3 (Z)

O

R2

R1

(1)

41 76–99% 14 examples

AgOAc (10 mol%) DBU (40 mol%) CO2 (1.5 MPa) Toluene, 30 °C R1 = H, R2 = Ar, R3 = alkyl

O

O O Alkyl

O

(2)

Ar Vinylene 42 62–94% 12 examples

Scheme 7.16 Silver-catalyzed cascade carboxylation and cyclization of propargyl alcohols with carbon dioxide.

When the secondary propargyl alcohols were employed under the present reaction conditions, it was found that the vinylene carbonates 42, which are useful as prodrugs for drug delivery systems and used as electrolyte additives of lithium ion batteries, were produced [29]. These vinylene carbonates were produced via the thermodynamic isomerization of the alkylidene cyclic carbonate (Scheme 7.16(2)). He and coworkers developed the efficient chemical fixation of carbon dioxide promoted by the Ag2 WO4 /Ph3 P or Ag2 CO3 /PPh3 system (Scheme 7.17) [30]. As previously mentioned [9], Ag2 WO4 works as a bifunctional catalyst for the

7.5 Cascade Carboxylation and Cyclization

Ag2WO4 (1 mol%) O

Ph3P (2 mol%) CO2 (Balloon), 25 °C

R3

R1, R2 = alkyl, R3 = H, Ph

OH R2

R

[(Ph3P)2Ag]2CO3 (1 mol%)

O R3

25 °C R1, R2 = alkyl, R3 = H, Ph

R1

44

CO2 (Balloon or 1.0 MPa)

43

O

R2

1

R3

(Z)

O

(Z)

O O

R2

R1

45

Scheme 7.17 Silver-catalyzed cascade carboxylation and cyclization of propargyl alcohols with carbon dioxide.

activation of the alkyne part of the propargyl alcohol 43 and carbon dioxide. In this reaction, Ag+ electrophilically activates the alkyne part, and WO4 2− forms the adduct with the carbon dioxide. It should be noted that this carbon dioxide fixation protocol smoothly proceeds with only 1 mol% of the silver catalyst and 2 mol% PPh3 , as well as at atmospheric pressure of the carbon dioxide at room temperature under solvent-free conditions. In the Ag2 CO3 /PPh3 system, it is proposed that [(Ph3 P)2 Ag]2 CO3 , which is in situ generated, acts as a bifunctional catalyst for the activation of an alkyne with carbon dioxide. Additionally, they successfully applied these methodologies for the one-pot synthesis of various oxazolidinones bearing exo-cyclic alkenes and carbamates 44 and 45 in moderate to high yields upon the alternative introduction of primary or secondary amines. Recently, a few examples for the synthesis of a cyclic carbonate through the reaction of the carbon dioxide incorporation reaction into propargyl alcohols were also achieved using heterogeneous catalysts [31], such as a silvercoordinated porous polymer [31a,b] and silver nanoparticles (Scheme 7.18) [31c]. These catalysts are highly efficient and reusable for the incorporation of carbon dioxide into propargyl alcohols 46, while a relatively large amount of the silver catalyst and a stoichiometric amount of DBU were required for 47 (2 mol%) CO2 (5.0 MPa), 40 °C OH R3

R2 46

R1

R1, R2 = alkyl, Ar R3 = H

O O O R2

AgNPs (10 mol%) DBU (1.0 equiv.) CO2 (0.1 MPa)

O

25 °C R1, R2 = alkyl, R3 = H

R2

(a) N

R1 Cl

O O

(b)

Ag

N CH3

PS-NHC-Ag (47)

R1

Scheme 7.18 Heterogeneous silver-catalyzed cascade carboxylation and cyclization of propargyl alcohols with carbon dioxide.

419

420

7 Silver-Catalyzed CO2 Incorporation

the homogeneous catalytic systems. The polystyrene-supported N-heterocyclic carbene silver complex 47 (PS–NHC–Ag) had a good catalytic activity and could be reused up to 15 times without considerable loss of its catalytic activity, though high pressure carbon dioxide was required (Scheme 7.18(1)) [31d]. In addition, Han and coworkers reported that silver nanoparticles (AgNPs) catalyzed the carboxylation and cyclization of propargyl alcohols and carbon dioxide and were recyclable at least five times (Scheme 7.18(2)) [31c]. 7.5.1.2

Catalytic Asymmetric Synthesis of Cyclic Carbonate

There are few examples for the catalytic asymmetric synthesis of cyclic carbonate [32]. As the most representative approaches, kinetic resolutions based on chiral transition metal-catalyzed carbon dioxide incorporation reactions into racemic epoxides are known. However, this method produces a maximum chemical yield of 50% for an enantiomer. Therefore, the development of a more versatile strategy for the asymmetric synthesis of cyclic carbonate in terms of chemical yields is quite important and challenging issue. As already described, silver complexes activate the carbon–carbon triple bond as a π-Lewis acid. Based on this observation, an optically active silver catalyst, which is in rapid equilibrium between the two alkynes in symmetric prochiral bispropargyl alcohols 48, was expected to selectively promote the nucleophilic attack on one of the carbon–carbon triple bonds with asymmetric desymmetrization. It was found that the asymmetric carbon dioxide incorporation into prochiral bispropargyl alcohols with desymmetrization by the combination of silver acetate and the chiral Schiff base ligand L* proceeds to afford the corresponding cyclic carbonates 49 with good to excellent enantiomeric excesses (Scheme 7.19). It was confirmed that (S)-cyclic carbonate was obtained from the reaction catalyzed by the complex with (R,R)-L* based on a vibrational circular dichroism (VCD) measurement in combination with the corresponding spectra predicted by DFT calculations [33].

OH R2

R1

O

AgOAc (3 mol%) L*(1 mol%) CO2 (1.0 MPa)

–

O R1

48

O Ph

(Z)

O

92% ee 98% yield

R2

Ph Ph

(Z)

O

O *

Et 93% ee 98% yield

p-Tol Ph

(Z)

O *

49 58–99% 47–93% ee 12 examples cat.

O *

FH2C

O R2

O O

(Z)

R1

AgL*

O

O *

Me

O R1

CHCl3, 0 °C

R1

O

N p-Tol

90% ee 99% yield

Scheme 7.19 Silver-catalyzed asymmetric synthesis of cyclic carbonate.

N

N

N L*

R1

7.5 Cascade Carboxylation and Cyclization

7.5.1.3 Three-Component Reaction of Propargyl Alcohols, Carbon Dioxide, and Nucleophiles

One of the useful applications of carbon dioxide incorporation into propargyl alcohols is the three-component reaction. The reaction between propargyl alcohols 50, carbon dioxide, and secondary amines 51 provided the corresponding carbamates 52 and 53 through the ring-opening reaction of the cyclic carbonates by secondary amines (Scheme 7.20) [34]. In the case of primary amines 55 instead of secondary ones, the intramolecular nucleophilic addition and dehydration produced the corresponding oxazolidinones 56 (Scheme 7.21). Alcohol AgOAc (1.5 mol%) DBU (30 mol%) CO2 (2.0 MPa), 90 °C

OH R2

R3

R4

1,4-Dioxane R1, R2 = alkyl, Ar, H R3 = H, Ar Ag2CO3 (1.5 mol%) Ph3P (6 mol%) CO2 (Balloon)

R1

50 + R4R5NH 51

O R1 N R5

R2 R3

O

(1)

O

52 70–93% 18 examples

R4

CH3CN, 30 °C R1, R2 = alkyl, R3 = H

O R1 N R5

R2 (2)

O O 53

68–98% 14 examples

Scheme 7.20 Silver-catalyzed cyclic carbonate formation and sequential ring-opening reaction.

Ag2WO4 (1 mol%)

O R3N

Ph3P (2 mol%) OH R2

R1

+

R2 R1 56 19–95% 11 examples

MS4A R1, R2 = alkyl

55

54

OH 2

R

O O R2

3

R NH2

O

R1

O

CO2 (0.5 MPa), 50 °C

R4NH2

R1

R3 HN O HO O

R3 HN O

R2 R1

R2 R1 O

R3N

O R3N

O HO

R

O

O

2

1

R

Scheme 7.21 Silver tungstate-catalyzed synthesis of cyclic carbamates.

O R

2

R1

421

422

7 Silver-Catalyzed CO2 Incorporation

derivatives 58 instead of amines could also be employed for the three-component reaction to give acyclic carbonate derivatives 59 (Scheme 7.22) [35].

OH R2

H

R1

Ag2CO3 (5 mol%) Ph3P (10 mol%) CO2 (1 MPa)

57 +

R3

CH3CN, 80 °C

R3OH

O R1 O

O R1 O

O 59

O Ph

Me H

O

Bn

O

O R1 = Me, 91% = Et, 93%

O

Bn

O

H

Bn

O

H

O O

86%

94%

O

n-C6H13 H

O

Bn

O

Me

94%

H

O

O

O 93%

H

O

O H O

O

Me O

O Bn

H

O

58

Bn

R2

O 95%

Scheme 7.22 Silver-catalyzed acyclic carbonate formation via ring-opening reaction of cyclic carbonate.

7.5.1.4

CO2 -Mediated Transformation of Propargyl Alcohols

Decarboxylative transformation is a well-known elementary process because carbon dioxide is a thermodynamically stable molecule, and the elimination of it from the intermediate could easily occur. Thus, the carbon dioxide mediation reaction via the carbon dioxide fixation – sequential decarboxylation reaction – could proceed in some cases. In the previously mentioned reactions, the silver-catalyzed reaction of propargyl alcohols with carbon dioxide selectively afforded the corresponding five-membered cyclic carbonates 41 in toluene (Path A in Scheme 7.23) [25], while in dichloromethane and chlorobenzene, the corresponding α,β-unsaturated carbonyl compound 60, generated via a Meyer–Schuster type reaction, was detected along with 41. The following reaction mechanism was proposed for the formation of 60: the hydroxy group of the substrate 40 reacts with carbon dioxide, resulting in the formation of the carbonate anion 61 as well as the reaction pathway for the production of the five-membeed cyclic carbonate. The resulting carbonate anion attacks the β-carbon of propargyl alcohol to promote the [3,3]-sigmatropic rearrangement into the allene enolate 62. The α,β-unsaturated carbonyl compounds would be obtained by the protonation of the allene enolate, involving the release of carbon dioxide (Path B

7.5 Cascade Carboxylation and Cyclization

O OH 1

R3

R2

O

–

R

Ag+, CO2

O AO

B

DBU

R2

R3

Path A R1

in toluene

R3 (Z)

O

R2

Ag+ 61

40

O R1

41

[3,3]-Sigmatropic rearrangement

Path B in formamide O

– O

O R3

R1

O R1

R2

R3 O C O

R2

60

62 Meyer–Schuster rearrangement +

OH R3

R2

R

H

1

H2O

OH2

+

R3

R2

R

–H2O

O R2

R3

Tautomerization

R2

R3

R1 HO

+

1

R3

R1

R1 R2

Scheme 7.23 Carbon dioxide-mediated Meyer–Schuster type rearrangement.

in Scheme 7.23). The reaction mechanism was confirmed by an isotropic labeling experiment using C18 O2 . It is reasonable to assume that the polarized structure with an elongated C—O bond in the carbonate intermediate would be stabilized in a polar solvent, thus enhancing the attack on the β-carbon in the activated propargyl alcohol. In fact, the selectivity toward the enone was improved in the case of DMF and DMA. Finally, it was found that formamide was the best choice to selectively obtain the corresponding enone 41. Various tertiary and secondary propargyl alcohols were efficiently converted into the corresponding α,β-unsaturated carbonyl compounds in high yield using a catalytic amount of silver methanesulfonate with DBU and carbon dioxide (Scheme 7.24) [36]. It should be noted that a Meyer–Schuster rearrangement generally needed to use harsh conditions such as strong acidic conditions. By using this method, a similar transformation reaction could be achieved under mild reaction conditions. Recently, the decarboxylative electrocyclization reaction of five-membered cyclic carbonates, prepared by the carbon dioxide fixation reaction with propargyl alcohol derivatives, was reported by the same group. When 1,4-enynes 63

423

424

7 Silver-Catalyzed CO2 Incorporation

AgOMs (10 mol%) CO2 (1.0 MPa) DBU (1.0 equiv.)

OH

R3

R2

R1

Formamide, r.t.

40

R1, R2 = Alkyl, Ar, H

O R3

R1 R2

60 29–98% 14 examples

R3 = CH2CH2Ph, Pr, n-Hex, OEt

Scheme 7.24 Silver-catalyzed synthesis of enones based on the Meyer–Schuster-type rearrangement.

having propargyl alcohol motifs were employed for the reaction in the presence of a silver catalyst and DBU under 1 MPa of carbon dioxide, the corresponding alkylidene five-memberd carbonates 64 were quantitatively obtained. After the removal of DBU by washing with water, 64 were treated with a catalytic amount of various Lewis acids, resulting in the formation of multi-substituted 2-cyclopentenone derivatives 65 in excellent yields with excellent stereoselectivities by the decarboxylative Nazarov cyclization (Scheme 7.25) [37]. Among the examined catalysts, a representative boron Lewis acid BF3 ⋅OEt2 gave the best result, but AgSbF6 also supplied the product 65a in a good yield. Nazarov cyclization is a conrotatory 4π-ring-closure reaction of divinyl ketones via a pentadienyl cation in the presence of acid catalysts. However, there are two problematic issues about the Nazarov cyclization: in general, (i) more than a stoichiometric amount of an acid is required for an efficient conversion, and (ii) the control of the position of the double bond in the produced 2-cyclopentanones is also difficult. These problems were successfully solved by the decarboxylative approach because ease of the elimination of the carbon dioxide from the cyclic carbonate realized the efficient catalytic cycle and the decarboxylation–sequential ring closure induced an excellent stereoselectivity. Interestingly, the geometry of the olefin part of the cyclic carbonates was perfectly reflected in the stereochemistry of the 2-cyclopentenones. Thus, (Z)-64a was employed for the Nazarov cyclization to afford cis-65a in good yield, stereospecifically. 7.5.1.5

Transformation of Amine Derivatives

It has been known that some amines efficiently capture carbon dioxide, and this feature is utilized for amine scrubbing technology, i.e. the purification of gases [38]. Therefore, amines having unsaturated bonds could also be used for cascade carboxylation and cyclization as substrates as well as propargyl alcohol derivatives. 7.5.1.6 Cascade Carboxylation and Cyclization of Unsaturated Amine Derivatives

The oxazolidinone preparation from carbon dioxide is one of the most attractive synthetic methods. The preparation of oxazolidinones 67 through carbon dioxide incorporation into various propargylamines 66 was achieved in high yields

7.5 Cascade Carboxylation and Cyclization

R1

R5

AgOAc (10 mol%) DBU (1.0 equiv.) CO2 (1.0 MPa)

R4

Toluene, 25 °C

OH R3 R2 63

R5 R

3

R4

LA

O O LA

5

R R3

O

64

O

R1

O R1

R2

O O

O

O

R1

R5 R3

R4

R4

O

Nazarov cyclization

R1

–CO2

R3

–LA

R2

R2

R2

R5 R4

65

64 O O

O

O

Ph

Me (E) Ph (E)-64a

O O

Me Ph

(Z)

(Z)-64a

ClCH2CH2Cl (0.1 M) r.t.

Me

Ph

LA BF3(OEt2)

Ph trans-65a Yield (%) 95

AgSbF6

86 O

BF3(OEt2)

O

Ph

LA (10 mol%)

(20 mol%) ClCH2CH2Cl (0.1 M) r.t.

Ph

Me

Ph cis-65a (88%) [trans-65a (99%

95%

62%

O

O

O

O

O Ph

Ph

R2

OH Tetronic acid

Ag+

10 mol% AgOAc CO2 (2.0 MPa) 4.0 equiv. MTBD

87

R1

O

R1

Ynone

O

R2

O

CO2

Base

O Ph

OH

OH 77%

OH 88%

97%

Scheme 7.37 Concept for synthesis of tetronic acids based on the silver-catalyzed carboxylation–cyclization and its scope. OMe

O MeO

EtO

n-BuLi (2 equiv.) BF3 • OEt2 (2.4 equiv.)

THF –78 °C OMe

AgOAc (20 mol%) CO2 (2.0 MPa) MTBD (4 equiv.)

O MeO

O MeO

CH3CN, 40 °C 72 h

O

OMe

OH 90 BBr3

89

O HO

O OH Aspulvinone E

Scheme 7.38 Facile approach to aspulvinone E.

OH

7.6 Conclusion

incorporation reaction, resulting in the formation of the corresponding tetronic acid 90 in 73% yield. The demethylation of two methoxy groups on it was deprotected by boron tribromide to furnish aspulvinone E in 98% yield. Overall, the synthesis of aspulvinone E was achieved in three steps. 7.5.1.12

Carbon Dioxide Incorporation Reaction Using Other Carbanions

Recently, the silver-catalyzed cascade carboxylation and cyclization of the trimethyl(2-methylenebut-3-yn-1-yl)silane derivatives 91 were developed [51]. The allylsilane compound is one of the useful reagents for new carbon–carbon bond formations. For example, Hosomi–Sakurai allylation has been used to provide homoallyl alcohols, which are an important framework for the total synthesis of natural products and medicinal compounds. Though allylsilane compounds have the additional potential for carbon dioxide incorporation, few systems involving the Lewis acid-mediated carboxylation have been reported. The present reaction was promoted by a silver salt and CsF to afford the corresponding 2-furanones 92 and 2-pyrones 93 in good to high yields (Scheme 7.39). When aromatic ring-substituted alkynes were used, 2-furanone derivatives were selectively obtained via the 5-exo-dig cyclization, whereas the reaction of the alkyl-substituted alkynes produced 2-pyrone derivatives with a high selectivity. CO2 (1.0 MPa) (IPr)AgCl (10 mol%) CsF (1.5 equiv.) MeOH (1.2 equiv.)

Me3Si 91

R

O

O O

O

DMF, 40 °C, 24 h

R

R 92

93

Yields (%)a R R1 = R1

H Me OMe CO2Et Ac CF3 c

Phc,d

92

93

78 76 66 74 72 78

Trace 5 9 —b —b —b 77 65

b

—b

a Isolated yield. b Not detected. c 50 °C. d Using AgOTf instead of (IPr)AgCl.

Scheme 7.39 Silver-catalyzed carboxylation and cyclization initiated by desilylation reaction.

7.6 Conclusion Recent developments in the silver-catalyzed carboxylation chemistry using carbon dioxide were described. In some cases, silver catalysts showed an effective reactivity unlike other transition metals, including coinage metals. In

435

436

7 Silver-Catalyzed CO2 Incorporation

particular, silver catalysts often exhibit unique and appropriate Lewis acidities even in the presence of several additives such as some reactants, bases, and metal salts. This feature plays an important role in the silver-catalyzed carbon–carbon bond-forming reactions and tandem reactions involving the carboxylation reaction. The silver-catalyzed carboxylation reaction using carbon dioxide as the C1 source has now become one of the representative and reliable bond formation reactions. Carbon dioxide is easily available, nontoxic, and inexpensive; therefore, development of reactions for the preparation of chemicals from carbon dioxide under mild reaction conditions will be of increasingly great industrial and academic interest in the future.

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439

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions Mahzad Dehghany, Josephine Eshon, Jessica M. Roberts, and Jennifer M. Schomaker University of Wisconsin, Department of Chemistry, 1101 University Avenue, Madison, WI 53706, USA

8.1 Introduction to Silver-Mediated Carbene Transfer Reactions The utility of homogeneous silver catalysts in organic synthesis has been underexplored compared with the other group 11 transition metals, copper, and gold. Traditionally, silver salts and their complexes have been employed mainly as oxidants, halide scavengers, additives, or heterogeneous catalysts for Wolff rearrangement reactions [1, 2]. The Wolff rearrangement is a well-known reaction that comprises the first step of the Arndt–Eistert synthesis, a method for the one-carbon homologation of activated carboxylic acids [3]. Arndt–Eistert homologations are typically catalyzed by silver(I) salts, although they can be performed under a variety of conditions [3]. While the mechanistic details of the Wolff rearrangement are still not completely understood, studies suggest that the reaction proceeds through the intermediacy of silver carbenes. This hypothesis was supported by an MS study carried out by Beauchamp and Stoltz, where dimethyl diazomalonate 1 was treated with a silver catalyst to form 2 (Scheme 8.1) [4]. Under these conditions, dissociation of the weakly coordinated MeCN ligand leads to the formation of complex 3, which undergoes further loss of CO and N2 to form 4. The loss of a second CO furnishes 5 through the intermediacy of a silver carbene. Further support of this mechanism pathway was conducted with substrates labeled with deuterium and 13 C, albeit using a copper-based catalyst. Hu and coworkers proposed a mechanistic pathway similar to that described by Beauchamp and Stoltz in their silver-promoted Wolff rearrangements of α-diazo-β-ketoesters (Scheme 8.2) [5]. In this case, formation of the proposed silver carbene was followed by rearrangement and migration to deliver the product. However, in recent years, there has been growing interest in exploring new reactions and applications for homogeneous silver catalysts [2]. In addition to the Wolff rearrangement, silver catalysts have been described for a range of other carbene insertion reactions, including cyclopropanation, cyclopropenation, Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

440

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions MeCN O

O MeO

O

Ag

OMe

O

O

N2

N2

CO OMe

MeO

OMe

2

O

N2, CO

O

MeO

OMe

1

+ Ag

–MeCN

+

MeO

MeCN

N2

Ag

Ag

MeO

OMe Ag

+

4

3

+

5

Scheme 8.1 General mechanism of the Wolff rearrangement. O O

R Ph

O

N

N2 OEt

Ph

Ag

N2

O

R N

Wolff rearrangement

O OEt

R

R N

Ph

OEt

Ag

N

Ph

OEt O

O

O

Scheme 8.2 Wolff rearrangement of α-diazo-β-ketoesters.

C–H insertion, and N–H insertion, all of which will be discussed in the following sections. While the focus is placed on silver catalysis, various rhodium and copper complexes are included when necessary for the purpose of comparison. Only new advances in silver-mediated carbene transfer chemistries reported since 2008 are included in this chapter.

8.2 Introduction to Cyclopropanation 8.2.1

General Catalysts for Cyclopropanation

Several general catalysts for the addition of metallocarbenes to alkenes are illustrated in Figure 8.1. For example, rhodium complexes supported by chiral carboxylates and carboxamidates are well known to catalyze enantioselective cyclopropanations [6–10]. Porphyrin scaffolds also furnish rhodium catalysts that show high asymmetric induction in alkene cyclopropanation. The other major class of catalysts for the enantioselective addition of metal carbenes to alkenes are based on copper(I) salts supported by a chiral ligand, including salicylaldimines, semicorrines, bis(oxazolines), bipyridines, and pybox ligands [6, 11–22].

O Rh

Ph

O

Rh catalysts R

N

O

O

N N

O

Rh

Rh

Rh

R

CO2Me

Rh

Rh2(5S-MEPY)4

Rh

CO2Me R Me Ph

I N

N Ph Rh2(4S-MACIM)4 Rh2(4S-MBOIM)4

RhTPPI

Ph

Rh N

N

Ph

R = Me, Ph, CF3 R Cu catalysts Ph N O

Me Cu

2 Salicylaldimines

N

Cu X X

O

O N

Semicorrins

t Bu

N

n

Me Me

N

R

N t Bu

Bis(oxazoline)

N

n R

R = i-Pr, CMe2Et, SiR3 Bipyridines

Ph Ph

O

O

N N

N i-Pr

pybox Ph

Ph Ph i-Pr

Ph

Mesityl

Mesityl NH HN

Figure 8.1 Representative examples of catalysts for alkene cyclopropanation via metallocarbenes.

8.2 Introduction to Cyclopropanation

R1 R2 R3

H 1 – B R1 R N N N R2 R2 N N N R3

R2

Br 3

Tp Tp Ms Tp *

Tp *,B r

R1

R2

Br

Br

Br

H

H

Mesityl

Me Me

H Br

Me Me

R3

Tris(pyrazolyl)borate ligands

Figure 8.2 Representative silver catalysts used for carbene transfer to alkenes.

In contrast to Rh and Cu catalysts for carbene transfer, silver catalysts for enantioselective cyclopropanation are rare. However, there are a number of reported racemic reactions promoted by simple silver salts or Ag(I) complexes containing tris(pyrazolyl)borate, bis(pyrazolyl)borate, or poly(pyrazolyl)borate ligands (Figure 8.2) [23]. 8.2.2

Recent Advances in Silver-Catalyzed Cyclopropanation

In 2015, Mack and coworkers reported an inexpensive and recyclable silver-foil catalyst for the cyclopropanation of alkenes with diazoacetates under mechanochemical conditions (Table 8.1) [24]. Using this method, the mechanochemical process could be carried out five consecutive times with minimal loss in catalyst activity. Mono- and disubstituted alkenes were viable substrates, undergoing cyclopropanation in good yields and diastereoselectivity, while tri- and tetrasubstituted alkenes gave no reaction under these conditions. Various diazoacetates were also tolerated in the reaction, giving products in similar yields and diastereoselectivity to the parent phenyl diazoacetate (Table 8.2). In 2013, Wang and coworkers reported a silver carbenoid-initiated enone cyclopropanation cascade for the construction of functionalized bicyclo[3.3.1]nonanes [25]. In the proposed mechanistic pathway (Scheme 8.3), electrophilic activation of the propargylic ester A by a silver cation triggers a 5-exo-dig attack (acyloxy migration) of the carbonyl group of B on the coordinated alkyne to give C. C rearranges to form the vinyl silver carbenoid intermediate D, which cyclopropanates the enone double bond, leading to intermediate E. Further rearrangement in either a 1,2- or 1,4-addition pathway gives the product bicyclo[3.3.1]nonanes F and G. 8.2.3

Recent Advances in Silver-Catalyzed Cyclopropenation

In 2011, the Davies group developed a mild silver triflate-catalyzed cyclopropenation of internal alkynes utilizing donor–acceptor-substituted diazoesters (Scheme 8.4) [26]. When the reaction was conducted with silver salts containing tightly bound counterions, such as NO3 − , PO4 3− , CF3 CO2− , CO3 2− , PhCO2− , and SO4 2− , only trace amounts of cyclopropenes were observed. However, the use of weakly coordinating counteranions for silver, particularly triflate, successfully converted disubstituted alkynes to the corresponding cyclopropenes

441

Table 8.1 Scope of alkene cyclopropanation catalyzed by silver foil. R4 R3

Ph

1 2 3 4 5 6 7 8

R1 4-MeOC6H4 4-MeC6H4 4-BrC6H4 4-ClC6H4 4-FC6H4 4-tBuC6H4 C6H5 C6H5

R2 H H H H H H CH3 H

R3 H H H H H H H CH3

Ag foil CO2Me

R2 Entry

MeO2C

N2

R1

R4

Yield (%)

R4

16 h R3 E/Z

H H H H H H H

90 92 89 90 85 96 88

92 : 8 96 : 4 98 : 2 95 : 5 98 : 2 98 : 2 85 : 15

H

86

92 : 8

Ph

Ph

R2

CO2Me

R4

R1

R2

R3

R1

Entry

R1

R2

R3

R4

9 10 11 12 13 14 15 16

C6H9 C6H5 C6H5 C6H5

H H H C6H5

H C6H5

H H C6H5

1-Naphthyl 2-Naphthyl C6H5 C6H5

H H C6H5 C6H5

H H H H C6H5 C6H5

H H H C6H5 H

Yield (%) 82 35 58 89 85 89 NR NR

E/Z 85 : 15 NA NA NA 95 : 5 98 : 2 — —

8.3 Introduction to C–H Insertion

Table 8.2 Effect of the diazoacetate on alkene cyclopropanation catalyzed by silver foil. Ph

N2

+

CO2R2

R1

16 h

CO2R2

CO2R2

Ag foil Ph

Ph

R1

R1

Entry

R1

R2

Yield (%)

E/Z

1 2 3 4 5 6

4-MeOC6H4 4-CF3C6H4 4-BrC6H4 4-tBuC6H4 H CO2Me

Me Me Me Me Et Me

95 85 90 95 88 NR

92 : 2 88 : 12 90 : 10 98 : 2 60 : 40 —

in good yields using a range of donor–acceptor-substituted diazo compounds. In cases where both a mono- or disubstituted alkene and alkyne were present, the cyclopropanation of the alkene was favored to yield a single diastereomer. When the olefin was more highly substituted, the cyclopropenation reaction was favored instead. However, no cyclopropenation was observed for the more electron-rich p-methoxylphenyl diazoacetate, which reflects the low reactivity of this silver-supported carbenoid. In 2017, the Bi group reported a silver-catalyzed [2+1] cyclopropenation of alkynes at room temperature using unstable N-nosylhydrazones as diazo surrogates (Table 8.3) [27]. The reaction was attempted with common carbene transfer catalysts, such as Rh2 (Oct)4 , Zn(OTf )2 , Cu(OTf )2 , and Pd(OAc)2 ; however, only AgOTf resulted in productive (85%) formation of the [2+1] product. A variety of aryl N-nosylhydrazones bearing formyl, nitro, cyano, and halogen functional groups were tolerated under the reaction conditions (Table 8.3). In addition, both linear and branched alkynes containing diverse functionalities, including alkynyl, halogen, ester, and amino groups, were successful in the reaction. The mechanism of the transformation was proposed to proceed through silver carbene intermediates.

8.3 Introduction to C–H Insertion 8.3.1 General Mechanism of C–H Functionalization via Transition Metal-catalyzed Carbene Transfer C–H functionalization via transition metal-catalyzed transfer of a carbene group into the C—H bond is a common strategy for adding functionality to a molecule. Early reports of this chemistry focused on intramolecular reactions; however, more recent advances expand these C—C bond-forming reactions to include intermolecular metallocarbene C–H insertions. Many groups, including those of Sulikowski, Burgess, Davies, Doyle, McKervey, Lovely, Katsuki, Browning, Dias, and Pérez, have made important advances in carbene transfer chemistry, as covered in the previous edition of this book [28–35].

443

O

O

O

O Ar

O Electrophilic

O

Ar

5-exo-dig attack

O

Activation

O Ag

O

Me O

Me O

Me O

A

O

Ag

O

+

Enone cyclopropanation

Ar

Me O O

O O

O Ar

O

HO

E

O

Me

Scheme 8.3 Proposed mechanism of Ag carbenoid enone cyclopropanation.

Me

F

1,4-Addition

Me

O Ar

O

O O

O D

B

O

Ar O

+

Ag

+

C

+

Ag

Ar

O

Ag-carbenoid formation

G

1,2-Addition

8.3 Introduction to C–H Insertion

Ph

Me

N2

+ Ph

Ph

10 mol% AgOTf CH2Cl2, rt

CO2Me

CO2Me

Ph

Me

Scheme 8.4 General example of silver-catalyzed cyclopropenation. Table 8.3 Effect of N-nosylhydrazone structures on the reactivity. R1

R2

NNHNs

R2

R2

6 mol% AgOTf NaH, CH2Cl2 40 °C, 18 h

R = 4-Cl, 85% R = H, 82% R = 3-MeO, 75% R = 2-Cl, 66% R = 4-CN, 76% R = 4-NO2, 78% R = 4-CHO, 85%

Pr Pr R

R2

R1

Pr

Pr F

Br Pr

Pr F

70%

OMe

Pr

Cl

78%

Pr Pr Pr

Pr

Ts N

N

60%

52%

R X = S, 54% X = O, 68%

Pr Pr

Pr

X

56%

Pr

Pr

R = H, 76% R = Br, 90%

Ph

Pr

Pr R

R = Ph, 59% R = TIPS, 84%

R1

R R

R = Me, 88% R = Et, 91% R = n-Bu, 75% R = Ph, 43%

R2

(R1 = Me, R2 = t-Bu) 55% (R1 = Me, R2 = Ph) 49% (R1 = n-Bu, R2 = Ph) 46%

OMe

Three possible mechanisms for metal-catalyzed C–H functionalization via carbene transfer are shown in Scheme 8.5 [36]. A carbene precursor, typically a diazoester or similar compound, reacts with the metal to form a highly electrophilic (in some cases) metallocarbene and release nitrogen gas. There are three classes of commonly employed diazo compounds (Figure 8.3):

445

R1

R5

R2

H

R1 R2 R3 4

R

R4 Pathway 1

LnM C

LnM C

R5

H

O

R2

H N

O

AgOTf

O

R1

N2 N

O O

R1

R2

Scheme 8.5 General mechanism for metal-catalyzed C–H functionalization via carbene transfer.

H

R1

R1 –N2

R2

Pathway 3

–N2

O

AgOTf N

Pathway 2

R3

O

R2

R2

R5

H

OH

N R

N2

R1

AgOTf O

O

R2

R1

N

N

O

N

N

N2

N

R1

O

OH

O R2

R1

H C

R2

R2 O

N

R5

R4

R3

R4

H

N2 MLn

O

AgOTf

8.3 Introduction to C–H Insertion

Figure 8.3 Representative examples of the different types of diazo carbene precursors.

N2

N2 EWG

EWG

Acceptor acceptor

R

N2 EWG

Acceptor

EDG

EWG

Donor–acceptor

acceptor–acceptor, acceptor, and donor–acceptor. However, the acceptor ethyl diazoacetate (EDA) has been employed most frequently in silver-catalyzed C–H functionalization, likely due to its reactivity and commercial availability [37]. The electrophilicity of the silver-stabilized carbene plays a large role in controlling the reactivity of the catalyst with the C—H bond to form the new C—C bond. Several transition metals, including rhodium and copper, have been shown to proceed through metallocarbene intermediates (Scheme 8.5, pathway 1). While there is some evidence for silver-supported carbenoids, carbene transfers initiated by silver can also occur through coordination of the metal with either the diazo group (pathway 2) or the carbonyl group of the carbene precursor (pathway 3). 8.3.2

General Catalysts for C–H Functionalization via Carbene Transfer

Various coinage metals, including Rh, Fe, Ru, Cu, and Ag, are commonly employed as catalysts for carbene transfer reactions. Porphyrins are popular ligands for Fe (Figure 8.4), while bridging carboxylates are popular for dinuclear rhodium complexes, as exemplified by Rh2 (S-NTTL)4 , Rh2 (S-DOSP)4 , and others. N-Heterocyclic carbenes (NHC) and polypyrazolylborates (Tp) are common ligands for the group 11 metals Cu(I), Ag(I), and Au(I) [38]. Among the known C–H functionalization catalysts, dinuclear rhodium complexes have been the most studied; however, within the group 11 metals, copper catalysts have been the most prevalent and are discussed here for direct comparisons to recently reported silver catalysts. C–H functionalizations with various CuTpX (TpX = trispyrazolylborate) complexes, containing either electron-donating or electron-withdrawing groups, have been extensively investigated by the Pérez group. These studies revealed that CuTpX complexes with electron-withdrawing groups (bromine and fluorine) on the Tp scaffold gave the highest yields in C–H functionalizations of cyclohexane and n-hexanes [34, 39–41]. These results were rationalized due to the increased electrophilicity of the putative metallocarbene. To support this hypothesis, carbonyl derivatives of CuTpX were synthesized, and their carbonyl stretching frequencies measured (Table 8.4). Indeed, (CO)CuTpX catalysts with electron-withdrawing groups displayed high CO stretching frequencies, due to the low electron density around the metal center. Similar IR studies were performed on silver complexes supported by Tp ligands [31, 42, 43]. High CO stretching frequencies ((CO)AgTp(CF3 )2 = 2178 cm−1 and (CO)AgTp(Br)3 = 2157 cm−1 ) were observed when the Tp ligands were electron poor; in fact, silver catalysts possessed more electrophilic metal centers than the analogous copper complexes. As a result, better catalytic activities were observed for the silver systems compared with the copper ones, even enabling functionalization of the primary C—H bonds in pentane to give A (Table 8.5).

447

R

N

H

R

N

O Rh

O

R

N N

O Rh

N N

O

O Rh

O O Rh P O O Rh

O Rh

SO2Ar

4

O 4

R

Rh2(S-DOSP)4

4 Rh2(S-PTTL)4

Rh2(S-NTTL)4

Porphyrins

O Rh

O Rh

O

Rh2(S-DOSP)4 Rh2(S-BNP)4

R

R

N

N

NHC

H

1

N N

R2 R R3

R1

R2

R1 B N R2 N N R2 N

H

Polypyrazolylborate

O

N R

R3 H

H

H

O

H R O N

O

Rh O O

H

Figure 8.4 Representative ligands and catalysts for C–H functionalization via carbene transfer.

Rh

R

N R

N

O

H O

H

Rh2(S-biTISP)4

4

8.3 Introduction to C–H Insertion

Table 8.4 Carbonyl stretching frequencies for (CO)CuTpX and (CO)AgTpX complexes. Entry

vco(cm–1)

Catalyst TpiPr2CuCO TpCuCO TpCF3CuCO TpBr3CuCO Tp(CF3)2CuCO CO TpC2F5AgCO TpBr3AgCO Tp(CF3)2AgCO

1 2 3 4 5 6 7 8 9

2056 2083 2100 2110 2137 2143 2153 2157 2178

Table 8.5 AgTpx -catalyzed carbene insertion into the C—H bonds of pentane. Tp(CF3)2 or TpBr3 CO2Et

N2 H

+

+ CO2Et

EtO2C

A

B

C

Tp(CF3)2

41%

47%

27%

TpBr3

27%

53%

13%

CO2Et

Computational studies of C–H carbene insertions catalyzed by AgTpx complexes suggest a mechanism where the rate-determining step is the formation of the metallocarbene species and the selectivity-determining step involves the metallocarbene interacting with the alkyl C—H bond, leading to an irreversible product-forming step [44–47]. Energy barriers for the interactions of different C—H bonds with silver- and copper-supported carbenes were calculated (Table 8.6). The silver complexes showed little to no barriers for Table 8.6 Calculated energy barriers for the interactions of C—H bonds with metallocarbenes. H H H

H H H H B N H N N N H N N H Tp

Alkane H3C–H H3CH2C–H (CH3)2HC–H (CH3)3C–H

Br Br Br

Br Br H Br B N Br N N N Br N N Br TpBr3

CuTpBr3 (kcal mol−1)

AgTpBr3 (kcal mol−1)

AgTp (kcal mol−1)

9.6 5.9 4.2 4.2

3.7 0.3 0 0

5.9 2.5 0.9 0.4

449

450

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

carbene insertion into secondary and tertiary C—H bonds and barriers of only 3.7–5.9 kcal mol−1 for insertion into strong primary C—H bonds. Overall, the silver complexes displayed lower energy barriers as compared with the analogous copper complexes. 8.3.3 Recent Advances in Silver-Catalyzed Alkane C–H Functionalization via Carbene Transfer In 2012, the Caulton and Mindiola groups reported the synthesis and reactions of a trinuclear silver cluster (Ag3 (μ2 -3,5-(CF3 )2 PyrPy)3 , where PyrPy = 2,2′ -pyridylpyrrolide (Table 8.7) [46]. At room temperature, the trinuclear silver cluster promoted carbene insertion into the C(sp3 )—H bonds of a range of alkanes, including ethane, hexane, cyclopentane, and cyclohexane. Cyclohexane and cyclopentane underwent C–H activation to form the ester products in good yields with minimal carbene dimerization. Pentane and hexane also underwent the C—H bond functionalization, with the largest preference for insertion at C2, followed by reaction at C3 and lastly C–C formation at C1. DFT calculations of the monomeric silver complex, Ag(3,5-(CF3 )2 PyrPy), suggested that the reaction proceeds through a silver-supported carbene, with the formation of this intermediate species proposed to be the rate-limiting step. In 2017, Pérez and coworkers reported the first silver-catalyzed carbene insertions carried out in water [47]. Initial studies focused on the cyclopropanation and aziridination of styrene using Cu-based catalysts previously reported by the group. Excellent yields were obtained, regardless of whether the reaction was carried out directly in water or using micelles. However, no examples of silver-catalyzed alkene functionalizations were reported. In the case of carbene insertion into the C—H bonds of cyclohexane, low conversion to the desired products was observed when Cu catalysts were employed (Table 8.8, entries 1–3). In contrast, silver catalysts supported by fluorine-containing Tp ligands (entries 5 and 6) gave moderate yields of the C–H functionalization products. Similar results were observed for other hydrocarbon precursors, including pentane, hexane, 2-methylbutane, and 2,3-dimethylbutane (Table 8.9). In all cases, the formation of ester A was preferred; however, depending on the length of the alkyl chain, insertion into either the primary or secondary C—H bond could be preferred. 8.3.4 Advances in Silver-Catalyzed Carbene Insertion into Alkene or Aromatic C(sp2 )—H Bonds In 2011, Yang and coworkers reported silver-catalyzed intramolecular C–H functionalizations leading to the synthesis of 3-alkylideneoxindoles (Table 8.10) [48]. Initial studies of diazoamide substrates used AgOTf in toluene at 100 ∘ C and led to formation of 3-methyleneoxindoles in good yields. Screening of silver salts, including AgSb6 , AgBF4 , AgNO3 , AgCO3 , and AgOAc, showed that AgOTf was the optimal silver salt. In addition, the Yang group determined the reaction was promoted by a variety of Lewis acids, including FeCl3 , TiCl4 , BF4 . Et2 O, and SnCl4 . Diazoamides with electron-donating and electron-withdrawing groups on the

Table 8.7 Scope of silver-catalyzed C–H functionalizations with a trinuclear silver cluster. CF3

Alkane

N2

+ H

5 mol% Ag(3,5-(CF3)2-PyrPy)-trimer CH2Cl2, 48–72 h

CO2Et

R

CF3

CO2Et

Product(s)

Yield (%)

Alkane

Ag N

Product(s)

CF3 CF3

Ag

Ag

N F3C

Alkane

N

N

N N

CF3

Yield (%) (C2 : C3 : C1)

CO2Et 84

CO2 Et

CO2Et

33 (8 : 2 : 1)

CO2Et CO2Et CO2Et

CO2Et 88

CO2Et

41 (5 : 2 : 1)

452

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

Table 8.8 Comparison of C–H functionalization in water using silver and copper catalysts. Catalyst

O

CO2Et

N2 H Entry 1 2 3 4 5 6a a Reaction

CO2Et

O CO2Et

Catalyst

A

B Yield A (%)

TpMsCu(thf) TpBr3Cu(NCMe) Tp(CF3)2,BrCu(thf) Tp*,BrAg Tp(CF3)2,BrAg(thf) Tp(CF3)2,BrAg(thf)

nd nd 3 2 45 41

Yield B (%) nd nd nd nd 20 6

was conducted with 2 % TPGS-750-M.

phenyl ring were competent substrates for the cyclization. Reaction conditions were mild to readily tolerate functional groups such as PhSO2 and PO(OEt)2 . Yang and coworkers proposed two possible mechanisms for the preceding transformation, neither of which involved the formation of a silver carbene. Rather, the reaction was hypothesized to proceed through coordination of either the carbonyl or the diazo group to silver, similar to pathways 2–3 in Scheme 8.5 (vide supra). Subsequent formation of an allyl carbocation after release of N2 was followed by cyclization of the resultant allyl carbocation and protonation to yield the C–H insertion product.

8.4 Silver-Catalyzed Carbene Insertion into N—H Bonds Carbene insertion into N—H bonds is typically catalyzed by copper and dinuclear rhodium complexes. However, scattered examples of silver-catalyzed carbene insertions into N—H bonds have been reported; these studies were covered previously and are only briefly mentioned here. In the early 2000s, investigations conducted by the Jorgensen and Hu groups utilized silver salts, including AgSbF5, AgClO4 , and AgOTf, often in conjunction with bis(oxazoline) (BOX) ligands for the insertion into N—H bonds [49–51]. More recently, Lee and coworkers [52] (Table 8.11) reported a Ag-catalyzed N–H insertion cascade reaction, affording highly functionalized azopyrazoles. To further determine the robustness and utility of this transformation, a diazo substrate was reacted with various arylhydrazine derivatives bearing both electron-donating (Table 8.12, entries 1–5) and electron-withdrawing groups (entries 6 and 7). While these substrates all afforded the desired azopyrazoles, the reactions of arylhydrazine derivatives bearing EWGs, such as F and Cl, gave slightly lower yields. The Lee group also demonstrated the ability of AgOTf to catalyze the analogous cascade reactions of 4-diazopyrazole-3-one with a series of arylhydrazine to afford azopyrazoles (Table 8.13). The proposed mechanism involves the formation of a silver carbenoid intermediate through the loss of N2 .

Table 8.9 Scope of silver-catalyzed carbene insertion into C(sp3 )—H bonds in water. Alkane

N2

+ H

Alkane

Tp(CF3)2,BrAg(thf) CO2Et Yield A (%)

R

CO2Et

O

R O

A Yield B (%)

Alkane

Yield A (%)

CO2Et B Yield B (%)

7

7

2

30

9

10

4

10

4

35

11

17

6

10

3

23 Preferred site of reaction

Table 8.10 Scope of silver-catalyzed cyclizations to 3-alkylideneoxindoles. H3C

R1

N2

N

R2

OH

5 mol% AgOTf R2

O

O

Dioxane, 100 °C

N

N

O

R1

R1

R1 = CH3, Bn, Ph R2 = CHO, CO2Et, SO2Ph, PO(OEt)2, COCH3 H3C

H 3C

OH

H3C

OH

H 3C

OH

O N 90% CH3 H3C

O N Bn H3C

OH

H3C

OH

71%

Br

H

I H3C

OH

N CH3 82% (36%)

O N CH3

H 3C

O

67%

66% Br

64%

SO2Ph

OH

OH

79%

N Bn

O N CH3 PO(OEt)2

O

O 61%

43%

OH

N Bn

N 84%

H 3C

OH

H3C

H3C H3C

O N Ph

H 3C

82%

O N Bn

65%

O

N Bn

I

O N Bn

CH3

OH

Br O N CH3 74%

O

O N Bn

91%

H3C

OH

H3C

H3C 82%

O N CH3

Table 8.11 Silver-catalyzed cascade reaction involving proposed carbenoid transfer into N—H bonds. R1 O

O OR2

R1

+

2

AgOTf

H2NHN

CH3CN, 70 °C 24 h

N2 Entry

Product

Diazo

Et

OEt

N

N2 O

2

N HO

O

n-Pr

OEt

N

N HO

O

O

i-Pr

Entry

O 4

N N

HO

Diazo

88 N N Ph

N

Ph

Product C5H11

O

C5H11

Yield (%)

OEt

N

N2

N HO

N N

95

n-Pr

N2

3

Yield (%) Et

O

O

1

N

N N Ph

91 Bn O

i-Pr OMe

N

N

N2 HO

N N Ph

5 92

O

Bn

N OMe

N2

N HO

N N

90

Table 8.12 Tolerance of arylhydrazine substitution in the silver-catalyzed cascade reaction. R1 O

O

Me

H2NHN

Arylhydrazine

Yield (%) Entry Arylhydrazine

Product Me

Me

N N

N H2NHN 5

Me

2

N N

91

3

N

H2NHN Et

N

Me

H2NHN 6

N N

HO

HO

F

Me

Me Et

N F

N

90

Et

F Me

Cl N

H2NHN 4

N HO

80

N N

HO

Me

i-Pr

87

N N

OMe

HO Me

Me

N

OMe

Me

Me N

N

Me

Yield (%) Me

Me 90

Me

Me

Product

MeO

N HO

H2NHN

N N Ar

Me

N

H2NHN

N HO

R4

Me 1

N

CH3CN, 70 °C 24 h

R3

R5

Me

AgOTf

+

OEt N2

Entry

R2

N

N

H2NHN

N N

HO

94 7

i-Pr i-Pr

N N

77

Cl Cl

Table 8.13 Silver-catalyzed synthesis of azopyrazoles bearing various aryl groups. Me

N N2 Entry

R

NHNH2

N +

HCl

O

Me

AgOTf N

CH3CN, 70 °C 12 h

HO

R Product

Arylhydrazine

Yield (%)

Entry

N

H2NHN

N

Product

H2NHN 91

N

2

N HO

MeO H2NHN

N N Ph

93

N

3 HO

N N

95

Ph Me

Cl H2NHN

N

N

N N

5 HO

Cl

95

Ph Me

Me N

OMe

HO

F

Me H2NHN

N

N

4

Ph

Yield (%) Me

F

N N

HO

N N Ph

Arylhydrazine

Me 1

N

N N Ph

6

H2NHN

N

N

80 HO

N N Ph

85

458

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

Silver-catalyzed carbene transfer into N—H bonds was expanded by the Wang group to include trifluoroethylation [53]. The ability to prepare fluorinecontaining molecules using a robust and direct synthetic route lends itself to a variety of applications, especially in the context of drug modification. Wang showed that AgSbF6 could catalyze the N-trifluoroethylation of anilines (Table 8.14), as well as the O-trifluoroethylation of amides (Table 8.15). A mechanism was proposed based on experimental observations that involved both ligand migration and carbene insertion into the N—H bond. The Zhou group built on Wang’s work by carrying out the carbene insertion into N—H bonds in the presence of fluorinating agents, such as N-fluorobenzenesulfonimide (NFSI), to afford gem-aminofluorination products (selected examples in Table 8.16) [53–55]. Both electron-donating and electron-withdrawing groups on the aryl group of the diazoketone were tolerated, as were electron-withdrawing groups on the aniline.

8.5 Silver-Catalyzed Carbene Insertion into O—H Bonds In 2011, Davies and coworkers reported a comparative study of Ag(I)- and Rh(III)-catalyzed reactions of methanol with vinyl diazoacetate [56]. Interestingly, the rhodium catalyst favored the typical carbenoid reactivity to furnish 9 as the major product, while the silver catalyst favored reaction at the vinylogous site to deliver mainly 7 (Table 8.17). Mechanistic investigations using MeOD and Rh2 (oct)4 as the catalyst lead to incorporation of the deuterium label at the C2 position, consistent with a mechanism proceeding through the insertion of a rhodium carbenoid into the O—D bond of MeOD (Scheme 8.6). Mechanistic investigations using AgOTf also incorporated the D label at C2, which is in agreement with the involvement of a zwitterionic intermediate in a proton transfer step (Scheme 8.6). In 2017, Sun and coworkers reported gold- and silver-catalyzed insertions of vinyl carbenes into O—H bonds [57]. Phenyl vinyl diazoacetates were treated with 2-pyridone or its sulfur analogue in the presence of a Xantphos(AuCl)2 /AgSbF6 catalyst, leading to the formation of α-functionalized esters (Table 8.18) in moderate to excellent yields. In contrast, employing AgSbF6 as the catalyst resulted in vinylogous selectivity (Table 8.19). The silver catalyst experienced a reduction in desired reactivity relative to Xantphos(AuCl)2 /AgSbF6 system, particularly when the extent of substitution on the alkene was increased.

8.6 Silver-Catalyzed Functionalization of Esters In 2014, Pérez and coworkers reported silver-catalyzed functionalization of esters via carbene transfer [58]. Treatment of ethyl propionate and EDA with 3 CF CF TpBr3 Ag(acetone) and F27 -Tp4Bo, 2 3 Ag(acetone) showed that the latter catalyst was more reactive. Both alkyl and aryl esters underwent successful carbene transfer in moderate yields (Table 8.20).

Table 8.14 Silver-catalyzed N-trifluoroethylation of various aniline derivatives. NH2 R

Entry

F3C

Product H N

1

Yield (%) CF3

92

O2N

H N

CF3

CF3

94

87

H N

CF3

93

Cl

H N

Cl

Cl

90

H N

CF3

75

12 Ph

CF3

H N

N

5

CF3

43

70

F

H N

CF3

F

F

82

F 69

9 Me

91 10

Cl

CF3

CF3

F CF3

H N

H N

F

F H N

CF3

N

94 13

Me

Yield (%)

H N

11

CF3

I H N

Product

MeO

7

8

CF3

R Yield (%) Entry

Product

6

F3C 4

H N

DCE, 50 °C, air 0.5–6 h

Br

H N

3

H

Entry

EtO2C 2

AgSbF6

N2

+

Ph

H N

CF3

72

14 90

F

Table 8.15 Silver-catalyzed O-trifluoroethylation of amide derivatives. O N

R1

R2

F3C

H Entry

Product N

H

Yield (%)

O

CF3

1

DCE, 40 °C, 2 h

N

N 92

O

6

N

87

N

O

N 4

N 5 Cl

82

O

O Me

O

CF3 94

Me

N

O

CF3

8

92

CF3 89

Me

O2N

97

CF3

Me

MeO

CF3

7 I

3

O Me

CF3

Me

Yield (%)

Product

Br

N Me

R1

Entry

Me

2

CF3 R2

O

AgSbF6

N2

+

F3C 9

CF3 90

N

98

8.8 Summary

Table 8.16 Silver-catalyzed carbene transfer to furnish new C—N and C—F bonds. O H

Ar

1

+

Ar

2

NH2

+

PhO2S

N

SO2Ph

F

N2

20 mol% AgNO3 2 equiv. K2CO3 DCE, rt

O F Ar 2

Ar1 NH

Entry

Ar1

Ar

1

C6H5

p-(CO2Et)C6H4

68

6

o-MeC6H4

p-FC6H4

63

2

p-MeC6H4

p-(CO2Et)C6H4

64

7

o-MeC6H4

p-CF3C6H4

73

3

p-MeOC6H4

p-(CO2Et)C6H4

44

8

o-MeC6H4

p-CNC6H4

67

4

p-ClC6H4

p-(CO2Et)C6H4

65

9

o-MeC6H4

m-CNC6H4

62

5

o-ClC6H4

p-(CO2Et)C6H4

56

10

o-MeC6H4

o-CNC6H4

60

2

Yield (%)

Entry

1

Ar

Ar2

Yield (%)

8.7 Silver-Catalyzed Si–H Functionalization Several examples of silicon–hydrogen bond functionalizations via carbene transfer have been reported in the literature. The Janssen and coworkers [59], Brook et al. [60], and Doyle and coworker [61] groups were early pioneers in the field, which has rapidly expanded in recent years to encompass the use of diverse transition metal catalysts, including Rh, Fe, Cu, and Ag. In 2013, Pérez and coworkers reported the Ag- and Cu-catalyzed insertion of carbenes into Si—H bonds [62]. A variety of Cu and Ag complexes were screened, with TpBr3 Cu(NCMe) and (TpBr3 Ag)2 demonstrating the best reactivity. Slow addition of the diazo compound was required to avoid problematic carbene dimerization. Mono-, di-, and trisubstituted silanes bearing either alkyl (Table 8.21, entries 1, 2, 6, and 7) or aryl groups (entries 3, 5, 8, and 9) were successful in the reaction, with the exception of Ph2 SiH2 (entry 4).

8.8 Summary The recent advances in silver-catalyzed carbene transfer reactions have resulted in major improvements and broader scope in the areas of alkene cyclopropanation, alkyne cyclopropenation, and C(sp3 )—H bond insertions. The development of electron-deficient ligands based on Tp scaffolds has led to highly electrophilic silver-supported carbene intermediates that are even capable of inserting into normally unreactive primary C—H bonds. New methods for the insertion of metal carbenes into N—H, O—H, and Si—H bonds have also been recently reported. Despite this progress, Ag-catalyzed carbene transfers lag far behind their Rh-based counterparts, particularly in the area of asymmetric cyclopropanations and C—H insertions. Nonetheless, the vast array of potential ligands for silver catalysts, coupled with the relatively low cost of this coinage metal, bodes well for significant advances in the near future.

461

Table 8.17 Comparison of the reactions of vinyl diazoacetate with rhodium and silver catalysts. CO2Me CO2Me CO2Me CO2Me MeO2C Catalyst N2 MeO2C MeO MeOH MeO MeO 23 °C Ph Ph Ph Ph Ph 6 7 10 8 9 Entry 1 2

Catalyst Rh2 (S-TBSP) AgOTf

Ratio (7 : 8 : 9 : 10) 0 : 0 : 89 : 11 89 : 5 : 6 : 0

Yield (%) 86 95

Rh2 (S-TBSP) H O Rh N SO2Ar

O Rh 4

Ar = C6H4 (4-t-Bu)

8.8 Summary

D MeO2C

1 CO2Me 2

CO2Me

2

N2

Rh2(oct)4

AgOTf MeO

MeO–D

MeO–D

Ph

Ph

Ph

95% D incorporation

CO2Me 2

D

95% D incorporation

Scheme 8.6 Deuterium labeling experiments.

Table 8.18 Selected scope for gold-catalyzed carbene transfers into O—H bonds. R1 X

R2

N H

O

CO2R4

5 mol% Xantphos (AuCl)2 10 mol% AgSb6 40 °C, 4 h, CH2Cl2

R2 = Ph; R4 = Me, 91% R2 = 4-MeC6H4; R4 = Me, 80%

4

CO2R

R

N2

X = O, S

N

2

R3

Me

S

R1 R3

N CO2R4

R2

N

Me

53%

CO2Me

Ph

X

O

N

83%

CO2Me

Ph

Table 8.19 Selected scope for silver-catalyzed carbene transfers into O—H bonds. N2

R1 X

O

N H

N 3

CO2R

R2

R2

X = O, S

R1

10 mol% AgSbF6 CO2R3

40 °C, 4 h, CH2Cl2

R2 = Ph; R3 = Me, 83% R2 = 4-MeC6H4; R3 = Me, 78%

S Ph

N

O

CO2R3

R2

0%

N

O Ph

CO2Me

0%

N Me

CO2Me

Table 8.20 Selected scope of silver-catalyzed carbene transfer reactions of esters. O R

F27-Tp4Bo,3CF2CF3Ag(acetone)

N2 H

OEt O

66% CO2Et

O O

O

50%

R

O

CO2Et

83% O

CO2Et

O O

48%

CO2Et

O

CO2Et

O O

O 52%

Room temperature

CO2Et

O

CO2Et

O 57%

CO2Et

463

464

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

Table 8.21 Selected scope of carbene transfer reactions into the Si—H bonds of silanes. N2

R3SiH

H

Catalyst CO2Et

R3Si

12 h

CO2Et

Entry

Silane

Slow addition TpBr3Cu(NCMe)

Slow addition (TpBr3Ag)2

1 2 3 4 5 6 7 8 9

Et3SiH Et2SiH2 Ph3SiH Ph2SiH2 PhSiH3 nPr3SiH Me2tBuSiH Me2PhSiH MePh2SiH

76 79 71 0 80 82 92 80 70

72 84 43 0 78 12 10 72 40

8.9 Introduction to Transition Metal-Catalyzed Nitrene Transfer Amine functionality occurs frequently in diverse pharmaceuticals, agrochemicals, bioactive natural products, and ligands for transition metal catalysts; thus, efficient methods for the selective and streamlined introduction of nitrogen into molecules are of interest from both academic and industrial perspectives. Transition metal-catalyzed nitrene transfer reactions represent one powerful strategy to introduce new C—N, S—N, and N—N bonds into compounds, often under mild conditions (Scheme 8.7). The most prevalent metal-catalyzed nitrene transfer reactions install nitrogen into a precursor molecule through either aziridination of a C=C bond or via the insertion of a stabilized metallonitrene species into a reactive C—H bond [63]. There are also scattered reports of sulfide and sulfoxide imination [64], as well as reactions of tertiary amines with metallonitrenes that result in the formation of new N—N bonds [65]. In the following sections, examples of silver-catalyzed nitrene transfers encompassing these general classes Aziridination R1

Imination

R2 +

Nitrogen source

R1

R1

R3

R4 R1

C–H amidation R

2

R

+

S

S

R1 + Nitrogen source

R2

or

Catalyst Oxidant

R3

N R3

O S

R2

R1

R3 + Nitrogen source Catalyst Oxidant

R1

R2

N-amidation

H R3

N

R2

O

Alkenes, alkynes, allenes, arenes

1

S or

Oxidant

R4

R3

Catalyst

Pg N R2

Nitrogen source

1

Catalyst

R

Oxidant

2

R

NHPg R3

R1 R2

N

NPg

R2

Scheme 8.7 General types of metal-catalyzed nitrene transfer reactions.

N

R3

8.9 Introduction to Transition Metal-Catalyzed Nitrene Transfer

of transformations are presented, with an emphasis on chemistry reported since 2008. A wide variety of transition metals have been reported to catalyze nitrene transfer, including Rh [66], Ru [67], Cu [68], Fe [69], Co [70], Mn [71], Ir [72], Au [73], and Ag [68f, 74] (selected examples of non-silver catalysts are illustrated in Figure 8.5). The generation of metallonitrenes has a long history, going back to Kwart and Khan’s description of the copper-catalyzed decomposition of benzosulfonyl azides [75]. This reaction was proposed to proceed through the formation of copper nitrene species that were capable of introducing nitrogen through either an aziridination or C–H insertion process. Breslow’s early work in the 1980s, employing MnIII (TPP) (TPP = tetraphenylporphyrin) and FeIII (TPP) catalysts, in combination with an iminoiodinane nitrogen source, showcased the ability of these metals to promote intramolecular C–H amidation [76]. In addition, Breslow’s report of C–H amidations promoted by Rh2 (OAc)4 served as inspiration for the later design of other high-performing dinuclear Rh catalysts for nitrene transfer [66]. In the early 1990s, the Evans et al. [68a, b] and Jacobsen and coworkers [68d] groups reported examples of Cu complexes supported by bis(oxazoline) (BOX) and salen-type ligands that catalyzed asymmetric aziridination reactions; however, efforts to expand the scope and versatility of transition metal-catalyzed enantioselective nitrene transfer reactions continues to be an ongoing challenge. More recently, beginning around the early 2000s, Du Bois and others developed a series of designer Rh2 Ln complexes supported by carboxylate and related bridging ligands to accomplish efficient nitrene transfer with good functional group tolerance [63, 66]. In particular, Du Bois’s Rh2 (esp)2 (esp = α,α,α′ ,α′ -tetramethyl-1,3-benzenedipropionic acid; Figure 8.5) [66d] complex has been a powerful catalyst for intra- and intermolecular aziridinations and C–H amidations and has enjoyed wide popularity for the late-stage functionalization of complex molecules. Ru catalysts supported by a variety of ligands, including salens, porphyrins, and bridging 2-hydroxypyridines, have also been reported, some of which are capable of enantioselective aziridinations of terminal and simple alkenes [67]. Nitrene transfer catalysts based on first-row transition metals, including Co, Fe, and Mn, are typically supported by ligands that include modified porphyrins, phthalocyanines, and other porphyrin mimics, selected examples of which are presented in Figure 8.5 [68–71]. One of the major challenges in metal-catalyzed nitrene transfer chemistry to date concerns the ability to predict which site will undergo reaction when multiple similarly reactive groups are present in a substrate [77]. Typically, reports largely tailor site selectivity through substrate control, where potential sites are well differentiated in terms of their reactivity. However, one of the “holy grails” in C–H functionalization involves developing chemistry that is predictable in discriminating among several potentially reactive C—H bonds. Catalyst-controlled nitrene transfers, where the catalyst bears the primary responsibility for dictating the specific site of amination, could permit the flexible installation of new C—N bonds at multiple sites of a substrate in a tunable manner. Such new catalyst manifolds would constitute powerful tools to introduce valuable nitrogen groups into an array of simple hydrocarbons and complex molecules.

465

R

R

Me Me

O

Me O O O Rh Rh O Me O O Me O O

Me

O

N O

Ru Ru N O N

N

N N M N Cl N N

N

N Cl

Me

N

R

Me Rh (esp) 2 2

O

O N tBu

tBu

H H R

M = Mn, R = tBu : [Mn(tBuPc)]Cl M = Fe, R = H : [FePc]Cl

Ru2(hp)4Cl

N

Cl

H H N Cl

N

Cl

Cl

Ligands for Cu catalysts Ar

R

R NH

N

N

Ar = MeO

HN

Co N

N

NH R

N CO N Ru O O Ar Ar

MeO HN

H R

Ar

R=

Cl Ar = Me3Si Cl

O

O [Co(porphyrin)]

Figure 8.5 Selected examples of transition metal catalysts for nitrene transfer reactions.

Ru(CO)(salen)

8.9 Introduction to Transition Metal-Catalyzed Nitrene Transfer

H

R1

B

N

R2

R1

R2

R3

Ph

Br

Br

Br

B

H

H

Mesityl

Ar

Tp*

Me

H

Me

Ar

Tp*,Br

Me

Br

Me

TpMs

R2

R2 N

N

R3

TpBr3

N

N

N

R1

R1

R

Ar

P

Ag N

N

CF3

tBu

tBu

PhBP3CF3Ph R2

N

N

P Ar Ar Ar

Ar =

R2

3

P

tBu

OTf

tBu

[(tBuBipy)2Ag]OTf

R2

R1

R1 N

tpa

N

R1

R1

R2

n = 1, 2

H

H

(phen)nAgOTf

Me H

Me Ph

N

(Me4phen)nAgOTf [(BP)AgOTf]2

N 3

R2

R1

R2

H

H

(o-Me)3tpa

Me

H

(p-Me)3tpa

H

Me

(p-MeO)3tpa

H

OMe

(p-Me2N)3tpa

H

NMe2

O

O R1

N

N

R1 R2

R2 BOX ligands

R1

R2

H H H Me Me

tBu Ph CHPh2 Me Ph

N N

N

N

N

t

Bu

t

Me

Me

Bu

N

Me N

N

N N

N

N

t

Bu [Ag(tBu3tpy)]2(OTf)

[Ag (Py5Me2)OTf]2

(anti-α-Me-Py3Pip)AgOTf

F2 O1

F3 F1

N1

S1 O2

F1

N3

Ag1 N2

F3

F2

F2

O2 N1 F3 O3 S1 N2′ Ag1 O1 O1′ Ag1′ N2 S1 O3′ F3′ N1′ O2′ F1′

O3

N4

O1 S1

F1

O2 O3

N4 N2 N3 Ag1 N1

F2′

[(Me4phen)AgOTf]2

[(tBuBipy)2Ag]OTf

[(Me4phen)2Ag]OTf N3 N2

N4 Ag1′

N1 N5′ Ag1

N2′

N3

N1′ C4′ N2′

N3′

N3′

Ag1′

N1′

N4′

[Ag(Py5Me2)OTf]2

N5

N4′

N2 Ag1 N1

N2′′

N4′ Ag1′′ C4

N1′′

(anti-α-Me-Py3Pip)AgOTf oligomer

Figure 8.6 Selected examples of ligands and silver catalysts for nitrene transfer reactions.

Silver-catalyzed nitrene transfer has received increasing attention in the past decade, due to the ability to readily tune the metal for divergent chemo- and site-selective nitrene transfer chemistries. The diverse ligand libraries that can support silver-catalyzed nitrene transfer [78–81] (Figure 8.6) enable tailoring of both the steric and electronic environments around the silver (Ag) center in a manner that is challenging to achieve with other reported transition metal scaffolds (Figure 8.5). In addition to the ligand identity, the coordination around the Ag center can be manipulated by changing the nature of the counteranion, the Ag–ligand ratio, and the solvent. Ag(I) supported by simple N-donor ligands are particularly useful catalysts that encompass a range of coordination geometries, including linear, tetrahedral, distorted tetrahedral, and seesaw (Figure 8.6, bottom) [79, 82]. This diversity stands in contrast to Rh2 Ln and Ru2 Ln complexes, which exhibit similar “paddlewheel-” or lantern-type coordination environments around the metal center and require significant alterations to the periphery of the ligand in order to exert a predictable effect on the reaction outcome across a broad range of substrates. In the same vein, scaffolds based on Co, Mn, and Fe employ porphyrin- and phthalocyanine-type ligands that tend to yield similar

467

468

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

coordination environments around the metal center, unless significant changes are made to the periphery of the porphyrin ring [68–71]. This chapter highlights the features of silver catalysis that have enabled recent advances in nitrene transfer over the past ten years. Descriptions of the underlying design principles are included with the intent of inspiring and enabling the design of increasingly selective amination reactions based on silver, particularly in the realm of asymmetric C—N bond formation. 8.9.1

General Catalysts for Silver-Catalyzed Nitrene Transfer

Figure 8.6 describes the scope of silver complexes reported to date that have been employed for silver-catalyzed nitrene transfer. The majority of these silver complexes are supported by simple N-dentate ligands, including bipyridines (bipy), phenanthrolines (phen), terpyridines (tpy), and bis(oxazolines) (BOX). The Pérez group has developed a series of ligands based on a trispyrazolylborate (Tp) scaffold, where the electrophilicity of the putative silver nitrene can be tuned by changing the nature of the R1 –R3 groups on the pyrazole rings [83]. An example of a phosphine-based borate ligand, PhBP3 CF3 Ph , has also been described by the Pérez group [84]. The Schomaker group reported successful nitrene transfer using a variety of bidentate phosphine ligands in studies of asymmetric silver-catalyzed aziridination; however, the penchant for ligand oxidation in the presence of hypervalent iodine reagents is problematic [85]. Finally, silver catalysts supported by multidentate ligands, including tris(2pyridylmethyl)amine (tpa), 2,6-bis[1,1-bis(2-pyridyl)ethyl]pyridine (Py5 Me2 ), and a trans-disubstituted piperidine (anti-α-Me-Py3 Pip), have shown useful selectivities for the amination of benzylic, allylic, and propargylic C—H bonds [79]. Selected X-ray crystal structures that highlight the diversity of coordination geometries in Ag complexes capable of promoting nitrene transfer are illustrated at the bottom of Figure 8.6 [79]. The coordination environment can vary as a result of changes in the Ag–ligand ratio, as shown by the complexes [(tBubipy)2 ]AgOTf and [(Me4 phen)2 ]AgOTf, displaying distorted tetrahedral geometries and outer-sphere triflate anions, and [(Me4 phen)AgOTf ]2 , where the solid-state structure exists as a dimer with bridging triflates [86]. In the solution state, both complexes are monomeric species with one ligand and one triflate bound to the metal center. In the case of [Ag(Py5 Me2 )]2 (OTf )2 (triflates are omitted in the crystal structure for clarity), the catalyst exists as a dimer in both the solution and solid state, with a Ag—Ag bond distance of ∼3.2 Å [87]. Steric hindrance around the Ag can also be varied, as (anti-α-Me-Py3 Pip)Ag(OTf ) (shown as an oligomer in the solid state) contains a more accessible metal center than [Ag(Py5 Me2 )]2 (OTf )2 . Another general feature of many silver complexes supported by N-dentate bipyridine and phenanthroline ligands is their conformational flexibility and dynamic behavior in solution [88]. For example, AgOTf supported by a (oMe)3 tpa ligand (Figure 8.7) [86] crystallizes as a dimer in the solid state but exhibits two different types of dynamic behavior in solution. The first involves the formation of monomeric vs dimeric species, while the second concerns the motion of one

O6

F5

Me MeN Ag N

N

N

Me

Me Me N Ag N

Dimer

N

4

Me

24 °C

N6

N5

Ag N

N Ag Me Me

Me

4a

4a′ 4b/4c 4b′ 4c′

(oMe)3tpaAgOTf

2 OTf N Me

–20 °C

Me

N

N

Me

OTf

N

Monomer

O3 O2

Ag2

0 °C

OTf

(oMe)3tpaAgOTf

F3

H3 N

N Me

N3

O1 S1

N2

Ag1

N

N Ag

N1

H2 H4

Me

N4

H1

F2 F1

O4

F4

N

Monomer

F6

O5

OTf Me

Me

4

Meb Mec Mea

–40 °C

Dimer –60 °C

N Me

–90 °C

N

4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9 2.8 2.7 2.6 2.5 2.4 2.3 2.2 2.1

f1 (ppm)

Figure 8.7 X-ray and solution-state behavior of AgOTf supported by an (oMe)3 tpa ligand.

470

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

of the pyridine “arms” on and off the metal center; other similar examples of the dynamic nature of these catalysts have been reported by the Schomaker group [86]. The lability of certain types of Ag—N bonds presents both advantages and unique challenges to catalyst design that require an understanding of how the dynamic behavior is impacted by the ligand. In many cases, these studies have been aided by computational investigations, variable temperature NMR (VT-NMR), and diffusion spectroscopy (DOSY). 8.9.2

Typical Nitrogen Sources for Silver-Catalyzed Nitrene Transfer

There are a variety of nitrogen sources that have been employed in metalcatalyzed nitrene transfer (Figure 8.8) [89–94]. The precursor can either contain the nitrogen in a “pre-oxidized” form, or a stoichiometric amount of an external oxidant can be used to generate the iminoiodinane in situ. Early efforts in the field primarily utilized isolable iminoiodinanes formed by the oxidation of sulfonamides, typically PhI=NNs (Ns = 4-benzenesulfonyl) or PhI=NTs (Ts = p-toluenesulfonyl). Other nitrene precursors that do not require the use of additional oxidant include N-tosyloxycarbamates [93], N-tosyloxysulfamates [93], and azides [69, 70, 92]. However, the benchtop stability of PhI=NAr and the limited number of catalysts able to access metallonitrenes from azide precursors limit their utility to some extent. Thus, it has become commonplace to use nitrogen sources, particularly carbamates and sulfamates, in combination with hypervalent iodine reagents, typically PhIO or PhI(OAc)2 , to generate the reactive iminoiodinanes in situ. However, an ongoing challenge in the field is to replace hypervalent iodine reagents with terminal oxidants that would be more attractive on a large scale, such as O2 and H2 O2 . 8.9.3 General Mechanistic Features of Metal-Catalyzed Nitrene Transfer There are two widely accepted pathways (Scheme 8.8) for nitrene transfer, where the nature of the metallonitrene and the reaction mechanism itself can have a Pre-oxidized nitrene precursors O S N O

X

X Me TsN=IPh NO2 NsN=IPh

I

R O R

O

N H

N3

O O S R N3

OTs

O O S N3

Me3Si

SESN3

Nitrene precursors requiring the addition of an oxidant

R

O O S NH

O

2

Cl3C

O S NH2 O Sulfonamides

O R

2

TcesNH2

Sulfamates

O2N

O O O S NH

R2

O

O

O NH2

Cl3C

O

R

NH2

N

R1 O O N O S NH

2

R

O O Me N S NH2 Boc

NH2

Pg

Carbamates

O S

O O S NH

O

NTs NH2

F3C

2

CF3

F

Ureas

O O O S NH2 F

HfsNH2

Figure 8.8 Common nitrogen sources for transition metal-catalyzed nitrene transfer.

DfsNH2

8.10 Aziridination R1 N

or

R2

R3

R2

R3

LnM

LVG

NR1

NHR1 M = Mn, Fe, Co, Cu, Ru, Rh, Ir, Ag

Concerted or stepwise pathway LnM=NR1 Singlet or R2

R3

LnM NR1 Triplet

LVG = IPh, N2 LVG

R2 O N

R1

O [M]

H Concerted, asynchronous transition state O R2 O [M] N R1 H Rapid radical rebound intermediate

Scheme 8.8 General mechanisms for transition metal-catalyzed nitrene transfer reactions.

significant impact on the chemoselectivity, site selectivity, and stereoselectivity of the amination [63c, 66b, 68d, 95–97]. Singlet metallonitrenes engage in concerted additions to C=C bonds or insertions into C—H bonds, where the stereochemical information of the substrate is retained in the product. Additionally, concerted nitrene transfer reactions show no response to the presence of radical inhibitors or radical clocks. In contrast, triplet metallonitrene species proceed through stepwise nitrene transfer pathways. In the case of aziridination, formation of the first C—N bond generates a carbon-centered radical; depending on the nature of the substrate and, consequently, the lifetime of this intermediate, the final C—N bond may form prior to C—C bond rotation and retain the stereochemical information present in the alkene precursor. In the case of stepwise C–H amination, a metal-stabilized nitrogen radical abstracts hydrogen from the substrate to furnish a carbon-centered radical. This intermediate may have a sufficiently long lifetime to destroy any stereochemical information present in the substrate; thus, in contrast to the singlet metallonitrene pathway, the reaction may respond to radical inhibitors and radical clocks. However, if the radical rebound process to form the C—N bond is rapid enough, stereochemical information may be efficiently transferred from substrate to product. In these situations, computational studies may be the only way to discern the subtleties of the reaction mechanism [98–101].

8.10 Aziridination 8.10.1

Intramolecular Aziridination

While this chapter focuses on advances in silver-catalyzed nitrene transfer since 2008, selected earlier results are included for the sake of continuity and comparison. In 2006, the He group reported examples of the intramolecular aziridination of homoallylic sulfamates using AgOTf supported by a 4,4′ ,4′′ -tri-tert-butyl-2,2′ :6′ ,2′′ -terpyridine (tBu3 tpy) ligand (Scheme 8.9) [78]. The catalyst consisted of a dimeric complex with a Ag—Ag bond distance of 2.842(2) Å; one triflate anion was bound to a distal silver, and the other triflate was outer sphere [74a]. The structure of the catalyst resting state was

471

472

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

O S NH2 O O

+ PhI(OAc)2

O O S N O

4 mol% AgOTf/tBu3tpy CH2Cl2, rt 52–65% isolated yields

Scheme 8.9 Intramolecular alkene aziridination using a [Ag2 (tButpy2 )(OTf )](OTf ) catalyst.

supported by X-ray crystallography and NMR spectroscopy, while the presence of a metallonitrene, consisting of a Ag core and either a =NTs or a =NSO2 Ph group, was suggested by electrospray mass spectrometry (ESI-MS). The Schomaker group reported the first examples of intramolecular silvercatalyzed aziridinations of allenes in 2013 [102]. In this study, a series of homoallenic carbamate precursors were treated with a AgOTf catalyst supported by either a 1,10-phenanthroline (phen) or 2,2′ -bipyridine (bipy) ligand (Table 8.22). In the absence of an allenic C—H bond, no competing C—H amination (entries 1–6) was noted, and the aziridine products were obtained in good to excellent yields, albeit in moderate E:Z ratios. In situations where a competing allenic C—H bond was present (entries 7–12), the chemoselectivity for aziridination Table 8.22 Selected scope for intramolecular allene aziridination catalyzed by a (phen)AgOTf catalyst. O

O H

R2

O

20 mol% AgOTf 25 mol% phen

O R1 R3

N

O +

R1

N

E:Z

Product

Yield (%)

Entry

H

N

C5H11

O

4:1

88%

7

H C5H11

H H

N

TIPSO

N

3:1

87%

8

H

N

2.6 : 1

83%

9

H C5H11

N

N

EtO2C

2.2 : 1

85%

10

Me Me

N

O

98%

N

11

H

H

3.7 : 1

67%

1.9 : 1

5.9 : 1

70%

O

—

>20 : 1

79%

2.6 : 1

11.5 : 1

87%

2.3 : 1

19 : 1

70%

O

H

O 6

>19 : 1

O

C5H11

N

O

H

Me

---

Me

Me

72%

O

N

O 5

4:1

O O

H

Me

3:1

H

O H

O

O O

H

4

Yield (%)

H N

Ph

Insertion (I) A:I

(bipy instead of phen)

O 3

R1

O O

O O

3:1

90%

12

Me

N H

O

O

O

H

H H

H N

O

O 2

+ R2

E:Z

Product

O 1

H O

NH2 2 equiv. PhIO, 4 Å MS R1 R2 H H 3 3 CH2Cl2, rt E R3 R R3 R Z Aziridination (A)

R3

Entry

R2

8.10 Aziridination

Table 8.23 Selected scope for tunable intramolecular nitrene transfer via changing AgOTf–ligand ratios. O

O H

R2

O O NH2

R1 R3 R3

x mol% AgOTf y mol% phen

R2

PhIO, 4 Å MS CH2Cl2, rt

R1 H E

Entry H

1

H

N

O H

N

TIPSO

H

N

Ph

H O

H

4

tBu

N

O

H

H

H H11C5

19 : 1 >19 : 1

58% 36% 62%

1 : 1.25 1:3

>19 : 1 24 : 1

61% 74%

O

1 : 1.25d 1:3

1 : 3.7 >19 : 1

18% (67%) 83%

O

1 : 1.25 1:3

1 : 5.9 >19 : 1

13% (79%) 76% (1%)

O

1 : 1.25 1:3

19 : 1

19 : 1

7% (87%)

N

H N

H O

H

H N O

H11C5

H

Me

N

6

H O

Me

H N O

Me Me

H O Me

N

H O

Me

H N O

Et

Et

H

H

O Me

N

8 H11C5

O

Yield

tBu

O

7

1 : 1.25 1:3 1 : 3c

O

O O

5

insertion (I)

O

O H

R1

O

O

18% (72%) 65% 71%

H N

H Ph

H

H

H N

1:4 13 : 1 >19 : 1

O

O

+ R2

1 : 1.25 1:3 1 : 3c

H N

H TBSO

H

H O

I:A

O

H O

+

AgOTf:phena,b

H11C5

H

N

3 R3 R3 R3 R Z Aziridination (A)

H N

H

O

R1 R2

O

H11C5

3

OH

Products O

2

N

O

Me

H N O

H

88%

H11C5

a ) Aziridination : 20 mol% AgOTf, 25 mol% phen, 2 equiv. PhIO, 4 Å MS, CH2Cl2, rt. b ) C–H insertion : 10 mol% AgOTf, 30 mol% phen, 3.5 equiv. PhIO, 4 Å MS, CH2Cl2, rt. c ) 10 mol% BHT was added. d ) 2,2′-Bipyridine ligand.

over C–H amination varied from 3.7 : 1 to >20 : 1, with similar E:Z ratios to the products obtained in entries 1–6. Further investigations by the Schomaker group showed that changing the AgOTf–ligand ratio resulted in the ability to tune the chemoselectivity of the nitrene transfer event (Table 8.23) [103, 104]. At near-equimolar amounts of AgOTf and phen, the active catalytic species was proposed to be a monomeric (phen)AgOTf complex. The use of (phen)AgOTf or (tBubipy)AgOTf favored aziridination over C–H insertion in good to excellent chemoselectivities to furnish the bicyclic methyleneaziridine products. In contrast, when the

473

474

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

phen–AgOTf loading was increased to 3 : 1, the aziridination event was suppressed, and reactivity favored for C–H amination with excellent chemoselectivity. X-ray crystallography, MALDI-MS, and VT-NMR studies suggested that the resting state of the catalyst is a monomeric [(phen)2 Ag]OTf complex. The reasons for the unusual tunability in this catalytic silver system are further discussed in Section 8.10.3. Changes to the AgOTf–ligand ratio were also effective for tuning the chemoselectivity in reactions of homoallylic carbamates (Table 8.24) [103]. Both cis- and trans-alkenes displayed high retention of stereochemical information (entries 1 and 2) in the products, suggestive of either a concerted pathway or a rapid radical rebound mechanism. In addition to the tunability offered by utilizing silver catalysts in combination with carbamate nitrene precursors, higher chemoselectivity could be achieved in many cases as compared with conventional dinuclear Rh catalysts. Despite the recent progress in Ag-catalyzed nitrene transfer reactions, the development of useful enantioselective versions of this chemistry has been challenging. In 2017, the Schomaker group reported the first examples of asymmetric, intramolecular Ag-catalyzed aziridinations of homoallylic carbamates (Table 8.25) [85]. The reactions displayed good chemo- and enantioselectivity in the presence of AgClO4 and a variety of bulky BOX ligands, most notably tBuBOX and Ph2 CHBOX. The use of additional AgClO4 aided in breaking down the polymeric PhIO, leading to an increased rate and higher overall conversion of the aziridination; fortunately, the background reaction with unligated AgClO4 was minimal. Other Lewis acids could be substituted for the additional AgClO4 , including Bi(OTf )3 and Sc(OTf )3 . Interestingly, a different substrate scope was observed in this chemistry, as compared with reports by Dauban and coworkers employing a similar copper catalyst with sulfamate nitrene precursors [105]. With the silver-catalyzed aziridination, both trans- and cis-1,2-disubstituted alkenes (Table 8.25, entries 1–6) gave good chemoselectivities, yields, and enantioselectivities of >90% in most cases. No evidence of isomerization was noted in the aziridine products, suggesting either a concerted or rapid radical rebound mechanism. This chemistry also enabled the first reported examples of the asymmetric aziridinations of 1,3,3′ -trisubstituted alkenes (entries 7–10). The aziridines were readily opened with a variety of carbon and heteroatomic nucleophiles at the distal carbon of the bicyclic aziridine with no erosion in the enantioselectivity [85].

8.10.2

Intermolecular Aziridination

In 2003, He and coworkers reported the first examples of intermolecular Ag-catalyzed aziridinations using AgNO3 supported by a tButpy ligand (representative example in Scheme 8.10) [74a]. The scope of this chemistry included monosubstituted styrenes, aliphatic alkenes, cyclic disubstituted alkenes, and 1,2-disubstituted styrenes. In addition to the use of PhI=NTs as the nitrogen source, the reaction could be run using TsNH2 and PhI(OAc)2 to generate the iminoiodinane in situ.

Table 8.24 Selected scope for tunable intramolecular nitrene transfer by changing AgOTf–ligand ratios. R2

R3

H

Catalyst NH2

O

Entry

A

N

1

H H

O

Et O Et

N

2

H Et

O

H

H

O H

N

3 H9C4

H

O Et

H

H9C4

O H 4 H Me

N

H H

R3

H N

H N

O

I

R1

H N

O

O R3

A: I

Yield

dr cis only

O

58% A 67% A 26% I 93% I

Rh2 (OAc)4 1 : 1.25 AgOTf : phen 1 : 3 AgOTf : phen

4.9 : 1 24 : 1 1 : 6.6

68% A 88% A 73% I

trans only

O

O

Rh2 (esp)2

1.8 : 1 9:1 19 : 1

35% A 85% A 66% I

— — —

1 : 1.25 AgOTf : phen 1 : 3 AgOTf : phen

Et H N

H

3.2 : 1 15.7 : 1 1 : 1.8 99% ee (one xtal)

Me

N

N

N

N

92% ee

O

84%

87% ee

81%

92% ee

O

81%

87% ee

O

84%

89% ee

O O

Me Et

N

O

O O

9

i-Pr

Me

N

Me

N

O H

87%

O

O

Ph

O

TBSO

O

5

ee

O

N

O 2

N tBu

Yield

O 1

O

O Ligand =

O O

10

8.10 Aziridination

+ PhI=NTs

2 mol% AgNO3/tBu3tpy CH3CN, 0 °C to rt

NTs

81% yield

Scheme 8.10 Intermolecular alkene aziridination using a [Ag2 (tButpy2 )(OTf )](OTf ) catalyst.

In 2010, Pérez and coworkers developed a regio- and stereoselective intermolecular aziridination of 2,4-dien-1-ols (Table 8.26) catalyzed by a Tp*,Br Ag complex, where reaction at the proximal alkene over the distal site of unsaturation was favored with selectivities ranging from 85 : 15 to 93 : 7 [106]. No erosion in the stereochemistry of the proximal alkene was observed during the aziridination, irrespective of the alkene geometry in the substrate. Regioselective ring opening of the vinyl aziridine products with KOH furnished useful 2-amino-1,3-dihydroxyalkane building blocks. In further mechanistic studies on this system, the Pérez group showed that the presence of both conjugation and the free allylic alcohol are important to attaining good control over regioselective aziridination of the proximal alkene (Scheme 8.11) [107]. As shown in Scheme 8.11(1)–(3), protection or removal of the allylic alcohol resulted in a significant erosion of the regioselectivity. Mechanistically, the hydroxyl proton was proposed to bind to the oxygen of the sulfonyl group (Scheme 8.11(4)) to direct the outcome of the aziridination event. The Schomaker group showed in 2016 that the nature of the ligand supporting AgOTf could alter the chemoselectivity of intermolecular nitrene transfer (Table 8.27) [108]. The reaction was tunable for both five- and six-membered cycloalkenes, where coupling a [Ag2 (tBu3 tpy)2 OTf ](OTf ) catalyst with a 2,2,2trifluoro-1-(trifluoromethyl)ethyl sulfamic ester (HfsNH2 ) enabled moderate to good chemoselectivity for aziridination over C–H insertion. A variety of simple substituted cycloalkenes were good substrates for aziridination (entries 1–8), where alkyl, aryl, or alkynyl groups at C1 of the alkene were tolerated. Substrates with multiple alkene and allylic C–H functionalities (entries 9–11) gave varying preferences for aziridination, based on both the specific steric and electronic features of the alkene(s) and the allylic C—H bonds. A series of acyclic alkenes (entries 12–15) gave excellent selectivity for aziridination and displayed no observable isomerization during reaction to the aziridination (entry 12). Mechanistically, these reactions did not show any response to the addition of a radical inhibitor, suggesting either a concerted nitrene transfer or rapid radical rebound. Computations showed that the key factor controlling the chemoselectivity of the reaction is the trajectory of approach of the substrate to the lowest energy transition state of the putative silver nitrene. 8.10.3

Mechanistic Insights into Silver-Catalyzed Aziridination

There are two generally accepted mechanisms of nitrene transfer, as previously illustrated in Scheme 8.8. Concerted nitrene transfer mechanisms occur when a metallonitrene in a singlet state adds or inserts directly into a C=C or C—H bond and transfers stereochemical information present in the starting material to the products. The other possibility involves a stepwise or radical pathway associated with a triplet state in the metal-supported nitrene. However, since the

477

Table 8.26 Intermolecular, regioselective aziridination of 2,4-dien-1-ols. R1

R2 R3

HO +

R4

5 mol% Tp*,Br CH2Cl2, rt 99% conversion

PhINTs Entry

R1

A:B

Product

HO

Ts R2

N

A trans:cis

N

HO

N

HO

4

Me HO

5

90 : 10

>98 : 98 : 98 : 98 : 98 : 98 : 98 : 98 : 2

OR

Ts 5 mol% Tp*,Br CH2Cl2, rt

+ PhINTs

Ts

N

(2)

N OH

R=H R = OAc

OH 41% 83%

50% 19 : 1

63% >20 : 1 cis/trans

0%

>20 : 1

58%

4%

15 : 1

72%

2%

36 : 1

97%

0%

>19 : 1

Hb

Hb

b

10

Me

4

73%

Ha Hb

OAc

7%

10 : 1

Ha

16% 3.4 : 1 Ha : Hb

4.6 : 1

Hb

11

Hc Me

Ha 4-ClC6H4 57%

6

6% 5.0 : 1 Ha:Hb

9.5 : 1

12

nPent

a

H

13 51%

OMe

>99 : 1 cis:trans

Ha 7

b

Ha C6H5 73%

Hb

a

Me

5

Hb

Hb

17% 9.0 : 1 Ha:Hb

3.0 : 1

16%

2.5 : 1

14

H

H

Ha Me 8

H 40% 1:4.8 syn:anti

15

Bold numbers indicate the animation chemoselectivity.

Pérez found that in contrast to the use of copper catalysts supported by Tp-type ligands, the use of TpMe2 Ag or Tp*Br Ag catalysts (Scheme 8.12) showed retention of stereochemistry in the aziridination of a variety of alkenes. Hammett studies showed the presence of a combination of polar and radical contributions to the reaction and little effect on the yield when BHT was added as a radical inhibitor. The lack of ring opening in the presence of a radical clock further supported a concerted nitrene transfer mechanism. In spite of these experimental results, DFT calculations on the TpMe2 Ag catalyst system using 1-hexene as the substrate and PhI=NTs as the nitrene source, showed that the sinlet Ag nitrene complex had a ground state 8 kcal mol−1 higher in energy than the triplet nitrene, suggesting that the mechanism was more complicated than appeared at first glance. Thus, the reaction was highly unlikely to proceed through a singlet metallonitrene, despite the experimental observation that the aziridination appeared to proceed in a concerted fashion. To resolve this apparent contradiction, Pérez proposed the mechanism shown in Scheme 8.12, where the alkene first reacts with a triplet electrophilic Ag-supported nitrene to transfer an electron from the alkene π-system into the Ag—N bond. The nature of the catalyst affects the position of the minimum energy crossing point (MECP),

8.10 Aziridination

H Ts N

B N N

Singlet (s) PhI

R2

R1

Me

PhI=NTs

TpMe2Ag

N Me2

Tp t→s

R1

N

Triplet (t) R2 TpMe2Ag Triplet

H

Me

Ts

B N

Br

N

N Ts

R

1

R2

N

N Me

TpMe2Ag

Me Me

Me

Tp*Br

N Me Me

Me Me N Br N

N N

Br

Me Me

Scheme 8.12 Proposed mechanism of aziridination catalyzed by TpX Ag.

with respect to the formation of the diradical intermediate expected in a stepwise nitrene transfer reaction. In the case of silver, the MECP is proposed to occur after the transition state of the first electron transfer; thus, a triplet diradical intermediate that could undergo C–C rotation to scramble the stereochemistry is never reached. This proposal explains why aziridinations catalyzed by TpX Ag catalysts appear to behave as concerted processes and present with retention of configuration, even though the reactive metallonitrene exists in a triplet ground state. The Schomaker and Hein groups undertook additional mechanistic studies to better understand the ability to tune the chemoselectivity of intramolecular silver-catalyzed nitrene transfer through changes in the Ag–ligand ratio (see Tables 8.23 and 8.24, vide supra) [109]. Several possibilities were considered as reasons for the divergent chemoselectivity, including the involvement of monomeric vs dimeric silver complexes, different mechanisms for aziridination promoted by LAgOTf vs C–H amination by L2 AgOTf, and steric differentiation between the two catalysts. Investigating the relationships between chemoselectivity and ligand concentration (Figure 8.9) showed that as the concentration of tBubipy was increased from 12.5 mM (12.5 mol%) to 30 mM (30 mol%) using identical amounts of AgOTf, a progressive and significant decrease in the rate of aziridination was noted, especially when the ligand loading was increased from 12.5 to 20 mM (Figure 8.9a) [109]. In contrast, the rate of C–H amination (Figure 8.9b) was less susceptible to increases in the amount of tBubipy, suggesting that the formation of the allenic amine product displays a pseudo-zero-order dependence on catalyst concentration. From these and other studies, tunable chemoselectivity was hypothesized to arise as a consequence of suppressing the rate of aziridination, as opposed to accelerating the rate of generation of the allenic amine at higher ligand loadings. In the proposed mechanism of chemodivergent silver-catalyzed nitrene transfer (Scheme 8.13), reversible formation of the iminoiodinane sets up a competition between water and the Ag catalyst to capture this intermediate and lead to productive formation of the Ag nitrene species. The detrimental role of water is remedied by the addition of molecular sieves, while the heterogeneous nature of PhIO limits the concentration of highly reactive, unbound nitrene

481

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

H

H

10 mM AgOTf x mM tBuBipy

O

Ph

O NH2

N

Ph

PhIO, 4 Å MS 0.1 M CH2Cl2, rt

0.08

H

Ph

N

H

O H

H

Ph O

+ O

HN O

O [tBuBipy] = 12.5 mM [tBuBipy] = 20 mM [tBuBipy] = 25 mM [tBuBipy] = 30 mM

0.1

H

[tBuBipy] = 12.5 mM [tBuBipy] = 20 mM [tBuBipy] = 25 mM [tBuBipy] = 30 mM

0.1

O

0.08

H

Ph O

HN

(M)

O (M)

482

0.06 Increase in [L] Suppresses aziridination

0.04

0.06 Increase in ligand Slight increase in C–H amination

0.04 0.02

0.02

0

0 0

10

20

(a)

40

30 Time (min)

0

50

10

20

(b)

30

40

50

Time (min)

Figure 8.9 Effect of the relative tBubipy ligand concentration on the rates of Ag-catalyzed aziridination (a) and C–H amination (b). O O R

N

PhIO + O

R = –(CH2)2Ph

Typically >9 : 1

H2N

O OR

HN

k–1 k1 AgL2

AgL

R

O

Typically> 9 : 1

O k2

RO

AgL (tBubipy)AgOTf

k4

LAg

+

O PhI +

O N

OR

N

PhI

OR

N

PhI

+

O k6 PhI

L2Ag N

OR

O

O H2N

AgL2 (tBubipy)2AgOTf

OR

Int-2 AgL2

Int-1

k7

+

O

AgL k3

k5

IPh

N

= OR

H2 N

R

O H

Scheme 8.13 Proposed mechanisms for tunable, chemoselective silver-catalyzed nitrene transfer.

intermediates. This may enable the catalyst to turn over the iminoiodinane as soon as it is generated, thus minimizing unproductive side reactions. This hypothesis is supported by the poor chemoselectivity and/or reactivity observed with common soluble hypervalent iodine oxidants, such as PhI(OAc)2 . Ag-supported nitrenes can engage in either aziridination or C–H insertion, depending on the coordination number at the metal center (Scheme 8.13). Based on calculations carried out by the Pérez group on silver complexes supported by trispyrazolylborate (Tp) ligands [99], it was proposed that chemoselective aziridinations also proceed via attack of a triplet metallonitrene species on the alkene to form the first C—N bond [109]. The triplet species then crosses over to the singlet state, forming the final aziridine C—N bond before any discrete diradical intermediates are formed; thus, the resulting reaction appears to be concerted in nature. The aziridination pathway is intrinsically faster than the C–H amination

8.10 Aziridination H

10 mol% AgOTf 12 mol% tpy

F +

OSO2NH2 F DfsNH2

Experimental A:I

6.5 : 1

Aziridination

3.5 equiv. PhIO CH2Cl2, 4 Å MS, rt

NHDfs

A

N

I

Computed A:I >19 : 1

17.0

16.5

OS1

TStpy,I,1

11.4

H H

9.38 8.27

TS

Minimum energy crossing point

Triplet 0.00 R

x

–8.32

x

ΔG (kcal mol–1)

tpy N

C–H insertion

Singlet

N

NDfs +

–16.0 H

Int

H

H 3

H 3

Inttpy,A,1

TStpy,A,1 –62.6

H H H 3

H

Barrierless radical recombination No effect of radical inhibitors

H H

3Int

tpy,I,1

–81.7 Product

R

Figure 8.10 Reaction coordinates of nitrene transfer catalyzed by [Ag2 (tBu3 tpy)2 OTf ](OTf ).

reaction (k3 > k6 ), with the combination of the low imidoiodinane concentration and the ability to partition the silver species between multiple coordination environments accounting for the unique behavior observed in this Ag-catalyzed nitrene transfer system. The Schomaker group also investigated the mechanism of intermolecular, chemoselective silver-catalyzed nitrene transfer [108]. As previously shown in Table 8.27, a [Ag2 (tBu3 tpy)2 OTf ](OTf ) catalyst favored aziridine formation over C–H insertion using HfsNH2 as the nitrene precursor. Calculations to understand the reactivity landscape in this system (Figure 8.10) showed that 3 TStpy,A,1 is lower in energy than 3 TStpy,I,1 (9.38 vs. 11.4 kcal mol−1 ), in agreement with the experimentally observed selectivity. Calculations also showed that OS1 TStpy,I,1 and OS1 TStpy,A,1 lead to the direct formation of product complexes, 1 PCtpy,I,1 and 1 PCtpy,A,1 , respectively (−98.5 and −84.6 kcal mol−1 ), without accessing a discrete intermediate. The observation that the aziridination resists inhibition by TEMPO suggests that direct access of the OS PES after 3 Inttpy (crosses in Figure 8.10) is the major reaction pathway. This “barrierless radical recombination” pathway is reminiscent of results reported by Pérez in their calculations of aziridination catalyzed by TpX Ag [99].

483

484

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

8.11 C—H Bond Amidation 8.11.1

Intramolecular C—H Bond Amidations

The He group was the first to report the silver-catalyzed intramolecular amidation of C—H bonds (Table 8.28) [74b]. While the scope of the chemistry was covered in the previous edition of this chapter, it is included here as a benchmark comparison for more recent catalysts for C–H amidation. Of particular note is the stereospecificity observed in entry 4, providing support for either a concerted nitrene transfer or rapid radical rebound process. The Schomaker group first reported that the identity of the ligand on silver could be altered to control the site selectivity of C–H amidation between tertiary alkyl C(sp3 )—H and benzylic C—H bonds (Table 8.29) [110]. The use of an excess amount of tBubipy (3 equiv.) compared with AgOTf (1 equiv.) resulted in a preference for amination of the more electron-rich tertiary alkyl C(sp3 )—H bond. The selectivity showed a complicated dependence on the nature of the dialkyl group at the tertiary C—H bond (entries 1–5), suggesting that the trajectory of approach of the C—H bond to the putative silver nitrene plays an important role in determining the site selectivity. The selectivity of the reaction responded more predictably to electronic effects as the preference for amination of the 3 ∘ C—H bond decreased with the introduction of an electron-donating methyl group (entry 6) on the aromatic ring and increased when an electron-withdrawing CF3 group was installed (entry 7). Changing the identity of the ligand from tBubipy to either Me4 phen or Py5 Me2 altered the site selectivity between the amination of the two competing tertiary alkyl C(sp3 )—H bonds (Table 8.30) [111]. Traditional explanations for site selectivity based on sterics or relative bond dissociation energies (BDEs) are not adequate when applied to tertiary C(sp3 )–H differentiation. The competing 3∘ C—H bonds of the substrates in Table 8.30 have essentially the same BDEs, but differ in their conformational flexibilities, depending on the size of the cycloalkyl group. The observation that (Me4 phen)AgOTf (entries 1, 2, and 4) increasingly favored amination of the cycloalkyl (Cy) C—H bond as the carbocycle increased in size from cPent to cHept might be attributed to the fluxional nature of cHept and the greater rate of pseudo-equatorial C—H bond oxidation by strain release during the amination event [111]. This may also explain the preference for Cy C–H amination in entry 9. In contrast, the bulky [(Py5 Me2 )AgOTf ]2 catalyst showed a greater response to steric effects, where the most accessible C—H bond was preferred with moderate selectivity. The development of catalysts displaying preference for the amination of benzylic C—H bonds over tertiary alkyl C(sp3 )—H bonds was reported in 2014 by the Schomaker group (Table 8.31) [110, 112]. Initial investigations carried out with (tpa)AgOTf and sulfamate precursors delivered promising selectivities for benzylic amination in CH2 Cl2 at room temperature [110]. Further reaction optimization showed that the use of CHCl3 as the solvent at −20 ∘ C improved the ratios of A:B (entries 2, 4, 9, and 12), provided the aryl group was not particularly electron poor (entry 6). The benzylic amines were obtained in >19 : 1 dr in favor of the syn-stereoisomer [112]. The bulky dimeric [(Py5 Me2 )AgOTf ]2

Table 8.28 Intramolecular C–H amidations of saturated C—H bonds. 4 mol% AgNO3 /tBu3tpy

O R

O

PhI(OAc)2 CH3CN, 82°C

NH2

Entry

Product

Yield 81%

Ph

O

O

R Entry

O H N

5

O O S O

HN

6

R

87%

78%

MeO 85% 7

HN

O O S O

83%

O O

HN

HN

Yield

HN

O

2

4

PhI(OAc)2 CH3CN, 82 °C

Product

5

O O S O

4 mol% AgNO3 /tBu3tpy

O O S NH2

O

Ph

H N

3

O

O

HN

1

HN R

O O S O

HN

90%

O 73% O

H N

O 58% O

8

O S O O

65%

Table 8.29 Intramolecular C–H amidation of saturated C—H bonds. H2N H

R1

O O S H O Ar

R2

Major product (A)

Entry

O O S HN O

1

Me Me O O S O HN

2 Et

3

10 mol% AgOTf 30 mol% tBuBipy

Et O O S HN O

R1

PhIO, 4 Å MS CH2Cl2, rt Yield

75%

O O S O

R2 A:B

R2

O O S NH

O B

Major product (A)

Entry

O O S HN O

5 iPr

Ar Yield

A:B

75%

2.6 : 1

77%

2.0 : 1

80%

6.3 : 1

Ph iPr

81%

O O S O HN

5.2 : 1

Ph 6

Me 81%

Me

5.2 : 1

Me O O S HN O

Ph

4

Ar

A

2.9 : 1

Ph

R1

+

HN

O O S O

7

HN

81% Ph

8.0 : 1

Me Me

CF3

Table 8.30 Selectivity in the amination of two competing tertiary alkyl C(sp3 )—H bonds. O H2N R1

H

R2 Entry

1

S O

O

10 mol% catalyst H R3 PhIO, 4 Å MS CH2Cl2, rt R4

Catalyst

R1

O O S O

HN

R2

(Me4phen) AgOTf

Me

+ R4 R2

A

Major product (A) O O S HN O

R3

Yield

A:B

95%

5.0 : 1

Me 2

(Me4phen) AgOTf

3

[(Py5Me2) AgOTf ]2

O O S HN O

Me

96%

7.3 : 1

96%

1.3 : 1

R1

O O S NH 3 R

O B

(Me4phen) AgOTf

5

[(Py5Me2) AgOTf ]2

6

Me

N N Me4phen Major product (B)

7

[(Py5Me2) AgOTf ]2

O

O O S NH

Me Me

O O HN S O

(Me4phen) AgOTf iPr

87%

1.8 : 1

83%

1.4 : 1

9 Me Me

iPr

2.5 : 1

N

Yield

A:B

97%

1 : 3.9

79%

1 : 4.6

99%

1 : 3.5

76%

1 : 2.1

Me Me

iPr

[(Py5Me2) AgOTf ]2

O O S NH

O

Me Me

iPr 93%

Py5Me2 N Me Me N

N

Catalyst

Me O O HN S O

N

Me

Entry

8 4

R4

Me Me

(Me4phen) AgOTf

10 [(Py5Me2) AgOTf ]2 iPr

iPr

O O S NH

O

Table 8.31 Silver catalysts for selective benzylic C—H bond amidation. O O O 10 mol% AgOTf H2N S O S 12.5 mol% ligand O HN H 1 H O R PhIO, 4 Å MS Ar solvent, temp A Ar R2 Entry

Major product (A)

1

O O S HN O

2 3

R=H

Me Me R = OMe

4 5

R R = CF3

6 7 8

O O S O

HN

9 10 11 12 13 14

15

O O S HN O Ph O O S HN O Ph Ph O O S HN O Ph Ph

iPr Me

R2

Ar

B

R2

Solvent

Temperature

A:B

Py5Me2 tpa

rt

α-Me-(anti)-Py3Pip

CH2Cl2 CHCl3 CHCl3

–20 –20

2.6 : 1 4.3 : 1 5.7 : 1

80 92 87

tpa α-Me-(anti)-Py3Pip

CHCl3 CHCl3

–20 –20

>19 : 1 >19 : 1

84 81 92 88

Yield (%)

tpa α-Me-(anti)-Py3Pip

CHCl3 CHCl3

–20 –20

1.4 : 1 1.8 : 1

Py5Me2 tpa

CH2Cl2 CHCl3 CHCl3

rt –20

7.6 : 1 8.6 : 1 12.8 : 1

95 94

–20

>19 : 1 >19 : 1 >19 : 1

77 63 63

–20

rt rt

87

tpa α-Me-(anti)-Py3Pip

CH2Cl2 CH2Cl2 CHCl3

Py5Me2

CH2Cl2

rt

2.7 : 1

83

Py5Me2

CH2Cl2

rt

8.4 : 1

81

Py5Me2

iPr

O O S NH 1 R

O

+

Ligand

α-Me-(anti)-Py3Pip

Ph

R1

Me

8.11 C—H Bond Amidation

catalyst was also capable of carrying out the amination of a secondary benzylic C—H bond with good selectivity and >19 : 1 syn/anti ratios, provided the tertiary alkyl C(sp3 )—H bond was sufficiently sterically congested (entries 8, 11, and 15) [87]. The selectivity decreased in cases where the C—H bond of an iPr group competed with the benzylic C—H bond (entries 1 and 14). The Schomaker group also reported a new catalyst based on a piperidine scaffold, (α-Me-anti-Py3 Pip)AgOTf (see Figure 8.6, vide supra), designed to limit the fluxional behavior of the silver complex in solution [79]. This catalyst did show an improved preference for benzylic C–H amination (entries 3, 5, 7, 10, and 13), although further optimization is required to achieve better selectivity for sterically hindered or electron-poor benzylic C—H bonds. The Schomaker group undertook studies to extend the utility of their site-selective silver catalysts to encompass chemo- and site-selective aminations of allylic C—H bonds (selected results in Table 8.32) [87, 112]. Three catalysts – (tpa)AgOTf, [(Py5 Me2 )AgOTf ]2 , and (α-Me-anti-Py3 Pip)AgOTf (Figure 8.6, vide supra) – were tested. [(Py5 Me2 )AgOTf ]2 , a dimeric catalyst with a KIE of 5.7, proved effective at suppressing competing alkene aziridination. The stepwise nature of nitrene transfer promoted by this complex translated into good selectivity for the allylic C—H bond with the lowest BDE (entry 1). However, as preliminary results furnished low dr using [(Py5 Me2 )AgOTf ]2 , studies with this catalyst were not further pursued. Both (tpa)AgOTf (entries 2–4, 6, and 8) and (α-Me-anti-Py3 Pip)AgOTf (entries 5, 7, and 9) gave no aziridination and good to excellent selectivity for allylic C–H amination over the competing reaction at either a tertiary alkyl C(sp3 )—H or benzylic C—H bond. The less conformationally flexible (α-Me-anti-Py3 Pip)AgOTf gave slightly better preference for generation of the allylic amine products and displayed improved dr in favor of the syn-diastereomer. Computational studies to ascertain the reasons for the observed selectivity are described in Figures 8.11 and 8.12 (vide infra) [112]. Chemo- and site-selective aminations of propargylic C—H bonds in the presence of competing alkyne and tertiary alkyl C(sp3 )–H functionalities was also explored using (tpa)AgOTf, [(Py5 Me2 )AgOTf ]2 , and (α-Me-anti-Py3 Pip)AgOTf (selected results in Table 8.33) [87, 112]. The (tpa)AgOTf catalyst (entries 2, 3, 7, and 11) gave variable results in terms of the selectivity and dr, while [(Py5 Me2 )AgOTf ]2 improved the preference for the amination of the propargylic C—H bond (entries 4, 6, 9, 10, and 12). However, the diastereoselectivities were poor, delivering essentially equal amounts of the syn- and anti-propargylamines. In the case of (α-Me-anti-Py3 Pip)AgOTf, the dr was significantly improved, favoring the syn-isomer; however, the preference for propargylic amination was decreased slightly as compared with [(Py5 Me2 )AgOTf ]2 . A tandem silver-catalyzed C–H amination/oxidation/addition reaction was developed by the Schomaker group to address diastereoselectivity issues that arise when nitrene insertions into tertiary chiral C—H bonds in substrates with two stereogenic racemic carbons are attempted [113]. In these cases, the resulting α-tertiary amines are obtained as mixtures of diastereomers, due to retention of stereochemistry at the tertiary C—H bond in the amidation reaction. This problem is solved by employing a one-pot silver-catalyzed nitrene

489

Table 8.32 Selectivity for allylic amidation in Ag-catalyzed nitrene transfer of alkenes with competing reactive C—H bonds. R1

H

O NH2 O S H O

R2

R2

PhIO, 4 Å MS CH2Cl2, rt

A

R3 R4

Entry

O O S O

1

Me HN

Py5Me2

>19 : 1

6.1 : 1

71% 1.4 : 1

tpa

>19 : 1

4.2 : 1

76% 5.9 : 1

Entry

tpa >19 : 1 O O S Me HN O α-Me-(anti)-Py Pip >19 : 1 3

15.7 : 1

84% 8.9 : 1 75% 8.6 : 1

8

Me

Me Me

>19 : 1

O O S NH R3

R1 R4 R2

Ligand (B + C) : A

O

R4

C B:C

Yield dr of B

tpa

>19 : 1

3.5 : 1

77% 6.7:1

α-Me-(anti)-Py3Pip

>19 : 1

3.7 : 1

69% 9.8:1

O O S O

tpa

>19 : 1

6.0 : 1

78% >19:1

α-Me-(anti)-Py3Pip

>19 : 1

6.4 : 1

72% >19:1

Ph

Me 7

Me

O O S O

Me HN

85% 13.6 : 1

tpa

R3

B

Major product (B)

6

6.6 : 1

Me

Me

5

Yield dr of B

B:C

>19 : 1

H

3

O O S O

R1 HN

R3 2 R4 R

(B + C) : A

Me O O S HN O

O O N S O

H

Me

2 H

4

Ligand

Major product (B)

R1

10 mol% AgOTf 12.5 mol% ligand

H

HN

Ph

Ph 9

8.11 C—H Bond Amidation

H2N H

O O

10 mol% AgOTf 12.5 mol% ligand

O S O H O

HN

O

Ph

Benzylic C–H amidation

H iBu

N

1.357 Å

SO2 N

Tertiary C–H amidation i

H

O 2.076 Å

O O O S NH

+

Ph

PhIO, 4 Å MS solvent, temp

Ph

S

2.108 Å

Bu

O

O2S

H H N

N

Ag N N

N

p–p 3.337 Å

N p–p 3.335 Å

Ag N N

Transition state (TS)-A

Reactant complex (RC)-A

Figure 8.11 Lowest energy reactant and transition state complexes for amidation of benzylic C—H bonds showing π–π interactions between catalyst and substrate can drive selectivity. O O S O

i

HN O H2N H

S O H O

10 mol% AgOTf

2.132 Å O2S Allylic C–H amidation

N

12.5 mol% ligand PhIO, 4 Å MS solvent, temp

Bu

+

O O O S NH

N

OTf

H H

1.419 Å

N

Ag N N

Tertiary C–H amidation

H

O

3.605 Å Ag–p interaction

Transition state (TS)-B

Figure 8.12 Lowest energy transition state complex for amidation of allylic C—H bonds showing Ag–π interactions between catalyst and substrate can drive selectivity.

transfer into activated and secondary benzylic or allylic C—H bond, followed by oxidation of the intermediate amine to afford the corresponding imine by addition of a catalytic amount of TEMPO. Subsequent reaction of the imine with a Grignard reagent furnishes the syn-stereoisomer of the 1,3-amino alcohol product in >19 : 1 dr (Table 8.34). This three-step one-pot method simplifies the preparation of substrates for the synthesis of α-tertiary amines and offers greater flexibility in the range of groups that can be introduced into the products. The effect of the aryl group electronics were minimal (entries 1–4, and 6), but steric effects due to ortho-substitution on the arene decreased the yield (entry 4). Oxidation of an allylic amine to the imine was not as effective as the oxidation of benzylic amines (entry 7); a variety of Grignard reagents could be employed in the final nucleophilic addition to the imine (entries 8–12). The silver catalyst, PhIO oxidant, and TEMPO additive were all crucial to the success of the reaction, although mechanistic studies suggested that the expected oxoammonium pathway was unlikely [113]. A proposed alternate mechanistic pathway for the amine-to-imine oxidation is illustrated in Scheme 8.14, where polymeric PhIO is broken down by either AgOTf or Ag(tpa)OTf acting as a

491

Table 8.33 Selectivity for propargylic C—H bond amidation over 3∘ alkyl and benzylic C–H amidation.

H

O NH2 O S H O

R2

PhIO, 4 Å MS CH2Cl2, rt

R3 R1 Entry 1 2 3 4 5 6 7 8

O O S O

Me Me

H11C5 O O S O

HN

Me

Ph O O S HN O

9

O

R3 R1

A A:B

B

Yield (%)

dr of A (syn : anti)

1 : 2.4 1.4 : 1 2.3 : 1 8.5 : 1 4.2 : 1

72 63 63 67 58

1.2 : 1 2.2 : 1 4.5 : 1 1.4 : 1 5.0 : 1

a-Me-(anti)-Py3Pip

7.2 : 1 7.2 : 1 10.3 : 1

81 82 86

1 : 1.4 11 : 1 12 : 1

[(Py5Me2)AgOTf]2

4.8 : 1

64

1 : 1.1

[(Py5Me2)AgOTf]2

18 : 1

82

1 : 1.6

(tpa)AgOTf a-Me-(anti)-Py3Pip

1.8 : 1 2.0 : 1

60 70

4.2 : 1 10.5 : 1

(tBubipy)2AgOTf (tpa)AgOTf (tpa)AgOTf (CHCl3, –20 °C) [(Py5Me2)AgOTf]2 a-Me-(anti)-Py3Pip [(Py5Me2)AgOTf]2 (tpa)AgOTf

Me

O O S NH 2 R

R2 R3

R1

Catalys

Major product (B)

HN

O O S O

HN

10 mol% catalyst

H11C5 O O S O

HN

10 H11C5

O O S O

11 12

HN H11C5

8.11 C—H Bond Amidation

Table 8.34 Scope of Ag-catalyzed C–H amidation/oxidation/nucleophilic addition to α-tertiary amines. 10 mol% AgOTf 12.5mol% tpa 3.5 equiv. PhIO

O H2N S O H O

0.05 M CH2Cl2 1 4Å MS, rt, 30 min R

R2

R1

Entry

Product O O S O

Me

57

47

>19 : 1

CF3

59

>19 : 1

Br

55

R1

R2 H

R3

Yield %

dr

O O S O

8 H

62

>19 : 1

43

>19 : 1

38

>19 : 1

54

>19 : 1

65

>19 : 1

Et

O O S O

HN 9 Ph

H

>19 : 1

Et

R O O S O

Me HN

5

Me

H

26

H

Me

>19 : 1

O O S O

HN

10

Et

Ph

O O S HN O

6

41

H O O S O

>19 : 1 11

Et

O O S HN O

7 Ph

Me

H

23

Ph

H

>19 : 1

Ph

N

Ph

O O N S O F

E Et + PhI

O O S HN O Ph

Et

Ph

O N

H

Et

OH O O I N S O H C

TEMPO

OH

O O S O

12

O

Et

HN

Et

H2O

Et

HN

iPr

Ph

HN

HN

>19 : 1

R OMe

CH2Cl2

Product

Ph

Et

H

Me

Entry

O O S O

R3MgBr R2

R1

Ph

3 4

R2

Et

H

O O S HN O

2

O O S N O

30 mol% TEMPO

Yield (%) dr

HN

1

O O S HN O

H Ph OH O O Ph I N S O Ph

D

AgOTf Et

I

Et A

O Ag B OTf

Monomeric

[PhIO]n Polymeric

Scheme 8.14 Proposed mechanistic pathway for the silver-catalyzed amine-to-imine oxidation.

493

494

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

standard Lewis acid to give the activated monomer B. This explains the requirement for a Ag salt or other Lewis acid for successful amine oxidation. Amine A (or related species) is activated via N-iodination with excess PhIO to give C after proton transfer. H-atom abstraction by TEMPO yields D and E; D loses PhI and a hydroxyl radical to form the imine product F. Regeneration of TEMPO occurs through loss of H2 O, explaining the necessity for molecular sieves in the reaction. This proposed pathway also accounts for the requirement that both AgOTf and PhIO be present in the amine oxidation step. 8.11.2

Intermolecular C—H Bond Amidation

He reported the first examples of intermolecular silver-catalyzed C–H amination using AgOTf supported by a bathophenanthroline (BP) ligand in 2007 [74c]. Key results are summarized in Table 8.35, indicating that substrates with more activated benzylic C—H bonds generally gave higher yields than less reactive secondary cyclic sp3 bonds (compare entries 1–5, and 10 with entries 6–9). Tertiary cyclic sp3 bonds were more reactive than secondary ones (compare entries 4, 5, 7, and 10 with entries 1, 2, 6, 8, and 9). Formation of the iminoiodinane using PhI(OAc)2 with NsNH2 gave lower yields than forming the PhI=NNs directly but was more operationally convenient. In 2008, the Pérez group reported intermolecular C–H amidation for a variety of hydrocarbon substrates using the silver scorpionate complex [Tp*,Br ]Ag ([Tp*,Br ] = hydrotris(4-bromo-3,5-dimethyl)pyrazolyl borate) (Table 8.36) [114]. Interestingly, if these reactions were carried out with the neat alkanes acting as the solvent at 80 ∘ C, diverse C–H functionalities, including primary, secondary, Table 8.35 Selectivity for propargylic over 3∘ alkyl and benzylic C–H amination. 5 mol% AgOTf/BP

H R1

Entry

R2

+

PhI=NNs

4 Å MS CH2Cl2, 50 °C

Product

Yield (%)

R1

Ph

Ph

NHNs BP =

R2

N

Entry

N

Product

Yield (%)

NHNs 1

70

6

68

7

25

8

57

9

NHNs

NHNs 2

3

35

NHNs

39

40

NHNs

NHNs NHNs 4

NHNs 33

NHNs NHNs 5

65

71

10 9

1

NHNs

8.11 C—H Bond Amidation

Table 8.36 Scope of silver pyrazolylborate-catalyzed intermolecular C–H amination of sp3 C—H bonds. H

Me 5 mol% R

H

+

PhI=NTs

Tp*,Br Ag

B N

Br R

N

NHTs

No solvent, 80 °C, 16 h

Me Tp*,Br

Entry

Product

Yield (%)

Entry

Product

3.1 1

1

65

4

9

N N

Me Me N Br N

Br

Me Me

Yield (%)

1

80

5.9 1

7

5 2

70

NHTs

80

12 3

75

6

NHTs

90

NHTs

and tertiary alkyl C(sp3 )—H bonds, were all capable of undergoing amination. The [Tp*,Br ]Ag catalyst gave significantly higher yields than catalysts and reaction conditions previously reported by the Pérez group [115]. A stereochemical probe experiment that utilized a 2.3 : 1 trans/cis mixture of 2-pentene showed a significant change in the trans/cis ratio of the aziridine products, with an overall decrease to 1 : 1.15. This result, coupled with the observation that the addition of BHT as a radical inhibitor furnished a significantly decreased yield, suggested the presence of a radical pathway and a stepwise nitrene transfer in intermolecular aminations catalyzed by Tp*,Br Ag. Other recent studies in intermolecular C–H amination carried out by the Pérez group were inspired by a Dauban and coworkers report that employed the chiral nitrene precursor (S)-N-(p-toluenesulfonyl)-p-toluenesulfonimidamide in combination with an enantioenriched dinuclear Rh catalyst [116]. In cases where the stereochemistry of the nitrene precursor matched that of the Rh catalyst, the amine products were obtained in high diastereoselectivities. Removal of the amine protecting group gave the free amines in high enantioselectivities. The Pérez group tested this same nitrene precursor using [Tp*,Br ]Ag (Table 8.37) in the intermolecular C–H aminations of substrates containing activated benzylic C—H bonds [117]. While the yields were excellent, the diastereoselectivities were poor; efforts to identify potential chiral Ag catalysts to improve the dr are ongoing and would comprise an important advance in stereoselective Ag-catalyzed nitrene transfer. Pérez also undertook studies involving this same chiral nitrene precursor using a variety of different hydrocarbons containing unactivated alkyl C(sp3 )—H bonds (Table 8.38) [117]. Interestingly, while nitrene transfer rarely occurs at primary C—H bonds, the use of pentane as the substrate (entry 1) resulted in primary and secondary C—H bond insertion products, albeit in poor dr in the case of the latter product. In contrast, when tertiary alkyl C(sp3 )—H bonds

495

Table 8.37 Intermolecular C–H amidation using a chiral nitrene precursor with a Tp*,Br Ag catalyst. H

Me NTs

O +

X 5 equiv. Entry

H2N

4 mol% Tp*,BrAg

S

1 equiv. Product

NHS*

Me Yield (%)

*

PhI(OAc)2 CH2Cl2, –30 °C, 72 h dr

Product

N

N N

Me Me N Br N

Br

Tp*Br

Me Me

Yield (%)

dr

90 (40% at rt)

66 : 34

99

56 : 44

NHS*

NHS* 1

Br Me

X

Entry

B N

82

52 : 48

3 Cl

NHS* 2

NHS* 99

MeO

55 : 45

4

Table 8.38 Intermolecular C–H amination using a chiral nitrene precursor with a Tp*,Br Ag catalyst. H

Me H R1

NTs

O R2

+

5 equiv.

H2N

S

1 equiv.

Entry

4 mol% Tp*,BrAg Me

Yield (%)

Product NHS*

NHS*

70

2

3

SHN* SHN*

2

R1

Br

R2

B N

Me Tp*Br Product

Entry

N N

Me Me N Br N Me Me

Yield (%)

NHS*

1 1

H

PhI(OAc)2 CH2Cl2, 40 °C, 7 h

NHS*

N

4

SHN*

1.2 5 equiv. alkane

25

30 equiv. alkane

70 5 25

SHN*

5 equiv. alkane

30

30 equiv. alkane

75

23

Br

498

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

were present in the substrate (entries 2–5), insertion of the metal–nitrene into the tertiary C—H bond was heavily favored. These reactions are proposed to proceed through the initial formation of a metallonitrene species, which then abstracts a hydrogen atom from the substrate, leading to a Ag-amido species and an organic radical. Radical rebound then forms the new C—N bond and regenerates the active catalyst. In 2014, Pérez and coworkers reported the synthesis of a fluorinated trisphosphinoborate (PhBP3 CF3 Ph) ligand as a phosphorus analogue of the Tp-type ligands previously developed in their group [84]. Unfortunately, silver catalysts supported by PhBP3 CF3 Ph were incapable of efficient alkene aziridination or amination of unactivated C—H bonds. However, (PhBP3 CF3 Ph)Ag(PPh3 ) successfully catalyzed the amidation of highly activated C—H bonds, such as those situated α to an oxygen atom (Table 8.39). The Schomaker group reported chemoselective intermolecular amination using a (tpa)AgOTf catalyst coupled with a 2,6-difluorophenyl sulfamic ester (DfsNH2 ) nitrogen source (Table 8.40) [108]. The reaction was explored with a series of substituted cyclohexenes. In cases where two different allylic C—H bonds were available, the reaction showed a moderate preference for the C–H amination of the less hindered allylic C—Ha bonds (entries 3–6). Moving the Me group to an allylic position (entry 7) decreased the selectivity for aziridination; while the preference for C–H amination was improved, a fair amount of allylic transposition was also noted. Substrates with multiple alkene and allylic C–H functionalities (entries 8 and 9) gave varying selectivity, based on the specific steric and electronic features of the alkene(s) and the allylic C—H bonds. The ability to tune for aziridination or C–H insertion did not hold for acyclic alkenes; computations showed that steric clashing between the substrate and the silver nitrene intermediate was problematic, dependent on the specific substitution pattern of the alkene. 8.11.3

Mechanistic Aspects of Site-selective C—H Bond Amidation

The Schomaker and Berry groups carried out extensive computational studies to explore the reasons why (tpa)AgOTf shows a preference for the amidation of benzylic, allylic, and propargylic C—H bonds over tertiary alkyl C(sp3 )—H bonds (Tables 8.31–8.33, vide supra) [112]. The site selectivity in competing reactions of benzylic and 3∘ alkyl C(sp3 )—H bonds (Table 8.31, vide supra) was investigated through DFT studies of pro-benzylic and pro-3∘ conformers of potential Ag nitrene intermediates based on Ag(OTf )tpa [112]. The lowest calculated energy state was the triplet state, with the Ag nitrene interaction showing partial σ- and π-bond character. The Ag nitrene reactant complex (RC-A) was best described as a Ag(II) nitrene•– (nitrene•– = nitrene radical anion) structure. Scanning of all critical points along the triplet potential surface (3 PES) for all possible Ag nitrene structures located all the transition states (TS) for either benzylic (both R and S products) or 3∘ C–H amination. Interestingly, substrate-aryl⋅⋅⋅tpa-pyridyl π⋅⋅⋅π interactions of 3.34 Å were identified in both the lowest energy conformations of the reactant complex, RC-A, and the transition state, TS-A (Figure 8.11). No such π⋅⋅⋅π interactions were found in any structures leading to amidation of the tertiary

Table 8.39 Amination of ethereal C—H bonds catalyzed by (PhBP3 CF3Ph )Ag(PPh3 ). H R1

R3 R2 +

PhI=NTs Entry

5 mol% (PhBP3CF3Ph)Ag(PPh3)

TsHN R1

substrate, rt, 5 h Product

Yield (%)

Ph B

R3 Ar P Ar

R2

Entry

Ar =

P Ar P Ar Ar Ar Product

CF3 PhBP3CF3Ph Yield (%)

NHTs 1

2

O

O

NHTs

75

4

71 O NHTs

NHTs 70

O

67

5

3

NHTs

NHTs 25 O

20 : 1 and syn/anti >20 : 1, which compared well with the experimental results of 6.6 : 1 and syn/anti 13.6 : 1. Preferential activation of the allylic C—H bond in TS-B likely results from an NCI between the Ag cation and the allylic π-system. In fact, this type of Ag⋅⋅⋅π interaction is well documented, with over 251 reported crystal structures of Ag–olefin complex structures [118]. The key feature of Ag complexes favoring benzylic and allylic C—H bond amidations, as compared to nitrene transfer catalysts based on Rh, Ru, and Fe, is a less saturated coordination sphere with an open site located cis to the Ag nitrene bond. This coordination environment, unique to Ag among the group 11 elements, allows for sufficient space between the pyridyl rings of the tpa ligand to engage in π-stacking interactions to drive site selectivity. In addition, the fourth coordination site on Ag cis to the putative Ag nitrene bond allows NCIs between

8.11 C—H Bond Amidation

π-electrons in substrates and the metal center. The presence of these NCIs are critical in tuning the energetics of the various transition states and accessible reactant conformers, thus impacting the regioselectivity and dr of NTs promoted by Ag(tpa)OTf. In the context of tunable, site-selective C—H bond amidation reported by the Schomaker group using (tpa)AgOTf and DfsNH2 (Table 8.40), calculations to understand the reactivity landscape in this system (Figure 8.13) showed that OS1 TStpa,I,1 (9.80 kcal mol−1 ) and 3 TStpa,I,1 (10.2 kcal mol−1 ) are lower in energy than 3 TStpa,A,1 (10.7 kcal mol−1 ), consistent with experimentally observed chemoselectivity [108]. Hydrogen atom abstraction (HAA) in the C–H amination yields intermediates (Int) on both the OS singlet (OS1 Inttpa,I,1 ) and triplet (3 Inttpa,I,1 ) potential energy surfaces (PES, −19.2 and −19.7 kcal mol−1 , respectively), with the triplet state being slightly favored. Radical rebound occurs with no energetic barrier after formation of OS1 Inttpa,I,1 on the OS singlet surface to give the allylic amine (−71.4 kcal mol−1 ). The presence of an intermediate after HAA on both the OS singlet and triplet PESs, coupled with how close the two intermediates are in energy, suggest that 3 Inttpa,I,1 is sufficiently long lived to be trapped by radical inhibitors. This finding is consistent with experimental observations, where TEMPO significantly decreased the yield of the allylic amine product. F

H

OSO2NH2

+

F DfsNH 2 Experimental A:I 1 : 5.8

10 mol% AgOTf 12 mol% tpa

NHDfs

1.2 equiv. PhIO CH2Cl2, 4 A MS, rt

I

A

10.7

10.2 H H

10.1 4.13

TS

H H 3TS

Triplet

ΔG (kcal mol–1)

N 3 tpa

Computed A:I 1 : 4.3

Aziridination C–H insertion

Singlet

N

NDfs +

0.00

tpa,A,1

H H

R

3

–9.09

OS1TS

Inttpa,A,1

Minimum energy crossing point

–9.53 tpa,I,1

–19.2 H

H

x

–19.7

–56.3

Int H H H

3R

H

Radical lifetime is long enough to show effects with inhibitors

Minimum energy crossing point 3Int tpa,I,1

–71.4

Product complex

Figure 8.13 Reaction coordinates of nitrene transfer catalyzed by (tpa)AgOTf.

501

502

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

8.12 Silver-Catalyzed N—N Bond Formation Recently, Pérez and coworkers expanded silver-catalyzed nitrene transfer to reactions of tertiary amines, leading to N—N bond formation [119]. While previous synthetic routes to prepare aminimides suffered from poor selectivity, narrow substrate scope, or low yields, silver catalysis demonstrated excellent selectivity for N—N bond formation over potential competing aziridination or C–H insertion pathways using tertiary amines with PhI=NTs as the nitrene source and [Tp*,Br Ag]2 as the catalyst (Table 8.41). The substrate scope showcased the tolerance of various functional groups. Clean conversion of substrates bearing alkene functionalities to their respective aminimides (entries 1–5) indicated the aptitude for this catalytic system to select N—N bond formation over aziridination. In addition, substrates containing available benzylic positions or activated C—H bonds yielded no competing C–H amination. Finally, no reactivity was observed for protected nitrogens, such as carboxamides or carbamates. The scope of this investigation demonstrated moderate to excellent yields (44–95%) for a wide array of motifs.

Table 8.41 Silver-catalyzed intermolecular N—N bond formation. N

R1

R3

R2

Entry

Product N N

1

+

PhI=NTs

[Tp*,BrAg]2 CH2Cl2, 16 h

Yield (%)

N

R1

N Ts R3

R2

Entry

Product

Ts 71

8

N

2

Ts

O 67

N 9

O

t-BuO

91

N 10

t-BuO

N N Ts

Ph

11 N N Ts O 6

Me N N Ts

N N

7

69 Ts

58

12

Me N Me N

Ts

88

92 Ph O

Me N N Ts

CF3

44

O 5

68

N N Ts

O 4

62

Ph N N Ts

O N N Ts

3

84

Me N N Ts

Ph

Me N N

Yield (%)

O

O

13 74

72 N

N Ts

8.13 Summary

In order to determine the ability for this catalytic system to tolerate more highly functionalized precursors, the N—N bond formation was applied to complex molecules to afford the corresponding aminimides of brucine (83% yield) and quinine (73% yield). This study contrasted the excellent selectivity afforded by the silver catalyst to that of a previously reported rhodium-catalyzed nitrene transfer reaction of brucine and cinchonidine, which suffered from competing C—C bond cleavage or promiscuous reactivity with different nitrogens, respectively. The Pérez group investigated the origin of chemoselectivity by analyzing the potential free energy profiles through DFT calculations. Computational studies included modeling the possible N-amidation and aziridination pathways for both singlet and triplet nitrene intermediates. The calculated potential energy surface indicated that generation of Tp*,Br Ag was followed by coordination of the nitrene source PhI=NTs to furnish the expected reactive metal nitrene intermediate. PhI dissociation afforded the closed-shell singlet metal nitrene intermediate, which reacted with the tertiary amine to form the new N—N bond. The transition state corresponding to N—N bond formation was identified, along with the N–N product complex. The presence of minimum energy crossing points (MECPs) on the potential energy surface allowed the transformation to occur through pathways with maximum free energies of 15.8 kcal mol−1 (starting from triplet state) or 17.9 kcal mol−1 (starting from closed-shell singlet), depending on the spin state of the metal nitrene complex intermediate. While the triplet energy surface occurring after the formation of the metal nitrene intermediate is energetically costly, an MECP that closely resembles the triplet intermediate allows the return to an energetically more accessible singlet state. Extrapolation of the aziridination potential energy surface showed that aziridination is kinetically disfavored compared to N—N bond formation, with energy barriers of 6.8 kcal mol−1 from the closed-shell singlet metal nitrene complex or 9.3 kcal mol−1 from the thermodynamically favored triplet metal nitrene complex.

8.13 Summary Since the first reports of silver-catalyzed nitrene transfer in 2003, several new complexes have been described that afford opportunities for selective aminations at specific sites in substrates that contain multiple reactive C=C and C—H groups. The diversity of coordination geometries available to Ag(I) complexes allows the reactivity of transient metal nitrenes to be manipulated through changes to the Ag–ligand ratio, diversification of ligand libraries, control over fluxional behavior, and the coordination geometry of the catalyst. New insights into the mechanisms of Ag nitrene transfer processes have been provided through experimental probes and computational analysis, culminating in the design of ligands to exploit NCIs between catalyst and substrate to drive selectivity. Despite recent progress, there are many challenges that ensure this field will remain an active area of investigation for the foreseeable future. For example, the identification of more reactive nitrene precursors, computational insights into subtle substrate–catalyst interactions that drive reactivity, and

503

504

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

the development of more selective catalysts, especially for intermolecular aminations and asymmetric nitrene transfers [91], will lead to expanded applicability to the synthesis of complex bioactive amines. Lastly, and perhaps most importantly, efforts to understand the factors dictating selectivity in reagentand catalyst-controlled nitrene transfer reactions will inspire efforts to apply these principles to other C–H and X–H functionalization reactions.

8.14 Introduction to Transition Metal-Catalyzed Silylene Transfer The development of new methodologies for the synthesis of compounds containing reactive C—Si bonds has inspired efforts to identify ways to exploit these functional handles in meaningful ways [78, 120–125]. Silylene transfer reactions have received increasing attention for the stereocontrolled introduction of C—Si bonds into readily available precursors [126]. These transformations are roughly divided into two major groups, with the first consisting of silylene transfer to spor sp2 -hybridized carbons, including those found in alkenes, alkynes, allenes, and carbonyl-containing compounds. The second class of reactions involves the formation of a Si—C bond between a silicon-containing precursor and allylic silanes or allylic sulfides. Silylene transfer reactions have been reported with a variety of transition metal catalysts, including Cu [127], Ni [128], In [129], Pd [130], and Zn [131]. Copperbased complexes, including copper halides and triflates, have been particularly popular catalysts for silylene transfer. For example, Woerpel and coworkers have achieved the effective transfer of silylene groups to carbonyl compounds (Scheme 8.15(1)) [127a] and olefins (Scheme 8.15(2)) [127b] using CuX (X = halide) or [Cu(OTf )2 ]PhH as catalysts. Studies showed these transformations to yield silacyclopropanes proceeded with high stereo- and regioselectivity. O R1

+

t-Bu t-Bu Si

H

CuBr2 –78 to 22 °C 54–61%

R2

[Cu(OTf)]2·PhH

+

t-Bu Si t-Bu

OMe

87% dr 70 : 30

t-Bu Si t-Bu O

R2 R1

(2) OMe +

Si t-Bu t-Bu

+ BnO

t-Bu Si t-Bu

[Cu(OTf)]2·PhMe 81%

(1)

t-Bu t-Bu Si BnO

OMe

Si t-Bu t-Bu

(3)

Scheme 8.15 Copper-based silylene transfer reactions to carbonyl compounds and olefins.

8.14 Introduction to Transition Metal-Catalyzed Silylene Transfer

In addition, Cu(OTf )2 PhMe was a competent catalyst for forming allylic silanes from protected allylic alcohols (Scheme 8.15(3)) [127]. Ni-based [128] systems, such as Ni(cod)2 , can transfer the silicon-containing moiety from an allylic silane to an alkyne to form a substituted silacyclopentene (Scheme 8.16). The substrate scope investigated by the Woerpel group indicated that 1-phenyl-1-propyne (Scheme 8.16(1)) and 3-hexyne (2) were competent alkynes for the corresponding π-bond insertion reaction; however, allenes, alkenes, and terminal alkynes lacked the desired reactivity and resulted in degradation of the starting material. Interestingly, alkene isomerization was observed in the case of reaction with 3-hexyne, but the expected product could be isolated with purification under basic conditions. Additionally, the authors observed double insertion when two equivalents of phenylacetylene were employed (Scheme 8.16(3)). Me Me Ph t-Bu t-Bu

Si

H c-C6H13

t-Bu t-Bu Si

Ni(cod)2

Me

C6D6 or toluene 22 °C

c-C6H13

Ph Me

+

t-Bu t-Bu Si

Me (1) Ph

Me c-C6H13

54% (56% isolated) 82 : 18 rr Et Me Et t-Bu

Si

H

Ni(cod)2

Me

C6D6 or toluene 22 °C

c-C6H13

t-Bu c-C6H13

t-Bu t-Bu Si

Et Et

+

Ph t-Bu

Si

H

t-Bu c-C6H13

Ni(cod)2 C6D6 or toluene 22 °C

Me

Ph t-Bu2Si

t-Bu2Si +

Me c-C6H13

(2)

Et

52% isolated

Ph

Me

Et

c-C6H13

10% isolated purification with NEt3 H

t-Bu t-Bu Si

Ph

17% (8% isolated)

Ph

(3)

c-C6H13 46% (19% isolated)

Scheme 8.16 Ni-catalyzed silylene transfer to alkynes.

The Woerpel group also studied the transfer of silylene groups in monosubstituted silacyclopropanes to methyl formate, as well as various ketones and aldehydes. The substrate scope demonstrated excellent control over the regioselectivity of the silylene transfer event, dependent on the specific metal salt employed. In the presence of ZnBr2 , the 1,2-oxasilacyclopentane product is obtained in 94 : 6 regioisomeric ratio (rr) and moderate diastereoselectivity (dr), while switching the metal additive to InBr3 reversed the rr and the dr, yielding the 1,3-oxasilacyclopentane as the major product (Scheme 8.17) [129]. The authors postulate regioselectivity stems from the difference in steric interactions

505

506

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

O

1,2-Regioisomer t-Bu t-Bu Si O

ZnBr2 CH2Cl2

Me i-Pr 94 : 6 rr 87 : 13 dr

1,3-Regioisomer H

Me

t-Bu t-Bu Si

t-Bu t-Bu Si O

InBr3

+

CH2Cl2

Me

i-Pr 4 : 96 rr 18 : 82 dr

i-Pr

Scheme 8.17 Catalyst control over regioselectivity for silylene insertion into carbonyl compounds. 1,2-regioisomer increases steric interactions

H

i-Pr

Si

H H

t-Bu

t-Bu

t-Bu H

i-Pr ZnBr

Br R

O

H

Si

H H

t-Bu H

ZnBr Br

O

R

Reduced steric clashing leads to 1,3-regioisomer

Figure 8.14 Steric interactions in the transition state disfavoring the 1,2-regioisomer with ZnBr2 .

in the transition states leading to the two regioisomers (Figure 8.14). In the case of the transition state leading to the 1,3-regiosomer, the t-Bu groups of the silicon experience reduced steric clashing, making this pathway more favorable. The use of ZnBr2 with di-tert-butylpyridine, H2 O, or menthol reversed the regioselectivity, which was attributed to either increased steric bulk or inhibition of siliconate formation. Pd-based catalysts, including Pd(dba)2 and those supported by triarylphosphine ligands, are known to promote silylene transfer reactions. Suginome and coworkers described a Pd(dba)2 -catalyzed transformation of silylboronic esters [130a] to the corresponding silacyclopentenes (Scheme 8.18). Similar reaction conditions also afforded bis-silylated [130b] indole derivatives in excellent yields. Pd catalysts supported by triphenylphosphine have been successful in promoting silylene transfer to both mono- and disubstituted alkynes to yield five- and three-membered silacycles, respectively [130c,d]. The initial development of silver-catalyzed silylene transfer reactions was pioneered primarily by the Woerpel group [131] in the early 2000s, but this chemistry has continued to expand into new chemical space. Woerpel’s initial forays into silver-catalyzed silylene transfer reactions were conducted to establish milder conditions to prepare silacyclopropane species. Building on previous reports of metal-catalyzed alkene transformations to yield three-membered rings [130c, 132], the Woerpel group investigated a series of different metal salts and found AgOTf to be a competent catalyst for the transfer of a silylene group to alkenes [131]. Additionally, while previous accounts of silacyclopropanation suffered from limited substrate scope, the silver-catalyzed system tolerated steric

Palladium-catalyzed silylboronic ester transfers

Me N

Me N SiMe2H

Si Me2

R2

R2 R

Me

R2

Et2N

Pd(dba)2

Me

Si R

R3

O B

Pd(dba)2

O

R1

PMePh2 toluene, rt or 50 °C

PMePh2 toluene, rt or 50 °C

R3

R2

R1

Si R2

Palladium-catalyzed silylene transfer to alkynes Pd(PPh3)4 t-Bu

t-Bu Si N

R1

H +

R2

50–80°C R3

85–98%

Terminal alkynes

Scheme 8.18 Pd-catalyzed silylene transfer reactions.

PdCl2(PPh3)2

t-Bu R2 t-Bu Si N R1

H

R2 + R1

R3 Disubstituted alkynes

t-Bu t-Bu Si Me

Me

80 to 120 °C 81–86%

t-Bu t-Bu Si R1

R2

508

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

hindrance while displaying excellent functional group compatibility. Since these initial investigations, Woerpel has further expanded the utility of silver-catalyzed silylene transfer reactions, showing the broad application of these methods to the construction of complex molecular architectures with high levels of regio- and stereoselectivity. The remainder of this section will discuss recent developments in this chemistry since 2008; representative classes of reactions to be described are included in Scheme 8.19.

8.15 Silver-Mediated Silylene Transfer Reactions 8.15.1

Olefins

The ability to functionalize C=C bonds to afford new C—Si bonds is appealing, as the resultant silicon-bearing synthons can be employed to build elaborate scaffolds for a diverse array of applications. As a result, numerous silylene transfer reactions to alkenes have been reported in the literature. For example, the Woerpel group utilized a AgO2 CCF3 -catalyzed silylene transfer to the alkene of homoallylic ethers (Scheme 8.20(1)–(3)) to promote a subsequent ring contraction [133] and afford a cyclopentane ring. The intended transformation was successful for an array of (−)-isopulegol derivatives (Scheme 8.20(1)); however, the silacyclopropanation products from smaller (Scheme 8.20(2)) or larger (Scheme 8.20(3)) rings did not undergo ring contraction. The lack of reactivity was hypothesized to be a result of the enhanced ring strain present in the four-membered ring product in the case of Scheme 8.20(2) or, in the case of Scheme 8.20(3), insufficient orbital overlap due to conformational effects. In addition, a monosubstituted protected allylic alcohol gave silacyclopropanation [134] of the alkene (Scheme 8.21), instead of the desired silylene insertion into the C—O bond (see Section 8.15.3). A better understanding of the mechanism of alkene silacyclopropanation was sought to optimize the stereoselectivity of the reaction. To this end, the Salvatella group utilized DFT calculations [135] to explore some key aspects of the silver-catalyzed silacyclopropanations of 11 (Scheme 8.22). The mechanism was proposed to involve a cationic Ag silylene species 17, which differs from the previously described nonionic pathway, demonstrated by computation to involve significantly higher activation barriers. While the stereocontrolled formation of seven-membered rings via alkene silacyclopropanation is challenging, Woerpel and coworkers were able to access seven-membered trans-alkene [136] intermediates by subjecting a series of 1,3-dienes to silver-catalyzed silylene transfer (Table 8.42). The intermediate silacyclopropanes were reacted with a series of aldehydes to first form the trans-alkenes 19a–f, followed by ring contraction to afford 20a–f. Overall, the reaction sequence gave moderate to high yields of the products. The proposed transition state for the addition of the intermediate allylic silacyclopropane (Table 8.42) to an aldehyde is illustrated in Scheme 8.23 and is

Allenes

Alkenes R1

R2

R3

R4

+

t-Bu Si t-Bu

Catalyst

t-Bu R2 +

t-Bu t-Bu t-Bu Si Catalyst O Si O R1 Me

R1

t-Bu t-Bu

Catalyst

t-Bu t-Bu Si

R4

R1

R3 R2

Allylic silanes Si(i-Pr)3 +

Si

O

t-Bu t-Bu

Catalyst

t-Bu t-Bu Si Si(i-Pr)3

R2 Allylic sulfides

Epoxides O

R2

R3

Me

Si

+

R4

R3

Carbonyls O O R1 O

R1

R4

t-Bu t-Bu R1 Si R2

R2

+

Si

R3

t-Bu t-Bu

t-Bu t-Bu O Si 2 R

Catalyst R1

Vinyl, propargylic epoxides O Typical silver catalysts

F3C

OAg

R1

SPh + R2

R3 O F3C S OAg O

Scheme 8.19 General classes of silver-catalyzed silylene transfer reactions.

Si

t-Bu t-Bu

Catalyst

t-Bu t-Bu Si R1

F3C

O S OAg O

Ag3PO4

R2

SPh

510

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions Silver-catalyzed ring contraction

t-Bu

OBn Me +

1 mol% AgO2CCF3

t-Bu t-Bu

Si

t-Bu Si

BnO

H Me

(1)

65%

Me

Me Effect of ring size on silylene transfer to olefin BnO

Me +

Si

1 mol% AgO2CCF3

t -Bu t -Bu

76% by NMR dr 1 : 1

OBn Me

(2)

Too much strain OBn

1 mol% AgO2CCF3

t-Bu Si t-Bu

+

t-Bu Si t-Bu Me

BnO

t-Bu Si t-Bu Me

82% by NMR dr 1 : 1

(3)

Insufficient overlap

Scheme 8.20 Silacyclopropanation of homoallylic ethers. Me +

Si

BnO

Me

0.5 mol% AgO2CCF3

t-Bu t-Bu

BnO

C6D6, rt 92%

Si

t-Bu t-Bu

Scheme 8.21 Silacyclopropanation of a protected vinyl alcohol.

R

t-Bu Si t-Bu

+

11

t-Bu

5 mol% Ag(PPh3)2OTf

t-Bu

Si

CD2Cl2

12

13

+

R

14 R

IR suggests bound and ionic triflate species

15 –OTf–

–OTf– Ag(PPh3)2OTf

Ag(PPh3)2

OTf–

15

(Ph3P)2Ag

OTf–

16

R

13

12

11 18

OTf– –OTf–

14

PPh3 17

– RHC=CH2

16

– PPh3

t-Bu PPh3 Si Ag t-Bu PPh3

Rapid disassociation leads to inability to observe discrete species on NMR time scale t-Bu Si t-Bu

–OTf– AgPPh3 17

OTf–

OTf t-Bu Si Ag PPh3 t-Bu 18

Scheme 8.22 Revised reaction mechanism of silver-catalyzed silacyclopropanation involving cationic Ag silylene species.

Table 8.42 One-pot synthesis of seven-membered ring trans-alkenes through silver-catalyzed silylene transfer to a diene followed by subsequent reaction with an aldehyde.

+

Si t-Bu

R2

R1

1 mol% AgO2CCF3 R

Bu tBu Si R3

H

2

R1

H

O

t

t-Bu

R1

R1 R2 R3

O H t-Bu t-Bu Si

t-Bu

R2

H Si

t-Bu

O 20a-f

Second intermediate (trans-alkenes) are 19a-f Entry

Yield (%)

Product

Entry

Product

H 1

OTIPS

H Si O t-Bu

t-Bu

i-Pr

19a 75 20a 80

4

19b 99 20b 67

5

t-Bu

H

OTIPS

Si O t-Bu

Me 2

t-Bu

H

Ph

t-Bu

H

OTIPS

Si O

H t-Bu Si O t-Bu

CH2CH2Ph

19e 75 20e 71

t-Bu

H 3

19d 84 20d 86

H Me

Si O t-Bu

Yield (%)

H

OTIPS Ph

H 19c 99 20c 99

6

t-Bu

H

t-Bu

Si O

Me Ph

19f 99 20f 51

R3

512

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

H

H

Me

t-Bu

H

OTIPS Si

O H

t-Bu

Ph

OTIPS H Ph

O

Si

H

Me

t-Bu H t-Bu

Scheme 8.23 Proposed transition state for addition of an allylic silacyclopropane to an aldehyde.

reminiscent of the Felkin–Ahn model employed to explain the stereoselectivity observed in aldol reactions. The differences in the rates of reaction of two enantiomers of a chiral aldehyde enable kinetic resolution to be achieved through silylene transfer. The Woerpel group undertook studies to improve the stereoselectivity of silylene transfer to alkenes by exploring the influence of substrate and ligand sterics on the reaction outcome [127b]. The experimental design involved placing a chiral center a suitable distance from the reaction site to minimize its influence on the stereoselectivity of the reaction, yet still allow for differentiation of the diastereomers by 1 H NMR spectral analysis. With the exception of no reactivity when strongly electron-donating ligands were present, these studies showed little to no influence of the ligand identity on dr or reaction rate (Table 8.43). In addition to exploring the impact of the ligand on the efficacy of silvercatalyzed silacyclopropanation reaction, Woerpel and coworkers also investigated the impact of the silver salt identity on the dr of the reaction (Table 8.44). Unfortunately, the identity of the counteranion had no appreciable effect on the dr. Woerpel also showed that the steric bulk was more important in determining the relative rate of the reaction, as compared with the electronics of the Table 8.43 The influence of ligand on silver-catalyzed silacyclopropanation. +

R*

AgO2CCF3

t-Bu Si t-Bu

42–85% dr ~1 : 1

X X

tBu

Si

tBu

tBu

+

Si

R*

tBu

R*

O O P OAg O

iPr O P N O iPr

X = PPh2, P(tolyl)2, OH R N

O

(S)-tBu,

O NH HN

O R=

Ph2P

Ph2P

(R)-iPr

PPh2 Ph2P

N H

PPh2

No reaction

8.15 Silver-Mediated Silylene Transfer Reactions

Table 8.44 Screening of silver salts for the silacyclopropanation reaction. Me

Me

Me + OMe

Si

t-Bu t-Bu

Me

AgX

Me OMe

Me t

Yield (%)

OMe

+

Me

Me

Me

Si Bu

Entry

t

Bu

t

AgX

Si Bu

dr

t

Bu

Entry

AgX

dr

1

AgOTf

71 : 29

73

3

AgO2CCF3

71 : 29

Yield (%) 77

2

AgOTs

71 : 29

96

4

Ag3PO4

67 : 33

87

system. Less sterically encumbered silyl ethers underwent the silacyclopropanation more quickly, presumably due to decreased interactions between the substituents on the C=C bond and those of the metal silylene species. The Woerpel group theorized that the alkene structure was the major driving force for the observed stereoselectivity, with the reaction responding to the bulk of the metal–ligand complex. A reaction mechanism was proposed in which the stereochemistry-determining step involved interaction between the metal, ligand, and silylene; the outcome is influenced by the extent and nature of the alkene substitution. 8.15.2

Carbonyl Compounds

Silylene transfer to carbonyl compounds furnishes α-hydroxy acids, which are ubiquitous in small molecules and key intermediates in the total syntheses of natural products [137]. Based on the demand for such motifs, Woerpel expanded the scope of previously reported methodologies that described the conversion of α-ketoesters to the corresponding α-hydroxy acids via a silylene transfer pathway (Table 8.45) [138]. Substrates investigated in more recent reports show a broader tolerance for substitution at the R1 and R2 positions, including aromatics and protected hydroxyl groups. It is important to note that bulk at the terminal alkene position (entries 7 and 8) or those involving a dearomatization step during these silver-catalyzed silylene transfers to α-ketoesters break down (entry 6). However, for the majority of the successful substrates, the reaction proceeded with moderate yields (62–75%) and excellent dr (≥97 : 3). Woerpel and coworkers also explored silylene transfer to α,β,γ,δ-unsaturated carbonyl compounds for the synthesis of oxasilacyclopentene intermediates (Table 8.46) [139]. Further functionalizations of the oxasilacyclopentenes were achieved through thermally induced diastereoselective addition to benzaldehyde. The reaction tolerated substrates containing a variety of dienoate substitution patterns; however, precursors yielding less nucleophilic allylic silanes resulted in lower yields, presumably due to increased degradation attributed to the longer reaction times (≥2 d). Dienoates bearing only hydrogen atoms at the γ-position were especially prone to low yields. The stereospecificity of these reactions was attributed to a Zimmerman–Traxler-like closed transition state (Scheme 8.24).

513

Table 8.45 Substrate scope for the preparation of α-hydroxy acids from α-ketoesters. O R2 +

O

R1 O

Entry

Product

t-Bu

t-Bu 10 mol% AgOTs Si

Me

Toluene, –25 °C

Me

dr Yield (%)

1

72

4

Product

Product

5

dr

Yield

HO CO2H

62

Ph

Ph

≥97 : 3

71

No reaction

O Me Me

O

TBDMSO HO CO2H

HO CO2H ≥97 : 3

(CH2)2OBn

Yield (%) Entry

7 70

HO CO2H Et

R2

HO CO2H ≥97 : 3

Ph

3

R1

Me

HO CO2H Me

dr

≥97 : 3

Ph

n-Bu

2

HO CO2H

HF/py

R1

HO CO2H ≥97 : 3

Ph

t-Bu Si O O O R2

Entry

HO CO2H

t-Bu

75

6

Ph

8 No reaction

O

No reaction

Ph Me Me

Table 8.46 Stereospecific preparation of trans-dioxasilacyclononenes. R1

O +

OEt

R2

t-Bu Si t-Bu

1 mol% AgO2CCF3

t-Bu t-Bu Si O

Product t-Bu

Yield (%)

Entry

59

4

t-Bu O Si

O

1

O

Ph Me

H

t-Bu O Si O Me O

Ph R2 Product

O

5

H

t-Bu O Si

O

38

t-Bu O Si O Me

Ph H

≥ 2d Me Me H

t-Bu

t-Bu O

67

H

Me

Ph Me

H

R1

Yield (%)

t-Bu O Si O Me O

t-Bu 77

53 ≥ 2d

O

O

Ph

≥ 2d

Ph

3

H

t-Bu Si

R3

t-Bu

t-Bu 2

Ph

R3

R3 Entry

O OEt

R2

t-Bu

O

R1

O

6

t-Bu O Si

O

37

Ph H

≥ 2d

516

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

t-Bu OEt Me Si

Me Ph

H

O

O Si

Me

t-Bu

O

t-Bu OEt

Me

t-Bu

O Ph

H

Scheme 8.24 Closed transition state consistent with experimentally observed stereoselectivity. Table 8.47 Silylene transfer to divinyl ketones to yield unsaturated heterocycles. t-Bu R1

O R2

Si

+

t-Bu t-Bu

t-Bu

10 mol% AgO2CCF3

Si O

tol-d8, –22 °C

R1

R2

t-Bu t-Bu Si O + R1

a

R2

b

Entry

R1

R2

a:b

1 2 3 4

i-Pr Me Me Me

Me Me i-Pr Ph

15 : 85 25 : 75 37 : 63 26 : 74

100 100 88 97

5

Ph

Me

27 : 73

100

NMR Yield (%)

The Woerpel group expanded their silylene transfer chemistry to engage divinyl ketones as substrates to produce 2-silyloxy-1,3-dienes in a regio- and stereoselective manner (Table 8.47) [140]. The observed silylene transfer was biased toward the β-substituted position, with the regioselectivity increasing as the steric bulk at the α-substituted site increased. Based on this experimental trend, the authors hypothesized that the regioselectivity arises from (i) steric congestion around the oxygen lone pair and (ii) the unfavorable alkene geometry caused by α-substitution, which results in a significant energy barrier to effective formation of the silacarbonyl ylide intermediate. The ability of these products to serve as dienes for Diels–Alder reactions was demonstrated via further transformations to functionalized cyclohexene rings (Scheme 8.25); chiral auxiliaries produced chiral cyclohexenes in a stereoselective fashion. O R1

R2 + Si

t-Bu t-Bu

10 mol% AgO2CCF3 THF

t-Bu t-Bu Si O R1

+ R2

t-Bu t-Bu Si O R1

EtO2C R2

CO2Et

100 °C, toluene, 3 d

R1

t-Bu t-Bu O Si R2 H CO2Et CO2Et

Scheme 8.25 One-pot preparation of Diels–Alder cycloadducts.

Finally, Woerpel and coworkers explored the insertion of four-membered silaoxetane into aldehydes to produce seven-membered rings bearing allene functionality (Table 8.48) [141]. This work was carried out in conjunction with studies on silylene transfer into the C—O bonds of propargylic epoxides (see Section 8.15.3) to showcase further applications of this chemistry. While allenes

Table 8.48 Synthesis of various seven-membered rings bearing allene functionalities. t-Bu t-Bu Si O Me

O Me

t-Bu Si t-Bu

+

AgOTs

R

H13C6

i-Pr

F3C

R

53% t-Bu t-Bu O Si O C6H13

t-Bu t-Bu O Si O

MeO

Me C6H13

Me

C6H13

t-Bu t-Bu O Si O Me

t-Bu t-Bu O Si O

H

H13C6

t-Bu t-Bu O Si O C6H13

O

Me

21% C6H13 t-Bu t-Bu O Si O

Me

54% C6H13

Me

60%

Me 49%

518

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

bearing alkyl and aromatic groups could be prepared, the scope of this chemistry was limited due to difficulties encountered with sterically congested substrates. Additionally, difficulties with purification contributed to low to moderate yields and diastereoselectivities for certain precursors (Tables 8.48 and 8.49). 8.15.3

C—O Bonds

Silver-catalyzed silylene transfers into C—O bonds are also prevalent in the literature. One such example, reported by Woerpel and coworkers, involves the silver-catalyzed insertion of silylenes into vinyl epoxides [142] to prepare allylic silanes as key intermediates (Table 8.50). These compounds were subjected to a second silylene transfer reaction with aldehydes or ketones to afford optically active trans-dioxasilacyclooctenes. While isolated yields were not reported for the vinyl epoxide intermediate species, the authors commented on the ability to observe the silaoxetanes via 1 H and 29 Si NMR spectroscopy. In addition to the studies described in Table 8.50, Woerpel and coworkers was able to show successful transfer of silylene groups to homoallylic ethers, yielding allylic silanes via ring contraction in moderate to good yields (Table 8.51) [133]. In addition, 1 H and 13 C NMR spectroscopy indicated this transformation produced the cyclopentane products as predominantly one stereoisomer. A single-crystal X-ray structure was used to determine the relative stereochemistry of the allylsilane products; based on this assignment, Woerpel proposed a mechanism involving the initial formation of a trans-fused ring system, followed by ring opening to a silacyclopropylcarbinyl cation and rearrangement to generate the final product (Scheme 8.26). The Woerpel group expanded their ability to form allylic silanes through silylene insertions into C—O bonds of benzyl-protected allylic alcohols [134]. The formation of disilane products was observed when the protected alcohol substrate lacked substitution at the allylic position or when no alkene was present (Scheme 8.27). However, additional substitution at the α-position afforded the allylic silane product resulting from one insertion event. Isolation of the monosilated compound and subsequent subjection to the reaction conditions led to no additional silylene transfer, suggesting reactions that yield disilanes might proceed through a mechanism where both insertion events occur simultaneously. The Woerpel group further developed silylene transfer to epoxides to furnish strained organosilacyclic compounds [143]. Their studies showed that AgO2 COCF3 catalyzed the transformation of a spiroepoxide to the corresponding strained organosilacyclic compound (Scheme 8.28). 29 Si NMR spectroscopy was particularly useful in confirming the formation of the oxasilabutane, as the downfield shift of the Si resonance to 38 ppm was reminiscent of a strained Lewis acidic Si atom. The vinyl epoxides investigated typically afforded a mixture of silaoxetane and oxasilacyclohexene products in excellent yields (91–97%). In instances involving diastereomeric epoxides, the stereochemical configuration at the allylic C—O bond (Table 8.52) was maintained. In order to explain the mixture of products observed, the authors proposed that different steric clashing is observed in the cis and trans conformations of the vinyl epoxides studied (Scheme 8.29).

Table 8.49 Preparation of diastereomeric allene derivatives. R1 O R2

AgOTs

3

R

Si

TBSO

t-Bu TBSO t-Bu

t-Bu t-Bu Si O R2 R1 R3

O Ph

H Ph

t-Bu t-Bu R3 O Si O R2 Ph + 1 R (CH2)2OTBS

t-Bu t-Bu R2 O Si O R3 (CH2)2OTBS

Entry

R1

R2

R3

Silaoxetane dr

Product dr

1

H

H

Me

70 : 30

73 : 27

32

2

Me

H

H

71 : 29

71 : 29

49

3

H

Me

H

33 : 67

37 : 63

46

R1

Yield (%)

520

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

Table 8.50 Silver-catalyzed silylene transfer into vinyl epoxides. 1

R

3

R

O

+

Si

t-Bu t-Bu

t-Bu t-Bu 2 mol% R1 O Si R3 AgOTs

R2

R1

O R4

O H

t-Bu

R2

Entry

Product

Yield (%)

H

O

t-Bu Si t-Bu

4

t-Bu

H O

Si

t-Bu

71

Ph H H

H

t-Bu

CO2-i-Pr

71

H H

H

H

OBn O

Si

t-Bu

Me

H H Me

t-Bu

O

Si

Me

O

O 3

H H

Yield (%)

O

5 H

Product H

H H

H

O

Si

t-Bu

R2

H

H t-Bu

Entry

72

i-Pr

O

2

t-Bu

R4

O

Si

H

O

1

R3

CO2 i-Pr

OBn

81

69

Me

H H

t-Bu OBn

Me

Table 8.51 Silver-catalyzed preparation of allylic silanes. OR Me +

Si

t-Bu t-Bu

t-Bu

1 mol% AgO2CCF3

t-Bu Si

RO

H

Me

50 °C, 1 h

Me Me t-Bu t-Bu Si BnO

Me

H

t-Bu t-Bu Si MeO

Me

Me

65%

Bn O Me

t-Bu Si

H

Me

t-Bu t-Bu Si SiMe2 t-BuO

Me

71%

t-Bu OBn t-Bu Si

t-Bu Me

H

Me

H

Me

82%

t-Bu t-Bu Si BnO

Me H

H Me Trans-fused ring

Silacyclopropylcarbinyl cation

Scheme 8.26 Proposed mechanism for allylsilane formation.

Me Ylide

8.15 Silver-Mediated Silylene Transfer Reactions

Allylic alcohols R t-Bu Me AgO2CCF3 t-Bu Si R = H BnO Me BnO Si t-Bu t-Bu

Me

+

Me

t-Bu AgO2CCF3 t-Bu R = Me

Si

Me

Me

t-Bu

Me

Si BnO t-Bu

Saturated alcohols +

Si

BnO

t-Bu t-Bu

AgO2CCF

t-Bu t-Bu Si Ph Si O t-Bu t-Bu

t-Bu t-Bu H Si BnO Si t-Bu t-Bu

+

Scheme 8.27 Substrate dependence in the mono- and disilation of benzyl-protected alcohols.

O

t-Bu Si t-Bu

+

t-Bu t-Bu O Si

AgO2COCF3

t-Bu t-Bu Me Si

MeLi

OH 29

Si resonance at 38 ppm

Confirms silylene insertion

Scheme 8.28 Silver-catalyzed formation of strained organosilacyclic intermediates.

Table 8.52 Effective silylene transfer into vinyl epoxides. t-Bu

t-Bu O

R2

+

Si

R1

t-Bu t-Bu O Si Me

t-Bu t-Bu

AgOTs (2 mol%) 91–97%

O Si R1

R2

a

b

a:b 80 : 20

O s-trans pathway R1 t-Bu t-Bu O Si

R2

Only [1,2] observed

O R2

R2

46 : 54

a:b

a:b >95 : 5

21

O R1

H

s-cis pathway

R1

t-Bu t-Bu AgLn Si

R1

R2

t-Bu t-Bu O Si Me PhH2CH2C

PhH2CH2C a:b 68 : 32

O

+

t-Bu Si

R1

t-Bu t-Bu O Si Me H

t-Bu t-Bu O Si H

t-Bu

R2

22 OTs

t-Bu t-Bu AgLn Si O R2 R1

OTs

t-Bu t-Bu O Si R2 R1

R1 +

O

t-Bu Si t-Bu

R2

Increasing sterics at R1 disfavors [3,4]

Scheme 8.29 Various pathways for silylene transfer to vinyl epoxides.

521

522

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

8.15.4

Allenes

Allenes are convenient three-carbon synthons that are readily manipulated to afford complex scaffolds; the potential for axial-to-point chirality transfer is an advantage of these precursors. Previous reports of allene silacyclopropanations via photochemical methods [144] gave no control over the stereo- and regioselectivity of the reaction. As such, Woerpel and coworkers sought a transition metal-catalyzed alternative [145] to afford these silacyclopropanes in a selective fashion. Reactions of allenes with a silylene transfer reagent catalyzed by Ag3 PO4 and AgO2 CCF3 gave the alkylidenesilacyclopropanes in moderate to excellent yields (70–91%; Table 8.53). Allenes of all substitution patterns were tolerated in the reaction, including tri- and tetrasubstituted precursors. Effective transfer of axial-to-point chirality was also observed, yielding enantioenriched products from the precursor allenes. Excellent regioselectivity (≥93 : 7) was observed for substrates with increased steric bulk at one terminus of the allene, with the exception of slightly lower rr (79 : 21) for the substrate bearing a phenyl substituent (entry 8). These strained alkylidenesilacyclopropanes could also be further reacted with carbonyl-containing compounds to afford oxasilacyclopentanes or furnish 1,2,4-triol products from epoxidation of the remaining alkene, followed by epoxide ring opening by water. Finally, Woerpel and coworkers showed that Ag3 PO4 was capable of catalyzing silylene transfer to an allene ether in a moderate isolated yield of 61% (Scheme 8.30) [128a]. 8.15.5

Allylic Silanes

As previously described in Section 8.15.1, the preparation of vinyl silanes can be achieved through silylene transfer to 1,3-dienes. Subsequent silver-catalyzed silylene transfer reaction to the allylic silane [146] forms the corresponding silacyclopropane product. In 2010, the Woerpel group demonstrated the ability to further transform allylic silanes by insertion into benzaldehyde. After observing 1,2-migration of allylic sulfides with AgO2 CCF3 (see Section 8.15.6), allylic silanes were subjected to similar reaction conditions to probe the scope of this reactivity. Instead of the anticipated formal migration, silacyclopropanation was observed. Further reaction with benzaldehyde afforded a mixture of compounds (Scheme 8.31), including products formed from hydrogen atom transfer and reaction with two equivalents of benzaldehyde. 8.15.6

Allylic Sulfides

In experiments similar to those described for allylic silanes in the previous section, Woerpel and coworkers attempted to form the analogous silacyclopropanes from silver-catalyzed silylene insertion into allylic sulfides [146]. Instead of the anticipated reactivity, functionalized silacyclobutanes were obtained as the major products. The substrate scope accommodated alkyl substitutions, including methyl and isopropyl groups, albeit in some low to moderate yields (Table 8.54).

Table 8.53 Silylene transfer to allenes to afford alkylidenesilacyclopropanes. R4 R1

•

3

R

+

Si

t-Bu t-Bu

5 mol% Ag3PO4 or

t-Bu

1 mol% AgO2CCF3

R1

t-Bu Si

R3 R2

R2 Entry

Yield (%)

Product t-Bu

t-Bu

Entry

Product

1

81 n-Pr

Si 5

H

n-Bu i-Pr t-Bu

t-Bu Si

Si Me

Me Me

91

6

H

Me

Me

t-Bu

t-Bu

Si

Si

3

H

77

7

Me

n-C6H13

85

SiMe3 t-Bu

t-Bu

t-Bu

t-Bu

Si

Si 4

70

c-C6H11

t-Bu

t-Bu

90

n-Bu

t-Bu

t-Bu 2

Yield (%)

t-Bu

t-Bu

OSi(i-Pr)3

Si

R4

H CH2OSi(t-Bu)Me2

77

8

Ph

H CH2OSi(i-Pr)3

84

524

8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

H

t-Bu t-Bu Si

Ag3PO4 +

H

H

t-Bu Si t-Bu

C6D6 or toluene 22°C OMe

OMe

Scheme 8.30 Silylene transfer into allene ether to afford corresponding silacyclopropanation. Hydrogen transfer

Ph

O

Si(i-Pr)3 5 mol% AgO2CCF3

+

t-Bu O t-Bu Si

22 °C

t-Bu t-Bu Si

Ph Si(i-Pr)3

t-Bu Si t-Bu

t-Bu t-Bu Si O

H

Si(i-Pr)3

10 mol% CuI 22 °C

Ph Si(i-Pr)3 t-Bu t-Bu Si O O

Silylene transfer with 2 equiv. PhCHO

Ph

Ph

Scheme 8.31 Silylene transfer to an allylic silane. Table 8.54 Silylene transfer to substituted allylic sulfides. R1

SPh

t-Bu Si t-Bu

+

R2 Entry

1

2

Product

dr

t-Bu t-Bu Si

i-Pr

H

SPh

t-Bu t-Bu Si H

100 : 0

Yield (%)

17

5 mol% AgO2CCF3 22 °C Entry

3

Me

SPh

41

4

R2

SPh

R1 Product

t-Bu t-Bu Si Me

92 : 8

t-Bu t-Bu Si

t-Bu t-Bu Si Me

dr

Yield (%)

Me 66 : 34

19

86 : 14

55

SPh H

SPh

To better understand the mechanistic subtleties that led to this unexpected reactivity, Woerpel and coworkers carried out a crossover experiment utilizing two different allylic sulfides (Scheme 8.32) and found only trace amounts of crossover products. This suggests the mechanism occurs in a stepwise fashion, with a strong preference for intramolecular reactivity. A pathway involving an episulfonium ion as a potential reactive intermediate was proposed; simultaneous ring opening by the silver species followed by ring closure forms the cyclobutane product (Scheme 8.33).

References

SPh

t-Bu t-Bu Si

t-Bu Si t-Bu

Me

Me

SPh

Trace crossover products t-Bu t-Bu Si

AgO2OCCF3

+

(2 mol%) S(p-Tol) 22 °C

Et

SPh t-Bu t-Bu Si

Et

Et

S(p-Tol)

t-Bu t-Bu Si

Me

S(p-Tol)

Scheme 8.32 Intermolecular competition experiments. Episulfonium ion intermediate Ph S

Ring opening

t-Bu Si t-Bu

Ring closure

Me [Ag]

Scheme 8.33 Proposed reaction mechanism involving concerted ring opening/closure.

8.16 Summary Since the initial reports of silver-based catalysts for silylene transfer, the ability to control both the regio- and stereoselectivity of C—Si and Si—O bond formations has been improved and tailored for diverse applications. Depending on the specific class of substrate employed, silylene transfer reactions lead to an array of interesting scaffolds, often with opportunities for further functionalization available through a second silylene transfer reaction. Mechanistic insights reported in many of these recently disclosed methods provide useful snapshots of reactivity that can be harnessed for future developments of silylene transfer reactions.

References 1 2 3 4 5 6 7 8 9 10

Kirmse, W. (2002). Eur. J. Org. Chem. 2193–2256. Lipshutz, B.H. and Yamamoto, Y. (2008). Chem. Rev. 108: 2793–2795. Newman, M.S. and Beal, P.F. (1950). J. Am. Chem. Soc. 72: 5163–5165. Julian, R.R., May, J.A., Stoltz, B.M., and Beauchamp, J.L. (2003). J. Am. Chem. Soc. 125: 4478–4486. Ma, B., Chen, F., Xu, X. et al. (2014). Adv. Synth. Catal. 356: 416–420. Sudrik, S.G., Maddanimath, T., Chaki, N.K. et al. (2003). Org. Lett. 5: 2355–2358. Doyle, M.P. and Protopopova, M.N. (1998). Tetrahedron 54: 7919–7946. Davies, H.M.L. (1993). Tetrahedron 49: 5203–5223. Ye, Y. and McKervey, A. (1994). Chem. Rev. 94: 1091–1160. Doyle, M.P. (1986). Chem. Rev. 86: 919–939.

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8 Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions

11 Doyle, M.P., Bimndes, B.D., Kazala, A.M. et al. (1990). Tetrahedron Lett. 31:

6613–6616. 12 Fritschi, H., Leutenegger, U., and Pfaltz, A. (1986). Angew. Chem. 25:

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533

9 Asymmetric Silver-Catalyzed Reactions Hélène Pellissier Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France

9.1 Introduction The enantioselective production of compounds is a central theme in current research. The broad utility of synthetic chiral molecules as single-enantiomer pharmaceuticals has made asymmetric catalysis a prominent area of investigation [1]. Especially, the use of transition metals has become in the last few decades a powerful tool to perform reactions in a highly enantioselective fashion [2]. Ag(I) is known to interact not only with π-donors, such as alkenes, alkynes, allenes, and aromatics, but also with N-donors, such as (thio)ethers, amines, and phosphines, making strong and stable complexes more easily than other metals related to the fact that Ag(+) is among the most soft acids [3]. Furthermore, the use of Ag(I) is economic relative to other expensive transition metals such as gold and platinum. However, among coinage metals including copper, silver, and gold, silver has been the most neglected in the area of organic chemistry for a long time, probably because of its moderate Lewis acidity. Indeed, it is only in 1990s that silver-catalyzed asymmetric reactions have emerged as important synthetic methods with the early reports of Ito and coworkers [4]. These have led to the development of an increasing number of novel enantioselective silver-catalyzed transformations of many types. Especially in the last decade, chiral silver complexes have been demonstrated to be highly efficient special mild Lewis acids, becoming catalysts of first choice for many types of asymmetric reactions generally performed under mild reaction conditions and through experimentally simple procedures. For example, the first enantioselective silver-catalyzed domino reactions including multicatalyzed ones have been only recently developed in addition to novel asymmetric silver-catalyzed Mannich reactions, cycloadditions, Michael additions, aldol-type reactions, alkynylations, allylations, cyclizations of allenes, etc. The goal of this chapter is to collect the major developments in enantioselective silver-catalyzed transformations published since 2008, since this field was most recently reviewed by Yamamoto and coworker in that year [5]. It must be noted that several specific reviews have also been dedicated to special silver-catalyzed reactions not especially asymmetric

Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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9 Asymmetric Silver-Catalyzed Reactions

including only few references dealing with chirality [6]. Moreover, a book was published by Harmata in 2010, dealing with the general use of silver in organic chemistry, which covered the literature up to 2008 [7]. The chapter is divided into 10 sections, dealing successively with enantioselective silver-catalyzed Mannich reactions, enantioselective silver-catalyzed 1,3-dipolar cycloadditions, enantioselective silver-catalyzed domino and tandem reactions, enantioselective silver-catalyzed Michael reactions, enantioselective silver-catalyzed aldol-type reactions, enantioselective silver-catalyzed alkynylations, enantioselective silver-catalyzed allylations, enantioselective silver-catalyzed cyclizations of allenes, enantioselective silver-catalyzed aminations, and miscellaneous enantioselective silver-catalyzed reactions.

9.2 Silver-Catalyzed Mannich Reactions 9.2.1 9.2.1.1

Vinylogous Mukaiyama–Mannich Reactions With Hoveyda–Snapper Catalysts

The Mannich reaction [8], occurring between a Schiff base and a nucleophile, constitutes one of the most powerful reactions for the construction of nitrogen-containing products [9]. Over the past two decades, the catalytic asymmetric Mannich reaction [10], which allows biologically important chiral α-amino carbonyl compounds and derivatives to be easily prepared [11], has been widely investigated on the basis of using either chiral organometallic catalysts or organocatalysts [12]. In 1998, Lectka and coworkers demonstrated for the first time that a combination of a 2,2′ -bis(diphenylphosphino)-1,1′ -binaphthyl (BINAP)-derived ligand with AgSbF6 behaved as a promising asymmetric catalyst system (10 mol%) in the Mukaiyama–Mannich reaction of α-imino esters with enol silanes, providing enantioselectivities of 90% to >99% ee [13]. Later, Hoveyda and Snapper found that another type of chiral catalyst generated in situ from an amino acid-derived phosphine and AgOAc employed at only 1–5 mol% of catalyst loading, earlier introduced by these authors to successfully promote the asymmetric cycloaddition reaction of Danishefsky’s diene with arylimines [14], was also able to promote asymmetric Mannich reactions of silyl enol ethers with aldimines with enantioselectivities of 89–98% ee in combination with moderate to excellent yields (51–98%) [15]. The asymmetric vinylogous Mannich reaction, as a variant of the Mannich reaction, has attracted increasing attention owing to its ability to directly deliver complicated and highly functionalized chiral δ-amino compounds. In 2006, Hoveyda and coworkers reported excellent results (up to 98% ee) in asymmetric vinylogous Mannich reactions of aryl aldimines with siloxyfurans by using only 1 mol% of related phosphine ligands bearing different amino acid residues in combination with AgOAc [16]. On the other hand, enantioselective vinylogous Mannich reactions of aldimines derived from alkyl-substituted aldehydes are less developed because they are generally achieved with diminished efficiency and diastereoselectivity than those of the more common aryl-substituted aldimines. In 2008, the same authors described a novel protocol for efficient

9.2 Silver-Catalyzed Mannich Reactions

three-component silver-catalyzed asymmetric vinylogous Mannich reactions of the more demanding alkyl-substituted aldimines, generated in situ from the corresponding aldehydes and o-thiomethyl-p-anisidine, with trimethylsiloxyfuran (R2 = H) [17]. This process was catalyzed by 5 mol% of a combination of AgOAc and a chiral tert-leucine-derived phosphine ligand in tetrahydrofuran (THF) as solvent at −78 ∘ C. As shown in Scheme 9.1, a range of aliphatic aldehydes led regioselectively to the corresponding unsaturated lactones as almost single anti-diastereomers (>96% de) with uniformly excellent enantioselectivity of >98% ee combined with moderate to high yields (50–90%). The lowest yield of 50% was obtained in the reaction of a t-Bu-substituted aldehyde (R1 = t-Bu). The process could also be applied for the first time to 5-methyl-substituted siloxyfuran (R2 = Me) that provided, by reaction with cyclohexylcarboxaldehyde (R1 = Cy) and o-thiomethyl-p-anisidine, the corresponding product as a single stereoisomer (>96% de, >98% ee) in 88% yield (Scheme 9.1). It must be noted that these results, allowing single stereoisomers to be obtained, could also be situated in Section 9.4 dealing with silver-catalyzed enantioselective domino reactions. t-Bu MeO

N

SMe

PPh2 NH2

R1

+ H

O

(5 mol%)

R2

O

H N

O

R1 = Cy, R2 = H: 90% R1 = i-Pr, R2 = H: 89% R1 = c-Pr, R2 = H: 88% R1 = i-Bu, R2 = H: 92%

OTMS

AgOAc (5 mol%) i-PrOH (1.1 equiv.) MgSO4 (2 equiv.) THF, –78 °C

R1 = t-Bu, R2 = H: 50% R1 = BnCH2, R2 = H: 79% R1 = n-Hex, R2 = H: 75% R1 = Cy, R2 = Me: 88%

MeS

OMe

OMe HN

R2

R1 O O >96% de >98% ee

Scheme 9.1 Three-component vinylogous Mukaiyama–Mannich reaction of aliphatic aldehydes, o-thiomethyl-p-anisidine and trimethylsiloxyfurans.

The efficiency and high degrees of enantiodifferentiation in the enantioselective vinylogous Mannich reactions described in Scheme 9.1 were not limited to alkyl-substituted aldimines. Indeed, these authors showed that the same reaction conditions could be applied to the reaction between phenyl or alkynyl aldimines derived from o-thiomethyl-p-anisidine or o-anisidine with trimethylsiloxyfuran, thus providing the corresponding Mannich products in good to quantitative yields (70% to >98%) and remarkable diastereo- and enantioselectivities of up to >98% de and >98% ee, respectively (Scheme 9.2) [17]. Generally, o-thiomethyl-p-anisidine-derived imines were more efficient than o-anisidine-derived imines (>98% yield vs. 89% yield for reactions with phenyl-substituted aldimines and 86% vs. 70% yield for reactions with

535

536

9 Asymmetric Silver-Catalyzed Reactions

t-Bu N

O PPh2 (5 mol%) AgOAc (5 mol%)

Y

X

+

N

H N

O

OTMS

Ph

X

OMe

Y

HN

MgSO4 (2 equiv.) i-PrOH (1.1 equiv.) THF, –78 °C

Ph O O

X = SMe, Y = OMe: >98%, >98% de, >98% ee X = OMe, Y = H: 86%, >98% de, 96% ee X X N

Y Same conditions

+ O

HN

OTMS Ph

Ph

Y

O O

X = SMe, Y = OMe: 89%, >98% de, >98% ee X = OMe, Y = H: 70%, >98% de, 95% ee

Scheme 9.2 Vinylogous Mukaiyama–Mannich reactions of phenyl/alkynyl aldimines derived from o-thiomethyl-p-anisidine/o-anisidine and trimethylsiloxyfuran.

alkynyl-substituted aldimines, respectively). Whereas reactions in all cases proceeded with excellent diastereoselectivity (>98% de), processes involving substrates bearing an S-containing N-aryl group were found to be more enantioselective than those involving substrates with an O-containing N-aryl group. Notably, in all cases, no trace of products arisen from the α-addition was detected. Ketimines are less reactive than aldimines, and consequently, they have been much less investigated in asymmetric Mannich reactions. In this context, the same authors have developed silver-catalyzed diastereo- and enantioselective vinylogous Mannich reactions of trimethylsiloxyfuran with α-ketimine esters [18]. As shown in Scheme 9.3, this was achieved by employing closely related reaction conditions, which regioselectively led to the formation of a range of unsaturated chiral lactones arisen from the reaction of the corresponding N-aryl aromatic α-ketimine esters with trimethylsiloxyfuran. These products bearing a N-substituted all-carbon quaternary stereogenic center were obtained as anti-diastereomers in 78% to >96% de, good to excellent yields of 72–95%, and high enantioselectivities of 87–94% ee, except when an ortho-bromo-substituted ketimine ester was employed as substrate, which led to the corresponding product in only 32% ee. The para-nitro unit in ketimine substrates was shown to be crucial to achieve high efficiency as well as diastereo- and enantioselectivities, while the latter were enhanced by the presence of a methoxy group ortho to the N-aryl group. To explain the stereoselectivity of the reaction, the authors have

t-Bu N MeO

NO2

N

PPh2

O

OTMS

O

OMe O

NO2

MeO

OMe

(10 mol%)

+

Ar

NO2

H N

MeO2C

+

NH

Ar

AgOAc (11 mol%) THF, –78 °C Then AcOH workup

MeO MeO2C

NH

Ar O

anti-Product major

O O

syn-Product minor

O

Proposed transition state: t-Bu N H Me Ph O + P Ag O

N

Amide-directed (endo) enol silane approach

Ar′ NO2

Ph –

H

N

OAc

SiMe3

Ar CO2Me

O

O

anti-Product major

Ar = Ph: 88%, 90% de, 92% ee (anti) Ar = 3-MeOC6H4: 95%, 90% de, 93% ee (anti) Ar = 3-ClC6H4: 72%, 84% de, 87% ee (anti) Ar = 4-BrC6H4: 80%, 90% de, 92% ee (anti) Ar = 4-IC6H4: 81%, >96% de, 93% ee (anti) Ar = 4-t-BuC6H4: 77%, 78% de, 90% ee (anti) Ar = 4-F3CC6H4: 87%, 90% de, 94% ee (anti) Ar = 2-Naph: 81%, >96% de, 91% ee (anti) Ar = 1-BrC6H4: 87%, >96% de, 32% ee (anti)

A

Scheme 9.3 Vinylogous Mukaiyama–Mannich reaction of α-ketimine esters and trimethylsiloxyfuran.

538

9 Asymmetric Silver-Catalyzed Reactions

proposed the endo-transition state A in which the substrate bound in a manner to minimize interaction with the bulky t-butyl amino acid substituent and the ketimine’s sterically hindered aryl substituent was situated trans to the Si-based nucleophile. Another noteworthy feature was the Lewis base activation of the siloxyfuran by the amide terminus, which led to the selective formation of the anti-products (Scheme 9.3). In addition, the same authors reported the synthesis of an iso-leucine-derived phosphine ligand (Scheme 9.4) to be combined with AgOAc and applied to the asymmetric vinylogous Mannich reactions of aryl aldimines with 5-methyl-2-trimethylsiloxyfuran [19]. As shown in Scheme 9.4, the process led to the formation of the corresponding chiral products, bearing an O-substituted quaternary carbon stereogenic center, as the major regioisomers (γ/α = 85 : 15) arising from a regioselective addition. The α-addition side products could be easily removed through oxidation. The scope of the process was extended to variously (substituted) aryl aldimines, providing the corresponding products in moderate yields (38–64%), albeit with general and remarkable diastereoand enantioselectivities of >96% de and >98% ee, respectively. These reaction conditions were applied to alkynyl aldimines, which afforded by reaction with 5-methyl-substituted trimethylsiloxyfuran the corresponding products in moderate yields (30–65%), high diastereoselectivities of 90% to >96% de, and moderate to high enantioselectivities of 75–94% ee (Scheme 9.4). It must be Et H N

N MeS

PPh2

OMe HN

(10 mol%)

+

N

MeS O

OTMS

O

Ar

Ar = Ph: 64% Ar = 1-BrC6H4: 38%

Ar

AgOAc (10 mol%) i-PrOH (2.2 equiv.) THF, –78 °C

O O >96% de, >98% ee γ/α = 85 : 15

Ar = 4-O2NC6H4: 39% Ar = 4-MeOC6H4: 56% MeS

MeS N

Same conditions

+ O

HN

OTMS R

R R = Ph: 58%, >96% de, 94% ee R = 4-MeOC6H4: 59%, >96% de, 94% ee R = 2-thienyl: 54%, >96% de, 94% ee

O O γ/α = 98 : 2

R = n-Pent: 30%, 90% de, 82% ee R = (i-Pr)3Si: 65%, >96% de, 75% ee

Scheme 9.4 Vinylogous Mukaiyama–Mannich reactions of aryl/alkynyl aldimines and 5-methyl-substituted trimethylsiloxyfuran.

9.2 Silver-Catalyzed Mannich Reactions

noted that the regioselectivity of the reaction of alkynyl aldimines was higher (γ/α = 98 : 2) than that of aryl aldimines (γ/α = 85 : 15). In addition, this catalyst system was also used at a 5 mol% catalyst loading to promote enantioselective vinylogous Mannich reactions involving siloxypyrroles as another type of nucleophilic partner [19]. As shown in Scheme 9.5, the silver-catalyzed Mannich reaction of a N-Boc-2-(trimethylsiloxy)pyrrole with a range of aryl and heteroaryl aldimines provided the corresponding chiral α,β-unsaturated δ-amino-γ-butyrolactams with an exceptional regioselectivity (γ-addition/α-addition = 98 : 2), moderate to excellent yields (62–97%), and almost complete anti-diastereoselectivity (>96% de) combined with good to excellent enantioselectivities of 83–98% ee. Additions to imines bearing a bromo-substituted aryl unit, an electron-withdrawing, or an electron-donating unit also proceeded with high efficiency and selectivity. The lowest yield of 62% was obtained in the case of a thienyl-containing product, which could be attributed to competitive chelation of the Ag-based complex with the S atom of the thienyl group. The scope of this methodology could be extended to alkyne-substituted aldimines, leading to the corresponding chiral alkynyl-substituted diamine products in 93–98% yields with exceptional γ-regioselectivity (γ-addition/α-addition = 98 : 2), excellent diastereoselectivity

Et H N

N MeS

OMe

PPh2 N

Ar

OTMS

Boc

Ar = Ph: 96%, 95% ee Ar = 1-BrC6H4: 87%, 97% ee Ar = 4-BrC6H4: 81%, 94% ee Ar = 4-O2NC6H4: 97%, 83% ee MeS N

OMe

OMe

HN

(5 mol%)

+

N

MeS

O

Ar

AgOAc (5 mol%) MeOH (1.1 equiv.) THF, –30 °C

BocN O >96% de γ/α = 98 : 2

Ar = 4-MeOC6H4: 96%, 97% ee Ar = 2-furyl: 92%, 94% ee Ar = 2-thienyl: 62%, 98% ee MeS

OMe

OMe Same conditions

+ N Boc

OTMS R

R R = Ph: 93%, 93% ee R = p-MeOC6H4: 98%, 86% ee

HN

R = Cy: 96%, 92% ee R = (i-Pr)3Si: 95%, 95% ee

BocN O >96% de γ/α = 98 : 2

Scheme 9.5 Vinylogous Mukaiyama–Mannich reactions of aryl/alkynyl aldimines and N-Boc-2-(trimethylsiloxy)pyrrole.

539

540

9 Asymmetric Silver-Catalyzed Reactions

(>96% de), and good to high enantioselectivities of 86–95% ee. As shown in Scheme 9.5, the acetylene group could bear an aryl, an alkyl, or a silyl substituent. Hoveyda–Snapper silver catalyst derived from a tert-leucine-bearing phosphine (Scheme 9.6) was previously used by Curti et al. to develop this type of reactions (Scheme 9.6) [20]. Indeed, the asymmetric vinylogous Mannich reaction of various aromatic, heteroaromatic, and aliphatic N-aryl aldimines with N-Boc-2-(trimethylsiloxy)pyrrole afforded the corresponding chiral α,β-unsaturated δ-amino-γ-butyrolactams with complete γ-regioselectivity (γ-addition/α-addition >99 : 1), moderate to quantitative yields (36–99%), moderate to excellent anti-diastereoselectivities of 74–98% de, and moderate enantioselectivities of 42–80% ee.

t-Bu N PPh2

OMe +

N R

N Boc

H N

O

OMe OMe NH

(10 mol%)

OTMS

AgOAc (10 mol%) i-PrOH/H2O (1.5 equiv.) THF, 0 °C

R NBoc O

R = Ph: 80%, 98% de, 80% ee R = 4-MeOC6H4: 94%, 96% de, 56% ee R = 4-BrC6H4: 98%, 98% de, 42% ee R = 4-O2NC6H4: 99%, 98% de, 42% ee

R = 2-Naph: 65%, 98% de, 50% ee R = 2-furyl: 90%, 98% de, 66% ee R = i-Bu: 52%, 98% de, 64% ee R = i-Pr: 36%, 74% de, 64% ee

Scheme 9.6 Vinylogous Mukaiyama–Mannich reaction of N-aryl aldimines and N-Boc-2-(trimethylsiloxy)pyrrole.

These authors also described a three-component version of Mannich reactions between various alkyl-substituted aldehydes, o-thiomethyl-p-anisidine, and N-Boc-2-(trimethylsiloxy)pyrrole by using the same catalyst system at a lower catalyst loading of 5 mol% [21]. As shown in Scheme 9.7, the reaction led to the corresponding vicinal chiral diamino carbonyl products in moderate to good yields (51–92%), with virtually complete γ-site and anti-selectivities combined with generally high enantioselectivities of 82–96% ee. The utility of the products was demonstrated in the synthesis of an unprecedented perhydrofuro[3,2-b]pyrrolone product, an aza-analog of naturally occurring (+)-goniofufurone (Scheme 9.7). Later in 2015, Hoveyda and coworkers reinvestigated the three-component Mannich reaction of cyclohexylcarboxaldehyde (R = Cy) with the same partners albeit in the presence of 5 mol% of an iso-leucine-derived phosphine ligand in combination with the same quantity of AgOAc, which led with almost complete regioselectivity (γ-addition:α-addition >98 : 2) to the corresponding Mannich product with anti-configuration in 82% yield, >96% de, and 91% ee [19].

9.2 Silver-Catalyzed Mannich Reactions t-Bu MeO

N

SMe

R

H

SMe NH

AgOAc (5 mol%) i-PrOH/H2O (1.5 equiv.) MgSO4 (2 equiv.) THF, –30 °C

O +

MeO OMe

O PPh2 (5 mol%)

NH2

+

H N

OTMS N Boc

R NBoc O >90% de

R = i-Bu: 90%, 96% ee R = Cy: 92%, 94% ee R = i-Bu: 75%, 95% ee R = Me: 69%, 96% ee MeO

R = BnCH2: 66%, 94% ee R = n-Hept: 79%, 94% ee R = TBSOCH2: 51%, 82% ee

SMe

H

H OH

O NH

O N Cbz H

O H NH

NBoc MeS

O

O H OH

O

OMe

Ph OH

(+)-Goniofufurone

Scheme 9.7 Three-component vinylogous Mukaiyama–Mannich reaction of aliphatic aldehydes, o-thiomethyl-p-anisidine and N-Boc-2-(trimethylsiloxy)pyrrole.

9.2.1.2

With Other Catalysts

In addition to the early use of BINAP-based silver catalysts [13], and to that of Hoveyda–Snapper silver catalysts derived from amino acid-bearing phosphines, other types of chiral silver phosphine catalysts have been successfully investigated in asymmetric Mannich reactions of various aldimines with trimethylsiloxyfuran. Therefore, Shi and coworker reported the synthesis of chiral phosphine-Schiff base-type ligands to be used in combination with AgOAc to promote the enantioselective Mannich reaction of aromatic N-aryl aldimines with trimethylsiloxyfuran [22]. Among them, ligand depicted in Scheme 9.8, possessing two electron-withdrawing groups (Cl) at 2- and 3-position of the benzene ring, was selected as optimal, allowing a range of chiral Mannich products to be achieved with complete regioselectivity in moderate to good yields (51–91%), moderate to good enantioselectivities of 38–81% ee, and in almost all cases as single anti-diastereomers (98% de), as shown in Scheme 9.8. Indeed, only using an aldimine having a 2,4-dimethoxy group on the benzene ring of Ar2 afforded the corresponding product in 50% de, presumably due to the electronic effect. Moreover, the lowest yield (51%) and enantioselectivity (38% ee) were obtained in the reaction of aldimine having a para-nitro substituent on the phenyl ring of Ar1 . It was found that the use of benzyl alcohol as super stoichiometric additive was important to achieve better yield and diastereoselectivity as well as enantioselectivity. The same authors also introduced chiral phosphine–oxazoline ligands to be combined with AgOAc to promote comparable reactions [23]. As shown

541

542

9 Asymmetric Silver-Catalyzed Reactions

N Cl PPh2

Cl HN

N Ar2

Ar1

(11 mol%)

+ O

OTMS

AgOAc (10 mol%) BnOH (1.8 equiv.) THF, –78 °C to r.t.

Ar1

Ar2 O O

Ar1 = 4-O2NC6H4, Ar2 = Ph: 51%, 98% de, 38% ee Ar1 = 4-MeOC6H4, Ar2 = Ph: 56%, 98% de, 62% ee Ar1 = 4-F3CC6H4, Ar2 = Ph: 90%, 98% de, 65% ee Ar1 = Ar2 = 4-BrC6H4: 78%, 98% de, 65% ee Ar1 = 4-BrC6H4, Ar2 = 1-F3CC6H4: 85%, 98% de, 55% ee Ar1 = 4-BrC6H4, Ar2 = 2,4-(MeO)2C6H3: 81%, 50% de, 80% ee Ar1 = Ph, Ar2 = 2,4-Cl2C6H3: 80%, 98% de, 81% ee Ar1 = Ph, Ar2 = 4-O2NC6H4: 91%, 98% de, 59% ee

Scheme 9.8 Vinylogous Mukaiyama–Mannich reaction of aromatic N-aryl aldimines and trimethylsiloxyfuran in the presence of a phosphine-Schiff base ligand.

in Scheme 9.9, better yields (76–95%) and enantioselectivities of 87–99% ee were obtained for a range of variously substituted chiral anti-butenolides produced from the reaction of the corresponding aromatic N-aryl aldimines with trimethylsiloxyfuran in the presence of 10 mol% of AgOAc combined with 10 mol% of an axially chiral phosphine-oxazoline ligand (Scheme 9.9) and 2,2,2-trifluoroethanol as super stoichiometric additive. The reaction was completely γ-regioselective, providing the anti-configured products with moderate to complete diastereoselectivity (34–98% de). To explain the stereoselectivity of the process, the authors have the transition state depicted in Scheme 9.9, in which the siloxyfuran approached the activated complex from one face of the imine with minimization of steric repulsion. Later, these authors reported the first catalytic asymmetric Mannich reaction of fluorinated aldimines with trimethylsiloxyfuran by using a closely related catalyst system [24]. Indeed, using a t-butyl-substituted chiral phosphine–oxazoline ligand (Scheme 9.10) in combination with AgOAc at a 10–11 mol% catalyst loading in the presence of a super stoichiometric amount of ethanol as additive allowed the asymmetric Mannich reaction of fluorinated aldimines with trimethylsiloxyfuran to be achieved in good to quantitative yields (70–99%), good anti-diastereoselectivity of up to >90% de, and moderate enantioselectivities of 32–81% ee, as shown in Scheme 9.10. This ligand was found much more enantioselective than differently substituted chiral phosphine–oxazoline ligands. The best results were obtained for the reaction of fluorinated aldimines bearing electron-rich aromatic groups, such as 4-methoxyphenyl group, which led to the corresponding products in quantitative yields, almost complete anti-diastereoselectivity (>90% de), and moderate to good enantioselectivities of 68–81% ee. A lower enantioselectivity of 56% ee was obtained for the reaction

9.2 Silver-Catalyzed Mannich Reactions O N

Ph

PPh2 HN Ar2

N

(10 mol%)

+

OTMS

O

Ar1

Ph

O N + Ag

Ph

Ar1 H

Me

N

P Ph Ar2

–OAc

O O

Si

Me Me

CF3CH2OH

Ar1

AgOAc (10 mol%) CF3CH2OH (1.8 equiv.) 4 Å MS CH2Cl2, –78 °C to r.t.

Proposed transition state:

Ar2

O O

Ar1 = 4-O2NC6H4, Ar2 = Ph: 80%, 34% de, 95% ee Ar1 = 4-MeOC6H4, Ar2 = Ph: 81%, 75% de, 99% ee Ar1 = 4-BrC6H4, Ar2 = Ph: 86%, 60% de, 99% ee Ar1 = 3-BrC6H4, Ar2 = Ph: 81%, 75% de, 93% ee Ar1 = 1-BrC6H4, Ar2 = Ph: 84%, 90% de, 94% ee Ar1 = Ph, Ar2 = 4-BrC6H4: 77%, 82% de, 87% ee Ar1 = Ph, Ar2 = 4-ClC6H4: 83%, 66% de, 94% ee Ar1 = Ph, Ar2 = 4-MeOC6H4: 91%, 98% de, 99% ee Ar1 = Ph, Ar2 = 4-Tol: 64%, 84% de, 94% ee Ar1 = Ph, Ar2 = 3-FC6H4: 95%, 82% de, 97% ee Ar1 = Ar2 = 4-BrC6H4: 76%, 44% de, 90% ee

Scheme 9.9 Vinylogous Mukaiyama–Mannich reaction of aromatic N-aryl aldimines with trimethylsiloxyfuran in the presence of a phosphine–oxazoline ligand.

O N

t-Bu

PPh2 HN N XF2C

R

(11 mol%)

+ O

OTMS

AgOAc (10 mol%) EtOH (1.8 equiv.) THF, –78 °C

X = F, R = 4-MeOC6H4: 99%, >90% de, 81% ee X = H, R = 4-MeOC6H4: 99%, >90% de, 74% ee X = Br, R = 4-MeOC6H4: 99%, >90% de, 68% ee X = Cl, R = 4-MeOC6H4: 99%, >90% de, 66% ee X = F, R = 4-ClC6H4: 94%, >90% de, 56% ee

R

XF2C O O X = F, R = Bn: 98%, >90% de, 74% ee X = H, R = Bn: 70%, 90% de, 32% ee X = Br, R = Bn: 99%, >90% de, 35% ee X = Cl, R = Bn: 99%, 86% de, 42% ee

Scheme 9.10 Vinylogous Mukaiyama–Mannich reaction of fluorinated aldimines and trimethylsiloxyfuran in the presence of another phosphine–oxazoline ligand.

of a fluorinated aldimine bearing an electron-poor aromatic group such as a 4-chlorophenyl group. On the other hand, N-benzyl fluorinated aldimines provided lower enantioselectivities (32–42% ee) except in the case of an aldimine containing a CF3 group, which led to the corresponding product in 74% ee. Notably, all the fluorinated aldimines gave the chiral products in good to excellent yields (70–99%) and diastereoselectivities (86% to >90% de). The synthetic utility of the products was displayed by removal of the N-aryl groups

543

544

9 Asymmetric Silver-Catalyzed Reactions

by treatment with PhI(OAc)2 in methanol under mild reaction conditions, affording the corresponding free amine chiral products. As an extension of the precedent methodology, the authors investigated the first asymmetric Mannich reaction of fluorinated aldimines bearing a chiral auxiliary, such as a (S)-1-phenylethyl group, with trimethylsiloxyfuran under the same reaction conditions [25]. As shown in Scheme 9.11, the process led to the corresponding fluorinated products in excellent yields (95–99%) and regio- and diastereoselectivies (>90% de). The high enantiomeric excesses (87–98% ee) of the reaction were determined after removing the chiral auxiliary through hydrogenation and reduction of the double bond of the butenolides followed by reaction with 4-bromobenzoic acid to give the corresponding fluorinated chiral amides. The authors have proposed the transition state model depicted in Scheme 9.11. To minimize steric interactions, the substrate was bound anti to the bulky t-butyl substituent of the oxazoline of the ligand. The catalyst-bound imine could react with the siloxyfuran through an endo-type addition, and consequently, the reaction of the chiral fluorinated aldimine with trimethylsiloxyfuran in the presence of the catalyst system led to the (4R,5R) stereoisomer predominantly. O N

t-Bu

PPh2

O Ph (1) Pd(OH)2 (40 mol%) H2, MeOH, r.t.

HN N XF2C

Ph

(11 mol%) +

OTMS

O

XF2C

AgOAc (10 mol%) EtOH (1.8 equiv.) THF, –78 °C

O O >90% de

Proposed transition state: O t-Bu

N Ph

+ Ag

P Ph

XF2C

–OAc

Ph

N

Me H

O

O Si

Me Me

(2) p-BrC6H4CO2H EDCI, BtOH DMF, r.t.

Br

NH XF2C O

O X = F: 75%, 97% ee X = H: 77%, 92% ee X = Br: 65%, 96% ee X = Cl: 70%, 96% ee X = CF3: 69%, 97% ee X = Ph: 66%, 98% ee X = 4-BrC6H4: 67%, 95% ee X = 4-ClC6H4: 79%, 96% ee X = 4-MeOC6H4: 70%, 87% ee X = 4-Tol: 52%, 92% ee

CH3CH2OH

Scheme 9.11 Vinylogous Mukaiyama–Mannich reaction of chiral fluorinated aldimines and trimethylsiloxyfuran in the presence of a phosphine-oxazoline ligand.

This catalyst system was also applied to develop the first asymmetric Mannich reactions between N-Boc aldimines and trimethylsiloxyfuran [26]. As shown in Scheme 9.12, the reaction of a range of aryl, heteroaryl, and alkyl N-Boc aldimines with trimethylsiloxyfuran afforded the corresponding chiral N-Boc-protected γ-butenolides in good yields (60–83%) and moderate to good anti-diastereo- and enantioselectivities of 60–75% de and 63–86% ee, respectively. The synthetic utility of the products was demonstrated by the easy removal of the N-Boc-protecting group with trifluoroacetic acid at room

9.2 Silver-Catalyzed Mannich Reactions

O N

t-Bu

PPh2 N

HN

Boc

(10 mol%) +

O

R

OTMS

AgOAc (10 mol%) EtOH (1.8 equiv.) CH2Cl2, –78 °C

R = 4-MeOC6H4: 83%, 72% de, 86% ee R = 3-MeOC6H4: 83%, 75% de, 78% ee R = 4-Tol: 72%, 60% de, 83% ee R = 3-Tol: 79%, 72% de, 86% ee R = 3,4,5-(MeO)3C6H2: 78%, 66% de, 76% ee R = Ph: 70%, 72% de, 77% ee

Boc

R O O

R = 4-FC6H4: 80%, 72% de, 63% ee R = 4-BrC6H4: 75%, 72% de, 67% ee R = 3-BrC6H4: 69%, 75% de, 73% ee R = 2-furyl: 69%, 75% de, 80% ee R = Cy: 75%, 72% de, 75% ee

Scheme 9.12 Vinylogous Mukaiyama–Mannich reaction of N-Boc aldimines and trimethylsiloxyfuran in the presence of a phosphine-oxazoline ligand.

temperature, providing the corresponding chiral free amines in excellent yields (92%). All the studies detailed above involved the use of chiral phosphine ligands having an additional nitrogen group. In 2013, Xu and coworkers decided to investigate the asymmetric Mannich reactions of aldimines with trimethylsiloxyfuran and other types of ligands, such as simple chiral monophosphines that did not bear an additional heteroatom [27]. Among these novel chiral ligands prepared from (R)-BINOL, the monophosphine depicted in Scheme 9.13 was Ph

PPh2

N Ar2

HN

Ar1

(5 mol%) +

O

OTMS

AgOAc (5 mol%) i-PrOH (1.5 equiv.) CH2Cl2, –78 °C to r.t.

Ar1 = Ar2 = Ph: 99%, 76% ee Ar1 = 4-EtOC6H4, Ar2 = Ph: 96%, 76% ee Ar1 = 2,4-Cl2C6H3, Ar2 = Ph: 92%, 53% ee Ar1 = Ph, Ar2 = 4-ClC6H4: 97%, 73% ee Ar1 = 3-ClC6H4, Ar2 = Ph: 98%, 78% ee Ar1 = 3-BrC6H4, Ar2 = Ph: 94%, 74% ee

Ar1

Ar2 O O >98% de

Ar1 = 4-ClC6H4, Ar2 = 3-BrC6H4: 96%, 77% ee Ar1 = 4-Tol, Ar2 = 3-BrC6H4: 91%, 76% ee Ar1 = 3-ClC6H4, Ar2 = 3-BrC6H4: 94%, 63% ee Ar1 = 1-MeOC6H4, Ar2 = Ph: 75%, 63% ee Ar1 = Ph, Ar2 = 3-pyridyl: 88%, 78% ee

Scheme 9.13 Vinylogous Mukaiyama–Mannich reaction of aromatic N-aryl aldimines and trimethylsiloxyfuran in the presence of a monophosphine ligand.

545

546

9 Asymmetric Silver-Catalyzed Reactions

selected as optimal in combination with AgOAc to promote the enantioselective Mannich reaction of various aromatic N-aryl aldimines with trimethylsiloxyfuran. As shown in Scheme 9.13, the reaction led to a range of chiral γ-butenolide derivatives in good to quantitative yields (75–99%) and exceptional anti-diastereoselectivity of >98% de, combined with moderate enantioselectivities (53–78% ee). With the aim of extending the scope of this methodology, the authors investigated the reaction of a N-(2-methoxybenzene) aldimine derived from an alkyl aldehyde such as cyclohexylcarboxaldehyde. Unfortunately, the corresponding Mannich product was formed in 30% ee, 50% yield, and 88% de. This study demonstrated that a chiral monophosphine without an additional heteroatom-donating group could exhibit a good enantiocontrol and high catalytic performances in silver-catalyzed asymmetric Mannich reactions. 9.2.2

Other Mannich-Type Reactions

The use of silyl enol ethers as nucleophilic reagents in asymmetric Mannich reactions is not ideal from the standpoint of atom economy. In this context, Zhou and coworkers introduced a novel silver catalyst system based on the combination of a chiral ferrocenylphosphine sulfur ligand (Scheme 9.14) with AgOAc to achieve direct asymmetric Mannich reactions of acetylacetone and N-Boc-protected aryl aldimines with enantioselectivities of up to 91% ee [28]. As shown in Scheme 9.14, in the presence of only 3–3.3 mol% of catalyst, a range of chiral amines was produced in good yields (67–99%) and high PAr′2 S

OMe

Fe

N

O

Boc

HN

Ar′ = 3,5-Me2C6H3 (3.3 mol%)

O

+

Ar = 4-MeOC6H4: 92%, 88% ee Ar = Ph: 67%, 86% ee Ar = 4-Tol: 82%, 88% ee Ar = 4-FC6H4: 99%, 91% ee

Ac

Ar = 4-BrC6H4: 81%, 90% ee Ar = 1-Tol: 86%, 88% ee Ar = 1-Naph: 95%, 88% ee Ar = 2-furyl: 88%, 80% ee O

N Ar

Boc

O +

R1

O

Ac

Ar

AgOAc (3 mol%) Et2O, –40 °C

Ar

Boc

Same conditions

R1

OR2 Ar

O OR2 NHBoc

Ar = 4-MeOC6H4, R1 = OBn, R2 = Bn: 86%, 78% ee Ar = R1 = Ph, R2 = Bn: 90%, 34% de, 78% ee

Scheme 9.14 Mannich reactions of 1,3-dicarbonyl compounds and N-Boc aryl aldimines in the presence of a ferrocenylphosphine sulfur ligand.

9.2 Silver-Catalyzed Mannich Reactions

enantioselectivities (86–91% ee) regardless of the electronic properties and steric hindrance of the phenyl ring of aldimines. A slightly lower enantioselectivity of 80% ee was obtained when a heteroaromatic aldimine (Ar = 2-furyl) was used. The same methodology could be applicable to other β-dicarbonyl compounds, such as malonates and β-ketoesters, as shown in Scheme 9.14. High isolated yields (86–90%) and good enantioselectivity of 78% ee were achieved for both products. Optically active α,β-diamino acids constitute an important class of biologically active products [11]. In this context, the asymmetric Mannich-type reaction of glycine Schiff base depicted in Scheme 9.15 and derivatives with imines provided an efficient and convenient route for the preparation of these compounds. In 2003, Jørgensen and coworkers reported the first example of enantioselective copper-catalyzed Mannich reaction of imino glycine alkyl esters with imines performed in the presence of a chiral phosphine-oxazoline ligand [29]. Ever since, other efficient catalyst systems have been developed for diastereo- and enantioselective Mannich reactions of glycine Schiff bases with aldimines by several groups. Among them, a combination of AgOAc with a chiral ferrocenyl oxazoline phosphine ligand (Scheme 9.15) employed at 3–3.3 mol% in THF at −25 ∘ C was found efficient to promote the Mannich reaction of N-tosyl aldimines with a glycine Schiff base to give the corresponding α,β-diamino methyl esters as mixtures of syn- and anti-diastereomers in general with excellent yields of 92–99% and high enantioselectivities of up to 97% ee [28]. The best results were achieved in the case of aliphatic aldimines, which led to the corresponding syn-products with 80–86% de, 97–99% yields, and high enantioselectivities of 93–96% ee (Scheme 9.15). A series of (hetero)aromatic aldimines with electron-withdrawing and electron-donating substituents also underwent the desired transformation to afford the corresponding Mannich products with high O N Fe

N R

Ts

N Ph

PAr′2

Ar′ = 4-F3CC6H4 (3.3 mol%)

Ph +

i-Pr

CO2Me

AgOAc (3 mol%) THF, –25 °C

Ph Ph

R

*

NHTs

N * CO2Me

R = Ph: 93%, syn/anti = 44 : 56, 91% ee (syn), 96% ee (anti) R = 1-BrC6H4: 97%, syn/anti = 39 : 61, 94% ee (syn), 97% ee (anti) R = 3-ClC6H4: 92%, syn/anti = 51 : 49, 97% ee (syn), 95% ee (anti) R = 4-MeOC6H4: 98%, syn/anti = 48 : 52, 91% ee (syn), 82% ee (anti) R = 2-Naph: 96%, syn/anti = 53 : 47, 92% ee (syn), 96% ee (anti) R = i-Pr: 99%, syn/anti = 93 : 7, 96% ee (syn) R = Cy: 97%, syn/anti = 90 : 10, 93% ee (syn), 91% ee (anti)

Scheme 9.15 Mannich reaction of N-tosyl aldimines and a glycine Schiff base in the presence of a ferrocenyl oxazoline phosphine ligand.

547

548

9 Asymmetric Silver-Catalyzed Reactions

yields (92–98%) and good to excellent enantioselectivities (82–97% ee) for both diastereomers albeit with low diastereoselectivities of 2–22% de (Scheme 9.15). Later, these reactions were reinvestigated by Fukuzawa and coworkers employing another ferrocenyl chiral ligand, such as ferrocenyl triazole phosphine ligand depicted in Scheme 9.16, used at 3 mol% of catalyst loading in combination with AgOAc [30]. The Mannich reaction of a range of N-tosyl aryl aldimines with a glycine Schiff base performed in THF at room temperature led to mixtures of syn- and anti-products with low to moderate diastereoselectivities of 12–50% de but in 99% yield in all cases and high enantioselectivities of 85–98% ee. The substitution pattern of the phenyl ring in the tosylimines was found to have an effect on the transformation. Therefore, the electron-withdrawing substituents in the ortho-position tended to produce higher syn-diastereoselectivity (36–50% de) than those observed with unsubstituted tosylimines (20% de). For these substrates, the enantioselectivities remained high. Three-electron-donating substituents had a slight, negative effect on the enantioselectivity of the reaction, whereas 4-electron-withdrawing substituents had almost no effect on the enantioselectivity. For these latter products, the syn/anti ratios were moderate (56 : 44 to 60 : 40).

Ph2P

Fe N N

t-BuS

N Ar

Ts

Ph (3 mol%)

Ph +

N Ph

N

CO2Me

AgOAc (3 mol%) THF, r.t.

Ar Ph * Ph

N

NHTs * CO2Me

99% yield Ar = Ph: syn/anti = 60 : 40, 98% ee (syn), 98% ee (anti) Ar = 1-FC6H4: syn/anti = 68 : 32, 98% ee (syn), 97% ee (anti) Ar = 1-ClC6H4: syn/anti = 71 : 29, 98% ee (syn), 97% ee (anti) Ar = 1-BrC6H4: syn/anti = 75 : 25, 95% ee (syn), 98% ee (anti) Ar = 1-Tol: syn/anti = 58 : 42, 95% ee (syn), 98% ee (anti) Ar = 4-ClC6H4: syn/anti = 58 : 42, 98% ee (syn), 98% ee (anti) Ar = 4-F3CC6H4: syn/anti = 56 : 44, 97% ee (syn), 96% ee (anti) Ar = 4-Tol: syn/anti = 60 : 40, 85% ee (syn), 94% ee (anti) Ar = 4-MeOC6H4: syn/anti = 57 : 43, 91% ee (syn), 91% ee (anti)

Scheme 9.16 Mannich reaction of N-tosyl aryl aldimines and a glycine Schiff base in the presence of a ferrocenyl triazole phosphine ligand.

In 2014, Sansano and workers demonstrated that these reactions could also be promoted by chiral phosphoramidite silver complexes [31]. Indeed, when the Mannich reaction of a series of N-tosyl aryl aldimines with a glycine Schiff base was performed in toluene at room temperature in the presence of a combination of 5 mol% of AgOTf and the same quantity of a chiral phosphoramidite ligand, it afforded the corresponding Mannich products in moderate yields (30–70%),

9.2 Silver-Catalyzed Mannich Reactions

syn-diastereoselectivities (0–60% de), and variable enantioselectivities of 2–99% ee (Scheme 9.17). In addition to the result obtained from the use of non-substituted benzaldehyde N-tosyl aldimine, which provided the corresponding syn-product in 96% ee, the presence of heteroatoms (Ar = 2-furyl) and para-halogenated arenes (Ar = 4-FC6 H4 ) in the aromatic part of imines allowed the best enantioselection (92–99% ee) to be achieved. The authors have proposed the transition state depicted in Scheme 9.17, in which the freshly generated azomethine ylide was coordinated by a silver atom and the nucleophilic attack occurred at the tosyl imine whose arylsulfonyl group was situated far away from the benzylidene moiety of the dipole. In this transition state, additional coordination between silver and sulfonamido group could not be ruled out. Ph O P N O

N

Ts

Ph + Ph

CO2Me

Proposed transition state (with Ar = Ph):

Ph O

N P

O

Ph Ag O Ts N OMe Ph N

Ph

Ar Ph

(5 mol%)

N

Ar

Ph

synProduct

AgOTf (5 mol%) toluene, r.t.

Ph

*

NHTs

N * CO2Me

Ar = Ph: 70%, syn/anti = 72 : 28, 96% ee (syn), 58% ee (anti) Ar = 1-Tol: 50%, syn/anti = 80 : 20, 14% ee (syn), 4% ee (anti) Ar = 1-ClC6H4: 55%, syn/anti = 56 : 44, 46% ee (syn), 90% de, combined with low to moderate enantioselectivities of 25–82% ee. α,α-Dicyanoolefin (X = CH2 ) emerged as the best substrate for the asymmetric Mannich reaction since its reactions with a series of aldimines bearing various substituents on the aromatic ring provided the highest enantioselectivities of 59–82% ee. The process was found sensitive to both the steric and the electronic properties of the substituents on the phenyl ring of aldimines. Generally, phenyl substituents bearing electron-donating groups (Ar = 4-MeOC6 H4 ) at the para-position gave a higher enantioselectivity compared with those with an electron-withdrawing group (Ar = 4-FC6 H4 or

549

550

9 Asymmetric Silver-Catalyzed Reactions

O Bn N Fe

PPh2 NC

N

Boc +

R1

NC

R2

NC

Ar

(3.3 mol%) AgOAc (3 mol%) Et2O, –25 °C

CN NHBoc

R1

Ar R2

Ar = R1 = Ph, R2 = Me: 79%, 74% de, 47% ee Ar = Ph, R1, R2 = (CH2)5: 90%, 88% de, 25% ee NC

CN

X X = CH2, O

With X = CH2: Ar = Ph: 88%, 86% de, 64% ee Ar = 4-MeOC6H4: 96%, >90% de, 82% ee Ar = 4-FC6H4: 91%, 84% de, 70% ee Ar = 4-BrC6H4: 84%, 74% de, 61% ee Ar = 1-Tol: 96%, >90% de, 59% ee With X = O: Ar = Ph: 96%, >90% de, 64% ee

Scheme 9.18 Mannich reaction of N-Boc aryl aldimines and α,α-dicyanoolefins in the presence of a ferrocenyl oxazoline phosphine ligand.

4-BrC6 H4 ). The best result (96% yield, >90% de, 82% ee) was reached in the case of reaction between α,α-dicyanoolefin (X = CH2 ) and para-methoxyphenyl aldimine. In 2012, Hui and coworkers developed asymmetric Mannich reactions of N-tosyl aldimines with oxazolones promoted by a synergistic ion pair consisting of a silver ion and a chiral BINOL-derived phosphate anion [32]. Performed at room temperature in dichloromethane as solvent, these processes provided chiral quaternary α,β-diamino acid derivatives in moderate to high yields (58–95%) and good to high diastereo- and enantioselectivities of up to 92% de and 99% ee, respectively. As shown in Scheme 9.19, the best results were generally achieved by using (hetero)aryl aldimines, which allowed enantioselectivities of 81–99% ee in combination with 75–95% yields for the corresponding products. An alkyl aldimine (R1 = n-Pr) led to the corresponding product in only 58% yield with lower enantioselectivity (75% ee). Concerning aryl aldimines, those bearing electron-donating groups provided excellent enantioselectivities (98–99% ee), while aldimines bearing electron-withdrawing groups at the para-position gave slightly lower enantioselectivities (82–91% ee). With respect to 1-substituents and the 2-naphthyl group, high enantioselectivities of 94–95% ee were also obtained, probably due to steric effects. In 2013, Kumagai and coworkers reported enantioselective silver-catalyzed Mannich-type reactions of α-sulfanyl lactones with N-Boc aldimines [33]. These reactions were promoted by a combination of 3 or 5 mol% of AgPF6 and a chiral Biphep-type ligand in the presence of the same quantity of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a base in toluene at −30 ∘ C.

9.2 Silver-Catalyzed Mannich Reactions

SiPh3 O

O P

O

N R1

SiPh3

Ph

Ts +

O Ag

O O

N R2

O NHTs O

(15 mol%) CH2Cl2, r.t.

Ph

R1 N

R2

R1 = Ph, R2 = Me: 94%, 88% de, 92% ee R1 = 4-Tol, R2 = Me: 92%, 92% de, 94% ee R1 = 4-ClC6H4, R2 = Me: 95%, 84% de, 81% ee R1 = Ph, R2 = i-Pr: 92%, 88% de, 95% ee R1 = 4-Tol, R2 = i-Pr: 84%, 90% de, 98% ee R1 = 4-MeOC6H4, R2 = i-Pr: 83%, 90% de, 99% ee R1 = 1-FC6H4, R2 = i-Pr: 93%, 90% de, 94% ee R1 = 4-FC6H4, R2 = i-Pr: 91%, 88% de, 82% ee R1 = 1-ClC6H4, R2 = i-Pr: 88%, 90% de, 95% ee R1 = 3-ClC6H4, R2 = i-Pr: 85%, 90% de, 82% ee R1 = 4-ClC6H4, R2 = i-Pr: 90%, 90% de, 91% ee R1 = 4-BrC6H4, R2 = i-Pr: 89%, 90% de, 86% ee R1 = 2-Naph, R2 = i-Pr: 88%, 75% de, 94% ee R1 = n-Pr, R2 = i-Pr: 58%, 82% de, 75% ee

Scheme 9.19 Mannich reaction of N-tosyl aldimines and oxazolones in the presence of a chiral ion-pair silver catalyst.

Soft–soft interaction between Ag+ and the sulfanyl moiety afforded in situ chemoselective activation of μ-sulfanyl lactones to catalytically generate the corresponding enolates by the synergistic action of the mild Brønsted base. The reaction of a range of aldimines with five-membered α-sulfanyl lactone (n = 1) led to the formation of a range of chiral β-amino-α-methylthio lactones, which bore two contiguous stereogenic centers. As shown in Scheme 9.20, these products were obtained in moderate to high yields (42–94%) and uniformly excellent enantioselectivities of 96–99% ee from the corresponding aryl, heteroaryl, and alkyl aldimines. Concerning the reaction of aromatic aldimines, the reactivity and diastereoselectivity were found dependent on the electronic nature of the substituents on the aromatic ring. Thus, aromatic imines bearing electron-deficient substituents produced the corresponding Mannich products in high diastereo- and enantioselectivities of >90% de and 99% ee, respectively. As the electron density of the aromatic ring increased, the diastereoselectivity of the reaction decreased steadily (86%, 75%, and 42% de). The face selection of the imines was compromised with electron-rich imines, presumably because the higher Lewis basicity of the imine nitrogen had a negative effect. The particularly low yield (42%) obtained in the reaction of a para-MeO-substituted imine was ascribed to its intrinsic low electrophilicity. Even heteroaryl and alkyl aldimines were tolerated, providing the corresponding products in 97–99% ee. Whereas six-membered α-sulfanyl lactone (n = 2) could be applicable as a

551

552

9 Asymmetric Silver-Catalyzed Reactions

MeO

PAr2

MeO

PAr2

Ar = 3,5-t-Bu2-4-MeOC6H2 O Boc N + MeS R

O ( )n

(3 or 5 mol%) AgPF6 (3 or 5 mol%) DBU (3 or 5 mol%) Toluene, –30 °C

Boc

NH

R MeS

O O ( )n

R = 4-FC6H4, n = 1: 79%, >90% de, 99% ee R = 4-ClC6H4, n = 1: 78%, >90% de, 99% ee R = 4-O2NC6H4, n = 1: 87%, >90% de, 99% ee R = Ph, n = 1: 80%, 86% de, 96% ee R = 4-Tol, n = 1: 70%, 75% de, 97% ee R = 4-MeOC6H4, n = 1: 42%, 72% de, 97% ee R = 4-TfOC6H4, n = 1: 79%, >90% de, 96% ee R = 2-furyl, n = 1: 94%, 72% de, 97% ee R = n-Pent, n = 1: 71%, >90% de, 99% ee R = 3-pyridyl, n = 2: 88%, >90% de, 82% ee R = BnCH2, n = 2: 49%, >90% de, 96% ee R = Ph, n = 3: 0%

Scheme 9.20 Mannich reaction of N-Boc aldimines and α-sulfanyl lactones in the presence of a Biphep-type ligand.

pronucleophile, less reactivity or lower enantioselectivity was observed (49% yield, 82% ee). On the other hand, the catalytic system failed to promote the reaction of a 𝜀-lactone (n = 3) to give the corresponding product, probably because of reluctant formation of the enolate. The utility of this methodology was shown by the conversion of the products into chiral trisubstituted aziridines that could be further transformed by treatment with Pd(OH)2 into important chiral α,α-disubstituted α-amino acid derivatives. In 2014, Yanagisawa et al. reported a novel example of enantioselective Mannich-type reaction of alkenyl trichloroacetates with N-aryl aromatic aldimines using a combination of AgOTf and (R)-Segphos as ligand [34]. The reaction employed N,N-diisopropylethylamine as a base and 2,2,2-trifluoroethanol as super stoichiometric additive. It afforded optically active β-amino ketones in uniformly excellent enantioselectivities of 96% to >99% ee, as shown in Scheme 9.21. These chiral products were obtained with syn-selectivity in moderate to good yields of up to 81% via the chiral silver enolates generated in situ in THF at −30 ∘ C. Remarkably, cyclic alkenyl trichloroacetates, such as cyclohexanone, cyclopentanone, and cycloheptanone derivatives, reacted with variously substituted N-aryl aromatic aldimines to provide the corresponding Mannich products with both remarkable diastereo- and enantioselectivities of >98% to >99% de and 98% to >99% ee, respectively. It is only in the case of an acyclic alkenyl trichloroacetate that the corresponding product was obtained with a low diastereoselectivity of 38% de combined with a low yield of 24% but with still

9.2 Silver-Catalyzed Mannich Reactions

O O O

PPh2 PPh2

O

N Ar2

Ar1 +

OCOCl3 R1 2

R

(R)-Segphos (10 mol%) AgOTf (20 mol%) i-Pr2NEt (40 mol%)

NHAr1

O R1

CF3CH2OH (3 equiv.)

Ar2 R

4 Å MS THF, –30 °C

2

syn-Major

R1, R2 = (CH2)4, Ar1 = Ar2 = Ph: 66%, >99% de, >99% ee R1, R2 = (CH2)4, Ar1 = 4-ClC6H4, Ar2 = Ph: 52%, >99% de, 98% ee R1, R2 = (CH2)4, Ar1 = 4-BrC6H4, Ar2 = Ph: 59%, >99% de, >99% ee R1, R2 = (CH2)4, Ar1 = 4-F3CC6H4, Ar2 = Ph: 80%, >99% de, >99% ee R1, R2 = (CH2)4, Ar1 = 4-F3COC6H4, Ar2 = Ph: 81%, >99% de, >99% ee R1, R2 = (CH2)4, Ar1 = 3-ClC6H4, Ar2 = Ph: 79%, >99% de, >99% ee R1, R2 = (CH2)4, Ar1 = Ph, Ar2 = 3-BrC6H4: 43%, 98% de, 99% ee R1, R2 = (CH2)4, Ar1 = Ph, Ar2 = 4-ClC6H4: 35%, 98% de, 99% ee R1, R2 = (CH2)4, Ar1 = Ph, Ar2 = 4-BrC6H4: 40%, >98% de, 99% ee R1, R2 = (CH2)4, Ar1 = Ph, Ar2 = 4-F3CC6H4: 58%, >98% de, >99% ee R1, R2 = (CH2)4, Ar1 = 4-F3COC6H4, Ar2 = 4-MeOC6H4: 31%, >98% de, >99% ee R1, R2 = (CH2)3, Ar1 = 4-F3COC6H4, Ar2 = Ph: 41%, >98% de, >99% ee R1, R2 = (CH2)5, Ar1 = 4-F3COC6H4, Ar2 = Ph: 53%, >98% de, 98% ee R1 = Et, R2 = Me, Ar1 = 4-F3COC6H4, Ar2 = Ph: 24%, 38% de, 96% ee

( )n Proposed chair transition state with R1, R2 = (CH2)n+2: Ar

H H 1

O

N Ag

Ar2 P

*

P

Scheme 9.21 Mannich reaction of N-aryl aromatic aldimines and alkenyl trichloroacetates in the presence of (R)-Segphos ligand.

high enantioselectivity (96% ee) (Scheme 9.21). Only benzaldimines possessing a N-protective group other than aromatic groups did not give satisfactory results. A plausible transition state for the reaction of cyclic alkenyl trichloroacetates is depicted in Scheme 9.21, in which the imine coordinates to a silver atom of the enolate to furnish a six-membered cyclic structure. Accordingly, from the cyclic E-enolate, the syn-Mannich product is formed through this chair-type transition state. In 2016, Peng and coworkers developed the first asymmetric Mannich reaction of isatin-based ketimines with α-diazomethylphosphonates promoted by a chiral silver phosphate catalyst [35]. The latter was in situ generated from Ag2 CO3 and a BINOL-derived phosphate. The reaction led to the formation of a series of chiral oxindoles bearing a quaternary stereocenter and an amino group at the C3 position with moderate to excellent yields of 43–95% and moderate to excellent enantioselectivities of 43–99% ee, as shown in Scheme 9.22.

553

554

9 Asymmetric Silver-Catalyzed Reactions

Ar O O P OH O Ar N Boc R2

O N

+ O P(OR1)2 N2

Ar = 2,6-(i-Pr)2-4-(t-BuC6H4)C6H2 (10 mol%) Ag2CO3 (5 mol%) 4 Å MS, –30 °C R2 Toluene/PhEt (1 : 1)

BocHN

N2 O P(OR1)2 O

N

43–95%, 43–99% ee R1 =

Me, Et, i-Pr R2 = H, 5-F, 7-F, 5-Cl, 6-Cl, 7-Cl, 5-Br, 6-Br, 5-I, 5-Me, 5-MeO, 5-Br-7-Me, 5F3C, 5O2N

Scheme 9.22 Mannich reaction of isatin-based ketimines and α-diazomethylphosphonates in the presence of a BINOL-derived phosphate ligand.

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions The 1,3-dipolar cycloaddition [36] occurs between a dipolarophile and a 1,3-dipolar compound, leading to various five-membered heterocycles [37]. For example, azomethine ylides are versatile reactive 1,3-dipoles that undergo cycloaddition reactions with electron-deficient alkenes to afford functionalized pyrrolidines. A wide variety of chiral catalysts have been applied to promote asymmetric versions of this process, providing chiral proline derivatives, which are key chiral building blocks found in a number of natural products and pharmaceutically important compounds. Concerning enantioselective silver-catalyzed 1,3-dipolar cycloadditions, which generally afford endo-cycloadducts diastereoselectively, the first example was reported by Grigg [4c]. It involved the reaction between ester-stabilized azomethine ylides with different activated olefins performed in the presence of stoichiometric amounts of AgOTf and a chiral proline-derived diphosphine ligand, providing the corresponding endo-cycloadducts in moderate to good yields (60–80%) and moderate enantioselectivities of up to 70% ee. It is later in 2002 that the first truly catalytic asymmetric reactions were reported by Zhang and coworkers using only 3 mol% of a combination of AgOAc with a chiral bis-ferrocenyl amide phosphine ligand [38]. A complete endo-diastereoselectivity and an excellent enantioselectivity of 97% ee combined with an 87% yield were obtained in the cycloaddition of an α-imino ester with dimethyl maleate. Inspired by this early work, several groups have developed other types of chiral ligands, such as aminophosphines, which, in combination with AgOAc, were successfully applied to promote 1,3-dipolar cycloadditions of α-imino esters with α,β-unsaturated esters with high enantioselectivities of up to 98% ee and yields of up to 98% [39]. In 2007, good results (89% ee) were also achieved by Zhou and coworker in comparable

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

reactions catalyzed with chiral ferrocene-derived P,S ligands [40]. The same year, Najera et al. investigated the formal 1,3-dipolar cycloadditions of azomethine ylides with other dipolarophiles, such as N-methylmaleimide, providing the corresponding bicyclic products with high endo-diastereo- and enantioselectivities in reactions catalyzed by a combination of BINAP with AgClO4 [41]. Besides chiral phosphine ligands, Jørgensen and coworkers introduced in 2005 the use of cinchona alkaloids, such as hydrocinchonine, which were used in the presence of AgF in the 1,3-dipolar cycloaddition of azomethine ylides with acrylates to give the corresponding chiral cycloadducts in moderate enantioselectivities of up to 73% ee [42]. In the period 2008–2014, different groups including those of Wang and coworkers [43], Najera and coworkers [44], Kobayashi and coworkers [45], Fukuzawa and coworkers [46], Martin and coworkers [47], Hu and coworkers [48], Carretero and coworkers [49], Zhao and coworkers [50], Gong and coworkers [51], and Deng and coworkers [52], among others [53] developed various other chiral silver catalysts based on not only bidentate ligands, including biphosphines, aminophosphines, sulfur-containing phosphines, bisoxazolines, and diimines, but also monodentate ligands such as phosphoramidites, which were successfully applied to asymmetric 1,3-dipolar cycloadditions of azomethine ylides with a variety of activated olefins including malonates, maleimides, acrylates, nitroalkenes, and more complicated alkenes bearing electron-deficient groups. Since this period 2008–2014 has been recently covered by several reviews [37], it will not be detailed in this section, which will only focus on the period 2015–2017. The two first subsections of Section 9.3 (Sections 9.3.1 and 9.3.2), dealing successively with asymmetric formal 1,3-dipolar cycloadditions of glycine imino esters with α,β-unsaturated carbonyl compounds and nitroalkenes as dipolarophiles, can be actually viewed as stepwise processes consisting of Michael additions followed by intramolecular Mannich (with α,β-unsaturated carbonyl compounds as dipolarophiles) or aza-Henzy (with nitroalkenes as dipolarophiles) reactions. 9.3.1 Formal 1,3-Dipolar Cycloadditions of Glycine Imino Esters and 𝛂,𝛃-Unsaturated Carbonyl Compounds Since 2015, novel chiral ligands as well as novel dipolarophiles have been investigated in asymmetric silver-catalyzed formal 1,3-dipolar cycloadditions. For example, Xia and coworkers studied for the first time chalcones and alkyl cinnamates as dipolarophiles in reaction with glycine imino esters [54]. Among a series of chiral mono- and biphosphine ligands investigated in these reactions, aromatic amide-derived nonbiaryl atropisomer ligand Xing-Phos was selected as optimal to yield the corresponding chiral chalcone-derived pyrrolidines bearing four contiguous stereogenic centers from chalcones and glycine imino esters. As shown in Scheme 9.23, the process was performed with 5.5 mol% of this ligand combined with 2.5 mol% of AgF as precatalyst in a 1 : 1 mixture of THF and ethanol at −20 ∘ C, which allowed a range of chiral products to be prepared in good to excellent yields of 80–98%, moderate to almost complete exo-diastereoselectivities (60% to >96% de), and high enantioselectivities (90–96% ee) regardless of the electronic nature substituents on the phenyl rings

555

556

9 Asymmetric Silver-Catalyzed Reactions

O O Ar1

S

H N

t-Bu Ph O Ar2

PPh2 N(i-Pr)2

Xing-Phos (5.5 mol%)

Ar1

AgF (2.5 mol%)

+

THF/EtOH (1 : 1), –20 °C Ar3

O Ar2

N

Ar3

CO2R

N H

CO2R

exo Ar1 = Ph, 4-MeOC6H4, 4-ClC6H4, 4-Tol, 3-MeOC6H4 Ar2 = Ph, 4-ClC6H4, 4-F3CC6H4, 4-MeOC6H4, 4-FC6H4, 4-MeOC6H4, 4-Tol Ar3 = Ph, 4-NCC6H4, 4-Tol, 4-MeOC6H4, 4-BrC6H4, 3-BrC6H4, 4-PhC6H4, 4-FC6H4, 4-F3CC6H4 R = Me, Et 80–98%, 60% to >96% de, 90–96% ee CO2Me

Ar2

AgF (2.5 mol%)

+ 1

Ar

Xing-Phos (5.5 mol%)

OMe

N

K2CO3 (20 mol%) THF/MeOH (1 : 1), –20 °C

Ar2

MeO2C Ar1

N H

CO2Me

O

Michael

L* Ar2 Ar1 O MeO Ag OMe O + N

Mannich

Ar1 = Ph, 4-MeOC6H4, 4-Tol, 4-BrC6H4, 3-BrC6H4, 4-PhC6H4, 4-F3CC6H4, 4-FC6H4, 3-ClC6H4, 1-ClC6H4 Ar2 = Ph, 4-ClC6H4, 4-Tol 58–86%, 80–98% de, 90–98% ee

Scheme 9.23 Formal 1,3-dipolar cycloadditions of glycine imino esters and chalcones/methyl cinnamates in the presence of Xing-Phos ligand.

of the chalcones and aryl imino esters. The scope of this methodology could be extended to even more challenging and less reactive alkenes such as alkyl cinnamates. Indeed, by applying closely related conditions with the additional presence of K2 CO3 as a base, the authors developed the first silver-catalyzed synthesis of cinnamate-derived chiral pyrrolidines with exo-diastereoselectivity through the catalytic asymmetric cycloaddition of the corresponding methyl cinnamates with glycine imino esters. These densely functionalized chiral products bearing four contiguous stereogenic centers were obtained in moderate to good yields (58–86%), good to excellent exo-diastereoselectivities (80–98% de), and very high enantioselectivities (90–98% ee) (Scheme 9.23). As in the reaction of chalcones, the substrate scope of the two substrates was found wide, since

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

a series of methyl cinnamates containing various groups on the phenyl ring (Ar2 ) as well as glycine imino esters derived from aromatic aldehydes bearing electron-deficient and electron-neutral substituents on the aryl rings reacted smoothly. Although the possibility of a concerted mechanism could not be excluded in the case of the base-free conditions (first reaction with chalcones), the authors have suggested that the cycloadditions evolved through a stepwise domino Michael/Mannich mechanism on the basis of experimental results (Scheme 9.23). In 2016, Oh and coworkers reinvestigated the formal 1,3-dipolar cycloaddition of chalcones with glycine imino esters in the presence of another type of chiral ligand combined with AgF at 10 mol% of catalyst loading in THF as solvent and tert-butanol as additive [55]. When promoted by a chiral multifunctional brucine diol at −15 ∘ C, the reaction of a range of aryl imino esters with various chalcones led to the exclusive formation of the corresponding endo-cycloadducts in moderate to quantitative yields (50–99%) and low to excellent enantioselectivities (22–98% ee), as shown in Scheme 9.24. Studying the substrate scope showed that the aryl substituent on the imino esters (Ar1 ) did not exert a significant effect on the observed enantioselectivities, while the electronic nature of the chalcone’s β-aryl substituent (Ar3 ) detrimentally influenced the observed enantioselectivities of the formed pyrrolidines. For example, the lowest enantioselectivities of 22–55% ee were obtained for chalcones bearing a para-tolyl group or a 1-, 3-, or 4-chloro-substituted phenyl group at the β-position. In this study, the authors have demonstrated that replacing AgF as metal source by CuOTf led to the

OMe OMe

O H

H O H O Ar3

HO Ar2

Ar

H

N OH (10 mol%) AgF (10 mol%)

+ 1

N

N

CO2Me

t-BuOH (10 mol%) THF, –15 °C

O Ar3

Ar2 Ar1

N H

CO2Me

endo >99% de Ar1 = Ph, 4-ClC6H4, 4-Tol, 4-FC6H4, 3-BrC6H4, 2-thienyl Ar2 = Ph, 4-ClC6H4 Ar3 = Ph, 4-Tol, 4-ClC6H4, 1-ClC6H4, 3-ClC6H4 50–99%, 22–98% ee

Scheme 9.24 Formal 1,3-dipolar cycloaddition of glycine imino esters and chalcones in the presence of a multifunctional brucine diol ligand.

557

558

9 Asymmetric Silver-Catalyzed Reactions

exclusive formation of the enantiomer of the same endo-cycloadduct in good to quantitative yields (67–99%) and with high enantioselectivities (87–98% ee). In 2015, Singh and coworkers reported an enantioselective silver-catalyzed desymmetrization of cyclopentene-1,3-diones based on a formal 1,3-dipolar cycloaddition with glycine imino esters [56]. Among a series of chiral ligands investigated, including (R)-BINAP, (R)-DTBM-Segphos, and various ferrophos ligands, the ferrocenylphosphine ligand depicted in Scheme 9.25 was found optimal to yield, at room temperature and at a low catalyst loading of 3 mol% in combination with 2 mol% of AgOAc, a series of chiral 5,5-fused bicyclopyrrolidines. These densely functionalized products bearing five contiguous stereogenic centers were produced in moderate to good yields (35–76%), moderate diastereoselectivities (50–60% de), and general high enantioselectivities (87–98% ee) (Scheme 9.25). Uniformly good results (58–76% yield, 50–66% de, and 87–98% ee) were obtained from various azomethine ylides bearing electron-donating as well as electron-withdrawing substituents on the aromatic group (R2 ). Even imino esters bearing a sterically bulky trisubstituted aromatic ring (R2 = 2,3-Me2 -4-MeOC6 H2 ) and a naphthyl moiety smoothly produced the corresponding products in good yields (65% and 76%, respectively) and excellent enantioselectivities (91 and 98% ee), respectively. Azomethine ylides containing cinnamyl and furyl rings also underwent the reaction in good yields (69–74%) and good to excellent enantioselectivities of 87% and 94% ee, respectively. Concerning the scope of cyclopentenediones, a wide range of electron-donating and electron-withdrawing substituents were well tolerated on the aromatic group R1 , providing the corresponding products in good yields (35–68%) and excellent enantioselectivities of 94–96% ee. However, it was found that the presence of a 3-substituent on the aromatic ring of these substrates had a deleterious effect in comparison with a 4-substituent, which could be related i-Pr N O O

Fe

PPh2

R1 (3 mol%) AgOAc (2 mol%)

O + R2

N

CO2Et

4 Å MS Et2O, r.t.

R2

O R1

HN EtO2C

O

R1 = Ph, 4-FC6H4, 3-Tol, 4-(i-Pr)C6H4, 3-BrC6H4, 3-MeOC6H4, 4-F3CC6H4, 3,5-Me2C6H3, 2-Naph, CH2=CH R2 = Ph, 4-ClC6H4, 4-Tol, 4-FC6H4, 4-MeOC6H4, 2,3-Me2C6H3, 2,3-Me2-4-MeOC6H2, 2-Naph, 2-furyl, (E)-PhCH=CH 35–76%, 50–60% de, 87–98% ee

Scheme 9.25 Formal 1,3-dipolar cycloaddition of glycine imino esters and cyclopentene-1,3-diones in the presence of a Ferrophos ligand.

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

to steric hindrance of the 3-substituent. In addition to substituted phenyl rings, the cyclopentenediones could bear a naphthyl (R1 = 2-Naph) and a vinyl group (R1 = vinyl), which gave the corresponding cycloadducts in moderate yields (68% and 63%, respectively) and excellent enantioselectivities of 95% and 94%, respectively, combined with a moderate diastereoselectivity of 50% de. The utility of this novel methodology was demonstrated by converting the bicyclic pyrrolidines into the corresponding enantiopure bicyclic pyrroles through oxidation with 2,3-dichloro-5,6-dicyanoquinone (DDQ) in toluene at room temperature without loss of enantioselectivity. These reactions were also developed by Wang and coworkers by using a (S)-TF-BiphamPhos-type ligand in dichloromethane as solvent in the presence of a base such as trimethylamine [57]. As shown in Scheme 9.26, the reaction of a wide range of cyclopentene-1,3-diones with various glycine imino esters afforded the corresponding chiral 5,5-fused bicyclic pyrrolidines as almost single diastereomers (>90% de) in all cases and with both high yields (82–93%) and enantioselectivities (92% to >99% ee). Outstanding results (89–91% yield and 92–99% ee) were achieved in the reaction of non-α-substituted imino esters (R4 = H) bearing electron-deficient, electron-rich, and electron-neutral substituents on the phenyl ring (R3 ) with 2-benzyl-2-methylcyclopent-4-ene-1,3-dione (R1 = Ph, R2 = Me). Additionally, imino esters bearing a cinnamyl group were also compatible, giving a high enantioselectivity (93% ee) with a lower yield (68%). It was worth noting that an alkyl imino ester (R3 = n-Bu) could also be applicable to the procedure, resulting in the desired product in 82% yield and 91% ee. Furthermore, several CF3 Br NH2 NHPPh2

F3C F3C O

Br

R1 CF3

R2

(5 mol%) AgOAc (5 mol%)

O + R R3

N

4

TEA CH2Cl2, –20 or 20 °C CO2Me (Cs2CO3)

R4

MeO2C

O R2

HN

R1

R3

O >90% de

R1 = Ph, 3-BrC6H4, 4-Tol, 3-ClC6H4, 4-BrC6H4, 2-Naph, CH2=CH R2 = Me, Et R3 = Ph, 4-ClC6H4, 3-ClC6H4, 4-Tol, 4-BrC6H4, 3-BrC6H4, 3-MeOC6H4, 2-Naph, 2-thienyl, (E)-PhCH=CH, n-Bu R4 = H, Me, Bn 82–93%, 92% to >99%ee

Scheme 9.26 Formal 1,3-dipolar cycloaddition of glycine imino esters and cyclopentene-1,3-diones in the presence of a (S)-TF-BiphamPhos ligand.

559

560

9 Asymmetric Silver-Catalyzed Reactions

α-methyl/benzyl-substituted imino esters (R4 = Me, Bn) remarkably led to the corresponding chiral bicyclic pyrrolidines bearing two quaternary stereogenic centers with both high yields (88–93%) and enantioselectivities (to >99% ee). In these latter cases of less reactive substrates, an inorganic base, such as Cs2 CO3 , was required as an additive, and the reactions were performed at room temperature instead of −20 ∘ C. Concerning the scope of the cyclopentenediones, it was found that the divergent substituents in the benzyl group did not display any significant effect on the catalytic activity and stereoselectivity, leading to products with 92–96% ee and 85–87% yield. High yield and excellent enantioselectivity were also obtained in the reaction of a naphthyl-substituted cyclopentenedione (84% yield and 94% ee). A cyclopentenedione combining methyl and allyl groups (R1 = vinyl, R2 = Me) and another one bearing an ethyl and a benzyl groups (R1 = Ph, R2 = Et) also provided excellent results (82–89% yield, 94–96% ee). On the other hand, Sansano and coworkers recently used (S)-BINAP as chiral ligand for Ag2 CO3 at 5 and 2.5 mol% catalyst loadings in toluene at −10 ∘ C to promote a three-component formal 1,3-dipolar cycloaddition between ethyl glyoxylate, phenylalanine ethyl ester, and variously N-substituted maleimides [58]. As shown in Scheme 9.27, the imino esters generated in situ reacted with various N-protected maleimides to give the corresponding highly functionalized octahydropyrrolo[3,4-c]pyrrole derivatives as single endo-diastereomers in uniformly excellent yields of 94–98% and with good to high enantioselectivities (77–92% ee). These biologically important products bore four contiguous stereogenic centers. Even a non-protected maleimide (R = H) yielded the corresponding bicyclic product in moderate yield of 65% albeit with a dramatically lower enantioselectivity (30% ee). A disadvantage of this process was related to the fact that it was limited to ethyl phenylalaninate as substrate. O

O EtO

H

+ R N

O

O

Toluene, –10 °C

Bn

+ H2N

(S)-BINAP (5 mol%) Ag2CO3 (2.5 mol%)

CO2Et

R = Me: 94%, 90% ee R = H: 65%, 30% ee R = Et: 96%, 85% ee

O

R N

O Bn

EtO2C

CO2Et N H endo >99% de

R = Bn: 95%, 77% ee R = Ph: 95%, 88% ee R = 4-BrC6H4: 98%, 92% ee

Scheme 9.27 Three-component formal 1,3-dipolar cycloaddition of ethyl glyoxylate, phenylalanine ethyl ester and maleimides in the presence of (S)-BINAP.

In 2016, Wang and coworkers developed a two-component version of related reactions promoted by 3 mol% of a catalyst generated in situ from AgOAc and a (S)-TF-BiphamPhos-derived ligand (Scheme 9.28) [59]. Actually, the reaction occurred between glycine imino esters and N-(2-t-butylphenyl)maleimide in dichloromethane at room temperature to yield the corresponding chiral bicyclic

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

CF3 Br NH2 NHPPh2

F3C F3C t-Bu O

O + R

N

(3 mol%) AgOAc (3 mol%) CH2Cl2, r.t.

R2 1

Br CF3

N

CO2Me

MeO2C HN R1

R2

O t-Bu N O

>90% de

R1 = Ph, 4-ClC6H4, 4-Tol, 3-ClC6H4, 4-BrC6H4, 3-BrC6H4, 1-FC6H4, 2-Naph, 4-MeOC6H4, 3-MeOC6H4, 2-thienyl, (E)-PhCH=CH, n-Bu R2 = H, Me, Et, n-Bu, i-Bu, t-Bu, Bn 86–99%, 90% to >99% ee

Scheme 9.28 Formal 1,3-dipolar cycloaddition of glycine imino esters and N-(2-t-butylphenyl)maleimide in the presence of a (S)-TF-BiphamPhos ligand.

products having four contiguous stereogenic centers in high yields (86–99%), excellent enantioselectivities (90% to >99% ee), and as almost single diastereomers (>90% de). The study of the substrate scope of the α-non-substituted imino esters (R2 = H) showed that they could be substituted by aromatic, heteroaromatic, and aliphatic groups (R1 ), providing comparably excellent results (86–99% yield and 90% to >99% ee). Furthermore, more sterically hindered imino esters derived from α-substituted-α-amino acids (R2 ≠ H) were compatible. Indeed, alanine-derived imino esters (R2 = Me) were proven to be excellent substrates regardless of electronic properties of aromatic substitutes (R1 ), giving access to the corresponding endo-products in 99% yield and 98% ee. Notably, excellent results (97–98% yield and 97% to >99% ee) were also obtained with substrates with larger steric hindrance (R2 = Et, n-Bu, i-Bu, t-Bu, or Bn). The utility of this methodology was demonstrated by the conversion of the products into 2H-pyrroles and polysubstituted pyrrole derivatives, which are structurally important nitrogen-containing heterocycles. Closely related reactions were also investigated by Xia and coworkers in the presence of Xing-Phos ligand as a chiral multifunctional ligand of AgF [60]. In this case, the reaction was performed in toluene at −20 ∘ C in the presence of a trace amount of water, which was shown to play an important role in the enhancement of the enantioselectivity. The reaction of a range of N-aryl-substituted maleimides with various aromatic imino esters led to the corresponding chiral pyrrolidines having four contiguous stereogenic centers as single endo-diastereomers (>96% de) in good to excellent yields (83–99%) and moderate to excellent enantioselectivities of 65–98% ee, as shown in Scheme 9.29. The enantioselectivity of the reaction was found to

561

562

9 Asymmetric Silver-Catalyzed Reactions

O O Ar2 N

+ Ar

N

PPh2 N(i-Pr)2

Xing-Phos (5.5 mol%) AgF (2.5 mol%)

O

1

H N S t-Bu Ph O

CO2R

H2O Toluene, –20 °C

Ar1

O N Ar2

HN MeO2C

O

>96% de Ar1

= Ph, 1-MeOC6H4, 3-MeOC6H4, 3-BrC6H4, 4-Tol, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-PhC6H4, 4-MeSC6H4, 3,5-F3CC6H3 Ar2 = Ph, 3-ClC6H4, 3-Tol, 3-BrC6H4, 4-EtOC6H4, 4-MeOC6H4, 4-BrC6H4, 3,5-Me2C6H3 R = Me, Et 83–99%, 65–98% ee

Scheme 9.29 Formal 1,3-dipolar cycloaddition of glycine imino esters and maleimides in the presence of Xing-Phos ligand.

be sensitive to the electronic nature of substituents borne by the aryl rings (Ar1 ) of the imino esters. For example, 4-methylphenyl-substituted imino methyl ester afforded the corresponding product in only 65% ee, while the corresponding 4-halogen-substituted-phenyl imino methyl esters provided high enantioselectivities (90–91% ee). Moreover, Sansano and coworkers recently reported the first enantioselective silver-catalyzed 1,3-dipolar cycloaddition of maleimides with glycine imino esters derived from 2,2-dimethoxyacetaldehyde [61]. It afforded under mild reaction conditions the corresponding chiral pyrrolidines exhibiting four contiguous stereogenic centers. The process employed a combination of AgF and a chiral Taniaphos ligand in toluene at room temperature in the absence of a base. The densely functionalized chiral products were obtained as single endo-diastereomers in good to quantitative yields (58–96%) and enantioselectivities (52–99% ee), as shown in Scheme 9.30. The interest in using this type of glycine imino esters was to gain a new functionalization on the pyrrolidine ring ready to be transformed into different functionalities. Another Taniaphos ligand was used by Kumar and coworkers in combination with AgOAc in diethylether at −78 ∘ C to promote the first enantioselective 1,3-dipolar cycloaddition of α-silylimines and benzopyrone-based trisubstituted olefins [62]. As shown in Scheme 9.31, it led to the corresponding tricyclic chiral pyrano-pyrrolidines bearing two quaternary stereogenic centers among three contiguous stereocenters. The major syn-diastereomers were obtained in high yields (76–94%), good to excellent diastereoselectivities (60% to >90% de), and uniformly high enantioselectivities (88–99% ee). The synthetic utility of this novel methodology was demonstrated through the conversion of some of these

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

PPh2 O Me2N

R1 N

R2

MeO

N

PPh2

(5 mol%) AgF (5 mol%)

O +

Fe

O MeO

Toluene, r.t.

N H

MeO

CO2Me

OMe

R1 N

O R2 CO2Me

58–96%, >99% de, 52–99% ee

1=

R Me, Bn, Ph, 4-AcC6H4, 4-ClC6H4, 4-BrC6H4, 3-ClC6H4, 2-MeOC6H4, H R2 = H, Bn, i-Bu

Scheme 9.30 Formal 1,3-dipolar cycloaddition of 2,2-dimethoxyacetaldehyde-derived glycine imino esters and maleimides in the presence of a Taniaphos ligand. i-Pr N

Fe

O

O PPh2

R1 R4 O + TMS

(10 mol%) AgOAc (10 mol%) Et2O, –78 °C

R2 N

CO2R3

O

R1 = CO2Me, CN R2 = Me, Et, i-Bu NH R4 R3 = Et, Me O 3 4 CO R R = H, Me, F, i-Pr, H R2 2 MeO, Br 76–94%, 60% to >90% de, 88–99% ee R1

Scheme 9.31 Formal 1,3-dipolar cycloaddition of α-silylimines and pyrone-based trisubstituted olefins in the presence of a Taniaphos ligand.

products into biologically interesting and highly complex tetracyclic scaffolds supporting four consecutive stereogenic centers with three quaternary carbons. In 2017, Wang et al. developed novel chiral amidophosphanes to be used as silver ligands in enantioselective 1,3-dipolar cycloadditions of glycine imino esters and diethyl maleate [63]. For example, an L-tert-leucine amidophosphane was employed at only 2 mol% of catalyst loading combined with 1 mol% of Ag2 CO3 in toluene at room temperature in the presence of triethylamine (TEA) as base to promote these reactions [64]. As shown in Scheme 9.32, they provided a range of chiral highly functionalized pyrrolidines with four contiguous stereocenters as single endo-diastereomers in moderate to quantitative yields (22% to >99%) and enantioselectivities (62–98% ee). It was shown that the reactions also occurred in the absence of TEA as base but with lower yields and enantioselectivities, especially for heterocyclic, aliphatic, and 2-substituted glycine imino esters.

563

564

9 Asymmetric Silver-Catalyzed Reactions

O CO2Et

Ph

CO2Et + R1

R2 N

CO2Me

N H

H N t-Bu O

PPh2

(2 mol%) Ag2CO3 (1 mol%)

EtO2C

TEA (5 mol%) Toluene, r.t.

R1

CO2Et R2 N H

CO2Me

endo

22% to >99%, >99% de, 62–98% ee R1 = Ph, 4-MeOC6H4, 4-Tol, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 1-Naph, 2-furyl, 3-pyridyl, Cy, 2-Naph, 3,4-Cl2C6H3, 2-Tol R2 = H, Me, Bn, 3-indolylmethyl, Ph

Scheme 9.32 Formal 1,3-dipolar cycloaddition of glycine imino esters and diethyl maleate in the presence of a tert-leucine-derived amidophosphane ligand.

9.3.2 Formal 1,3-Dipolar Cycloadditions of Glycine Imino Esters and Nitroalkenes Nitroalkenes are known to be Michael acceptors for the conjugate addition of glycine imino esters [65]. In particular, the latter substrates have been employed as azomethine ylide precursors in enantioselective formal 1,3-dipolar cycloadditions with nitroalkenes evolving through domino Michael/aza-Henry reactions. A number of these reactions have been catalyzed by various types of chiral metal complexes and organocatalysts for the construction of chiral prolinates mainly obtained with the exo-configuration under the control of chiral metal catalysts. In 2015, Najera and coworkers reported one example of these reactions catalyzed by 5 mol% of a combination of a chiral phosphoramidite ligand with a silver precatalyst, such as AgOBz or AgOTf, in the presence of 5 mol% of TEA as base in toluene at room temperature [66]. As shown in Scheme 9.33, the reaction of a series of aromatic glycine imino esters with nitroalkenes afforded the corresponding polysubstituted exo-4-nitroprolinates bearing four contiguous stereogenic centers in moderate to high yields (33–92%), good to excellent enantioselectivities (84% to >98% ee), and variable diastereoselectivities of up to 86% de. These reactions were actually investigated in the presence of three types of precatalysts including AgOBz, AgOTf, and also Cu(OTf )2 for comparison. High chemical yields, exo-diastereoselectivities, and enantioselectivities were obtained in the reactions of aryl nitroalkenes performed with AgOBz as the precatalyst. On the other hand, AgOTf was recommended as the precatalyst for imines derived from aromatic aldehydes other than benzaldehyde (Ar ≠ Ph), while Cu(OTf )2 was more suitable for reactions involving α-substituted imino esters (R1 ≠ H). Concerning the use of AgOBz as precatalyst, the lowest diastereoselectivity (0% de) and yield (33%) were observed in the case of the reaction of a nitroalkene bearing an aliphatic substituent (R2 = cyclohexyl), which, however, yielded the corresponding product with an excellent enantioselectivity of 96% ee. On the other hand, the best result was obtained in the reaction of 4-tolyl-substituted nitroalkene, which afforded

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

Ph O P N O Ph

R2

O2N

(5 mol%) AgOBz or AgOTf (5 mol%)

+ R1 Ar

N

TEA (5 mol%) Toluene, 25 °C

CO2Me

R2

O2N

R1 Ar

N H

CO2Me

exo-Major

Ar = Ph, 1-Tol, 3-Tol, 4-Tol, 4-MeOC6H4, 4-FC6H4, 4-BrC6H4, 2-Naph R1 = H, Me, i-Bu, Bn R2 = Ph, 4-Tol, 4-FC6H4, 1-BrC6H4, 3-BrC6H4, 4-BrC6H4, 2-furyl, Cy, 33–92%, 0–86% de, 84% to >98% ee

Scheme 9.33 Formal 1,3-dipolar cycloaddition of glycine imino esters and nitroalkenes in the presence of a phosphoramidite ligand.

via reaction with a phenyl imino ester (Ar = Ph, R1 = H) the corresponding product to be produced in 92% yield, 86% de, and 98% ee. In general, in comparison with chiral copper catalysts, the silver complexes were more versatile and less sensitive to sterically congested substrates. Xing-Phos ligand was recently applied to this type of reactions by Xia and coworkers [67]. As shown in Scheme 9.34, in the presence of 5.5 mol% of this ligand combined with 2.5 mol% of AgF as precatalyst in THF at −20 ∘ C, a series of aromatic nitroalkenes (R3 = aryl) were found to react with aryl as well as alkyl imino esters to give the corresponding highly substituted chiral 4-nitroprolinates

O

R3

O2N + R1

N

H N S t-Bu Ph O

PPh2 N(i-Pr)2

Xing-Phos (5.5 mol%) AgF (2.5 mol%) THF, –20 °C

CO2R2

R3

O2N R1

N H

CO2R2

exo-Major

R1 = Ph, 4-MeOC6H4, 4-ClC6H4, 4-Tol,4-FC6H4, 4-BrC6H4, 4-F3CC6H4, 3-BrC6H4, 3-MeOC6H4, 4-PhC6H4, 1-MeOC6H4, 2-Naph, i-Pr R2 = Me, Et R3 = Ph, 4-Tol, 2,3-(MeO)2C6H3, 3,4-(MeO)2C6H3, 4-MeOC6H4, 4-PhC6H4, CH2Bn 82–99%, 68% to >98% de, 77–99% ee

Scheme 9.34 Formal 1,3-dipolar cycloaddition of glycine imino esters and nitroalkenes in the presence of Xing-Phos ligand.

565

566

9 Asymmetric Silver-Catalyzed Reactions

in uniformly high yields (82–99%) and enantioselectivities (88–99% ee) along with moderate to complete exo-diastereoselectivities of 68 to >98% de. The lowest enantioselectivity (77% ee) was obtained in the reaction of an alkyl nitroalkene (R3 = CH2 Bn). In 2016, an endo-selective version of these processes was described by Fukuzawa and coworkers [68]. It involved the use of 5 mol% of AgOAc combined with the same quantity of ThioClickFerrophos ligand (Scheme 9.35) in 1,4-dioxane at room temperature. The reaction of various aryl and heteroaryl nitroalkenes with a range of (hetero)aryl imino esters afforded the corresponding chiral pyrrolidines as endo-cycloadducts in moderate to good yields of 51–86%, good to high diastereoselectivities of 82–92% de, and enantioselectivities of 86–97% ee (Scheme 9.35). In the case of the reaction of an alkyl imino ester (R = Cy), both lower yield and diastereoselectivity were obtained (47% yield and 76% de) albeit with high enantioselectivity (93% ee).

Ph2P Fe

N N N

t-BuS O2N Ar

+ R

N

CO2Me

Ph (5 mol%) AgOAc (5 mol%) 1,4-Dioxane, r.t.

Ar

O2N R

N H

CO2Me

endo-Major R = Ph, 1-Tol, 3-Tol, 4-Tol, 4-MeOC6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 1-Naph, 2-thienyl, Cy Ar = Ph, 1-Tol, 4-Tol, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 2-furyl, ferrocenyl 47–86%, 76–92% de, 86–97% ee

Scheme 9.35 Formal 1,3-dipolar cycloadditions of glycine imino esters and nitroalkenes in the presence of a ThioClickFerrophos ligand.

In 2016, Sansano and coworkers developed enantioselective 1,3-dipolar cycloadditions of α-imino γ-lactones and nitroalkenes in the presence of (R,R)-Me-Duphos ligand and AgF in toluene at 0 ∘ C [69]. The reactions led to the corresponding chiral spirolactones in moderate to good yields (40–73%), moderate to excellent endo-diastereoselectivities (48–98% de), and moderate to excellent enantioselectivities (50–96% ee), as shown in Scheme 9.36. With the aim of synthesizing biologically interesting chiral heterocycles bearing both methylisoxazole and pyrrolidine moieties, Wang and coworkers have developed enantioselective silver-catalyzed 1,3-dipolar cycloadditions of glycine imino esters and 3-methyl-4-nitro-5-styrilisoxazoles in the presence of different types of ligands [70]. As shown in Scheme 9.37, according to the nature of the ligand employed in combination to AgOAc, the reaction was remarkably endo- or exo-selective. Indeed, the use of a Phosferrox chiral ligand

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

P O2N

P R

+

Ar

(R,R)-Me-Duphos (5 mol%) AgF (5 mol%)

O2N R

NH

Toluene, 0 °C

N

Ar

O O

O

O

40–73%, 48–98% de, 50–96% ee

Ar = Ph, 1-Tol, 3-Tol, 4-Tol, 4-MeOC6H4, 4-BrC6H4, 2-Naph, 2-furyl R = Ph, 4-FC6H4, 2-BrC6H4, 3-BrC6H4, 2-furyl, Cy, i-Bu

Scheme 9.36 Formal 1,3-dipolar cycloaddition of α-imino γ-lactones and nitroalkenes in the presence of (R,R)-Me-Duphos ligand. O

Fe

R2

N

MeO2C

CO2Me + R1

O2N N

t-Bu

N PPh2

(5 mol%) AgOAc (5 mol%)

R1

TEA, CH2Cl2, r.t.

O2N

NH R2 O N

O 57–92%, >90% de, 64–91% ee

endo R = Ph, 3-Tol, 4-ClC6H4, 3-Tol, 1-MeO, 4-MeO, 1-MeO, c-Pr, (E)-PhCH=CH R2 = 4-Cl, 3-Cl, 4-Br, 1-Tol, 4-MeO, Ph, 2-furyl, 1-Naph, 2-Naph 1

Ph O P N R2 R1

N

O Ph CO2Me

+ Ph

O2N

(5 mol%) AgOAc (5 mol%) TEA, CH2Cl2, 0 °C

N

MeO2C R2

NH R1

Ph O2N

O N

O 63–96%, >90% de, 82–93% ee

exo

R1 = 4-Tol, 4-ClC6H4, 4-BrC6H4, 3-Tol, 4-MeO, 1-MeO, 3-MeO, 2-thienyl, n-Bu R2 = H, Me

Scheme 9.37 Formal 1,3-dipolar cycloadditions of glycine imino esters and 3-methyl-4-nitro5-styrilisoxazoles in the presence of MonoPhos and Phosferrox ligands.

567

568

9 Asymmetric Silver-Catalyzed Reactions

in dichloromethane at room temperature in the presence of TEA as base led to the formation of the corresponding endo-cycloadducts in good yields (57–92%), uniformly high endo-diastereoselectivity (>90% de), and good to high enantioselectivities (64–91% ee). On the other hand, when a chiral MonoPhos ligand was employed under the same reaction conditions albeit at 0 ∘ C, it afforded the corresponding exo-cycloadducts with high yields (63–96%), >90% de, and high enantioselectivities (82–93% ee). 9.3.3 Formal 1,3-Dipolar Cycloadditions of Isocyanoacetates and 𝛂,𝛃-Unsaturated Carbonyl Compounds Escolano and coworkers have described enantioselective formal 1,3-dipolar cycloadditions of isocyanoacetates with α,β-unsaturated ketones evolving through domino Michael/cyclization reactions [71]. The reaction of isocyanoacetates (R2 = Bn, H) with α,β-unsaturated ketones performed in the presence of a combination of a chiral bifunctional cinchona alkaloid, such as cupreine, and AgNO3 provided the corresponding chiral functionalized 2,3-dihydropyrroles in low to high yields (20–85%) and enantioselectivities of 16–89% ee, as shown in Scheme 9.38. In this process, the two catalysts interacted cooperatively. AgNO3 increased the acidity of the pronucleophile, and the bifunctional cupreine

N OH N OH O NC

R1O2C

+

O

Cupreine (10 mol%) AgNO3 (5 mol%) R3

R1O2C *

CH2Cl2, r.t.

R2

R3 R2 N H

R1 = Me, Et, t-Bu R2 = H, Bn R3 = Me, Et 20–85%, 16–89% ee

Michael/ cyclization

–

N O

O

H

N O

+ N

–

O R1

C

AgLn

R2

H O

R3

Scheme 9.38 Formal 1,3-dipolar cycloaddition of isocyanoacetates and α,β-unsaturated ketones.

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

catalyst was responsible for the dual activation through hydrogen bonding interactions, as shown in Scheme 9.38. In 2012, Shi and coworkers reported the first example of a cinchona alkaloid-derived squaramide/AgSbF6 cooperative catalytic system for the highly diastereo- and enantioselective formal 1,3-dipolar cycloadditions of isocyanoacetates (R2 = H, aryl, alkyl) with maleimide [72]. As shown in Scheme 9.39, a range of chiral 1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole derivatives were synthesized in moderate to high yields (50–98%) and excellent diastereoselectivities of >90% de, along with moderate to high enantioselectivities of up to 92% ee through cooperative catalysis with AgSbF6 and a cinchona alkaloid-derived squaramide. The highest enantioselectivities of 74–90% ee were achieved in the reaction of N-aryl maleimides with α-aryl isocyanoesters, while only 10–65% ee

N ArHN

HN N

O O Ar = 3,5-(CF3)2C6H3 (5 mol%) AgSbF6 (10 mol%)

O NC

R1O2C

N R3

+

R2

CH2Cl2, r.t. 3 Å MS

R2 O

CO2R1 O N R3

N

O

Cyclization

Michael N O H N+

N H H

O N Ar H

O– OR1 R2 Through Re face

2+

N+

C– Ag

O

Re-face attack

N R3 O

R1 = Me, Et, Bn, t-Bu R2 = Ph, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-Tol, 3-FC6H4, 3-Tol, 1-BrC6H4, 1-Tol, i-Pr, Bn, H R3 = Ph, 4-FC6H4, 4-BrC6H4, 4-Tol, 4-MeOC6H4, 3-ClC6H4, 3-MeOC6H4, Bn, Me 50–98%, 82% to >90% de, 10–92% ee

Scheme 9.39 Formal 1,3-dipolar cycloaddition of isocyanoacetates and maleimides.

569

570

9 Asymmetric Silver-Catalyzed Reactions

were obtained in the reaction of α-alkyl isocyanoesters or N-alkyl maleimides albeit combined with excellent diastereoselectivity (>90% de) and good yields (67–85%). To explain the stereoselectivity of the domino Michael/cyclization reaction, the authors have proposed the transition state model depicted in Scheme 9.39, in which one carbonyl group of the maleimide was hydrogen bonded to the squaramide motif, while the α-proton of the isocyanoacetate was easily deprotonated by the quinuclidine nitrogen of the cinchona catalyst due to the activation of Ag(I) chelating to the terminal carbon of the isocyano group. A single hydrogen bond was then formed between the OH group of the enolized isocyanoacetate and the tertiary amine of the cinchona alkaloid. A weak hydrogen bond between the OR1 group of the enolized isocyanoacetate and the NH group in the squaramide moiety, as well as an interaction between Ag(I) and the other carbonyl group of the maleimide, could be formed concurrently, thus forcing the isocyanoacetate enolate to attack the maleimide from the Re face, thereby leading to the formation of two newly generated stereocenters with the (R,R)-configuration. Subsequently, a 5-endo-dig cyclization took place assisted by electrophilic silver isocyanide activation. The third stereocenter was formed as S-configuration after the cyclization step. In 2016, isocyanoacetates were also used as substrates by Xie and coworkers in enantioselective formal 1,3-dipolar cycloadditions with 2-(2-aminophenyl)acrylates [73]. The reaction was cooperatively promoted by a combination of 5 mol% of AgNO3 and 6 mol% of a chiral cinchona alkaloid in acetonitrile at room temperature. It proceeded through the sequential Michael addition of metalated isocyanoacetates to acrylates, the intramolecular nucleophilic addition of the thus-formed enolates to the isocyano group, and the intramolecular attack of the nucleophilic amido to the thus-produced 2H-pyrrolidine intermediates. As shown in Scheme 9.40, a range of densely functionalized chiral cis-3a,8a-hexahydropyrrolo[2,3-b]indoles could be achieved through this methodology in good to quantitative yields (73–99%) and variable diastereo- and enantioselectivities of up to >90% and 90% ee, respectively. It must be noted that this core scaffold is present in a large array of biologically important natural products. A wide range of functional groups, such as substituents on the phenyls and alkenes, various ester groups, both on the acrylates and isocyanoacetates, and various amino-protecting groups in acrylates, could be tolerated in the domino reaction, producing the tricyclic chiral products bearing up to four contiguous stereogenic centers in good yields albeit with generally low diastereoselectivities except for β-substituted 2-(2-amidophenyl)-acrylates, which afforded the corresponding products as single diastereomers (>19 : 1 dr) in good enantioselectivities of 71–82% ee. In 2015, Zhao and coworkers investigated for the first time the cyclization of allenoates with isocyanoacetates [74]. These reactions were performed in the presence of a chiral silver catalyst generated in situ from Ag2 O and a cinchona alkaloid-based phosphine ligand in chloroform at −20 ∘ C. When an unsubstituted isocyanide, such as methyl isocyanoacetate, was reacted with various allenoates (Scheme 9.41), it regioselectively afforded the corresponding

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

PPh2 H N R1

N

R2 OMe

O R4

CO2R3 X

NHPG

N (6 mol%) AgNO3 (5 mol%)

+

R2

CO2R5

NH

MeCN, r.t.

O CN

R4

R1 R3O2C X

N PG

OR5 Cyclization

Michael/cyclization R1 R O2C

R2

3

R4

X

NH PG

CO2R5

N+ Ag

R1 = R2 = R4 = H, R3 = R5 = Et, PG = Piv, X = CH: 93%, 1.6 : 1 dr, 85% ee/88% ee R1 = R2 = H, R3 = R5 = Et, R4 = Me, PG = Piv, X = CH: 89%, 1.4 : 1 dr, 80% ee/85% ee R1 = R2 = H, R3 = R5 = Et, R4 = Cl, PG = Piv, X = CH: 86%, 2.3 : 1 dr, 59% ee/65% ee R1 = H, R2 = Ph, R4 = Cl, R3 = R5 = Et, PG = Piv, X = CH: 87%, >19 : 1 dr, 80% ee R1 = H, R2 = n-Pr, R3 = R5 = Et, R4 = Cl, PG = Piv, X = CH: 85%, >19 : 1 dr, 71% ee/82% ee R1 = R2 = R4 = H, R3 = R5 = Et, PG = Piv, X = N: 84%, 2.4 : 1 dr, 78% ee/77% ee R1 = R2 = R4 = H, R3 = R5 = Bn, PG = Piv, X = CH: 97%, 1.4 : 1 dr, 77% ee/82% ee R1 = R2 = R4 = H, R3 =t-Bu, R5 = Et, PG = Piv, X = CH: 75%, 2.4 : 1 dr, 88% ee/90% ee R1 = R2 = R4 = H, R3 = t-Bu, R5 = 1-Adamantyl, PG = Piv, X = CH: 99%, 4 : 1 dr, 0% ee/18% ee R1 = R2 = R4 = H, R3 = t-Bu, R5 = Et, PG = Tos, X = CH: 83%, 3 : 1 dr, 12% ee/41% ee R1 = R2 = R4 = H, R3 = t-Bu, R5 = Et, PG = Ac, X = CH: 73%, 2 : 1 dr, 7% ee/11% ee R1 = R2 = R4 = H, R3 = R5 = t-Bu, PG = Boc, X = CH: 82%, 2 : 1 dr, 6% ee/6% ee

Scheme 9.40 Formal 1,3-dipolar cycloaddition of isocyanoacetates and 2-(2-aminophenyl)acrylates.

571

572

9 Asymmetric Silver-Catalyzed Reactions

PPh2 HN

O

N N

R

CO2Me C CH2

CO2Me

(20 mol%) Ag2O (10 mol%)

+ CN

CO2Me

CHCl3, –20 °C CO2Me

[3+2]

N

MeO2C R 1,3-H shift

N

MeO2C R

R = Bn, CH2(4-Tol), CH2(4-MeOC6H4), CH2(4-BrC6H4), CH2(4-FC6H4), CH2(4-F3CC6H4), CH2(3-BrC6H4), CH2(1-Tol), CH2(1-BrC6H4), CH2(1-F3CC6H4), allyl, Et, n-Hept 73–92%, 80–96% ee R1

CO2R2 C CH2

R3

R3

+ CN

CO2Me

Same conditions CO2Me

N

R2O2C R1

R1 = Bn, CH2(1-FC6H4), CH2(1-BrC6H4), CH2(1-Tol), CH2(4-FC6H4), CH2(4-Tol), CH2(3-BrC6H4), CH2(3,5-MeO2C6H2), allyl R2 = Me, Et R3 = Bn, Me 58–90%, 72% to >90% de, 82–96% ee

Scheme 9.41 Formal 1,3-dipolar cycloadditions of isocyanoacetates and allenoates.

chiral 3H-pyrroles in good to high yields of 73–92% and enantioselectivities of 80–96% ee. Actually, these products arose from a [3 + 2]-cyclization followed by a 1,3-H shift (Scheme 9.41). A wide variety of methyl allenoates bearing different alkyl groups were compatible, providing uniformly good results. To further extend the scope of this catalytic system, the reaction of allenoates with substituted isocyanoacetates was investigated under the same conditions. In this case, the direct [3 + 2]-cyclization products possessing an exocyclic olefin were obtained in moderate to high yields and diastereoselectivities of 58–90% and 72% to >90% de, respectively, in combination with high enantioselectivities of 82–96% ee (Scheme 9.41). A range of chiral heterocycles could be achieved from the reactions of benzyl- and methyl-substituted isocyanoacetates with variously alkyl-substituted ethyl and methyl allenoates.

9.3 Silver-Catalyzed 1,3-Dipolar Cycloadditions

9.3.4

Other 1,3-Dipolar Cycloadditions

In 2016, Feng and coworkers reported the first catalytic asymmetric inverse-electron-demand 1,3-dipolar cycloaddition of isoquinolinium methylides with enecarbamates based on chiral silver catalysis [75]. This process was promoted by a combination of AgBF4 as precatalyst with a chiral N, N ′ -dioxide ligand in THF at 0 ∘ C. It led to the corresponding optically active pyrroloisoquinolines (X = CH) as almost single diastereomers (>90% de) in moderate to quantitative yields (33–99%) and moderate to high enantioselectivities of 77–95% ee, as shown in Scheme 9.42. The best enantioselectivities of 91–95% ee were obtained in the reaction of an enecarbamate with a pentafluorobenzyl carboxyl group (R1 = C6 F5 CH2 ), while the lowest one (77% ee) was obtained with an enecarbamate bearing a tert-butyl carboxyl group (R1 = t-Bu). Generally, enecarbamates with an electron-deficient substituent on the benzyl group (R1 ) provided the corresponding products in higher enantioselectivities than those with an electron-donating substituent. Moreover, the scope of the azomethine ylides was investigated by reacting optimal enecarbamate bearing a pentafluorobenzyl carboxyl group. Isoquinolinium methylides with electron-deficient substituents (R2 ), such as Cl or Br, at 4- or 5-position were well tolerated to give the corresponding products in 80–99% yields and 95% ee. An isoquinolinium methylide with electron-rich OMe group at the 5-position was also a suitable substrate, delivering the corresponding product in 82% yield and 91% ee. However, when the OMe substituent was situated at the 6-position of the substrate, the corresponding product was achieved in much lower yield (33%) but with still high de and ee (>90% de and 91% ee). It is worth noting that a

R2 Y

X N

O CN CN

+ N H

CO2R1

N N O O NHR′ R′HN R′ = (S)-PhCHMe (12 mol%) AgBF4 (10 mol%) THF, 0 °C

O R2 Y

X N *

CN

*

CN NHCO2R1

>90% de R1

= Bn, 1-FC6H4CH2, 4-FC6H4CH2, 3-ClC6H4CH2, 4-ClC6H4CH2, 4-BrC6H4CH2, C6F5CH2, 4-F3CC6H4CH2, 4-MeOCH2, Me, Et, i-Pr, t-Bu R2 = H, Br, Cl, OMe X = CH, N Y = H, OMe 33–99%, 77–95% ee

Scheme 9.42 Inverse-electron-demand 1,3-dipolar cycloaddition of isoquinolinium/phthalazinium methylides and enecarbamates.

573

574

9 Asymmetric Silver-Catalyzed Reactions

phthalazinium dicyanomethylide (X = N, R2 = Y = H) was also a suitable dipole, leading to the desired pyrrolophthalazine in 91% yield, >90% de, and 95% ee.

9.4 Silver-Catalyzed Domino and Tandem Reactions A domino reaction has been strictly defined by Tietze as a process in which two or more bond-forming transformations occur based on functionalities formed in the previous step in which no additional reagents, catalysts, or additives can be added to the reaction vessel, nor can reaction conditions be changed [76]. Domino reactions [77] allow the synthesis of a wide variety of complex molecules including natural products and biologically active compounds to be economically achieved on the basis of one-pot processes avoiding the use of costly and time-consuming protection–deprotection processes, as well as purification procedures of intermediates [76, 78]. The first example of asymmetric silver-catalyzed domino reaction was reported in 1990 by Ito and coworkers, who employed chiral ferrocenylphosphine–silver(I) complexes as chiral catalysts to promote asymmetric domino aldol/cyclization reactions of aldehydes with tosylmethyl isocyanide [4a]. In the presence of only 1 mol% of catalyst loading, this reaction afforded the corresponding chiral 5-alkyl-4-tosyl-2-oxazolines in enantioselectivities of up to 86% ee. Ever since, a range of various enantioselective silver-catalyzed domino reactions, including multicomponent ones as well as multicatalyzed ones [6f, 79], have been successfully developed by several groups. 9.4.1

Domino and Tandem Reactions Initiated by a Michael Addition

It must be noted that this section does not include asymmetric formal [3 + 2]-cycloadditions of azomethine ylides derived from glycine imino esters with α,β-unsaturated carbonyl compounds or nitroalkenes, which are supposed to evolve through domino Michael/Mannich or Michael/aza-Henry reactions, respectively, since these transformations are collected in separate Section 9.3 (Sections 9.3.1 and 9.3.2). Similarly, asymmetric formal [3 + 2]-cycloadditions of isocyanoacetates with α,β-unsaturated carbonyl compounds, which evolve through domino Michael/cyclization reactions, have also been included in Section 9.3 (Section 9.3.3) but could be situated in Section 9.4 for the same mechanistic reasons. In the last few years, several types of enantioselective domino and tandem reactions initiated by Michael additions have been developed based on the use silver catalysts sometimes combined with organocatalysts. Tandem-catalyzed reactions refer to the synthetic strategies of modular combination of catalytic reactions into one synthetic operation, occurring one after the other and working in conjunction with each other with minimum workup or change in conditions in comparison with domino reactions defined by Tietze. A recent example of asymmetric tandem reactions based on sequential silver catalysis and organocatalysis was reported by Enders and coworkers [80]. It allowed the enantioselective synthesis of biologically interesting five-membered

9.4 Silver-Catalyzed Domino and Tandem Reactions

annulated hydroxycoumarins with enantioselectivities of up to 99% ee to be achieved from the reaction between the corresponding 4-hydroxycoumarins and aryl-substituted enynones. As shown in Scheme 9.43, the first step of the sequence involved the Michael addition of 4-hydroxycoumarins to aryl-substituted enynones catalyzed by 20 mol% of a cinchona-derived primary amine in THF at 4 ∘ C in the presence of (S)-N-Boc alanine as chiral additive, yielding the corresponding Michael products. Studies revealed that THF, which was used as solvent in this first step, was inappropriate for the subsequent silver-catalyzed cyclization. Thus, before the second step, the solvent had to be changed to toluene prior to the addition of Ag2 CO3 , which was compatible to the organocatalyst. Then, a hydroxyalkoxylation afforded the final domino tricyclic products in moderate to high yields (54–91%) and enantioselectivities of 70–99% ee. In the case of aryl-substituted enynones, the cyclization occurred through 5-exo-dig cyclization to give the corresponding domino chiral products in good to high yields and enantioselectivities irrespective of electronic and steric effects of substituents, although bulky substituents normally resulted in an increased reaction time in the cyclization step. Moreover, hydroxycoumarins bearing different substituents were also tolerated. In contrast, enynones bearing aliphatic substituents led to the formation of the corresponding 6-endo-products with comparable enantioselectivities of 89–90% ee but combined with lower yields of 32–52% due to a less selective ring formation (Scheme 9.43). Later in 2016, the same authors described enantioselective silver-catalyzed true domino Michael/hydroxyalkoxylation reactions between 2-hydroxy-1,4naphthoquinones and alkyne-tethered nitroalkenes [81]. As shown in Scheme 9.44, the process was sequentially promoted by a silver catalyst such as AgOTf (15 mol%) and a chiral squaramide employed at a remarkably low catalyst loading of 0.5 mol% in dichloromethane at room temperature. It led to the corresponding chiral 4H-pyranonaphthoquinones in low to excellent yields (23–94%) and uniformly high enantioselectivities (89–99% ee). The authors have proposed a sequential catalysis to explain the results. In a first catalytic cycle, the squaramide acted as a bifunctional catalyst that activated the nitroolefin by its squaramide moiety and the deprotonation of the 2-hydroxy-1,4-naphthoquinone by its tertiary amine group, facilitating the Michael addition. Then, the deprotonated 2-hydroxy-1,4-naphthoquinone attacked the fixed nitroolefin from the Re face to provide the Michael adduct. In a second catalytic cycle, the silver catalyst promoted the electrophilic activation of the alkyne to facilitate the hydroalkoxylation, providing the final product. This novel process is highly useful, owing to the interesting biological activities associated with the naphthoquinone derivatives. In 2015, the same authors reported another domino Michael-initiated asymmetric reaction between alkyne-tethered nitroalkenes and 5-pyrazolones based on relay multicatalysis with a cinchona-derived squaramide and Ag2 CO3 [82]. The domino Michael/hydroalkoxylation reaction was performed in dichloromethane at −20 ∘ C, providing the corresponding chiral functionalized pyrano-annulated pyrazole derivatives in moderate to excellent yields (48–95%) and high enantioselectivities (77–95% ee), irrespective of the steric or electronic nature of the substituents of alkynes (R1 ), which could be aromatic,

575

576

9 Asymmetric Silver-Catalyzed Reactions

With aryl-substituted enynones: OMe N OH NH2 R

(1)

O

O

O

+

Ar

N

(20 mol%) (S)-Boc-N-alanine (40 mol%) THF, 4 °C

O O R

(2) Ag2CO3 (10 mol%)

O

O

Toluene, r.t. Ar Silver catalysis

Organocatalysis

5-exo-dig cyclization

Michael Ar Ag O

OH R O

O

Ar = Ph, 4-FC6H4, 4-BrC6H4, 4-F3CC6H4, 2,3-CH2OCH2C6H3, 3-Tol, 3-MeOC6H4, 1-ClC6H4, 2-Naph, 1-Naph, 2-furyl, 2-thienyl, H R = H, 6-Me, 6,7-CH2OCH2, 7-MeO, 6-Cl 54–91%, 70–99% ee With alkyl-substituted enynones: OH R O

O

O

O

Same conditions +

O O

O

R = n-Bu: 52%, 90% ee R = c-Pent: 32%, 89% ee

R Silver catalysis

Organocatalysis Michael R OH

O

6-endo-dig cyclization

Ag O

O

Scheme 9.43 Tandem Michael/hydroalkoxylation reactions of 4-hydroxycoumarins and enynones.

9.4 Silver-Catalyzed Domino and Tandem Reactions

CF3

O R1

F3C

O

O

N H

N H

N

OH

O (0.5 mol%) AgOTf (15 mol%)

R2 O +

R1

O

CH2Cl2, r.t.

R2

R3

O

NO2 23–94%, 89–99% ee

NO2

R3

Silver catalysis

Organocatalysis

Hydroalkoxylation

Michael O OH

O

R3

[Ag] NO2

R1 = H, OMe, Me, F R2 = H, Me R3 = Ph, 1-Naph, 2-Naph, 2-ClC6H4, 2-BrC6H4, 4-F3CC6H4, 3-MeOC6H4, 3-Tol, 2-Tol, 3,4-(OCH2O)C6H3, 2-furyl, 2-thienyl, n-Bu, c-Pent

Scheme 9.44 Domino Michael/hydroalkoxylation reaction of 2-hydro-1,4-naphthoquinones and alkyne-tethered nitroalkenes.

heteroaromatic, and aliphatic groups (Scheme 9.45). Only the internal alkynes with bulky substituents on the 2-position (R1 = 2-BrC6 H4 , 2-ClC6 H4 , or 1-naphthyl) gave slightly lower yields (74–77%). Interestingly, in all examples, a clean cyclization to the 6-endo-derived products was observed. Moreover, different pyrazolinones led to similar results. The authors have proposed relay catalysis concept to explain this process in which the first Michael addition was organocatalyzed and the second step promoted by the silver catalyst. In 2016, a closely related cinchona-derived squaramide was combined with Ag2 O by the same authors to catalyze the synthesis of multifunctionalized chiral five-membered spiropyrazolones [83]. As shown in Scheme 9.46, these products were formed through domino Michael/Conia-ene reactions of 5-pyrazolones with another type of alkyne-tethered nitroalkenes in chloroform at −40 ∘ C to room temperature. Notably, the process employed only 1 mol% of the organocatalyst and generally 3 mol% of Ag2 O, which successively and respectively catalyzed the two steps of the domino reaction according to relay catalysis. Moderate to excellent yields and enantioselectivities of up to 99% and 99% ee, respectively, were achieved in combination with high diastereoselectivities of 78% to >90% de

577

578

9 Asymmetric Silver-Catalyzed Reactions

O

O

NH

N H

CF3

N N

R2 N N MeO

R3

O

CF3 R2

(1 mol%) Ag2CO3 (10 mol%)

+ NO2

O

CH2Cl2, –20 °C

R1

N N R3 NO2

R1 Ag2CO3

Organocatalyst

6-endo-dig cyclization

Michael R

2

N N R3

HO

NO2 R1

Ag

R1 = Ph, 1-BrC6H4, 4-F3CC6H4, 1-ClC6H4, 3-Tol, 3-MeOC6H4, 3,4-OCHOC6H3, 1-Naph, 2-Naph, 1-furyl, 1-thienyl, n-Bu, c-Pent R2 = Ph, 1-ClC6H4, 4-ClC6H4, Me R3 = Me, CF3 48–95%, 77–95% ee

Scheme 9.45 Domino Michael/hydroalkoxylation reaction of 5-pyrazolones and alkyne-tethered nitroalkenes.

in the reactions of differently substituted pyrazolones and terminal alkynes. In general, the electronic nature of the substituent did not influence the outcome of the reaction; however, bulky nitroalkenes led to lower yields of 27–54%. The application of nitroalkenes with internal alkynes bearing aliphatic substituents (R4 = Cy, n-Bu) was also feasible, although higher catalyst loadings in Ag2 O (10 mol% instead of 3 mol%) had to be used to achieve comparable results. In another area, Xu and coworkers recently reported the first enantioselective silver-catalyzed tandem Michael/cyclocondensation reaction of a glycine aldimino ester with chalcones [84]. As shown in Scheme 9.47, the process was catalyzed by a chiral silver complex in situ generated from AgOAc and chiral Xing-Phos ligand in methanol at −20 ∘ C in the presence of Me2 NCy as base, leading to the corresponding intermediate Michael products. The latter were subsequently submitted to cyclocondensation by treatment with aqueous HCl to afford the corresponding chiral cis-pyrrolines in uniformly high yields (81–98%) and excellent enantioselectivities (89–97% ee).

9.4 Silver-Catalyzed Domino and Tandem Reactions

O

O

NH

N H

CF3

N R3 N N O

N R2

MeO

O2N

(1 mol%) Ag2O (3 or 10 mol%)

+ R1

CF3

NO2

R1

O N N

CHCl3, –40 °C to r.t.

R3

R2 R4 R4 Organocatalyst

Ag2O

Michael

Conia-ene reaction

O2N HO R1

N N

R3

R2 R4 R1 = H, OMe, F, Cl R2 = Me, Et, i-Pr, CF3, Ph R3 = Ph, 1-ClC6H4, 4-ClC6H4, 4-Tol, Me

R4 = H, Cy, n-Bu 27–99%, 78% to >90% de, 42–99% ee

Scheme 9.46 Domino Michael/Conia-ene reaction of 5-pyrazolones and alkyne-tethered nitroalkenes.

9.4.2

Domino Reactions Initiated by an Aldol Reaction

In 2011, Dixon and coworkers developed asymmetric domino aldol/cyclization reactions of branched aliphatic as well as aromatic aldehydes with isocyanoacetates as well as α-substituted ones by using a new class of chiral aminophosphine precatalysts derived from 9-amino(9-deoxy) epicinchona alkaloids in combination with Ag(I) salts, such as Ag2 O [85]. The corresponding chiral oxazolines were obtained in 50–93% yields and good to high diastereoselectivities (up to 98% de), along with good to excellent enantioselectivities (up to 98% ee), as shown in Scheme 9.48. This protocol could be performed by mixing together the cinchona organocatalyst and Ag2 O, which interacted cooperatively (Scheme 9.48). Moreover, the possibility of lowering the catalyst loading to 2 mol% of chiral aminophosphine and 0.5 mol% of Ag2 O was demonstrated since under these conditions, yields of 44–90% were obtained in combination with diastereo- and enantioselectivities of up to 86% de and 94% ee, respectively. Interestingly, when α-substituted isocyanoacetates were used, the opposite facial selectivity in the nucleophilic component was observed.

579

580

9 Asymmetric Silver-Catalyzed Reactions

H N

O

Ar1

PPh2

S (1) t-Bu Ph

O

N(i-Pr)2 O Xing-Phos (5.5 mol%)

Ar2 +

Ar1

AgOAc (2.5 mol%) N

Ar2

Me2NCy (10 mol%)

CO2Me

CO2Me

81–98%, 89–97% ee

MeOH, –20 °C (2) 1 M HCl

Ag2O

Ar2

Michael

N

Cyclocondensation Ar1

O N

CO2Me

Ar1 = Ph, 4-F3CC6H4, 4-Tol, 4-MeOC6H4, 4-FC6H4,4-ClC6H4, 4-BrC6H4, 3-Tol, 3-MeOC6H4, 2-furyl Ar2 = Ph, 4-Tol, 4-MeOC6H4, 4-FC6H4, 4-ClC6H4, 3-MeOC6H4, 2-pyridyl

Scheme 9.47 Tandem Michael/cyclocondensation reaction of a glycine aldimino ester with chalcones.

N HN

Ph2P

N

O

CN

1

R

+ 2

CO2R

(5 mol%) Ag2O (2.5 mol%)

O R3

H

Ar

*

AcOEt or MTBE 4 Å MS

HN + NH

Ag CN –O

R1 = H, Ph, Bn R2 = Me, t-Bu R3 = Ph, 3-BrC6H4, 4-FC6H4, 4-MeOC6H4, 3-FC6H4, 4-BrC6H4,

R3

R1 CO2R2

R3

PPh2

O

N

O

H

O R1

OR2 3-MeOC6H4, 4-ClC6H4, 4-MeO2CC6H4, MeO2C(Me)2C, t-Bu, i-Pr 50–93%, 82–98% de, 61–98% ee

Scheme 9.48 Domino aldol/cyclization reaction of aldehydes and isocyanoacetates.

9.4 Silver-Catalyzed Domino and Tandem Reactions

As an extension of the methodology, the same authors very recently developed a short asymmetric synthesis of (−)-chloramphenicol, being the first one that relied on a catalytic enantio- and diastereoselective aldol reaction [86]. As shown in Scheme 9.49, the key step of this strategy involved the silver-catalyzed domino aldol/cyclization reaction of p-nitrobenzaldehyde with an isocyanoacetate to give the corresponding trans-oxazoline in 68% yield, along with a good diastereoselectivity of 84% de and a high enantioselectivity of 93% ee (Scheme 9.49). These results were obtained when the reaction was catalyzed in the presence of 5 mol% of the chiral cinchona alkaloid. The domino product was further converted into the desired antibiotic through three supplementary steps. The scope of this reaction, catalyzed by other silver complexes derived from chiral cinchona alkaloids, was extended to various alkyl isocyanoacetates, providing the corresponding oxazolines in comparable yields of 56–80% and diastereo- and enantioselectivities of 76–82% de and 78–87% ee, respectively (Scheme 9.49). These authors applied a combination of Ag2 O and a chiral quinine-derived aminophosphine ligand, respectively, used at loadings of 2.5 and 5 mol%, in AcOEt at −20 ∘ C to related novel silver-catalyzed enantioselective domino reactions of isocyanoacetates with ketones instead of aldehydes [87]. The domino process began with the aldol reaction of unactivated aryl alkyl ketones with isocyanoacetates to give the corresponding aldol products, which further cyclized to afford chiral oxazolines possessing a fully substituted stereocenter in 55–84% yields and good to excellent diastereo- and enantioselectivities (70–92% de and 82–98% ee). Several methyl aryl ketones with either electron-withdrawing or electron-donating groups afforded the trans-configured oxazolines as well as methyl heteroaryl ketones. In addition to methyl aryl ketones, other alkyl aryl ketones, such as ethyl, n-propyl, and t-butyl aryl ketones, led to the corresponding domino products with comparable efficiency. The synthetic utility of this novel methodology was shown by converting some of the oxazolines through hydrolysis into amino acid derivatives. To explain the stereochemical outcome of the process, the authors have proposed the transition state depicted in Scheme 9.50 in which the phosphorus and amide nitrogen atoms of the ligand, the oxygen atom of the ketone, and the terminal carbon atom of the isonitrile coordinated to a Ag(I) ion through a tetrahedral arrangement. Additional transition state stabilization was provided through hydrogen bonding of the protonated quinuclidine to the coordinated ketone oxygen atom. Notably, this interaction created a well-defined chiral pocket that could readily differentiate the enantiotopic faces of the bound ketone; unfavorable steric interactions forced the aryl group to be located away from the quinuclidine, and the attack of the enolate occurred preferentially to the Re face. In 2015, an efficient enantioselective synthesis of densely functionalized dihydrofuran derivatives was recently developed by Singh and coworkers on the basis of the first example of asymmetric silver-catalyzed domino aldol/cycloisomerization reaction of ynones with cyclic 1,3-diketones [88]. As shown in Scheme 9.51, the process was promoted by a chiral silver catalyst generated in situ from 10 mol% of AgOTf and 5 mol% of (R)-BINAP in dichloromethane at −60 ∘ C and provided the corresponding highly functionalized chiral dihydrofurans bearing an exocyclic double bond at the C2 position in

581

OMe N NH N

CHO + CN

OH

OCHPh2

N

O

(5 mol%) Ag2O (2.5 mol%)

O2N

68%, 84% de, 93% ee

N HN O

CHO + O2N

OR

CN O

O CHCl2

(–)-Chloramphenicol

O2 N

Ph2P

OH HN

CO2CHPh2

4 Å MS AcOEt, 20 °C

O

O2N

PPh2

O

N

(X = H or OMe) (5 mol%) Ag2O (2.5 mol%)

O

N CO2R

4 Å MS AcOEt, 20 °C O2 N

With X = H: R = t-Bu: 70%, 82% de, 78% ee R = Me: 80%, 76% de, 82% ee R = Bn: 61%, 80% de, 87% ee With X = OMe: R = Bn: 64%, 80% de, 87% ee R = 4-MeOC6H4CH2: 63%, 78% de, 86% ee R = 3,5-(F3C)2C6H3CH2: 56%, 80% de, 84% ee

Scheme 9.49 Domino aldol/cyclization reactions of p-nitrobenzaldehyde and isocyanoacetates and synthesis of (−)-chloramphenicol.

9.4 Silver-Catalyzed Domino and Tandem Reactions

OMe N NH N

OR1

CN O

Ar

O (5 mol%) Ag2O (2.5 mol%)

O

+

PPh2

R2

O

N

Ar

4 Å MS AcOEt, –20 °C

R2

CO2R1

R1 = Me, Et, t-Bu R2 = Me, Et, n-Pr, i-Bu Ar = Ph, 4-MeOC6H4, 4-O2NC6H4, 4-BrC6H4, 4-NCC6H4, 4-Tol, 4-FC6H4, 2-thienyl, pyrazin-2-yl, 5-methylthiazol-2-yl, 5-Br-thiophen-2-yl, 4-F-3-BrC6H3, 3,5-(F3C)2C6H3 55–84%, 70–92% de, 82–98% ee R2 OMe

+ NH O

Proposed transition state:

Ar– O

Ag C N N

OR1

N

PPh2

O

Scheme 9.50 Domino aldol/cyclization reaction of ketones and isocyanoacetates.

low to excellent yields (26–95%) and moderate to excellent enantioselectivities (44–98% ee). A range of ynones with various aryl-substituted terminals underwent the reaction with cyclohexanedione as well as heteroaryl-, naphthyl-, and n-butyl-substituted ynones. The presence of substituents on the 1,3-diketone was tolerated. When, instead of an ester (EWG = CO2 Et), which allowed 56–98% ee, a trifluoromethyl group (EWG = CF3 ) was used as an activating group in the ynone, the corresponding dihydrofuran was obtained in 58% yield and 44% ee. Notably, the presence of an exocyclic double bond and a hydroxyl group in the domino products provides wide scope for further structural manipulation. 9.4.3

Domino Reactions Initiated by a Cyclization

1,2-Dihydroisoquinolines and their derivatives constitute an important class of heterocyclic compounds found in numerous natural and pharmaceutical products [89]. In this context, their asymmetric synthesis is particularly challenging. In 2012, You and coworkers reported a novel access to chiral multifunctional 1,2-dihydroisoquinolines based on enantioselective silver-catalyzed reactions of 1-alkynylaryl aldimines with indoles [90]. These domino cyclization/Friedel–Crafts processes were catalyzed by 10 mol% of

583

584

9 Asymmetric Silver-Catalyzed Reactions

O O EWG

+

R1

O R4

R2 R2 R3 R3 R4

AgOTf (10 mol%) (R)-BINAP (5 mol%) 4 Å MS CH2Cl2, –60 °C

O EWG OH H

Aldol R1

O R4 R

R2 R2 R3 3 4R

EWG R1

OH

O

O R4

R2 R2 R3 R3 R4

5-exo-dig cycloisomerization

R1 = Ph, R2 = R4 = H, R3 = Me, EWG = CO2Et: 70%, 90% ee R1 = Ph, R2 = Me, R3 = R4 = H, EWG = CO2Et: 51%, 92% ee R1 = Ph, R2 = R3 = H, R4 = Me, EWG = CO2Et: 26%, 56% ee R1 = Ph, R2 = R4 = H, R3 = Me, EWG = CO2Me: 70%, 87% ee R1 = 4-FC6H4, R2 = R4 = R3 = H, EWG = CO2Et: 82%, 85% ee R1 = 4-O2NC6H4, R2 = R4 = R3 = H, EWG = CO2Et: 95%, 71% ee R1 = 4-Tol, R2 = R4 = R3 = H, EWG = CO2Et: 66%, 93% ee R1 = 1-Tol, R2 = R4 = R3 = H, EWG = CO2Et: 40%, 98% ee R1 = 4-MeOC6H4, R2 = R4 = R3 = H, EWG = CO2Et: 42%, 96% ee R1 = 2-Naph, R2 = R4 = R3 = H, EWG = CO2Et: 75%, 96% ee R1 = 2-thienyl, R2 = R4 = R3 = H, EWG = CO2Et: 85%, 80% ee R1 = n-Bu, R2 = R4 = R3 = H, EWG = CO2Et: 64%, 95% ee R1 = Ph, R2 = R4 = R3 = H, EWG = CF3: 58%, 44% ee

Scheme 9.51 Domino aldol/cycloisomerization reaction of ynones and 1,3-cyclohexanediones.

a chiral silver BINOL-derived phosphate in toluene at 40 ∘ C, leading to a range of domino products in low to excellent yields (26–95%) and low to high enantioselectivities (10–89% ee). As shown in Scheme 9.52, the best enantioselectivity of 89% ee was obtained for the reaction of the substrate containing an electron-withdrawing group. In addition to phenyl-substituted alkynes (R2 = Ph), alkyl-substituted alkynes (R2 = Cy or n-Bu) could also be well tolerated with good yields (80–95%) but decreased enantioselectivities (10–54% ee). Concerning the nucleophilic partner, various substituted indoles bearing either electron-donating or electron-withdrawing groups reacted to give the corresponding products with moderate to high yields (26–95%) and moderate ee values (33–54% ee). Interestingly, a N-methyl indole also gave the corresponding product in 41% yield and 59% ee. In 2014, Terada et al. described another type of asymmetric domino reactions based on the use of a chiral pentafluorophenyl-substituted silver phosphate employed at room temperature at 10 mol% of catalyst loading in THF or AcOEt as solvent [91]. The reaction involved 1-alkynylaryl ketones as substrates that reacted through intramolecular cyclization to generate an ion pair composed of the isobenzopyrylium intermediate B and chiral phosphate. The latter was subsequently reduced with Hantzsch esters to afford the corresponding chiral 1H-isochromenes in good to excellent yields (68–98%). When alkyl ketones

9.4 Silver-Catalyzed Domino and Tandem Reactions

Ar O

O P

OAg

O R3

Ar

N R4

Ar = 2,6-(i-Pr)2-4-t-BuC6H2 (10 mol%)

+

R4

R3

N

Toluene, 40 °C R1

N

R1

NTs

Ts R2

R2 Friedel–Crafts

Cyclization

+ Ts N

R1

R3 N R4

R2 Ag

X–

(X = chiral anion) R1 = R3 = R4 = H, R2 = Ph: 73%, 56% ee R1 = 6,7-(MeO)2, R3 = R4 = H, R2 = Ph: 57%, 32% ee R1 = 7-F, R3 = R4 = H, R2 = Ph: 65%, 89% ee R1 = R3 = R4 = H, R2 = Cy: 95%, 54% ee R1 = R3 = R4 = H, R2 = n-Bu: 80%, 10% ee R1 = R4 = H, R2 = Ph, R3 = 7-Me: 95%, 54% ee R1 = R4 = H, R2 = Ph, R3 = 5-OMe: 26%, 48% ee R1 = R4 = H, R2 = Ph, R3 = 6-Cl: 50%, 33% ee R1 = R3 = H, R2 = Ph, R4 = Me: 41%, 59% ee

Scheme 9.52 Domino cyclization/Friedel–Crafts reaction of ortho-alkynylaryl aldimines and indoles.

(R1 = alkyl) were used as substrates, the best results were obtained when the reactions were performed in THF as solvent with the domino products obtained in 87–98% yields with enantioselectivities of 67–87% ee when an aryl group was introduced at the R2 position of ketones while the presence of an alkyl group at this position led to comparable yield (89%) albeit combined with a lower enantioselectivity (22% ee) (Scheme 9.53). On the other hand, the highest enantioselectivities (88–92% ee) associated with 68–90% yields were obtained in the reaction of aryl ketones (R1 = aryl) bearing an aryl substituent on the alkyne (R2 ). The presence of an alkyl substituent at this position of aryl ketones provided a decreased enantioselectivity (49% ee) in 86% yield. The utility of this novel methodology was demonstrated in the asymmetric synthesis of the 9-oxabicyclo[3.3.1]nona-2,6-diene framework, which is found in biologically active molecules.

585

586

9 Asymmetric Silver-Catalyzed Reactions

C6F5 O

O P

OAg

O R2

C6F5

R2

(10 mol%) O

R3 R1

4

R1 4

R O2 C

CO2R

N H = Me or Et (1.1 equiv.)

R4

Cyclization

O

R3

5 Å MS THF or AcOEt, r.t.

R4O2C N H

Ag R2 O

R3

+

X–

CO2R4

Enantioselective reduction

R1 B X = chiral anion In AcOEt with R4 = Me:

In THF with R4 = Et: 1

2

R = Me, R = 4-Tol, R = H: 98%, 81% ee

R1 = R2 = Ph, R3 = H: 85%, 92% ee

R1

R2

R1 = 4-MeOC6H4, R2 = Ph, R3 = H: 81%, 90% ee

= Me,

3

= 4-F3CC6H4,

R3

= H: 87%, 67% ee

R1 = Me, R2 = 4-MeOC6H4, R3 = H: 92%, 80% ee R1 = n-Pr, R2 = Ph, R3 = H: 95%, 81% ee

R1 = 4-BrC6H4, R2 = Ph, R3 = H: 81%, 91% ee

R1 = i-Bu, R2 = Ph, R3 = H: 89%, 82% ee

R1 = 3-MeOC6H4, R2 = Ph, R3 = H: 81%, 91% ee

1

R = Me,

R2

R1

R2

= Me,

= Ph,

R3

= n-Bu,

= F: 89%, 87% ee

R3

= H: 89%, 22% ee

R1 = 4-F3CC6H4, R2 = Ph, R3 = H: 84%, 91% ee R1 = 1-TBSOC6H4, R2 = Ph, R3 = H: 90%, 88% ee R1 = R2 = Ph, R3 = F: 68%, 90% ee R1 = Ph, R2 = n-Bu, R3 = H: 86%, 49% ee

Scheme 9.53 Domino intramolecular cyclization/reduction reaction of ortho-alkynylaryl ketones.

In 2014, another type of asymmetric domino reaction was reported by Yao and coworkers on the basis of relay catalysis arising from the combined use of 2.5 mol% of AgOAc with 3.75 mol% of a chiral phosphoric acid [92]. The reaction involved 3-alkynylacrylaldehydes and 2-hydroxystyrenes as substrates in DCE at room temperature, providing a mixture of two chiral polycyclic products. As shown in Scheme 9.54, the alkyne bond of the substrate was activated by Ag(I), initiating the cycloisomerization to afford a Ag(I)–pyrylium/chiral phosphate ionic pair C. Then, protonolysis of the C—Ag bond with AcOH regenerated AgOAc and yielded the key chiral pyrylium phosphate ionic pair D. Subsequently, the hydrogen bonding of the phosphate of this intermediate with the 2-hydroxystyrene substrate led to an asymmetric oxa-Diels–Alder cycloaddition, leading to carbocation E. Finally, the latter was attacked internally by the phenolic hydroxyl group through an SN 2 (attack at C1 position) or an

9.4 Silver-Catalyzed Domino and Tandem Reactions Ar′ O O P O OH R2

Ar + CHO

R2

AgOAc (2.5 mol%) DCE, r.t.

R1

Ar

O

Ar′ Ar′ = 2,4,6-(i-Pr)3C6H2 (3.75 mol%) OH

Ar R1

+

R2

H

O 9–50%, 15–92% ee

R1

O H O

12–67%, 9–92% ee

Ar = 4-NCC6H4, 4-Tol, 4-MeO2CC6H4, 4-BrC6H4, 3-MeOC6H4, 3,4,5-(MeO)3C6H2, Ph R1 = H, MeO2C, Br, OMe R2 = H, Br, Me

Proposed mechanism: L*-Ag

Ar

Ag

Ar

Ar

Cycloisomerization

Ag-L*

O+ CHO

CHO L*–

R2 Ar

L*– + O

R2

3 2

1

SN 2 HO

AcOH

OH

Ag-L*

H

R1

Ar

R1

SN2′

O+

[4 + 2] E

L*– SN2′

SN2

D

Ar

O

Ar R1

R2 H H

AgOAc + L*

C

R3

O

O

R1

H R2

H O

Scheme 9.54 Domino cycloisomerization/oxa-Diels–Alder/intramolecular nucleophilic substitution reaction of 3-alkynylacrylaldehydes and 2-hydroxystyrenes.

SN 2′ (attack at C3 position) mechanism, providing the final products (9–50% and 12–67% yields, 15–92% ee and 9–92% ee, respectively, for the two polycyclic products). The development of multimetallic catalytic systems and their application to asymmetric catalysis is an emerging area in modern organic synthesis [93]. In 2009, Tanaka and coworkers reported a rare example of asymmetric domino reaction promoted by a combination of cationic rhodium(I) and silver(I) complexes [94]. As shown in Scheme 9.55, the reaction of alkynylaryl aldehydes with isatins performed in the presence of 5 mol% of [Rh(cod)2 ]BF4 , 10 mol% of AgBF4 ,

587

588

9 Asymmetric Silver-Catalyzed Reactions OMe F3C MeO

CF3 CF3

P P

O

Fe

O

CF3

O N R2

O (5 mol%) [Rh(cod)2]BF4 (5 mol%) AgBF4 (10 mol%)

+ CHO

R1 O N

PPh3 (5 mol%) CH2Cl2, r.t. R1

R2

R1 = n-Bu, Cy, Cl(CH2)3, 2-isopropenyl, Ph, 1-ClC6H4 R2 = Me, H, Ph 52–96%, 94% to >99% ee O

Possible mechanism: O

H CHO

N R2

+ O

Rh/Ag Cyclization

H O M

R oxa-Diels–Alder 1

R1

+ O

R1

O CHO O

–M N R2

N R2

M O

M = Rh/Ag

R1 O

R1

O

M

+

O

F O

O

–M

R1

N R2

O N

G

R2

Scheme 9.55 Domino cyclization/oxa-Diels–Alder reaction of isatins and alkynylaryl aldehydes.

and 5 mol% of a chiral ferrocenyl ligand in dichloromethane at room temperature with 5 mol% of triphenylphosphine as an additive led to the corresponding densely functionalized tetrasubstituted alkenes in moderate to excellent yields (52–96%) and uniformly excellent enantioselectivities (94% to >99% ee). Indeed, alkyl-, alkenyl-, and aryl-substituted 2-alkynylbenzaldehydes provided excellent results in reaction with N-methyl-, N-phenyl-, and even N-H isatins. To explain the results, the authors have proposed the mechanism depicted in Scheme 9.55 in which the exact roles of the two metals were not clarified. Previously, Porco and coworkers demonstrated that a cationic silver(I) complex could react with a 2-alkynylbenzaldehyde to form the corresponding benzopyrylium intermediate [95]. On this basis, the authors tentatively proposed that AgBF4 could catalyze the formation of intermediate ketoaldehyde F, but when the reaction was performed with AgBF4 and in the absence of [Rh(cod)2 ]BF4 , it was found that this intermediate was not produced but an unidentified mixture of products derived from the 2-alkynylbenzaldehyde. This result suggested that rhodium(I) and silver(I) complexes cooperatively catalyzed the process with the exact role of AgBF4 not clarified although demonstrated indispensable to reach good yields. Intermediate ketoaldehyde F, arising from domino cyclization/oxa-Diels–Alder

9.4 Silver-Catalyzed Domino and Tandem Reactions

cycloaddition, could then undergo an enantioselective intramolecular ketone hydroacylation through rhodacycle G to yield the final chiral tetrasubstituted alkene. 9.4.4

Domino Reactions Initiated by a Mannich Reaction

While a range of chiral catalysts including either metal-based or metal-free catalyst systems are known to successfully promote asymmetric domino Mannich/cyclization reactions of isocyanoesters with aldimines, the analogous asymmetric transformation of the significantly less reactive ketimines remains challenging in spite of its potential to provide a direct route to chiral imidazolines possessing vicinal stereogenic centers including a fully substituted β-carbon atom. In 2014, Dixon and coworker reported the first enantioselective domino Mannich/cyclization reaction of isocyanoacetates with ketimines, which was based on the combined cooperative use of Ag2 O with a cinchona alkaloid-derived aminophosphine organocatalyst [96]. As shown in Scheme 9.56, a range of chiral

N NH N

OR1

CN O

N

+ Ar

PPh2

O

DPP

(20 mol%) Ag2O (5 mol%)

R2

4 Å MS AcOEt, –20 °C

DPP N Ar R2

N CO2R1

R1 = CHPh2, R2 = Me, Ar = Ph: 70%, 68% de, 96% ee R1 = t-Bu, R2 = Me, Ar = Ph: 92%, 98% de, 96% ee R1 = t-Bu, R2 = Me, Ar = 4-O2NC6H4: 87%, 60% de, 95% ee R1 = t-Bu, R2 = Me, Ar = 4-ClC6H4: 96%, 92% de, 93% ee R1 = t-Bu, R2 = Me, Ar = 4-Tol: 78%, 80% de, 98% ee R1 = t-Bu, R2 = Me, Ar = 4-MeOC6H4: 87%, 50% de, 99% ee R1 = t-Bu, R2 = Et, Ar = Ph: 85%, 76% de, 97% ee R1 = CHPh2, R2 = Me, Ar = 4-ClC6H4: 83%, 72% de, 97% ee R1 = CHPh2, R2 = Me, Ar = 4-Tol: 96%, 90% de, 96% ee R1 = CHPh2, R2 = Me, Ar = 4-MeOC6H4: 96%, 46% de, 98% ee R1 = CHPh2, R2 = Et, Ar = Ph: 80%, 62% de, 90% ee R1 = CHPh2, R2 = Me, Ar = 3-MeOC6H4: 82%, 48% de, 96% ee R1 = CHPh2, R2 = Me, Ar = 1-MeOC6H4: 96%, 60% de, 97% ee R1 = CHPh2, R2 = Me, Ar = 4-PhC6H4: 97%, 80% de, 97% ee R1 = CHPh2, R2 = Me, Ar = 4-BrC6H4: 98%, 56% de, 94% ee R1 = CHPh2, R2 = Me, Ar = 1-BrC6H4: 97%, 98% de, 96% ee R1 = CHPh2, R2 = Me, Ar = 1-FC6H4: 95%, 68% de, 96% ee R1 = CHPh2, R2 = Me, Ar = 4-FC6H4: 95%, 66% de, 96% ee R1 = CHPh2, R2 = Me, Ar = 3,4-Cl2C6H3: 84%, 70% de, 95% ee

Scheme 9.56 Domino Mannich/cyclization reaction of ketimines and isocyanoacetates.

589

590

9 Asymmetric Silver-Catalyzed Reactions

imidazolines were prepared in good to excellent yields (62–98%) and uniformly excellent enantioselectivities (90–99% ee) while the diastereoselectivity ranged from 46% to 98% de. The lowest values of 46–50% de were obtained with aryl alkyl ketones bearing a methoxy group on the phenyl ring. However, these substrates afforded high enantioselectivities (98–99% ee). Later in 2016, the same authors investigated related reactions between α-substituted isocyanoacetates and ketimines [97]. In this case, the reaction was catalyzed by a combination of Ag2 O with a chiral cinchona alkaloid-derived aminophosphine ligand. As shown in Scheme 9.57, the domino Mannich/cyclization reaction led to the corresponding chiral imidazolines as single diastereomers (>96% de). The latter were subsequently N-deprotected by treatment with aqueous HCl to give the final imidazolines in moderate to high yields (28–90%) and uniformly high enantioselectivities (87–95% ee). In addition to a series of aromatic and heteroaromatic ketimines, an aliphatic one (R3 = BnCH2 ) was found compatible, providing a high enantioselectivity (87% ee) albeit combined with a low yield (28%). The synthetic utility of this novel methodology was demonstrated by converting some products through hydrolysis into fully substituted α,β-diamino acids. OMe N NH N

PPh2

O

R1

(10 mol%) 1 M HCl DPP Ag O (5 mol%) DPP N N NH N 2 3 + N CN R1 R1 CH Cl , r.t. R R3 2 2 4 Å MS 3 O CO2R2 R CO2R2 AcOEt, –20 °C >96% de 28–90%, R1 = Me, Et, n-Bu 87–95% ee R2 = Me, t-Bu 3 = Ph, 4-Tol, 4-PhC H , 4-FC H , 4-ClC H , 4-MeOC H , R 6 4 6 4 6 4 6 4 3-ClC6H4, 2-FC6H4, 3-pyridyl, 2-furyl, BnCH2 OR2

Scheme 9.57 Domino Mannich/cyclization reaction of ketimines and α-substituted isocyanoacetates.

In 2014, a chiral cinchona alkaloid-derived squaramide was combined by Shi and Zhao with AgOAc to cooperatively catalyze enantioselective domino Mannich/cyclization reactions of α-substituted isocyanoacetates with cyclic trifluoromethylated ketimines [98]. In the presence of 5 mol% of this catalyst system in THF at 0 ∘ C, the process afforded the corresponding chiral trifluoromethyl-substituted tetrahydroimidazo[1,5-c]quinazoline derivatives in good to quantitative yields of 76–99% along with a high diastereoselectivity of >88% de and uniformly excellent enantioselectivities of up to 98% ee (Scheme 9.58). On the other hand, when the reaction conditions were applied

9.4 Silver-Catalyzed Domino and Tandem Reactions

OMe N Ph NH

HN Ph

N HO O

O (5 mol%) AgOAc (5 mol%)

CF3 NC

N

X

+

N R3

1

R

O

CO2

R2

THF, 0 °C R1 F3C

Mannich X

CO2R2 N C N– N R3

N H OH O

R3 N Si face

+ N CF3 H OR2

N O R3 >88% de Cyclization

O

R1 = 4-BrC6H4, R2 = Me, R3 = PMB, X = 6-Cl: 99%, 98% ee

N

R1 = 4-Tol, R2 = Me, R3 = PMB, X = 6-Cl: 99%, 97% ee R1 = 4-MeOC6H4, R2 = Me, R3 = PMB, X = 6-Cl: 99%, 95% ee

N H N

N

X

R1 = 4-ClC6H4, R2 = Me, R3 = PMB, X = 6-Cl: 99%, 97% ee

O

Ph Ph

CO2R2 N

R1 = Ph, R2 = Me, R3 = PMB, X = 6-Cl: 99%, 98% ee R1 = 4-FC6H4, R2 = Me, R3 = PMB, X = 6-Cl: 95%, 98% ee

Proposed transition state: O

R1 F3C

O

OMe

R1 = 3-FC6H4, R2 = Me, R3 = PMB, X = 6-Cl: 91%, 94% ee R1 = 3-Tol, R2 = Me, R3 = PMB, X = 6-Cl: 99%, 96% ee R1 = Ph, R2 = Bn, R3 = PMB, X = 6-Cl: 99%, 97% ee R1 = Ph, R2 = t-Bu, R3 = PMB, X = 6-Cl: 99%, 95% ee R1 = Bn, R2 = Me, R3 = PMB, X = 6-Cl: 98%, 58% ee

X Ag

C

N

R1

R1 = Ph, R2 = Me, R3 = PMB, X = 6-F: 95%, 98% ee R1 = Ph, R2 = Me, R3 = PMB, X = 6-Me: 91%, 97% ee

Through Re face

R1 = Ph, R2 = Me, R3 = PMB, X = 6-MeO: 98%, 95% ee R1 = Ph, R2 = Me, R3 = PMB, X = 5-Me: 81%, 98% ee R1 = Ph, R2 = Me, R3 = PMB, X = H: 76%, 97% ee R1 = Ph, R2 = Me, R3 = H, X = 6-Cl: 99%, 91% ee

Scheme 9.58 Domino Mannich/cyclization reaction of cyclic trifluoromethylated ketimines and isocyanoacetates.

to an alkyl-substituted isocyanoacetate (R1 = Bn), the corresponding domino product was produced in only 58% ee albeit in excellent yield (98%). Concerning the scope of ketimines, they could bear electron-withdrawing, electron-donating, or electron-neutral substituents on the phenyl ring, providing comparable excellent results. Moreover, a N-unprotected ketimine (R3 = H) was found to lead to the corresponding product in 99% yield and 91% ee. On the other hand, replacing the trifluoromethyl group on the starting quinazolinones by a methyl group prevented the reaction, which indicated that the strong electron-withdrawing trifluoromethyl group was pivotal for the domino reaction to occur. The authors have proposed the transition state depicted in Scheme 9.58. The α-proton of the isocyanoacetate was easily deprotonated by the quinuclidine nitrogen of the

591

592

9 Asymmetric Silver-Catalyzed Reactions

organocatalyst due to the interaction of Ag(I) with the isocyano group, resulting in a single H-bonding interaction between the OH group of the enolized isocyanoacetate and the tertiary amine and a weak hydrogen bonding between the OMe group of the enolized isocyanoacetate and the NH in the squaramide moiety. Simultaneously, the cyclic N-acyl ketimine was activated and oriented through hydrogen bonding with the NH and OH groups of the multihydrogen bonding donor squaramide catalyst, thus forcing the isocyanoacetate enolate to be delivered through its Re face of the enol to the Si face of the imine moiety, leading to the formation of two stereogenic centers. Then, an intramolecular 5-endo-dig cyclization occurred to afford the final product. 9.4.5

Miscellaneous Domino Reactions

In 2008, Hoveyda and coworkers developed enantioselective silver-catalyzed three-component domino imine formation/aza-Diels–Alder reactions evolving between aliphatic aldehydes, o-thiomethyl-p-anisidine, and Danishefsky’s diene [17]. Performed in the presence of 5 mol% of a combination of AgOAc with a chiral tert-leucine-derived phosphine ligand in THF at 0 ∘ C, the reaction led to the corresponding chiral dihydropiperidines in moderate to good yields (53–88%) and uniformly high enantioselectivities (90–95% ee), as shown in Scheme 9.59. The cycloadditions were effective with aldimines generated in situ bearing an n-alkyl substituent as well as those carrying heteroatom-containing functional groups. However, aza-Diels–Alder reactions with the latter class of substrates afforded the corresponding cycloadducts in lower yields (53–66% vs. 88%). t-Bu MeO

SMe NH2 O

OTMS

+

+ R

H

N

H N

O PPh2 (5 mol%) AgOAc (5 mol%) i-PrOH (1.1 equiv.) MgSO4 (2 equiv.) OMe THF, 0 °C

OMe

R N

MeO

SMe

O R = i-Bu: 88%, 92% ee R = BnCH2: 88%, 93% ee R = MeO2C(CH2)2: 53%, 90% ee R = BnOCH2: 66%, 95% ee

Scheme 9.59 Three-component domino imine formation/aza-Diels–Alder reaction of aliphatic aldehydes, o-thiomethyl-p-anisidine and Danishefsky’s diene.

In order to develop a novel synthesis of biologically active natural alkaloid (−)-cephalotaxine, which contains a 1-azaspiro[4.4]nonane ring unit, Tu and coworkers have introduced asymmetric domino hydroamination/semipinacol rearrangement reactions of cyclobutanols promoted by a chiral silver catalyst derived from a chiral phosphoric acid [99]. As shown in Scheme 9.60, the use of 20 mol% of this preformed catalyst in carbon tetrachloride as solvent at 25 ∘ C allowed a range of chiral azaspirocyclic products to be synthesized in uniformly high yields of 90–99% combined with moderate enantioselectivities of 55–82% ee. They arose from an intramolecular hydroamination of arylsulfonyl-protected substrates to give iminium intermediates H and I, which subsequently underwent a semipinacol rearrangement to provide the final azaspirocycles.

9.4 Silver-Catalyzed Domino and Tandem Reactions

Ar O

O P

OAg

O Ar

Ar = 9-anthracenyl

NHR

O

(20 mol%) CCl4, 25 °C 5 Å MS

OH

N R

Hydroamination

+ N R

N R

HO H R = Ts: 99%, 82% ee R = C6H5SO2: 90%, 67% ee R = 1-TolSO2: 96%, 62% ee R = 3-TolSO2: 99%, 66% ee R = 4-BrC6H4SO2: 96%, 79% ee R = 4-ClC6H4SO2: 92%, 82% ee R = 4-FC6H4SO2: 98%, 70% ee

Semipinacol rearrangement

–

O I

R = 4-IC6H4SO2: 99%, 78% ee R = 4-t-BuC6H4SO2: 94%, 71% ee R = 4-F3CC6H4SO2: 98%, 72% ee R = 4-MeOC6H4SO2: 99%, 65% ee R = 1-NaphSO2: 92%, 55% ee R = 2-NaphSO2: 90%, 66% ee

Scheme 9.60 Domino hydroamination/semipinacol rearrangement reaction of alkyne-tethered cyclobutanols.

In 2013, (R)-BINAP was employed as ligand by Dudding and coworker to promote silver-catalyzed asymmetric domino reactions between alkyl 2-formylbenzoates and allyltrimethoxysilane [100]. As shown in Scheme 9.61, in the presence of 6–10 mol% of this ligand associated to the same quantity of AgF, the process yielded a series of chiral C3-substituted phthalides in moderate yields of 52–73% and low to good enantioselectivities of 33–86% ee. The substrate scope showed that elongation of the n-alkyl chain (R1 ) of the starting unsubstituted (R2 = H) alkyl 2-formylbenzoates improved the enantioselectivities (80–86% ee for R1 = Et, n-Hex, n-C12 H25 vs. 71% ee for R1 = Me). The methodology could also be applied to a Merrifield resin-bound substrate, which led to the corresponding product in 68% yield and 76% ee. To explain these results, the authors proposed the mechanistic cycle depicted in Scheme 9.61 in which a short-lived complex J was initially formed from the alkyl 2-formylbenzoate, the allyltrimethoxysilane, and the catalyst. Then, a fluoride-assisted transmetalation occurred to give a highly reactive Ag allyl species that underwent allylation via K in a Re-stereofacial C—C bond-forming process, providing the Ag alkoxy bound intermediate L. Finally, an intramolecular transesterification occurred to yield the product and regenerate the catalyst.

593

594

9 Asymmetric Silver-Catalyzed Reactions

O R2

Si(OMe)3 OR1

AgF (6–10 mol%) (R)-BINAP (6–10 mol%)

O

R2

+

O

CHO

MeOH, –20 °C

R1 = Me, R2 = H: 68%, 71% ee R1 = Me, R2 = Br: 57%, 39% ee R1 = Me, R2 = NO2: 52%, 33% ee R1 = Me, R2 = Ph: 67%, 61% ee R1 = Me, R2 = OMe: 55%, 86% ee

R1 = Et, R2 = H: 58%, 80% ee R1 = n-Hex, R2 = H: 73%, 86% ee R1 = C12H25, R2 = H: 70%, 86% ee R1 = Bn, R2 = H: 54%, 63% ee R1 = Merrifield resin, R2 = H: 68%, 76% ee

Proposed mechanism: O O

R2

R2

OR1

P Ag F

O + Si(OMe)4

CHO +

F

Ag

P

P OMe MeO + Si MeO

OMe MeO Si H MeO

Ag F

Ag

O O

P

F

Ag F O Ag O F

P

OR1

OR1 R2

Si(OMe)3

P

R2 K

J

P OMe MeO + Si MeO

Ag F H

Ag

O O

P

F

OR1 R2 L

Scheme 9.61 Domino allylation/transesterification reaction of alkyl 2-formylbenzoates and allyltrimethoxysilane.

9.5 Silver-Catalyzed Michael Reactions

9.5 Silver-Catalyzed Michael Reactions 𝛂,𝛃-Unsaturated Carbonyl Compounds as Acceptors

9.5.1

Michael-type reactions [101] represent one of the most powerful tools for the stereocontrolled formation of carbon–carbon as well as carbon–heteroatom bonds [102]. A range of chiral metals and chiral organocatalysts have been applied to promote these reactions. In 2005, Kobayashi et al. reported the first enantioselective silver-catalyzed Michael addition of β-ketoesters to α,β-unsaturated ketones, performed in water in the presence of AgOTf and BINAP derivatives as ligands with promising enantioselectivities of up to 83% ee [103]. Ever since, it must be recognized that still few publications have been reported dealing with the use of chiral silver catalysts in catalytic Michael additions of nucleophiles to various acceptors in an enantioselective fashion. As a recent example, Fukuzawa and coworkers have developed highly enantioselective silver-catalyzed conjugate additions of diphenylidene glycine imino methyl ester to various arylidene and alkylidene malonates, providing the corresponding chiral Michael products in moderate to quantitative yields of 36–99% (Scheme 9.62) [104]. Performed in the presence of 5 mol% of a combination of AgOAc and a chiral P,S-ligand in THF at room temperature and in the absence of a base in almost all cases, the process yielded the syn-products as major diastereomers with 88–94% de and 90–99% ee in the case of arylidene malonates. An alkylidene malonate (R = Cy) led to the corresponding syn-product in 60% yield with a lower diastereoselectivity of 60% de with an excellent enantioselectivity of 97% ee. The scope of arylidene ethyl malonates was found large since aryl, heteroaryl, and a ferrocenyl-substituted malonates were compatible. In the reaction of ferrocenyl-substituted malonate and alkylidene malonate, the presence of 25 mol% of Cs2 CO3 as base allowed the reaction performance to be improved.

Ph2P Fe Ph Ph

t-BuS N

CO2Me

Ph

CO2Et

(5 mol%) AgOAc (5 mol%)

+ R

N N N

CO2Et CO2Et

THF, r.t.

Ph Ph

R N

CO2Et CO2Me

syn, major

R = Ph, 1-Tol, 4-Tol, 4-MeOC6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 2-Naph, 2-pyridyl, 2-thienyl, (C5H5)2Fe: 36–99%, syn/anti = 89/11–97/3, 90–99% ee (syn) R = Cy: 60%, syn/anti = 80/20, 97% ee (syn)

Scheme 9.62 Michael reaction of arylidene/alkylidene malonates and a glycine Schiff base.

595

596

9 Asymmetric Silver-Catalyzed Reactions

These authors also investigated the related Michael addition of diphenylene glycine imino methyl ester to α,β-unsaturated ketones [104]. Using the same catalyst system in the presence of 20 mol% of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a base in THF at −40 ∘ C, the Michael reaction of a range of aromatic α,β-unsaturated ketones (R = aryl, heteroaryl) led to the corresponding chiral products in high yields (82–93%) and enantioselectivities of 97–99% ee (Scheme 9.63). Notably, a ferrocenyl-substituted α,β-unsaturated ketone was also compatible, providing the corresponding product in 84% yield and 90% ee. Moreover, the reaction of an aliphatic α,β-unsaturated ketone, such as methyl vinyl ketone (R = Me), gave the corresponding product in 92% yield and 96% ee. It must be noted that this study represented the first enantioselective silver-catalyzed conjugate addition of glycine derivatives to α,β-unsaturated ketones. Ph2P Fe t-BuS

Ph Ph

N

CO2Me

+

N N N

DABCO (20 mol%) THF, –40 °C

O

O

R

Ph (5 mol%) AgOAc (5 mol%)

Ph Ph

OMe

N O

R R = Ph, 4-Tol, 2,6-Me2C6H3, 4-MeOC6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4 ferrocenyl: 82–93%, 90–99% ee R = Me: 92%, 96% ee

Scheme 9.63 Michael reaction of α,β-unsaturated ketones and a glycine Schiff base.

The use of heterogeneous chiral catalysts in organic synthesis not only allows catalyst recovery and reuse but also simplifies the separation of catalyst and products and even avoids metal contamination of the products. However, the development of this type of catalysts has lagged far behind advances in homogeneous chiral catalysts in terms of performance and scope of reactions [105]. In this context, Kobayashi and coworkers have developed heterogeneous chiral nanoparticles related to their advantages, such as high stability, robustness, and reusability [106]. Indeed, polymer-incarcerated Rh/Ag nanoparticles were prepared and further applied in the presence of chiral ligands to the asymmetric Michael addition of aryl boronic acids to α,β-unsaturated ketones to give the corresponding Michael products. Ligand depicted in Scheme 9.64 employed at a loading of only 1 mol% was selected as optimal ligand in these reactions when combined with 0.75 mol% of the bimetallic heterogeneous catalyst. Among α,β-unsaturated ketones investigated, 2-cyclohexenone provided the best results since by reaction with a series of variously substituted aryl boronic acids, it provided the corresponding Michael products in both high yields and enantioselectivities of 81–99% and 93–98% ee,

9.5 Silver-Catalyzed Michael Reactions

i-Pr

OH (1 mol%) O R2

R1

+

ArB(OH)2

Ar

PI/CB Rh/Ag (0.75 mol%)

O R2

R1 *

Toluene/H2O, 100°C

R1 = i-Pr, Me, n-Pent PI: polymer incarcerated CB : carbon black R2 = Me, Ph, Et R1, R2 = (CH2)3, (CH2)2 Ar = Ph, 3-Tol, 1-Tol, 3,5-Me2C6H3, 4-t-BuC6H4, 4-FC6H4 4-FC6H4, 1-MeOC6H4, 4-MeOC6H4, 3-MeOC6H4, 1-Naph 40–100%, 74–98% ee

Scheme 9.64 Michael reaction of α,β-unsaturated ketones and aryl boronic acids.

respectively. Acyclic α,β-unsaturated ketones were also well tolerated, leading to the corresponding products in generally lower yields (70–91%) and enantioselectivities of 74–96% ee (Scheme 9.64). The catalyst system could be recycled several times by simple operations while remaining high yields and excellent enantioselectivities. The same authors also reported the synthesis of another bimetallic nanoparticle system from rhodium nanocomposites of polystyrene-based copolymers with cross-linking moieties and carbon black that was further applied in the presence of a chiral ligand as a catalyst system in asymmetric Michael additions of aryl boronic acids to α,β-unsaturated esters [107]. In this case, the best results were achieved when the reaction was performed with the chiral ligand depicted in Scheme 9.65 employed at a remarkably low catalyst loading of 0.05 mol% in combination with only 0.25 mol% of the heterogeneous Rh/Ag catalyst. A range of β-arylated products derived from 3-aryl α,β-unsaturated esters were obtained in high yields of 68–95% and high enantioselectivities of 92–99% ee (Scheme 9.65). i-Pr

O NHt-Bu

(0.05 mol%) PI/CB Rh/Ag (0.25 mol%)

O Ar1

OR

+

Ar2B(OH)2

Ar2 1

Toluene/H2O, 100 °C

Ar

*

O OR

PI: polymer incarcerated CB: carbon black Ar1 = Ph, 1-Tol, 4-MeOC6H4 R = Et, Me, i-Pr, t-Bu Ar2 = Ph, 3-MeOC6H4, 4-FC6H4, 4-MeOC6H4, 1-MeOC6H4 68–95%, 92–99% ee

Scheme 9.65 Michael reaction of α,β-unsaturated esters and aryl boronic acids.

597

598

9 Asymmetric Silver-Catalyzed Reactions

Furthermore, the catalyst could be successfully recovered and reused without significant loss of activity. In comparison with the previously developed heterogeneous catalyst in Scheme 9.65, this catalyst system presented the advantages to provide higher enantioselectivities at very low catalyst loadings in metal and ligand. 9.5.2

Nitroalkenes as Acceptors

Nitroalkenes are also good Michael acceptors for the conjugate addition of glycine imino esters [65], leading to α-imino-γ-nitro ester products that can be transformed into biologically interesting α,γ-diamino acids through consecutive hydrolysis and reduction. It must be noted that relatively few asymmetric versions of these reactions have been reported. Among them, a highly efficient methodology was developed by Fukuzawa and coworkers by using a combination of 5 mol% of AgOAc with 5.5 mol% of a ferrocenyl triazole-based P,S-ligand [108], already employed by the same authors in enantioselective silver-catalyzed Mannich reactions between N-tosyl aryl aldimines and a glycine Schiff base (Scheme 9.16) [30]. As shown in Scheme 9.66, the application of this catalyst system to the reaction of glycine imino methyl ester with various aryl nitroalkenes in the presence of 18 mol% of TEA as a base in THF at −25 ∘ C afforded the corresponding chiral Michael products as single anti-diastereomers in high yields of 80–97% and excellent enantioselectivities of 95–99% ee. Uniformly excellent enantioselectivities were reached for a range of nitrostyrenes regardless of the electronic properties and position of the substituents on the phenyl ring. Even (E)-2-(2-nitrovinyl)naphthalene and 2-nitrovinylferrocene reacted to give the corresponding enantiopure products (99% ee).

Ph2P Fe Ph N Ph

O OMe

+ Ar

NO2

t-BuS

N N N Ph

(5.5 mol%) AgOAc (5 mol%) TEA (18 mol%) THF, –25 °C

Ar

O

O2N

OMe

Ph

N

Ph >99% de

Ar = Ph: 97%, 99% ee Ar = 4-Tol: 96%, 97% ee Ar = 1-Tol: 93%, 97% ee Ar = 4-MeOC6H4: 96%, 98% ee Ar = 4-FC6H4: 93%, 95% ee Ar = 4-ClC6H4: 93%, 98% ee Ar = 4-BrC6H4: 95%, 97% ee Ar = 4-F3CC6H4: 95%, 99% ee Ar = 2-Naph: 93%, 99% ee Ar = ferrocenyl: 80%, 99% ee

Scheme 9.66 Michael reaction of nitroalkenes and a glycine Schiff base.

The same catalyst system was also applied by these authors to promote asymmetric Michael additions of cyclic imino esters to aryl nitroalkenes [109]. In this case, no additional base was required, and the best results were achieved by performing the reactions in diethyl ether as solvent. As shown in Scheme 9.67, the process led to chiral densely functionalized 1-pyrroline derivatives in both high yields and enantioselectivities of 82–98% and 83–98% ee, respectively, and to good to almost complete anti-diastereoselectivity (78–98% de). A wide range

9.5 Silver-Catalyzed Michael Reactions

Ph2P Fe

N N N

t-BuS Ar

1

N

CO2Me

+

Ph

O2N

(5.5 mol%) AgOAc (5 mol%) Ar1

Ar2

NO2

Et2O, –20 °C

Ar2 N

CO2Me

anti-Major

Ar1 = Ph, 4-Tol, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4 Ar2 = Ph, 3-Tol, 4-Tol, 1-MeOC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 4-O2NC6H4, 2-thienyl, ferrocenyl 54–98%, anti/syn = 89 : 11–99 : 1, 83–98% ee (anti)

Scheme 9.67 Michael reaction of nitroalkenes and 1-pyrroline esters.

of 1-pyrroline esters and aryl nitroalkenes could be employed as substrates, including both electron-withdrawing or electron-donating substituted ones and even heteroaryl- and ferrocenyl-substituted nitroalkenes. The para-nitrophenyl substituent was an exception, providing a low yield of 54% (vs. 82–98%) of the corresponding conjugate product albeit with excellent enantioselectivity of 98% ee. To complete this study, the authors showed that promoting the reactions with CuOAc instead of AgOAc and in the presence of a chiral ferrocenyl oxazoline phosphine ligand allowed the reversed syn-diastereomers to be achieved in comparable very high enantioselectivities (94% to >99% ee) and high yields (69–86%). In 2017, the same authors also reported the Michael addition of 2-oxazolineand 2-thiazoline-4-carboxylates to aryl nitroalkenes by using the same catalyst system [110]. As shown in Scheme 9.68, the process afforded predominantly the corresponding anti-products bearing a quaternary sterogenic center in moderate to high yields (62–97%) and enantioselectivities (75–96% ee). It was found that alkyl-substituted nitroalkenes were not suitable substrates, giving poor yields (≤5%). 9.5.3

Other Acceptors

Glycine imino methyl ester could be added by the same authors to another type of Michael acceptors, arylidene diphosphonates [111]. This process was previously successfully catalyzed by Wang and coworkers with chiral copper complexes [112]. As shown in Scheme 9.69, the use of 5 mol% of a combination of AgOAc with a ferrocenyl triazole-based P,S-ligand in THF at −20 ∘ C in the presence of 25 mol% of Cs2 CO3 as a base yielded the corresponding chiral Michael products as major syn-diastereomers in good to quantitative yields (64–99%) and uniformly high enantioselectivities of 90–98% ee. The syn-diastereoselectivity

599

600

9 Asymmetric Silver-Catalyzed Reactions

Ph2P Fe

X Ph

N N N

t-BuS N

CO2Me

Ph

O2N

(5.5 mol%)

X

AgOAc (5 mol%)

+ NO2

Ar

Ph

TEA (20 mol%) THF, r.t.

N

Ar CO2Me

anti-Major

X = O: 64–93%, anti/syn = 91 : 9–99 : 1, 75–93% ee X = S: 62–97%, anti/syn = 99 : 1, 90–96% ee Ar = Ph, 1-Tol, 4-Tol, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 4-O2NC6H4, 2-thienyl

Scheme 9.68 Michael reaction of nitroalkenes and 2-oxazoline- and 2-thiazoline-4-carboxylates.

Ph2P Fe Ph Ph

OMe

N O

+

N N N

t-BuS Ph (5 mol%) AgOAc (5 mol%) Cs2CO3 (25 mol%)

Ar

P(O)(OEt)2

P(O)(OEt)2 Ar Ph Ph

P(O)(OEt)2 OMe

N

THF, –20 °C

P(O)(OEt)2

O syn-Major

Ar = Ph, 1-Tol, 3-Tol, 4-Tol, 4-MeOC6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-O2NC6H4, 2-Naph, 4-pyridyl, 4-thienyl 64–99%, syn/anti = 76 : 24–86 : 14, 90–98% ee (syn)

Scheme 9.69 Michael reaction of arylidene diphosphonates and a glycine Schiff base.

of the reaction ranged from 52% to 62% de. The conditions were compatible with a series of 1-, 3-, and 4-substituted benzylidene diphosphonates bearing electron-donating and electron-withdrawing substituents. Regardless of the electronic nature or position of the substituent, the corresponding syn-adducts were produced preferentially with high enantioselectivities. Substituent effects on the yields were also small, and products were obtained in high yields (70–99%) except for the 1-methyl substrate, which provided the corresponding product in only 64% yield, probably due to steric hindrance. Moreover, the presence

9.6 Silver-Catalyzed Aldol-Type Reactions

of heteroaryl substituents, such as a pyridylidene and 2-thienylidene, on the Michael acceptor allowed excellent results (96–98% ee) to be achieved.

9.6 Silver-Catalyzed Aldol-Type Reactions 9.6.1

Aldol Reactions

A wide variety of chiral catalyst systems including metals as well as organocatalysts have been successfully developed to promote catalytic asymmetric aldol reactions [113]. The first example of this type of reactions catalyzed by silver was reported in 1990 by Ito and coworkers who used chiral ferrocenylphosphine–silver(I) complexes as efficient chiral catalysts in asymmetric aldol-type reactions of aldehydes with tosylmethyl isocyanide [4a]. The aldol products were not isolated since the aldol reaction was followed by cyclization to directly afford the corresponding chiral 5-alkyl-4-tosyl-2-oxazolines through a domino reaction. The catalyst system was used at only 1 mol% of catalyst loading, providing the cyclic domino products in enantioselectivities of up to 86% ee. In 1991, the same authors applied a related catalyst to the first silver-catalyzed asymmetric aldol-type reaction of tributyltin enolates with aldehydes, which allowed the corresponding simple aldol products to be achieved with enantioselectivities of up to 90% ee in combination with high yields (86–96%) [4b]. In these reactions, the tributyltin enolates were generated from the corresponding enol acetates and Bu3 SnOMe. Generally, the processes evolved through anti-diastereoselectivity in contrast to those promoted by Lewis acids other than silver complexes [114]. Later in 1997, Yamamoto and coworkers promoted these reactions by a combination of AgOTf (15 mol%) with BINAP (6 mol%), which led to the corresponding chiral β-hydroxy carbonyl compounds in enantioselectivities of up to 95% ee and moderate to good yields (33–83%) [4e]. Even if these reactions provided good results, they presented the disadvantage of using a stoichiometric amount of toxic organostannane compounds. In order to improve this point, these authors later developed an alternative asymmetric aldol reaction occurring between benzaldehyde and alkenyl trichloroacetate derived from cyclohexanone based on the same catalyst system using only 5 mol% of Bu3 SnOMe, which resulted in the formation of the corresponding aldol product in 82% yield, 84% de, and 95% ee [115]. In 2009, the same authors applied this catalyst system to the asymmetric aldol reactions of alkenyl trichloroacetates with α-ketoesters [116]. The process was promoted by a combination of 20 mol% of AgOTf, 10 mol% of (R)-BINAP, and 8 mol% of Bu2 Sn(OMe)2 in the presence of methanol as super stoichiometric additive in THF at −20 ∘ C. As shown in Scheme 9.70, the reaction began by the reaction of the alkenyl trichloroacetate with Bu2 Sn(OMe)2 to give tin enolate M along with methyl trichloroacetate. Then, enolate M is added to the β-ketoester enantioselectively in the presence of the chiral silver catalyst, affording the tin alkoxide of aldol product N, which was subsequently protonated with methanol, resulting in the formation of the final product with regeneration of Bu2 Sn(OMe)2 . Under these simple reaction conditions, various chiral

601

OCOCl3 R2

(R)-BINAP (10 mol%) AgOTf (20 mol%)

O

+

R1

R

3

OCOCl3

CO2Me

O HO CO2Me R1

Bu2Sn(OMe)2 (8 mol%) MeOH (5 equiv.) 3 Å MS THF, –20 °C

R1, R2 = (CH2)4, R3 = Ph: 99%, 32% de, 74% ee

R1, R2 = (CH2)4, R3 = 4-BrC6H4: 99%, 6% de, 61% ee

R3

R1, R2 = (CH2)4, R3 = 4-MeOC6H4: 86%, 66% de, 90% ee

R2

R1 = R3 = Ph, R2 = Me: 38%, >98% de, 93% ee R1 = Ph, R2 = R3 = Me: 40%, 4% de, 60% ee

R3 = Ph: 58%, 94% de, 89% ee Proposed catalytic cycle: O HO CO2Me R1

OCOCl3

R3 R2

R1

Bu2Sn(OMe)2

R2

MeOH

MeOCOCl3 OSnBu2(OMe) CO2Me R3

O R1 R2

OSnBu2(OMe)

R1 R2

M

N O R3 (R)-BINAP/AgOTf

Scheme 9.70 Aldol reaction of α-ketoesters and alkenyl trichloroacetates.

CO2Me

9.6 Silver-Catalyzed Aldol-Type Reactions

β-hydroxyketones bearing a tertiary carbon center were obtained in moderate to quantitative yields (38–99%), low to complete diastereoselectivities (4% to >98% de), and moderate to high enantioselectivities of 60–93% ee (Scheme 9.70). It was found that cyclic as well as acyclic alkenyl trichloroacetates were tolerated although the latter needed reaction times longer than those required by cyclic substrates to produce satisfactory yields (24 hours vs. 4–5 hours). Concerning the scope of α-ketoesters, the best results were reached with aryl α-ketoesters. The substituent at the para-position of methyl benzoylformate (R3 = aryl) was found to influence both the diastereo- and enantioselectivities of the reaction. For example, for the para-methoxy derivative (R3 = 4-MeOC6 H4 ), the enantioselectivity of the process reached 90% ee in combination with 66% de, while the para-bromo derivative (R3 = 4-BrC6 H4 ) provided only 61% ee and 6% de. This study represented the first example of an asymmetric aldol reaction of ketones using alkenyl esters as masked enolates. With the need of extending the scope of this methodology, the authors investigated the reactivity of classical ketones, such as acetophenone and cyclohexanone, under similar reaction conditions, albeit without success. Later in 2014, the same authors demonstrated that it was possible to completely avoid the use of toxic organotin compounds in the asymmetric aldol reactions of alkenyl trihaloacetates with aldehydes by employing N,N-diisopropylethylamine as a base in the presence of methanol [117]. Indeed, in this case, the chiral silver catalyst, composed of 8 mol% of (S)-BINAP combined with 16 mol% of AgOTf, reacted with methanol in the presence of this base to afford the corresponding (S)-BINAP-AgOMe, which actually constituted the true catalyst of the aldol reaction (Scheme 9.71). Next, the thus-generated chiral silver methoxide attacked the alkenyl trihaloacetate to yield chiral silver enolate O. The following addition of this enolate to the aldehyde provided chiral silver alkoxide of aldol product P. Finally, the protonation of P with methanol resulted in the formation of the final chiral β-hydroxy ketone with regeneration of the chiral silver methoxide. Under these novel environmentally benign conditions, the aldol condensation of a range of alkenyl trihaloacetates to various aldehydes led to the corresponding chiral α-alkyl-β-hydroxyketones with up to 99% yield, 98% de, and 95% ee, as shown in Scheme 9.71. In the reaction of a cyclic alkenyl trichloroacetate (R1 ,R2 = (CH2 )4 , X = Cl) with various aromatic, heteroaromatic, and aliphatic aldehydes, the anti-aldol products were obtained as major diastereomers in low to quantitative yields (16–99%), low to good diastereoselectivities of 34–82% de, and moderate to high enantioselectivities of 65–94% ee. In the case of aromatic aldehydes, enantioselectivities of 89–94% ee were achieved with the presence of electron-donating as well as electron-withdrawing substituents on the phenyl ring. Lower diastereo- and enantioselectivities were obtained in the reactions of heteroaryl, α,β-unsaturated, and aliphatic aldehydes (34–48% de and 65–78% ee). In addition to mono- and bicyclic alkenyl trichloroacetates, the authors demonstrated that a 1-tetralone-derived alkenyl trifluoroacetate provided the corresponding anti-products in high yields, diastereoselectivities, and enantioselectivities of 78–88%, 86–92% de, and 90–95% ee, respectively. On the other hand, the diastereoselectivity of the reaction was reversed when using acyclic (Z)-alkenyl trifluoroacetate (R1 = Ph, R2 = Me, X = F, E/Z = 8 : 92), which led to the corresponding products as major syn-diastereomers with high

603

604

9 Asymmetric Silver-Catalyzed Reactions

OCOX3

(S)-BINAP (8 mol%) AgOTf (16 mol%)

O

+

R1

R3

R2

H

OH

O

* * R3 R2

R1 i-Pr2NEt (40 mol%) MeOH THF, r.t.

R1, R2 = (CH2)4, R3 = Ph, X = Cl: 92%, 72% de (anti), 94% ee (anti) R1, R2 = (CH2)4, R3 = 4-MeOC6H4, X = Cl: 91%, 70% de (anti), 91% ee (anti) R1, R2 = (CH2)4, R3 = 1-MeOC6H4, X = Cl: 99%, 82% de (anti), 89% ee (anti) R1, R2 = (CH2)4, R3 = 4-F3CC6H4, X = Cl: 65%, 82% de (anti), 92% ee (anti) R1, R2 = (CH2)4, R3 = 2-thienyl, X = Cl: 95%, 34% de (anti), 78% ee (anti) R1, R2 = (CH2)4, R3 = (E)-PhCH=CH, X = Cl: 98%, 36% de (anti), 66% ee (anti) R1, R2 = (CH2)4, R3 = BnCH2, X = Cl: 16%, 48% de (anti), 65% ee (anti) R1 = R3 = Ph, R2 =Me (E/Z = 8 : 92), X = F: 73%, 98% de (syn), 89% ee (syn) R1 = Ph, R2 = Me (E/Z = 8 : 92), R3 = 4-MeOC6H4, X = F: 94%, 90% de (syn), 73% ee (syn) OCOX3 R3 = Ph, X = Cl: 81%, 84% de (anti), 75% ee (anti) R3 = 4-MeOC6H4, X = Cl: 49%, 86% de (anti), 80% ee (anti) R3 = Ph, X = F: 88%, 92% de (anti), 95%ee (anti) R3 = 4-MeOC6H4, X = F: 78%, 86% de (anti), 90% ee (anti) Proposed catalytic cycle:

* P P Ag O O

O Ag

R3

*

O

P P

H

R1

* * R3 R2 P

R1

R2 O MeOCOCX3

MeOH OCOX3 R

1

R

1

R i-Pr2EtHN+ TfO–

OH

O

(S)-BINAP/AgOMe 2

MeOH, i-Pr2NEt

* * R3 R2

(S)-BINAP/AgOTf Proposed transition states:

R3

R2

H

H P * R1 + Ag O P O E

O R1

H P * R1 + R O Ag P O H Z R2 3

OH R3

R2 anti-Product

O R1

OH R3

R2 syn-Product

Scheme 9.71 Aldol reaction of aldehydes and alkenyl trihaloacetates.

9.6 Silver-Catalyzed Aldol-Type Reactions

diastereoselectivities of 90–98% de, good yields of 73–94%, and moderate to good enantioselectivities of 73–89% ee. To explain these results, the authors have proposed the cyclic transition state structures depicted in Scheme 9.71 that explained the formation of the anti-aldol products from (E)-silver enolates and that of the syn-aldol products from (Z)-silver enolates. Other types of asymmetric silver-catalyzed aldol reactions have been developed by several groups, such as Mukaiyama aldol reactions of aldehydes with silyl enolates. For example, in 2000, Yamagishi and coworkers catalyzed these reactions by a combination of AgPF6 and BINAP with moderate enantioselectivities of up to 69% ee [118]. In 2001, Yamamoto and coworkers reported higher enantioselectivities of up to 97% ee for major syn-diastereomeric aldol products arisen from comparable reactions based on the use of 4-Tol-BINAP combined with AgTf [119]. Later in 2006, high enantioselectivities (96% ee) were also achieved by Hoveyda and coworkers in the Mukaiyama aldol reaction of silyl enolates with α-ketoesters by using another type of silver catalyst system, such as a chiral amino acid-based ligand combined with AgF2 [120]. On the other hand, in asymmetric direct aldol reactions [113b], the aldol donor and acceptor are used directly, without needing the preformation or preactivation of the enolate species for enantioselective C—C bond formation. The in situ catalytic generation of active enolates from aldol donors is the initial step in direct aldol reactions, and consequently the scope of the aldol donor is usually limited to carbonyl compounds bearing protons of relatively high acidity. Although the electronegativity values of sulfur and carbon atoms are similar, α-sulfanyl carbonyl compounds have an inherently more acidic α-proton than the parent carbonyl compounds because the sulfide functionality stabilizes the α-carbanion through appreciable stereoelectronic effects [121]. In this context, Kumagai and coworkers have developed enantioselective silver-catalyzed direct aldol reactions of α-sulfanyl lactones with aldehydes [122]. As shown in Scheme 9.72, the reactions were performed in toluene at −20 ∘ C in the presence of DBU as a base and a combination of 3 or 5 mol% of AgPF6 as precatalyst with a chiral Biphep-type ligand. They afforded a range of chiral, densely functionalized lactones in moderate to high yields (50–93%), good to high syn-diastereoselectivities (80% to >90% de), and general excellent enantioselectivities of 89–99% ee. In particular, α,α-nonbranched aldehydes, susceptible to side self-aldol condensations under strongly basic conditions, provided the corresponding aldol products in good yields and selectivities. This selectivity probably resulted from the preferential enolization of the α-sulfanyl lactones, because of the soft–soft interaction between silver and the α-sulfanyl group. Moreover, aldehydes bearing alkyl substituents and those with oxygen-containing substituents were tolerated, giving the corresponding aldol products with high syn-diastereoselectivities of up to >90% de, combined with high enantioselectivities of 98–99% ee. Remarkably, even the use of formaldehyde was successful (93% yield, 89% ee), demonstrating that the process was not sensitive to moisture. The scope of aldehydes was also extended to those bearing a carbamate or ester group, leading to the corresponding products in 82–86% de and 98–99% ee as well as to an α-pyridyl-substituted aldehyde, which provided a comparably good result (86% de, 98% ee). In addition to five-membered lactones, a six-membered substrate produced remarkable

605

606

9 Asymmetric Silver-Catalyzed Reactions

MeO MeO

O + ( )n

O R

PAr2

Ar = 3,5-(t-Bu)2-4-MeOC6H2 (3 or 5 mol%) AgPF6 (3 or 5 mol%)

O MeS

PAr2

H

DBU (3 or 5 mol%)

OH O R MeS

O ( )n

Toluene, –20 °C

R = BnCH2, n = 1: 93%, 90% de, 99% ee R = n-Hept, n = 1: 77%, 86% de, 99% ee R = i-Bu, n =1: 81%, 82% de, 99% ee R = BnOCH2, n = 1: 85%, 80% de, 99% ee R = PMBOCH2, n = 1: 81%, 86% de, 98% ee R = TBSOCH2, n = 1: 87% >90% de, 98% ee R = H: 93%, n = 1, 89% ee R = CbzNH(CH2)2, n = 1: 89% 82% de, 98% ee R = EtO2C(CH2)2, n = 1: 70%, 86% de, 99% ee R = 2-pyridyl-(CH2)2, n = 1: 58%, 86% de, 98% ee R = BnCH2, n = 2: 79%, >90% de, 99% ee R = BnOCH2, n = 2: 92% >90% de, 99% ee R = 2-furyl, n = 1: 50%, 88% de, 96% ee

Scheme 9.72 Aldol reaction of aldehydes and α-sulfanyl lactones.

results with 79–92% yields, >90% de, and 99% ee. In contrast, a seven-membered lactone only produced a trace amount of the corresponding aldol product. The utility of this novel methodology was demonstrated in the development of a total synthesis of viridofungin A and NA 808, which are serine palmitoyl transferase inhibitors. 9.6.2

Nitroso-aldol Reactions

The asymmetric nitroso-aldol reaction constitutes a powerful method to introduce a hydroxyl group at the α-position of a carbonyl compound [123]. In 2003, Yamamoto and coworker demonstrated that a BINAP-derived silver catalyst promoted the regioselective asymmetric O-nitroso-aldol reaction of tin enolates with moderate to excellent enantioselectivities of 52–97% ee combined with general high yields (65–92%) [124]. Further studies by the same authors showed that the regio- and enantioselectivities of these reactions were dependent on the structure of the active catalytic silver complex [125]. For example, by using a bimetallic silver triflate derived from a chiral biphosphine, it was possible to reverse the regioselectivity of the reaction to afford preferentially the N-aldol product with almost complete regioselectivity (N:O >99 : 1) and high enantioselectivities of up to 98% ee. With the aim of avoiding the use of toxic tin enolates,

9.6 Silver-Catalyzed Aldol-Type Reactions

Yamamoto and coworkers recently developed enantioselective silver-catalyzed O-nitroso-aldol reactions with silyl enol ethers [126]. Among a series of chiral phosphite ligands derived from BINOL, ligand depicted in Scheme 9.73 was selected as optimal when combined with AgBF4 in the presence of CsF as fluoride source at −78 ∘ C. Under these conditions, various cyclic silyl enol ethers reacted with PhNO to yield the corresponding O-nitroso-aldol products with a very high regioselectivity (O/N ≥98 : 2) and moderate to excellent enantioselectivities of 64–99% ee (Scheme 9.73). It was found that, in the absence of the fluoride source, the reaction did not proceed at all. The generality of the process was shown with a variety of silyl enol ethers. Six-membered substrates derived from unsubstituted cyclohexanone (R = H, n = 1) provided the corresponding products in 72–85% yields and uniformly excellent enantioselectivities of Ph O P OPh O Ph OSiMe2TMS R

+

PhNO

O

(10 mol%) AgBF4 (10 mol%)

O NHPh * R X ()

CsF (2 equiv.)

X ( )n

n

THF, MeOH, –78°C

R = H, X = CH2, n = 1: 85%, 95% ee R = H, X = C(Me)2, n = 1: 72%, 98% ee R = H, X = C[O(CH2)2O], n = 1: 85%, 96% ee R = H, X = O, n = 1: 66%, 97% ee R = H, X = CH2, n = 0: 41%, 90% ee R = H, X = CH2, n = 2: 37%, 64% ee R = Ph, X = CH2, n = 1: 99%, 79% ee R = 2-Naph, X = CH2, n = 1: 80%, 76% ee

OSiMe2TMS

O

OSiMe2TMS +

84%, 92% ee

PhNO

O NHPh

Same conditions

Ph

Ph (S) 99% ee

91%, >98% de, 99% ee

O

OSiMe2TMS +

PhNO

Same conditions

O NHPh Ph

Ph (R) 99% ee

(R,R)-product

70%, 82% de, 99% ee

Scheme 9.73 O-Nitroso-aldol reactions of silyl enol ethers.

(R,S)-product

607

608

9 Asymmetric Silver-Catalyzed Reactions

95–98% ee. Moreover, a tetrahydropyran derivative was a suitable substrate, leading to the corresponding product in 66% yield and 97% ee. The reaction of a five-membered silyl enol ether also gave the corresponding product with 90% ee and 41% yield, while a seven-membered substrate provided a lower enantioselectivity of 64% ee. Furthermore, 2-substituted (R ≠ H) cyclohexanone derivatives yielded the corresponding products in high yields (80–99%) and moderate to good enantioselectivities of 76–79% ee. On the other hand, a better result (84% yield and 92% ee) was obtained in the reaction of an α-tetralone derivative. To complete this study, the authors also investigated the diastereoselectivity of the reaction of two chiral silyl enol ethers. As shown in Scheme 9.73, the reaction of a (S)-configured substrate with PhNO under the same conditions led to the corresponding (2R,3R)-product as a single stereoisomer (>98% de, 99% ee) in 91% yield, while the enantiomeric (R)-substrate led to the (2R,3S)-configured product with a good diastereoselectivity of 82% de combined with 99% ee and 70% yield. These results showed that the stereochemical outcome of the O-nitroso-aldol reaction could be controlled by the catalyst regardless of the configuration of the silyl enol ether substrate at C3. In 2009, Yanagisawa et al. demonstrated that Bu2 Sn(OMe)2 catalyzed the N-nitroso-aldol reaction between alkenyl trichloroacetates and PhNO in the presence of methanol [127]. With the aim of developing an asymmetric version of this process, the same group performed these reactions in the presence of 5 mol% of a combination of AgOAc with a P-chiral ligand such as (R,R)-t-Bu-QuinoxP* [128]. Under these conditions, the reaction of a range of alkenyl trichloroacetates derived from cyclopentanone, cyclohexanone, and cycloheptanone with nitrosobenzene derivatives led to mixtures of the corresponding chiral O-adducts and N-adducts in variable yields of 28–81%, with generally high enantioselectivities of 90–99% ee, and with O/N ratios of 63 : 37 to 97 : 3 (Scheme 9.74). Indeed, the major products of the reaction were α-aminooxyketones while the corresponding α-hydroxyamino ketones always constituted the minor products. The scope of the reaction could be extended to 1-tetralone derivatives for which nearly exclusive O-selectivity (O/N = 96 : 4 to >99 : 1) in addition to excellent enantioselectivity (97–99% ee) was observed. As in the asymmetric aldol reaction of α-ketoesters with alkenyl trichloroacetates (Scheme 9.70), the process evolved through the formation of a tin enolate from the reaction of a alkenyl trichloroacetate with Bu2 Sn(OMe)2 . Then, this enolate added to PhNO (R1 = R2 = H) enantioselectively in the presence of the chiral silver catalyst to afford the tin alkoxide of O- and N-aldol products, which were subsequently protonated with methanol, resulting in the formation of the final products with regeneration of Bu2 Sn(OMe)2 . To explain the stereoselectivity of the reaction, the authors proposed the transition state depicted in Scheme 9.74. Initially, the silver atom of the catalyst coordinates to the nitrogen atom of PhNO. The tin enolate then approaches the oxygen atom of PhNO while avoiding steric repulsion from a tert-butyl group of the chiral ligand. Thus, aminooxylation occurs selectively at the Si face of the tin enolate to yield the final (S)-α-aminooxyketone.

9.6 Silver-Catalyzed Aldol-Type Reactions t-Bu

4

R R4

( )n

N

P

(R,R)-t-Bu-QuinoxP* (5 mol%) AgOAc (5 mol%)

ON +

P

t-Bu

R2

OCOCl3

N

R1

R3 R3

R4

R1

O O

R4

( )n

Bu2Sn(OMe)2 (10 mol%) MeOH (30 equiv.) Toluene, –78 °C

3

+

N H

R4

OH R2

O

* N

R4

( )n

R2

R1

R3 R3

3

R R

N-product

O-product

R1 = R2 = R3 = R4 = H, n = 1: 65%, O/N = 89/11, 99% ee (O-product) R1 = Br, R2 = R3 = R4 = H, n = 1: 28%, O/N = 63/37, 90% ee (O-product) R1 = Me, R2= R3 = R4 = H, n = 1: 40%, O/N = 90/10, 99% ee (O-product) R1 = R3 = R4 = H, R2 = Me, n = 1: 67%, O/N = 76/24, 99% ee (O-product ) R1 = R2 = R3 = R4 = H, n = 0: 81%, O/N = 76/24, 97% ee (O-product) R1 = R2 = R3 = R4 = H, n = 2: 72%, O/N = 68/32, 96% ee (O-product) R1 = R2 = R3 = H, R4 = Me, n = 1: 71%, O/N = 97/3, 97% ee (O-product) R1 = R2 = R4 = H, R3 = Me, n = 1: 68%, O/N = 91/9, 97% ee (O-product) OCOCl3

O +

Same conditions

PhNO

R

OH

O O

NHPh

N Ph

+

R

* R

O-product

N-product

R = OMe: 90%, O/N = 96 : 4, 97% ee (O-product) R = H: 92%, O/N >99 : 1, 99% ee (O-product) Proposed transition states (R1 = R2 = R3 = R4 = H, n = 1): O R O H

O

Me t-Bu

t-Bu Ag

P

Disfavored

N O

O S O

N P N

Me

NHPh

SnBu2OMe

NHPh

H O SnBu2OMe

Favored

Scheme 9.74 O- and N-Nitroso-aldol reactions of alkenyl trichloroacetates.

In 2016, the same authors developed related nitroso-aldol reactions of alkenyl trifluoroacetates with nitrosoarenes by using a combination of AgOAc and the same chiral ligand (R,R)-t-Bu-QuinoxP* albeit in the absence of an organotin catalyst [129]. Indeed in this case, the reaction was performed in the presence of N, N-diisopropylethylamine as the base precatalyst and methanol. As shown in Scheme 9.75, the reaction between various cyclic alkenyl trifluoroacetates with nitrosoarenes led to mixtures of the corresponding chiral O- and N-adducts in moderate to quantitative yields of 54% to >99% and enantioselectivities of 72–99% ee along with O/N ratios of 52 : 48 to >99 : 1. In contrast, acyclic alkenyl trifluoroacetates furnished the opposite N-selectivity, as shown in Scheme 9.75.

609

610

9 Asymmetric Silver-Catalyzed Reactions t-Bu

OCOF3

N ( )n

R1

P

N

P t-Bu

O R2

+

N

R2

(R,R)-t-Bu-QuinoxP* (3 mol%) AgOAc (3 mol%) i-Pr2NEt (20 mol%) MeOH (5 equiv.) Toluene, –78 °C

O

HN O

O

+

( )n

R1

R1

R2 = H,

N * ( )n

R2

N-product

O-product R1 = OMe,

OH

n = 1: 84%, O/N = 90:10, 96% ee (O-product)

R1 = R2 = H, n = 1: 98%, O/N = 99:1, 99% ee (O-product) R1 = H, R2 = 2-Me, n = 1: 67%, O/N >99:1, 99% ee (O-product) R1 = H, R2 = 4-Me, n = 1: 91%, O/N >99:1, 99% ee (O-product) R1 = H, R2 = 2-Bu, n = 1: >99%, O/N >99:1, 96% ee (O-product) R1 = H, R2 = 2-iPr, n = 1: >99%, O/N 57:43, 86% ee (O-product) R1 = H, R2 = 4-CF3, n = 1: 54%, O/N 52:48, 72% ee (O-product) R1 = H, R2 = 4-Br, n = 1: 76%, O/N 52:48, 72% ee (O-product) R1 = R2 = H, n = 0: 99%, O/N = 93:7, 95% ee (O-product) R1 = H, R2 = 3-OMe, n = 1: 95%, O/N 95:5, 97% ee (O-product) R1 = R2 = H, n = 2: 94%, O/N = 99:1, 99% ee (O-product) OCOCF3 +

Ph R

O Same conditions PhNO

Ph

O

NHPh O

R O-product

+

Ph

OH * N Ph R

N-product

R = Me: >99%, O/N = 35/65, 92% ee (O-product) R = n-Pr: 86%, O/N = 40/60, 80% ee (O-product)

Scheme 9.75 O-Nitroso-aldol reactions of alkenyl trifluoroacetates.

9.7 Silver-Catalyzed Alkynylations Alkynes and derivatives [33, 130] constitute key building blocks in organic chemistry related to their versatile reactivities [6g, 131]. The nucleophilic addition of terminal alkynes to imines constitutes an alternative pathway for the production of propargylamines. In particular, chiral propargylamines are important building blocks for the synthesis of natural products, pharmaceuticals, and pesticides [132]. While the asymmetric alkynylation of imines represents the most direct route to reach these important products, efficient methodologies still remain rare. Among them, Chen and coworkers have developed a general enantioselective silver-catalyzed addition of aliphatic as well as aromatic alkynes to a range of N-aryl aromatic aldimines performed at room temperature in chlorobenzene in the presence of only 0.5 mol% of (R)-BINAP combined with 1 mol% of AgOTf [133]. As shown in Scheme 9.76, the corresponding chiral propargylamines were obtained in uniformly high yields (83–95%) albeit with low to moderate enantioselectivities of 23–76% ee. The lowest enantioselectivities of 23–34% ee were obtained in the reaction of aniline derivatives bearing electron-withdrawing or electron-donating groups at the para-position (Ar2 = 4-MeO2 CC6 H4 , 4-O2 NC6 H4 , or 4-MeOC6 H4 ), whereas higher enantioselectivities (37–76% ee) were obtained in the reaction of unsubstituted aniline derivatives (Ar2 = Ph). The reaction tolerated a variety of terminal alkynes. Both electron-donating-

9.7 Silver-Catalyzed Alkynylations

N

Ar2

Ar2

(R)-BINAP (0.5 mol%) AgOTf (1 mol%)

+

Ar

Ar1

PhCl, r.t.

R

1

HN

R 1

Ar = Ph, 4-Tol, 1-Tol, 1-FC6H4, 3-BrC6H4, 4-ClC6H4 Ar2 = Ph, 4-O2NC6H4, 4-MeO2CC6H4, 4-MeOC6H4 R = Ph, 4-MeOC6H4, 4-F3CC6H4, n-Bu 83–95%, 23–76% ee

Scheme 9.76 Addition of alkynes to N-aryl aromatic aldimines.

and electron-withdrawing-substituted phenylalkynes gave high yields (92–94%) combined with moderate enantioselectivities (43–56% ee) while 1-hexyne led to the corresponding product in 84% yield and 65% ee. On the other hand, internal alkynes were found not suitable for this transformation, presumably due to their lower reactivity compared with terminal alkynes. Interestingly in this process, the authors discovered that the ligand-to-silver precatalyst ratio played a crucial role in the reaction outcome, since no reaction occurred in the absence of ligand or in the presence of an excess of ligand. The extension of the silver-catalyzed asymmetric imine alkynylation to other challenging and unexplored imines, such as seven-membered cyclic imines, was achieved by Liu and coworkers [134]. As shown in Scheme 9.77, the reaction of seven-membered dibenzo[b,f ] [1,4]oxazepines with various alkynes performed at 15 ∘ C in 1,4-dioxane as solvent and promoted by a combination of 5 mol% of AgOAc and 10 mol% of a chiral phosphoric acid as ligand yielded the corresponding chiral oxazepine derivatives in moderate to excellent yields of Ar O O P OH O Y

X

Z

Z

Ar = 9-phenanthryl (10 mol%) AgOAc (5 mol%)

W N

O

+ R

W′ Y′

Y

X

Ar

1,4-Dioxane, 15 °C

W NH

O W′

R Y′

R = Ph, 4-Tol, 4-MeOC6H4, 4-FC6H4, 1-FC6H4, 3-thienyl, 1-cyclohexenyl, 2-propenyl, (E)-PhCH=CH X = H, Me, Cl; Y = H, Cl, F Z = H, Me; W = H, Me Y′ = H, Me, F; W′ = H, Me, Cl 44–96%, 78–99% ee

Scheme 9.77 Addition of alkynes to seven-membered cyclic imine dibenzo[b,f ][1,4]oxazepines.

611

612

9 Asymmetric Silver-Catalyzed Reactions

44–96% and good to excellent enantioselectivities of 78–99% ee. A broad scope of alkynes including arylacetylenes, heteroaryl acetylenes, and enynes were compatible providing the highest enantioselectivities (generally 90–99% ee). Various substituents on the imine were also tolerated. The scope of the precedent methodology could also be extended to other conjugated alkynes, such as 1,3-diynes, as shown in Scheme 9.78 [134]. Indeed, a terminal 1,3-diyne reacted with differently substituted seven-membered dibenzo[b,f ] [1,4]oxazepines under the same reaction conditions to give the corresponding chiral densely functionalized oxazepine derivatives in both moderate to high yields of 53–90% and enantioselectivities of 63–96% ee. This efficient process provided a facile access to optically active 11-substituted-10,11-dihydrodibenzo[b,f ][1,4]oxazepine derivatives containing two carbon–carbon triple bonds, allowing easy subsequent transformations to be achieved. Ar O O P OH O Y

X Z

N

O

+ Ph

Z′ Y′

Ar = 9-phenanthryl (10 mol%) AgOAc (5 mol%)

Z

1,4-Dioxane, 15 °C

Z′

X = H, Cl Y = H, Me, t-Bu, Cl Z = H, Me, Cl Y′ = H, Me, F Z′ = H, Me, Cl 53–90%, 63–96% ee

Y

X

Ar

NH

O

Ph Y′

Scheme 9.78 Addition of a 1,3-diyne to seven-membered cyclic imine dibenzo[b,f ][1,4]oxazepines.

In 2011, Jarvo and coworker developed a silver-catalyzed enantioselective propargylation reaction of aldimines with allenyl boronic acid pinacol ester, generating the corresponding homopropargylic sulfonamide products in moderate to quantitative yields of 40–99% and good to excellent enantioselectivities of 74–98% ee [135]. As shown in Scheme 9.79, the reaction was promoted by a chiral silver catalyst in situ generated from 10 mol% of AgF and 12 mol% of a chiral Walphos-type biphosphine at −20 ∘ C. Concerning (hetero)aromatic imines that provided the best results, the presence of either electron-donating or electron-withdrawing groups on the aryl group (R) was tolerated, giving uniformly high enantioselectivities of 90–98% ee in combination with 70–99% yields. On the other hand, vinylic and aliphatic aldimines led to the corresponding products in lower yields and enantioselectivities of 40–47%

9.7 Silver-Catalyzed Alkynylations

PPh2 PAr′2 Fe

N

Ts +

R

Ar′ = 3,5-(F3C)2C6H3 (12 mol%) AgF (10 mol%)

C Bpin

KOt-Bu (20 mol%) t-BuOH (1.1 equiv.) MeOH then THF, –20 °C

NHTs R

R = Ph, 4-BrC6H4, 4-F3CC6H4, 1-BrC6H4, 3,4-(MeO)2C6H3, 2-Naph, 2-furyl: 70–99%, 90–98% ee R = PhCH=C(Me), CH2=CH–CH2–C(Me)2: 40–47%, 74–89 % ee

NHTs

Ph AgOAc (1 equiv.)

Ph

Ts N

CH2Cl2, 40 °C 97% ee

99%, 97% ee

Scheme 9.79 Addition of allenyl boronic acid pinacol ester to aldimines.

and 74–89% ee, respectively (Scheme 9.79). To demonstrate the synthetic utility of this methodology, the authors further performed the silver-catalyzed intramolecular hydroamination of one product (R = Ph), which underwent 5-endo-dig cyclization resulting in an anti-Markovnikov adduct. Importantly, the cyclization reaction did not affect the newly formed stereogenic center and provided an enantiomerically enriched 2-pyrroline in 99% yield and 97% ee, constituting a useful building block in the synthesis of bioactive pyrrolidines and alkaloids. In 2015, the same authors applied a related catalyst system using a diastereomeric ligand albeit combined with AgPF6 as precatalyst instead of AgF to promote the first silver-catalyzed enantioselective propargylation of cyclic N-sulfonylketimines [136]. As shown in Scheme 9.80, the reaction of allenyl boronic acid pinacol ester with many aryl as well as alkyl cyclic N-sulfonylketimines led to the corresponding homopropargylic products in moderate to high yields of 62–89% and uniformly very high enantioselectivities of 90–98% ee. Remarkably, alkylketimines gave results (72–88% yield, 96–98% ee) comparable with variously substituted diarylketimines (62–89% yield, 90–98% ee). To emphasize the utility of the pendant terminal alkyne of the formed products, the authors synthesized spirocyclic, alkenyl, and allyl derivatives through enyne ring-closing metathesis, Sonogashira cross-coupling, and reduction reactions that proceeded without loss of enantioselectivity. The scope of this methodology was extended to less reactive cyclic sulfamate ketimines that constitute a related class of N-sulfonylketimines that react with

613

614

9 Asymmetric Silver-Catalyzed Reactions

PPh2 PAr′2 Fe

O O S N

Ar′ = 3,5-(F3C)2C6H3 (12 mol%) AgPF6 (10 mol%)

C

+ R

Bpin

O O S NH

KOt-Bu (20 mol%) t-BuOH (1.1 equiv.) DMF, r.t.

R

With R = Ph, 3,4-F2C6H3, 3-ClC6H4, 3-F3CC6H4, 4-MeOC6H4, 2-furyl, 2-thienyl: 62–89%, 90–98% ee With R = n-Bu, Me, CH2=CH(CH2)2, (OCH2CH2O)CH(CH2)2: 72–88%, 96–98% ee O O

O

O S

N

+ R

Same conditions

C

O

O S

NH R

Bpin Me: 76%, 98% ee R = Et: 51%, 98% ee

Scheme 9.80 Additions of allenyl boronic acid pinacol ester to cyclic N-sulfonylketimines.

nucleophiles to provide sulfamidates. As shown in Scheme 9.80, the addition of allenyl boronic acid pinacol ester to these substrates led to the corresponding homopropargylic sulfamidates in moderate to good yields (51–76%) and excellent enantioselectivity (98% ee). In addition to imines, allenyl boronic acid pinacol ester has been added to ketones and α-ketoesters in the presence of a chiral silver catalyst derived from AgF and a chiral Walphos-type biphosphine [137]. As shown in Scheme 9.81, the reaction of methyl (hetero)aryl ketones (R = Me) provided the corresponding chiral tertiary alcohols in moderate to high yields (48–95%) and enantioselectivities (71–90% ee), while α-ketoesters (R = CO2 t-Bu) provided the corresponding products in 73–82% yields and slightly better enantioselectivities (86–91% ee). Remarkably, even a dialkyl ketone, such as methyl homobenzyl ketone, led to the corresponding alkynylated product in 60% yield and 71% ee. More interestingly, the reaction conditions were applicable to benzophenones, which allowed their enantioselective propargylation to be reported for the first time. As shown in Scheme 9.81, the ability of the silver catalyst to distinguish between the two aromatic rings of benzophenones led to enantioenriched diaryl carbinols, which are present in a variety of drugs and medicinal agents. These products were generated in moderate to excellent yields (52–95%) combined with high to excellent enantioselectivities (80–97% ee). Various substituents were tolerated in the ortho-position including methyl group and halogens. In another area, Fan and coworkers have developed the first highly efficient asymmetric ring opening of oxabenzonorbornadienes with terminal alkynes,

9.7 Silver-Catalyzed Alkynylations

PCy2 PAr′2 Fe

O

C

+

O

R4

R2 R3

Ar

R5 Same conditions

R1

HO * R4

R2

C Bpin

R

Ar = Ph, 1-BrC6H4, 1-ClC6H4, 1-O2NC6H4, 2-thienyl R = Me 48–95%, 71–90% ee Ar = Ph, 2-Naph, 4-MeOC6H4 R = CO2t-Bu 73–82%, 86–91% ee

R1

+

HO

NaOt-Bu (15 or 30 mol%) Bpin t-BuOH (1.1 equiv.) MeOH then MTBE, –20 °C

R

Ar

Ar′ = 3,5-(F3C)2C6H3 (5 mol%) AgF (5 mol%)

R5

R3 R1 = R3 = CF3, R2 = R5 = H, R4 = Me: 92%, 97% ee R1 = R3 = F, R2 = R5 = H, R4 = Br: 85%, 87% ee R1 = R3 = R5 = H, R2 = CN, R4 = Cl: 95%, 80% ee R1 = CF3, R2 = R3 = R5 = H, R4 = Cl: 93%, 81% ee R1 = R3 = R4 = H, R2 = CN, R5 = F: 52%, 90% ee

Scheme 9.81 Additions of allenyl boronic acid pinacol ester to ketones and α-ketoesters.

which was catalyzed by 5 mol% of a combination of AgOTf and Pd(OAc)2 in the presence of a chiral Phanephos-derived ligand [138]. As shown in Scheme 9.82, the reaction performed at 0 ∘ C in DME as solvent led to the corresponding chiral ring-opened products in moderate to excellent yields of 54–95% combined with uniformly excellent enantioselectivities of 90–99% ee. This ligand was selected as optimal among a range of other ones including (R)-BINAP and derivatives, (R)-Synphos, (R)-MeO-Biphep, and (R)-Phanephos. Various substituted aryl acetylenes were proved applicable, providing the corresponding alkynylated products in high enantioselectivities of 90–99% ee. However, some adverse effects of the electronic or positional properties of the substituents on the reactions were observed. For example, strong electron-donating groups, such as methoxy on the 4- or 1-position of the phenyl ring (R3 ), were found to reduce the enantioselectivities of the reactions to 90% ee. On the other hand, the presence of electron-withdrawing substituents on the para-position of the phenyl ring of the alkyne allowed the best results to be achieved (87–95% yields, 95–99% ee). Notably, trimethylacetylene could also serve as a proper carbon nucleophile (R3 = TMS) and produced the corresponding product in 74% yield along with a high enantioselectivity of 97% ee. In contrast to aryl acetylenes, alkyl acetylenes were not tolerated, since no reaction occurred even with extended reaction

615

616

9 Asymmetric Silver-Catalyzed Reactions

PAr2

PAr2 Ar = 3,5-Me2C6H3 (6 mol%) AgOF (5 mol%) Pd(OAc)2 (5 mol%)

R1 R2 O R2

+ R3

DME, 0 °C

R1

R1 R2 R2 R1

OH

R3

R1 =

H, Me, OMe R2 = H, Me, OMe, Br R2, R2 = OCH2O R3 = Ph, 4-MeOC6H4, 1-MeOC6H4, 3-MeOC6H4, 3,5-Me2C6H3, 4-Tol, 4-FC6H4, 4-F3COC6H4, 4-BrC6H4, 4-NCC6H4, 4-F3CC6H4, TMS 54–95%, 90–99% ee

Scheme 9.82 Ag/Pd-catalyzed ring-opening reaction of oxabenzonorbornadienes with alkynes.

times. Concerning the scope of the oxabenzonorbornadienes, those having electron-withdrawing groups and sterically bulky substituents on the phenyl ring required longer reaction times.

9.8 Silver-Catalyzed Allylations The asymmetric allylation of carbonyl compounds constitutes a useful method to synthesize chiral homoallylic alcohols, which can be further easily converted into important building blocks, such as β-hydroxy carbonyl compounds and derivatives [139]. In 1996, Yamamoto and Yanagisawa introduced a combination of AgOTf with (R)-BINAP as novel catalytic system, which was demonstrated to promote highly enantioselective silver-catalyzed allylation of aldehydes with allylic stannanes, providing the corresponding chiral homoallylic alcohols in excellent enantioselectivities of up to 96% ee and high yields of up to 88% [4d]. In 2008, Studer and coworker investigated the asymmetric silver-catalyzed cyclohexadienyl transfer from 1,4-cyclohexadienyltributyltin to various aromatic aldehydes using a combination of AgOTf and (S)-BINAP as catalyst system [140]. The reaction led to the corresponding chiral 1,4-cyclohexadienylphenylmethanols in good to quantitative yields of 80–99% and moderate to high enantioselectivities of 56–90% ee (determined for the corresponding oxidized products), as shown in Scheme 9.83. These products were further submitted to oxidation by treatment with DDQ to give the corresponding biologically interesting arylphenylmethanols. Studying the scope of aromatic aldehydes, the authors obtained the best result (99% yield and 92% ee) in the reaction of 4-chlorobenzaldehyde. Another nice combination of high yield and enantioselectivity of 91% and 90% ee, respectively, was achieved in the reaction of 2-naphthaldehyde.

9.8 Silver-Catalyzed Allylations

SnBu3

O Ar

H

+

OH

(S)-BINAP (10 mol%) AgOTf (10 mol%)

Ar

Toluene, –50 °C 78–99% DDQ Benzene, r.t. OH

Ar = Ph, 4-Tol, 4-(i-Pr)C6H4, 4-(t-Bu)C6H4, 4-ClC6H4, 4-BrC6H4, 4-IC6H4, 4-F3CC6H4, 4-MeOC6H4, 1-Tol, 1-MeOC6H4, 3-Tol, 3-BrC6H4, 3-MeOC6H4, 2-Naph

Ar 68–90%, 56–90% ee

Scheme 9.83 Allylation of aromatic aldehydes with 1,4-cyclohexadienyltributyltin.

Although reactions involving allylic stannanes as nucleophiles yielded the desired products in high enantioselectivities, they had the disadvantage to being environmentally less benign organotin compounds. To overcome this problem, Yamamoto and coworkers have applied their catalyst system based on a combination of Tol-BINAP with AgF to promote enantioselective Sakurai–Hosomi-type allylation of aldehydes with allyltrimethoxysilane as allyl donor, which allowed the corresponding homoallylic alcohols to be obtained in enantioselectivities of up to 94% ee in good yields (70–90%) [141]. In 2012, Dudding and coworker reinvestigated these reactions by using a combination of AgF with (R)-BINAP in methanol at −20 ∘ C [142]. As shown in Scheme 9.84, the reaction of allyltrimethoxysilane with various 1-substituted benzaldehydes led to the corresponding chiral homoallylic alcohols in moderate to high yields (64–91%). The latter were subsequently submitted to a Mizoroki–Heck reaction to afford the corresponding C1 -chiral 3-methylene-indan-1-ols in good yields X

O H

X

OH

(R)-BINAP (6–10 mol%) AgF (6–10 mol%) +

Y

MeOH, –20 °C Si(OMe)3

Y 64–91% X = Cl, Br, I Y = H, OMe, F [(Ph3P)2]PdCl2 (2 mol%) OH

Y 70–76%, 58–80% ee

Scheme 9.84 Allylation of aromatic aldehydes with allyltrimethoxysilane.

617

618

9 Asymmetric Silver-Catalyzed Reactions

(70–76%) and moderate to good enantioselectivities (58–80% ee). It must be noted that the sterically demanding 1-trifluoromethylsulfonylated benzaldehyde did not react. This novel sequence constituted a new entry to chiral indanol derivatives, which are key substructures within a number of biologically active compounds. In 2005, Yamamoto and coworker reported asymmetric allylation reactions of ketones with allyltrimethoxysilane performed by using (R)-Difluorphos as chiral ligand in combination with AgF, providing the corresponding tertiary homoallylic alcohols with enantioselectivities of up to 96% ee [143]. Encouraged by these results, the same authors later investigated the asymmetric allylation of aldimines with allyltrimethoxysilane that is still challenging [144]. In this case, the use of monophosphine ligands combined with AgF provided generally better results than diphosphine ligands, such as (R)-Difluorphos, in the synthesis of the corresponding chiral homoallylamines, except for the imine bearing a 1-PhOC6 H4 group that reacted in 82% ee (vs. 60% ee). As shown in Scheme 9.85, when the reaction of various phenyl N-aryl aldimines and allyltrimethoxysilane was catalyzed by 5 mol% of a combination of AgF with a monophosphine ligand (Scheme 9.85), it yielded the corresponding chiral homoallylamines in quantitative yields and moderate enantioselectivities of 60–77% ee.

N

Ar +

Si(OMe)3

Ph

With L* =

OMe PPh2

(5 mol%) Ar = 1-Naph: >99%, 77% ee Ar = 2-Naph: >99%, 70% ee Ar = 4-PhOC6H4 >99%, 60% ee

AgF (5 mol%) L* (2.5 or 5 mol%) MeOH (1 equiv.) THF, –20 °C

F

O

F

O

F

O

F

O

With L* =

NHAr Ph

PPh2 PPh2

(R)-Difluorophos (2.5 mol%) Ar = 4-PhOC6H4 70%, 82% ee

Scheme 9.85 Allylation of phenyl N-aryl aldimines with allyltrimethoxysilane.

A catalytic asymmetric borono variant of Hosomi–Sakurai reactions was reported by Kobayashi and coworkers [145]. Although nontoxic allyl boronates have been neglected as allylation agents, they present significant advantages in comparison with more nucleophilic silicon-based compounds, such as superior stability and unique reactivity and selectivity. For example, pinacol allyl boronate reacted with a range of Csp3 intermediates, such as N,O-aminals, to give the corresponding homoallylamides in uniformly high yields of 88–99%. The process was performed in the presence of a preformed silver BINOL-derived phosphate and indium(I) chloride at room temperature. It must be noted that, in the absence

9.9 Silver-Catalyzed Cyclizations of Allenes

of the latter, the silver catalyst displayed only low reactivity and asymmetric induction. The reaction conditions were applied to a series of aromatic and heteroaromatic N,O-aminals that provided the corresponding homoallylamides in both excellent yields and enantioselectivities of 94–99% and 90–96% ee, respectively, while slightly lower yields and enantioselectivities (88–96% and 72–96% ee) were obtained in the case of aliphatic N,O-aminals. The authors have proposed that the reaction evolved through an SN 1 mechanism with iminium ion species Q as a key intermediate, which supported the critical role of the chiral counteranion (Scheme 9.86). This study has demonstrated that boronates were dramatically more reactive and selective than classic silicon-based reagents, constituting the first highly enantioselective Hosomi–Sakurai reactions with Csp3 centers. Proposed mechanism: –

NHBz R

OMe

Ag-X*

+ NHBz

X*

H

R

B(pin)

NHBz R

Q

Scheme 9.86 Allylation of N,O-aminals with pinacol allyl boronate.

In 2014, Rios and coworkers developed a novel highly diastereoselective synthesis of highly functionalized alkyl-azaarene systems [146]. This methodology included a synergistic catalysis event, involving activation of an alkyl azaarene with AgOAc and Lewis base (DABCO) activation of a Morita–Baylis–Hillman carbonate. It led to the corresponding racemic allylated alkyl azaarenes with good yields and high diastereoselectivities (up to 88% de). Initial experiments have been done in order to develop an enantioselective version of this process. For example, the use of chiral ligands, such as (R)-BINAP or a cinchona alkaloid ligand, allowed the allylated products to be produced in moderate to high yields (54–90%) and high diastereoselectivity (>88% de) but with low to moderate enantioselectivities (30–50% ee).

9.9 Silver-Catalyzed Cyclizations of Allenes The addition of heteroatoms to activated C=C bond constitutes a useful methodology to reach a variety of functionalized molecules. In particular, the intramolecular asymmetric transition metal-catalyzed nucleophile addition to allenols and amino allenes constitutes a powerful tool for the synthesis of various chiral heterocycles [32]. While several metals are capable of promoting these reactions, silver remains one of the most effective catalysts. In 2009, Hii and coworkers demonstrated that silver-catalyzed reactions of δ-allenols regioselectively afforded the corresponding vinyl-substituted tetrahydrofurans through 5-exo-trig cyclization, while the use of other Lewis acids, such as Sn(OTf )2 or Zn(OTf )2 , favored the 6-exo-dig cyclization to give tetrahydropyran rings [147]. Later in 2012, an asymmetric version of this reaction was described for the first

619

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9 Asymmetric Silver-Catalyzed Reactions

time by this group by using silver salts of chiral acids. As shown in Scheme 9.87, moderate enantioselectivities of up to 73% ee combined with almost quantitative yields were achieved in the intramolecular cyclization of γ-allenic alcohols. This reaction was run at room temperature, yielding the corresponding chiral tetrahydrofurans when it was promoted by a chiral preformed TADDOL-derived phosphate silver catalyst [148]. In the same study, the authors also reported the first asymmetric silver-catalyzed intramolecular hydroamination of γ-allenic amines to yield the corresponding chiral N-protected pyrrolidines. In this case, a preformed phosphinate catalyst was found much more active than the previously mentioned phosphate catalyst, allowing conversions of 84–100% to be achieved in combination with moderate enantioselectivities of 46–68% ee, as shown in Scheme 9.87. Pyridine was used as an additive that resulted in an accelerative effect on the reaction (24 hours vs. 60 hours). Moreover, the catalyst system was applicable to different N-protecting groups, including sulfonamides, carbamates, and benzyl groups. Ph Ph O O

O O P O OAg Ph Ph

C ( )n

OH Ph

Ph

C H

DCE, r.t.

NHX

(15 mol%) Pyridine (15 mol%) DCE, 23 °C

n = 2 : 99%, 73% ee n = 1 : 98%, 41% ee

Ph Ph ( )n

O O O P OAg O

Ph Ph H

O *

(15 mol%)

X N * Ph Ph

X = Ts: 100% conversion, 68% ee X = 1-NaphSO2: 85% conversion, 46% ee X = Cbz: 84% conversion, 52% ee X = Bn: 100% conversion, 5% ee X = 4-Ns: 60% conversion, 14% ee X = MesSO2: 38% conversion, 39% ee

Scheme 9.87 Intramolecular cyclizations of γ-allenic alcohols and amines.

In 2016, Michelet and coworkers described enantioselective silver-catalyzed intramolecular cyclizations of γ-allenic alcohols performed for the first time in the presence of atropisomeric bidentate ligands [149]. Indeed, novel MeOBiphep-based silver catalysts were found efficient to promote these reactions at 10 ∘ C in dichloroethane as solvent in the presence of three equivalents of methanol. It provided the corresponding chiral vinyltetrahydrofurans in moderate to quantitative yields (46–99%) and low to good enantioselectivities (14–83% ee), as shown in Scheme 9.88. The first enantioselective intramolecular silver-catalyzed reaction of α-allenols was developed by Hong and coworkers [150]. This was promoted by a chiral preformed BINOL-derived phosphate silver catalyst in dichloromethane at −10 ∘ C, leading to the corresponding chiral 2,5-dihydrofurans in moderate to high conversions and enantioselectivities (44–68% and 41–93% ee). It evolved through kinetic resolution, providing the recovered enantioenriched substrates with moderate to excellent enantioselectivities (53–99% ee) along with the corresponding chiral cyclic products. The optimal chiral catalyst was selected

9.9 Silver-Catalyzed Cyclizations of Allenes

Br PAr2 PAr2

MeO MeO

Br Ar = 4-t-BuO2CC6H4 (7.5 mol%) AgSbF6 (15 mol%)

C R R

O

MeOH (3 equiv.) DCE, 10 °C

OH

R R 46–99%, 14–83% ee

R = Ph, 4-ClC6H4, 4-MeOC6H4 R, R = (CH2)5

Scheme 9.88 Intramolecular hydroalkoxylation of γ-allenic alcohols.

among a range of other silver complexes generated in situ from various types of ligands, such as BINAP, bisoxazolines, salen-type diimines, and monodentate phosphoramidites, combined with silver salts, such as AgNO3 and AgOTf, all of which provided low levels of enantioselectivity. The substrate scope showed that aryl-substituted α-allenic alcohols could bear both electron-deficient and electron-rich substituents, yielding the corresponding dihydrofurans with uniformly high levels of induction (82–90% ee), while the enantioenriched substrates were recovered in moderate to high enantioselectivities of 53–99% ee along with conversions of 44–56% (Scheme 9.89). Alkyl- and alkenyl-substituted α-allenic alcohols also underwent the reaction with generally a higher reaction Ar O P O

O OAg

Ar H

OH R

C

H

Ar = 2-Naph (20 mol%) CH2Cl2, –10 °C

R

O

H

OH

+ R

C

H

R = Ph, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-Tol, 4-(TBDPSO)C6H4, 3-Tol, 3-ClC6H4, 1-ClC6H4, 1-Tol, 2-Naph 44–56% conversion, 82–90% ee (product), 53–99% ee (substrate) R = Bn, n-Hept, Cy, BnO(CH2)3, 1-cyclohexenyl, t-Bu, PhCH=C(Me), BnCH2CH=C(Me) 48–68% conversion, 41–93% ee (product), 77–99% ee (substrate)

Scheme 9.89 Intramolecular hydroalkoxylation of α-allenic alcohols through kinetic resolution.

621

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9 Asymmetric Silver-Catalyzed Reactions

rate (48–68% conversions), leading to the corresponding products in moderate to high enantioselectivities of 41–93% ee, while the recovered substrates were obtained in excellent enantioselectivities of 77–99% ee. Earlier in 2010, Mikami and coworkers developed intramolecular asymmetric hydroalkoxylation of γ-allenic alcohols to give the corresponding chiral dihydrofuran derivatives in the presence of a combination of a neutral dinuclear gold complex with a chiral silver phosphate catalyst [151]. As shown in Scheme 9.90, in the presence of only 2.5 mol% of this catalyst system, the reaction of a range of γ-allenic alcohols led to the corresponding chiral tetrahydrofurans in good to excellent yields (75–98%) along with moderate to high enantioselectivities (70–95% ee). In this study, the role of the silver chiral complex was proposed by the authors to be that of a chiral anion donor (Scheme 9.90).

Ar O P O

O OAg

Ar Ar = 4-(4-t-BuC6H4)C6H4 (2.5 mol%) Ar′2 P AuCl Ar′2 P AuCl

R1 R1 2

R

OH

C

Ar′ = 3,5-Me2C6H3 (2.5 mol%)

Toluene, 0 or 10 or –20 °C

R2

O

R2 R2

R1 R1

R1 = Ph, R2 = H: 94%, 87% ee

R1 = H, R2, R2 = (CH2)4: 97%, 90% ee

R1 = 4-MeOC6H4, R2 = H: 85%, 95% ee

R1 = H, R2, R2 = (CH2)5: 98%, 95% ee

1

2

R = 4-ClC6H4, R = H: 75%, 77% ee 1=

R

1

H,

R2 =

R1 = Ph, R2 = Me: 75%, 70% ee R1 = Ph, R2, R2 = (CH2)5: 92%, 75% ee

Me: 97%, 93% ee

2

R = H, R = Et: 89%, 95% ee Possible active catalyst: Ar′2 + P Au Ar′2 P AuCl

Ar –

O

O

O

P O Ar

Scheme 9.90 Intramolecular hydroalkoxylation of γ-allenic alcohols through Au/Ag catalysis.

9.10 Silver-Catalyzed Aminations

9.10 Silver-Catalyzed Aminations The electrophilic amination reaction constitutes a direct method to stereoselectively form C—N bonds. Many efforts have been made in the enantioselective α-amination of carbonyl compounds, such as aldehydes, ketones, α-ketoesters, α-cyano esters, and other compounds, using azodicarboxylates as the nitrogen source since the pioneering work reported by Evans in 1997 [152]. In particular, the asymmetric α-amination of carbonyl compounds is an efficient route to important chiral α-amino acid derivatives [153]. Early in 2000, Kobayashi and coworkers reported that AgClO4 combined with BINAP as chiral ligand facilitated the asymmetric amination of silyl enolates with azo diester compounds with enantioselectivities of up to 86% ee [154]. More recently, Zhou and coworkers developed an efficient enantioselective silver-catalyzed α-amination of glycine Schiff bases with azodicarboxylates to give the corresponding chiral α,α-diamino carbonyl compounds [155]. When promoted by a combination of 3 mol% of AgOAc and 3.3 mol% of a Taniaphos-type ligand in toluene at −25 ∘ C, the process afforded these products in excellent yields of 93–98% associated with moderate to excellent enantioselectivities of 75–98% ee (Scheme 9.91). The NMe2 Fe PPh2 Ph2P

Ph N CO2R2

Ph

(3.3 mol%) AgOAc (3 mol%)

+ R1O2C N N CO2R1

Toluene, –25 °C

R1 = t-Bu, R2 = Me: 95%, 98% ee R1 = t-Bu, R2 = Et: 98%, 98% ee R O2C 1 2 Ph N CO2R1 R = t-Bu, R = p-BrC6H4: 95%, 96% ee R1 = R2 = t-Bu: 93%, 75% ee * Ph N CO2R2 R1 = i-Pr, R2 = Me: 98%, 92% ee R1 = Bn, R2 = Me: 98%, 76% ee R1 = Et, R2 = Me: 98%, 75% ee H N

1

Proposed mechanism: H R1O2C N Ph N CO2R1 * Ph N CO2R2

AcO Ag

Ph

Ph

OR2

– N N CO2R1 CO2R1 S

N Ph

AcOH

* Ph

L L Ag O + N

Ph

L * L

Ph

CO2R2

* L L Ag O + N OR2 – R

1

R O2C N N CO2R1

Scheme 9.91 α-Amination of glycine Schiff bases with azodicarboxylates.

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9 Asymmetric Silver-Catalyzed Reactions

steric properties of both substrates were found crucial for the enantioselectivity of the reaction. For example, with increasing steric hindrance of the substituents in the glycine Schiff bases, the stereoselectivity decreased dramatically from 98% ee (for R2 = Me) to 75% ee (for R2 = t-Bu) in reaction with di-tert-butyl azodicarboxylate (R1 = t-Bu). In contrast, an improvement of enantioselectivities from 75% ee (for R1 = Et) to 98% ee (for R1 = t-Bu) was observed through increasing the steric hindrance of the substituents in azodicarboxylates. Actually, the best enantioselectivity of 98% ee was reached in the asymmetric amination reaction of di-tert-butyl azodicarboxylate (R1 = t-Bu) with benzophenone imine glycine methyl or ethyl ester (R2 = Me or Et). To explain the results, the authors have proposed the mechanism depicted in Scheme 9.91, beginning with the deprotonation of the glycine Schiff base promoted by the chiral silver catalyst to generate reactive silver-bound azomethine ylide dipole R. Subsequently, R underwent enantioselective addition to the azodicarboxylate, resulting in the formation of intermediate S, which reacted with acetic acid to give the final product and regenerate the catalyst. In 2014, Yanagisawa et al. reported the asymmetric α-amination of alkenyl trifluoroacetates with dialkyl azodicarboxylates promoted by a chiral silver catalyst generated in situ from 2 mol% of (R)-DTBM-Segphos and 2 mol% of AgOTf in the presence of CF3 CH2 OH [156]. The reaction was supposed to evolve through a chiral silver enolate to afford various optically active α-hydrazino ketones with quantitative yields and enantioselectivities of up to 97% ee (Scheme 9.92). The products, arising from the reaction of cyclic alkenyl trifluoroacetates, such as 1-tetralone derivatives (n = 1) and 1-benzosuberone derivatives (n = 2), were obtained with the best enantioselectivities of 90–97% ee. The reaction of acyclic alkenyl trifluoroacetates also furnished the corresponding products in quantitative yields, albeit with low enantioselectivities (17–31% ee) (Scheme 9.92). A plausible mechanism cycle was proposed by the authors, which began with the reaction between the chiral silver catalyst with CF3 CH2 OH in the presence of an appropriate base, such as the azo diester or the α-aminated product, to generate the corresponding complex (R)-DTBM-Segphos-AgOCH2 CF3 , which was considered to be the true catalyst of the process. Subsequently, this chiral silver alkoxide attacked the alkenyl trifluoroacetate to yield chiral silver enolate T and CF3 CH2 OCOCF3 . Then, chiral silver enolate T underwent amination with the azo diester to afford chiral silver amide of α-hydrazino ketone S. Finally, protonation of chiral silver amide S with CF3 CH2 OH resulted in the formation of the chiral final product and the regeneration of the chiral silver alkoxide. It must be noted that this study represented the first example of an enantioselective α-amination catalyzed by a chiral silver alkoxide.

9.11 Silver-Catalyzed Miscellaneous Reactions In 2013, Doyle and coworkers reported a highly diastereo- and enantioselective silver-catalyzed asymmetric formal [3 + 3]-cycloaddition of nitrones with donor–acceptor cyclopropane [157]. The formal cycloaddition occurred with

9.11 Silver-Catalyzed Miscellaneous Reactions

O O

PAr2 PAr2

O OCOCF3

X

Ar = 3,5-t-Bu2-4-MeOC6H2 (R)-DTBM-Segphos (2 mol%) AgOF (2 mol%)

( )n +

RO2C N N CO2R

Ph

OCOCF3 R1

O

CF3CH2OH (20 equiv.) THF/DMF(5 : 1), –78 °C

NHCO2R * N CO R 2

O

X

( )n

R = Me, X = H, n = 0: >99%, 71% ee R = Me, X = H, n = 1: >99%, 95% ee R = n-Pr, X = H, n = 1: >99%, 97% ee R = Me, X = H, n = 2: >99%, 96% ee R = Me, X = OMe, n = 1: >99%, 90% ee R = i-Pr, X = OMe, n = 1: >99%, 96% ee

+ R2O2C

N N

CO2R2

O Same conditions Ph

NHCO2R2 * N CO2R2 R1

R1 = Me, R2 = Et: >99%, 17% ee R1 = n-Pr, R2 = Me:> 99%, 31% ee Proposed mechanism:

O

Ag

R1

P * P R3

RO2C N N CO2R

R2 T

* P Ag CO2R N O * N R1 CO2R R2 R3 S P

CF3CH2OH

CF3CH2OCOCF3

OCOCF3 R3 R1 R2

P AgOCH2CF3 P

*

O R1

Base-H+ TfO–

HN * N

R2 R3

CO2R CO2R

CF3CH2OH base *

P AgOTf P

Scheme 9.92 α-Aminations of alkenyl trifluoroacetates with azodicarboxylates.

625

626

9 Asymmetric Silver-Catalyzed Reactions

an exceptional stereocontrol in dichloromethane at −78 ∘ C in the presence of 10 mol% of AgSbF6 combined with 12 mol% of a chiral bisoxazoline as ligand. It led, after subsequent deprotection by treatment with TBAF, to the corresponding chiral cis-disubstituted 3,6-dihydro-1,2-oxazine derivatives as single cis-diastereomers with high yields (71–95%) and enantioselectivities (79–97% ee) (Scheme 9.93). It must be noted that the donor–acceptor cyclopropene was generated in situ by treatment of the corresponding γ-phenyl-enoldiazoacetate with Rh2 (OAc)2 . The scope of the process was extended to a range of nitrones, which led to the corresponding products with enantioselectivities generally >90% ee. A lower enantioselectivity of 82% ee was obtained with a nitrone bearing an electron-withdrawing substituent on the N-phenyl group (Ar1 = p-BrC6 H4 ), but nitrones with an electron-donating substituent on the N-phenyl group with or without an electron-withdrawing substituent on the α-phenyl group showed higher enantioselectivities of up to 97% ee. Moreover, a 2-furyl nitrone (Ar1 = Ph, Ar2 = 2-furyl) gave the desired product in 95% yield and 79% ee. To explain these results, the authors have proposed the possible involvement of a silver carbene species in the cycloaddition process without excluding the possibility of a Lewis acid-promoted pathway. OTBS CO2Me

Ph

N2 Rh2(OAc)2 O Ph

O N

N

t-Bu TBSO

CO2t-Bu

+ Ar1

+ – O N Ar2

t-Bu (12 mol%) AgSbF6 (10 mol%) CH2Cl2, –78 °C Then TBAF, 0°C

Ph Ar1

O N Ar2

OH CO2t-Bu

>99% de

Ar1 = Ph, 4-MeOC6H4, 4-BrC6H4, 1-MeOC6H4 Ar2 = Ph, 4-BrC6H4, 4-ClC6H4, 4-MeOC6H4, 4-F3CC6H4, 1-ClC6H4, 3-ClC6H4, 4-ClC6H4, 4-Tol, 4-FC6H4, 2-Naph, 1-BrC6H4, 1-F3CC6H4, 4-MeO2CC6H4, 2-furyl 71–95%, 79–97% ee

Scheme 9.93 Formal [3 + 3]-cycloaddition of nitrones and a donor–acceptor cyclopropene.

The Friedel–Crafts reaction of aromatic compounds with aldehydes or ketones constitutes a fundamental reaction in organic chemistry; however, its enantioselective catalytic version is still an unexplored field. The asymmetric Friedel–Crafts reaction of indoles provides a direct access to chiral indole derivatives that constitute privileged products in medicinal chemistry [158]. Only a few highly enantioselective processes based on chiral metal complexes

9.11 Silver-Catalyzed Miscellaneous Reactions

have been reported for the asymmetric Friedel–Crafts alkylation of indoles with β,γ-unsaturated α-ketoesters. Among them, an efficient process was developed by Feng and coworkers by using a chiral silver catalyst in situ generated from 10 mol% of AgSbF6 and 10 mol% of a chiral N, N ′ -dioxide ligand in THF at −20 ∘ C [159]. As shown in Scheme 9.94, the reaction proceeded well for many differently substituted β,γ-unsaturated α-ketoesters and indoles, independently of the electron-donating or electron-withdrawing character of the substituents, yielding the corresponding (S)-indole α-ketoesters in moderate to high yields (51–94%) and general high enantioselectivities (81–90% ee). Moreover, heteroaromatic and fused ring substrates were also compatible, giving the desired products with comparable enantioselectivity (84% ee). In this study, the authors also demonstrated the reversal of the enantioselectivity of this process through changing silver into samarium and by using a closely related ligand. Indeed, using a combination of a related N, N ′ -dioxide chiral ligand with Sm(OTf )3 at a low catalyst loading of 0.5 mol% allowed a range of (R)-indole α-ketoesters to be prepared in yields and enantioselectivities of up to 99% and 98% ee, respectively.

O R N H + O Ar

CO2Me

N O

N O

O

NHCHPh2 Ph2HCHN (10 mol%) AgSbF6 (10 mol%) THF, –20 °C

Ar CO2Me O

R N H

Ar = Ph, 3-BrC6H4, 1-ClC6H4, 2,4-Cl2C6H3, 4-FC6H4, 4-BrC6H4, 2-thienyl, 2-Naph R = H, 5-Me, 5-F, 5-Cl, 5-Br 51–94%, 81–90% ee

Scheme 9.94 Friedel–Crafts reaction of indoles and β,γ-unsaturated α-ketoesters.

In another context, Yamada and coworkers have reported enantioselective silver-catalyzed carbon dioxide incorporation into bispropargylic alcohols [160]. The process was performed in the presence of a combination of AgOAc and a chiral Schiff base ligand in chloroform at 0 or 5 ∘ C, providing the corresponding chiral cyclic carbonates in good to quantitative yields (58–99%) and moderate to high enantioselectivities (47–93% ee) (Scheme 9.95). The best enantioselectivities of 90–93% ee were obtained in the reaction of phenyl- and para-tolyl-substituted bispropargylic alcohols (R1 = Ph or 4-Tol). In the case of sterically hindered t-butyl-substituted phenyl derivative (R1 = Ph, R2 = t-Bu), a lower enantioselectivity of 82% ee was obtained. Bispropargylic alcohols with variously substituted phenyl groups (R1 = 3-MeOC6 H4 , 4-F3 CC6 H4 , 4-BrC6 H4 ) were also compatible but provided generally slightly lower enantioselectivities (79–87% ee) regardless of the electron-donating and electron-withdrawing

627

628

9 Asymmetric Silver-Catalyzed Reactions

N

N

OH N R1

R2

+ CO2

R1

N

(1–5 mol%) AgOAc (1–12 mol%) CHCl3, 0 or 5 °C

O O R1

*

O

R2

R1

R1 = Ph, 4-Tol, 3-MeOC6H4, 4-F3CC6H4, 4-BrC6H4 R2 = Me, Et, CH2F, CH2Bn, i-Pr, t-Bu 58–99%, 79–93% ee R1 = CH2=C(Me), BnOCH2 R2 = Me 91–97%, 47–80% ee

Scheme 9.95 Carbon dioxide incorporation into bispropargylic alcohols.

substituents. In addition, an alkene-substituted alkyne (R1 = C(Me)=CH2 ) smoothly reacted to give the corresponding product in 91% yield and 80% ee, whereas a much lower enantioselectivity of 47% ee was obtained in the case of an alkyl-substituted alkyne (R1 = CH2 OBn) albeit combined with an excellent yield of 97%. A cooperative bimetallic catalysis was applied by Shibasaki and coworkers to develop an asymmetric Conia-ene reaction of alkyne-tethered β-ketoesters [161]. The catalyst system was constituted by a combination of AgOAc and La(Oi-Pr)3 , with chiral amide-based ligands. In this system, the enolate of the substrate was generated through activation of a carbonyl group by a hard Lewis acid such as lanthanum complex, which subsequently coupled with a silver-activated alkyne in an asymmetric environment. As shown in Scheme 9.96, an enantioselective Conia-ene reaction occurred between the alkyne moiety and the β-ketoester group of the substrates to afford the corresponding chiral cyclopentane derivatives bearing an exocyclic olefin and two distinct α-carbonyl groups at a quaternary center. The best results were obtained by performing the reactions in ethyl acetate as solvent at 0 ∘ C in the presence of triphenylphosphine as an additive. Generally, the products were achieved in good to quantitative yields (63–100%). However, the reaction of a β-ketoester bearing an electron-donating methoxy substituent (R1 = 4-MeOC6 H4 , R2 = OEt) provided a low yield (26%) but with a high enantioselectivity (93% ee). In all cases of substrates, including aliphatic β-ketoesters (R1 = alkyl) and a malonamate (R1 = NH2 ), the products were generated in uniformly high enantioselectivities (83–96% ee). The authors showed that no reaction occurred in the absence of one of the two metal catalysts, thus demonstrating that simultaneous activation of the 1,3-dicarbonyl group by the hard Lewis acidic lanthanum and the alkyne group by the soft Lewis acidic silver was crucial to promote the Conia-ene reaction. Remarkably, for some substrates a La/Ag catalyst loading as low as

9.11 Silver-Catalyzed Miscellaneous Reactions

X

OH O N H

O

O

R1

R2

H N

OH

O

(X = i-Pr)(1–20 mol%) or (X = t-Bu) (5–10 mol%) AgOAc (0.5–10 mol%) La(Oi–Pr)3 (0.5–10 mol%)

O

O R2

R1

PPh3 (0.5–10 mol%) AcOEt, 0 °C With X = i-Pr: R1 = NH2, Ph, 2-Naph, 4-FC6H4, 4-MeOC6H4, Me R2 = OMe, OEt 26–100%, 83–96% ee with X = t-Bu: R1 = Me, Et, n-Pr R2 = OMe, OEt 86–100%, 83–91% ee

Scheme 9.96 Conia-ene reaction of alkyne-tethered β-ketoesters/malonamate through Ag/La catalysis.

0.5 mol% combined to 1 mol% of chiral ligand was sufficient to afford excellent results. Later in 2017, Enders and coworkers reinvestigated these reactions through cooperative silver and amine catalysis [162]. Indeed, a novel cooperative catalytic system consisting of a silver salt and a chiral cinchona alkaloid-derived diamine was found effective to promote the enantioselective Conia-ene reaction of alkyne-tethered β-ketoesters into the corresponding chiral cyclopentane derivatives. These products were achieved in uniformly high yields (89–97%) and low to excellent enantioselectivities (11–95% ee), as shown in Scheme 9.97. In 2013, another multicatalyst system was developed by Ma and Song and further applied to asymmetric addition reactions of organoboronic acids to OMe NH2 N O R1

O R2

(20 mol%) AgNTf2 (MeCN) (2.5 mol%)

O R1

O R2

TFA (20 mol%) MeOH, 0 °C 89–97%, 11–95% ee R1 = Me, Et R2 = OEt, OMe, OBu, Oallyl, Oi-Pr, Ot-Bu, OBn

Scheme 9.97 Conia-ene reaction of alkyne-tethered β-ketoesters/malonamate through Ag/amine catalysis.

629

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9 Asymmetric Silver-Catalyzed Reactions

aldehydes [163]. Indeed, these authors reported the synthesis of a novel planar chiral N-heterocyclic carbene silver complex derived from [2.2]paracyclophane. This was employed in combination with RhCl3 to promote the addition of aromatic boronic acids to aryl aldehydes to afford the corresponding chiral alcohols in moderate to high yields (52–94%) and low to moderate enantioselectivities of up to 67% ee (Scheme 9.98). The reactions were performed at 40 ∘ C in the presence of potassium fluoride as super stoichiometric additive in a 5 : 1 mixture of tert-butanol/methanol as solvent. Moreover, the use of ultrasound irradiation allowed the yields to be enhanced due to higher catalytic activities. The reaction conditions were applicable to various aryl aldehydes and aromatic boronic acids bearing a wide variety of functional groups. In most cases, the reaction proceeded with notable efficiency with up to 94% yield by using only 3 mol% of catalyst loading. It was found that the electronic properties of the aryl aldehyde had an important effect on the enantioselectivity of the reaction. With electron-deficient aryl aldehydes, the catalyst system was more enantioselective (48–67% ee), while electron-rich aryl aldehydes provided lower enantioselectivities of 39–41% ee. In contrast, heteroaryl aldehydes, such as 2-furylaldehyde and 2-thienylaldehyde, led to the corresponding alcohols by reaction with various aromatic boronic acids in low enantioselectivities of 5–24% ee albeit with moderate to high yields (59–91%). Moreover, heteroaromatic boronic acids (Ar2 = 2-furyl or 2-thienyl) only reacted with an aromatic aldehyde bearing a pi-donor substituent (Ar1 = 4-MeOC6 H4 ) with good to high yields (82–94%) albeit low enantioselectivities of 10–27% ee. This study constituted the first use of ultrasonic irradiation in asymmetric arylation. Br OMe MeO Ag N

O Ar1

+ H

Ar2B(OH)2

N

(3 mol%) RhCl3 (3 mol%) KF (6 equiv.) t-BuOH/MeOH (5 : 1) Ultrasound 40 °C

OH 1

Ar * Ar2

Ar1 = 1-Naph, Ph, 4-ClC6H4, 4-MeO2CC6H4, 3-MeOC6H4, 2,4,6-Me3C6H2, 2-furyl, 2-thienyl, 3-pyridyl Ar2 = Ph, 1-MeOC6H4, 3-MeOC6H4, 1-Naph, 1-MeOC6H4, 3-MeOC6H4, 2-furyl, 2-thienyl 52–94%, 5–67% ee

Scheme 9.98 Addition of organoboronic acids to aldehydes through Ag/Rh catalysis.

In 2015, an asymmetric silver-catalyzed dearomatizing spirocyclization strategy was reported by Taylor and Unsworth, allowing the conversion of simple heteroaromatic compounds containing ynone side chains into synthetically useful chiral functionalized spirocyclic products [164]. This process was promoted

9.11 Silver-Catalyzed Miscellaneous Reactions

by only 1 mol% of the silver salt of a chiral phosphoric acid in chloroform at −10 ∘ C and was insensitive to both air and moisture. As shown in Scheme 9.99, these simple reaction conditions were applicable to various substrates including aryl-substituted ynones as well as a methyl-substituted ynone (R = Me). The best result (100% yield and 78% ee) was seen in the reaction of phenyl-substituted ynone (R = Ph, X = H). Furthermore, a quantitative yield combined with 72% ee was obtained in the reaction of a methyl-substituted ynone (R = Me, X = H). Ar O

O P

O

O

O

X N H

OAg

Ar

R

Ar = 9-phenanthryl (1 mol%)

R X

CHCl3, –10 °C

N

R = Ph, 4-BrC6H4, 4-MeOC6H4, 3-MeOC6H4, Me X = H, Me 62–100%, 40–78% ee

Scheme 9.99 Dearomatization of aromatic ynones through spirocyclization.

In 2016, Fan and coworkers reported the first asymmetric ring-opening reaction of azabenzonorbornadienes with carboxylic acids [165]. As shown in Scheme 9.100, the process was catalyzed by a mixture of AgOTf and Pd(OAc)2 in the presence of (R)-BINOL as ligand, leading to the corresponding chiral cis-hydronaphthalene derivatives in moderate to high yields (53–92%) and uniformly excellent enantioselectivities (94–99% ee). Both aryl and alkyl carboxylic acids were suitable nucleophiles. X N AgOTf (50 mol%) Pd(OAc)2 (25 mol%) (R)-BINAP (30 mol%)

+

DME, 70 °C

O R1

OH

X

NH R1

O O

53–92%, 94–99% ee

X = Boc, Ts, Ns, Ac R1 = Ph, 4-MeOC6H4, 4-Tol, 3-Tol, 2-Tol, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-IC6H4, 2-Naph, (E)-PhCH=CH, BnCH2, Me, Et n-Pr, i-Pr, Cy R2 = H, Me, Br R2, R2 = O(CH2)2O

Scheme 9.100 Ring-opening reaction of azabenzonorbornadienes with carboxylic acids through Ag/Pd catalysis.

631

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9 Asymmetric Silver-Catalyzed Reactions

t-Bu OMe

O O O O

Ts N Ar2 +

R

t-Bu 2 t-Bu

P P

OMe t-Bu

2 Ar2

(S)-DTBM-Segphos (3.75 mol%) AgSbF6 (2.5 mol%)

N Ar1

Ts NH

m-Xylene, 15 °C

Ar1 NH

R 72–99%, 84–95% ee

R = H, Me Ar1 = Ph, 4-ClC6H4, 4-Tol, 3-Tol, 2-Tol, 4-IC6H4, 4-BrC6H4, 2-BrC6H4, mesityl

Ar2 = Ph, 4-ClC6H4, 4-Tol, 3-ClC6H4, 4-BrC6H4, 2-ClC6H4, 4-(t-Bu)C6H4, 4-MeOC6H4

Ts N R3

R3

R3 +

R1 NH R2

Same conditions

R3 N R1

Ts NH

2

R

27–98%, 77–97% ee

R, R = (CH2)4, (CH2)3, (CH2)5, CH2CH=CHCH2 R = Et R1 = H, Ph, 4-MeOC6H4, 4-Tol, 3-Tol, 2-Tol, mesityl, 4-BrC6H4 R2 = H, Me

Scheme 9.101 Aminolysis of N-tosylaziridines.

In 2017, Chai et al. reported the enantioselective silver-catalyzed aminolysis of N-tosylaziridines achieved for the first time in the presence of a single silver(I) complex derived from a chiral diphosphine ligand [166]. As shown in Scheme 9.101, the ring opening of various 2-aryl-N-tosylaziridines with primary and secondary anilines and aliphatic amines as nucleophiles was promoted by a combination of AgSbF6 and (S)-DTBM-Segphos as ligand, leading to the corresponding chiral 1,2-diamines in good to quantitative yields (72–99%) and enantioselectivities (84–95% ee). The reaction conditions were also applied to the desymmetrization of meso-N-tosylaziridines with primary anilines to give the corresponding chiral vicinal diamines in low to quantitative yields (27–98%) and good to excellent enantioselectivities (77–97% ee).

9.12 Conclusions

9.12 Conclusions This chapter updates the major progress in the field of enantioselective transformations promoted by chiral silver catalysts, illustrating the power of these special mild Lewis acid catalysts to provide new reaction pathways, even if this field is still in its infancy. Especially in the last decade, chiral silver complexes have become catalysts of first choice for many types of asymmetric reactions generally performed under mild reaction conditions and through experimentally simple procedures. Indeed, a steadily growing number of novel enantioselective silver-catalyzed reactions have been developed in the last decade, including Mannich reactions, formal 1,3-dipolar cycloadditions, domino and tandem reactions, Michael reactions, aldol-type reactions, alkynylations, allylations, cyclizations of allenes, aminations, etc., allowing the synthesis of new chiral cyclic as well as acyclic products to be achieved with high enantioselectivities. For example, highly enantioselective silver-catalyzed processes have been recently described for the first time, such as aldol reactions of ketones using alkenyl esters as masked enolates with 93% ee, conjugate additions of glycine derivatives to α,β-unsaturated ketones with 99% ee, cycloadditions of cinnamates with glycine imino esters with 98% ee, cyclizations of allenoates with activated isocyanides with 96% ee, inverse-electron-demand 1,3-dipolar cycloadditions of isoquinolinium methylides with enecarbamates with 95% ee, propargylations of cyclic N-sulfonylketimines and benzophenones with allenyl boronic acid pinacol esters with 98% ee, ring openings of oxabenzonorbornadienes with terminal alkynes with 99% ee, Hosomi–Sakurai reactions of Csp3 centers with 96% ee, and intramolecular silver-catalyzed reactions of α-allenols with 93% ee. Furthermore, it is only recently that a wide range of powerful asymmetric silver-catalyzed domino (and tandem) reactions have been reported for the first time. Among the best results are domino imine formation/aza-Diels–Alder cycloaddition reactions of aldehydes, o-thiomethyl-p-anisidine, and Danishefsky’s diene, domino aldol/cycloisomerization reactions of ynones with cyclic 1,3-diketones, and domino aldol/cyclization reactions of ketones with isocyanoacetates, all providing enantioselectivities of up to 95–98% ee. This type of fascinating one-pot reactions has also been widely developed in recent years by using silver catalysts in combination with organocatalysts, also providing remarkable results. For example, enantioselectivities of up to 99% ee were reached in domino aldol/cyclization reactions of aldehydes with isocyanoacetates, domino Mannich/cyclization reactions of ketimines with isocyanoacetates, domino Michael/cyclization reactions of N-aryl maleimides with isocyanoacetates, tandem Michael/hydroalkoxylation reactions of enynones with 4-hydroxycoumarins and of alkyne-tethered nitroalkenes with 5-pyrazolones, domino Michael/Conia-ene reactions of 5-pyrazolones with alkynes-tethered nitroalkenes, and domino cyclization/oxa-Diels–Alder cycloaddition reactions of isatins with alkynylaryl aldehydes. The excellent results reported in the last

633

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9 Asymmetric Silver-Catalyzed Reactions

decade have demonstrated the high efficiency of silver catalysts in asymmetric catalysis, owing to their mild Lewis acidity, opening the way for developing new catalytic systems to perform reactions, such as C—C bond formations, C—heteroatoms bond formations, or C—H functionalizations. Indeed, a bright future is undeniable for more sustainable novel and enantioselective silver-catalyzed transformations.

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10 Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives Zhenhua Jia, Mingxin Liu, and Chao-Jun Li McGill University, Department of Chemistry, 801 Sherbrooke Street West, Montreal, QC H3A 0B4, Canada

Alcohol, aldehyde, and carboxylic acid are closely related families of chemicals. These chemicals, and their derivatives, are vastly useful in almost all aspect of modern chemical industry, producing solvents, fuels, active pharmaceutical ingredients (APIs), preservatives, etc. [1]. The catalytic oxidation and reduction of aldehydes (alcohols) are of particular importance, which enables transformation between these useful chemicals (Figure 10.1).

10.1 Homogeneous Silver-Catalyzed Reduction of Aldehyde Silver has been neglected in catalytic organic transformations for a long time, probably because of its moderate Lewis acidity and resistance to oxidation-state changes [2]. However, in the last few decades, homogeneous silver-catalyzed reactions have seen important developments. Silver(I) is known to interact with π-donors such as alkenes, alkynes, allenes, and aromatics, as well as with n-donors such as (thio)ethers, amines, and phosphines, making strong and stable complexes more easily than other metals, and thus silver cation is among the soft Lewis acids [3]. Moreover, the use of silver is more economical relative to other expensive transition metals such as gold and platinum. Since 2003, Li group has been studying AgI catalyst toward nucleophilic addition of aldehyde and its derivatives and found AgI to be the most efficient catalyst for aldehyde–alkyne–amine (A3 ) coupling reaction [4] and the only catalyst capable of direct addition of alkyne toward aldehydes and ketones in water (Figure 10.2) [5]. The efficiency of AgI catalyst toward nucleophilic aldehyde addition also inspires new strategy in the design of aldehyde reduction and oxidation catalyst. The reduction of carbonyl compounds to alcohols is one of the most widely used and fundamental reactions in organic chemistry [6]. Several classical methods exist for such commonly encountered transformations, including chemical reductions, bioreductions, hydrogenations, and transfer hydrogenations. Chemical reductions by LiAlH4 , nickel–aluminum alloy, and various Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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Figure 10.1 Reactions that connect alcohol, aldehyde, and carboxylic acid.

O R H Aldehyde Oxidation Reduction

Oxidation

Reduction

OH R

O Oxidation

H

R

Reduction

Alcohol

OH

Carboxylic acid

O R1

n

+

H

N H

n

Cat. silver salt

+

R2

H

N

Water

n = 0, 1, 2

R1

(a) R3 O 1

R

+

R2

H

Cat. silver salt

HO

Water

R1

R3

R2

R2

(b)

Figure 10.2 (a) Silver-catalyzed aldehyde–alkyne–amine (A3 ) coupling and (b) alkyne– carbonyl addition.

borane reagents (such as zinc borohydride, NaBH4 , BH3 -THF, and amine boranes) have been the most widely utilized methods to achieve the reduction of carbonyl groups [7]. However, these reagents are generally hazardous to handle and often do not show chemoselectivity between aldehydes and ketones (Scheme 10.1) [8]. Biocatalytic reductions with baker’s yeast reductase usually require a specific temperature, pH value, and expensive enzymes [9]. O R

H

Reduction Conditions

OH R

(a) O + R (b)

H

M-H

Caution work-up

OH R

Excess metal hydride

Scheme 10.1 (a) Reduction of aldehyde and (b) classical method.

Transition metal-catalyzed hydrogenation and transfer hydrogenation often rely on precious metal catalysts such as Pd, Pt, Rh, Ru, and Ir [10]. Recently, there have been important advances in using cheaper iron [11] and cobalt [12] catalysts for hydrogenations and transfer hydrogenations of carbonyl compounds; however, they are often sensitive to moisture and water (Scheme 10.2). In this chapter, we will review the silver-catalyzed reduction of aldehyde, including hydrosilylation, hydrogenation, and transfer hydrogenation.

10.1 Homogeneous Silver-Catalyzed Reduction of Aldehyde

Transition-Metal-Catalyzed Hydrogenation and Transfer Hydrogenation of Aldehyde O R

+ H

H2 or other [H] source

OH

Transition metal catalysts including Pd, Pt, Rh, Ru, Ir, Fe, and Co

R

This Chapter: Silver-Catalyzed Reduction of Aldehyde

O

R

H

R

Hydrosilylation of aldehyde Hydrogenation of aldehyde Transfer hydrogenation of aldehyde

OH

Silver

Scheme 10.2 Transition metal-catalyzed hydrogenation and transfer hydrogenation of aldehyde.

10.1.1

Silver-Catalyzed Hydrosilylation of Aldehyde

In 2006, Stradiotto and coworkers described a rare silver-catalyzed hydrosilylation of aldehydes 1 in THF to give silyl ethers 2 (Scheme 10.3) [13]. They utilized 3 mol% AgOTf as catalyst and 20 mol% Et3 P as ligand to promote this transformation cleanly with up to 99% yield. They identified the Me2 PhSiOTf as a by-product, which suggests the possible intermediates involving AgH species. However, when Me3 SiOTf was employed in place of AgOTf, the desired product was not observed. Stradiotto’s work: 3 mol% AgOTf 20 mol% Ligand PhMe2SiH

O R

H

THF 70 °C, 24 h

1

OSiMe2Ph

P

R Ligand: Et3P

2

Scheme 10.3 Silver-catalyzed hydrosilylation of aldehydes.

Afterward, Li et al. reported a highly efficient and chemoselective catalytic reduction of aldehydes by using simple silanes 3 as reducing agents in water (Scheme 10.4) [14]. They employed AgPF6 as catalyst, dppf as ligand, and DIPEA (N,N-diisopropylethylamine) as base to reduce aldehydes to the corresponding alcohols 4 with trace of the silyl ether 5. Li’s work: O

n-Pr R H + H Si n-Pr n-Pr 3 1

5 mol% AgPF6 7.5 mol% Ligand 20 mol% DIPEA Water 100 °C, 24 h

OH

OSi(n-Pr)3 +

R 4

Ph2P

R 5

Yield of 4 up to 96% Ratio of 4 : 5 up to 24 : 1

Scheme 10.4 Silver-catalyzed hydrosilylation of aldehydes in water.

Fe

PPh2

Ligand: dppf

647

648

10 Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives

Both electron-donating and electron-withdrawing substituents on the aromatic ring were well tolerated. Heterocyclic aldehydes such as furfural and 3-pyridinecarboxaldehyde were also suitable substrates for this reduction process. They also accomplished this transformation with the use of aliphatic aldehydes 6, giving 8 moderate yield. Ketones 7 are essentially inert under the same reaction conditions, and 9 was not detected. Therefore, this protocol provides an interesting chemoselective reduction of aldehydes in the presence of ketones (Scheme 10.5). Competing experiment O Me

H +

6 O Me

Me

n-Pr H Si n-Pr n-Pr 3

5 mol% AgPF6 7.5 mol% dppf 20 mol% DIPEA

Me

OH 8

Water 100 °C, 24 h

Me

Me 9 not detected

(6/7 = 1 : 1)

7

OH

Scheme 10.5 Chemoselective reduction of aldehyde in the presence of ketone.

To further confirm the mechanism, an isotopic labeling experiment using (n-Pr)3 SiD (11) under optimized conditions afforded labeled product 12, with complete deuteration (the amount of 13 was not determined). When D2 O was employed as solvent, a similar result for 14 (and 15) was observed with silane 3 as in H2 O (Scheme 10.6). All of these experiments strongly supported the mechanism that the silane mediated this reduction in water. O H

+

10

n-Pr D Si n-Pr n-Pr

5 mol% AgPF6 7.5 mol% dppf 20 mol% DIPEA

OH D H

Water 100 °C, 24 h

11

+

OSi(n-Pr)3 D H 13

12

Isolated yield of 12 = 23% NMR yield of 13: not determined O H

10

+

n-Pr H Si n-Pr n-Pr

5 mol% AgPF6 7.5 mol% dppf 20 mol% DIPEA

OD H H

D2O 100 °C, 24 h

3

14

+

OSi(n-Pr)3 H H 15

NMR yield of 14 = 92%; NMR yield of 15 = 8% Ratio of 14/15 = 12

Scheme 10.6 Isotopic labeling experiments.

10.1 Homogeneous Silver-Catalyzed Reduction of Aldehyde

10.1.2

Silver-Catalyzed Hydrogenation of Aldehyde

In 1950s, Halpern and Webster disclosed that inorganic substrates, such as [Cr2 O7 ]2− and Fe3+ , could be reduced through catalytic hydrogenation in aqueous solution [15]. Surprisingly, homogeneous complexes of silver have never been shown any practical catalytic organotransformation through activating molecular hydrogen to reduce organic compounds, until Li et al. reported the first silver-catalyzed hydrogenation of aldehydes in water in 2013, revealing an unprecedented reactivity for silver (Scheme 10.7) [16]. They tested a series of monodentate and bidentate ligands by using AgPF6 as the catalyst. Among these, the Buchwald ligand (XPhos) was more effective than the others. Under optimized reaction conditions, both electron-donating and electron-withdrawing groups on the aromatic ring were well tolerated. Heterocyclic aldehydes were also suitable substrates for this reductive process, affording the corresponding products. When aliphatic aldehydes were examined in this silver-catalyzed hydrogenation process, the corresponding aliphatic alcohols were obtained in excellent yields. Moreover, for substrates with multiple functional groups, a unique chemoselectivity was observed as well (Scheme 10.8). Cinnamaldehyde (16), which bears a C=C double bond, was reduced to the corresponding unsaturated alcohol 17 in moderate yield. When benzalacetone (18) was treated under the standard conditions, the C=C double bond was reduced to 19 with preservation of the carbonyl group.

O H2 (40 bar)

+

H

R

5 mol% AgPF6 7.5 mol% Ligand 20 mol% DIPEA Water 100 °C, 24 h

1

PCy2 iPr

OH iPr

R 4

iPr Ligand: XPhos

Scheme 10.7 Silver-catalyzed hydrogenation in water.

O

+

H2 (40 bar)

Water 100 °C, 24 h

16 O CH3 + 18

5 mol% AgPF6 7.5 mol% XPhos 20 mol% DIPEA

H2 (40 bar)

5 mol% AgPF6 7.5 mol% XPhos 20 mol% DIPEA Water 100 °C, 24 h

OH 17 45% O CH3 19 27%

Scheme 10.8 Chemoselectivity in silver-catalyzed hydrogenation in water.

649

650

10 Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives

AgPF6 L Path A

PF6–

Base + H2

Path C

H2

LAg

BaseH H2

H L Ag H

Path B

L Ag H

H H L Ag R

O

R

R

O

O

OAg L H OAgL H

H

R OH

H

R

H O Ag L

R

OH

BaseH H

+ Base R

H

LAg

R

OH H

R

Scheme 10.9 Possible mechanisms for silver-catalyzed hydrogenation of aldehyde.

There are three possible ways for the silver-catalyzed H2 activation. The first one is via a base-assisted hydrogen activation mechanism (path A, Scheme 10.9). In this pathway, the heterolytic cleavage of the H—H bond is realized by the cooperation of Ag and the base to afford a silver hydride complex and a quaternary ammonium cation. The hydride complex then reacts with the aldehyde to generate a Ag—O complex. Thereafter, the protonation of the resulting complex by the quaternary ammonium cation affords the alcohol and completes the catalytic cycle. The second route is a ligand-assisted hydrogen activation mechanism (path B, Scheme 10.9). In this pathway, the ligand acts as a proton acceptor in the H—H bond cleavage step. The third possible route is an oxidative addition in which the AgI inserts into the H−H bond to form a AgIII intermediate (path C, Scheme 10.9). Fu and coworkers utilized density functional theory (DFT) methods to elucidate the dominant mechanism for the silver-catalyzed hydrogenation of aldehydes with H2 [17]. Their calculation results indicate that the base-assisted hydrogen activation mechanism (path A) is the most favored one. The ligand XPhos is not a good proton acceptor compared with the base DIPEA, resulting in high-energy ligand-protonated intermediates in path B. The energy demand of the oxidative addition mechanism is estimated to be much higher because of the instability of cationic AgIII hydride complexes, and therefore, path C is also excluded. In addition, they found that XPhos tends to coordinate with the Ag center by both the phosphine and the π-bond of the isopropyl-substituted phenyl group (Scheme 10.10).

10.1 Homogeneous Silver-Catalyzed Reduction of Aldehyde

δ+ δ– Base H P Ag H I

R R R

π-Coordination

Scheme 10.10 The potential coordination between ligand and silver.

10.1.3

Silver-Catalyzed Transfer Hydrogenation of Aldehyde

Transfer hydrogenation, as an important avenue among transition metalcatalyzed carbonyl reductions, has received much academic attention for its advantages over direct hydrogenations such as the precluding of storage and transportation of hydrogen gas and dangerous high-pressure manipulations. Since Noyori and Hashiguchi pioneered transition metal-catalyzed transfer hydrogenation [18], various catalyst systems have been developed to achieve such transformations, involving scarce and expensive ruthenium, iridium, rhodium, and palladium complexes. To overcome these shortcomings, abundant metal catalysts, such as nickel and iron, have also been applied in the transfer hydrogenation most recently.

O H +

R

HCO2Na

10 mol% AgF 20 mol% Ligand 20 mol% DIPEA Water 100 °C, 24 h, in air

20

OH

PCy2 Me2N

R 21

O H

R

+

HCO2H DIPEA

22

10 mol% AgF 20 mol% Ligand 20 mol% CsF 10 mol% TfOH 7 equiv. PhCl Water 100 °C, 24 h, in air

Ligand: DavePhos

OMe MeO i-Pr

PCy2 i-Pr

i-Pr Ligand: BrettPhos

or

MeO

OH

R

PCy2 OMe

Ligand: SPhos

Scheme 10.11 Silver-catalyzed transfer hydrogenation of aldehydes in water.

23

651

652

10 Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives

In 2014, Li and coworkers reported a simple, efficient, and chemoselective silver-catalyzed transfer hydrogenation of aldehydes 20 into alcohols 21 in air and water for the first time by using formate as a convenient source of hydrogen (Scheme 10.11) [19]. The use of AgF-DavePhos as catalyst generated a selective reduction of aromatic aldehydes, whereas both aromatic 20 and aliphatic aldehydes 22 were reduced efficiently to 21 and 23 with AgF-BrettPhos and AgF-SPhos catalysts.

10.2 Silver-Catalyzed Oxidation of Alcohol, Aldehyde, and Their Derivatives Silver-catalyzed oxidation of alcohol was explored relatively early. Up till present, silver-catalyzed oxidation of methanol (24) remains one of the primary industrial processes for formaldehyde (25) production. The initial discovery of this catalytic process was developed by Chauvel in 1973 [20]. Silver metal was used as heterogeneous catalyst, and two reactions take place simultaneously: the aerobic process and the anaerobic dehydrogenation (Scheme 10.12). Compared with other catalysts for oxidation of 24 such as Fe/Mo or Fe/V, the silver catalyst operates at a higher temperature (250–400 ∘ C for Fe/Mo and Fe/V, 650 ∘ C for Ag). [Ag] 2 CH3OH + O2 24

2 HCHO + 2 H2O 25 [Ag]

CH3OH 24

HCHO + H2 25

Scheme 10.12 Reactions took place in heterogeneous Ag-catalyzed aerobic oxidation of methanol.

Silver has also been playing an important role throughout the history of aldehyde chemistry. Although mostly used stoichiometrically (oxidant) [21], the Tollens’ reagent exhibits impressive efficiency and wide adaptability in aldehyde oxidation. The efficiency of Tollens’ reagent even enables titration analysis. It was of particular curiosity for the chemistry community whether silver can perform aldehyde oxidation catalytically. However, it was not until 2007 when the first homogeneous silver-catalyzed aldehyde oxidation using hydrogen peroxide (H2 O2 ) was reported [22]. 1 was readily oxidized by sustainable oxidant into the corresponding carboxylic acid (26). The reaction shows high efficiency for a wide range of aldehydes including aromatic, aliphatic, and unsaturated ones under mild reaction conditions. On the other hand, disadvantages of the method are the requirement of excessive concentrated oxidant and organic solvent (Scheme 10.13). The dehydrogenation of alcohol can be generally facilitated by a catalyst– hydride intermediate. Although a silver hydride species was suggested by many earlier works (recently confirmed by Sadighi and coworkers [23, 24]) [25], Ag—H bond stability was questioned for a long time due to possible self-oxidation

10.2 Silver-Catalyzed Oxidation of Alcohol, Aldehyde, and Their Derivatives

Cat. AgNO3 Ex. 30% H2O2

O R

H

50 °C, THF

O R

OH 26

1

Scheme 10.13 The first homogeneous Ag(I)-catalyzed aldehyde oxidation by H2 O2 in 2007. OH R

O

H

R

Hydrogen borrowing

HN R

R′

H

Ag-H

R′ H

H2N

N R

R′ H

Figure 10.3 Heterogeneous silver-catalyzed “hydrogen-borrowing” reaction.

enabled by the high oxidation potential of Ag+ . In 2012, silver was reported for the first time to heterogeneously catalyze N-alkylation of amine with alcohol [26]. The reaction proceeds via a “hydrogen-borrowing” mechanism: (i) dehydrogenation of alcohol to give aldehyde and Ag—H, (ii) amine addition to carbonyl to give imine, and (iii) hydrogenation of imine by Ag—H to give alkylated amine (Figure 10.3). Such a mechanism was never reported with silver catalyst and thus inspires further applications with silver as catalyst. Another example for Ag—H intermediate to participate in reaction crucial step was reported by Friend and coworkers in their heterogeneous silver-catalyzed oxidative amidation of aldehyde using oxygen [27]. In the reaction, oxygen was first chemisorbed on silver surface, similar to the mechanism illustrated by Twigg for the classical silver-catalyzed aerobic oxidation of ethylene [28–30]. The oxygen atom then deprotonates amine into amide anion to enable nucleophilic attack on aldehyde, followed by β-H elimination to release the amide product and the Ag—H, which was rapidly oxidized by adsorbed oxygen into Ag—OH (Figure 10.4). This work further revealed the application of silver as a powerful catalyst for oxidation/reduction reaction, especially for clean and greener reactant such as oxygen or hydrogen. In the same year of 2012, Inoue reported the aerobic oxidation of alcohols and aldehydes using gold/silver nanoparticles [31]. The catalyst was shown to enable aerobic oxidation of various alcohols, aldehydes, and amines into the corresponding carbonyls, carboxylic acids, and imines. Intriguingly, it was later found that the increase in silver component enhances the oxidation ability of the catalyst, which further supports the strong affinity of silver toward oxygen (Figure 10.5) [32]. It also implies the stronger affinity of gold toward hydride compared with silver, possibly due to gold being a softer Lewis acid.

653

654

10 Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives

R1 O2

N H

O

R2 R

R1

O

O Ag

H N

R2 OH O

Ag

Ag

1/2 O2

R1

R2 N

R O

R1

R2 H N R O

O Ag

OH O Ag

–H2O

Figure 10.4 Heterogeneous silver-catalyzed oxidative amidation of aldehyde in 2012.

R2 R

1

R1

2

R R2 3 R3 R 2 R 1 1 N R O R N H R1 OH R2 1 NO2 R Ar R2 NH 2 Ar H H

Au>99Ag1NPore

Ph

OH

Ph

NH

O N

O O

Au90Ag10NPore

Figure 10.5 Inoue’s heterogeneous Ag/Au-catalyzed oxidation and reduction reactions. Source: Copyright obtained from ACS.

It was known by chemists that silver can afford stable +2 oxidation state such as AgII F2 . Such reaction intermediate could give an even faster and more efficient oxidation of compounds compared with AgI . However, due to its strong oxidation potential [33, 34], AgII intermediates are more difficult to obtain and stabilize in a reaction mechanism. In 2014, Jiang and coworkers reported an efficient homogeneous silver-catalyzed oxidation of alcohols and aldehydes using air as oxidant [35]. Stabilized by electron-donating N-heterocyclic carbene (NHC) ligand, an NHC—AgII -peroxo intermediate was presented. The intermediate rapidly oxidizes the corresponding alcohol and aldehyde into the desired product (Figure 10.6). The oxidation can even be stopped at the aldehyde stage using temperature control. Although the only disadvantage is the requirement for strictly anhydrous reaction conditions, this work opens more potential application of using ligand to enable silver catalyst to undergo unprecedented mechanism. Although the involvement of AgII intermediate shows potent catalyst efficiency, the volatile reaction intermediate is difficult to generate and easy to afford side reactions. In 2015, Li and coworkers reported a powerful homogeneous

10.2 Silver-Catalyzed Oxidation of Alcohol, Aldehyde, and Their Derivatives

O O T II (NHC)n Ag H O H Ph

T O2

TS

T-S switch

OH

–

O – OH

N N

I (NHC)nAg

O OH H O

BH

O–

Ph NHC:

S

B–

I (NHC)nAgOBn (n = 1 or 2) Ph

Ph OH–

Base + 1/2 O2

I (NHC)nAgOOH

PhCHO

Figure 10.6 Jiang’s homogeneous NHC—Ag-catalyzed aerobic oxidation of alcohol and aldehyde. Source: Copyright obtained from ACS.

NHC—Ag-catalyzed aerobic oxidation of various aldehydes [36]. During the reaction, the oxidation step occurs via β-H elimination of a tetrahedral intermediate generated by OH− nucleophilic addition, affording the Ag—H intermediate that reduces atmospheric oxygen efficiently (Figure 10.7). Despite the usefulness of silver catalyst in oxidation reactions, homogeneous silver catalysts are often toxic and difficult to isolate from reaction product. Therefore, more researches were focused on heterogenizing the homogeneous silver catalyst, for example, by using silver nanoparticle (Ag NP). In 2016, Li and coworkers reported the use of Ag NP as an alternative for their previous reported homogeneous AgI catalyst to carry out aldehyde oxidation and reduction (Scheme 10.14) [37]. In this study, 20 can be either reduced by H2 into 21 or oxidized by oxygen into the corresponding carboxylic acid (27) rapidly. Along with the heterogenized silver, iron(II, III) oxide (Fe3 O4 ) was also introduced to support the NP, making the catalyst very easy to be recycled by magnetic power. The catalyst achieved impressive efficiency for oxidation and reduction of a variety of aldehydes. One of the most important properties of silver salts, which was long known by chemists, is their light sensitivity. This implies the potential of using silver as catalyst for photochemistry. In 2016, Yao and coworkers reported the use of heterogeneous silver as photocatalyst for oxidative amidation of aldehydes [38]. In this study, Ag NP was supported by a robust and versatile g-C3 N4 . Commercial compact fluorescent lamp (CFL) was used as light source with the power input as low as 25 W (Scheme 10.15). 20 underwent oxidative amidation into the corresponding amide (28). Impressive efficiency and adaptability of various aldehydes and amines were achieved using simple air as the sole oxidant. Inspired by the efficiency of silver as aerobic oxidation catalyst, in early 2018, Li and coworkers reported another efficient oxidative method to produce

655

Ag2O + IPr HCl IPr O Ag H R O R

O

Ag

O OH

O R

Ag

R R

IPr OH R

H

NaOH/H 2O

O O

IPr Ag OH H

Hydride extraction cycle

IPr-Ag-OH IPr-Ag-H

O2 O O O

IPr-Ag-H IPr-Ag-O-OH

O

O

IPr-Ag-Cl O

Oxygen activation cycle

IPr O Ag O OH R H

R

O

AgOH

IPr

H OH

MeCN

H 2O

R

O

OH– O–

H

Figure 10.7 Li’s homogeneous Ag(I)-catalyzed aerobic oxidation of aldehyde in water.

R

O OH

R

IPr Ag H OH

O R

Ag

H OH

IPr

10.3 Conclusion

O

O Ag-Fe3O4@CMC cat. (6.5 mol%)

H

R

H2O (0.17 M), O2 (air), 24 h, 55 °C

OH

R

20

27

Scheme 10.14 Heterogenization of Li’s aldehyde aerobic oxidation catalyst. O

O H

R

+

HN

R2

Ag/g-C3N4, THF

R3

Air, 25 W CFL ambient temp.

20

N

R

R2 R3

28

Scheme 10.15 Silver as heterogeneous photocatalyst for aerobic oxidative amidation of aldehyde.

carboxylic acid: an aerobic oxidative cleavage of 1,2-diols homogeneously catalyzed by silver [39]. This transformation used to rely heavily on stoichiometric high-valent heavy metal or periodate compound as oxidant. In Li’s report, a wide scope of 1,2-diols, including aromatic, aliphatic, linear, cyclic, internal, and terminal 1,2-diols, are all capable of undergoing the cleavage into the corresponding carboxylic acids or carbonyl products. Natural product substrates were also successfully cleaved (Scheme 10.16), including the oxidative cleavage of estrogen derivative 29 into the corresponding 30 and cholesterol derivative 31 into 32, demonstrating the synthetic utility of this method. HO O OH H H

H

H

H

O2 (1 atm), THF/MeOH (V/V = 5 : 1) MeO

MeO 29 0.1 mmol

H

30 94%

37 °C, 12 h 94% conversion

H

H

HO HO

H

AgOTf (10 mol%) NaOMe (3 equiv.)

H

H 31 0.1 mmol

AgOTf (10 mol%) NaOMe (3 equiv.) O2 (1 atm), THF/MeOH (V/V = 5 :1)

H

H HOOC HOOC

H

H

H

37 °C, 12 h 32 82%

Scheme 10.16 Li’s aerobic oxidative cleavage of 1,2-diol natural products.

10.3 Conclusion In this chapter, we have summarized the recent progress of silver-catalyzed reduction and oxidation of aldehydes. Although, compared with other classical transition metals such as Ru, Rh, Pd, etc., Ag receives much less attention

657

658

10 Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives

in catalytic applications, it has been demonstrated that Ag indeed possesses unique catalytic activities, especially toward carbonyl compound. In addition, the reaction is usually fast, clean, and more sustainable with Ag as catalyst, indicating a promising future for more research into Ag catalysis.

Acknowledgment Z. J. gratefully acknowledges the financial support from Nanjing Tech University and the SICAM Fellowship from Jiangsu National Synergetic Innovation Center for Advanced Materials. M. L. and C.-J. L. are grateful for the Canada Research Chair (Tier 1) foundation, Natural Science and Engineering Research Council of Canada, Fonds de recherche du Quebec – Nature et technologies, Canada Foundation for Innovation (CFI), and McGill University for financial support.

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D.C., Das, A.R., and Ranu, B.C. (1990). J. Org. Chem. 55: 5799–5801. (i) Wang, Z., Wroblewski, A.E., and Verkade, J.G. (1999). J. Org. Chem. 64: 8021–8023. (j) Zhang, W. and Shi, M. (2006). Chem. Commun. 45: 1218–1220. Byung, T.C. and Sang, K.K. (2005). Tetrahedron 61: 5725–5734. (a) Deetz, J.S., Luehr, C.A., and Vallee, B.L. (1984). Biochemistry 23: 6822–6828. (b) Kaluzna, I.A., Feske, B.D., Wittayanan, W. et al. (2005). J. Org. Chem. 70: 342–345. (c) Kaluzna, I.A., Matsuda, T., Sewell, A.K., and Stewart, J.D. (2004). J. Am. Chem. Soc. 126: 12827–12832. (d) Rodríguez, S., Kayser, M., and Stewart, J.D. (1999). Org. Lett. 1: 1153–1155. (a) Rylander, P.N. (1967). Catalytic Hydrogenation over Platinum Metals, 21. New York: Academic Press. (b) James, B.R. (1973). Homogeneous Hydrogenation. New York: Wiley. (c) Ikariya, T., Murata, K., and Noyori, R. (2006). Org. Biomol. Chem. 4: 393–406. (d) Knowles, W.S. and Noyori, R. (2007). Acc. Chem. Res. 40: 1238–1239. (a) Casey, C.P. and Guan, H. (2007). J. Am. Chem. Soc. 129: 5816–5817. (b) Langer, R., Leitus, G., Ben-David, Y., and Milstein, D. (2011). Angew. Chem. Int. Ed. 50: 2120–2124. (c) Bart, S.C., Lobkovsky, E., and Chirik, P.J. (2004). J. Am. Chem. Soc. 126: 13794–13807. (d) Daida, E.J. and Peters, J.C. (2004). Inorg. Chem. 43: 7474–7485. Zhang, G., Scott, B.L., and Hanson, S.K. (2012). Angew. Chem. Int. Ed. 51: 12102–12106. Wile, B.M. and Stradiotto, M. (2006). Chem. Commun. 39: 4104–4106. Jia, Z., Liu, M., Li, X. et al. (2013). Synlett 24: 2049–2056. (a) Halpern, J. (1956). Q. Rev. Chem. Soc. 10: 463–479. (b) Webster, A.H. and Halpern, J. (1956). J. Phys. Chem. 60: 280–285. (c) Webster, A.H. and Halpern, J. (1957). J. Phys. Chem. 61: 1239–1245. (d) Webster, A.H. and Halpern, J. (1957). J. Phys. Chem. 61: 1245–1248. (e) Halpern, J. (1959). J. Phys. Chem. 63: 398–403. Jia, Z., Zhou, F., Liu, M. et al. (2013). Angew. Chem. Int. Ed. 52: 11871–11874. Jiang, Y.Y., Yu, H.Z., and Fu, Y. (2014). Organometallics 33: 6577–6584. Noyori, R. and Hashiguchi, S. (1997). Acc. Chem. Res. 30: 97–102. Liu, M., Zhou, F., Jia, Z., and Li, C.-J. (2014). Org. Chem. Front. 1: 161–166. Chauvel, A.R., Courty, P.R., Maux, R., and Petitpas, C. (1973). Hydrocarbon Process. 52: 179. Oshitna, K. and Tollens, B. (1901). Ber. Dtsch. Chem. Ges. 34: 1425. Chakraborty, D., Gowda, R.R., and Malik, P. (2009). Tetrahedron Lett. 50: 6553–6556. Jordan, A.J., Lalic, G., and Sadighi, J.P. (2016). Chem. Rev. 116: 8318–8372. Tate, B.K., Nguyen, J.T., Bacsa, J., and Sadighi, J.P. (2015). Chem. Eur. J. 21: 10160–10169. Beck, M.T., Gimesi, I., and Farkas, J. (1963). Nature 197: 73. Liu, H., Chuah, G.-K., and Jaenicke, S. (2012). J. Catal. 292: 130–137. Siler, C.G.F., Xu, B., Madix, R.J., and Friend, C.M. (2012). J. Am. Chem. Soc. 134: 12604–12610. Twigg, G.H. (1946). Proc. R. Soc. London, Ser. A 188: 92–104. Twigg, G.H. (1946). Proc. R. Soc. London, Ser. A 188: 105–122.

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30 Twigg, G.H. (1946). Proc. R. Soc. London, Ser. A 188: 123–141. 31 Asao, N., Hatakeyama, N., Menggenbateer et al. (2012). Chem. Commun. 48:

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10356–10364. 33 Petrucci, R.H., Harwood, W.S., Herring, G.E., and Madura, J. (2007). General

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661

11 Silver Complexes in Organic Transformations Guichun Fang and Xihe Bi Northeast Normal University, Department of Chemistry, Renmin Street 5268, Changchun 130024, China

11.1 Introduction In recent years, silver catalysts have unexpectedly occupied a place in the synthetic organic chemist’s arsenal and opened a new road for the synthesis of organic molecules, which have been well documented in the recent literatures [1]. Besides being the single electron transfer (SET) oxidant [1c,e, 2], silver could be used as both powerful σ- and π-activators (e.g. alkynes, alkenes, allenes, and aromatics) [1b,e, 3]. In comparison with the simple silver salts (e.g. AgI, Ag2 CO3 , AgSbF6 , and AgOTf ), the silver complexes with N- and P-based ligands (e.g. phen, Py, bipy, PPh3 , PCy3 , BINAP), have proven to be more stable and reactive to efficiently decrease energy barrier for transformations [1a, 4]. In particular, the synergistic utility of chiral ligands, such as BINAP, t-Bu-QuinoxP*, amino acid-derived phosphine ligands, multifunctional brucine diol, cinchona alkaloid, N,N ′ -dioxide ligand, and chiral Schiff base with silver(I), as well as the chiral ion pairs (e.g. BINOL phosphates), has improved the stereoselectivity of the reactions, allowing the success of rapid development in the asymmetric synthesis [1a, 4d, 5]. In this chapter, we focus on the highly reactivity of the silver complexes to promote organic reactions. However, considering the extensive development of the field of ligand chemistry, we concentrate on ligands that are coordinated to silver metal and have shown special catalytic activity and wide utility in the field of contemporary silver catalysis. Accordingly, the present chapter is divided into several sections, including N-heterocyclic carbene (NHC)–silver(I) complexes [6], chiral silver phosphates [7], P,O-type ligand silver(I) complexes [8], trispyrazolylborate–silver(I) [4a,d, 9], and silver complexes with pyridine-containing ligands in the organic transformations [4b]. We anticipate that this chapter might be inspiring to further developments in silver catalysis and explore the challenging reactions.

Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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11 Silver Complexes in Organic Transformations

11.2 NHC–Silver(I) Complexes NHCs are a kind of cyclic carbenes that have at least one α-amino substituent in their ring [10], which can be traced back to 1991 when Arduengo isolated the first free, stable, and bottle-able NHC [11]. Over the course of the past decades, the success story of NHC compounds in organic, inorganic, and organometallic chemistry has been achieved owing to the their relative stability and easy preparation that give access to a large variety of structures with diverse topologies and electron-donating properties [10a,b,d,g, 12]. These stable NHCs, i.e. IPr (unsaturated backbone) and SIPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) (Figure 11.1), have been found to be excellent σ-donors to metals (as shown in Figure 11.1), which make them considered as an important class of ligands in organometallics and catalysis [6e, 13]. Among these complexes [6d,e], NHC–silver (NHC–Ag) complexes have received special attention due to their structural diversity, easy accessibility [6b,c, 14], and wide range of applications including being effective carbene transfer agents [6b,e] and having good biological activities [6g, 15]. The first NHC–Ag complex, i.e. [AgOTf(IMes)2 ] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene), was reported by the Arduengo group in 1993, generated from a free NHC with silver(I) triflate [16]. To date, NHC–Ag complexes have been extensively synthesized by using the silver base route, typically by (i) preparation of the free carbene and subsequent reaction with a silver salt; (ii) in situ reaction of imidazolium salts with basic silver reagents, such as Ag2 O, Ag2 CO3 , and AgOAc; and (iii) in situ reaction of imidazolium salts with a base in the presence of a silver salt [6a–c, 17]. However, in contrast to numerous carbene transfers to other metals, the use of silver–NHC complexes as catalysts is severely limited [6b,d,e,f, 14, 18]. In 2005, Fernandez and coworkers described the first publication for the NHC–Ag(I)-catalyzed reaction that involved the catalytic diboration/oxidation of alkenes with bis(catecholato)diboron 1, affording the corresponding diols 2 (Scheme 11.1) [19]. The results of diboration by using [(L)2 Ag]AgCl2 were highly impacted by the electronic effect, presenting the styrene with electron-deficient substituents that delivered poor conversions. Afterward, NHC–Ag(I) complexes have been employed as both homogeneous and heterogeneous catalysts in organic transformations [6d, 14, 20], with representative successes in ring-opening polymerization of l-lactide [21], alkynylation [1b, 22], carbomagnesiation of terminal alkenes [23], cyanosilylation of imines [24], CO2 fixation [1d, 25], and dehalogenative coupling reaction with phenols, alcohols, and thiols [26].

N N

N

N

N

M

C N

IPr

SIPr

Figure 11.1 NHC ligands and the first isolated NHC–Ag(I) complex.

– Mes Mes OTf N N Ag N N Mes Mes

[AgOTf(IMes)2]

11.2 NHC–Silver(I) Complexes

L=

O

N

OH

(1) [(L)2Ag]AgCl2 (5 mol%), THF, RT

+ [B(cat)] 2

R

Me N

OH

R

(2) H2O2, NaOH up to 90% conv.

1

2

Scheme 11.1 NHC–Ag(I)-catalyzed diboration/oxidation of alkenes with bis(catecholato)diboron.

11.2.1

A3 Coupling Reaction

Since 2003, the Li group developed the first example of silver-catalyzed A3 coupling of aldehyde, amine, and alkynes for the synthesis of propargylamines [27]. A range of structurally diverse NHC–Ag(I) complexes have been synthesized and employed in such transformation toward high efficiency, wide reaction scopes, and facile and available conditions (e.g. temperature and air/light factors), as well as catalyst recovery (Scheme 11.2) [1b, 22]. The first example of NHC–Ag(I)-catalyzed A3 coupling reaction was reported in 2008, in which the in situ generated polystyrene-supported NHC–Ag(I) complex 4 [PS-NHC–Ag(I)] was claimed to be highly effective under solvent-free conditions at decreased temperature, in contrast to the parent NHC–Ag(I) 3 [28]. This procedure was compatible with a wide range of substrate scopes and excellent functional group compatibility, efficiently affording the corresponding

+

R CHO

R1

N H

R2

+

H

Navarro and coworkers [29] SIPr–Ag(I) 5 (1–3 mol%) MeOH, RT, air, 0.25–24 h 16 examples 82–95% iPr iPr

Wang and coworkers [28] PS-NHC–Ag(I) 4 (2 mol%) Solvent free, RT-50 °C, N2, 24 h 24 examples up to 96%

N

N PS Cl

Ag

N R1

R3

R = H, Ar, alkyl R1, R2 = cyclic/acyclic alkyl, Ar, Het, etc. R3 = Ar,alkyl

N Bn

Bn

R

NHC–Ag(I) 3–8

R3

N

R2 Cl

Ag 3

N Bn

Cai and coworkers [30] 6 (0.1 mol% of Ag), CH2Cl2 RT–60 °C, air, 12–24 h 18 examples 65–94% N N N

N

Me

N N

Ag

iPr Ag iPr

PS

Br

OAc –

2PF6

–

iPr N

N N

N Ag

Ag

N N Me

N N N

Me

Me Me

7 (1.5 mol%) Dioxane, 80 °C Tang and coworkers [31]

N

iPr

iPr Ag iPr iPr iPr N N iPr iPr

PF6 8 (4 mol%) MeOH, MW, 110 °C CH3CN, flow,130 °C Lamaty and coworkers [32a]

Scheme 11.2 Selective examples for NHC–Ag(I) complexes catalyzed A3 reactions.

663

664

11 Silver Complexes in Organic Transformations

propargylamines in good to excellent yields. Moreover, the catalyst 4 could be easily recovered and recycled for 12 runs without a substantial loss in its catalytic activity. Further, the reaction was modified with considerably low loading of (1 mol%) SIPr-Ag(I) 5 in methanol at room temperature in air in much shorter reaction times, in which the unactivated aryl aldehydes worked well at room temperature [29], while the use of NHC–Ag halides of 1-cyclohexyl-3-arylmethylimidazolylidenes (CyNaph–NHC)AgX as catalyst runs at 100 ∘ C [33]. The A3 coupling reaction also underwent efficiently even in the presence of as low as 0.1 mol% of polymer-supported NHC–Ag(I) 6 as a reusable catalyst [30]. Analogously, a series of dinuclear NHC–Ag complexes derived from 1-[2-(pyrazol-1-yl)phenyl]imidazole (e.g. NHC–Ag(I) 7) were also utilized to catalyze this A3 coupling reaction, thus providing propargylamines in excellent yields within two hours [31]. The homoleptic and cationic [Ag(PF6 )(IPr)2 ] 8 was also identified as an efficient catalyst for the A3 coupling reaction and afforded propargylamines in short reaction times under microwave irradiation at 110 ∘ C or continuous flow at 130 ∘ C [32]. Very recently, Zhang’s group developed a tandem A3 coupling/click protocol by using the polyacrylonitrile fiber-supported NHC–Ag(I) complex 9 [PANF-NHC–Ag(I)] as catalyst under batch (60 ∘ C) and continuous flow methods, which resulted in the desired fused triazoles 10 (Scheme 11.3) [34]. Furthermore, the AgAAC reaction of alkynes and azides was achieved by using a NHC–Ag(I) complex (from imidazolium salts) displaying better reactivity than simple silver salts [35]. R

R1 N3

O

+ R1

+

N H

H

Ag(I) 9 (1 mol%)

N

CH3CN, 60 °C

N3 R 9

CN O O

Cl

HN O

NH

NH2 9

N

N N

N N

HN CN

N

Ag

R1 10 R 5 examples 75–87%

Scheme 11.3 Cascade A3 coupling and 1,3-dipolar cycloaddition reactions.

In addition, the nucleophilic addition of terminal alkynes to carbonyl compounds was also accomplished by using NHC–Ag complexes. In 2011, Li and coworkers reported the direct alkynylation of substituted isatins 12 with aryl/alkyl-substituted alkynes, which occurred in the presence of catalytic amount of NHC–Ag(I) 11 with steric bulky phenyl group (e.g. [AgCl(IMes)],

11.2 NHC–Silver(I) Complexes

[AgCl(SIMes)], [AgCl(IPr)], and [AgCl(SIPr)] and diisopropylethylamine (DIPEA) in water under air atmosphere (Scheme 11.4) [36]. This water-media reaction into chemical 13 performed without the presynthesis of metal acetylides from terminal alkynes with organometallic reagents such as alkyl Grignard reagents, alkyl lithium reagents, and KOH. R HO

O R R

O

O

R

N 12 R′

R

NHC–Ag(I) 11 (5 mol%)

+ H2O, DIPEA (10 mol%) 40 °C, Air 30–99% Dipp N

N Ag Cl

N

– BF4 Cy +

N

Ag R

R = 2,4,6-(CH3)3, 2,6-(iPr)2

11

N 13 R′

N Dipp

N Cy

Dipp = 2,6-(iPr)2C6H3

14

Scheme 11.4 NHC–Ag(I)-catalyzed alkynylation of substituted isatins.

Further, the alkynylation of (non-)substituted isatin with terminal alkynes was conducted by using heteroleptic bis-NHC–Ag(I) complex 14 as catalyst and methanol/water mixtures as solvent in air without the presence of any additives [37]. The process was highly applicable for non-substituted isatin and tolerated with a wide range of aryl/alkyl/heteroaryl-substituted alkynes, giving the diverse propargylic alcohols in excellent yields (90–99%). In addition, the same catalytic system 14 worked well with trifluoroacetophenone and phenylacetylene to afford the propargylic alcohol derivatives in good to excellent yields [38]. The stoichiometric mechanistic experiment revealed that the formation of silver acetylide complex and the concomitant loss of one imidazolium salts were involved in the catalytic cycle. 11.2.2

CO2 Insertions

Recently, silver catalysis has been powerfully applied in CO2 insertions, which enables CO2 to be used as C1 building block to incorporate with epoxides, propargylic alcohols, amines, alkynes, and alkenes producing diverse molecules under mild conditions [1b,d]. In 2012, Çetinkaya and coworkers developed the first example of NHC–Ag(I)-catalyzed CO2 insertion for the synthesis of terminal epoxides [25]. Ionic [Ag(Cn mim)2 ]2 [Ag2 Br4 ] (Cn mim = 1-(Cn H2n+1 )-3-methylimidazol-2-ylidene; n = 4–18) catalysts displayed good reactivity and converted styrene oxide to styrene carbonate in 77–92% yields in the presence of 4-dimethylaminopyridine (DMAP) as a cocatalyst and under solvent-free conditions. Furthermore, carboxylation of terminal alkynes was developed to form target propiolic acids of importance in feedstocks or intermediates in the synthesis [39].

665

666

11 Silver Complexes in Organic Transformations

At this point, NHC–Ag(I) complexes have proven excellent catalytic activity to access propiolic acids 20 (Scheme 11.5). The first NHC–Ag(I)-catalyzed carboxylation of terminal alkynes was reported by Zhang and coworkers with the treatment of poly-NHC-supported silver nanoparticle as a heterogeneous catalyst and Cs2 CO3 as base, delivering various propiolic acids in good to excellent yields at room temperature [40]. When compared with poly-NHC–Cu(I) (5 mol%) [41], poly-NHC–Ag(I) exhibited better results even at low catalyst loading (0.3 mol% of Ag). Afterward, a variety of NHC–Ag(I) complexes was synthesized and tested for the catalytic carboxylation reactions were reported [1b, 42]. Among these, the well-defined mononuclear and dinuclear NHC–Ag(I) complexes 16 and 19 [43], 18 [44], and 17 (in situ from Ag2 O/KI/NHC precursor) [45] displayed excellent reactivity to reduce the low loading of Ag (even as low as 0.1 mol%), while the mononuclear morpholine-functionalized Ag(I)–NHC 15 needed 10 mol% [46]. NHC–Ag(I) CO2

+

R

R = Ar, alkyl, Het

R 20 p-Tolyl

O iPr

iPr

Cl Ag

N

N

N iPr Ag iPr Cl

O

p-Tolyl

N

N N

COOH

Base, temp., Sol.

Cl

p-Tolyl

N

p-Tolyl 16

N

SO3K

17

N

SO3Na

N

Ar N

Ag

Ag I

N

p-Tolyl = 4-CH3C6H4

15

N

N Ag

Ag Cl N

O3S 18

N Ar 19 Ar = 4-OMe/MeC6H4

Scheme 11.5 Carboxylation of alkynes with NHC–silver complexes.

Very recently, the three-component approach for carboxylative coupling of terminal alkynes with CO2 and butyl iodide was realized by using 2 mol% of 1,3-bis(4-methylbenzyl) imidazol-2-ylidene silver chloride 19 as a catalyst and 1.5 equiv. of Cs2 CO3 as base in dimethylformamide (DMF) at 40 ∘ C and led to the expected products with 77–94% yields [47]. Similarly, the simple silver salt Ag2 WO4 with catalytic amount also produced the comparable yield of products within 24-hours reaction time [48]. Additionally, the carboxylative cyclization of propargylic alcohols with CO2 offers a direct route for the synthesis of α-alkylidene cyclic carbonate 22. In 2013, a use of polystyrene-supported NHC–Ag(I) complex 21 (2 mol%) as reusable catalyst was reported and furnished the corresponding products in

11.2 NHC–Silver(I) Complexes

high to excellent yields (51–99%) (Scheme 11.6) [49]. In comparison with the simple silver(I) versions, the method runs with low catalyst loading and without base additive, albeit suffering from terminal tertiary and secondary and 5 MPa CO2 . Further, a considerably reduced CO2 pressure was available under the catalysis of in situ generated sulfonated NHC–Ag 17 (2 mol% of Ag), affording the α-alkylidene cyclic carbonates in moderate to excellent yields [50]. O R1 R2

OH + CO2 5 MPa

PS–NHC–Ag(I) 21 (2 mol%)

O

N Cl

Ag

R1 R2

22

R1, R2 = H, alkyl, Ar

PS

O

40 °C, 24 h 51–99%

SO3K N () 3

N N Me

Ag I 17

21

Scheme 11.6 Catalytic carboxylative cyclization of propargylic alcohols with CO2 .

Analogously, the treatment of allenylmethylamines 23 with CO2 led to the selective synthesis of the five-membered urethanes 24 in good yields (Scheme 11.7) [51]. In this reaction the NHC ligand and pressurized CO2 played a vital role to suppress the competitive intramolecular hydroamination. In contrast to the Ag–NHC catalyst, e.g. (IPr)AgOAc, the series of NHC–Cu(I) and NHC–Au(I) delivered very poor results. R1 R

+ CO2 NHR2

1 MPa

23 R, R1 = H, alkyl; R2 = Ar, alkyl

(IPr)AgOAc (2 mol%)

O

2-Propanol 30 °C, 6 h

R2 N

O

R1 R

24 80–87%

Scheme 11.7 Carboxylative cyclization of allenylmethylamines.

11.2.3

Borylation Reactions

The transition metal-catalyzed C–H borylation is one of the ideal methods for the production of various carbon–boron bonds [52]. Considering the underdeveloped C(sp)–H borylation of terminal alkynes, in 2014, Hu’s group [53] developed the version with B(OiPr)pin under the cooperation of AgCl, ligand 25, and PPh3 , in the absence of equivalent amount of strong base such as n-BuLi [54] (Scheme 11.8). The approach afforded the desired alkynyl boronates 26 in good to excellent yields and in gram-scale operation. Further, the Ag(I) catalyst could be recovered in the presence of PPh3 and BF3 systems.

667

668

11 Silver Complexes in Organic Transformations

R

(1) AgCl / 25 / PPh3 (1/1/1 mol%) Cs2CO3, DMF, 50 °C

H +

N R

(2) 1 M HCl, 0 °C

B(OiPr)pin

R = Ar, alkyl, TMS, OPh, etc.

Bpin

26 15 examples 68–95%

N

N N

NHC 25

Scheme 11.8 Borylation of terminal alkynes.

11.2.4

Hydroborylation

In view of the significant progress that has been made in the copper-catalyzed hydroboration of alkynes [55], the extension of silver salts remains underdeveloped. In connection to this, Yoshida et al. proved [AgCl(IMes)] as a potent catalyst for the formal hydroboration of alkynes with B2 (pin)2 (bis(pinacolato)diboron), affording β-borylalkenes 27 in good yields (up to 89%) with high regio- and stereoselectivity (Scheme 11.9) [56]. The excellent chemoselectivity was observed while using this catalyst to enyne system. Of note, the symmetrical internal alkyne like diphenylacetylene also underwent the stereoselective hydroboration to afford (Z)-borylstilbene in 95% yield. Other unsaturated C—C bonds were also tested, such as allenes and 3-methylcyclohexenone, and delivered good selectivity. Besides, the use of AgOTf and Et3 P or NHC ligand is capable to promote the chemoselective hydrosilylation of aromatic and aliphatic aldehydes with Me2 PhSiH, such as α,β-unsaturated aldehydes and 4-acetylbenzaldehyde [57]. (pin)B–B(pin) [AgCl(IMes)] (2 mol%) R

H

H

R = alkyl, c-alkyl

KOtBu (6 mol%) MeOH, 50 °C, 2–10 h

R

B(pin)

β

27 18 examples up to 89%, β/α upto >99 : 1

Scheme 11.9 Regioselective formal hydroboration of alkynes.

11.2.5

Carbene Transfer with Diazo Compounds

Conversions of diazo compounds with transition metals into metallocarbene species are a well-established process [58]. In 2005, Pérez and coworkers synthesized the coinage metal complexes IPrMCl (IPr = 1,3-bis-(diisopropylphenyl) imidazol-2-ylidene) and demonstrated carbene insertion with ethyl diazoacetate (EDA). For Cu and Ag, ethyl cyclohepta-2,4,6-trienecarboxylate was obtained as the main product via Buchner reaction, while the arene Csp2 −H bond insertion was efficient in the presence of the IPrAuCl complex [59]. The sp3 C−H insertion of cyclohexane and EDA also commenced in the presence of IPrAgCl with NaBAr′ 4 (Ar′ = 3,5-(CF3 )2 C6 H3 ) [59b]. In comparison, the silver complexes supported by trispyrazolylborate ligands and pyridine-containing ligands have

11.2 NHC–Silver(I) Complexes

been extensively applied for carbene transfer conversions, rather than NHC–Ag complexes [4b, 60]. [2+1] Cycloaddition of aldehyde with carbenes catalyzed by transition metals is the available synthetic method for the preparation of oxiranes. [61]. In 2014, Chen and coworkers developed the first silver carbenoids for oxirane synthesis (Scheme 11.10(1)) [62]. Under the optimized conditions, a number of oxiranes 28 was prepared in moderate to high yields in the presence of 5 mol% [AgCl(IPr)] and 5 mol% of AgOTf. A mechanism containing a carbonyl ylide intermediate 31 and an intramolecular cyclization was proposed to form the oxirane unit. N2

+ COOR1

R

[AgCl(IPr)] (5 mol%) AgOTf (5 mol%)

O R2

DCM, RT, 8 h

Ar

[AgCl(IPr)] (5 mol%) AgOTf (5 mol%)

Ar′-CHO CO2Me

O

Ar′

+ E1

E2

CHCl3, RT, 12 h

E1

O 31

CO2Me Ar

(1)

Ar CO2Me (2) E2

30 25 examples up to 98%

29 E1, E2 = ester, amide E1 = ester, ketone; E2 = H Ar′

R2

28 18 examples 33–95%

R = Ar, 3-isochromenyl; R1 = Me, Et R2 = Ar, cinnamyl, alkynyl

N2

O

R R1OOC

Ar′ MeO2C

O

Ph CO2Me

δ– δ+ 32

Scheme 11.10 Conversions of carbonyl ylides with aryldiazo compounds.

A further extension of vital carbonyl ylides to the 1,3-dipolar cycloaddition with electron-deficient alkyne/olefins was developed under similar [AgCl(IPr)]/AgOTf conditions (Scheme 11.10(2)) [63]. The three-component [2+2+1] cycloaddition of diazoesters with aldehydes and alkynes/alkenes 29 led to the formation of 2,5-dihydrofurans and tetrahydrofurans 29 with high regio- and diastereoselectivities. A wide range of C2 synthon 29 including aryl/alkenyl aldehydes and alkyne/olefin dipolarophiles was applicable under the optimal conditions. While using unsymmetrical alkyne/olefin substrates, single regioisomers were afforded in good yields. Besides, in the case of vinyl ester and vinyl ketone substrates, the in situ generated carbonyl ylides favored conversion to endo-adducts in good yields with high diastereoselectivities, plausibly owing to the preference of the endo-transition state 32. In 2015, the Straub group prepared and characterized the d10 ML2 -type carbene complexes 34 without heteroatom stabilization for the first time, which was run by carbene transfer of [IPr**MNTf2 ] (M = Ag, Cu) 33 with Mes2 CN2 in dichloromethane (DCM) DCM (Scheme 11.11) [64]. In comparison, the carbenoid character of group 11 metal carbene complexes (M=CMes2 ) increases in the order of Au ≪ Cu < Ag.

669

670

11 Silver Complexes in Organic Transformations

Ar Ar Ar N Ar Ar F3CO2S

N Ar Ag N

Ar

Ar

Ar

Ar

Ar

N Ar

+ Mes2CN2 DCM, 4 °C

Ar

N Ar Ag

Ar

Ar NTf2

Ar = (p-tBu)C6H4

SO2CF3

33

34

Scheme 11.11 First d10 ML2 -type carbene complexes (NHC)Ag=CMes2 .

11.2.6

Cyclization Reactions

Recently, the cooperation of Lewis acids and nucleophilic NHCs in synergistic dual activation catalytic approaches has been developed rapidly, in particular in the field of asymmetric catalysis [12c, 65]. The aptness of organo-NHC catalysis is mainly attributed to their umpolung reactivity, resulting from the NHC lone pair that is highly nucleophilic to react with unsaturated aldehyde and ketones [66]. In 2010, Wu and coworkers reported a highly efficient AgOTf and NHC that cocatalyzed three-component reaction for the synthesis of 2-amino-1,2-dihydroisoquinolines, starting from N ′ -(2-alkynylbenzylidene)hydrazide, methanol with α,β-unsaturated aldehyde [67]. The NHC was proposed to activate the α,β-unsaturated aldehyde and formed the in situ homoenolate, which then reacted with the isoquinolinium-2-yl amide intermediates. Further, a (IMes)AgCl-catalyzed four-component reaction of aromatic aldehyde with malononitrile, ammonium acetate, and ketone was developed, affording a range of multi-substituted and fused pyridines 35 under very mild conditions within 10 minutes (Scheme 11.12) [68]. Remarkably, the equilibrium between neutral and ionic forms of Ag(I)–NHCs in solution offered opportunity for the NHC component to act as a Brønsted base in catalysis. Hence, the use of individual AgOTf and NHC also led to the products 35 in good yields. More recently, Hii and coworkers synthesized the [(NHC)Ag(carboxylate)] complexes and demonstrated the intramolecular 5-exo-dig cyclization of propargylic amides 36 to oxazolidines 37 (Scheme 11.13) [69]. The optimal result with [Ag(OBz-Cl)(IPent)] (IPent = 2,6-(CHEt2 )2 C6 H3 ; OBz-Cl = 4-ClC6 H4 ) overcomes limitations of earlier catalytic scopes (R1 = electron-withdrawing amide substituents) and served as highly complementary of the version [Ag(4-MeO-Py)2 ][PF6 ] [70] in their reaction scope. Further, the analogues monomeric [Ag(OBz)(SIPr)] compound also found comparative reactivity for the annulation [71]. Moreover, in 2009, Lassaletta’s laboratory reported the first application of NHC−silver complexes in asymmetric synthesis. In which, the authors developed the 10 new kinds of C2-symmetric S/C/S ligand-based NHC−Ag complexes for the asymmetric 1,3-dipolar cycloaddition of azomethine ylides (imino glycinates) 39 with tertiary-butyl acrylate (Scheme 11.14) [72]. Among the complexes tested, the NHC−Ag(I) complex 38 (5 mol%) with DIPEA (N,N-diisopropylethylamine, 10 mol%) led to the formation of the desired

11.2 NHC–Silver(I) Complexes

R

O [AgCl(IMes)] (2 mol%) R CHO +

NC

(1) CH2(CN)2 (2) NH4OAc ethanol, RT, 10 min

H2N

N

35 13 examples, 83–94%

Dual catalysis of NHC–Ag in the catalytic cycle Ag

NH

O

NH4OAc

Ag CN

NH

HN

Ag–NHC

N

Ar NC

CN

–H2O

Ar

H

NHC CN

Ar

+ O

NH

NH2

NH2 CN

N

CN

Ar

O2 (air)

CN

HN

CN

HN

Ar

–H2

Ar

H

Scheme 11.12 One-pot four-component synthesis of multi-substituted pyridines. R1

[Ag(OBz-Cl)(IPent)] (10 mol%)

O

R1

HN R2

4

R

R

N CD2Cl2, 23 °C

= Ph, Me, CO2Et, CH2

CH , etc.

N

2 R3 R

R3 36

R1

R4

O

37 13 examples up to >99%

O

R

p-ClPh

Ag O N R

R R = (CHEt2)2

Scheme 11.13 [Ag(OBz-Cl)(IPent)]-catalyzed 5-exo-dig cyclization of propargylic amides. COOtBu + Ar

N

Et2O, –25 °C, 84 h COOMe

39

(NHC)AgBr 38 (5 mol%) DIPEA (10 mol%)

t

BuO2C Ar

N N H

COOMe

40 6 examples 52–93%, 70–80% ee

S Cy

N Ag

S Cy

Br 38

Scheme 11.14 Asymmetric 1,3-DC of azomethine ylides with electrophilic alkenes.

endo-cycloadducts 40 in 52–93% yields with excellent enantioselectivities (70–80% ee) and endo-selectivities. Afterward, several anionic NHC−Ag(I) complexes bearing N-acyl iminoimidazolium ylide proligands were synthesized and applied to the [3+2] heterocycloaddition of azomethine ylides with electrophilic alkenes affording the single endo-adducts, albeit simple salts provide equal yields with short reaction time [73].

671

672

11 Silver Complexes in Organic Transformations

11.2.7

Oxidation of Alcohols

Metal-catalyzed oxidation of alcohols has attracted much attention and is alternative to “traditional” methods, since employing molecular oxygen as oxidant still represents an important task for catalysis. Concerning the discovery of NHC−Ag(I) complexes, their potential application in aerobic oxidations has not been fully elucidated. In 2014, Jiang and coworkers reported the first NHC−Ag(I) complex 41 catalyzed selective oxidation of alcohols using air as oxidant at low catalyst loading and mild temperature (Scheme 11.15) [20]. Diversely functionalized benzylic and some allylic alcohols could be transformed to give the desired aldehydes in excellent yields in the presence of BnMe3 NOH (BTHAH) as base, which could be further converted to imines with amines in one-pot fashion. Direct oxidation of alcohols to carboxylic acids was also achieved by using KOH as a base at an increased temperature. NHC-Ag 41 (0.1 mol%) KOH (6 equiv.) R COOH 4 Å MS, DME, dry air 60 °C, 24 h

Up to 99% Br

Br

N

NHC–Ag 41 (0.1 mol%) BnMe3NOH (1.1 equiv.) R

OH

R CHO Up to 99%

NHC–Ag 41 (0.1 mol%) BnMe3NOH (1.1 equiv.) 4 Å MS, toluene, dry air, RT, 12 h

R′ NH2

N N

N

Ag AgBr2 R

N

N

N

N Br

4 Å MS, toluene dry air, RT, 12 h

41

N

R′

Up to 99%

Br

Scheme 11.15 Selective oxidation of alcohols into aldehydes, carboxylic acids, and imines.

11.2.8

Semi-hydrogenation of Alkynes

Hydride complexes of copper, silver, and gold encompass a broad array of structures, and their distinctive reactivity has enabled dramatic recent advances in synthesis and catalysis [74]. NHC ligands were examined as supporting ligands for silver hydrides, such as {[(NHC)Ag]2 (μ-H)}+ salts and (NHC)AgH[B(C6 F5 )3 ] adduct [75]. In 2015, Karunananda and Mankad disclosed the catalytic semi-hydrogenation of alkynes via a unique cooperative H2 activation reaction by heterobimetallic NHC complex [Ag-Rp(IMes)] 42 (Scheme 11.16) [76]. This system performed with excellent functional group compatibility and unusual E-selectivity to furnish the trans-alkene in 71–91% yields. A transient silver hydride is proposed to form upon the activation of H2 across the Ag—Ru bond, but there is no experimental evidence for the participation of silver hydrides.

11.2 NHC–Silver(I) Complexes

R1

R2

H2 (1 atm) (IMes)AgRp (20 mol%)

OC Ru CO R1

R1 = Ar R2 = H, Ar, nBu

Ag

R2

Xylene, 150 °C, 24 h

N

Up to 99% conv. 71–91%

N 42

Scheme 11.16 Semi-hydrogenation of alkynes with [(IMes)Ag-Rp].

11.2.9

Synthesis and Application of Organosilver Complexes

Silver complexes with carbanions, such as alkylsilver and silver acetylide, are a kind of important compounds, which are likely intermediates in catalytic C—C bond couplings, in particular for the reactions with organometallic reagents. Recently Shen and coworkers have prepared the thermally stable, well-defined (NHC)-supported (difluoromethyl)silver complexes 43 (i.e. [Ag(CF2 H)(SIPr)]) (SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) via metathesis of alkoxy silver precursors with (difluoromethyl)trimethylsilane and demonstrated silver-mediated difluoromethylation and difluorothiomethylation of various electrophiles (e.g. diaryliodonium salts, vinyl(aryl)iodonium salts, aryldiazonium salts) and the palladium/silver-cocatalyzed difluoromethylation of aryl halides (Scheme 11.17) [77]. TMSCF2H (2 equiv.) SIPr-AgCl

SIPr-AgCF2H

NaOtBu THF, RT, 1.5 h

CF2H

CuI (2 equiv.) CH3CN RT, 30 min

R2 i

i

Pr

N

6 examples 71–94%

CH3CN RT, 30 min

Pr

N i

R

N2CF2H

Ar2I OTf

13 examples 68–93%

CF2H

N2BF4

R2

R

1

43

R1

I

OTf Ph

CuI (1.5 equiv.) CH3CN RT, 30 min

Pr

8 examples 74–90%

Ag CF2H i

Pr

O 43

R3

O

Cl R3

CF2H CuI (5 mol%) Phen (5 mol%) 10 examples CH3CN, RT, 2 h 55–93%

Scheme 11.17 Difluoromethylation of diaryliodonium salts, vinyl(aryl)iodonium salts, aryldiazonium salts, and acid chlorides with [Ag(CF2 H)(NHC)].

Furthermore, a series of stable mononuclear and dinuclear complexes of silver with carbanion ligands 44 featuring sp3 -, sp2 -, and sp-hybridization supported by the NHC ligand SIPr was synthesized (Scheme 11.18). The mononuclear

673

674

11 Silver Complexes in Organic Transformations

(SIPr)Ag

R

OtBu

(SIPr)Ag

THF, rt

R

44

R = Me, Et, CF3, alkynyl R: Et2Zn, MeMgBr, phenylacetylene, TMSCF3 Scheme 11.18 Synthesis of silver complexes with carbanion ligands featuring sp3 -, sp2 -, and sp-hybridization.

alkylsilver compounds (SIPr)Ag–R were found as carbon nucleophiles toward CO2 , forming carboxylates [Ag(O2 CR)(SIPr)] [78]. Besides, the [AgCl(IMes)] was found to catalyze the regioselective carbomagnesiation of terminal alkynes with various alkyl Grignard reagents in the presence of 1,2-dibromoethane as a reoxidizing reagent [23].

11.3 Chiral Silver Phosphates Enantioselective metal-catalyzed transformations are a cornerstone of modern synthetic organic chemistry [79]. Over the last decade, the limits of this discipline have been pushed even further, notably through the design of original ligands, such as the well-applied chiral phosphane ligands or the use of multiple stereodifferentiation approaches [1a, 4e, 80]. In recent years the asymmetric counterion-directed catalysis (ACDC) approach (first reported by Arndtsen and coworkers in 2000) has emerged as a powerful and attractive tool in asymmetric synthesis [81], whereby the counterion of a catalytically active cationic metal species is significantly employed as vehicle for the transfer of stereochemical information to the reaction products [7b, 82]. The use of BINOL-derived hindered phosphate (BINOL = 1,1′ -bi-2-naphthyl), as shown in Figure 11.2, as the chirality carrier constituted a real breakthrough, as high enantioselectivities were achieved for a variety of transformations [7b,c, 83]. Based on the literatures available, the two most commonly encountered forms involving the phosphate anions acting as either a ligand or a counterion for the metal were proposed, but a study of definite role for the phosphoric acid is still ongoing [84]. 3,3′-Position can be tuned for reactivity/selectivity R

Lewis base

O O P O O

Provide chiral environment R=H R = 9-phenanthryl R = 9-anthrycenyl

H–Nu Ag+ X Y

R Lewis acid

R = 2,4,6-(iPr)3C6H2 R = SiPh3 ...

Figure 11.2 A generic model for Lewis acid activations using chiral silver phosphates.

11.3 Chiral Silver Phosphates

In view of the reactivity of chiral phosphoric acid of silver complexes, the phosphoric acid acts as a chiral anion donor [85] that still retains its Lewis basic site, while the metal can behave as a Lewis acid catalyst (Figure 11.2) [1b, 82d, 83]. In general, the chiral phosphoric acids activate their substrates through hydrogen bonding interactions or ion-pair complexes, while the substitution at 3,3′ -position allows the modulation of the steric and electronic properties providing a satisfactory chiral environment [7b, 86]. As a result, the use of silver salts of BINOL-derived hindered phosphate has promoted a variety of transformations, including asymmetric alkynylation, allylation, Mannich reaction, cycloisomerization, hetero-Diels–Alder reaction, etc. [7b,c]. Furthermore, the silver phosphate complexes were easily synthesized from simple silver salts and the corresponding phosphoric acids at room temperature. Hence, the application of silver salts and PA for the individual reaction conditions is highly presumed involving some interaction between the metal and the acid [83, 87]. 11.3.1

Alkynylation

In 2007, Rueping et al. developed a novel enantioselective alkynylation of α-imino esters 45 with electron-rich terminal alkynes 46 by using the cooperative catalytic chiral phosphoric acid CPA-1 with silver salt (Scheme 11.19) [7a]. This transformation offers the first example of addition of organometallic compound to aldimine under dual catalysis including chiral Brønsted acids and metal catalysts [82a] and afforded chiral propargylamines 47 with high yields (60–93%) and enantioselectivity (e.r. up to 96 : 4). For the mechanism, the authors proposed a combination of two well-differentiated and parallel catalytic cycles, i.e. the addition of metallic alkynylides to imines (cycle I) and the use of chiral Brønsted acids as chiral imine activators (cycle II). A further extension to more general alkynes and other challenging and unexplored alkynes such as arylacetylenes, conjugated enynes, and 1,3-diynes was achieved under the combined CPA-1 and AgOAc conditions. As a result, optically active oxazepine derivatives were obtained with excellent enantioselectivities from the corresponding seven-membered cyclic imines [88]. 11.3.2

Mannich Reaction

In 2012, Hui and coworkers reported an asymmetric Mannich reaction of N-tosyl aldimines 49 with oxazolones 48 promoted by a chiral silver phosphate as catalyst (Scheme 11.20) [89]. Performed at room temperature in dichloromethane as solvent, the approach furnished valuable chiral quaternary α,β-diamino acid derivatives 50 in moderate to high yields (58−95%) and good to high diastereo- and enantioselectivities (up to 92% d.r. and 99% ee), which were ready to hydrolyze to the corresponding α,β-diamino acids 51. Further, the Peng research group demonstrated an asymmetric Mannich reaction between α-diazomethylphosphonates 53 and isatin-based ketimines 52 (Scheme 11.21) [90]. By using a catalytic chiral silver phosphate derived from CPA-3 with steric bulk of the substituents at the 3,3′ -position, the methodology for the first time provided the construction of a series of chiral oxindoles 54

675

PMP

Ar

N

45

PMP

+ CO2Me

H

AgOAc (5 mol%) CPA-1 (10 mol%)

46

PhMe, 30 °C 10–12 h

Ar

R NH * CO2Me 47

8 examples 60–93% e.r. up to 96 : 4

Ar = Ph, PMP, 4-MePh, 3,6-(OMe)2Ph, etc.

O O P OH O

Organocatalysis

R CPA-1, R = 9-phenanthryl

Metal catalysis O O * P – O H O

Ar N

PMP AgLn

H

MeO2C Cycle II

Cycle I Ar

45

O *

O

P

O

[AgLn]

OH 47

Scheme 11.19 Silver-catalyzed enantioselective alkynylation of α-imino esters.

11.3 Chiral Silver Phosphates R O

O O P OAg O

O Ph

R R = SiPh3

48 + R2

O HN Ts

R1

N

(15 mol%)

N

Ph

DCM, RT

Ts 49

R1 = Me, iPr R2 = Ar, alkyl

NHTs H+

O R1

N

R2

NHBz

R2 R1

CO2H

51

50 Up to 95% and 25 : 1 d.r. Up to 99% ee

Scheme 11.20 Asymmetric Mannich reaction of N-tosyl aldimines with oxazolones. O N PG Ar

O N 52

+

O P OMe OMe N2 53

Ag2CO3 (5 mol%) CPA-3 (10 mol%) 4 Å MS, toluene –30 °C Up to 95% Up to 99% ee

PG NH

R

P(OMe)2

O O P OH O

N2 O

Ar N 54

R CPA-3, R = 2,6-(iPr)2– 4-(4-tBu-C6H4)-C6H2

Scheme 11.21 Asymmetric Mannich reaction of isatin-based ketimines.

bearing a quaternary stereocenter and amino group at the C3 position with up to 95% yields and 99% ee. 11.3.3

Intramolecular Annulation

In 2009, Hii and coworkers reported a regioselective silver-catalyzed 5-exo-trig cyclization of γ-allenols 55 to produce vinyl-substituted tetrahydrofurans 56, while the use of other Lewis acids, such as Sn(OTf )2 or Zn(OTf )2 , favored the 6-exo-dig cyclization, affording tetrahydropyran scaffolds [91]. An enantioselective version of this cyclization (Scheme 11.22a) was achieved by the same group with the aid of chiral silver phosphates, i.e. oxophosphorus(V) phosphinate (β-CgPOOH) and phosphate (TADDOL–POOH) complexes of silver. Thereby, γ-allenols and γ-allenic acids enabled their conversion to tetrahydrofurans or lactones, respectively. The weakly attractive non-covalent interactions between the ligand and the substrate in the transition state structures led to the high enantioselectivities (up to 73% ee) of the reaction. While treating α-allenic alcohols 57 with the chiral silver phosphate, performance with both cycloisomeric kinetic resolution to 2,5-dihydrofurans 58 and recovery starting material 59 with excellent enantioselectivities was observed (Scheme 11.22b) [92]. Among the different catalysts, solvents, and temperatures screened, 20 mol% of (S)-dipP-Ag in dichloromethane at −10 ∘ C was proved appropriate for this resolution process, with a range of aryl-, alkyl-, and alkenyl-substituted α-allenic alcohols, affording the desired 2,5-dihydrofurans 58 (25–64% yields, 41–93% ee) and compound 59 (30–55% yields, 53 to >99% ee) along with S = 6.8–189.

677

678

11 Silver Complexes in Organic Transformations

(a) Addition of O–H and N–H bonds to allenes R2 R2 R1

L*Ag (15 mol%)

ZH

•

Y = Ph2, H2; Z = O Y=Z=O Y = Ph; Z = N-PG

55

R2

Y

DCE, RT

Y

R1

R2

R1 R1

Z *

56 Up to 99% Up to 73% ee

(b) Kinetic resolution of α-allenic alcohols OH

R

(S)-dipP-Ag (20 mol%) C

R

58

59

20 examples, S = 6.8–189 58 59

O

O P O

O

25–64% yields 30–54% yields

41–93% ee 53 to >99% ee R

Ph Ph

β-CgPOOH

C

R

R = Ar, alkyl, alkenyl

O P OH O

OH

+

DCM, –10 °C, 18.5–248 h

rac 57

O O

O

Ph Ph

TADDOL-POOH

O OH

O O P O O R R = 1,1′-biphenyl, dipP

Scheme 11.22 Silver-catalyzed enantioselective transformations of allenes.

11.3.4

Cycloisomerization

In recent years, transition metal-catalyzed (e.g. copper, silver) cycloisomerizations of ortho-alkynylaryl aldimines have been intensively explored and have become one of the most powerful methodologies for accessing isoquinoline frameworks [93]. In 2012, the You group reported a chiral silver phosphate-catalyzed reaction of 1-alkynylaryl aldimines 60 with indoles 61 bearing either electron-donating or electron-withdrawing groups (Scheme 11.23(1)) [94]. The reaction performed via in situ cyclization of alkynyl imines followed by a Friedel−Crafts reaction with indoles, affording the adduct products 62 in R-configuration with moderate enantioselectivity (10–89% ee). Optimization studies revealed that better result was obtained with the sliver phosphate Ag[(S)-PA-3], rather than the individual phosphoric acid and Ag2 CO3 catalysts. Notably, the highly enantioenriched products could be efficiently obtained by silica gel column chromatography. An analogous cycloisomerization between 2-(1-alkynyl)-2-alkene-1-ones 63 and indoles 64 was also developed in 2011 through silver or copper catalysis, albeit the application of copper salts of (S)-TRIP at −15 ∘ C furnished products 65 with a bit better enantioselectivity (72–93% ee) than the analogous silver catalyst (Scheme 11.23(2)) [95]. Very recently, a one-pot synthesis of 1-substituted 1H-isochromenes 68 was developed by the synergetic catalysis of diphenyl phosphate (DPP) and silver salts

11.3 Chiral Silver Phosphates

R4

R3 NTs

R1

+

N

Ag[(S)-PA-3] (10 mol%)

R3 N R4

R2 61

60

Toluene, 40 °C 26–95% 10–89%ee

R1

R2 O

R

R6

Ar

+

N H 63 R4

O +

R5

R2

R1

Ar 66

R3 67

R5

Cu[(S)-TRIP]2 (5 mol%) C6H5F, –15 °C 4 Å MS 72–93% ee

Ag2CO3 (2.5 mol%) 10 mol% DPP Hexane, 40 °C 27 examples Up to 97%; Up to 9 : 1 d.r.

(2)

H R6

64

O

(1)

62

5

O

Ts

N

Ar N H 65

R1(O)C R4

R3 R2 (3)

O

R5

Ar 68

R O O P OH O

PA-3, R = 2,6-(iPr)24-(4-tBuC6H4)-C6H2 TRIP, R = 2,4,6-(iPr)3C6H2

O P PhO OH

PhO

DPP

R

Scheme 11.23 Asymmetric synthesis of 1,2-dihydroisoquinolines, substituted furans, and 1-substituted 1H-isochromenes.

(Scheme 11.23(3)) [96]. Treatment of 2-alkynylbenzaldehydes 66 and ketones 67 resulted in the desired isochromenes in medium to excellent yields with diastereomeric ratios of up to 9 : 1. A trial of enantioselective synthesis was conducted with 10% (R)-TRIP catalyst and Ag2 CO3 , albeit affording low yield. By using the strategy of ACDC, Terada et al. in 2014 developed the tandem cyclization/asymmetric transfer–hydrogenation reaction of ortho-alkynylaryl ketones 69. The reaction underwent with a chiral silver phosphate catalyst Ag[CPA-5] and a Hantzsch ester (1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate esters) as the reductant, affording a range of 1H-isochromene derivatives 70 in 68–98% yield and high enantioselectivity (up to 92% ee) (Scheme 11.24) [97]. Notably, the control experiments with possible intermediates suggested that an ionic pair comprising a silver-containing isobenzopyrylium species and a chiral phosphate could be the key reactive intermediate for this cascade reaction. Simultaneously, the Akiyama group reported another enantioselective approach by using cooperated Cu(OTf )2 /CPA-4/Ag2 CO3 catalysis, providing isochromenes 71 in good yields and enantioselectivity (up to 97% ee) [98].

679

680

11 Silver Complexes in Organic Transformations Hantzsch ester Cu(OTf)2 (5 mol%) Ag2CO3 (5 mol%) CPA-4 (10 mol%)

R3 O

R1

O R3

R1

THF, 4 Å MS 50 °C

R2 69

70

Hantzsch ester Ag[CPA-5] (10 mol%)

R3

R2 71

75–90% Up to 97% ee

68–98% Up to 92% ee

SiPh3

C6F5

O

O

O P

O

Ag(I)Ln R2

O P

OH

O C6F5

SiPh3 CPA-4

O

R1

THF, 5 Å MS or EtOAc, RT 2 R

OAg

R1

O R3

O

O P

O

*

O

Ag[CPA-5]

Scheme 11.24 Tandem intramolecular cyclization/asymmetric transfer hydrogenation of o-alkynylacetophenones.

In 2013, Wang and coworkers reported a conversion of propargylic ester-tethered cyclohexadienones 72 into bicyclo[3.3.1]nonane derivatives 73, in which the propargylic ester moiety played a role as the precursor to produce the carbonyl ylide intermediate 72-1 (Scheme 11.25) [99]. In the presence of racemic phosphoric acid PA-6 bearing four CF3 groups and AgSbF6 , the tandem reaction proceeded through a unique sequence involving silver-carbenoid species 72-2 generated in situ via the 5-exo-dig-mode, subsequent enone cyclopropanation initiation, cyclopropyl vinyl ester hydrolytic fragmentation, and competitive carbonyl addition vs 1,4-conjugative addition events. The treatment of substrates 72 with asymmetrically substituted cyclohexadienones favored 1,2-addition and exclusively yielded products 73 with complete stereochemical control; otherwise, the 1,4-conjugative addition would lead to the isomers 74. Further, the asymmetric annulation of 3-alkynylacrylaldehydes 75 with 2-hydroxystyrenes 76 via the synergetic catalysis of AgOAc and chiral phosphoric acid (i.e. (S)-TRIP) was reported to access novel benzo-fused polycyclic products 77 and 78 in one-pot manner (Scheme 11.26) [100]. This reaction proceeded through the initial alkyne−carbonyl cycloisomerization to form pyrylium intermediate and follow counteranion-directed asymmetric oxa-[4+2]-cycloaddition and intramolecular SN 2 or SN 2′ substitution in intermediate 75-1 to provide the different configurations of the final products. Experimental results displayed that increasing steric hindrance of the alkenyl moieties and the presence of electron deficiency at aryl substituents in 2-hydroxystyrenes 76 favored the SN 2′ step to yield product 78. Very recently, a new 6-endo-dig oxocyclization/[4+2] cycloaddition cascade was achieved with the cocatalysis of Ag and BiNPO4 H (1,1′ -binaphthyl-2,2′ -diyl hydrogen phosphate) (Scheme 11.27) [101]. The β-alkynyl ketones 79 were first transformed into methyleneisochromenes 79-1 with a nucleophilic site, enabling their 1,6-addition reactions with para-quinone methides 80 (p-QMs)

11.3 Chiral Silver Phosphates

R O O P OH O

Ar O O

O

R2

R PA-6 (10 mol%)

Y

72 Y = O, CH2

OH

O H

R3

R = 3,5-(CF3)2C6H3 AgSbF6 (50 mol%) H2O (1.1 equiv.) DCE,RT

R1 R3

R2 R1

R3

O Ar Y

O

H Ar O

OO

O

73 Up to 95%

O

74

Ar O O

O

5-exo-dig attack

O

[Ag]

R3 O

Ar

Ar

O

O

O

[Ag] [Ag]

R3 O

Ar

O

[Ag] R3

H2O

OR P

O

n

O

72-2 RO

1,2-A dditio

O

O

R3 O

72-1

73

O

O

H O

H

O

O

O

H

PA-6 O

n

dditio 1,4-A

74

R3

O

Ar

O

H

R3

O

O

O

Ar

O

R1 H

Scheme 11.25 Construction of functionalized bicyclo[3.3.1]nonanes 73. R1

O

75

+

R1 H

AgOAc (2.5 mol%) (S)-TRIP (3.75 mol%)

R3 2

R2

R3 OH 76

O

DCE, RT, 6.5 h–12 d H

77 Up to 95% ee

R1 TRIP

+

R2 O 78 Up to 91% ee

R2

O SN2′

R O

R3

O H

R3

75-1

Scheme 11.26 Asymmetric annulation of 3-alkynylacrylaldehydes with styrene-type olefins.

681

682

11 Silver Complexes in Organic Transformations

R4 O

R3 O

R1

tBu

tBu

+

OH

R2 79

tBu

AgTFA (10 mol%) R1 BiNPO4H (20 mol%)

O OH

CH3CN, 50 °C 25 examples

R4

O R3 R2

80

tBu

[Ag]

81

O R3

R3 O

O R2

[Ag]

Ar′

–[Ag]

+ R2

H+

80

–H+

tBu

1,6-Addition

tBu

R2 O

tBu

R3 HO

79-1

OH tBu

Scheme 11.27 Ag/BiNPO4 H-cocatalyzed spiroketalization of β-alkynyl ketones.

catalyzed by Brønsted acid (BiNPO4 H) through [4+2] cycloaddition toward spiro-[chromane-2,1′ -isochromene] derivatives 81, with generally good yields and high diastereoselectivity. The present dual catalytic system provides an efficient and practical approach for constructing 6,6-dibenzannulated spiroketals 81. In a study to directly synthesize spirocyclic products [102], in 2015, Taylor and Unsworth and coworkers reported a simple and practical approach to afford spirocyclic indolenines by using catalytic AgOTf in dichloromethane at room temperature. The cyclization of significant synthetic value proceeded by activation of the alkyne 82 by silver(I), followed by nucleophilic attack of the indole through its C3 position. Further, an asymmetric variant of this reaction was run with chiral silver phosphate Ag[CPA-1] in place of AgOTf, affording the indolenines 83 in moderate to good enantioselectivity (40–78% ee, Scheme 11.28) [103]. A recent report for the conversion of ynone into spirocyclic indolenine was efficiently operated with silica-supported AgNO3 (AgNO3 –SiO2 ) [104]. A variety of functionalized indolyl ynones were converted into tetracyclic compounds 86 (Scheme 11.29) with excellent diastereoselectivity through the one-pot spirocyclization/trapping under simple AgOTf catalysis, followed by subsequent acid-mediated protecting group cleavage. When using the Ag[(R)-PA-2] complex in place of AgOTf, the product 85 was delivered from indolyl ynone 84 in 60% yield and (S)-configuration (e.r. 89 : 11), which could be purified by recrystallization from ethanol (Scheme 11.29) [105]. Analogously, the Wang group developed a highly enantioselective tandem cyclization/trapping of alkyne-tethered indole 87 (Scheme 11.29) [106]. This silver(I)/chiral phosphoric acid dual catalysis system offered an efficient and selective entry for the synthesis of polycyclic indolines 88 that have been found as the key scaffold in bioactive molecules, e.g. akuammiline alkaloids. Mechanistic studies revealed that not only does the chiral phosphoric acid provides

11.3 Chiral Silver Phosphates

O

O ( )n

Ag[CPA-1] (1 mol%)

R2

Ar

O

[Ag]

( )n N H 82 n = 1,2

R1

DCM, RT

( )n

R1 R2

Ar

Ar

N H

R

N 83 62–100% 40–78% ee

O O P OAg O

2

R = H, Me, Ph R1 = H, Me, Ar

R1 R2

R R = 9-phenanthryl

Scheme 11.28 Chiral silver phosphate-catalyzed dearomatization of aromatic ynones. R O O P O OAg O

N H

OH 84

O

O

R R = 9-anthrycenyl

Ag[CPA-7] (5 mol%) CHCl3, –30 °C, 21 h then H+

( )n X

O N H H

N H 86 X = O, NMe n = 1, 2

85, 60% (89 : 11 e.r.)

NHZ

AgBF4/CPA-7 (10 mol%) R′ N H

87

R′ = H, Me, MeO, Cl, Br Z = CO2R′, SO2Ar

Toluene, 4 Å MS or Ag[CPA–7]

[Ag]

ZHN R′ 88

N H

N Z

Up to 99% Up to 98 : 2 e.r.

N H

Scheme 11.29 Enantioselective tandem cyclization/trapping of alkyne-tethered indoles.

the chiral environment, but also the phosphate anion acts as a base to accelerate proton transfer. However, the presence of N in -methyl in alkyne-tethered indole led to low yield due to the blocking of the key hydrogen bond; in the situation, phosphate only served as an X-type ligand to silver(I). 11.3.5

Enantioselective Semipinacol Rearrangement

In 2009, Tu and coworkers demonstrated the potential of bifunctional phosphoric acids for simultaneous activation of the nucleophilic and electrophilic sites in a reaction. Taking allylic alcohols 89 in CCl4 with 10 mol% of catalyst (R)-TRIP or the corresponding Ag salt resulted in a smooth transformation to give spirocycles 90 in good yields and high selectivities (74–98% ee) (Scheme 11.30) [107]. The reaction plausibly proceeded with the aid of bifunctional activation of the alcohol and hydrogen bonding activation of the enol–ether moiety. Alternatively,

683

11 Silver Complexes in Organic Transformations

O

Ag[(R)-TRIP] or (R)-TRIP (10 mol%)

OH

R

O

( )n 90

TS1

TS2 (counterion)

O

O

R ( )n

O R

CCl4, RT or 0 °C n = 0,1 51–98%; 74–98% ee

( )n 89

O

H R

O H

( )n

O O P H O ∗ O

O O P O ∗

–O

Scheme 11.30 Enantioselective semipinacol rearrangement to chiral spiroethers.

a counterion mechanism (TS2), whereby the enol ether is initially protonated, was also reasonable. In contrast, the presence of Ag[(R)-TRIP] would strongly suggest the involvement of a chiral counterion effect (TS2) rather than hydrogen bonding between the catalyst and substrate. Further, the same group extended the chiral counterion activation mode for the asymmetric formal synthesis of (−)-cephalotaxine. A key process involving the silver-catalyzed 5-endo-dig cyclization of homopropargylic sulfonamide 91 was designed, providing the core of cephalotaxine (i.e. product 94) in a gram scale (Scheme 11.31) [108]. In the presence of chiral silver phosphate catalyst Ag[(S)-PA-7], azaspirocycle 93 was obtained from cyclobutanol 91 through a tandem hydroamination to intermediate 92 and enantioselective semipinacol rearrangement reaction. Ag[(S)-PA-7] (20 mol%)

NHTs

5 Å MS,CCl4

OH 91

NTs

O O O P O X O X = Ag, H

–AgL

N Ts O 93

HO 92

NTs

*

684

NTs –

O

O

N

O H 94 69%, 80% ee

Scheme 11.31 Formal synthesis of (−)-cephalotaxine via hydroamination/semipinacol rearrangement.

The dual activation mode with chiral silver phosphates was also applied to the synthesis of cycloalkanones 96 in excellent enantioselectivity (up 96 % ee), which featured an all-carbon quaternary stereocenter (Scheme 11.32) [109]. Based on

11.3 Chiral Silver Phosphates

Ag[(R)-PA-7] (5 mol%)

OH Ar

–20 °C or –25 °C CHCl3 Up to 96% ee

H

O 95

H

O

Ar O

H Ar

O

O 96

H

O Ag O P

Scheme 11.32 Asymmetric construction of α-quaternary cyclopentanones.

this asymmetric semipinacol rearrangement of olefin aldehyde 95, two utility for the synthesis of (−)-1,14-herbertenediol and (−)-aphanorphine were demonstrated efficiently. 11.3.6

Asymmetric Hetero-Diels–Alder Reaction

In 2014, Gong and coworkers identified the steric bulky silver phosphate complex Ag[(R)-TRIP] as an efficient catalyst for the asymmetric hetero-Diels–Alder reaction of diazenes 98 with various functionalized dienes 97, providing the corresponding piperazine derivatives 99 in excellent yields (89–99%) and excellent ee values (up to 97% ee) (Scheme 11.33) [110]. Learning from the DFT calculations, the water molecule was found to participate in the catalysis by coordination to silver phosphate. More interestingly, hydroxyl group containing dienes completely provided the different regioisomers 100 in excellent yields (94–96%) and enantioselectivities (up to 98% ee). This unusual regioselectivity might be due to the hydrogen bonding interaction between hydroxy group of diene with phosphate and coordinated to the Ag(I), which stabilizes the transition states. Recently, the ACDC approach with a chiral silver(I) BINOL phosphate (i.e. Ag[(S)-BiNPO4 H]) was applied to the asymmetric 1,3-dipolar cycloaddition of azomethine ylides and electrophilic alkenes to provide the core of hepatitis C virus inhibitor GSK 625433 [111]. FG R/H

97 + O

Boc

N

N 98

FG

Ag[(R)-TRIP] [H2O] (10 mol%)

N H

Ar

DCM, –40 °C 4–90 h

HO N N

Boc NHAr

R/H O

FG ≠ OH 99 89–99% Up to 97% ee

or

O N N

NHAr Boc

R/H FG = OH 100 94–96% Up to 98% ee

Scheme 11.33 Asymmetric hetero-Diels–Alder reaction of diazenes with dienes.

A novel asymmetric synthesis of tetracyclic octahydro-dipyrroloquinolines 102 was achieved by the chiral silver phosphate-catalyzed tandem hydroamination/formal Povarov reaction of aminoalkynes (Scheme 11.34) [112]. The

685

686

11 Silver Complexes in Organic Transformations

Y

H N

Y L*Ag (0.5–4 mol%)

HH N

R 25 examples Up to >99% Up to 99% ee, >99: 1% dr

101

Ar O O P OAg O Ar

Y N H

R

R

Ar = 2,4,6-(iPr)3Ph

102

L*Ag Hydroamination [Ag] Y

H

[Ag] Y

–

N

H

O

Y P

*

O R

–

N

O

P

O R

* R

N

H

–

O

Y O N

P

*

R

Scheme 11.34 Tandem hydroamination/formal Povarov reaction of aminoalkynes.

reaction was proposed involving chiral counteranion-controlled iminium ion intermediates, in which both diastereoselectivity and enantioselectivity are controlled by the chiral phosphate counteranion. The approach significantly offered a novel and efficient route for the asymmetric inverse-electron-demand hetero-Diels−Alder (IEHDA) reactions of imines and dienophiles, which have suffered from great challenges because of low association of iminium ions with conventional neutral catalytic centers. It was reasonable to extend different dienophiles to react with the key in situ generated iminium ions. Furthermore, this methodology was applied to enantioselective synthesis of incargranine B aglycone epimer in only two steps. 11.3.7

Miscellaneous Reaction

Toste’s laboratory in 2008 reported an enantioselective ring opening of meso-aziridinium and episulfonium cations with the combination of a chiral silver salt and Ag2 CO3 (Scheme 11.35) [113]. β-Chloro tertiary amine 103 underwent chloride abstraction to generate an aziridinium/phosphate ion pair 104 (and insoluble AgCl). Further ring opening by an alcohol nucleophile forms the enantiomeric (R,R) products 105, with deprotonation by the phosphate closing the catalytic cycle. Because of the insolubility of Ag2 CO3 , the Ag[(S)-TRIP] is kept away from the substrate, which was allowed to act as a chiral anion phase-transfer process. The recent computational results from both classical and quantum methods revealed that nonclassical hydrogen bond CH· · ·O interaction 106 caused the excellent enantioselectivity for this transformation. It was also revealed the solvent environment, e.g. nonpolar solvent toluene, is critical for the reaction to occur, since it affected the stability of ion-pair intermediate [114].

11.3 Chiral Silver Phosphates

Ph

Cl

Ph

N R2

Ag[(S)-TRIP)] (15 mol%) Ag2CO3 (0.6 equiv.)

R1

Toluene, 50 °C 4 Å MS, 24–36 h

Ph R1 N 2 R Ph

O– O

± 103

R3-OH

Ph

OR3

Ph

N R2

O

P

R1

(R,R)-105 50–95%, 90–99% ee

O

* 104 N

O O

P

O –

O

H C Ph H C Ph

106

H O R3

Scheme 11.35 Asymmetric ring opening of meso-aziridinium.

Very recently, Harada and coworkers developed a new asymmetric intramolecular dearomatization of phenol derivatives 107 with the treatment of Ag[(S)-TRIP] and highly functionalized α-diazoacetamides, whereas a Rh or Cu catalyst caused C–H insertion and a Büchner reaction (Scheme 11.36) [115]. The methodology provides a facile access to functionalized chiral spirolactams 108 possessing an all-carbon quaternary stereogenic center with a high level of enantiocontrol. With the acid of the chiral phosphate, the carbocation-like character on 109 facilitated electrophilic addition of Ag carbenoid to phenol moiety and enabled the chemoselectivity of the phenol dearomatization. R3

R1

( )n R3 N

R2

O

HO 107

N2

Ag[(S)-TRIP] (10 mol%)

PhCOOH (1 equiv.) O 2-Butanone 0 °C, 72 h

( )n N

R1 R

N

O R2

R1

O H

O Ag

108

R2

3

109

Up to 97%; Up to 99 : 1 e.r.

–

O

O P O O *

Scheme 11.36 Asymmetric intramolecular dearomatization of phenols with α-diazoacetamides.

The asymmetric C–H phosphonylation of allylamine 110 with phosphite 111 was realized by using the perfluorophenyl BINOL-derived silver phosphate PA-5 (Scheme 11.37). Mechanistically, the allylamine first proceeded a Ag2 CO3 -mediated C–H oxidation to allylamine intermediates, followed by controlled phosphite attack from the Re face and protonation to yield the final product, chiral α-amino phosphonate 112 with high enantioselectivity [116].

687

688

11 Silver Complexes in Organic Transformations

O R1 R2

N H 110

HP(OiPr)2 111 Ag2CO3 (1.1 equiv.) CPA-5 (10 mol%) m-Xylene, Ar, 50 °C

Ph O O P * O H O

O

R2 112 C6F5

OiPr P

P(OiPr)2

R1

R1 = H, Br, OMe; R2 = Ar, Het 22 examples; up to 92% ee H

O

H N

O

OiPr

O P

O N Ar

H

111

OH

C6F5 CPA-5

Scheme 11.37 Enantioselective C–H phosphonylation of allylamines.

11.4 P,O-type Silver Complexes In contrast with the well-applied copper(I)-catalyzed azide–alkyne cycloaddition (AAC) reactions, the silver catalysis for the synthesis of 1,4-disubstituted-1,2,3 triazoles remains less developed [1b]. In 2011, McNulty and coworkers isolated the P,O-type silver complexes from the reaction of silver(I) species with amides of the tunable 2-di-phenylphosphinobenzoic acid (SHOP) ligand in dichloromethane [8a]. For instance, the crystalline 1 : 1 complex 113 of the diisopropylamide ligand was found as a robust and homogeneous catalyst, to develop an AAC reaction (Scheme 11.38). Alkynes and azides worked well in the presence of 20 mol% of complex 113 as catalyst and 20 mol% of caprylic acid as an additive in toluene at room temperature, furnishing the corresponding triazoles 115 in good to excellent yields (72–99%), albeit it required excess azides (4.8 fold) for the complete conversion of alkynes. Further, several P-containing ligands were tested for this AAC reaction with AgOAc; as a result, the complex 114 (2–2.5 mol%) as a catalyst and caprylic acid (20 mol%) as an additive in toluene at 90 ∘ C were optimum for the full conversion. Consequently, the desired 1,4-triazoles 116 were afforded in good to excellent yields, with a wide range of substrates and well functional group tolerance (Scheme 11.38) [8b]. The X-ray analysis of catalyst 114 was revealed a weak ligation between Ag and the amide (Ag–N) when compared to the structure 113. A recent DFT study showed that the mechanism of AgAAC reaction was involved in a stepwise process with a silver(I)–acetylide intermediate, and binuclear paths invoked two silver(I) instead of the mononuclear paths [117]. The silver complex 114 with 1 mol% was used as homogeneous catalyst in the intramolecular hydroamination of 2-ethynylanilines under mild conditions, yielding a wide range of desired 2-substituted indoles in excellent yields, which run in the absence of any base in DMF at room temperature [118]. In 2014, Valliant and coworkers disclosed the first synthesis of functionalized carboranes 118 from alkynes with B10 H12 (CH3 CN)2 under facile and

11.4 P,O-type Silver Complexes

H

N3

+ R′

R

[Ag] 113 (20 mol%) Caprylic acid (20 mol%)

R′ R

+

R′

115 17 examples, 72–99%

Me

iPr

Me

O O Ag O P Ph Ph

R

Caprylic acid (20 mol%) Toluene, 90 °C, 24 h

Me

N

N N N R′

[Ag] 114 (2-2.5 mol%)

N3

R = Ar, alkyl R′ = Ar, alkyl, Bn Me

N

Toluene, RT, 48 h

R = H, Me, OMe, F, Cl, Br R′ = H, OMe, Cl, NO2, Br R

N

N

116 16 examples, 68–99%

iPr

N

O O Ag O P

Me

113

Me

114

Scheme 11.38 P,O-type ligand-based silver(I) complexes catalyzed AAC reaction.

easy-operated conditions (Scheme 11.39) [119]. In contrast to the conventional methods (required high temperature) [120], this P,O-type silver complex 117 (10 mol%) conducted at either 40 ∘ C or even at room temperature enabled a range of alkynes (even with sensitive functional groups 119a–119c) well tolerated. Based on the mechanistic study, a binuclear path invoked two silver(I), i.e. bimetallic intermediate 120 was plausibly involved during the reaction.

R1

R

Toluene 40 °C or RT R = Ph, CH2Br, CH2OH, C3H6CN, PhtNCH2, etc. R1 = Ph, H

H C

N

O C

OtBu

R C

B10H12(CH3CN)2 117 (10 mol%)

C C

H

C

R1

N O + – P Ag X t t Bu Bu 117

118 11 examples 47–93% TMS C H C

X = NO3, OAc

N O P Ag t Bu tBu

R

t Bu Ag t Bu P O

119a, 86%

119b, 88% (40 °C) 119c, 47% (40 °C) 63% (RT)

120

N

Scheme 11.39 Silver complex 117 catalyzed synthesis of carboranes with alkynes.

689

690

11 Silver Complexes in Organic Transformations

11.5 Tpx -silver Complexes (Trispyrazolylborate Ligands) Tris(pyrazolyl)borates (Tpx ), e.g. [HBPz)3 ]− , [HB(3,5-(CF3 )2 Pz)3 ]− , and [HB(3,4,5-Br3 Pz)3 ]− , were first reported in 1967 and are a very useful class of monoanionic, nitrogen-based, and auxiliary ligands in coordination and organometallic and bioinorganic chemistry (Figure 11.3) [121, 122]. They readily ′ ′′ coordinate, usually as face-capping tridentate ligands (𝜅 3-N,N ,N ), to a wide variety of metal ions, affording thermally stable metal complexes. The first silver complex of tripyrazolylborates was reported by Dias and Jin [123]. In general, such compounds were prepared by heating an alkali metal borohydride (e.g. KBH4 , NaBH4 ) with excess pyrazoles at about 180 ∘ C. The desired sodium salts further treated with AgOTf in tetrahydrofuran (THF) as adduct to yield the corresponding Tpx Ag(THF) complexes (Scheme 11.40) [121b, 124]. It is reasonable to modify the steric and electronic properties of these ligands by varying the number and nature of substituents on the pyrazolyl rings and on the boron atom, which leads to fine-tune the properties of the corresponding silver complexes [4a, 125]. 11.5.1

Carbene Transfer Reactions

Silver complexes supported by weakly coordinating ligands such as tris(pyrazolyl) borates are excellent catalysts for carbene transfers with diazo reagents, e.g. EDA (ethyl diazoacetate), to saturated and unsaturated substrates [4a, 9, 125a]. A range of reactions such as cyclopropanation [126], C–H insertion [127], and Si—H bond functionalization [128] has been reported (Figure 11.4). It has been found that this combination leads to addition and subsequent rearrangement with aromatic systems (namely, the Büchner reaction) [126] and rearrangement of halonium ylides [129]. Pérez and coworkers have made great advances in this field and reviewed the progress achieved by illustration of the different 1

R H 1 B N R R2 N1 N N 2 R R2 N N 4 3 2 R3 3 3 R R R1 5

Tpx

CF3 H B N CF3 N N N N N CF3 3 F3C CF3

F3C 5

H B N N N N N N [HB(Pz)3]–

[HB(3,5-(CF3)2Pz)3]–

Br H B N Br Br N1 N N Br Br N N 4 2 Br 3 Br Br Br 5

[HB(3,4,5-Br3Pz)3]–

Figure 11.3 Tripyrazolylborate ligands (Tpx ).

1

R 3

R2 R3

NH N

(1) NaBH4 –3H2 (2) THF (3) AgOTf/ –NaOTf

R1 R2 R3

R1 H 1 B N R R2 N N N R2 N N R3 R3 Ag THF

Scheme 11.40 Typical approach for the synthesis of Tpx Ag(THF) complexes.

11.5 Tpx -silver Complexes (Trispyrazolylborate Ligands)

N2

R

R

2 1R

1

R2

N2 R

R

R1

x

Tp Ag R1

TpxAg

R2 1

R Nu

R C

121

X H (X = C, N, O, Si, etc.)

Nu R2

R1 Ph

R2

R

R2

R1 X

Nu

R1 R2

Nu TpxAg C R1 R2

R2

Figure 11.4 General Tpx Ag-based carbene transfer to saturated and unsaturated substrates. Nu = Nucleophile.

behaviors of coinage metals such as gold, silver, and copper [9, 130]. A formation of a strongly electrophilic metallocarbene intermediate 121 that reacts with nucleophiles to give the desired products is the key for these carbene transfer reactions [60]. One of the most significant applications is the functionalization of unactivated C–H bonds [9, 130] (Scheme 11.41). The order of reactivity found is parallel to that of bond dissociation energies, that is, tertiary C–H > secondary C–H > primary C–H > methane. With respect to the catalytic activity of Tpx Ag complexes for the C–H insertion at primary sites of acyclic hydrocarbons, it was showed that the most efficient catalysts are those based on silver associated with ligands bearing electron-withdrawing groups, to allow the complexes in which the metal has strong electrophilic character, such as [TpBr3 Ag(L)] [127d], [Tp(CF3 )2 Ag(THF)] [127a,f ], and [FN − Tp4Bo,3Cn F2n+1 Ag(L)] (N = 6n + 15; n = 1, 2, 3, 4, 6; L = acetone or THF) [131]. For instance, the perfluorinated FN − Tp4Bo,3Rf Ag(L) (FN − Tp4Bo,3Rf = perfluorinated hydrotris(indazolyl)borate ligand; L = acetone or tetrahydrofuran) were synthesized and applied as catalyst for the CHCOOEt group transfer to the C–H bonds of linear, branched, and cyclic alkanes, providing the corresponding C–H insertion products in excellent yields with high turnover number (TON) values and low catalyst loadings [131a,b]. In the case of hexane, the functionalization of the methyl C–H bonds has been achieved with the highest regioselectivity known to date with this diazo compound. In addition, the complex [F27 − Tp4Bo,3CF2 CF3 Ag(acetone)] was found to provide α-(acyloxy)acetates in moderate to high yields [132]. During the process, EDA was first converted to metallocarbene and generated zwitterionic intermediates with esters, which was then converted to the final product. On the basis of the DFT Becke3LYP calculations, these transformations are known to occur through the intermediacy of reactive metallocarbene intermediates [133], generated by extrusion of dinitrogen from the diazo molecule, which reacts with the hydrocarbon [134] (Scheme 11.42). The reaction is found to be

691

692

11 Silver Complexes in Organic Transformations

H C

H

H

TpxAg(L)

N2

+

COOEt

C

C COOEt H

CF3 Br Br R R R F3C F Br CF3 Br Br Br B B N B N Br N Br N N N N N N N N F N Br N N Br N N Br Br N N CF3 Br Br F3C F Br CF3 Br Br Br Ag Ag Ag

TpBr3Ag(acetone)

N2

F

F F

H B N N N N N N

Rf

F F

F FF

Rf F

Rf Ag (THF) FNTp4Bo,3RfAg(THF) Rf = CF3, CF2CF3, (CF2)2CF3, (CF2)3CF3, (CF2)5CF3

THF

Acetone

THF TpBr3Ag(THF)

+

Tp(CF3)2Ag(THF)

Scheme 11.41 Tpx -silver complex-catalyzed C–H functionalization of alkanes.

under kinetic control, and the selectivity (in particular regioselectivity) is decided in the step with a low-barrier transition state where the key bond-breaking and bond-forming processes take place in a concerted way. This contributes to the selectivity of C–H insertion with challenging secondary and primary C—H bonds and their product distribution in one reaction. Moreover, the stereochemistry control for final products 122 greatly impacts by electric effect and steric hindrance of the substituents, to generate transition states with energy as low as possible [135]. B

B

B N N M

N H

MeO2C

CO2Me * TpM C H “C” H

+ H CR1R2R3

N N N M MeO2C C H H C R1 R3 R2

N N M

N

+ MeO2C 122

R

R1 2 3R

Scheme 11.42 General mechanism of alkane C–H bond activation.

Among the series of highly electrophilic and fluorinated Tpx -silver complexescatalyzed alkane C–H bond activation [127c, 130a], [Tp(CF3 )2 Ag(C2 H4 )] catalyst affords significantly higher amounts of the primary C–H insertion product. It was found that when using more acidic silver sites and sterically more crowded auxiliary ligands as catalyst, the amount of primary C–H bond activated product increases, and the order is [MeTpCF3 Ag(C2 H4 )] < [MeTpC2 F5 Ag(C2 H4 )] < [Tp(CF3 )2 Ag(C2 H4 )] ≈ [Tp(CF3 )2 Ag(THF)] (Figure 11.5) [127c]. This observation supports the contention of catalysts with less electron density at the metal site that assists more selectivity for primary C–H bond activation with diazoacetate reagents. The boron-protected, electron-rich methyl group induced ligand

11.5 Tpx -silver Complexes (Trispyrazolylborate Ligands) Me

Me

H

CF3 CF 3 B B B N N N N N N N N N < < N N N N N N N N N Ag F3C Ag C F C F Ag F3C CF3 2 5C F CF3 CF CF3 2 5 2 5 3 H2C CH2 H2C CH2 H2C CH2 F3C

MeTpCF3Ag(C2H4)

MeTpC2F5Ag(C2H4)

H F3C

F3C

Tp(CF3)2Ag(C2H4)

CF3CF 3 B N N N N N N Ag CF3CF 3 THF

Tp(CF3)2Ag(THF)

Figure 11.5 Silver(I) complexes of fluorinated scorpionates.

rigidity, which enhances the ligand steric effects in silver. Product distributions suggest that sterically bulky auxiliary ligands (TpCF3 vs TpC2 F5 ) slightly facilitated primary C—H bond activation. Even the simplest CH4 can work well with EDA for carbene transfer reactions. The functionalization of methane toward ethyl propionate 123 was successfully performed by using Tpx -silver complexes in supercritical carbon dioxide as the reaction medium (Scheme 11.43) [131c, 136]. This research represented a great breakthrough for the long-standing problem of methane C—H bond functionalization with diazoacetates [137]. The Tpx -silver complexes possessed distinguished property and selectivity in the primary C—H bond activation, in comparison with Tp(CF3 )2 ,Br Ag(THF) and Tp(CF3 )2 ,Br Cu(NCMe) [138]. For the class of Tpx -silver complexes, perfluorinated tris(indazolyl)borate ligands are proved to display higher reactivity to activate the primary C—H bonds than perbrominated tris(pyrazolyl)borate ligands, with the increased order [TpBr3 Ag]2 ≪ [F21 − Tp4Bo,3CF2 CF3 Ag(acetone)] < [F21 − Tp4Bo,3CF2 CF3 Ag(THF)]. Besides, concerning the number of perfluorinated group, experiments showed that the F27 , F33 , and F39 displayed very close reactivity, while F51 was the best catalyst for the primary C–H insertion [130a]. FN-Tp4Bo,3RfAg(L)

H3C

sc-CO2 PT = 250 atm, 40 °C, 14 h

H

N2

+

CH4

H

COOEt

COOEt H 123

Catalyst loading: 0.03 mmol Initial molar ratio EDA:TpxAg = 100 : 1

F

F

F F Rf

F F

H B N N N N N N

F F

F FF

Rf = CF3 Rf = CF2CF3

F21-Tp4Bo,3CF3 F27-Tp4Bo,3CF2CF3

Rf F

Rf

Scheme 11.43 Silver-promoted methane functionalization with EDA.

+ N2

693

694

11 Silver Complexes in Organic Transformations

11.5.2

Nitrene Transfer Reactions

Apart from the carbene transfer reactions, in 2010, the Perez group reported the aziridination of dienes 124 bearing a terminal hydroxy group by using several Tpx M complexes (M = Cu, Ag) as a catalyst [139]. To access vinyl aziridines 125, a low catalyst loading and stoichiometric mixtures of diene and PhI=NTs as the nitrene source were employed. The catalyst [Tp*,Br Ag]2 was proved highly regioselective toward the aziridination of the double bond vicinal to the hydroxy end of the substrate (up to > 85 : 15) and highly stereospecific with an array of dienes (trans > 98%) (Scheme 11.44). Both experimental results and systematic DFT study showed that the hydroxy group in dienes 124 played a crucial role in the regioselectivity [140]. Further, the vinylaziridine product was applied as a model substrate for ring-opening reactions using different S, N, and O nucleophiles to form the β-amino alcohol derivatives 126 and 127. NHTs R

HO R

HO

Ts

[Tp*,BrAg]2 PhI NTs

HO

124 Me Me B Me N Br N NN Br Br N N Me Me Me Tp*,Br Ar (Ar = 4-MeC6H4) O S O N

Ar O S O LnM N O H

MLn + OH

126 XR′ R

125 Conv. >99% Regioselectivity >85% Stereoselectivity >98%

H

R

N

R

NHTs R

HO 127

XR′

XR′ = OH, NH2, SPh

Ts OH N R 125

Scheme 11.44 Silver-catalyzed aziridination of dienes and the proposed mechanism.

Up to now, the mechanisms of the olefin aziridination reactions via nitrene transfer remain controversial, albeit a concerted or stepwise mechanism was highly suggested, and a sequence of reports has been revealed to disclose the actual paths [4b, 141]. For the above results of conversion, Perez and coworkers found that it was not fully run by concerted or stepwise mechanisms. Based on the experimental and computational results, a possible mechanism was proposed as shown in Scheme 11.45 [142]. In all cases, the reaction starts with the formation of a metal-nitrene species that holds some radical character, and therefore the aziridination reaction proceeds through the radical mechanism, but the radical inhibitor experiments were unaffected. The silver-based systems, however, hold a minimum energy crossing point (MECP) between the triplet and closed-shell singlet surfaces, which induces the direct formation of the

11.5 Tpx -silver Complexes (Trispyrazolylborate Ligands)

R1

R2 R1 R2

TpxM N Triplet

–TpxM M = Ag

Ts

t s Stereospecific

TpxM N Ts M = Cu

s

t

t –PhI

s

Tp M + PhI=NTs

R2 TpxCu

N Ts

R2 N Ts

–CuTpx Stereospecific

R1 x

R1

Rotation, then t s Not stereospecific

R1

R2 N Ts

+ CuTpx

Scheme 11.45 Possible mechanistic proposal for aziridination of olefins.

aziridines, and stereochemistry of the olefin is retained. However, in the case of copper, a radical intermediate is formed, and this intermediate constitutes the starting point for competition steps involving ring closure (through an MECP between the open-shell singlet and triplet surfaces) or carbon–carbon bond rotation and explains the loss of stereochemistry with a given substrate. Overall, a mechanism that involves both the singlet and the triplet pathways was highly plausible based on the experiments. In 2007, He and coworkers reported the first silver-based catalytic system for C–H amination by using [Ag2 (OTf )2 (bp)2 ] (bp = 4,7-diphenyl-1,10phenanthroline) complex with PhI=NNs [143], which was highly applicable for the substrates with activated C–H bonds, i.e. benzyl functions. Perez and coworkers, in 2008, extended the C–H amination to a wide range of unactivated linear and branched alkanes 128 by using Tpx Ag complexes as the catalysts (Scheme 11.46) [144]. The dimer complex [Tp*,Br Ag]2 was found to be the most active, inducing the formation of the amines 129 in moderate to high yield (65–90%). The mechanistic study clearly indicated that the reaction plausibly proceeded via the intermediacy of radical species, in which tertiary sites displayed the highest reactivity. A further report to alkane C–H amination was developed with a chiral sulfonimidamide as the nitrene source, in the presence of the silver complex [Tp*,Br Ag]2 , and furnished the expected C–N bonds in moderate to high yields [145]. Very recently, the same group achieved the highly chemoselective N-amidation of tertiary amines using Tpx -silver complex [Tp*,Br Ag]2 as catalyst and PhI=NTs as nitrene source, thus opening up a new strategy for the synthesis of functionalized aminimides 130 (Scheme 11.47) [146]. The process is highly selective even in the presence of olefin and other functional groups. This methodology is suitable not only for the simple tertiary amines but also for complex natural products such as brucine and quinine, where the reaction was selectively occurred at the tertiary amine site rather than in other functional groups. The theoretical DFT studies proved that this selective N-amidation reaction proceeds through the triplet silver nitrene intermediate.

695

696

11 Silver Complexes in Organic Transformations

R1

H

+

R3 R2 128

PhI=NTs

HN Ts R1 R2 R3 129

[Tp*,Br3Ag]2 (5 mol%) 80 °C, 4 h

HN Ts R1 R2 R3

PhI=NTs TpxAg

PhI R1 R2

+ TpxAg NHTs

TpxAg NTs

R3

R1 R2

H R3

Scheme 11.46 Silver(I)-scorpionate-catalyzed amination of alkanes.

R R1

N

R2

[Tp*,BrAg]2 (5 mol%) PhI NTs

R R1

DCM, 50 °C, 16 h

Me N Bn Me N Ts 88%

H

N N Ts 67%

MeO

H N O

N Ts

R2

13 examples, 44–95%

MeO

N

N

130 N Ts N N

HO

H H

MeO

H 83%

Ts

N 73%

Scheme 11.47 Silver-catalyzed N-amidation reaction with amines.

11.6 Silver Complexes with Pyridine-Containing Ligands Pyridine-containing ligands have attracted great interest owing to their wide range of potential fields of applications and because they have been successfully employed in catalysis [4b], biology [147], magnetic resonance imaging [148], supramolecular chemistry [149], and self-assembly [150], etc. Among the reports dealing with pyridine-containing metal complexes, representative backbones with simple pyridine, phenanthroline, pyridine-containing macrocycle (Pc-L), and pyridylpyrrolide (Figure 11.6), have been widely studied relevant to catalytic applications [151]. In view of the pyridine-containing ligands, there are synthesized uni-, bi-, and polydentate nitrogen-base complexes of silver(I) [152]. For most cases,

11.6 Silver Complexes with Pyridine-Containing Ligands

R

R

N

N N

R R

R

N

N Ts N

N

bipy R = H dtbpy R = tBu

R tBu

phen R = H bp R = Ph N

Me

Me

3terpy

terpy

N

Ph

R = tBu R=H

Pc-L CF3

N Me N

N

N 3

N Ts N

N

N

N

R

N NH

F 3C

N N

N

N

R R=H tpa (p-NMe)3tpa R = NMe3

anti-α-Me-Py3Pip

Py5Me2

Pyridylpyrrolide

Figure 11.6 Representative ligands with pyridine rings. –OTf

N N

Ag

N Ag

N

R

R

N

N

N

–

OTf

(phen)AgOTf

(OTf)2

N

(tpa)AgOTf t Bu

N

N

Ag

Ag

N

N N

O

t Bu

N t Bu

F3C

O t Bu

N N Ag

N

–

NO3

N

N

N

N N Ag N OTf

(phen)2AgOTf O

N

Ag OTf

N

N

N

N CF3 N

Ag N

N

N t Bu

F3C

N

Ag

CF3 Ag

CF3 N

Ag N

CF3

t Bu

[(Py 5Me2)AgOTf] 2

t

( Bu 3tpy)Ag(NO3)

Ag 3(μ2-3,5-(CF3)2PyrPy)3

Figure 11.7 Pyridine-containing ligands of Ag(I) with uni-, bi-, and polydentate nitrogen.

the uni- and bidentate bases derivative of pyridine, variously hindered by 2-substituents, are used as main adducts of 1 : 2 (unidentate N-base) or 1 : 1 (bidentate N,N′ -base) AgX:L stoichiometry. For example, (phen)AgOTf [153], (phen)2 AgOTf [154], and [Ag(py)2 ][OTf ] [152] complexes have been identified and applied in catalytic transformations (Figure 11.7). Also, dinuclear types like [Ag2 (tBu3 tpy)2 (NO3 )](NO3 ) (tBu3 tpy = 4,4′ ,4′′ -tri-tert-butylterpyridine) [155], [(Py5 Me2 )AgOTf ]2 (Py5 Me2 = 2,6-bis[1,1-bis(2-pyridyl)ethyl]pyridine) [156], and argentate trinuclear cluster Ag3 (μ2-3,5-(CF3 )2 PyrPy)3 (3,5-(CF3 )2 PyrPy = 2,2′ -pyridylpyrrolide-ligand) [157] have been used as catalysts.

697

698

11 Silver Complexes in Organic Transformations

11.6.1 Silver-Catalyzed Nitrene Transfer (Aziridination vs C–H Amination) The chemoselective C–N bond formation, e.g. aziridination and C−H amination, especially in substrates bearing both reactive C—H and C=C bonds, is a particularly challenging task, as these compounds often give rise to multiple products or exhibit substrate-controlled selectivity. To overcome substrate-controlled selectivity, a sequence of reports has been developed via metal catalysts, including Rh, Ru, Cu, Fe, Co, Mn, and Ag catalysts to access chemoselectivity, site selectivity, and chemo/stereoselectivity of the conversions [60, 158]. The Schomaker group has been committed to this topic and has recently offered a comprehensive summary of the variety of design principles with tunable, Ag-catalyzed aminations to determine the effect on chemoselectivity, site selectivity, and chemo/stereoselectivity, as well as potentiality in intermolecular C–H aminations (Figure 11.8) [1c, 4b, 159]. Ag(I) supported by simple N-donor ligands accommodates a diverse range of coordination geometries, from linear to tetrahedral to seesaw, enabling the electronic and steric parameters of the catalyst to be tuned independently. The factors including ligands (Figure 11.6), Ag salt counteranion, Ag/ligand ratio, the solvent, and temperature all influence the fluxional and dynamic behavior of Ag(I) complexes in solution, thereby enabling the different selectivity of the reactions. Consequently, ammonia resources bearing functional groups including tertiary C(sp3 )−H, benzylic, allylic, and propargylic C—H bonds were designed to demonstrate selectivity by varying suitable ligands. With respect to mechanisms of nitrene transfers, in general (Figure 11.9), treatment of a nitrogen transfer reagent (e.g. carbamates and sulfamates) with an oxidant (e.g. PhI(OAc)2 , PhI(OTFA)2 ) generates an imidoiodinane (LVG = NR1 ), which eventually forms a metal-supported singlet or triplet nitrene intermediate. Whether addition or insertion of this species into a C=C or C—H bond occurs in a concerted or stepwise fashion, it can impact the chemoselectivity, site selectivity, and stereoselectivity of the reaction. Both experiments and calculation studies have been done to understand the singlet/triplet paths of the nitrene transfers and achieved significant progress, but they remain controversial [141, 158a]. In 2003, the He group isolated and identified a disilver complex [Ag2 (tBu3 tpy)2 (NO3 )](NO3 ) (tBu3 tpy = 4,4′ ,4′′ -tri-tert-butylterpyridine) and demonstrated the Chemoselectivity O O S H2N O R Aziridination

Site selectivity O O S H2N O R

H C–H insertion

H

Chemo/stereoselectivity O

3° alkyl H

Alk Alk

R = alkyl, Ar, vinyl, alkynyl or even 3° alkyl

R1

N

O

R2 H L* = (S,S)-tBuBOX R1,2 = alkyl

Figure 11.8 Chemoselectivity, site selectivity, and stereoselectivity C–N bond formation via silver catalysis.

11.6 Silver Complexes with Pyridine-Containing Ligands R1 N

or R2

R3

R2

AgLn

R3

1

R

HN R1

O

Concerted or stepwise pathway

R2

[O]

N LVG

LnAg N

NH2

X = C, SO

R1

Triplet or

R3

O X

LVG = IPh, N2 LVG

LnAg N R1 Singlet R2 O N R1 H

O

O R2 O AgLn N R1 H

AgLn

Rapid radical rebound intermediate

Concerted, asynchronous TS

Figure 11.9 General mechanism of nitrene transfers.

olefin aziridination with a nitrenoid source PhI=NTs in acetonitrile at ambient temperature (Scheme 11.48) [155]. A further report that, in 2015, Murugesu and coworkers first synthesized an unprecedented trinuclear Ag(I) complex with 2,4,6-tris(2-pyrimidyl)-1,3,5-triazineas (TPymT) was developed. The trinuclear Ag(I) was also applied as catalyst to the aziridination with terminal olefins and led to the formation of aziridines in good to excellent yields [160]. Due to the strong affinity of Ag· · ·Ag interactions and π· · ·π stacking of the TPymT ligands, a hexanuclear species was formed in solution. R1

R3

+ PhI NTs

R2

+

R2 N Ts

PhI

NO3

N

6+

O tBu

N N Ag

tBu

R3

tBu

O

N

R1

0 °C to RT, CH3CN 10 examples, 66–91%

O tBu

AgNO3 and tBu3tpy (2 mol%)

AgI

N

N

N

N

N

Ag N

N

N

N

N

N

AgI

N tBu

AgI N N N N N N N AgI AgI N N I

I

Ag

N Ag N

AgI

tBu

[Ag2(tBu3tpy)2(NO3)](NO3)

Scheme 11.48 Ag(I) complex-catalyzed aziridination of olefins.

N

N

N

N

N

N

N AgI

6NO3–

699

700

11 Silver Complexes in Organic Transformations

Notably, olefin aziridination of functionalized dienes 131 was challenging; but in 2010 Pérez and coworkers reported an efficient regio- and stereospecific transformation in the presence of [Tp*,Br Ag]2 catalysis (Scheme 11.49) [139]. With the concentration on the mechanisms, a concomitant involvement of the singlet and triplet pathways was revealed by the authors [142]. The reaction starts with the formation of a silver-nitrene species that holds some radical character, and therefore the aziridination reaction proceeds through an approximate radical mechanism. The silver-based systems, however, hold an MECP between the triplet and closed-shell singlet surfaces, which induces the direct formation of the aziridines 132, and maintain stereochemistry of the olefin.

R

HO

PhI 131

HO

NTs

Conversion >99% Regioselectivity >85% Stereoselectivity >98% R1

TpxAg

s

+

t

Me Me N R Br N NN Br Br N N Me Me Me Tp*,Br

Ts

[Tp*,BrAg]2

Me

N 132

R2

Triplet

–TpxAg

R2 Ts

B

R1

TpxAg=N

PhI NHTs –PhI

H

t s Stereospecific

TpxM N Ts

R1

R2 N Ts

Scheme 11.49 [Tp*,Br Ag]2 -catalyzed region- and stereospecific aziridination of dienes.

Furthermore, the He group in 2004 reported that in the presence of the disilver complex [Ag2 (tBu3 tpy)2 (NO3 )](NO3 )] and PhI(OAc)2 as the oxidant, an intramolecular C–H amidation reaction of secondary saturated C—H bonds was available to furnish the five- or six-membered ring targets 134, depending on the structure of sulfamates and carbamates 133 (Scheme 11.50) [161]. Similarly, with the treatment of AgNO3 /tBu3 tpy/PhI(OAc)2 system, sulfonylamides (typically NsNH2 , Ns = p-nitrosulfonyl) acted as nitrene precursor and occurred the novel imination of sulfoxides and sulfides, efficiently affording sulfoximines and sulfilimines, respectively [162].

H2N

O X

O

R

133 Sulfamates or carbamates

AgNO3 (2 mol%) 3tpy (2 mol%)

tBu

PhI(OAc)2 (1.4 or 2 equiv.) CH3CN, 82 °C

HN R

O X

O

( )n

134 n = 1, 2

Scheme 11.50 C–H amidation reaction of secondary saturated C—H bonds.

Analogously, Shi and coworkers in 2014 developed a silver-promoted intramolecular amination of linear triflamide (1,1,1-trifluoromethanesulfonamide) (Scheme 11.51) [163]. By employing silver(I) as a catalyst, dtbpy (4,4′ -di-tert-butyl bipyridine) as a ligand, and PhI(OCOCF3 )2 as an oxidant, pyrrolidines 136 and

11.6 Silver Complexes with Pyridine-Containing Ligands

H R1

Tf N

AgOAc-dtbpy (20 mol%) PhI(OTFA)2

NHTf R3

R3 R1

K2CO3 (2 equiv.) PhCl/DCE, 120 °C

R2 135

R2 136 –AgLn

CF3 H

N N AgIII OTFA TfN

TFAO

R1

R3

R

H

137

AgIIILn NTf

TFA R1

R3

N H

Tf

2

135-2

AgOAc (1 equiv.) dtbpy (20 mol%) PhI(OTFA)2 K2CO3 (2 equiv.) PhCl/DCE, 120 °C

R3 R

R2

R1

R2

O AgIIILn NTf

R1

R2 135-1 R3

O H

R3 R2 R

N

R1

Tf 138

Scheme 11.51 Silver-promoted direct amination of unactivated C–H bonds.

1,2,3,4-tetrahydroquinolines 138 were provided via the C–H amination of butyl and 3-aryl propyl amines (sp3 and sp2 C—H bonds 135 and 137, respectively) without additional directing groups. This method displayed preference for primary Csp3 —H bonds and exhibited distinct chemo- and regioselectivity. With the chelation of the electron-rich ligand, the Ag(I) complex was oxidized to Ag(III) by PhI(OTFA)2 , which then formed the activated N–Ag(III) species 135-1. Subsequently, with the assistance of trifluoroacetate anion to C–Ag(III), deprotonation of the C(sp3 )—H bond/metallization with the electrophilic Ag(III) occurred, giving 135-2 with release of a trifluoroacetic acid (TFA). The following reductive elimination produced the pyrrolidine 136 and regenerated the Ag(I) catalyst to fulfill the catalytic cycle. A further calculation report also supported the Ag(III) process and excluded an alternative radical path [164]. In comparison, under similar Ag(I)/dtbpy/PhI(OTFA)2 conditions, a novel selective cleavage of an inert C—C bond followed by C—O/N bond formation was achieved (Scheme 11.52) [165]. In this case, an N-centered radical path was plausible, which then induced a long-distance aryl migration via intermediated 139-1 from a carbon to a nitrogen center. The more electron-rich aryl groups of the γ,γ-diaryl-substituted triflic amides 139 showed better performance than electron-deficient aryl motifs during the migration. In addition, the migration products 140 were easily converted to the corresponding γ-hydroxy amines and tetrahydroquinoline derivatives under mild conditions. For a hydrocarbon precursor with multiple reactive sites, the nitrene transfer can lead to either aziridination of the activated C=C bond or C−H insertion of C—H bond. The Schomaker research group developed a novel Ag-based

701

702

11 Silver Complexes in Organic Transformations

R1

Tf N

Ar R2 R

AgOAc (20 mol%) dtbpy (20 mol%) H PhI(OTFA)2 (2 equiv.)

R1 TFAO

K2CO3 (2 equiv.) PhCl/DCE, 120 °C R1, R2 = H, Me R = H, Ph, tBu, F, Cl, etc. Ar is more electron deficient

139

R

Ar

R1

Tf N 2

N Tf

Ar

R

R2

R

140 21 examples 44–74%

139-1

Scheme 11.52 Long-distance aryl migration with γ,γ-diaryl-substituted triflic amides.

catalyst system to solve the chemoselectivity, simply by tuning the ratio of metal and the same ligand (Scheme 11.53) [166]. The ability for Ag with phen ligand possessing multiple coordination geometries [167] (e.g. (phen)AgOTf and (phen)2 AgOTf ) provides an opportunity to promote the chemoselective aminations (aziridination vs C−H insertion) in a molecule containing carbamate and unsaturated C=C double bonds [168]. Based on the experimental results and kinetic studies, chemodivergence of aziridination or C−H insertion likely resulted from the differing steric environment around the Ag nitrene [168]. The active Ag nitrene species in situ generated from imidoiodinane 141 carried out aziridination or C−H insertion, depending on the Ag coordination number, albeit the aziridination was intrinsically efficient than the C−H amination. It was also revealed that the aziridination rate was suppressed as steric congestion increased in Ag(L)2 OTf; however the C−H insertion rate decreased only slightly when using Ag(L)OTf instead of Ag(L)2 OTf [167]. O 1

R

N

(phen)AgOTf O

R2 O 2

R

R1

N H

O

O R1

O

1 : 1.25 AgOTf:phen

R2 H H

PhIO

H R2

141

C R1

O

(phen)2AgOTf NH2 1 : 3 AgOTf:phen

O NH2

R1, R2 = alkyl, H

O

R1

PhIO

H H

O

R2 HN

R2

H

O

C

N H H

O

R1

Scheme 11.53 Catalyst-controlled nitrene transfer to aziridination vs C−H insertion.

Even the more complex molecules containing carbamate moieties can be applied to the C−H amination [169], hence, the selective silver-catalyzed protocol has emerged as a key step for the total synthesis of bioactive products, such as the (−)-N-methylwelwitindolinone C isothiocyanate, and its isonitrile analogue [169a,b]. The reactions efficiently underwent by using AgOTf/bathophenanthroline catalysis and PhI(OA)2 as an oxidant. Quite recently, the Schomaker group described the first general intramolecular, asymmetric aziridination in the presence of chiral ligand tBuBOX and AgClO4 (Scheme 11.54). As a result, a range of [4.1.0]-carbamate-tethered aziridines 143 was obtained from the di- and trisubstituted homoallylic carbamates 142 in good yields and ee values of up to 92% [170].

11.6 Silver Complexes with Pyridine-Containing Ligands

R3 R2

O

AgClO4 (20 mol%) tBuBOX (10 mol%)

O NH2

O R1 142

R1 R2

PhIO (2 equiv.) 4 Å MS, DCM, –20 °C Up to 92% ee, Up to 87%

N

O

O O

N

N tBu

R3 143

tBuBOX

tBu

Scheme 11.54 Enantioselective intramolecular silver-catalyzed aziridinations.

With respect to the challenging saturated C—H bonds 144 with different chemical environments, Schomaker and coworkers offered a simple ligand-tuned silver complex-catalyzed regioselective C—H bond aminations (Scheme 11.55) [171]. Silver catalysts supported by bipy derivatives (e.g. tBu or OMe) appear to prefer amination of the most electron-rich C—H bond to yield products 146. But the presence of silver supported by a tpa ligand is more sensitive to the competing steric environment around the C—H bond, and the bond dissociation energy, which leads to the activated α-conjugated C—H bonds 144, including alkynyl, aryl, and alkenyl groups, delivered products 145. Based on the experimental and computational results, the involvement of π· · ·π (between one of the pyridine ligand arms and the aryl group of the substrate) and Ag· · ·π interactions between catalyst and substrate (144-1 to 144-3 as shown in Scheme 11.55) had great impact on the selectivity of the reactions, primarily by lowering the energy of the directed transition state and reaction conformers. Therefore, the C–H amination of activated α-conjugated C—H bonds was preferred over the 3∘ alkyl C(sp3 )—H bonds [171b]. O O S O

AgOTf (10 mol%) tpa (12.5 mol%)

H

N N N Ag

R

(tpa)AgOTf

Alk R

144 R = alkynyl, Ar, alkenyl

tBu

O O S NH O

AgOTf (10 mol%) dtbpy (30 mol%)

N

O

H

O2S

N

N

iBu

π-π

Ag

O2S

H

N

N

N

144-1

H

O

N

N

Ag

N

tBu

144-2

H H

O

OTf

H

O2S

OTf

N

N

N

N

tBu

iBu

H H

tBu

N Ag

R2

146 Up to >8 : 1 selectivity iBu

–OTf

R1

R′

PhIO, 4 Å MS DCM, RT

H

N

OTf

145 Up to >10 : 1 selectivity

Alk

O

R1 R2

PhIO, 4 Å MS DCM, RT

NH2

O2S

HN

N

N

Ag

N

N

N

144-3

Scheme 11.55 Selective amination of C—H bonds for activated α-conjugated C—H bonds.

703

704

11 Silver Complexes in Organic Transformations

Moreover, with respect to the tpa ligands, the site selectivity was revealed and greatly impacted by the steric or conformational effects, which led to the different nature of the major conformer of silver species in solution, rather than electronic effects [167]. Confirmed by the X-ray crystallography and VT NMR studies, the presence of Ag(I) and tpa in solution allows a fluxional coordination mode including monomeric structures (tridentate coordination) and dimeric structure. Thereby, the low-coordinate silver complexes favored reaction with activated α-conjugated C—H bonds, while tetradentate complexes gave rise to activate 3∘ alkyl C(sp3 )—H bonds, perhaps because of the generation of more electrophilic silver nitrene species or a more favorable trajectory for C—H bond activation with the putative silver nitrene. Inspired by this, two piperidine-based ligands, i.e. (α-Me)-syn-Py3 Pip and (α-Me)-anti-Py3 Pip, were designed for the studies of the site selectivity of nitrene transfers. Additionally, the silver complex, [(Py5 Me2 )AgOTf ]2 , coordinated with steric bulk N-ligands, also successfully catalyzed these activated secondary C—H bonds in 147 over tertiary alkyl C(sp3 )—H bonds, affording the desired 1,2,3-oxathiazinane 2,2-dioxide scaffolds 148 in satisfactory yields and good site selectivity (up to 20 : 1, Scheme 11.56) [172]. (OTf)2 O2S H

O

N

NH2 Alk Alk

R

147 R = alkynyl, Ar, alkenyl

O O S O

AgOTf (10 mol%) Py5Me2 (12 mol%) PhIO, 4 Å MS DCM, RT

HN

N

N

N

Alk

Ag

Ag Alk 148

N

N

R N

N

N

N

Up to >20 : 1 [(Py5Me2)AgOTf]2

Scheme 11.56 Site-selective C(sp3 )–H amination of activated secondary C—H bonds.

Further, the site-selective C–H aminations of competing and differentiated 3∘ C—H bonds 149 was discussed (Scheme 11.57) [156]. The authors found that in most cases, the use of silver complex with Me4 phen favored kinetically accessible C—H bonds that cyclic C—H bond over acyclic C—H bond to afford products 150, while [(Py5 Me2 )AgOTf ]2 displayed better reactivity for the activated C—H bonds to give targets 151. However, in challenging substrates, the orthogonal reactive site was favored using Rh2 (TPA)4 through a concerted path. Moreover, with the experimental results, the mechanism for the [(Py5 Me2 )AgOTf ]2 catalyst was proposed involving a nitrene transfer and H-atom transfer (HAT) process with the formation of long-lived radical intermediates. The intermolecular amination versions of C–H groups were also developed under silver catalysis. In 2007, He and his team developed a direct and intermolecular secondary C–H amination, in the presence of [Ag2 (OTf )2 (bp)2 ] (bp = 4,7-diphenyl-1,10-phenanthroline) complex as the catalyst and PhI=NNs as the nitrenoid source, in which the benzylic C—H bonds displayed better reactivity (Scheme 11.58) [143].

11.6 Silver Complexes with Pyridine-Containing Ligands

O

(Me4phen)AgOTf

HN

O2 S

O

150

R2

NH2 SO2 R2

R1 149 AgOTf (10 mol%) Ligand (12.5 mol%) PhIO (3.5 equiv.) DCM, RT

[(Py5Me2)AgOTf]2

O

1 2 R1 R , R = alkyl, calkyl 1 R = Ar, R2 = alkyl, calkyl, Ar

O2 S

NH R2 R1

151

Scheme 11.57 Tunable C−H amination of different tertiary C—H bonds.

Ph H

PhI=NNs [Ag2(OTf)2(bp)2] (2 mol%)

NHNs N N Ag

Ph

DCM, 50 °C Up to 71% yield

OTf

Ph Ph

N

N Ag

Scheme 11.58 [Ag2 (OTf )2 (bp)2 ]-catalyzed intermolecular C–H amination.

Recently, Schomaker and coworkers developed a novel and simple catalysttunable olefin aziridination vs C−H amination in a homoallylic carbamate 152, simply by using tBu3 tpy and tpa ligand, respectively (Scheme 11.59) [173]. Among the nitrene precursor tested, HfsNH2 ((CF3 )2 CHOSO2 NH2 ) and DfsNH2 (2,6-F2 C6 H3 (OSO2 NH2 )) proved the best selectivity for the individual aziridination and C–H insertion. In contrast to the concerted path of nitrene transfer (via a three-member ring transition state), and the mechanisms with Tpx Ag proposed by Pérez and coworkers [142], two distinct nitrene transfer mechanisms were proposed based on the experiments and the computational results. In detail, in the presence of Ag tpa system, a stepwise mechanism with radical intermediates was plausibly involved. The in situ formed Ag(tpa)−nitrene complex sequentially followed by HAT step to yield radical intermediates (plausibly 3 Inttpa,I and OS1 TStpa,I PES – potential energy surface), which followed by radical rebound to give the C–H amination product 153. Due to the requirement of conversion from 3 Inttpa,I to OS1 TStpa,I to give the final product 153, allowing 3 Inttpa,I could be long enough to be trapped by radical inhibitors. While with silver-tBu3 tpy catalyst, a late transition state from Ag−nitrene complex 155 followed by a barrierless recombination step produces aziridines 154 that preserve stereochemistry. The major distinction between these two mechanisms appears to be the extent to which the Ag—N bond breaks during the HAT transition state. Furthermore, the specific structure of the Ag−nitrene intermediates with ligands potentially provided control on the selectivity of the reactions via change of the size of the bound counteranion within the same ligand coordination.

705

706

11 Silver Complexes in Organic Transformations

[(tBu3tpy)AgOTf]2 R

NHfs

(tpa)AgOTf R

AgOTf (10 mol%) Bu3tpy (12 mol%) PhIO (3.5 equiv.) HfsNH2

H

154 15 examples A:I 2.5 : 1 to >19 : 1

152

NHDfs 153

OTf

3Int

Concerted RO3S

R R H C H N

OTf

N Ag N N H H N SO3Ar′ N

155

AgLn

PhIO (1.2 equiv.) DfsNH2

13 examples I:A 2.7 : 1 to >19 : 1

N TfO N N Ag Ag N SO3(CF3)2 N N N

RO3S

R

AgOTf (10 mol%) tpa (12 mol%)

t

OS1TS

tpa,I

R R H C H N

RO3S

AgLn Barrierless rebound

Products

Products

H H N Ag N N N SO3Ar′ N tpa,I

R R H C H N AgLn

HAT

Radical intermediates

Scheme 11.59 Tunable olefin aziridination vs C−H amination in homoallylic carbamates.

11.6.2

Carbene Insertion

The trinuclear argentate complex Ag3 (μ2-3,5-(CF3 )2 PyrPy)3 (PyrPy = 2,2′ pyridylpyrrolide) was first reported by Caulton and coworkers in 2011, by treatment of the corresponding H(3,5-(CF3 )2PyrPy) with Ag2 O in acetonitrile at room temperature overnight [157, 174]. They are proved easy to prepare and are air and water stable. This complex features with 2,2′ -pyridylpyrrolide ligand [3,5-(CF3 )2 PyrPy] that has an electron-rich pyrrolide moiety but carries two electron-withdrawing CF3 substituents in the pyrrolide ring. The attachment of a cisoid bidentate pyridylpyrrolide ligand to monovalent silver, in the absence of an additional ligand/Lewis base source, leads to an unprecedented structure of a trimer in which the pyridylpyrrolide twists internally to bridge two metals. With analysis and comparison to the property of halogen-rich variants of trispyrazolylborate (Tpx ) ligand metal complexes, Ag3 (μ2-3,5-(CF3 )2 PyrPy)3 has consistency with electrophilicity being central to alkane C−H insertions for the synthesis of esters 156. In this regard, the Caulton group demonstrated the potentiality of Ag3 (μ2-3,5-(CF3 )2 PyrPy)3 to catalyze the insertion of carbene from EDA into aliphatic C—H bonds of ethane and other linear and branched hydrocarbons (Scheme 11.60(1)). The reactions all performed under mild and

11.6 Silver Complexes with Pyridine-Containing Ligands

H F3C N CF3 N

F3C

N

Ag

N

H3C CF3 Ag

5 mol% of [Ag] as monomer CO2Et

CF3

O

DCM or C6F6 RT, 3 d

O 156

(1)

CO2Et

N– + + N

N

Ag

H H

N– + N+

[Ag3] (5 mol%) CO2Et

DCM, RT 100%

(2)

N

157 CF3

Ag3(µ2-3,5-(CF3)2PyrPy)3

N– + R C N + N

5 mol% [Ag3] CO2Et

DCM, 60 °C

R

O OEt (3)

N 158

Scheme 11.60 Ag3 (μ2-3,5-(CF3 )2 PyrPy)3 complex and applications in carbene transfers.

diluted conditions without the need for slow addition of EDA, albeit resulting in low yields and highly suffered from 2∘ carbon selectivity [4c]. The catalyst further enabled an insertion of the carbene of EDA into the C—C bond of a series of arenes to ultimately ring open them and form the corresponding cycloheptatrienes 157 (Scheme 11.60(2)). The experimental and theoretical studies revealed that the C=C insertion displays low TS energy and preference over C–H insertion. For monosubstituted benzene, it was theoretically showed that 3,4-insertion product would be easily formed than the 1,2-insertion product [175]. In addition, under the silver catalysis, a [3+2]-cycloaddition of several nitriles, i.e. R–CN (R = Me, Ph, tBu) and N2 CHCO2 Et, to disubstituted oxazoles 158 was first developed, even in the presence of light and air (Scheme 11.60(3)). Structural and theoretical studies implied a three-coordinate silver carbene complex, (3,5-(CF3 )2 PyrPy)Ag–(:CHCO2 Et), to be responsible in a stepwise nitrile addition and cyclization step to form the oxazole ring [176]. 11.6.3

Hydrofunctionalization

In 2008, Helquist and coworkers reported the intramolecular hydroamination of a variety of primary aminoalkynes 159 by using silver–phenanthroline complexes, such as [Ag(Phen)OTf ] as the catalyst (Scheme 11.61(1)) [153]. In comparison with simple silver salts, these complexes are light stable and enable a catalytic alkyne hydroamination into heterocycles 160. Later, the complex [Ag(Phen)OTf ] was used in the intramolecular chloroamination of allenes 161 with N-chlorosuccinimide using 2,6-lutidine as a base, to afford chloroamination products 162, which can be further converted to functionalized 3-pyrroline and pyrrole derivatives 163 (Scheme 11.61(2)). This approach proceeds under mild conditions and tolerates a variety of functional groups [177]. The bis(pyridyl)silver(I) complexes, such as [Ag(Py)2 ][OTf ], are a class of disilver salts [152]. In 2013, the Hii group implemented these bis(pyridyl)silver(I)

707

708

11 Silver Complexes in Organic Transformations

N R2

R1

n

N

R3

NH2

Ag

–

X

R4

N

R2

CH3CN, 4 h, 70 °C

159

160

N

O NHR1

+

.

R2

(1)

R1

n

N Cl

R3

N Ag OTf –

R3

R4(C)

R3

Cl

(2)

2,6-Lutidine

N R1

O

161

R

2

R2

N R1

162

163

Scheme 11.61 Silver-catalyzed intramolecular hydroamination and chloroamination.

complexes in the first intramolecular hydroamination of (homo)propargylic trichloroacetimidates 164, producing methylene-substituted heterocycles 165 with 29–99% yields and (Z)-selectivity, through 5- and 6-exo-dig annulations (Scheme 11.62) [178]. The primary role of the liberated pyridine was to serve as a Brønsted base to abstract the imine hydrogen and sequester the released triflic acid, thereby preventing competitive side reactions. Further, they revealed that the rate of this reaction is highly sensitive to the ligand electronic properties; the reaction rate was greatly enhanced by electron-withdrawing groups on pyridine ([Ag(4-Y-py)2 ]+ , Y = OAc > H > Me > OMe) [179]. Cl3C NH O R1

R2

164 n = 0,1

O

( )n 165

[Ag(Py)2][OTf]

N

O

N TMS

TMS

O ( )2

R3 R2

CCl3

CCl3

N

R1

(Z)-selectivity

PyHOTf

H

Cl3C

N

O

CH3CN or acetone 23–60 °C 16 examples

( )n

N

CCl3

[Ag(Py)2][OTf] (10 mol%)

R3

TMS

TfO-Ag(Py)

Ag(Py)

H H

H NOE

Scheme 11.62 Silver-catalyzed intramolecular hydroamination of (homo)propargylic trichloroacetimidates.

An exclusive 5-exo-dig cyclization of propargylic amides 166 was established by a similar bis(pyridyl)silver(I) complexes 168 (Scheme 11.63) [70]. But a

11.6 Silver Complexes with Pyridine-Containing Ligands

– N Ag PF6 2 R1 168 (1–15 mol%)

MeO R1 O HN R2

R4

23 °C, DCM

R3 166

R1 ≠ OEt, CH=CH2, CO2Et, CH2CO2Et

O

R4

N 2 R3 R

167 16 examples Up to >99%

Scheme 11.63 Bis(pyridyl)silver(I)-catalyzed cyclization of propargylic amides to oxazolines.

different electronic demand was observed between this ligand-accelerated O–H addition processes due to the electron-rich [Ag(4-OMe-Py)2 ]+ 168 that allowed the best results of forming oxazolines 167. With internal alkynes a mixture of E- and Z-isomers was obtained depending on the pattern of substitution on the substrate. While the substrate bears electron-withdrawing amide substituents, NHC–Ag complexes, i.e. [Ag(OBz-Cl)(IPent)], were found more applicable for the transformation [69]. 11.6.4

Hunsdiecker Reaction

In 2012, the Li group identified the stable Ag(Phen)2 OTf as an efficient catalyst for the decarboxylative chlorination of aliphatic carboxylic acids (Scheme 11.64(1)) [154]. A wide range of 2∘ and 3∘ -aliphatic carboxylic acids were well compatible under the simple and mild conditions and led to alkyl chlorides 169 in moderate and excellent yields. A radical mechanism was proposed involving a decarboxylation of carboxylic acids to form alkyl radicals and a chlorine atom transfer with t-BuOCl (tert-butyl hypochlorite). The stable and easily available t-BuOCl was revealed not only as the chloride source and the oxidant to yield the dinuclear Ag(II) complex 170. But recently in the calculations by Zhang, a catalytic cycle including four steps, proton-coupled two-electron transfer, oxidative decarboxylation, formation of Ag(II)–Cl (chlorine source), and chlorine abstraction, was proposed. It was first suggested that this kind of reaction is driven by the proton-coupled two-electron transfer (Scheme 11.64(2)), which leads to the formation of (Phen)2 Ag(II) species, carboxylate, chloridion, and t-BuOH. Then the oxidative decarboxylation and formation of Ag(II)–Cl take place at the same time. The resultant alkyl radical from the former abstracts the chlorine atom of (Phen)2 Ag(II)–Cl to give the final product [180]. With the cooperation of Ag(Phen)2 OTf/t-BuOCl, a further report of simple sp3 C—H bonds was demonstrated in the C—Cl bond formations, including benzylic, tertiary, and secondary C(sp3 )—H bonds (Scheme 11.65(1)) [181]. In the situation, benzylic and secondary C–H were highly compatible with two equivalents of t-BuOCl under argon environment; meanwhile substrates containing electron-rich aromatic facilitated Caryl –H chlorination. Moreover, with Ag(Phen)2 OTf as the catalyst and dibromoisocyanuric acid as the brominating agent, various aliphatic carboxylic acids underwent decarboxylative bromination to provide the corresponding alkyl bromides under mild conditions

709

710

11 Silver Complexes in Organic Transformations

Ag(Phen)2OTf (5 mol%) t BuOCl (1.5 equiv.)

R–CO2H 1°, 2°, 3° alkyl

(1)

169

Cl OtBu

R–Cl

Ag(II)

R–Cl

CH3CN, RT or 45 °C 37 examples, 60–95%

Ag(I) Cl

Cl

(II)Ag

Ag(I) R

170

Ag(II)

OtBu RCO2H

CO2 Ag(II)

Cl

R

Ag(I) O O

Cl Ag(II) Ag(II) O SET O R

RCOOH + 2Ag(phen)2+ + tBuO–Cl

HOtBu

2Ag(phen)22+ + tBuO–H + Cl– + RCOO–

(2)

Scheme 11.64 Decarboxylative chlorination of aliphatic carboxylic acids and the proposed mechanisms. R R′ C H R″

R–CO2H 1°, 2°, 3° Alkyl

Ag(Phen)2OTf (0.2 mol%) t-BuOCl (2–3 equiv.) CH3CN, RT, 48 h Air or Ar Dibromoisocyanuric acid Ag(Phen)2OTf (2.5–10 mol%)

R R′ C Cl R″

(1)

Up to 94%

R–Br

(2)

DCE, RT 30 examples, 42–93%

Scheme 11.65 Ag(Phen)2 OTf-catalyzed C–halogen bond formations.

(Scheme 11.65(2)) [182]. The reaction not only was efficient and general but also enjoyed wide functional group compatibility. 11.6.5

Twelve-membered Pyridine-containing Ligands (Pc-Ls)

The introduction of a pyridine moiety into the skeleton of tetraazamacrocycles, known as 12-membered pyridine-containing ligands, (Pc-L, Figure 11.10) with increased conformational rigidity and different basicity has been developed as ligands [151a, 183]. In 2014, the group of Abbiati and Caselli synthesized and disclosed the full characterization of [silver(I)(pyridine-containing ligand)] complexes and their organometallic reactivity [184]. Compared with simple silver salts, [Ag(I)(Pc-L)] complexes display great advantages including solubility, enhanced stability, and the ease of handling. They have demonstrated fine catalytic activity in the regiospecific domino synthesis of 1-alkoxy-isochromenes

11.6 Silver Complexes with Pyridine-Containing Ligands

Figure 11.10 Pyridine-containing ligand (Pc-L) and numbering scheme adopted.

1 N Ts N 9 12 3 N S O 6 O 8 N 4 R R Ar 13 R1

Ar = Ph, 1-Np R = H, iPr R1 = H, Me

172 from 2-alkynylbenzaldehydes 171 under mild conditions (Scheme 11.66) [184a] and the A3 coupling reactions of aldehydes, terminal alkynes, and amines under microwave conditions [185]. OR2

O [Ag] (5 mol%)

H 1

R 171 R1 = Ar, nPr R2 = Me, iPr, Cy

R2OH Toluene, 30 °C

O

Ts N R1

172 12 examples 86–99%

N Ag

X– N Ts

N Ph X = BF4, TfO, Tf2N

Scheme 11.66 [Ag(I)(Pc-L)] complexes in the synthesis of 1-alkoxy-isochromenes.

Further, the authors isolated several well-defined cationic silver(I) complexes that contained chiral natural amino acids (e.g. 173 with active-pendant arm) and employed as competent catalysts for the Henry (nitro-aldol) reaction (Scheme 11.67(1)). Either electron-poor aromatic aldehydes or other activated aldehydes such as furfural and o-alkynylarylaldehydes were reacted well and led to the β-nitroalcohol products 175 in good to excellent yields. Remarkably, in the design for the generation of cycloisomerization product isochromenes 178, limitation was observed as addition products 177 were more favored from 2-alkynylbenzaldehydes 176 as starting material, promoted by the chiral [Ag(I)(Pc-L)] complexe 174 (Scheme 11.67(2)) [186]. 11.6.6

Miscellaneous Reactions

Treatment of sulfoximines 179 with TMSCF3 in the presence of Ag2 CO3 and ligand 1,10-phenanthroline under dioxygen condition afforded Ntrifluoromethylation 180 in moderate and good yields (Scheme 11.68) [187]. Learning from the primary mechanism studies, the novel method was proposed via a CF3 radical process, when the use of Ag(I)/phen was vital to stabilize (phen)AgCF3 species that further converted to CF3 radical along with Ag(0). Arylated fluoroalkyl halides are important synthetic reagents, albeit mild and versatile methods for their synthesis are lacking. But recently Vicic and coworker offered an available entry to produce arylated fluoroalkyl bromides 182 that possess various chain lengths of fluoroalkyl halide functionality (Scheme 11.69). Treatment of the in situ generated fluoroalkylated silyl reagents 181 in the presence of AgF and phenanthroline could be converted to [(phen)Ag(CF2 )n Br]

711

712

11 Silver Complexes in Organic Transformations

O R1

+

R2

H

OH

173 (10 mol%)

NO2

R2

R1

Cs2CO3 (10 mol%) DCM, 30 °C, 12 h

1

NO2

175 21 examples, Up to 97% OH NO2 174 (10 mol%)

R = Ar, Cy, Het O H

+ R2

NO2

TEA (10 mol%) DCM, RT

X R3

N Ag

BF4– N Ag

Ts N

N CbzHN

(2) R1

178 4 examples up to 54% +

N Ts

NO2 O

R3 177 8 examples up to 83%

R2 = H, Me; R3 = Ar, alkyl, SiMe3 X = N, CH +

R2

+

R2

X

176

Ts N

(1)

BF4–

N Ts

N

(CH2)4

Me

Np

173

CO2Me

174

Scheme 11.67 Henry (nitro-aldol) reaction via [Ag(I)(Pc-L)] complexes as catalysts. O R1 S NH + R2 179

Me3SiCF3

Ag2CO3 (20 mol%) 1,10-phen (40 mol%) 1,4-Dioxane, O2, 60 °C

O R1 S N CF3 R2 180 20 examples 33–85%

R1 = Ar, Bn; R2 = alkyl, c-alkyl, Ar

Scheme 11.68 Silver-catalyzed N-trifluoromethylation with sulfoximines.

F F F F Br

TMS

F F F F 181

AgF phen

N

F F F F Br

Ag N

F F F F

64% 182

+ CuI + ArI

CH3CN RT to 50 °C

F F F F Br

Ar

F F F F 183 21 examples Up to >99%

Scheme 11.69 Synthesis of arylated fluoroalkyl halides with fluoroalkylated silyl reagents.

species 182. The latter were isolated and sequentially coupled with aryl iodides in a one-pot manner, through transferring both the phen and the fluoroalkyl bromide chain to copper(I) iodide [188]. Along with the recent development of the field of silver catalysis, silver in various forms, such as salts, nanoparticles, nanocomposites, metal–organic

11.7 Summary

i

Pr

H

X–

Ag N iPr P H

i

X– i

Pr

Ag Pr P

iPr iPr

P

H Ag N

X–

X–

L Ag 184 X = SbF6

185

186

N

187

Figure 11.11 Examples of cationic and neutral silver(I)–L complexes (L = Buchwald-type biaryl phosphanes).

frameworks, and polymeric complexes, as well as ligand variants, has been designed and investigated on their characterizations and reactivity. In this view the reactions, e.g. (asymmetric) A3 coupling reaction [22] and alkyne–azide cycloaddition [189], often emerge as the model experiments to evaluate the catalytic activity [1e]. Besides the NHC ligands, N-centered ligands such as imidazoles [190], acridines [191], pyridines [185, 192], biaryl phosphanes [193], and enantiopure pyboxs [194] have been studied for the A3 coupling reactions. For example, a spectrum of cationic and neutral silver(I)–L complexes (L = Buchwald-type biaryl phosphanes) with nitrogen co-ligands were synthesized and characterized, e.g. 184–187 (Figure 11.11) possessing excellent reactivity in Mannich A3 coupling of phenylacetylene, pyrrolidine, and aqueous formaldehyde. The isolated complex 187 strongly supported the mechanism for the reaction, and 184 and 185 reasonably acted as precatalysts for such reaction in toluene or CH2 Cl2 [193].

11.7 Summary This chapter presents and discusses the most important contributions in catalysis about silver complexes; special focus is given for the aspects involving NHC–Ag(I) complexes, chiral silver phosphates, P,O-type ligand silver(I) complexes, trispyrazoloborate–silver(I), and silver complexes with pyridine-containing ligands as the catalysts in organic reactions. This overview shows that the presence of ligands, such as NHC–Ag(I), TpX –Ag(I), Ag(Phen)2 OTf, and [Ag(I)(Pc-L)] complexes make the corresponding silver complexes stable and reactive to facilitate the reactions with a decreased energy barrier. In particular, the synergistic utility of the chiral ion pairs (e.g. BINOL phosphates) has improved the stereoselectivity of the reactions, enabling the success and development of asymmetric synthesis. In addition, the TpX –Ag(I) complexes have displayed significant catalytic reactivity for carbine transfers and have illustrated a sequence of experimental results of considerable synthetic value in the challenging and tough task during C—H bond insertions. What’s more, the effect on Ag(I) supported by N-donor ligands has been discussed, which have been applied and offered entries to overcome the substrate-controlled selectivity and achieve chemoselectivity, site selectivity,

713

714

11 Silver Complexes in Organic Transformations

and stereoselectivity of aminations and lead to tunable results, e.g. direct C−H aminations and aziridinations. It can be expected that with the treatment of such useful catalysts, further design and developments of silver catalysis can be witnessed, to meet the challenges in organic synthesis.

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13

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2017: 3589–3603. (b) Costa, J. and Delgado, R. (1993). Inorg. Chem. 32: 5257–5265. Nicola, C.D., Effendy, Marchetti, F., Nervi, C. Pettinari, C., and Robinson, W. (2010). Dalton Trans. 39: 908–922. Carney, J.M., Donoghue, P.J., Wuest, W.M. et al. (2008). Org. Lett. 10: 3903–3906. Wang, Z., Zhu, L., Yin, F. et al. (2012). J. Am. Chem. Soc. 134: 4258–4263. Cui, Y. and He, C. (2003). J. Am. Chem. Soc. 125: 16202–16203. Corbin, J.R. and Schomaker, J.M. (2017). Chem. Commun. 53: 4346–4349. Flores, J.A., Andino, J.G., Tsvetkov, N.P. et al. (2011). Inorg. Chem. 50: 8121–8131. (a) Park, Y., Kim, Y., and Chang, S. (2017). Chem. Rev. 117: 9247–9301. (b) Roizen, J.L., Harvey, M.E., and Du Bois, J. (2012). Acc. Chem. Res. 45: 911–922. Li, Z. and He, C. (2006). Eur. J. Org. Chem. 2006: 4313–4322. Safin, D.A., Pialat, A., Korobkov, I., and Murugesu, M. (2015). Chem. Eur. J. 21: 6144–6149. Cui, Y. and He, C. (2004). Angew. Chem. Int. Ed. 43: 4210–4212. Cho, G.Y. and Bolm, C. (2005). Org. Lett. 7: 4983–4985. Yang, M., Su, B., Wang, Y. et al. (2014). Nat. Commun. 5: 4707–4712. Zhang, X. (2017). J. Organomet. Chem. 832: 1–8. Zhou, T., Luo, F.-X., Yang, M.-Y., and Shi, Z.-J. (2015). J. Am. Chem. Soc. 137: 14586–14589. (a) Rigoli, J.W., Weatherly, C.D., Alderson, J.M. et al. (2013). J. Am. Chem. Soc. 135: 17238–17241. (b) Rigoli, J.W., Weatherly, C.D., Vo, B.T. et al. (2013). Org. Lett. 15: 290–293. Huang, M., Corbin, J.R., Dolan, N.S. et al. (2017). Inorg. Chem. 56: 6725–6733. Weatherly, C., Alderson, J.M., Berry, J.F. et al. (2017). Organometallics 36: 1649–1661. (a) Huters, A.D., Quasdorf, K.W., Styduhar, E.D., and Garg, N.K. (2011). J. Am. Chem. Soc. 133: 15797–15799. (b) Quasdorf, K.W., Huters, A.D., Lodewyk, M.W. et al. (2012). J. Am. Chem. Soc. 134: 1396–1399. (c) Hughes, J.M.E. and Gleason, J.L. (2017). Angew. Chem. Int. Ed. 56: 10830–10834. Ju, M., Weatherly, C.D., Guzei, I.A., and Schomaker, J.M. (2017). Angew. Chem. Int. Ed. 56: 9944–9948. (a) Alderson, J.M., Phelps, A.M., Scamp, R.J. et al. (2014). J. Am. Chem. Soc. 136: 16720–16723. (b) Huang, M., Yang, T., Paretsky, J.D. et al. (2017). J. Am. Chem. Soc. 139: 17376–17386. Scamp, R.J., Jirak, J.G., Dolan, N.S. et al. (2016). Org. Lett. 18: 3014–3017. Dolan, N.S., Scamp, R.J., Yang, T. et al. (2016). J. Am. Chem. Soc. 138: 14658–14667. Andino, J.G., Flores, J.A., Karty, J.A. et al. (2010). Inorg. Chem. 49: 7626–7628.

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175 Komine, N., Flores, J.A., Pal, K. et al. (2013). Organometallics 32: 3185–3191. 176 Flores, J.A., Pal, K., Carroll, M.E. et al. (2014). Organometallics 33:

1544–1552. 177 Sai, M. and Matsubara, S. (2011). Org. Lett. 13: 4676–4679. 178 Wong, V.H.L., Hor, T.S.A., and Hii, K.K. (2013). Chem. Commun. 49:

9272–9274. 179 Wong, V.H.L., White, A.J.P., Hor, T.S.A., and Hii, K.K. (2015). Adv. Synth. 180 181 182 183 184

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Catal. 357: 2485–2491. Zhang, X. (2016). Theor. Chem. Acc. 135: 144–152. Ozawa, J. and Kanai, M. (2017). Org. Lett. 19: 1430–1433. Tan, X., Song, T., Wang, Z. et al. (2017). Org. Lett. 19: 1634–1637. (a) Rezaeivala, M. and Keypour, H. (2014). Coord. Chem. Rev. 280: 203–253. (b) Stetter, H., Frank, W., and Mertens, R. (1981). Tetrahedron 37: 767–772. (a) Dell’Acqua, M., Castano, B., Cecchini, C. et al. (2014). J. Org. Chem. 79: 3494–3505. (b) Pedrazzini, T., Pirovano, P., Dell’Acqua, M. et al. (2015). Eur. J. Inorg. Chem. 2015: 5089–5098. Trose, M., Dell’Acqua, M., Pedrazzini, T. et al. (2014). J. Org. Chem. 79: 7311–7320. Tseberlidis, G., Dell’Acqua, M., Valcarenghi, D. et al. (2016). RSC Adv. 6: 97404–97419. Teng, F., Cheng, J., and Bolm, C. (2015). Org. Lett. 17: 3166–3169. Kaplan, P.T. and Vicic, D.A. (2016). Org. Lett. 18: 884–886. Connell, T.U., Schieber, C., Silvestri, I.P. et al. (2014). Inorg. Chem. 53: 6503–6511. Trivedi, M., Singh, G., Kumar, A., and Rath, N.P. (2015). Inorg. Chim. Acta 438: 255–263. Prakash, O., Joshi, H., Kumar, U. et al. (2015). Dalton Trans. 44: 1962–1968. Chen, J.-J., Gan, Z.-L., Huang, Q., and Yi, X.-Y. (2017). Inorg. Chim. Acta 466: 93–99. Grirrane, A., Álvarez, E., García, H., and Corma, A. (2016). Chem. Eur. J. 22: 340–354. Borrajo-Calleja, G.M., Julián, d.E., Bayón, E. et al. (2016). Inorg. Chem. 55: 8794–8807.

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12 Silver Nanoparticles in Organic Transformations Alain Y. Li, Alexandra Gellé, Andreanne Segalla, and Audrey Moores Centre for Green Chemistry and Catalysis, Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada

12.1 Introduction The past decades have seen a tremendous development in nanoscience, resulting in successful applications in fields, such as medicine, energy, sensing, environmental remediation, and agriculture [1–3]. Owing to their unique properties – such as high surface-to-volume ratio, extensive size shape, and compositional tunability, and amenability to recovery – they are particularly interesting in the context of sustainable science and in particular for catalysis [4]. The use of silver nanomaterials for catalysis has a long history, with alcohol oxidation being investigated in the 1880s [5, 6] and ethylene epoxidation patented in the 1930s [7]. The research on Ag nanoparticles (NPs) for catalysis is yet very dynamic to date, developing both known processes for improved activity, selectivity, or scope and novel ones, and has been the topic of recent reviews [8–11]. Silver is a versatile element, differing from gold in that only half of its supplies is used toward jewelry, the rest being geared toward industrial applications, including alloys, batteries, dentistry, glass coatings, LED chips, medicine, nuclear reactors, photography, photovoltaic (or solar) energy, tracking chips, semiconductors, touch screens, water purification, wood preservatives, and many other uses [12]. Silver is key in some chemical processes, as will be discussed below. In this review, we are covering the catalytic processes catalyzed by Ag NPs, with a special interest in the scope and mechanism of these reactions. Because of the specific position of the Ag+ /Ag0 couple redox potential (E∘ = +0.7996 V), Ag has the ability to oxidize and then reduce back to metal zero under mild conditions, making Ag-based NPs good catalysts in both reductive and oxidative processes. As developed in more details below, the role of Ag(I) species is not innocent and has been investigated for a number of reactions, both experimentally and in silico. Hence they are covered below under epoxidation of alkenes, oxidation of alcohols, and reduction reactions. Ag NPs also have an interesting optical property, the localized surface plasmon resonance (LSPR), which was at the center of recent development in catalysis for both oxidation and reduction. Finally, we complete Silver Catalysis in Organic Synthesis, First Edition. Edited by Chao-Jun Li and Xihe Bi. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2019 by Wiley-VCH Verlag GmbH & Co. KGaA.

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our survey with alkynylation, oxidation couplings, and miscellaneous processes toward nitrile hydrolysis, silanol chemistry, and Lewis acid catalysis.

12.2 Epoxidation of Alkenes Alkene epoxidation is a critical process in the chemical industry. Since Lefort’s patent on 1931 on direct epoxidation of ethylene into ethylene oxide (EO) using oxygen and silver [7], four different major and industrially used variations have been discovered by Union Carbide, Scientific Design Co. [13], Japan Catalytic Chemical Co., and Shell International Chemicals BV [14]. Eleven percentage of ethylene is used for EO production and constitutes the 14th most produced organic chemical (20 million tonnes in 2009) [15]. Although air is convenient as a reactant, pure oxygen is preferred in newer processes as it allows achieving higher reaction rates [16]. EO is primarily used to access ethylene glycols (monomer, oligomers, and polymers). Ethylene glycol itself is used as antifreeze and also as monomer for the production of polyesters, including polyethylene terephthalate. Propylene oxide (PO) is also produced industrially by epoxidation, for about half of its production, but it relies on organic oxidants, such as cumene hydroperoxide (Sumitomo process) [17]. Epoxidation of propylene by silver is still lacking in selectivity to be applicable in the large scale. Hence, because of the importance of alkene oxide for major industrial streams, the epoxidation reaction is crucial. As we will present below, Ag-based nanomaterials occupy a central place in this chemistry, and research is very active in this area to oxidize not only ethylene and propylene but also styrene and several others. Importantly, for this process, the role of surface oxides, chlorides, or other additives is often non-innocent in triggering both activity and selectivity. 12.2.1

Epoxidation of Ethylene

EO is an essential gateway chemical. The reference industrial catalyst for this reaction consists of large silver NPs (100–200 nm) supported (c. 15 wt%) on low-surface-area alumina, with alkaline species as promoters [18]. Ethylene epoxidation is competing with isomerization of the product toward acetaldehyde (AA) through re-adsorption on the catalyst and combustion by C–H activation (Scheme 12.1). Indeed, EO formation is reported to be moderately exothermic when the complete oxidation of ethylene and EO to CO2 is strongly exothermic [19]. Since 1931 when metallic silver was first shown to be an active catalyst for ethylene epoxidation with a selectivity of around 40–50% [20], several additives have been studied to improve its selectivity. Adding ppm levels of chlorine-containing molecules in the reaction stream, such as vinyl chloride [21], or oxides, including cesium oxides [22] and rhenium oxides [23], helps increase the selectivity of the reaction, with typical values found in modern literature around 80%. Increasing

12.2 Epoxidation of Alkenes

O AA

Isomerization to acetaldehyde

1/2 O2 –105 kJ 3O2 −1

–1327 kJ mol

mol−1

EO O

5/2 O2 2CO2 –1223 kJ mol−1 2H2O

Combustion pathway

Scheme 12.1 Ethylene epoxidation and competing processes.

the selectivity and avoiding combustion are crucial to reducing CO2 emission, considering the scale of EO production (more than 27 million tons is projected in 2017 [24]). Furthermore, a 1% improvement in selectivity would result in tens of millions of dollars per year of financial gain, underlining this other important aspect of the process [25]. Finally, using more sustainable synthetic methods and supports is also crucial, as pointed by Li and coworkers [26], using biomass to prepare the catalyst. The ethylene epoxidation mechanism with Ag has been extensively studied, as attested by Bukhtiyarov and Knop-Gericke, and around 1000 papers have been published on that subject [27]. Therefore, we provide here an overview of the field and refer the reader to this review and other seminal ones [20, 28]. It is generally accepted that chemisorbed atomic electrophilic oxygen adds to ethylene in the rate-determining step to form EO [28]. Indeed, X-ray photoelectron spectroscopy (XPS) showed two different types of oxygen atoms during reaction: a nucleophilic oxygen species with an O1s binding energy (BE) of ≈528.5 eV was observed and associated with the total combustion pathway, whereas an electrophilic oxygen species with an O1s BE of ≈530 eV is characteristic of the epoxidation reaction [29]. Although nucleophilic oxygen atoms have been well characterized [30], the nature of electrophilic one has remained elusive until a very recent report by Jones et al. [31]. They showed that sulfur impurities in Ag or ethylene resulted in the generation of SO4 species adsorbed on the surface that are the source of electrophilic atomic oxygen, as shown by in situ XPS technique. Medlin first showed theoretically and experimentally for butadiene that an oxametallacycle (OMC) intermediate formed on the surface of metallic silver, which can then go through 1,2-ring closure to form the epoxide product [32]. Eventually, Linic then proved that a similar pathway for ethylene occurred [33, 34]. Depending on the silver surface the OMC intermediate forms, it favors either EO for (100) and (110) faces or AA for (111) faces. Therefore, engineered silver structures such as nanowires or nanocubes, featuring predominantly (100) faces, greatly enhance selectivity [35]. Cheng et al. further explored this structure/activity relationship and established the following order for EO selectivity – (110) > (100) > (111) > (211) – as a consequence of the difference in adsorption strength and geometry of the OMC intermediate on the different surface (Scheme 12.2) [36].

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12 Silver Nanoparticles in Organic Transformations

1/2 O2 +

H H H Ag H O Agn

O

O

CO2 + H2O

Oxametallacycle (OMC)

Scheme 12.2 Mechanism of ethylene epoxidation mediated by silver through an oxometallacycle intermediate (adsorption steps omitted).

The amount of low valence sites also correlates with low selectivity [37]. To minimize their presence, larger NPs can be used, or low coordination sites can be poisoned using chlorides. Furthermore, surface and subsurface chlorine weakens Ag–O interactions, making oxygen more reactive for epoxidation. Chemisorbed chlorine also helps selectivity by assisting EO desorption, as long-standing EO adsorption is associated with its combustion or isomerization to AA [38]. Interestingly, Basset and coworkers showed that AgCl nanocubes were not active for ethylene epoxidation, thus linking the structural difference between AgCl and Cl-exposed Ag to distinct activities [39]. Upon a mild NH4 OH washing, surface chloride could be removed and the cubes became active for catalysis. Cs acts as a binder between Ag and its support enhancing the catalyst coverage, as shown by Minahan et al. for Ag and Al2 O3 . This will minimize the surface area of basic sites on alumina, lowering the combustion pathway [40]. Furthermore, Linic and Barteau showed that Cs and Cl both favorably affected the epoxidation transition state by an electric field/dipole interaction. Used in conjunction with Cl, these two additives can cooperatively boost the catalyst by electronic effects [41]. Though other transition metals can perform epoxidation through an OMC intermediate, they are either too stable and favor AA formation as the thermodynamic product or too unstable and do not allow epoxidation at all. Mavrikakis et al. showed that Ag happens to be in the sweet spot where the OMC intermediate and EO are equally stable on the metal surface, therefore favoring the epoxidation [42]. van Santen and coworkers compared the energetic barriers for ethylene oxidation for the three coinage metal oxides (Au, Ag, Cu) using density functional theory (DFT) calculations [43]. Among the (100) oxide surfaces, Ag2 O was shown to be the only one suitable for the catalytic epoxidation of ethylene. Ag2 O allows a barrier-free direct epoxidation of ethylene using surface atomic oxygen and does not react again with EO to decompose it. While Cu2 O is suitable for catalytic epoxidation, it can isomerize EO to AA. Since Au2 O is an unstable species, it cannot be regenerated, which disqualifies it as catalyst for epoxidation. As for Ag2 O (001) surfaces, the selectivity decreases with the presence of oxygen-vacant sites, where the formation of AA is favored. These oxygen-vacant sites are less likely to form in the presence of chlorine and cesium [44]. However cesium alone will decrease the selectivity by the formation of CsOx surface complexes that consume surface oxygen.

12.2 Epoxidation of Alkenes

12.2.2

Epoxidation of Propylene

PO is an important bulk chemical to manufacture polyurethane, unsaturated resins, surfactants, and other products (2.28 × 106 ton/year, with a 4%/year increase). Industrially, it is produced by either the chlorohydrin process or stoichiometric epoxidation, such as the Halcon process [45]. In the chlorohydrin process, it produces a large amount of chlorinated by-products that are toxic and can also erode equipment. As for the Halcon process, tert-butyl hydroperoxide is used as an oxidant, and PO is produced together with an equimolar amount of tert-butanol by-product [46]. Degussa-Uhde built in 2009 a new plant involving a more efficient process: hydrogen peroxide to propylene oxide (HPPO). Here, only water is generated as a by-product, using titanium silicalite as a catalyst. However, its commercialization has been hindered largely by the supply and demand of H2 O2 [47]. Contrary to EO, PO industrial production does not rely on silver catalyst. The epoxidation of propylene with H2 and O2 over Au catalysts supported on Ti-containing materials was first reported by the Haruta group (Scheme 12.3) [48]. Although hydrogen does not contribute to the end product, it helps generate a peroxo species at the interface of Au0 and Ti4+ , which is the active species. This said, hydrogen is not required in the case of silver. OH [Ti4+]

Au O

H2, O2

[Ti4+]

–H2O O O Au Au [Ti4+] O O H Peroxo species

Scheme 12.3 Haruta’s proposed mechanism for Au@TiO2 -catalyzed propylene epoxidation through a peroxo intermediate.

Contrary to ethylene epoxidation, the additional presence of an alpha proton on propylene leads into additional selectivity issues since it can be attacked by a nucleophilic oxygen atom adsorbed on the Ag surface [49]. Therefore authors such as Lambert [50, 51] and Lu [52] proposed using Cu as a catalyst, though so far the selectivity has been limited to 70%. Dai et al. recently provided DFT calculations for rationalizing the intermediates involved in Ag-catalyzed propylene epoxidation [53]. They revised the OMC intermediate, arguing that adsorbed atomic oxygen on Ag surfaces favored both direct epoxidation and α-H-abstraction, which leads to combustion (Scheme 12.4) [54]. Indeed, both pathways are exothermic (−0.14 and −0.16 eV, respectively, for Ag(100)), and the combustion pathway is actually kinetically favored (the energy barrier is at 0.29 eV, against 0.44 eV for epoxidation on Ag(100)). This stems from the strong nucleophilic character of the adsorbed atomic oxygen that will readily attack the α-H rather than forming the epoxide. However, by considering a new intermediate involving molecular dioxygen (OOMC), they showed that both oxygen atoms were less likely to exert α-H-abstraction. It can electrophilically attack the C=C bond, giving a higher epoxidation selectivity. One cannot exclude the coexistence of these pathways

727

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12 Silver Nanoparticles in Organic Transformations

O* αH

Ag

αH O Ag

Combustion CO2, H2O

Ag

Ag Ag

Ag

Ag

Ag

(Disfavored) O2*

O O Ag Ag Ag Ag OOMC

O PO

Scheme 12.4 Molecular oxygen vs. atomic oxygen absorption’s influence on propylene epoxidation selectivity.

during the reaction, but this constitutes a good rationale in catalyst design for tuning the selectivity. A breakthrough in the field of Ag catalysis was made by the Vajda group when they reported the successful use of Ag3 nanoclusters supported on amorphous alumina for this reaction [55]. These clusters are known to sinter (aggregate into bigger NPs) upon heating above 110 ∘ C and stabilize at 3.5 nm around 200 ∘ C. These small NPs proved to be extremely reactive for propylene epoxidation and showed an increased activity as a function of temperature, while selectivity drops past 140 ∘ C (Scheme 12.5). At 100 ∘ C, the highest selectivity was obtained (c. 90% selectivity to PO, with 10% acrolein formed). For both Ag3 and Ag NPs, the rate of PO molecules formed per surface silver atom was ∼1 s−1 at 110 ∘ C, which is much greater than that reported for any Ag catalyst. CO2 1/2 O2

O

O Propylene oxide (PO)

Acrolein (Acr)

Scheme 12.5 Epoxidation reaction of propylene and competing side reactions.

The Vajda group showed that O2 dissociation proceeded most favorably at the Ag/Al2 O3 interface [56]. Ag-borne O atoms were found to be responsible for PO formation, while Al2 O3 -borne ones were responsible for acrolein formation. In addition, the barrier to O2 dissociation on these Ag@Al2 O3 was small compared with that on crystalline Ag surfaces, which accounts for a higher activity overall. Ag20 nanoclusters have been studied in the context of propylene epoxidation through DFT calculations by Kuz’menko and coworkers [57]. Molecular oxygen coordinates preferentially on edge or apex positions of Ag NPs, leading into an electron density transfer from silver to oxygen and generating cationic Agδ+ sites. These sites also favorably bind propylene and go through a four-member OMC

12.2 Epoxidation of Alkenes

intermediate that has a low activation barrier toward PO formation. Similarly to ethylene epoxidation, (100) Ag facets were more selective than (111) facets [58], and chlorides boosted the selectivity to PO [59]. Lu and coworkers reported the use of bimetallic Ag–Cu catalysts supported on BaCO3 for propylene epoxidation [52]. The highest PO selectivity of 55.1% and the propylene conversion of 3.6% were achieved over Ag95 –Cu5 @BaCO3 bimetallic catalyst. The doping of 5% Cu in Ag helped increase the electropositivity of Ag, as shown by XPS, and boosted oxygen adsorption to restrain Ag NP agglomeration. A selectivity of 71.2% was achieved by the same group by impregnating ppm levels of CuCl2 on the catalyst, where Cl− effect has been shown to exalt Ag’s electropositivity [60]. Other Ag supports have been successfully reported since for this reaction, such as molybdenum oxide-impregnated silver supported on zirconium oxide (Ag–MoO3 @ZrO2 ) [61], as well as Ag–Y2 O3 –K2 O@Al2 O3 [62], ball-milled Ag@CaCO3 [63, 64], and Ag@NaCl [65]. 12.2.3

Epoxidation of Styrene and Other Alkenes

Styrene epoxidation has been reported in a wider variety of methods, including enzymatic systems for enantioselective epoxidations such as P450 [66], styrene monooxygenase [67], or microbial systems [68]. Industrially, oxidation of styrene is carried out by using stoichiometric amounts of organic peracids as oxidant. tert-Butyl hydrogen peroxide (TBHP) [69, 70], H2 O2 [71], molecular oxygen [72– 74], and mixtures [75] are more common oxidants on the lab scale. Ag catalysts are also active for this reaction, and, again, (100) facets provided the best activity, as shown by Li and coworkers [76]. As a result, the rate for this reaction over Ag nanocubes was more than fourteen times higher than that on nanoplates and four times higher than that on near-spherical NPs. Luck and coworker reported the use of mesoporous MCM-41 silica as a support for Ag NPs [77]. Using TBHP as a radical initiator (the actual oxidant being air), they managed to oxidize 4 alkenes with varying selectivities (Scheme 12.6). Cyclohexene gave 2-cyclohexen-1-one as a major product, whereas cyclooctene gave the corresponding epoxide as a major product. Benzaldehyde was formed in majority when styrene was oxidized. Using 1,2-dichloroethane (DCE) as a solvent, the Ag surfaces passivated completely via formation of an AgCl layer. The same effect can be observed by using NaCl in a H2 O/tBuOH. H2 O2 could not be

R

R′

Ag@MCM-41 (5 mol%) TBHP for the first cycle H2O2 for subsequent cycles (5 mol%)

O R

DCE/MeCN (10/1), air, 90 °C, 24–72 h

R′

(Recyclable 4 times) O +

O n

n

n

n = 1 : 99% conversion, 68% selectivity for the enone n = 3 : 75% conversion, 98% selectivity for the epoxide

Scheme 12.6 Ag@MCM-41-catalyzed oxidations of olefins.

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12 Silver Nanoparticles in Organic Transformations

used as a radical initiator with the fresh catalyst as it decomposed immediately upon exposure to the catalyst. On subsequent recycling cycles however, due to the surface passivation of the catalyst with chlorides, H2 O2 was compatible and used instead of TBHP. Chen and coworkers reported the synthesis of magnetically recyclable Ag@Fe3 O4 performed under hydrothermal conditions [78]. It was active for styrene epoxidation using TBHP, affording a turnover frequency (TOF) of 1473 mmol mol−1 h−1 with the added benefit of being recyclable five times with no deactivation. The presence of Fe3 O4 was claimed to assist the epoxidation by providing additional reactive oxygen sites. The authors eventually developed a series of magnetically supported mixed metal–Ag NPs AgM1−x @Fe2+x O4 (M = Co, Ni, Mn, Zn) [79]. Li and coworkers used carbon nanofibers (CNFs) as supports for various forms of Ag nanocatalysts [80, 81]. By electrospinning deposition, they decorated CNF with Ag NPs before they were calcinated to obtain the active catalyst (Scheme 12.7). Whether an oxide was added as a promoter or not (MgO, Al2 O3 ), their optimized conditions all gave similar results for the epoxidation of styrene (43% conversion, 39% selectivity to styrene oxide). Ag-M-CNF (30 mg) TBHP (6 equiv.)

O

5 ml iPrOH, 80 °C, 8 h 43% conversion 39% selectivity M = MgO, Al2O3, no oxide

Scheme 12.7 CNF-supported Ag for styrene epoxidation.

Magnesium and aluminum oxides as double-layered oxides (DLO) have been exploited by Xu and coworkers as well, showing improved catalytic performances (Scheme 12.8) [82]. O

Ag@DLO (2.76 %) TBHP (7 equiv.), MeCN, 82 °C,18 h

80% conversion 90% selectivity

Scheme 12.8 Epoxidation of styrene catalyzed by Ag@DLO.

The Li group eventually opted for a different strategy by loading silver in zeolite using supercritical carbon dioxide and hydrogen as a reductant [83, 84]. These small and monodisperse NPs (3–6 nm) showed an improved performance for styrene epoxidation using different oxides to tune the selectivity to styrene oxide or benzaldehyde (Scheme 12.9). Activated layered manganese oxides are inexpensive supports that can be used for styrene epoxidation in conjunction with sodium carbonate, hydrogen

12.2 Epoxidation of Alkenes

Ag@4A-zeolite (2 wt%) oxidant

O O

+

MeCN, 82 °C TBHP (24 h) 98% conversion 89% selectivity to styrene oxide

H2O2 (6 h) 84% conversion 96% selectivity to benzaldehyde

Scheme 12.9 Zeolite-supported Ag for styrene epoxidation.

peroxide, and either gold or silver, as shown by Bagherzadeh and coworkers (Scheme 12.10) [85]. A mechanism was proposed by the authors where silver and manganese act in conjunction to activate the alkene (Scheme 12.11). Sodium carbonate helps activate hydrogen peroxide into HCO4 − [86], which ultimately provides the oxygen atom for the epoxidation. Ag@MnOx (3.4 mol%) H2O2 (4 equiv.), NaHCO3 (20 mol%)

R′

R

MeCN, rt., 4 h

R

O

R′ 31–93% conversion 6 examples (recyclable 4 times)

Scheme 12.10 Ag supported on manganese oxide for alkene epoxidation using hydrogen peroxide.

R

O R′ AgMnOx

R′ R

R

O O O

R

R′

R′

O AgMnOx

AgMnOx HCO4–

HCO3–

H2O

H2O2

Scheme 12.11 Proposed mechanism for carbonate-assisted epoxidation of alkenes.

Raichur and coworkers reported the synthesis of hollow silver nanocages built using silica as a sacrificial template [87]. Because of the increased surface area, the nanocages showed high reactivity and selectivity toward TBHP-induced alkene epoxidation and were recyclable up to four times (Scheme 12.12). Methyltrimethoxysilane/3-mercaptopropyltrimethoxysilane hybrid films (Ag@MeTMS/MPTPS) have been showed by Macquarrie and coworkers to be

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12 Silver Nanoparticles in Organic Transformations

R

R′

Ag nanocage (20 w/w%) TBHP (1–2 equiv.)

O R

MeCN, 65 °C, 4 h

R′ 63–82% conversion 80–89% selectivity 6 examples (recyclable 4 times)

Scheme 12.12 Ag nanocage as recyclable catalyst for alkene epoxidation.

suitable supports for silver in catalyzing styrene epoxidation under microwave [88]. The thiols allowed the stabilization of Ag NPs, making the catalyst recyclable up to four times. However, it was shown that Ag slowly leached into solution, thus explaining the high selectivity and activity, similar to the one of homogeneous AgNO3 (Scheme 12.13). O

Ag@MeTMS/MPTMS (1 wt%) H2O2 (2 equiv.), 142 °C, mW, 15 min

>99% conversion 76% selectivity

Scheme 12.13 Epoxidation of styrene catalyzed by Ag@MeTMS/MPTPS under microwave.

Bal and coworkers used Ag/Mn3 O4 nanowhiskers for styrene epoxidation, using cetyl alcohol as a soft template to obtain the nanowhiskers after calcination [89]. Their system is remarkable in that they used oxygen (10 bar) as an oxidant, affording a full selectivity to styrene oxide (Scheme 12.14). The catalyst did not leach and was recyclable up to five times. Ag–Mn3O4 nanowhiskers

O

O2 (10 bar), 80 °C, 25 h 100% conversion 67% selectivity (recyclable 5 times)

Scheme 12.14 Styrene epoxidation under oxygen with Ag/Mn3 O4 nanowhiskers.

Polyoxometalates (POM) such as H5 PV2 Mo10 O40 are also suitable supports for catalysis, as shown by Neumann and coworker [90]. This particular species was shown to inhibit free radical autoxidation reactions by the same group [91, 92] and possess a high anionic charge for NP stabilization [93]. Both properties supported their use in the silver-catalyzed epoxidation of alkenes in air. Among the metals tested, Ru and Ag proved to give the best catalytic results, though they observed some product loss due to the formation of oxygenated polymeric products (Scheme 12.15).

12.3 Alcohol Oxidation

R

R′

O

Ag-POM@Al2O3, O2 (2 bar) CF3-Ph, 170 °C, 30–60 min

R R′ 18–66 yield% 6 examples

Scheme 12.15 Aerobic epoxidation of alkenes using Ag-POM supported on alumina.

Kobe et al. finally pointed in their survey on industrial epoxidation the emergence of 3,4-epoxybut-1-ene (EpB) production, developed by Eastman Chemical Company [15]. EpB has four nonequivalent carbons along with two functional groups (epoxy and vinyl), hence its considerable potential as a chemical intermediate. For example, Eastman Chemical Company proposed the manufacturing of 1,4-butanediol from EpB [94], which is itself a precursor of THF and biodegradable plastics such as poly(butylene succinate) [95]. In conclusion, the silver-catalyzed epoxidation of simple alkenes such as ethylene and propylene, using oxygen as an oxidant, has been widely studied. In contrast, a wider variety of oxidants has been reported for bigger alkenes, reflecting the better availability of peroxides on the lab scale with oxygen remaining the most atom-economical choice. For all cases, the trend for facet selectivity is consistent, with the (100) facet favoring the formation of the epoxide.

12.3 Alcohol Oxidation The oxidation of methanol to formaldehyde over Ag is considered to be the first successful example of heterogeneous catalysis [96]. Along with Cu- and Au-catalyzed oxidation of methanol, these represent one of the oldest industrial catalytic technologies dating back to the 1880s and the first non-Pt-based catalytic industrial processes. Since then, Ag has gradually been replaced by Fe/Mo catalysts in the industry for methanol oxidation, now accounting for 45% of world’s production of formaldehyde [5, 6]. On the lab scale, the reactivity of Ag NPs has been extended to the oxidation of a variety of benzylic and aliphatic alcohols using oxygen as an oxidant and will be covered in this part. The mechanism of alcohol oxidation over metal NPs was described in an excellent review by Davis and coworkers [97] and is illustrated in Scheme 12.16. First, the hydroxy group is deprotonated, while the alkoxide binds to the metal surface. For coinage metals, this step typically requires the presence of a base since they feature poor ability for alcohol proton abstraction, unlike platinum-group metals (PGM) (see 12.4.1 Carbonyl reduction) [98]. Indeed, M—H bonds are poorly stable when M is a coinage metal [99]. With metal oxide support such as Al2 O3 or SiO2 , the lattice oxygen can act as the base. As explained below, alternatively, silver oxide can also act as a base. Then, a β-hydride elimination occurs, leading to the formation of the carbonyl. The metal hydride then gets oxidized. If dioxygen is present, the overall reaction is called aerobic oxidation, and the hydride is quenched to form water. In cases where aldehydes are formed from primary alcohols, selectivity can be an issue as the aldehyde may react further with water

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12 Silver Nanoparticles in Organic Transformations

[B]: base or basic site [M]: active site on the NP R′ H H

R O

HO

O

Deprotonation, Metal-alkoxide formation R

O

R′ H

[B]–, [M]

H

HO Over-oxidation

[M]–

R′ β-Hydride elimination

R + O

H [M]–

No O2, H+ R

OH

R + [B]-H

H

R + H 2O O

O2 R′ = H

H2 Metal hydride oxidation

Scheme 12.16 Mechanism of the metal nanoparticle-catalyzed alcohol oxidation.

to form geminal diols and ultimately carboxylic acids by β-hydride elimination. Conversely, if anaerobic conditions are used, the hydride can recombine with the proton from the first step to form hydrogen gas. Here, the poor binding affinity of Ag for hydrides helps drive the dehydrogenation forward (see 3.1-carbonyl reduction). In this case, the overall reaction is called alcohol dehydrogenation. Since no oxygen is present, there is no over-oxidation issue. Furthermore, the presence of water may lead to catalyst deactivation [100]. However, Liu et al. questioned the distinction between alcohol aerobic oxidation and dehydrogenation in a recent study [101]. From a thermodynamics standpoint, alcohol dehydrogenation is energetically uphill, with a positive enthalpy of reaction. Entropy being the sole driving force, only temperatures above 200 ∘ C may favor the equilibrium toward the carbonyl and H2 products. For example, the Gibbs free energy of the dehydrogenation of benzyl alcohol to benzaldehyde and H2 is +33.4 kJ mol−1 at 25 ∘ C, but this decreases to +20.6 kJ mol−1 at 120 ∘ C and +9.7 kJ mol−1 at 200 ∘ C. Water formation having a highly negative Gibbs free energy of −230.8 kJ mol−1 under standard conditions seems the only way to rationalize alcohol oxidation at low temperatures. This suggests that trace amounts of oxygen in the reaction are necessary to drive the reaction under such conditions. This also explains why reported alcohol dehydrogenation-based oxidation processes are typically taking place under harsher conditions than their aerobic counterparts. The nature and speciation of the Ag NP surface is central to the catalytic alcohol oxidation, as highlighted by Yang et al. [102]. The absorption of O2 on the silver surface and the formation of Ag–O pairs play a key role in its reactivity. According to Sanderson’s classification of transition metal oxides, the oxygen in the Ag–O pair bears the strongest negative effective charge (−0.46e), along with Cu2 O (−0.44e) [103]. This provides the basic site on the surface for deprotonating the hydroxy function. On the other side, an acidic site must be provided to abstract the α-hydrogen of the alcohol. Ag+ is a soft acid according to Misono’s classification, with a parameter of 3.99, compared with harder acids such as Cu+ and Cu2+ [104]. This will minimize the interaction with the hydroxy group and avoid alcohol dehydration into alkenes, which is another unwanted outcome in alcohol oxidation (Scheme 12.17). Therefore, the Ag–O pair acts as a strong Lewis base/soft Lewis acid pair, whereby the good basicity of the O site favors alcohol

12.3 Alcohol Oxidation

O

O2, –H2O

Oδ–

H

Agδ+

O

H H

R

Aerobic oxidation

H

H H

O [M] R

–H2O

H

Dehydration

O

O2 Over-oxidation HO

R

O

–H2 Dehydrogenation

H

R

R

H R

H

Scheme 12.17 Alcohol oxidation: pathways and side reactions.

dehydrogenation, while the low acidity of the Ag site limits dehydration side reactions. Cu oxide, on the contrary, features weaker Lewis base/stronger Lewis acid pair and is less efficient for the selective oxidation of alcohols. In the following, we describe selected examples of both proposed pathways for this reaction: the aerobic oxidation and the dehydrogenation. 12.3.1

Aerobic Alcohol Oxidation

One of the most efficient systems in terms of silver loading was proposed by Hosseini-Monfared and coworker where they supported Ag on different graphene-based supports for the aerobic oxidation of benzyl alcohol (Scheme 12.18) [105]. N-Hydroxyphthalimide (NHPI) was used to increase both the oxidation conversion (from 7% without NHPI to 61%) and selectivity to benzaldehyde (from 19% to 58%). Indeed NHPI has been shown previously to react with cobalt to generate N-oxyl radicals by electron transfer, initiating a radical chain mechanism with alkene and oxygen to generate epoxides [106]. By functionalizing graphene with thiols (Ag@GOSH), they enabled a better adhesion and dispersion of Ag on the support, making it recyclable five times with no silver leaching.

OH

Ag@GO or Ag@GOSH (1.3 mol% Ag), NHPI MeCN/PhCl (5/1) O2 (1 atm), 80 °C

O O

N-OH NHPI O

Ag@GO: 33% conversion, 55% selectivity Ag@GOSH: 61% conversion, 58% selectivity (recyclable 5 times)

Scheme 12.18 Graphite-supported Ag NPs for aerobic oxidation of benzyl alcohol.

CeO2 is able to reversibly bind O2 and can serve as an oxygen storage material. In the context of catalytic oxidation, it helps provide active oxygen sites. For instance, Kundakovic and Flytzani-Stephanopoulos boosted Ag and Cu oxide catalytic activity in methane oxidation by supporting them onto CeO2 [107]. Beier

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et al. exploited this material for the oxidation of alcohols using a mixture of CeO2 NPs and Ag supported on SiO2 (Scheme 12.19) [100]. They compared the catalytic activity of Ag@SiO2 with Pd supported on Al2 O3 , showing that Ag benefited more from CeO2 addition (6–98% conversion increase) than Pd (81–94% conversion) with a high selectivity (>95% for Ag in both cases and