Organic synthesis : state of the art 2013-2015 9780190646165, 0190646160

Table of contents :
Content: PrefaceOrganic Functional Group Interconversion and Protection1. Organic Functional Group Interconversion 2. Organic Functional Group Interconversion3. Organic Functional Group Interconversion4. Oxidation5. Functional Group Oxidation and Reduction6. Oxidation of Organic Functional Groups7. New Methods for Reduction and for Oxidation8. Reductions9. Reduction of Organic Functional Groups10. Organic Functional Group Protection11. Organic Functional Group Protection and Deprotection12. Organic Functional Group Protection13. Functional Group Protection: The Pohl Synthesis of b-1,4-Mannuronate OligomersFlow Methods14. Flow Chemistry: The Direct Production of Drug Metabolites15. Developments in Flow Chemistry16. Flow ChemistryC-H Functionalization17. Selective Functionalization of C-H Bonds 18. C-H Functionalization: The Snyder Synthesis of (+)-Scholarisine A19. C-H Functionalization: The Maimone Synthesis of Podophyllotoxin20. C-H Functionalization: The Shaw Synthesis of E-d-ViniferinCarbon-Carbon Bond Construction21. C-C Bond Construction: The Zhu Synthesis of Goniomitine22. C-C Bond Construction: The Kingsbury Synthesis of (-)-Dihydrocuscohygrine23. C-C Bond Construction: The Galano Synthesis of 8-F3t-Isoprostane24. C-C Bond Construction: The Hou Synthesis of (-)-Brevipolide HReactions of Alkenes25. Alkenes26. Alkene Reactions: The Xu/Loh Synthesis of Vitamin A127. Reactions of Alkenes28. Reactions of Alkenes: The Usami Synthesis of (-)-Pericosine EEnantioselective Construction of Acyclic Stereogenic Centers29. Construction of Single Stereocenters30. Enantioselective Synthesis of Alcohols and Amines: The Zhu Synthesis of (+)-Trigonoliimine A31. Enantioselective Synthesis of Alcohols and Amines: The Kim Synthesis of (+)-Frontalin32. Enantioselective Synthesis of Alcohols and Amines: The Doi Synthesis of Apratoxin C33. Construction of Alkylated Stereocenters34. Enantioselective Construction of Alkylated Centers: The Rawal Synthesis of (+)-Fornicin C35. Alkylated Stereogenic Centers: The Jia Synthesis of (-)-Goniomitine36. Construction of Alkylated Stereogenic Centers: The Zhu Synthesis of (-)-Rhazinilam37. Construction of Multiple Stereocenters38. Arrays of Stereogenic Centers: The Yadav Synthesis of Nhatrangin A39. Arrays of Stereogenic Centers: The Thomson Synthesis of (-)-Galcatin40. Arrays of Stereogenic Centers: The Shin/Chandrasekhar Synthesis of (+)-LactacystinConstruction of C-O Rings41. C-O Ring Construction. The Martin and Martin Synthesis of Teurilene 42. C-O Ring Formation43. C-O Ring Construction: The Tong Synthesis of (-)-Aculeatin A44. C-O Ring Construction: The Smith Synthesis of (+)-18-epi-Latrunculol A45. C-O Ring Construction: The Oger/Lee/Galano Synthesis of 7(RS)-ST-D8-11-dihomo-Isofuran46. C-O Ring-Containing Natural Products: Cyanolide A (Krische), Bisabosqual A (Parker), Iso-Eriobrucinol A (Hsung), Trichodermolide A (Hiroya), Batrachotoxin Core (Du Bois) 47. Total Synthesis of C-O Natural Products48. C-O Natural Products: DihomoIsoF (Lee/Galano), Pyrenolide D (Gracza), Clavilactone A (Li), Psoracorylifol A (Tong), Bermudenynol (Kim), Aspercyclide C (Hirama)49. C-O Ring Construction: Sauropus hexoside (Xie/Wu), (+)-Ipomeamarone (Usuki), Decytospolide A (Fujioka), Cytospolide P (Goswami), (+)-Didemniserinolipid B (Tong), Gymnothelignan N (She)50. C-O Ring Containing Natural Products: (+)-Isatisine A (Panek), Cephalasporolide E (Sartillo-Piscil), (+)-Xestodecalactone (Jennings), Colchilomycin B (Banwell), Lactimidomycin (Georg), 5,6-Dihydrocineromycin B (Furstner)Construction of C-N Rings51. C-N Ring Construction: The Waser Synthesis of Jerantinine E52. C-N Ring Construction: The Glorius Synthesis of ent-Monomorine53. C-N Ring Construction: The Weinreb Synthesis of Myrioneurinol54. C-N Ring Construction: The Hattori Synthesis of (+)-Spectaline55. Alkaloid Synthesis: (-)-L-Batzellaside A (Toyooka), Limazepine A (Zemribo), (+)-Febrifugine (Pansare), Amathaspiramide F (Tambar), Allomatrine (Brown), Lyconadine C (Waters), Tabersonine (Andrade)56. Alkaloid Synthesis: Penaresidin A (Subba Reddy), Allokainic Acid (Saicic), Sedacryptine (Rutjes), Lepistine (Yokoshima/Fukuyama), Septicine (Hanessian), Lyconadin C (Dai)57. Alkaloid Synthesis: Indolizidine 223AB (Cha), Lepadiformine (Kim), Kainic Acid (Fukuyama), Gephyrotoxin (Smith), Premarineosin A (Reynolds)58. Alkaloid Synthesis: (-)-a-Kainic Acid (Ohshima), Serpentine (Scheidt), (-)-Galanthamine (Jia), (+)-Trigolutes B (Gong), Sarain A (Yokoshima/Fukuyama), DZ-2384 (Harran)Substituted Benzene Derivatives59. Preparation of Benzene Derivatives: The Yu/Baran Synthesis of (+)-Hongoquercin A60. Substituted Benzenes: The Garg Synthesis of Tubingensin A61. Substituted Benzenes: The Li Synthesis of Rubriflordilactone A62. Preparation of Substituted Benzenes: The Beaudry Synthesis of ArundamineHeteroaromatic Derivatives63. Preparation of Heterocycles: The Boukouvalas Synthesis of (-)-Auxofuran64. Heteroaromatic Synthesis: The Tokuyama Synthesis of (-)-Rhazinilam65. Heteroaromatics: The Zhou/Li Synthesis of Goniomitine66. Heteroaromatic Construction: The Li Synthesis of Mycoleptodiscin AOrganocatalyzed C-C Ring Construction67. Organocatalyzed C-C Ring Construction: The Carreira Synthesis of (+)-Crotogoudin68. Organocatalyzed C-C Ring Construction: The Jorgenson Synthesis of (+)-Estrone69. Organocatalyzed C-C Ring Construction: The Bradshaw/Bonjoch Synthesis of (-)-Cermizine B70. Organocatalyzed C-C Ring Construction: The Mihovilovic Synthesis of Piperenol BMetal-Mediated C-C Ring Construction71. Metal-mediated C-C Ring Construction: The Carreira Synthesis of (+)-Asperolide C72. Metal-Mediated C-C Ring Construction: The Sun/Lin Synthesis of Huperzine A73. Metal-Mediated C-C Ring Construction: The Ding Synthesis of (-)-Indoxamycin B74. Metal-Mediated C-C Ring Construction: The Lei Synthesis of (-)-Huperzine QIntermolecular and Intramolecular Diels-Alder Reactions75. Diels-Alder Cycloaddition: Pancratistatin (Cho), Reddy (Nootkatone), Zhang/Lee (Platensimycin), Nakada (Scabronine G), Isoglaziovianol (Trauner)76. Diels-Alder Cycloaddition: Fawcettimine (Zhai), Sculponeatin N (Zhai), Elansolid B1 (Kirschning), Frondosin A (Wright), Kingianin H (Parker), Rufescenolide (Snyder)77. Diels-Alder Cycloaddition: Nicolaioidesin B (Coster), Lycorine (Cho), Bucidarasin A (Nakada), Maoecrystal V (Thomson), Kuwanon J (Wulff/Lei), Vinigrol (Kaliappan)78. Diels-Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (-)-G-J aglycone (Paddon-Row/Sherburn), IBIR-22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone)Stereocontrolled C-C Ring Construction79. Other Methods for C-C Ring Construction: Pinolinone (Bach), Agelastatin A (Batey), Panaginsene (Lee), Salvileucalin D, Salvileucalin C (Ding), ent-Codeine (Hudlicky), Walsucochin B (Xie/Shi)80. Carbocyclic Ring Construction: The Nicolaou Synthesis of Myceliothermophin EClassics in Total Synthesis81. The Inoue Synthesis of 19-Hydroxysarmentogenin 82. The Nakada Synthesis of (+)-Ophiobolin A 83. The Herzon Synthesis of (-)-Acutumine84. The Njardarson Synthesis of Vinigrol85. The Gin Synthesis of Neofinaconitine86. The Li Synthesis of Daphenylline87. The Baran Synthesis of Ingenol88. The Furstner Synthesis of Amphidinolide F89. The Deslongchamps Synthesis of (+)-Cassaine90. The Kan Synthesis of the Streptomyces Alkaloid SB-20320791. The Trost Synthesis of (-)-Lasonolide A92. The Fukuyama Synthesis of (-)-Lepenine93. The Smith Synthesis of (-)-Calyciphylline N94. The Paterson Synthesis of (-)-Leiodermatolide95. The Fuwa Synthesis of Didemnaketal B96. The Lee Synthesis of (-)-Crinipellin A97. The Snyder Synthesis of Psylloborine A98. The Morken Synthesis of (+)-Discodermolide99. The Trauner Synthesis of (-)-Nitidasin100. The Hoveyda Synthesis of Disorazole C1101. The Smith Synthesis of (-)-Nodulisporic Acid D102. The Sato/Chida Synthesis of Paclitaxel (Taxol (R))103. The Johnson Synthesis of Paspaline104. The Ding Synthesis of Steenkrotin A

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Organic Synthesis

ORGANIC SYNTHESIS STATE OF THE ART 2013–​2015 Douglass F. Taber and

Tristan H. Lambert

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1 Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford is a registered trade mark of Oxford University Press in the UK and certain other countries. Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America. © Oxford University Press 2017 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by license, or under terms agreed with the appropriate reproduction rights organization. Inquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above. You must not circulate this work in any other form and you must impose this same condition on any acquirer. Library of Congress Cataloging-in-Publication Data Names: Taber, D. F. (Douglass F.), 1948- | Lambert, Tristan H. Title: Organic synthesis : state of the art, 2013-2015 / Douglass F. Taber and Tristan H. Lambert. Description: New York, NY : Oxford University Press, [2017] | Includes bibliographical references and index. Identifiers: LCCN 2016040523 | ISBN 9780190646165 (hardback) Subjects: LCSH: Organic compounds—Synthesis—Research. Classification: LCC QD262 .T286 2017 | DDC 547/.2—dc23 LC record available at https: //lccn.loc.gov/2016040523 9 8 7 6 5 4 3 2 1 Printed by Sheridan Books, Inc., United States of America

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Contents

xi Preface Part I  Organic Functional Group Interconversion and Protection

2  1. Organic Functional Group Interconversion 4  2. Organic Functional Group Interconversion 6  3. Organic Functional Group Interconversion 8 4. Oxidation 10  5. Functional Group Oxidation and Reduction 12  6. Oxidation of Organic Functional Groups 14  7. New Methods for Reduction and for Oxidation 16  8. Reductions 18  9. Reduction of Organic Functional Groups 20  10. Organic Functional Group Protection 22  11. Organic Functional Group Protection and Deprotection 24  12. Organic Functional Group Protection 26  13. Functional Group Protection: The Pohl Synthesis of β-​1,4-​Mannuronate Oligomers Part II  Flow Methods

28  14. Flow Chemistry: The Direct Production of Drug Metabolites 30  15. Developments in Flow Chemistry 32  16. Flow Chemistry Part III  C–​H Functionalization

34  36  38  40 

17. Selective Functionalization of C–​H Bonds 18. C–​H Functionalization: The Snyder Synthesis of (+)-​Scholarisine A 19. C–​H Functionalization: The Maimone Synthesis of Podophyllotoxin 20. C–​H Functionalization: The Shaw Synthesis of E-​δ-​Viniferin

Part IV  Carbon–​Carbon Bond Construction

42  21. C–​C Bond Construction: The Zhu Synthesis of Goniomitine 44  22. C–​C Bond Construction: The Kingsbury Synthesis of (−)-​Dihydrocuscohygrine

Contents  vi

46  23. C–​C Bond Construction: The Galano Synthesis of 8-​F3t-​Isoprostane 48  24. C–​C Bond Construction: The Hou Synthesis of (−)-​Brevipolide H Part V  Reactions of Alkenes

50  52  54  56 

25. Alkenes 26. Alkene Reactions: The Xu/​Loh Synthesis of Vitamin A1 27. Reactions of Alkenes 28. Reactions of Alkenes: The Usami Synthesis of (−)-​Pericosine E

Part VI  Enantioselective Construction of Acyclic Stereogenic Centers

58  29. Construction of Single Stereocenters 60  30. Enantioselective Synthesis of Alcohols and Amines: The Zhu Synthesis of (+)-​Trigonoliimine A 62  31. Enantioselective Synthesis of Alcohols and Amines: The Kim Synthesis of (+)-​Frontalin 64  32. Enantioselective Synthesis of Alcohols and Amines: The Doi Synthesis of Apratoxin C 66  33. Construction of Alkylated Stereocenters 68  34. Enantioselective Construction of Alkylated Centers: The Rawal Synthesis of (+)-​Fornicin C 70  35. Alkylated Stereogenic Centers: The Jia Synthesis of (−)-​Goniomitine 72  36. Construction of Alkylated Stereogenic Centers: The Zhu Synthesis of (−)-​Rhazinilam 74  37. Construction of Multiple Stereocenters 76  38. Arrays of Stereogenic Centers: The Yadav Synthesis of Nhatrangin A 78  39. Arrays of Stereogenic Centers: The Thomson Synthesis of (−)-​Galactin 80  40. Arrays of Stereogenic Centers: The Shin/​Chandrasekhar Synthesis of (+)-​Lactacystin Part VII  Construction of C–​O Rings

82  84  86  88  90  92 

94  96 

41. C–​O Ring Construction: The Martín and Martín Synthesis of Teurilene 42. C–​O Ring Formation 43. C–​O Ring Construction: The Tong Synthesis of (−)-​Aculeatin A 44. C–​O Ring Construction: The Smith Synthesis of (+)-​18-​epi-​Latrunculol A 45. C–​O Ring Construction: The Oger/​Lee/​Galano Synthesis of 7(RS)-​ST-​∆8-​11-​dihomo-​Isofuran 46. C–​O Ring-​Containing Natural Products: Cyanolide A (Krische), Bisabosqual A (Parker), Iso-​Eriobrucinol A (Hsung), Trichodermatide A (Hiroya), Batrachotoxin Core (Du Bois) 47. Total Synthesis of C–​O Natural Products 48. C–​O Natural Products: DihomoIsoF (Lee/​Galano), Pyrenolide D (Gracza), Clavilactone A (Li), Psoracorylifol A (Tong), Bermudenynol (Kim), Aspercyclide C (Hirama)

Part VIII  Construction of C–​N Rings

102  104  106  108  110 

51. 52. 53. 54. 55.

C–​N Ring Construction: The Waser Synthesis of Jerantinine E C–​N Ring Construction: The Glorius Synthesis of ent-​Monomorine C–​N Ring Construction: The Weinreb Synthesis of Myrioneurinol C–​N Ring Construction: The Hattori Synthesis of (+)-​Spectaline Alkaloid Synthesis: (−)-​L -​Batzellaside A (Toyooka), Limazepine A (Zemribo), (+)-​Febrifugine (Pansare), Amathaspiramide F (Tambar), Allomatrine (Brown), Lyconadine C (Waters), Tabersonine (Andrade) 112  56. Alkaloid Synthesis: Penaresidin A (Subba Reddy), Allokainic Acid (Saicic), Sedacryptine (Rutjes), Lepistine (Yokoshima/​Fukuyama), Septicine (Hanessian), Lyconadin C (Dai) 114  57. Alkaloid Synthesis: Indolizidine 223AB (Cha), Lepadiformine (Kim), Kainic Acid (Fukuyama), Gephyrotoxin (Smith), Premarineosin A (Reynolds) 116  58. Alkaloid Synthesis: (−)-​α-​Kainic Acid (Ohshima), Serpentine (Scheidt), (−)-​Galanthamine ( Jia), (+)-​Trigolutes B (Gong), Sarain A (Yokoshima/​Fukuyama), DZ-​2384 (Harran) Part IX  Substituted Benzene Derivatives

118  59. Preparation of Benzene Derivatives: The Yu/​Baran Synthesis of (+)-​Hongoquercin A 120  60. Substituted Benzenes: The Garg Synthesis of Tubingensin A 122  61. Substituted Benzenes: The Li Synthesis of Rubriflordilactone A 124  62. Preparation of Substituted Benzenes: The Beaudry Synthesis of Arundamine Part X  Heteroaromatic Derivatives

126  63. Preparation of Heterocycles: The Boukouvalas Synthesis of (−)-​Auxofuran 128  64. Heteroaromatic Synthesis: The Tokuyama Synthesis of (−)-​Rhazinilam 130  65. Heteroaromatics: The Zhou/​Li Synthesis of Goniomitine 132  66. Heteroaromatic Construction: The Li Synthesis of Mycoleptodiscin A

vii  Contents

98  49. C–​O Ring Construction: Sauropus Hexoside (Xie/​Wu), (+)-​Ipomeamarone (Usuki), Decytospolide A (Fujioka), Cytospolide P (Goswami), (+)-​Didemniserinolipid B (Tong), Gymnothelignan N (She) 100  50. C–​O Ring-​Containing Natural Products: (+)-​Isatisine A (Panek), Cephalasporolide E (Sartillo-​Piscil), (+)-​Xestodecalactone ( Jennings), Colchilomycin B (Banwell), Lactimidomycin (Georg), 5,6-​Dihydrocineromycin B (Fürstner)

Contents  viii

Part XI  Organocatalyzed C–​C Ring Construction

134  67. Organocatalyzed C–​C Ring Construction: The Carreira Synthesis of (+)-​Crotogoudin 136  68. Organocatalyzed C–​C Ring Construction: The Jørgenson Synthesis of (+)-​Estrone 138  69. Organocatalyzed C–​C Ring Construction: The Bradshaw/​Bonjoch Synthesis of (−)-​Cermizine B 140  70. Organocatalyzed C–​C Ring Construction: The Mihovilovic Synthesis of Piperenol B Part XII  Metal-​Mediated C–​C Ring Construction

142  71. Metal-​Mediated C–​C Ring Construction: The Carreira Synthesis of (+)-​Asperolide C 144  72. Metal-​Mediated C–​C Ring Construction: The Sun/​Lin Synthesis of Huperzine A 146  73. Metal-​Mediated C–​C Ring Construction: The Ding Synthesis of (−)-​Indoxamycin B 148  74. Metal-​Mediated C–​C Ring Construction: The Lei Synthesis of (−)-​Huperzine Q Part XIII  Intermolecular and Intramolecular Diels-​Alder Reactions

150  75. Diels–​Alder Cycloaddition: Pancratistatin (Cho), Nootkatone (Reddy), Platensimycin (Zhang/​Lee), Scabronine G (Nakada), Isoglaziovianol (Trauner) 152  76. Diels–​Alder Cycloaddition: Fawcettimine (Zhai), Sculponeatin N (Zhai), Elansolid B1 (Kirschning), Frondosin A (Wright), Kingianin H (Parker), Rufescenolide (Snyder) 154  77. Diels–​Alder Cycloaddition: Nicolaioidesin B (Coster), Lycorine (Cho), Bucidirasin A (Nakada), Maoecrystal V (Thomson), Kuwanon J (Wulff/​Lei), Vinigrol (Kaliappan) 156  78. Diels–​Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (−)-​G-​J Aglycone (Paddon-​Row/​Sherburn), IBIR-​22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone) Part XIV  Stereocontrolled C–​C Ring Construction

158  79. Other Methods for C–​C Ring Construction: Pinolinone (Bach), Agelastatin A (Batey), Panaginsene (Lee), Salvileucalin D, Salvileucalin C (Ding), ent-​Codeine (Hudlicky), Walsucochin B (Xie/​Shi) 160  80. Carbocyclic Ring Construction: The Nicolaou Synthesis of Myceliothermophin E

162  164  166  168  170  172  174  176  178  180  182  184  186  188  190  192  194  196  198  200  202  204  206  208 

81. The Inoue Synthesis of 19-​Hydroxysarmentogenin 82. The Nakada Synthesis of (+)-​Ophiobolin A 83. The Herzon Synthesis of (−)-​Acutumine 84. The Njardarson Synthesis of Vinigrol 85. The Gin Synthesis of Neofinaconitine 86. The Li Synthesis of Daphenylline 87. The Baran Synthesis of Ingenol 88. The Fürstner Synthesis of Amphidinolide F 89. The Deslongchamps Synthesis of (+)-​Cassaine 90. The Kan Synthesis of the Streptomyces Alkaloid SB-​203207 91. The Trost Synthesis of (−)-​Lasonolide A 92. The Fukuyama Synthesis of (−)-​Lepenine 93. The Smith Synthesis of (−)-​Calyciphylline N 94. The Paterson Synthesis of (−)-​Leiodermatolide 95. The Fuwa Synthesis of Didemnaketal B 96. The Lee Synthesis of (−)-​Crinipellin A 97. The Snyder Synthesis of Psylloborine A 98. The Morken Synthesis of (+)-​Discodermolide 99. The Trauner Synthesis of (−)-​Nitidasin 100. The Hoveyda Synthesis of Disorazole C1 101. The Smith Synthesis of (−)-​Nodulisporic Acid D 102. The Sato/​Chida Synthesis of Paclitaxel (Taxol®) 103. The Johnson Synthesis of Paspaline 104. The Ding Synthesis of Steenkrotin A

211  Author Index 241  Reaction Index

ix  Contents

Part XV  Classics in Total Synthesis

 xi

Preface

This volume is made up of the weekly Organic Highlights published online (http://​ www.organic-​chemistry.org) in 2014 and 2015, arranged by topic. These columns are still available online, with active links to the journal articles cited. This volume also includes a cumulated subject/​transformation index for all six volumes in this series, going back to 2003. The leading references in these volumes together provide a thorough and easily used guide to modern organic synthesis. This project originated with a discussion of the challenge of updating the classic reference work Comprehensive Organic Transformations: A Guide to Functional Group Preparations by Richard C. Larock (2nd ed.; Wiley-​VCH, 1999). Our objective was to provide immediate awareness of important new developments in organic synthesis, and at the same time to develop a readily accessible reference work. We were able to go far beyond functional group transformation, adding ring construction and control of relative and absolute configuration. The popularity of both the website (4450 subscribers worldwide) and of the previous volumes in this series attest to the success of this approach. The chapters in these volumes are arranged by topic, making it particularly easy to browse for information. These six volumes together (and the later biennial volumes that will follow) are a valuable resource that should be on the bookshelf of every practicing organic synthesis chemist. If they save a coworker even a day of working time, they will have more than paid for themselves. Douglass F. Taber Philadelphia, PA April 1, 2016

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ORGANIC SYNTHESIS STATE OF THE ART 2013–​2015

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1. Organic Functional Group Interconversion Douglass F. Taber May 26, 2014

Alois Fürstner of the Max-​Planck-​Institut Mülheim devised (Angew. Chem. Int. Ed. 2013, 52, 14050) a Ru catalyst for the trans-​selective hydroboration of an alkyne 1 to 2. Qingbin Liu of Hebei Normal University and Chanjuan Xi of Tsinghua University coupled (Org. Lett. 2013, 15, 5174)  the alkenyl zirconocene derived from 3 with an acyl azide to give the amide 4. Chulbom Lee of Seoul National University used (Angew. Chem. Int. Ed. 2013, 52, 10023) a Rh catalyst to convert a terminal alkyne 5 to the ester 6. Laura L. Anderson of the University of Illinois, Chicago devised (Org. Lett. 2013, 15, 4830) a protocol for the conversion of a terminal alkyne 7 to the α-​amino aldehyde 9.

Dewen Dong of the Changchun Institute of Applied Chemistry developed (J. Org. Chem. 2013, 78, 11956) conditions for the monohydrolysis of a bis nitrile 10 to the monoamide 11. Aiwen Lei of Wuhan University optimized (Chem. Commun. 2013, 49, 7923) a Ni catalyst for the conversion of the alkene 12 to the enamide 13. Kazushi Mashima of Osaka University optimized (Adv. Synth. Catal. 2013, 355, 3391) a boronic ester catalyst for the conversion of an amide 14 to the ester 15. Jean-​François Paquin of the Université Laval prepared (Eur. J. Org. Chem. 2013, 4325) the amide 17 by coupling an amine with the activated intermediate from reaction of an acid 16 with Xtal-​Fluor E.

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Ning Jiao of Peking University effected (Angew. Chem. Int. Ed. 2013, 52, 7850)  cleavage of the aryl alkyne 28 to the amide 29. Wujiong Xia of the Harbin Institute of Technology used (Org. Lett. 2013, 15, 624) visible light to convert the aldehyde 30 to the ketone 31. Xihe Bi and Qun Liu of Northeast Normal University described (Angew. Chem. Int. Ed. 2013, 52, 11303) the complementary degradation (not illustrated) of an aryl methyl ketone to the aromatic aldehyde.

3  Organic Functional Group Interconversion

Steven Fletcher of the University of Maryland School of Pharmacy designed (Tetrahedron Lett. 2013, 54, 4624) the azodicarbonyl dimorpholide 18 as a reagent for the Mitsunobu coupling of 19 with 20. The reduced form of 18 was readily separated by extraction into water and reoxidized. Jens Deutsch of the Universität Rostock found (Chem. Eur. J. 2013, 19, 17702) simple ligands for the Ru-​mediated borrowed hydrogen conversion of an alcohol 22 to the amine 23. Ronald T. Raines of the University of Wisconsin devised (J. Am. Chem. Soc. 2013, 135, 14936) a phosphinoester for the efficient conversion in water of an azide 24 to the diazo 25. In the course of a synthesis of Birkenal, Shigefumi Kuwahara of Tohoku University effected (Eur. J. Org. Chem. 2013, 2780) elimination of the lactone 26 to the alkene 27. At higher temperatures the product 27 was isomerized to the endocyclic alkene.

4

2. Organic Functional Group Interconversion Douglass F. Taber March 9, 2015

Gojko Lalic of the University of Washington developed (Angew. Chem. Int. Ed. 2014, 53, 6473) conditions for the preparation of the fluoride 2 by SN2 displacement of the triflate 1. Ross M. Denton of the University of Nottingham showed (Tetrahedron Lett. 2014, 55, 799) that a polymer-​bound phosphine oxide activated with oxalyl bromide would convert an alcohol 3 to the bromide 4. The polymer could be filtered off and reactivated directly. Jonas C.  Peters and Gregory C.  Fu of Caltech devised (J. Am. Chem. Soc. 2014, 136, 2162) a photochemically-​activated Cu catalyst that mediated the displacement of the bromide 5 by the amide 6 to give 7. Mark L. Trudell of the University of New Orleans used (Synthesis 2014, 46, 230) an Ir catalyst to couple the amide 9 with the alcohol 8, leading to 10.

Tohru Fukuyama of Nagoya University converted (Org. Lett. 2014, 16, 727)  the unsaturated aldehyde 11 into the ester 12. As the transformation proceeded via protonation of the enolized acyl cyanide, the less stable diastereomer was formed kinetically. Brindaban C. Ranu of the Indian Association for the Cultivation of Science developed (Org. Lett. 2014, 16, 1040) conditions for the coupling of an alkenyl halide 13 with a phenol, leading to the vinyl ether 14. Inter alia, this would be a convenient way to hydrolyze an alkenyl halide to the aldehyde. Vinyl ethers can also be oxidized directly to the ester, and to the unsaturated aldehyde. Pallavi Sharma and John E. Moses of the University of Lincoln observed (Org. Lett. 2014, 16, 2158) that the cyanation of the alkenyl halide 15 delivered 16, with retention of the geometry of the alkene. Jitendra K.  Bera of the Indian Institute of Technology Kanpur uncovered (Tetrahedron Lett. 2014, 55, 1444) “on water” conditions for the hydrolysis of a terminal alkyne 17 to the methyl ketone 18.

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Danfeng Huang and Yulai Hu of Northwest Normal University prepared (Synthesis 2014, 46, 320) the Weinreb amide 24 directly from the carboxylic acid 23, with activation by PCl3. Without racemization, Bhubaneswar Mandal of the Indian Institute of Technology Guwahati coupled (J. Org. Chem. 2014, 79, 5420) the protected amino acid 25 with the amino ester 26 to give 28, using the readily-​prepared activating agent 27. Renata Marcia de Figueiredo and Jean-​Marc Campagne of the Institut Charles Gerhardt Montpellier devised (Angew. Chem. Int. Ed. 2014, 53, 5389) a strategy for peptide construction in the opposite direction, coupling the activated urea 29 with 25 to give 28. Kounosuke Oisaki and Motomu Kanai of the University of Tokyo established (Angew. Chem. Int. Ed. 2014, 53, 6501) a strategy for the cleavage of a peptide at a serine residue. Oxidation of 30 led to 31 and 32. More complex peptides were also cleaved specifically.

5  Organic Functional Group Interconversion

Jiannan Xiang and Weimin He of Hunan University prepared (Eur. J. Org. Chem. 2014, 2668)  the keto phosphonate 20 by hydrolysis of the alkynyl phosphonate 19. Ken-​ichi Fujita of the National Institute of Advanced Industrial Science and Technology cyclized (Tetrahedron Lett. 2014, 55, 3013)  the alkyne 21 with CO2, leading to 22.

6

3. Organic Functional Group Interconversion Douglass F. Taber May 25, 2015

Feng Li of the Nanjing University of Science and Technology devised (Chem. Commun. 2014, 50, 8303) a combination of reagents that directly converted the alcohol 1 to the protected amine 2. Yong-​Sheng Bao and Bao Zhaorigetu of Inner Mongolia Normal University selectively (J. Org. Chem. 2014, 79, 6715) demethylated the tertiary amine 4, leading to the amide 5. Christopher W. Bielawski of the University of Texas developed (Chem. Eur. J. 2014, 20, 13487) the reagent 7 for the conversion of an alcohol 6 to the bromide 8. The diiodo analogue of 7 also worked well.

Ross Denton of the University of Nottingham showed (Chem. Commun. 2014, 50, 7340) that the reagent 10 efficiently mediated the Mitsunobu coupling of 9 with benzoic acid to give 11. The other product of the reaction, Ph3P=O, could be converted back to 10. Silas P. Cook of Indiana University established (J. Am. Chem. Soc. 2014, 136, 9521) conditions for the selective conversion of the bromide 12 to the boronate 13. Gwilherm Evano of the Université Libre de Bruxelles converted (Chem. Commun. 2014, 50, 11907) the alkenyl iodide 14 to the nitrile 15 using acetone cyanohydrin as the nitrile anion source. Seth B.  Herzon of Yale University developed (Angew. Chem. Int. Ed. 2014, 53, 7892)  an improved Ru catalyst for the hydration of a terminal alkyne 16 to the

 7

Yi-​Si Feng and Hua-​Jian Xu of the Hefei University of Technology found (Org. Lett. 2014, 16, 4586) that a carboxylic acid 23 could be coupled with diphenyl disulfide under decarboxylating conditions, leading to the sulfide 24. Kenneth M. Doll of USDA Peoria observed (ACS Catal. 2014, 4, 3517) that decarboxylation of the unsaturated carboxylic acid 25 with a Ru catalyst delivered the alkene 26 as a mixture of regioisomers. Orson L. Sydora of Chevron Phillips and Mark Stradiotto and Laura Turculet of Dalhousie University used (Chem. Eur. J. 2014, 20, 13918) a Co catalyst to effect the room temperature equilibrating hydroboration of an internal alkene 27 to the terminal boronate 28.

Maddi Sridar Reddy of the Central Drug Research Institute rearranged (J. Org. Chem. 2014, 79, 823) the propargylic acetate 29 to the unsaturated amide 30. In a modern-​day version of the Willgerodt reaction, Thanh Binh Nguyen of Gif-​sur-​Yvette prepared (Org. Lett. 2014, 16, 310) the thioamide 33 by coupling the alkyne 31 with the amine 32 in the presence of elemental sulfur.

7  Organic Functional Group Interconversion

aldehyde 17. Clément Mazet of the University of Geneva used (Chem. Commun. 2014, 50, 10592) an Ir catalyst for the isomerization of a 2,2-​disubstituted epoxide 18 to the aldehyde 19. Laurent El Kaïm of the Ecole Polytechnique, Laurence Grimaud of UMPC, and Roland Jacquot and Philippe Marion of Solvay showed (Synthesis 2014, 46, 1802) that in the presence of glutaronitrile 21, AlCl3 was an effective catalyst for the conversion of an acid 20 to the nitrile 22.

8

4. Oxidation Eric D. Nacsa and Tristan H. Lambert March 24, 2014

Huanfeng Jiang at the South China University of Technology developed (J. Am. Chem. Soc. 2013, 135, 5286) the palladium-​catalyzed dehydrogenative aminohalogenation of methyl acrylate with aniline 1. A  1,3-​hydrogen shift/​chlorination catalyzed by an iridium complex was reported (Angew. Chem. Int. Ed. 2013, 52, 6273) by Belén Martín-​Matute at Stockholm University. Robert M.  Waymouth discovered (J. Am. Chem. Soc. 2013, 135, 7593) the chemoselective oxidation of polyol 5 by a cationic palladium species. A ruthenium(II) hydride was found to catalyze the conversion of alcohols such as 7 to carboxylic acids using water as the oxygen source as disclosed (Nature Chem. 2013, 5, 122) by David Milstein at the Weizmann Institute of Science in Israel.

Susan K. Hanson at the Los Alamos National Laboratory in New Mexico reported (Org. Lett. 2013, 15, 650) the acceptorless dehydrogenation of alcohols catalyzed by cobalt complex 12 to form imines such as 13 upon reaction with an amine. A collaboration led by Pedro J. Pérez at the University of Huelva in Spain studied (J. Am. Chem. Soc. 2013, 135, 3887) the oxidation of alkanes under catalysis with copper complex 15, primarily yielding alcohols and ketones, such as in the conversion of cyclohexane (14) to cyclohexanol (16) and cyclohexanone (17).

A remarkable symmetry-​breaking Wacker oxidation of diene 18 to produce 19 was the key step in the total synthesis of (+)-​obolactone reported (Org. Lett. 2013, 15, 1294) by Reinhard Brückner at the University of Freiburg in Germany. Kiyotomi

 9

As part of a program to develop environmentally sustainable procedures, Caterina Fusco at the University of Bari in Italy described (Tetrahedron Lett. 2013, 54, 515) the oxidative cleavage of lactam 22 by methyl(trifluoromethyl)dioxirane in water to produce ω-​nitro acid 24. Motomu Kanai at the University of Tokyo reported (Org. Lett. 2013, 15, 1918) the β-​functionalization of tertiary aromatic amine 25 with nitroolefin 26 to produce 27 by iron catalysis.

Norio Shibata at the Nagoya Institute of Technology discovered (J. Am. Chem. Soc. 2013, 135, 8782)  a novel trifluoromethylthiolation reagent, iodonium ylide 29. In situ reduction of the more convenient trifluoromethanesulfonyl group by copper(I) functionalized enamine 28 at the α-​position to generate 30. A  team led by Vikram C.  Purohit at Teva Pharmaceuticals in Pennsylvania found (Org. Lett. 2013, 15, 1650) that iodoarenesulfonic acid 32 catalyzed an oxidative 1,2-​shift of α-​substituted styrene 31 to furnish ketone 33.

The oxidative coupling of acid 34 to alkyne 35 via an α-​oxo gold carbene intermediate was reported (Angew. Chem. Int. Ed. 2013, 52, 6508)  by Liming Zhang at the University of California Santa Barbara. The steric nature of the ligand was critical since substituted piperidines, such as that found in the optimal catalyst 36, gave higher efficiencies. Finally, Luc Neuville at the French National Centre for Scientific Research described (Org. Lett. 2013, 15, 1752) a copper system that coupled amidine 39 with alkyne 40 to produce the highly substituted imidazole 41.

9  Oxidation

Kaneda at the University of Osaka found (Angew. Chem. Int. Ed. 2013, 52, 5961) that a palladium salt catalyzes the conversion of electron-​deficient internal olefin 20 to ketone 21.

10

5. Functional Group Oxidation and Reduction Douglass F. Taber May 19, 2014

Christophe Darcel and Jean-​Baptiste Sortais of the CNRS-​Université Rennes 1 reduced (Chem. Commun. 2013, 49, 10010) an acid 1 to the aldehyde 2 with a Mn catalyst under photostimulation. The same authors also used (Angew. Chem. Int. Ed. 2013, 52, 8045) an Fe catalyst to reduce an ester (not illustrated) to the corresponding aldehyde. Yasushi Tsuji of Kyoto University employed (Adv. Synth. Catal. 2013, 355, 3420) a Pd catalyst to reduce acid to the aldehydes. Chao-​Jun Li of McGill University found (Angew. Chem. Int. Ed. 2013, 52, 11871) that a Ag catalyst in water would reduce an aldehyde 3 to the alcohol 4. Ketones were not reduced under these conditions.

David Milstein of the Weizmann Institute of Science devised (Angew. Chem. Int. Ed. 2013, 52, 14131)  an Fe catalyst for the E-​selective reduction of an alkyne 5 to the alkene 6. Debabrata Maiti of IIT Bombay effected (Chem. Commun. 2013, 49, 8362) reductive cleavage of a nitrile 7 to the alkane 8. Aryl nitriles were also reduced. Professor Li used (Eur. J.  Org. Chem. 2013, 6496)  an Ir catalyst and hydrazine under H-​transfer conditions to reduce an alcohol 9 to the hydrocarbon 10. Kenneth M.  Nicholas of the University of Oklahoma reduced (Chem. Commun. 2013, 49, 8199) the diol 11 to the alkene 12 with a V catalyst. Qiang Liu of Lanzhou University and Li-​Zhu Wu of the Technical Institute of Physics and Chemistry showed (Eur. J. Org. Chem. 2013, 7528) that irradiation in the presence of a photoredox catalyst and a Hantzsch ester removed the sulfonyl group of 13.

 1

Combining oxidation and reduction in the presence of a Ru catalyst, Soon Hyeok Hong of Seoul National University prepared (J. Am. Chem. Soc. 2013, 135, 11704) the amide 27 by combining the nitrile 25 with the alcohol 26. Francisco M. Guerra of the Universidad de Cádiz developed (Eur. J. Org. Chem. 2013, 8307) a Cu–​Al oxide catalyst that proved effective for the γ-​hydroxylation of an enone 28, delivering 29 with high diasteroselectivity.

11  Functional Group Oxidation and Reduction

Selective oxidation is a powerful tool for organic synthesis. Eike B. Bauer of the University of Missouri St. Louis oxidized (Chem. Commun. 2013, 49, 5889) the diol 15 to the ketone 16 with an Fe catalyst and 30% hydrogen peroxide. Yan-​qin Yuan of Lishui University and Jiannan Xiang of Hunan University selectively (Org. Lett. 2013, 15, 4654) thiolated the ether 17 to 18, that has the aldehyde oxidation state. Chengjian Zhu of Nanjing University converted (Adv. Synth. Catal. 2013, 355, 3558) the aldehyde 19 to the thioester 20 by oxidation in the presence of diphenyl disulfide. Shannon S. Stahl of the University of Wisconsin optimized (Org. Lett. 2013, 15, 5072) the oxidation of a primary alcohol 21 in the presence of methanol to the methyl ester 22. Nathaniel K.  Szymczak of the University of Michigan observed (J. Am. Chem. Soc. 2013, 135, 16352) the remarkable oxidation of the amine 23 to the nitrile 24, with release of H2 gas.

12

6. Oxidation of Organic Functional Groups Douglass F. Taber March 16, 2015

Cancheng Guo of Hunan University devised (J. Org. Chem. 2014, 79, 2709)  conditions for the oxidative cleavage of an alkyne 1 to the esters 2 and 3. Hirokazu Arimoto of Tohoku University found (Chem. Commun. 2014, 50, 2758)  that IBX oxidized a primary alcohol 4 to the acid 5 one carbon shorter. David Milstein of the Weizmann Institute of Science uncovered (J. Am. Chem. Soc. 2014, 136, 2998) conditions for the direct oxidation of the cyclic amine 6 to the lactam 7, with concomitant evolution of H2.

Cyclic ene sulfonamides such as 9 are versatile synthetic intermediates. Henri Doucet of the Université de Rennes reported (Adv. Synth. Catal. 2014, 356, 119) the regioselective conversion of 8 to 9. In this case, the oxidizing agent was the organo-​ PdBr intermediate. There have been many reports of the functionalization of the oxygenated carbons of cyclic ethers, as exemplified by the conversion of 10 to 11, observed (J. Org. Chem. 2014, 79, 3847) by Jianlin Han of Nanjing University. If these methods were regioselective with an acyclic benzyl ether, this could be a new method for the removal of that common protecting group. Jianliang Xiao of the University of Liverpool described (J. Am. Chem. Soc. 2014, 136, 8350) a selective benzylic ether oxidation that converted 12 to 13.

Baris Temelli of Hacettepe University effected (Synthesis 2014, 46, 1407)  the conversion of a primary nitro compound 14 into the corresponding nitrile 15. Jean-​ Michel Vatèle of Université Lyon 1 oxidized (Synlett 2014, 25, 1275)  the primary alcohol 16 to the nitrile 17.

 13

Tun-​Cheng Chien of the National Taiwan Normal University added (Org. Lett. 2014, 16, 892)  hydroxylamine to the nitrile 24 to generate the amidoxime (not illustrated). Further addition of TsCl led to rearrangement to the cyanamide 25. Bhubaneswar Mandal of the Indian Institute of Technology Guwahati used (J. Org. Chem. 2014, 79, 3765) ethyl 2-​cyano-​2-​(4-​nitrophenylsulfonyloxyimino)acetate (4-​ NBsOXY) to convert the acid 26 into the N-​hydroxyamide (not illustrated). Further exposure to the activating agent led to rearrangement to the isocyanate (not illustrated), that was coupled with the amine 27 to give the urea 28.

13  Oxidation of Organic Functional Groups

Many methods have been put forward for the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones. Piperidinium oxy radicals such as TEMPO are widely used to catalyze this transformation. Yoshikazu Kimura of Iharanikkei Chemical Industry Co. Ltd. established (Synlett 2014, 25, 596) a manufacturing process for crystalline NaOCl•5H2O that served as the bulk oxidant for the conversion of 18 to 19. Neither a ketone nor an aldehyde was chlorinated under the reaction conditions. Yoshiharu Iwabuchi of Tohoku University showed (Angew. Chem. Int. Ed. 2014, 53, 3236) that with his piperidinium oxy radical AZADO and Cu catalysis, air could be the bulk oxidant for the otherwise difficult conversion of the amino alcohol 20 to the amino ketone 21. Using solvent acetone as the hydride acceptor and a highly active Ru catalyst, Zhengkun Yu of the Dalian Institute of Chemical Physics converted (Tetrahedron Lett. 2014, 55, 1585) the alcohol 18 to the alcohol 19 in just 30 minutes. Jian Chen of Central China Normal University described (Tetrahedron Lett. 2014, 55, 1736) the oxidation of the alkene 22 to the α-​aryl ketone 23.

14

7. New Methods for Reduction and for Oxidation Douglass F. Taber May 18, 2015

Clemens Krempner of Texas Tech University devised (Chem. Eur. J. 2014, 20, 14959) a very active Al catalyst for the Meerwein-​Ponndorf-​Verley reduction of a ketone 1 to the alcohol 2. Louis Fensterbank and Cyril Ollivier of UMPC and Jean-​Philippe Goddard of the Université de Haute-​Alsace showed (Adv. Synth. Catal. 2014, 356, 2756) that visible light could mediate the reduction of the O-​thiocarbamate 3 to 4. Soon Hyeok Hong of Seoul National University used (Org. Lett. 2014, 16, 4404) hydrogen from the diol 6 to reduce the nitrile 5, leading directly to the protected amine 7.

Alex Adronov of McMaster University (J. Org. Chem. 2014, 79, 7728)  and Thibault Cantat of Gif-​sur-​Yvette (Chem. Commun. 2014, 50, 9349) observed that an aryl amide 8 could be reduced to the amine 9 under conditions that left alkyl amides unchanged. Paul J. Chirik of Princeton University developed (J. Am. Chem. Soc. 2014, 136, 13178) a Co catalyst for the alcohol-​directed reduction of a proximal alkene, converting 10 selectively to 11. Yoichiro Kuninobu and Motomu Kanai of the University of Tokyo used (Synlett 2014, 25, 1869) stoichiometric Mo(CO)6 to desulfurize 12 to 13. Utpal Bora of Tezpur University oxidized (Tetrahedron Lett. 2014, 55, 5029) the alcohol 14 to the aldehyde 15 with t-​butyl hydroperoxide, using the inexpensive and reusable VOSO4 as the catalyst. The oxidation of an alcohol to the acid is often carried out in two steps, alcohol to aldehyde and aldehyde to carboxylic acid. Kenneth B. Wagener of the University of Florida developed (Tetrahedron Lett. 2014, 55, 4452) a protocol for the direct oxidation of an alcohol 16 to the acid 17. Prodeep Phukan of Gauhati University devised (Tetrahedron Lett. 2014, 55, 5358)  a catalyst-​free

 15

Katsuhiko Moriyama and Hideo Togo of Chiba University effected (Org. Lett. 2014, 16, 3812)  the oxidative debenzylation of 20 to the ketone 21. Christian Ochsenfeld and Dirk Trauner of the University of Munich used (J. Org. Chem. 2014, 79, 9812) Swern conditions to selectively oxidize the TES ether 22 to the aldehyde 23. Satoshi Minakata of Osaka University devised (Org. Lett. 2014, 16, 4646) conditions for the oxidative decarboxylation of a β,γ-​unsaturated acid 24 to the allylic acetate 25. Justin J. Maresh of DePaul University prepared (Tetrahedron Lett. 2014, 55, 5047) the aldehyde 27 by oxidative decarboxylation of the amino acid 26. Dirk E. De Vos of KU Leuven used (Eur. J. Org. Chem. 2014, 6649) electrochemically-​generated hypobromite for the oxidative decarboxylation of an amino acid to the corresponding nitrile (not illustrated). Yujiro Hayashi of Tohoku University established (Chem. Eur. J. 2014, 20, 15753) conditions for the Nef oxidation of a nitro alkene 28 to the enone 29.

15  New Methods for Reduction and for Oxidation

procedure for the oxidation of a primary alcohol 18 to the ester 19. The aldehyde corresponding to 18 (not illustrated) was also efficiently oxidized to 19.

16

8. Reductions Jeffrey S. Bandar March 31, 2014

Manfred T.  Reetz at the Max-​ Planck-​ Institut Mülheim and Philipps-​ Universität Marburg developed (J. Am. Chem. Soc. 2013, 135, 1665)  a mutated Thermoethanolicus brockii alcohol dehydrogenase for the enantioselective reduction of 4-​alkylidene cyclohexanone 1. Using a new C2-​symmetic chiral bisphosphine ligand (Wingphos, 5), Wenjun Tang at the Shanghai Institute of Organic Chemistry reported (Angew. Chem. Int. Ed. 2013, 52, 4235) the rhodium-​catalyzed asymmetric hydrogenation of β-​aryl enamide 3. Qi-​Lin Zhou of Nankai University utilized chiral spirophosphine oxazoline iridium complexes 8a and 8b for the asymmetric hydrogenation of unsaturated piperidine carboxylic acid 6 (Angew. Chem. Int. Ed. 2013, 52, 6072)  and 1,1-​diarylethylene 9 (Angew. Chem. Int. Ed. 2013, 52, 1556) with excellent selectivities.

The iron-​catalyzed chemoselective hydrogenation of α,β-​unsaturated aldehyde 11 was demonstrated (Angew. Chem. Int. Ed. 2013, 52, 5120) by Matthias Beller at the University of Rostock. Jeffrey S. Johnson at the University of North Carolina at Chapel Hill showed (J. Am. Chem. Soc. 2013, 135, 594) that asymmetric transfer hydrogenation of racemic acyl phosphonate 14 yielded β-​stereogenic α-​hydroxy phosphonate 16, a reversal in diastereoselectivity observed in the case of α-​keto ester analogues.

Gojko Lalic of the University of Washington developed (Org. Lett. 2013, 15, 1112) a monophasic copper catalyst system for the selective semireduction of terminal

 17

Bernhard Breit at the University of Freiburg found (Angew. Chem. Int. Ed. 2013, 52, 2231) that a bimetallic Pd/​Re/​graphite catalyst system was highly active for the hydrogenation of tertiary amide 21 to amine 22. Professor Beller also discovered (Chem. Eur. J. 2013, 19, 4437) that a commercially available ruthenium complex allowed for the effective transfer hydrogenation of aromatic nitrile 23 to benzyl amine 24. Notably, no reductive amination side products were observed.

Maurice Brookhart at the University of North Carolina at Chapel Hill used (Org. Lett. 2013, 15, 496) tris(pentafluorophenyl)borane as a highly active catalyst for the selective reduction of carboxylic acid 25 to aldehyde 26 with triethylsilane as a hydride source. The mild reduction of trans-​2-​phenylcyclopropane-​1-​carboxylic acid derivative 27 via a modified McFadyen-​Stevens reaction was reported (Chem. Sci. 2013, 4, 1111) by Tohru Fukuyama of the University of Tokyo.

A straightforward method for the hydrofluorination of tosylhydrazone 29 to produce fluoroalkane 30 using readily available reagents was demonstrated (Chem. Comm. 2013, 49, 2154) by Lal Dhar S. Yadav of the University of Allahabad. Corey R. J. Stephenson at the University of Michigan combined (Chem. Comm. 2013, 49, 4352) a Garegg-​Samuelsson reaction with photoredox flow chemistry to develop a one-​pot procedure for the deoxygenation of alcohol 31.

17  Reductions

alkyne 17. Alois Fürstner and coworkers at Max-​Planck-​Institut Mülheim reported (Angew. Chem. Int. Ed. 2013, 52, 355) the ruthenium-​catalyzed trans-​selective hydrogenation of alkyne 19. Macrocyclic alkynes could also be selectively hydrogenated to E-​alkenes using this methodology.

18

9. Reduction of Organic Functional Groups Douglass F. Taber March 23, 2015

Cornelis J. Elsevier of the University of Amsterdam developed (ACS Catal. 2014, 4, 1349)  an improved Pd-​based protocol for the hydrogenation of an alkyne 1 to the Z-​alkene 2. Yongbo Zhou and Shuang-Feng Yin of Hunan University showed (Adv. Synth. Catal. 2014, 356, 765) that under Cu catalysis, hypophosphorous acid selectively reduced the terminal alkyne of 3 to the ene-​yne 4. Hidefumi Makabe of Shinshu University found (Tetrahedron Lett. 2014, 55, 2822)  that the iodoalkyne 5 was reduced to the iodoalkene 6 by diimide, conveniently generated from the arenesulfonyl hydrazide. Manat Pohmakotr of Mahidol University used (Eur. J. Org. Chem. 2014, 1708) P-​2 Ni to reduce the sulfoxide 7 to the alkene 8.

Shinya Furakawa and Takayuki Komatsu of the Tokyo Institute of Technology devised (ACS Catal. 2014, 4, 1441) a Pd catalyst for the selective reduction of the nitro group of 9 to the aniline 10. Hiroshi Kominami of Kinki University employed (Chem. Commun. 2014, 50, 4558) a Ti-​promoted Ag catalyst to deoxygenate the epoxide 11 to the alkene 12. Benjamin R. Buckley and K. G. Upul Wijayantha of Loughborough University described (Synlett 2014, 25, 197) an alternative protocol (not illustrated) for epoxide deoxygenation.

Xiaohui Fan of Lanzhou Jiaotong University observed (Eur. J. Org. Chem. 2014, 498) that the reduction of 13 to 14 proceeded without cyclopropane opening, suggesting the reaction did not involve substantial charge separation. Michel R. Gagné of the University of North Carolina deployed (Angew. Chem. Int. Ed. 2014, 53, 1646) catalytic trispentafluorophenylborane to selectively reduce 15 to 16. Gojko Lalic of the University of Washington reduced (Angew. Chem. Int. Ed. 2014, 53, 752) a secondary

 19

Marc Lemaire of the Université Claude-​Bernard Lyon 1 converted (Tetrahedron Lett. 2014, 55, 23) the nitrile 19 to the aldehyde 20 by V-​catalyzed reduction followed by hydrolysis. Matthias Beller of the Universität Rostock showed (Chem. Eur. J. 2014, 20, 4227) that a nitrile 21 could be reduced to the amine 22 with very little by-​product dimer. Hongwei Gu of Soochow University used (Chem. Commun. 2014, 50, 3512) a Pt catalyst to deliberately prepare the mixed secondary amine 25 from the nitrile 23 and the added primary amine 24. Neil T.  Fairweather of Procter & Gamble and Hairon Guan of the University of Cincinnati devised (J. Am. Chem. Soc. 2014, 136, 7869)  an iron catalyst for the hydrogenation of an ester 26 to the alcohol 27. Victor Snieckus of Queen’s University introduced (Org. Lett. 2014, 16, 390) an improved in situ preparation of Schwartz’s reagent, using it, inter alia, to reduce the amide 28 to the aldehyde 29.

19  Reduction of Organic Functional Groups

iodide 17 to the hydrocarbon 18 under Cu catalysis. Primary bromides and triflates could also be reduced, while many other functional groups, including tosylates, were stable.

20

10. Organic Functional Group Protection Douglass F. Taber June 9, 2014

Dithianes such as 1 are readily prepared, from the corresponding ketone or by alkylation. Masayuki Kirihara of the Shizuoka Institute of Science and Technology developed (Tetrahedron Lett. 2013, 54, 5477) an oxidative method for the deprotection of 1 to 2. Konrad Tiefenbacher of the Technische Universität München devised (J. Am. Chem. Soc. 2013, 135, 16213) a hexameric resorcinarene capsule that selectively catalyzed the hydrolysis of the smaller acetal 3 to 4 in the presence of a longer chain acetal. David J.  Gorin of Smith College reported (J. Org. Chem. 2013, 78, 11606)  the methylation of an acid 5 to 6 using dimethyl carbonate as the donor. Two peroxide-​ based methods (J. Org. Chem. 2013, 78, 9898; Org. Lett. 2013, 15, 3326) for carboxylic acid methylation (not illustrated) were also recently described. Hisashi Yamamoto of the University of Chicago showed (Angew. Chem. Int. Ed. 2013, 52, 7198) that the “supersilyl” ester 8, prepared from 7, was stable enough to be deprotonated and alkylated, but was easily removed.

Michal Szostak and David J. Procter of the University of Manchester uncovered (Angew. Chem. Int. Ed. 2013, 52, 7237) the remarkable cleavage of a C–​N bond in an amide 9, leading to the secondary amide 10. This could offer an alternative strategy for difficult-​to-​hydrolyze amides. Richard B. Silverman of Northwestern University described (J. Org. Chem. 2013, 78, 10931) improved protocols for the formation and removal of the N-​protecting 2,5-​dimethylpyrrole 11 to give 12. Huanfeng Jiang of the South China University of Technology showed (Chem. Commun. 2013, 49, 6102) that an arenesulfonamide 14 can be prepared by oxidation of the corresponding sodium arenesulfinate 13. Douglas A.  Klumpp of Northern Illinois University prepared (Tetrahedron Lett. 2013, 54, 5945)  sulfonamides (not illustrated) by combining a sulfonyl fluoride with a silyl amine. K.  Rajender Reddy of the Indian Institute of Chemical Technology developed (Chem. Commun. 2013, 49, 6686) a new route to a urea 17, by oxidative coupling of an amine 15 with a formamide 16.

 21

Pavel Nagorny of the University of Michigan employed (Angew. Chem. Int. Ed. 2013, 52, 12932) an enantiomerically-​pure phosphoric acid to effect regioselective protection of 26 with 27 to give 28. Under simple acidic conditions, the other regioisomer dominated. Kian L.  Tan, now at Novartis, designed (Nature Chem. 2013, 5, 790)  an enantiomerically-​pure imidazole to catalyze selective acylation. The selectivity with the arabinose derivative 29 was particularly striking. Under catalysis by N-​methyl imidazole, mesylation was predominantly at position 2 to give 30, as illustrated. With the (−) catalyst, mesylation was at position 3, and with the (+) enantiomer of the catalyst mesylation occurred selectively at position 4.

21  Organic Functional Group Protection

Davir González-​ Calderón and Carlos Gonzáles-​ Romero of the Universidad Autónoma del Estado de México used (Tetrahedron Lett. 2013, 54, 5130)  CuSO4 hydrate in methanol to remove the t-​butyldimethylsilyl ether of 18 to give 19 in the presence of triisopropylsilyl (TIPS) and diphenyl t-​butylsilyl (TBDPS) ethers. Shoji Akai and Ken-​ichi Sato of Kanagawa University developed (J. Org. Chem. 2013, 78, 8802)  a nitrosative protocol for the cleavage of the N-​phenylcarbamoyl protecting group of 20 to give 21. Shino Manabe and Yukishige Ito of RIKEN showed (Chem. Commun. 2013, 49, 8332) that the sulfonylcarbamate protecting group of 22 was stable to strong base, but was smoothly removed under mild conditions, leading to 23. Hirokazu Urabe of the Tokyo Institute of Technology reported (Adv. Synth. Catal. 2012, 354, 3480) the oxidation of the benzyl ether 24 to 25. The oxidized product 25 is primed for alcohol deprotection under either hydrolytic or mildly reductive conditions.

2

11. Organic Functional Group Protection and Deprotection Douglass F. Taber September 29, 2014

Martin Oestreich of the Technische Universität Berlin developed (Eur. J. Org. Chem. 2014, 2077) the Birch reduction product 2 as a donor for the silylation of an alcohol 1 to give 3. Atahualpa Pinto of the SUNY College of Environmental Science and Forestry devised (Tetrahedron Lett. 2014, 55, 2600) conditions for the monosilylation of the diol 4 to give 5. Quanxuan Zhang of Michigan State University reported (Tetrahedron Lett. 2014, 55, 3384)  the preparation (not illustrated) of the mono-​THP ethers of symmetrical diols. The product from the Mitsunobu coupling of an acid with an alcohol 6 can be difficult to purify. Takashi Sugimura of the University of Hyogo showed (Synthesis 2013, 45, 931) that the oxidation product from 7 and the reduction product from 8 could both be removed from the product 9 by simple extraction.

David Milstein of the Weizmann Institute of Science found (Angew. Chem. Int. Ed. 2014, 53, 4685) that an Fe catalyst could be used to reduce the trifluoroacetate 10 to 11. Jean-​Michel Vatèle of the Université Lyon 1 oxidized (Synlett 2014, 25, 115) the benzylidene acetal 12 selectively to the monobenzoate 13. Xinyu Liu of the University of Pittsburgh organized (Chem. Commun. 2014, 50, 3155) a family of acid-​sensitive esters that can be selectively removed in the presence of other esters, as exemplified by the conversion of 14 to 15. Ryo Yazaki and Takashi Ohshima of Kyushu University observed (Angew. Chem. Int. Ed. 2014, 53, 1611) that an amine would add spontaneously to acrylonitrile 17

 23

1,2-​Addition to t-​butylsulfanylimines is widely used to construct aminated stereogenic centers. Xiaodong Yang and Hongbin Zhang of Yunnan University established (Chem. Commun. 2014, 50, 6259) a general protocol for cleaving the N–​S bond in the product 22 to give the desired free amine 23. John A. Murphy of the University of Strathclyde demonstrated (J. Org. Chem. 2014, 79, 3731; Angew. Chem. Int. Ed. 2014, 53, 474) many applications for the powerful photoreductant 25, including the deprotection of the sulfonamide 24 to give the free amine 26. Willi Bannwarth of the Albert-​Ludwigs-​Universität Freiburg created (Chem. Eur. J. 2014, 20, 1258)  an expanded family of chelating amides that could be selectively activated with Fe, Zn, and Cu respectively, enabling the conversion of 27 to 28. Dirk Trauner of the Ludwig-​Maximilian-​Universität München observed (Tetrahedron Lett. 2014, 55, 59) that an Evans acyl oxazolidinone aldol product could easily be cleaved to 30 if it was first converted into the xanthate 29. N. Jung and Stefan Bräse of the Karlsruhe Institute of Technology devised (Org. Lett. 2014, 16, 1036) an odorless polymeric reagent for the conversion of an aldehyde 31 to the dithiane 32. José Vicente of the Universidad de Murcia found (Tetrahedron Lett. 2014, 55, 1141) Pd-​catalyzed conditions for the deprotection of 33 to 34 without dehydration of the sensitive tertiary alcohol.

23  Organic Functional Group Protection and Deprotection

to give 18. In the presence of a Cu catalyst, alcohols added to 17 even more readily, allowing the preparation of 18 from 16. Diego Gamba-​Sánchez of the Universidad de los Andes used (J. Org. Chem. 2014, 79, 4544) simple Fe catalysts to activate a wide range of amides, including 20, to become acylating agents, converting 19 to 21.

24

12. Organic Functional Group Protection Douglass F. Taber June 8, 2015

Sentaro Okamoto of Kanagawa University developed (Tetrahedron Lett. 2014, 55, 7039) an organocatalyst that mediated the selective acylation of 1 to give the primary acetate 2. Philip A. Albiniak of Ball State University devised (Tetrahedron Lett. 2014, 55, 7133) a reagent 4 for the simple preparation of a t-​butyl ether 5 from an alcohol 3.

Attempted deprotection of 6 tended to divert to the dioxolane. Toshio Nishikawa of Nagoya University developed (Synlett 2014, 25, 2498) an oxidative protocol that gave clean conversion to the desired 7. Alan S. Goodman of Rutgers University found (Angew. Chem. Int. Ed. 2014, 53, 10160) an Ir catalyst that generated the p­ henol 9 from the aryl alkyl ether 8. In the course of a synthesis of Sch 725674, Kavirayani R. Prasad of the Indian Institute of Science, Bangalore deprotected (Org. Lett. 2014, 16, 4001) the dithiane 10 to yield the sensitive aldol product 11. Karl Anker Jørgensen of Aarhus University observed (Chem. Commun. 2014, 50, 15689) that the nitro isoxazole 12, having served to activate sequential Michael addition, was readily cleaved to the acid 13.

Jiang Cheng of Changzhou University used (Chem. Commun. 2014, 50, 8412)  CuCN to convert 14 to 15. Pradeep Kumar of CSIR-​National Chemistry Laboratory effected (Tetrahedron Lett. 2014, 55, 7172)  oxidative deallylation of 16, leading to 17. Hiroyuki Morimoto and Takashi Ohshima of Kyushu University found (Chem. Commun. 2014, 50, 12623) that NH4I promoted the hydrazinolysis of

 25

Automated peptide synthesis can be hindered by difficult sequences. Judit Tulla-​ Puche and Fernando Albericio of IRB Barcelona showed (Chem. Eur. J. 2014, 20, 15031) that the substituted benzyl group of 24 facilitated such syntheses, and that it could be readily removed to give 25 by exposure to NH4I and trifluoroacetic acid. Akihiro Orita of the Okayama University of Science demonstrated (Chem. Lett. 2014, 43, 1610)  that the diphenylphosphoryl group of 26 was orthogonal to the alternative silyl protection. Silyl alkynes were stable to CH3MgBr, that converted 26 to 27, and 26 was stable to TBAF and to AgBF4, reagents that desilylated terminal alkynes. The cyclic alkyne of 28 is much more reactive than the terminal alkyne. Suguru Yoshida and Takamitsu Hosoya of the Tokyo Medical and Dental University found (J. Am. Chem. Soc. 2014, 136, 13590) that click chemistry could be selectively carried out on the terminal alkyne if the cyclic alkyne was first protected as the stoichiometric Cu complex 29.

25  Organic Functional Group Protection

the amide 18, giving 19 without racemization. Franco Ghelfi of the Università degli Studi di Modena e Reggio Emilia prepared (Eur. J. Org. Chem. 2014, 6734) 21 by desulfonylating 20 to 21 with H2SO4 in acetic acid. Hans Adolfsson of Stockholm University reduced (Org. Lett. 2014, 16, 680) the amide 22 to the enamine 23. The N-​vinyl amine could be hydrolyzed, but it is also a versatile intermediate for other transformations.

26

13. Functional Group Protection: The Pohl Synthesis of ϐ-​1,4-​Mannuronate Oligomers Douglass F. Taber October 26, 2015

D. Srinivasa Reddy of the National Chemical Laboratory converted (Org. Lett. 2015, 17, 2090)  the selenide 1 to the alkene 2 under ozonolysis conditions. Takamitsu Hosoya of the Tokyo Medical and Dental University found (Chem. Commun. 2015, 51, 8745) that even highly strained alkynes such as 4 can be generated from a sulfinyl vinyl triflate 3.

An alkyne can be protected as the dicobalt hexacarbonyl complex. Joe B. Gilroy and Mark S. Workentin of the University of Western Ontario found (Chem. Commun. 2015, 51, 6647)  that following click chemistry on a non-​protected distal alkyne, deprotection of 5 to 6 could be effected by exposure to TMNO. Stefan Bräse of the Karlsruhe Institute of Technology and Irina A. Balova of Saint Petersburg State University showed (J. Org. Chem. 2015, 80, 5546) that the bend of the Co complex of 7 enabled ring-​closing metathesis, leading after deprotection to 8. Morten Meldal of the University of Copenhagen devised (Eur. J. Org. Chem. 2015, 1433) 9, the base-​labile protected form of the aldehyde 10. Nicholas Gathergood of Dublin City University and Stephen J. Connon of the University of Dublin developed (Eur. J. Org. Chem. 2015, 188) an imidazolium catalyst for the exchange deprotection of 11 to 13, with the inexpensive aldehyde 12 as the acceptor. Peter J. Lindsay-​Scott of Eli Lilly demonstrated (Org. Lett. 2015, 17, 476) that on exposure to KF, the isoxazole 14 unraveled to the nitrile 15. Masato Kitamura of Nagoya University observed (Tetrahedron 2015, 71, 6559) that the allyl ester of 16 could be removed to give 17, with the other alkene not affected.

 27

Hidetoshi Ohta and Yutaka Watanabe of Ehime University used (Tetrahedron Lett. 2015, 56, 2910) a nickel catalyst to prepare 23 by the silylation of 22. Qi Zhang and Yonghai Chai of Shaanxi Normal University desilylated (Synthesis 2015, 47, 55) 24 to 25 using a gold catalyst. There are many technical challenges to iterative oligosaccharide synthesis. Nicola L. B. Pohl of Indiana University developed (Org. Lett. 2015, 17, 2642) the perfluoroalkyl group of 26 to enable efficient machine-​based assembly, as illustrated by the preparation of the β-​1,5-​mannuronate six-​mer 28 by repeated exposure to near-​stoichiometric amounts of 27. The perfluoro group was removed by exchange metathesis, leading to an allyl ether that was reduced in the subsequent debenzylation step.

27  Functional Group Protection

Benzyl ethers are among the most common of alcohol protecting groups. Yongxiang Liu and Maosheng Cheng of Shenyang Pharmaceutical University showed (Adv. Synth. Catal. 2015, 357, 1029) that 18 could be converted to 19 simply by exposure to benzyl alcohol in the presence of a gold catalyst. Reko Leino of Åbo Akademi University developed (Synthesis 2015, 47, 1749)  an iron catalyst for the reductive benzylation of 20 to 21. Related results (not illustrated) were reported (Org. Lett. 2015, 17, 1778) by Chae S. Yi of Marquette University.

28

14. Flow Chemistry: The Direct Production of Drug Metabolites Douglass F. Taber September 22, 2014

Several overviews of flow chemistry appeared recently. Katherine S.  Elvira and Andrew J.  deMello of ETH Zürich wrote (Nature Chem. 2013, 5, 905)  on microfluidic reactor technology. D.  Tyler McQuade of Florida State University and the Max Planck Institute Mühlenberg reviewed (J. Org. Chem. 2013, 78, 6384) applications and equipment. Jun-​ichi Yoshida of Kyoto University focused (Chem. Commun. 2013, 49, 9896)  on transformations that cannot be effected under batch conditions. Detlev Belder of the Universität Leipzig reported (Chem. Commun. 2013, 49, 11644)  flow reactions coupled to subsequent micropreparative separations. Leroy Cronin of the University of Glasgow described (Chem. Sci. 2013, 4, 3099) combining 3D printing of an apparatus and liquid handling for convenient chemical synthesis and purification. Many of the reactions of organic synthesis have now been adapted to flow conditions. We will highlight those transformations that incorporate particularly useful features. One of those is convenient handling of gaseous reagents. C. Oliver Kappe of the Karl-​Franzens-​University Graz generated (Angew. Chem. Int. Ed. 2013, 52, 10241) diimide in situ to reduce 1 to 2. David J. Cole-​Hamilton immobilized (Angew. Chem. Int. Ed. 2013, 52, 9805) Ru DuPHOS on a heteropoly acid support, allowing the flow hydrogenation of neat 3 to 4 in high ee. Steven V. Ley of the University of Cambridge added (Org. Process Res. Dev. 2013, 17, 1183) ammonia to 5 to give the thiourea 6. Alain Favre-​Réguillon of the Conservatoire National des Arts et Métiers used (Org. Lett. 2013, 15, 5978) oxygen to directly oxidize the aldehyde 7 to the carboxylic acid 8.

Professor Kappe showed (J. Org. Chem. 2013, 78, 10567) that supercritical acetonitrile directly converted an acid 9 to the nitrile 10. Hisao Yoshida of Nagoya University added (Chem. Commun. 2013, 49, 3793) acetonitrile to nitrobenzene 11 to give the para isomer 12 with high regioselectively. Kristin E. Price of Pfizer Groton coupled (Org. Lett. 2013, 15, 4342) 13 to 14 to give 15 with very low loading of the Pd catalyst. Andrew Livingston of Imperial College demonstrated (Org. Process Res. Dev. 2013, 17, 967) the utility of nanofiltration under flow conditions to minimize Pd levels in a Heck product. Andreas Kirschning reported (Angew. Chem. Int. Ed. 2013,

 29

Rapid heating was also the key to the Kondrat’eva assembly of the pyridine 20 from 18 and cyclopentene 19 reported (Org. Lett. 2013, 15, 3550) by Robert Britton of Simon Fraser University and Rainer E. Martin of Roche Basel. A flow technique allowed (Org. Process Res. Dev. 2013, 17, 1137) Kai Guo of the Nanjing University of Technology to optimize the preparation and separation of epoxidized soybean oil, represented here by the conversion of linoleic acid 21 to 22. Maurizio Benaglia and Alessandra Puglisi of the Università degli Studi di Milano passed (Org. Lett. 2013, 15, 3590) 23 and 24 through a column packed with an organocatalyst to give 25 in substantial ee. Srinivas Gangula employed (Org. Process Res. Dev. 2013, 17, 1272) a flow technique to optimize the two-​step coupling of 26 with 27 followed by oxidation to give 28.

Gregory P. Roth of the Sanford-​Burnham Medical Research Institute took advantage (ACS Med. Chem. Lett. 2013, 4, 1119) of the ease with which electrolysis is carried out under flow conditions to oxidize Diclofenac 29 to its metabolites. With added NaHSO3, the product was the phenol 30. When glutathione was added after the oxidation, the product was the adduct 31.

29  Flow Chemistry

52, 9813) on high frequency inductive coupling for the flow thermal conversion of 16 to 17.

30

15. Developments in Flow Chemistry Douglass F. Taber January 12, 2015

Klavs S. Jensen of MIT showed (Angew. Chem. Int. Ed. 2014, 53, 470) that “batch” kinetics could be developed in flow by online IR analysis and continuous control. Professor Jensen also demonstrated (Org. Process Res. Dev. 2014, 18, 402) the continuous flow production of an active pharmaceutical product, the direct renin inhibitor aliskiren, over two steps and two crystallizations, starting from two advanced intermediates. Michael Werner and Rainer E. Martin of Hoffmann-​La Roche AG Basel combined (Angew. Chem. Int. Ed. 2014, 53, 1704) flow synthesis with a flow-​based bioassay to develop structure–​activity relationships for a series of β-​secretase inhibitors. Carlos Mateos of Lilly S. A. and C. Oliver Kappe of the University of Graz used (J. Org. Chem. 2014, 79, 223)  flow photolysis to promote the bromination of 1 to 2. Alessandro Palmieri of the University of Camerino and Stefano Protti of the University of Pavia added (Adv. Synth. Catal. 2014, 356, 753) the aldehyde 3 to the acceptor 4 to give, after in-​flow reduction, the lactone 5. Peter H. Seeberger of the Max Planck Institute Mühlenberg showed (Org. Lett. 2014, 16, 1794) that the tumbling action of flow photolysis made the production of 7 by the unlinking of 6 from the polymer bead particularly efficient.

Enzymes can also be used under flow conditions. Jörg Pietruszka of the Heinrich-​ Heine-​Universität Düsseldorf employed (Adv. Synth. Catal. 2014, 356, 1007) commercial laccase to prepare 10 by coupling 8 with 9. Gas–​liquid mixing under flow conditions can also be effective. Núria López of ICIQ Catalonia and Javier Pérez-​R amírez of ETH Zurich developed (Chem. Eur J. 2014, 20, 5926) conditions for the selective hydrogenation of an alkyne 11 to the cis alkene 12. Jun-​ichi Yoshida of Kyoto University trapped (Chem. Eur J. 2014, 20, 7931) the intermediate organolithium from 13 with CO2 to give a carboxylate that was carried on to the purifiable O-​Su ester 14, ready for further coupling. Timothy F. Jamison, also of

 31

Thomas Wirth of Cardiff University combined (Synlett 2014, 25, 871) the diazo ester 21, generated in flow, with the aldehyde 20 to give an intermediate that was transformed in a third flow step into the β-​keto ester 22. Michael A.  McGuire of GlaxoSmithKline and Michael G. Organ of York University found (Chem. Eur. J. 2014, 20, 6603)  that the diazonium salt could be generated from 23 and in situ coupled with 24 under Pd catalysis to give the ester 25. André B. Charette of the Université de Montréal effected (Synlett 2014, 25, 1409) hydrolysis of the iodide 26 to the phenol, and then in a subsequent flow step benzylation of the phenoxide, leading to 27. Anastatios Polyzos of CSIRO and David W. Lupton of Monash University reduced (ACS Catal. 2014, 4, 2070) the acid chloride 28 to the aldehyde 30 by first forming the thioester with the mercaptan 29. Oliver Trapp of the Ruprecht-​Karls-​Universität Heidelberg cyclized (Adv. Synth. Catal. 2014, 356, 2081) 31 to 32 using an improved immobilized Grubbs Ru catalyst.

One of the great advantages of flow synthesis is the ease with which electrochemical transformations can be included. This is illustrated by the reductive cyclization of 33 to 34, reported (Tetrahedron Lett. 2014, 55, 1299) by Mitsuhiro Okimoto of the Kitami Institute of Technology.

31  Developments in Flow Chemistry

MIT, prepared (Angew. Chem. Int. Ed. 2014, 53, 3353) the amino phenol 17 by adding the chloromagnesium amide from 16 to the intermediate benzyne from 15, then oxidizing the product with air. Professor Kappe used (J. Org. Chem. 2014, 79, 1555) in situ generated diazomethane to convert the acid 18 to the chloroketone 19.

32

16. Flow Chemistry Douglass F. Taber September 28, 2015

Arturo Macchi of the University of Ottawa and Dominique M. Roberge of Lonza summarized (Org. Process Res. Dev. 2014, 18, 1286) a “toolbox approach” for the evolution from batch to continuous chemical synthesis. Michael D. Organ of York University developed (Org. Process Res. Dev. 2014, 18, 1315) a flow reactor with inline analytics, and Timothy D.  White of Eli Lilly described (Org. Process Res. Dev. 2014, 18, 1482) the continuous production of solid products under flow conditions. Electrochemical reduction and oxidation are particularly easy under flow conditions. Steven V.  Ley of the University of Cambridge oxidized (Org. Lett. 2014, 16, 4618) 1 under flow conditions, then condensed the product with tryptamine 2 to prepare the indole alkaloid Nazlinine 3. Thomas Wirth of Cardiff University electrolyzed (Org. Process Res. Dev. 2014, 18, 1377) the carbonate 4 in a non-​divided cell to return the deprotected phenol 5.

Timothy Noël of the Eindhoven University of Technology gathered (Chem. Eur. J. 2014, 20, 10562) an overview of photochemical transformations under flow conditions. Kevin I.  Booker-​Milburn of the University of Bristol observed (Chem. Eur. J. 2014, 20, 15226) superior yields for the coupling of 6 with 7 to form 8 under flow compared to batch conditions. Koichi Fukase of Osaka University and Ilhyong Ryu of Osaka Prefecture University converted (Chem. Eur. J. 2014, 20, 12750) 9 selectively to 10 under flow conditions. Alexei A. Lapkin, also of the University of Cambridge, optimized (Org. Process Res. Dev. 2014, 18, 1443) the singlet oxygen conversion of 11 to 12. Shawn K. Collins of the Université de Montréal cyclized (Org. Process Res. Dev. 2014, 18, 1571) 13 to 14.

There have been several advances in the use of enzymes under flow conditions. Rodrigo O. M. A. de Souza of the Federal University of Rio de Janeiro found (Org. Process Res. Dev. 2014, 18, 1372)  that lipase in a microemulsion-​based organogel

 3

Flow conditions are particularly suited for the transient generation of reactive intermediates. Dionicio Siegel, now at the University of California San Diego used (Org. Lett. 2014, 16, 3628)  in situ generated phthaloyl peroxide 22 to oxidize 21 to 23. Katja Buehler of TU Dortmund University employed (Org. Process Res. Dev. 2014, 18, 1516) a combination of enzymes to effect the oxidation of 24 to 25. Thomas L. LaPorte of Bristol-​Myers Squibb depended (Org. Process Res. Dev. 2014, 18, 1492)  on flow conditions to control the exothermic oxidation of 26 to 27. Frederic G.  Buono of Boehringer Ingelheim found (Org. Process Res. Dev. 2014, 18, 1527) flow conditions useful for optimizing the preparation of 30 by the addition of 29 to 28. Toby Broom of GlaxoSmithKline generated (Org. Process Res. Dev. 2014, 18, 1354) the trifluoroborate 32, ready for Suzuki-​Miyaura coupling, from 31 under flow conditions.

The value of flow was underlined by the preparation of 34 from 33 developed (Org. Process Res. Dev. 2014, 18, 1360) by C. Oliver Kappe of the University of Graz. The explosive trinitro intermediate could be generated and then reduced without any need for isolation.

33  Flow Chemistry

efficiently converted coupled 15 with 16 to make 17. Timothy F.  Jamison of MIT developed (Org. Lett. 2014, 16, 6092) a catch-​and-​release protocol for the reductive amination of 18 with 19 to give 20.

34

17. Selective Functionalization of C–​H Bonds Douglass F. Taber January 27, 2014

Jianhui Huang and Kang Zhao of Tianjin University devised (Chem. Commun. 2013, 49, 1211) a protocol for the oxidation of a terminal alkene 1 to the valuable four-​carbon synthon 2. M. Christina White of the University of Illinois effected (J. Am. Chem. Soc. 2013, 135, 7831) the oxidation of the terminal alkene 3 to the enone 4. Miquel Costas of the Universitat de Girona developed (J. Org. Chem. 2013, 78, 1421; Chem. Eur. J. 2013, 19, 1908) a family of Fe catalysts for the oxidation of methylenes to ketones. Depending on the catalyst, any of the three ketones from the oxidation of 5, including 6, could be made the dominant product.

Yumei Xiao and Zhaohai Qin of China Agricultural University optimized (Synthesis 2013, 45, 615) the Co-​catalyzed oxidation of the methyl group of 7 to give the aldehyde 8. Thanh Binh Nguyen of CNRS Gif-​sur-​Yvette established (J. Am. Chem. Soc. 2013, 135, 118) a protocol (not illustrated) for the oxidation of methyl groups on heteroaromatics. Shunsuke Chiba of Nanyang Technological University cyclized (Org. Lett. 2013, 15, 212, 3214) the amidine 9 to 10, and the hydrazone 11 to 12. These cyclizations proceeded by sequential C–​H abstraction followed by recombination, and so were racemizing. In contrast, the conversion of 13 to 14, developed (Science 2013, 340, 591) by Theodore A. Betley of Harvard University, proceeded with substantial retention of absolute configuration.

 35

Directed palladation of distal C–​H bonds continues to be developed. Srinivasarao Arulananda Babu of the Indian Institute of Science Education and Research effected (Org. Lett. 2013, 15, 3238) diastereoselective arylation of the cyclopropane 21 with 22 to give 23. M. Angeles Fernández-​Ibáñez and Juan C. Carretero of the Universidad Autónoma de Madrid showed (Chem. Sci. 2013, 4, 175) that the pyridylsulfonamide of 24 was an effective directing group for the arylation with 25 to give 26. Jin-​Quan Yu of Scripps/​La Jolla devised (J. Am. Chem. Soc. 2013, 135, 3387)  a protocol for the direct alkynylation of 27 with 28 to give 29. Gong Chen of Pennsylvania State University established (J. Am. Chem. Soc. 2013, 135, 2124) conditions for sp3-​sp3 coupling, combining 30 with 31 to give 32.

35  Selective Functionalization of C–H Bonds

Tsutomu Katsuki of Kyushu University designed (Angew. Chem. Int. Ed. 2013, 52, 1739) a Ru catalyst that was selective for the allylic position of the E-​alkene 15 to give 16. Amination was highly regioselective, and proceeded with excellent ee. Ilhyong Ryu of Osaka Prefecture University and Maurizio Fagnoni of the University of Pavia reported (Org. Lett. 2013, 15, 2554) the direct carbonylation of 17 to the amide 18. David W. C. MacMillan of Princeton University devised (Science 2013, 339, 1593) a protocol for the β-​arylation of an aldehyde 19 to give 20.

36

18. C–​H Functionalization: The Snyder Synthesis of (+)-​Scholarisine A Douglass F. Taber September 8, 2014

Thomas R. Hoye of the University of Minnesota devised (Nature 2013, 501, 531) the reagent 2, that cyclized to a benzyne that in turn dehydrogenated the alkane 1 to the alkene 3, and 4. Abigail G. Doyle of Princeton University developed (J. Am. Chem. Soc. 2013, 135, 12990) a reagent combination for the allylic fluorination of a terminal alkene 5 to the branched product 6.

Yan Zhang and Jianbo Wang of Peking University oxidized (Angew. Chem. Int. Ed. 2013, 52, 10573) the methyl group of 7 to give the nitrile 8. Hanmin Huang of the Lanzhou Institute of Chemical Physics found (Org. Lett. 2013, 15, 3370) conditions for the carbonylation of the benzylic site of 9, leading to coupling with 10 to form the amide 11.

Yu Rao of Tsinghua University effected (Angew. Chem. Int. Ed. 2013, 52, 13606) the direct methoxylation of 12, to give 13. Pd-​mediated methoxylation had previously been described (Chem. Sci. 2013, 4, 4187) by Bing-​Feng Shi of Zhejiang University. M.  Christina White of the University of Illinois, Urbana found (J. Am. Chem. Soc. 2013, 135, 14052) that with variant ligands on the Fe catalyst, the oxidation of 14 could be directed selectively to either 15 or 16.

C–​H bonds can also be converted to C–​N bonds. Sukbok Chang of KAIST oxidized (J. Am. Chem. Soc. 2013, 135, 12861) the unsaturated ester 17 with 18 to form

 37

Ethers are easily oxidized. Taking advantage of this, Yun Liang of Hunan Normal University coupled (Synthesis 2013, 45, 3137) the bromoalkyne 23 with tetrahydrofuran 22 to give 24. Guangbin Dong of the University of Texas, Austin devised (J. Am. Chem. Soc. 2013, 135, 17747) a protocol for the β-​arylation of ketones, including the preparation of 27 by the coupling of 25 with 26. Huw M. L. Davies of Emory University cyclized (Org. Lett. 2013, 15, 6120) the diazo ester 28 to the β-​lactone, that under the conditions of the reaction lost CO2 to give the allyl silane 29 with high geometric control. Richard S.  Grainger of the University of Birmingham generated (Org. Biomol. Chem. 2013, 11, 6856)  the alkylidene carbene from 30 using two different procedures. Addition of lithiated TMS diazomethane led to a reactive free alkylidene, that primarily inserted into the Si–​O bond to give 32. Chloromethylenation followed by exposure to KHMDS gave a less reactive, more slowly reacting carbene, that gave a much larger proportion of the desired 31.

(+)-​Scholarisine A  35 was isolated from Alstonia scholaris, used in traditional Chinese medicine for the treatment of respiratory disease. Scott A.  Snyder, now at Scripps/​Florida, devised (J. Am. Chem. Soc. 2013, 135, 12964) a concise synthesis of 35, a key step of which was the cyclization of 33 to 34.

37  C–H Functionalization

the enamide 18. Gong Chen of Pennsylvania State University cyclized (Angew. Chem. Int. Ed. 2013, 52, 11124)  the amide 20 to the γ-​lactam 21. Professor Shi reported (Angew. Chem. Int. Ed. 2013, 52, 13588) a related approach to β-​lactams.

38

19. C–​H Functionalization: The Maimone Synthesis of Podophyllotoxin Douglass F. Taber January 26, 2015

Matthias Beller of the Universität Rostock developed (Angew. Chem. Int. Ed. 2014, 53, 6477) a Rh catalyst for the acceptorless dehydrogenation of an alkane 1 to the alkene 2. Bhisma K. Patel of the Indian Institute of Technology Guwahati effected (Org. Lett. 2014, 16, 3086) oxidation of cyclohexane 3 and 4 to form the allylic benzoate 5.

Justin Du Bois of Stanford University devised (Chem. Sci. 2014, 5, 656)  an organocatalyst that mediated the hydroxylation of 6 to 7. Vladimir Gevorgyan of the University of Illinois, Chicago hydrosilylated (Nature Chem. 2014, 6, 122) 8 to give an intermediate that, after Ir-​catalyzed intramolecular C–​H functionalization followed by oxidation, was converted to the diacetate 9. Sukbok Chang of KAIST used (J. Am. Chem. Soc. 2014, 136, 4141) the methoxime of 10 to direct selective amination of the adjacent methyl group, leading to 11. John F. Hartwig of the University of California, Berkeley effected (J. Am. Chem. Soc. 2014, 136, 2555) diastereoselective Cu-​catalyzed amination of 12 with 13 to make 14.

David W. C. MacMillan of Princeton University accomplished (J. Am. Chem. Soc. 2014, 136, 6858)  β-​alkylation of the aldehyde 15 with acrylonitrile 16 to give 17. Yunyang Wei of the Nanjing University of Science and Technology alkenylated (Chem. Sci. 2014, 5, 2379) cyclohexane 3 with the styrene 18, leading to 19.

 39

Philippe Dauban of CNRS Gif-​sur-​Yvette prepared (Eur. J.  Org. Chem. 2014, 66) the useful crystalline chiron 27 by asymmetric amination of the enol triflate 26 with 25. Matthew J. Gaunt of the University of Cambridge showed (J. Am. Chem. Soc. 2014, 136, 8851) that the phenylative cyclization of 28 with 29 to 30 proceeded with near-​perfect retention of absolute configuration.

Podophyllotoxin 34 is the core of the clinically-​important anticancer agents etoposide and teniposide. Thomas J. Maimone, also of the University of California, Berkeley, devised (Angew. Chem. Int. Ed. 2014, 53, 3115) a two-​step conversion of 31 to 34 that took advantage of recent developments in Pd-​catalyzed C–​H arylation, coupling with 32 to make 33. This approach will allow the incorporation of almost any aryl group.

39  C–H Functionalization

Bin Wu of the Kunming Institute of Botany described (Org. Lett. 2014, 16, 480) the Pd-​mediated cyclization of 20 to 21. Similar results using Cu catalysis were reported (Angew. Chem. Int. Ed. 2014, 53, 3496, 3706)  by Yoichiro Kuninobu and Motomu Kanai of the University of Tokyo and by Haibo Ge of IUPUI. Jin-​Quan Yu of Scripps La Jolla constructed (J. Am. Chem. Soc. 2014, 136, 5267) the lactam 24 by γ-​alkenylation of the amide 22 with 23, followed by cyclization.

40

20. C–​H Functionalization: The Shaw Synthesis of E-​δ-​Viniferin Douglass F. Taber September 14, 2015

Thomas Lectka of Johns Hopkins University reported (J. Org. Chem. 2014, 79, 8895) a simple protocol for free radical monofluorination, exemplified by the conversion of 1 to 2. Michael K.  Hilinski of the University of Virginia used (Org. Lett. 2014, 16, 6504) a catalytic amount of the ketone 4 to mediate the oxidation of 3 to 5. Oxidation of 3 with DMDO gave the regioisomeric tertiary alcohol (not illustrated).

Jeung Gon Kim and Sukbok Chang of KAIST used (Chem. Commun. 2014, 50, 12073)  an Ir catalyst to convert 6 selectively to the primary sulfonamide 7. Paul J. Chirik of Princeton University employed (J. Am. Chem. Soc. 2014, 136, 12108) a Co catalyst to effect the migration of the internal alkene of 8 to the terminal alkene, that then underwent dehydrogenative silylation with 9 to deliver the allyl silane 10. Jiang Cheng of Changzhou University developed (J. Org. Chem. 2014, 79, 9847)  conditions for the aminoalkylation of cyclohexane 11 with 12 to give 13. Ilhyong Ryu of Osaka Prefecture University and Maurizio Fagnoni of the University of Pavia observed (Chem. Sci. 2014, 5, 2893) high selectivity in the addition of 14 to 15. Of the five possible regioisomers, 16 dominated.

In another light-​mediated transformation, Shin Kamijo of Yamaguchi University and Masayuki Inoue of the University of Tokyo added (Chem. Sci. 2014, 5, 4339) 17 to 18 to give 19. Huw M. L. Davies of Emory University established (J. Am. Chem. Soc. 2014, 136, 17718) conditions for the enantioselective alkylation of a methyl ether 21

 41

James A. Bull of Imperial College London effected (Org. Lett. 2014, 16, 4956) selective cis-​arylation of the proline-​derived amide 23 with 24 to give 25. E. Peter Kündig of the University of Geneva coupled (Chem. Eur. J. 2014, 20, 15021) the amine 27 with 26, then cyclized that product to the indoline 28. The enantiomeric Pd catalyst delivered the regioisomeric C–​H insertion product. Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne observed (Angew. Chem. Int. Ed. 2014, 53, 1818) the efficient cyclization of 29 to 30. Chi-​Ming Che of the University of Hong Kong converted (Angew. Chem. Int. Ed. 2014, 53, 14175) the ketone of 31 into the dialkyl diazo compound in situ, then used a Ru catalyst to cyclize that with high diastereocontrol to 32.

The reversatrol dimer E-​δ-​viniferin 35 is induced in grapes by fungal infection. En route to 35, Jared T. Shaw of University of California Davis oxidized (J. Am. Chem. Soc. 2014, 136, 15142) the hydrazone of 33 to the diaryl diazo intermediate, then cyclized that with a Rh catalyst to 34 in high ee.

41  C–H Functionalization

with 20 to give the ester 22. Selective methyl insertion was observed even with much more complex substrates. The trichloroethyl ester was critical for this transformation.

42

21. C–​C Bond Construction: The Zhu Synthesis of Goniomitine Douglass F. Taber March 10, 2014

Non-​enolizable β-​keto esters such as 3 are fragile and difficult to prepare. Karl J. Hale of Queen’s University Belfast devised (Org. Lett. 2013, 15, 370) soft enolization conditions for methoxycarbonylation of 1 with 2. Zheng Huang of the Shanghai Institute of Organic Chemistry coupled (Org. Lett. 2013, 15, 1144) 4 with 5 under Ir catalysis to make 6. Tomoya Miura and Masahiro Murakami of Kyoto University combined (Angew. Chem. Int. Ed. 2013, 52, 3883) the diazo precursor 8 with the allylic alcohol 7 to give 9, the product of Claisen rearrangement. Tsuyoshi Satoh of the Tokyo University of Science showed (Tetrahedron Lett. 2013, 54, 2533) that the combination of the carbenoid 10 with a ketone enolate 11 led to the cyclopropanol (not illustrated). Jin Kun Cha of Wayne State University found (Org. Lett. 2013, 15, 1780) that such cyclopropanols coupled with an acid chloride 12 under Pd catalysis to give the diketone 13.

Christopher J. O’Brien of Dublin City University established (Chem. Eur. J. 2013, 19, 5854) conditions for the catalytic Wittig reaction of 14 with 15 to give 16, with in situ reduction of the phosphine oxide. Amir H. Hoveyda of Boston College showed (Org. Lett. 2013, 15, 1414) that the allene of 17 underwent selective borylation, leading after coupling with 18 to the triene 19. Damian W. Young of the Broad Institute demonstrated (Org. Lett. 2013, 15, 1218) that ring-​closing metathesis gave the alkenyl silane 20 with high geometric control. Halogenation to give 21 could then proceed with either retention or inversion of alkene geometry.

 43

43  C–C Bond Construction

Jianwei Sun of the Hong Kong University of Science and Technology and Zigang Li of the Shenzen Graduate School of Peking University condensed (J. Am. Chem. Soc. 2013, 135, 4680) the alkyne 22 with 23 to give the trisubstituted alkene 24 with high geometric control. The condensation worked equally well with medium and large ring ethers. Hua-​Jian Xu of the Hefei University of Technology combined (Org. Lett. 2013, 15, 1472) the bromo alkyne 25 with the carboxylate 26 to give the nitrile 27. Gregory B. Dudley of Florida State University effected (Tetrahedron Lett. 2013, 54, 1312) fragmentation of the triflate 28 to the alkyne 29. Doug E. Frantz of the University of Texas at San Antonio eliminated (J. Am. Chem. Soc. 2013, 135, 4970) the triflate of the prochiral 30 to deliver the allene 31 in high ee. Keiji Maruoka, also of Kyoto University, developed (Nature Chem. 2013, 5, 240) phase transfer conditions for the addition of 32 to 33 to give 34 in high ee.

Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne coupled (Angew. Chem. Int. Ed. 2013, 52, 3272) the alkenyl triflate 35 with the carboxylate 36 to give 37. Several more steps led to the indole alkaloid goniomitine 38.

4

22. C–​C Bond Construction: The Kingsbury Synthesis of (−)-​Dihydrocuscohygrine Douglass F. Taber June 30, 2014

Akio Baba of Osaka University combined (Chem. Lett. 2013, 42, 1551)  reduction of the acid 1 with subsequent condensation with the ketene silyl acetal 2 to directly give the coupled product 3. Song-​Lin Zhang of Soochow University showed (Chem. Commun. 2013, 49, 10635) that the allyl Sm reagent 5 could be added to an aldehyde 4 under reducing conditions, leading to the alkene 6. In a related development, Patrick Perlmutter of Monash University reduced (Org. Lett. 2013, 15, 4327) the intermediate lactol from addition of the alkyl lithium reagent 8 to the lactone 7, to give the alcohol 9. Yoshihiro Miyake, now at Nagoya University, and Yoshiaki Nishibayashi of the University of Tokyo added (Chem. Commun. 2013, 49, 7854) the benzyl radical from the decarboxylation of 10 to the acceptor 11 to give 12. Yasuharu Yoshimi of the University of Fukui (Tetrahedron Lett. 2013, 54, 4324) and Larry E. Overman of the University of California, Irvine (J. Am. Chem. Soc. 2013, 135, 15342) reported related results.

David Milstein of the Weizmann Institute of Science developed (Angew. Chem. Int. Ed. 2013, 52, 14131) an Fe catalyst for the hydrogenation of an alkyne 13 to the E-​ alkene 14. Zhi-​Xiang Yu of Peking University showed (Org. Lett. 2013, 15, 4634) that kinetic isomerization of the alkene 15 led selectively to the Z-​alkene 16. Umasish Jama of Jadavpur University prepared (Eur. J. Org. Chem. 2013, 4823) the nitroalkene 18 by condensing nitromethane with the aldehyde 17. Vladimir A.  D’yakonov of the Russian Academy of Sciences, Ufa described (Chem. Commun. 2013, 49, 8401; Tetrahedron 2013, 69, 8516) the remarkably selective coupling of the allene 19 with the allene 20 to give the Z,Z-​diene 21.

 45

45  C–C Bond Construction

Sang-​Hyeup Lee of the Catholic University of Daegu assembled (Synlett 2013, 24, 1953) the ketone 24 by coupling the alkynyl aluminum 23 with the nitrile 22. Jean-​Marc Weibel and Patrick Pale of the Université de Strasbourg showed (Chem. Eur. J. 2013, 19, 8765) that the alkenyl nosylate (p-​nitrobenzenesulfonate) 25 coupled smoothly with 26, leading to the enyne 27. Reinhold Zimmer and Hans-​Ulrich Reissig of the Freie Universität Berlin described (Synthesis 2013, 45, 2752) similar results with alkenyl nonaflates.

Shengmin Ma of the Shanghai Institute of Organic Chemistry prepared (J. Am. Chem. Soc. 2013, 135, 11517) the allene 29 by the enantioselective carbonylation of a racemic carbonate 28. Junliang Zhang of East China Normal University and Jianwei Sun of the Hong Kong University of Science and Technology developed (J. Am. Chem. Soc. 2013, 135, 18020) an organocatalyst for the enantioselective coupling of nitromethane with 30 to deliver 31.

Alkyl diazo intermediates are sufficiently stable that they can be quickly handled. Jason S. Kingsbury, now at Pomona College, added (J. Org. Chem. 2013, 78, 10573) the diazo alkane from 32 twice to formaldehyde to give the ketone 33 with minimal racemization. Reduction followed by reductive methylation then completed the synthesis of the Erythroxylon coca alkaloid (−)-​dihydrocuscohygrine 34.

46

23. C–​C Bond Construction: The Galano Synthesis of 8-​F3t-​Isoprostane Douglass F. Taber January 19, 2015

Nobuaki Kambe of Osaka University devised (Synthesis 2014, 46, 1583)  simple conditions for coupling an alkyl halide 1 with a Grignard reagent 2, leading to 3. Michael J. Chetcuti and Vincent Ritleng of the Université de Strasbourg arylated (Chem. Commun. 2014, 50, 4624) the ketone 4 with 5 to give 6. Ilhyong Ryu of Osaka Prefecture University effected (J. Org. Chem. 2014, 79, 3999) net conjugate acylation of the enone 8 to give 9 by reducing 7 in the presence of carbon monoxide. Yasushi Obora of Kansai University employed (Chem. Commun. 2014, 50, 2491) a borrowed hydrogen strategy to effect the net methylation of 10 to 11. There have been many examples of the alkylation of ketones using variations on this strategy.

Robert H.  Grubbs and Brian M.  Stoltz of Caltech decarboxylated (Adv. Synth. Catal. 2014, 356, 130)  an acid 12 to the corresponding alpha olefin 13. Lindsey O. Davis of Berry College combined (Tetrahedron Lett. 2014, 55, 3100) the imine 14 with the aldehyde 15 in the presence of 16 to give the enone 17. Masahiro Miyazawa of the University of Toyoma maintained (Synlett 2014, 25, 531) the geometric purity of 18 while coupling it with Me3Al to give the diene 19. Naoki Kanoh of Tohoku University used (Eur. J. Org. Chem. 2014, 1376) the Micalizio protocol to add 22 with 21 to 20 to give the triene 23.

 47

Zhaoguo Zhang of Shanghai Jiao Tong University and Tahar Ayad and Virginie Ratovelomanana-​Vidal of Chimie ParisTech coupled (ACS Catal. 2014, 4, 44)  31 with the dienyl bromide 30 to deliver the disubstituted allene 32 in high ee. Amir H. Hoveyda of Boston College developed (Angew. Chem. Int. Ed. 2013, 52, 7694) a procedure for the preparation of alkynes such as 33 in substantial ee. He showed that 33 could be isomerized to the corresponding trisubstituted allene 34 with maintenance of the ee.

The isoprostanes and neuroprostanes, products of non-​enzymatic oxidation of essential fatty acids, have physiologically-​important receptors in the human body. Facing difficulty in assembling the upper sidechain of 8-​F3t-​isoprostane 37, Jean-​Marie Galano of University Montpellier I and II turned (Chem. Eur. J. 2014, 20, 6374) to alkyne metathesis. Indeed, 35 readily cyclized to 36, that was carried on to 37.

47  C–C Bond Construction

Xile Hu of the Ecole Polytechnique Fédérale de Lausanne coupled (Org. Lett. 2014, 16, 2566) 25 with the iodide 24 to give the alkyne 26. Keiji Tanino of Hokkaido University prepared (Tetrahedron Lett. 2014, 55, 1097) the α-​quaternary alkyne 29 by 1,2-​addition of 28 to the ketone 27 followed by pinacol rearrangement.

48

24. C–​C Bond Construction: The Hou Synthesis of (−)-​Brevipolide H Douglass F. Taber June 29, 2015

Yao Fu and Lei Liu of the University of Science and Technology of China devised (Chem. Eur. J. 2014, 20, 15334) conditions for the coupling of a halide 2 with a tosylate 1 with inversion of absolute configuration, leading to 3. Hegui Gong of Shanghai University coupled (J. Am. Chem. Soc. 2014, 136, 17645) the glucosyl bromide 4 with an anhydride 5 to give the ketone 6.

Luigi Vaccaro of the Università di Perugia showed (Org. Lett. 2014, 16, 5721) that TBAF promoted the opening of the epoxide 7 with the ketene silyl acetal 8, leading to the lactone 9. Valérie Desvergnes and Yannick Landais of the University of Bordeaux assembled (Chem. Eur. J. 2014, 20, 9336) the diketone 12 by using a Stetter catalyst to promote the conjugate addition of the acyl silane 11 to the enone 10. Thomas Werner of the Leibniz-​Institute for Catalysis reported (Eur. J. Org. Chem. 2014, 6873)  the enantioselective conversion of the prochiral triketone 13 to the bicyclic enone 15 by an intramolecular Wittig reaction, mediated by 14. Elizabeth H. Krenske of the University of Queensland and Christopher J. O’Brien also reported (Angew. Chem. Int. Ed. 2014, 53, 12907) progress (not illustrated) on catalytic Wittig reactions.

Michael J. Krische of the University of Texas showed (J. Am. Chem. Soc. 2014, 136, 11902) that Ru-​mediated addition of 17 to the aldehyde derived in situ from 16 gave 18 with high Z-​selectivity. Vladimir Gevorgyan of the University of Illinois at Chicago constructed (J. Am. Chem. Soc. 2014, 136, 17926) the trisubstituted alkene 20 by the

 49

Boris A.  Trofimov of the Irkutsk Institute of Chemistry Siberian Branch developed (Eur. J.  Org. Chem. 2014, 4663)  aqueous conditions for the preparation of a propargylic alcohol 26 by the addition of an alkyne 25 to the ketone 24. Huanfeng Jiang of the South China University of Technology prepared (Angew. Chem. Int. Ed. 2014, 53, 14485) the alkyne 28 by the oxidative elimination of the tosylhydrazone 27. Matthias Brewer of the University of Vermont fragmented (J. Org. Chem. 2014, 79, 6037) the ketone 29 to the keto alkyne 31 by the addition of ethyl diazoacetate 30 followed by exposure of the adduct to SnCl4. Mariappan Periasamy of the University of Hyderabad prepared (Eur. J. Org. Chem. 2014, 6067) a propargylic amine by combining 32, 33, and 34, then eliminated it to the enantiomerically pure allene 35 by warming with ZnBr2.

The breviolides, isolated from Hyptis brevipes and Lippia alva, are inhibitors of the chemokine receptor CCR5. Preparing the starting material for a synthesis of ent-​ brevipolide 39, Duen-​Ren Hou of National Central University took advantage (Org. Lett. 2014, 16, 5328) of the superior reactivity of allylic alcohols in Ru-​mediated cross metathesis, combining 36 with 37 to make 38.

49  C–C Bond Construction

intramolecular Heck cyclization of 19. Kálmán J. Szabó of Stockholm University optimized (Chem. Commun. 2014, 50, 9207) the Pd-​catalyzed borylation of the alkene 21 followed by in situ addition to the aldehyde 22 to give 23.

50

25. Alkenes Allison K. Griffith and Tristan H. Lambert March 17, 2014

The α-​C–​H functionalization of piperidine catalyzed by tantalum complex 1 to produce amine 2 was developed (Org. Lett. 2013, 15, 2182) by Laurel L. Schafer at the University of British Columbia. An asymmetric diamination of diene 3 with diaziridine reagent 4 under palladium catalysis to furnish cyclic sulfamide 5 was developed (Org. Lett. 2013, 15, 796) by Yian Shi at Colorado State University. Enantioenriched β-​fluoropiperdine 8 was prepared (Angew. Chem. Int. Ed. 2013, 52, 2469) via aminofluorocyclization of 6 with hypervalent iodide 7, as reported by Cristina Nevado at the University of Zurich. Erick M. Carreira at ETH Zürich disclosed (J. Am. Chem. Soc. 2013, 135, 6814) a ruthenium-​catalyzed hydrocarbamoylation of allylic formamide 9 to yield pyrrolidone 10.

Hans-​Günther Schmalz at the University of Köln disclosed (Angew. Chem. Int. Ed. 2013, 52, 1576) an asymmetric hydrocyanation of styrene 11 with Ni(cod)2 and phosphine–​phosphite ligand 12 to yield exclusively the branched cyanide 13. A similar transformation of styrene 11 to the hydroxycarbonylated product 15 was catalyzed (Chem. Commun. 2013, 49, 3306) by palladium complex 14, as reported by Matthew L. Clarke at the University of St Andrews.

Feng-​Ling Qing at the Chinese Academy of Sciences found (Angew. Chem. Int. Ed. 2013, 52, 2198) that the hydrotrifluoromethylation of unactivated alkene 16 to 17 was catalyzed by silver nitrate. The same transformation was also reported (J. Am.

 51

Clark R. Landis at the University of Wisconsin, Madison reported (Angew. Chem. Int. Ed. 2013, 52, 1564) a one-​pot asymmetric hydroformylation using 21 followed by Wittig olefination to transform alkene 19 into the γ-​chiral α,β-​unsaturated carbonyl compound 20. Debabrata Mati at the Indian Institute of Technology Bombay found (J. Am. Chem. Soc. 2013, 135, 3355) that alkene 22 could be nitrated stereoselectively with silver nitrite and TEMPO to form alkene 23.

Damian W. Young at the Broad Institute disclosed (Org. Lett. 2013, 15, 1218) that a macrocyclic vinylsiloxane 24, which was synthesized via an E-​selective ring closing metathesis reaction, could be functionalized to make either E-​ or Z-​alkenes, 25 and 26.

A ruthenium catalyst 28 exhibiting Z-​selectivity for the homodimerization of alkene 27 was disclosed (J. Am. Chem. Soc. 2013, 135, 1276) by Robert H. Grubbs at Caltech. Meanwhile, a Z-​selective cross metathesis of vinyl-​B(pin) 30 and alkene 32 with a molybdenum catalyst 31 was disclosed (J. Am. Chem. Soc. 2013, 135, 6026) by Amir H. Hoveyda at Boston College.

51  Alkenes

Chem. Soc. 2013, 135, 2505) by Véronique Gouverneur at the University of Oxford using a ruthenium photocatalyst and the Umemoto reagent 18.

52

26. Alkene Reactions: The Xu/​Loh Synthesis of Vitamin A1 Douglass F. Taber September 15, 2014

Abdolreza Rezaeifard and Maasoumeh Jafarpour of the University of Birjand devised (J. Am. Chem. Soc. 2013, 135, 10036) an easily-​scaled protocol for the Mo-catalyzed “on water” epoxidation of an alkene 1 to 2, using molecular O2. Needing to epoxidize the sensitive alkene 3 to 5, Douglass F. Taber of the University of Delaware developed (Org. Synth. 2013, 90, 350) a convenient preparation of mmol quantities of the versatile oxidant dimethyldioxirane 4.

Robert H.  Grubbs of Caltech showed (Angew. Chem. Int. Ed. 2013, 52, 9751)  that the Wacker oxidation of internal alkenes could proceed with high regioselectivity, as exemplified by the conversion of 6 to 7. David A. Nicewicz of the University of North Carolina demonstrated (J. Am. Chem. Soc. 2013, 135, 10334) the remarkable anti-​Markovnikov addition of the acid 9 to the alkene 8, to give 10. Pieter C. A. Bruijnincx and Robertus J. M. Klein Gebbink of the University of Utrecht established (Chem. Eur. J. 2013, 19, 15012) a robust one-​pot protocol for epoxidation, epoxide hydrolysis and periodate cleavage, for the net oxidative cleavage of the alkene 11 to the aldehydes 12 and 13. Tomoki Ogoshi of Kanazawa University observed (Org. Lett. 2013, 15, 3742) that permanganate with a phase transfer catalyst could selectively oxidize the linear alkene 14 to 15 in the presence of branched alkenes. Davood Azarifar of Bu-​Ali Sina University devised (Synlett 2013, 24, 1377) the reagent 17 as a useful alternative to ozone, as illustrated by the oxidation of 16 to 18. Ning Jiao of Peking University effected (J. Am. Chem. Soc. 2013, 135, 11692) the unsymmetrical cleavage of the alkene 19 to the nitrile aldehyde 20.

 53

53  Alkene Reactions

Tiow-​Gan Ong of the Academia Sinica added (Org. Lett. 2013, 15, 5358) 22 to the alkene 21 to give the linear product 23. This could be hydrolyzed to the acid, or reduced and hydrolyzed to the aldehyde. Joost N.  H. Reek of the University of Amsterdam isomerized (ACS Catal. 2013, 3, 2939) the terminal alkene of 24 to the internal alkene, then hydroformylated that directly to give the α-​methyl branched aldehyde 25. Laurel L. Schafer of the University of British Columbia developed (Angew. Chem. Int. Ed. 2013, 52, 9144; see also Chem. Eur. J. 2013, 19, 8751) an improved Ta catalyst that allowed the room-​temperature aminoalkylation of 26 to give 28. Jianrong (Steve) Zhou of Nanyang Technological University optimized (Chem. Commun. 2013, 49, 10236) the branched Heck reaction, adding 30 to 29 to give 31.

Yun-​He Xu of the University of Science and Technology of China and Teck-​ Peng Loh of that institution and Nanyang Technological University uncovered the Pd-​mediated coupling of t-​butyl acrylate (Chem. Sci. 2013, 4, 4520, not illustrated) and methyl vinyl ketone 33 (Org. Lett. 2013, 15, 5531) to an alkene 32 to give the polyene 34. This was a key step in their synthesis of Vitamin A1 35.

54

27. Reactions of Alkenes Douglass F. Taber March 30, 2015

The catalytic reduction of the alkene 1 gave the cis-​fused product (not illustrated), by kinetic H2 addition to the less congested face of the alkene. Ryan A. Shenvi of Scripps La Jolla found (J. Am. Chem. Soc. 2014, 136, 1300) conditions for stepwise HAT, converting 1 to the thermodynamically-​favored trans-​fused ketone 2. Seth B. Herzon of Yale University devised (J. Am. Chem. Soc. 2014, 136, 6884) a protocol for the reduction, mediated by 4, of the double bond of a haloalkene 3 to give the saturated halide 5. The Shenvi conditions also reduced a haloalkene to the saturated halide.

Daniel J.  Weix of the University of Rochester and Patrick L.  Holland, also of Yale University, established (J. Am. Chem. Soc. 2014, 136, 945) conditions for the kinetic isomerization of a terminal alkene 6 to the Z internal alkene 7. Christoforos G. Kokotos of the University of Athens showed (J. Org. Chem. 2014, 79, 4270) that the ketone 9, used catalytically, markedly accelerated the Payne epoxidation of 8 to 10. Note that Helena M. C. Ferraz of the Universidade of São Paulo reported (Tetrahedron Lett. 2000, 41, 5021) several years ago that alkene epoxidation was also easily carried out with DMDO generated in situ from acetone and oxone. Theodore A. Betley of Harvard University prepared (Chem. Sci. 2014, 5, 1526) the allylic amine 12 by reacting the alkene 11 with 1-​azidoadamantane in the presence of an iron catalyst. Rodney A. Fernandes of the Indian Institute of Technology Bombay developed (J. Org. Chem. 2014, 79, 5787) efficient conditions for the Wacker oxidation of a terminal alkene 6 to the methyl ketone 13. Yong-​Qiang Wang of Northwest University oxidized (Org. Lett. 2014, 16, 1610) the alkene 6 to the enone 14. Peili Teo of the National University of Singapore devised (Chem. Commun. 2014, 50, 2608) conditions for the Markovnikov hydration of the alkene 6 to the alcohol 15. Internal alkenes were inert under these conditions, but Yoshikazo Kitano of the Tokyo University of Agriculture and Technology effected (Synthesis 2014, 46, 1455)  the Markovnikov amination (not illustrated) of more highly substituted alkenes.

 5

55  Reactions of Alkenes

Andrei V. Malkov of Loughborough University and Pavel Kocovsky of Stockholm University converted (Chem. Eur. J. 2014, 20, 4542) the alkene 16 to the unsaturated ester 17. Guangbin Dong of the University of Texas at Austin showed (Science 2014, 345, 68) that a ketone 18 could be alkylated with an alkene 11, leading to the α-​alkyl ketone 19. Uttam K. Tambar of University of Texas Southwestern Medical Center activated (Angew. Chem. Int. Ed. 2014, 53, 1664) the alkene 20 by exposure to the commercial reagent 21, then directly coupled that intermediate product with a Grignard reagent 22 to give 23.

M. Christina White of the University of Illinois, Urbana oxidized (J. Am. Chem. Soc. 2014, 136, 5750) the alkene 24 in the presence of 25 to give the coupled product 26. Shang-​Dong Yang of Lanzhou University showed (Org. Lett. 2014, 16, 3118) that the electron-​deficient arene 27 could couple with 24 under oxidative conditions, leading to 28. Phil S. Baran, also of Scripps La Jolla, assembled (J. Am. Chem. Soc. 2014, 136, 1304) the ketone 31 by adding the alkene 29 in a conjugate sense to the enone 30.

56

28. Reactions of Alkenes: The Usami Synthesis of (−)-​Pericosine E Douglass F. Taber September 21, 2015

Dasheng Leow of the National Tsing Hua University used (Eur. J. Org. Chem. 2014, 7347) photolysis to activate the air oxidation of hydrazine to generate diimide, that then reduced 1 selectively to 2. Kevin M. Peese of Bristol-​Myers Squibb effected (Org. Lett. 2014, 16, 4444) ring-​closing metathesis of 3 followed by in situ reduction to form 4.

Jitendra K.  Bera of the Indian Institute of Technology Kanpur effected (J. Am. Chem. Soc. 2014, 136, 13987) gentle oxidative cleavage of cyclooctene 5 to the dialdehyde 6. Arumugam Sudalai of the National Chemical Laboratory observed (Org. Lett. 2014, 16, 5674) high regioselectivity in the oxidation of the alkene 7 to the ketone 8.

Hao Xu of Georgia State University also observed (J. Am. Chem. Soc. 2014, 136, 13186) high regioselectivity in the oxidation of the alkene 9 with 10, leading to the urethane 11. Justin Du Bois of Stanford University developed (J. Am. Chem. Soc. 2014, 136, 13506) mild conditions for the net double amination of the alkene 12 with 13, leading to 14. Jiaxi Xu and Pingfan Li of the Beijing University of Chemical Technology devised (Org. Lett. 2014, 16, 6036) a protocol for the allylic thiomethylation of an alkene with 16, converting 15 to 17. Matthias Beller of the Leibniz-​Institüt für Katalyse combined

 57

Phil S.  Baran of Scripps/​La Jolla added (Angew. Chem. Int. Ed. 2014, 53, 14382) the diazo dienone 21 to the alkene 20 to give, after exposure to HCl, the arylated product 22. Markus R.  Heinrich of the Friedrich-​Alexander-​Universität Erlangen-​Nürnberg employed (Chem. Eur. J. 2014, 20, 15344) Selectfluor as both an oxidizing and a fluorinating agent in the related addition of 24 to 23 to give 25. Debabrata Maiti at the Indian Institute of Technology Bombay activated (J. Am. Chem. Soc. 2014, 136, 13602) the ortho position of 27, then added that intermediate to 26 to give 28. John F. Bower of the University of Bristol used (J. Am. Chem. Soc. 2014, 136, 10258) an Ir catalyst to achieve the opposite regioselectivity in the addition of 30 to 29 to give 31. Although originally isolated from the sea hare Aplysia kurodai, (−)-​pericosine E 35 was later shown to in fact be produced by the fungus Periconia byssoides. In the course of a synthesis of 35, Yoshihide Usami of the Osaka University of Pharmaceutical Sciences found (Org. Lett. 2014, 16, 3760)  that trifluoromethyl methyl dioxirane (TFDO) 33 epoxidized 32 to 34 with high selectivity.

57  Reactions of Alkenes

(Chem. Eur. J. 2014, 20, 15692) hydroformylation, aldol condensation, and reduction to convert the alkene 18 to the ketone 19.

58

29. Construction of Single Stereocenters Tristan H. Lambert February 10, 2014

Haifeng Du at the Chinese Academy of Sciences reported (J. Am. Chem. Soc. 2013, 135, 6810) the borane-​catalyzed asymmetric hydrogenation of imine 1 to 2 using the diene 3 as a chiral ligand for boron. A single-​enzyme cascade for the reductive transamination of acetophenone 4 with amine 5 to produce enantiopure sec-​phenethylamine 6 was developed (Chem. Commun. 2013, 49, 161) by Per Berglund at the KTH Royal Institute of Technology in Sweden. A group at Boehringer Ingelheim in Ridgefield, Connecticut, led by Jonathan T.  Reeves, disclosed (J. Am. Chem. Soc. 2013, 135, 5565) a procedure for the addition of DMF anion to N-​sulfinyl imine 7 to furnish tert-​leucine amide 8 with high diastereoselectivity. The tertiary carbinamine 10 was synthesized (Org. Lett. 2013, 15, 34) via the carbolithiation/​rearrangement of vinylurea 9 as reported by Jonathan Clayden at the University of Manchester.

Gregory C. Fu at Caltech reported (Angew. Chem. Int. Ed. 2013, 52, 2525) that the chiral phosphine 12 catalyzed the enantioselective addition of trifluoroacetamide to allene 11 to produce γ-​amino ester 13 in enantioenriched form. Adeline Vallribera at the Autonomous University of Barcelona found (Org. Lett. 2013, 15, 1448) that a europium pybox complex effected the highly enantioselective α-​amination of β-​ketoester 14 to generate 15 on the way to the Parkinson’s disease co-​drug L-​carbidopa.

Hisashi Yamamoto at the University of Chicago and Chubu University reported (J. Am. Chem. Soc. 2013, 135, 3411) that a halfnium(IV) complex of the bishydroxamic acid 17 catalyzed the enantioselective epoxidation of the tertiary homoallylic alcohol 16 to 18. The rearrangement of the allylic carbonate 19 to produce allyl ether 21 with

 59

The asymmetric vinylogous aldol reaction of 3-​methyl-​2-​cyclohexen-​1-​one 22 and α-​keto ester 23 to furnish tertiary carbinol 25 using the bifunctional catalyst 24 was developed (Org. Lett. 2013, 15, 220) by Paolo Melchiorre at ICREA and ICIQ in Spain. The enantioselective catalytic addition of methyl Grignard to nonanal 26 to give 28 using the ligand 27 in the presence of excess titanium(IV) isopropoxide was reported (Adv. Synth. Catal. 2013, 355, 1249) by Beatriz Maciá at Manchester Metropolitan University and Miguel Yus at Alicante University in Spain.

Chun-​Jiang Wang at Nankai University found (Org. Lett. 2013, 15, 3448) that thiourea 30 catalyzed the enantioselective conjugate addition of thiophenol to ester 29 to give 31. Kazuaki Ishihara at Nagoya University demonstrated (Angew. Chem. Int. Ed. 2013, 52, 4549) that a cooperative catalyst complex derived from BINOL 33 and dibutylmagnesium with water catalyzed the highly enantioselective addition of diphenylphosphine oxide to ester 32 to furnish 34.

Finally, Takashi Ooi at Nagoya University reported (Chem. Sci. 2013, 4, 1308) that the addition of azlactone 37 to methyl propiolate can lead to either the E-​product 35 or the Z-​product 39 with high enantioselectivity using catalysts 36 or 38, respectively. Selectivity for the isomeric products is proposed to arise by control of the protonation pathway of the intermediate allenic enolates that result from the conjugate addition step.

59  Construction of Single Stereocenters

high ee under iridium catalysis in the presence of ligand 20 was disclosed (Org. Lett. 2013, 15, 512) by Hyunsoo Han at the University of Texas, San Antonio.

60

30. Enantioselective Synthesis of Alcohols and Amines: The Zhu Synthesis of (+)-​Trigonoliimine A Douglass F. Taber July 14, 2014

The enantioselective epoxidation of a terminal alkene 1 has been a long-​sought goal of organic synthesis. Albrecht Berkessel of the University of Cologne devised (Angew. Chem. Int. Ed. 2013, 52, 8467) a Ti catalyst that mediated the conversion of 1 to 2. Zhi Li of the National University of Singapore described (Chem. Commun. 2013, 49, 11572) a cell-​based system that effected the enantioselective epoxidation of 3 to 4.

Antonio Mezzetti of ETH Zürich and Francesco Santoro of Firmenich SA carried out (Angew. Chem. Int. Ed. 2013, 52, 10352)  the enantioselective hydrogenation of 5 to the allylic alcohol 6. Elena Fernández of the Universitat Rovira i Virgilli and Andrew Whiting of Durham University devised (Org. Lett. 2013, 15, 4810)  a protocol for the enantioselective conjugate borylation of the imine derived from 7, leading to the secondary alcohol 8. Benjamin List of the Max-​Planck-​Institute für Kohlenforschung, Mülheim and Choong Eui Song of Sungkyunkwan University condensed (Angew. Chem. Int. Ed. 2013, 52, 12143) the thioester 10 with the aldehyde 9 to give the alcohol 11.

Toshiro Harada of the Kyoto Institute of Technology developed (Org. Lett. 2013, 15, 4198) a general procedure for the enantioselective addition of a terminal alkene 12 to an aldehyde 9. As illustrated by the preparation of 13, this appears to be tolerant of a variety of organic functional groups. Professor Harada also established (Chem. Eur.

 61

Chun-​Jiang Wang and Xumu Zhang of Wuhan University hydrogenated (Angew. Chem. Int. Ed. 2013, 52, 8416) the alkyne 16 to the protected allylic amine 17. Keiji Maruoka of Kyoto University effected (J. Am. Chem. Soc. 2013, 135, 18036)  the enantioselective α-​amination of an aldehyde 18, to give 19. David W. C. MacMillan of Princeton University described (J. Am. Chem. Soc. 2013, 135, 11521) a complementary approach, not illustrated. David J. Fox of the University of Warwick reduced (Chem. Commun. 2013, 49, 10022) the ketone 20, then rearranged the resulting secondary alcohol to the α-​amino amide 21. α-​Quaternary amines are particularly sought after. Xiao-​Ying Xu and Li-​Xin Wang of the Chengdu Institute of Organic Chemistry added (Eur. J.  Org. Chem. 2013, 2864)  the aldehyde 22 to the azodicarboxylate 23 to give 24. Yuko Otani of the University of Tokyo and Kei Takeda of Hiroshima University found (Angew. Chem. Int. Ed. 2013, 52, 12956) that, depending on the choice of base, the readily-​available enantiomerically enriched 25 could be acylated to give either enantiomer of 26.

Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne developed (Angew. Chem. Int. Ed. 2013, 52, 12714) yet another approach to α-​quaternary amines. The enantioselective addition of the isonitrile 27 to the vinyl selenone 28 to give 29 established the key quaternary center of (+)-​trigonoliimine A 30.

61  Enantioselective Synthesis of Alcohols and Amines

J. 2013, 19, 17707) a protocol for the enantioselective addition of an alkyne 14 to an aldehyde to give the branched product 15.

62

31. Enantioselective Synthesis of Alcohols and Amines: The Kim Synthesis of (+)-​Frontalin Douglass F. Taber February 9, 2015

Vlada B.  Urlacher of the Heinrich-​Heine University Düsseldorf showed (Chem. Commun. 2014, 50, 4089) that the P450 monooxygenase CYP154A8 from Nocardia farcinica could monohydroxylate n-​octane 1 to 2 with high regioselectivity and ee. Fener Chen of Fudan University used (J. Org. Chem. 2014, 79, 2723)  an organocatalyst to open the prochiral anhydride 3 to the monoester 4. Amir H. Hoveyda of Boston College added (Angew. Chem. Int. Ed. 2014, 53, 3387) (pinacolato)borane to the enone 5 to give 6, that was readily oxidized to the tertiary alcohol.

Matthias Breuning of the University of Bayreuth designed (Chem. Commun. 2014, 50, 6623) a Cu catalyst for the enantioselective Henry addition of nitromethane to the aldehyde 7 to give 8. Benjamin List of the Max-​Planck-​Institute für Kohlenforschung optimized (Synlett 2014, 25, 932) the proline-​catalyzed formation of the aldol product 10 from the aldehyde 9. Christian Wolf of Georgetown University devised (Chem. Commun. 2014, 50, 3151) the alkyne 12, that could be added to the aldehyde 11 to give 13 in high ee. Keiji Maruoka of Kyoto University developed (Org. Lett. 2014, 16, 1530) practical conditions for the organocatalyzed addition of an aldehyde 14 to an in situ-​generated nitroso urethane, leading, after reduction, to the alcohol 15. Satoko Kezuka of Tokai University added (Tetrahedron Lett. 2014, 55, 2818) the benzyloxyamine 17 to the nitro alkene 16 to give the coupled product 18 in high ee. Xiaohua Liu and Xiaoming Feng of Sichuan University developed (Angew. Chem. Int. Ed. 2014, 53, 1636) a Pd catalyst for the preparation of 20 by the enantioselective amination of the diazo ester

 63

Claudio Palomo of the Universidad Pais Vasco devised (Chem. Eur. J. 2014, 20, 6526)  an organocatalyst for the enantioselective addition of 25 to the imine 24. The product was readily desufonylated to 26. Gilles Dujardin of the Université du Maine and Sandrine Py of the Université Joseph Fourier showed (Org. Lett. 2014, 16, 1936) that the dipolar cycloaddition of 27 to the vinyl ether 28 proceeded with high diastereocontrol. The three alkyl branches of the product 29 were readily differentiated one from another. Frontalin 33 is an insect pheromone that has also been detected in elephants. Hee-​ Doo Kim of Sookmyung Women’s University prepared 33 (Synlett 2014, 25, 251) by the highly diastereocontrolled 1,2-​addition of 31 to the ketone 30 to give 32.

63  Enantioselective Synthesis of Alcohols and Amines

19. Shou-​Fei Zhu and Qi-​Lin Zhou of Nankai University described (Angew. Chem. Int. Ed. 2014, 53, 2978) related work, not illustrated, on the enantioselective aryloxylation of an α-​diazo ester. Alan Armstrong of Imperial College London, taking advantage (J. Org. Chem. 2014, 79, 3895) of the ready availability of enantiomerically secondary selenides such as 21, showed that it could be combined with 22 to give the α-​chiral amine 23.

64

32. Enantioselective Synthesis of Alcohols and Amines: The Doi Synthesis of Apratoxin C Douglass F. Taber July 13, 2015

Hiromitsu Takayama of Chiba University used (Org. Lett. 2014, 16, 5000) the Itsuno-​ Corey protocol to reduce the enone 1 to the allylic alcohol 2. Peiming Gu of Ningxia University developed (Org. Lett. 2014, 16, 5339) a Cu catalyst that cyclized the prochiral 3 to 4 in high ee. Xiaoming Feng of Sichuan University effected (Org. Lett. 2014, 16, 3938) enantioselective Baeyer–​Villiger oxidation of the racemic cyclopentanone 5, converting one enantiomer to the δ-​lactone 6.

The velocity of catalytic osmylation is often limited by slow turnover of the intermediate osmate ester. Koichi Narasaka, then at the University of Tokyo, showed (Chem. Lett. 1988, 1721) that the efficiency of the transformation was improved by the addition of stoichiometric phenyl boronic acid. Kilian Muñiz, now at ICIQ Tarragona, established (Chem. Eur. J. 2005, 11, 3951)  that this acceleration also worked with Sharpless asymmetric dihydroxylation. D. Christopher Braddock of Imperial College London took advantage (Chem. Commun. 2014, 50, 13725)  of these observations, converting myrcene 7 selectively to the cyclic boronate 8. Michael P. Doyle of the University of Maryland developed (J. Org. Chem. 2014, 79, 12185) a Rh catalyst for the ene reaction of 9 with 10 to give 11. Adriaan J. Minnaard of the University of Groningen devised (Chem. Eur. J. 2014, 20, 14250) a Cu catalyst that mediated the face selective addition of 13 to 12, establishing the oxygenated quaternary center of 14. Tomonori Misaki and Takashi Sugimura of the University of Hyogo used (Chem. Lett. 2014, 43, 1826) Michael addition of 15 to 16 to construct the oxygenated quaternary center of 17. Jon C.  Antilla of the University of South Florida assembled (Chem. Commun. 2014, 50, 14187)  the δ-​lactone 20 by adding the diene 19 to the α-​keto ester 18. Zhiyong Wang of the University of Science and Technology of China reported (Org. Lett. 2014, 16, 3564) related results.

 65

The cyanobacteria-​derived cyclodepsipeptides, exemplified by apratoxin C 35, show promising anticancer activity. Takayuki Doi of Tohoku University prepared (J. Org. Chem. 2014, 79, 8000) 34, the starting material for 35, by condensing acetone 33 with isobutyraldehyde 32 on a multigram scale.

65  Enantioselective Synthesis of Alcohols and Amines

Jonathan A. Ellman of Yale University achieved (Angew. Chem. Int. Ed. 2014, 53, 11329)  substantial enantioselectivity in the addition of thioacetic acid 22 to the nitroalkene 21 to give 23. Subhash P. Chavan of the National Chemistry Laboratory prepared (Tetrahedron Lett. 2014, 55, 5905)  the allylic amine 25 by reduction of the aziridine 24. Petri M.  Pihko of the University of Jyväskylä prepared (Org. Lett. 2014, 16, 5152) the Mannich adduct 28 by adding the β-​keto ester 26 to the imine 27. Stéphane P. Roche of Florida Atlantic University and Eric N. Jacobsen of Harvard University described (J. Am. Chem. Soc. 2014, 136, 12872)  a related study (not illustrated) catalytically converting α-​chloroglycinates to α-​amino esters in high ee. Takashi Ooi of Nagoya University prepared (ACS Catal. 2014, 4, 4304)  the α-​quaternary allylic amine 31 by coupling 29 with the imine 30.

6

33. Construction of Alkylated Stereocenters Zara M. Seibel and Tristan H. Lambert February 17, 2014

Hirohisa Ohmiya and Masaya Sawamura at Hokkaido University reported (Angew. Chem. Int. Ed. 2013, 52, 5350) the copper-​catalyzed, γ-​selective allylation of terminal alkyne 1 to produce the chiral skipped enyne 3 with high ee. A method to synthesize asymmetric skipped diene 6 via copper-​catalyzed allylic allylation of diene 4 was developed (Chem. Commun. 2013, 49, 3309) by Ben L. Feringa at the University of Groningen. Prof. Feringa also disclosed (J. Am. Chem. Soc. 2013, 135, 2140) the regioselective and enantioselective allyl–​allyl coupling of bromide 7 with allyl Grignard under Cu catalysis in the presence of phosphoramidite 8. James P. Morken of Boston College reported (Org. Lett. 2013, 15, 1432) the cross-​coupling of allylboronate 11 with a mixture of alkenes 10a,b under palladium catalysis to produce diene 13 with high ee.

Jian Liao at the Chengdu Institute of Biology Chinese Academy of Sciences and the University of Chinese Academy of Sciences reported (Angew. Chem. Int. Ed. 2013, 52, 4207)  the palladium-​catalyzed allylic alkylation of indole using the chiral bis(sulfoxide) phosphine ligand 15. Yi-​Xia Jia at the Zhejiang University of Technology reported (J. Am. Chem. Soc. 2013, 135, 2983) the enantioselective alkylation of indole to produce the trifluoromethyl adduct 19 using nickel catalysis in the presence of bisoxazoline ligand 18.

Sarah E. Reisman at the California Institute of Technology disclosed (J. Am. Chem. Soc. 2013, 135, 7442)  the reductive cross-​coupling of acid chloride 20 and benzyl

 67

Matthew S. Sigman at the University of Utah reported (J. Am. Chem. Soc. 2013, 135, 6830)  the redox–​relay oxidative Heck arylation of alkenyl alcohol 27 with boronic acid 26 using a palladium catalyst and pyridine oxazole ligand 28 to produce the γ-​substituted aldehyde 29. Karl Anker Jørgenson at Aarhus University disclosed (J. Am. Chem. Soc. 2013, 135, 8063) the 1,6-​Michael addition of alkylidene lactone 30 to dienal 31 using proline-​derived catalyst 32 and catalytic Hünig’s base.

Qi-​Lin Zhou at Nankai University reported (Angew. Chem. Int. Ed. 2013, 52, 1556) the carboxyl-​directed asymmetric hydrogenation of alkene 34 using chiral iridium catalyst 35. An asymmetric hydrogenation of enone 37 using an enoate reductase and dihydropyridine 38, a synthetic substitute for natural nicotinamide that preserves the natural activity and selectivity of the reductase, was reported (Org. Lett. 2013, 15, 180) by Frank Hollmann at the Delft University of Technology.

Andrew D. Smith at the University of St Andrews disclosed (Chem. Sci. 2013, 4, 2193) the enantioselective Michael addition of diketone 42 to anhydride 41 under catalysis by isothiourea 43 and PS-​BEMP, a polymer-​supported phosphorine base. Finally, Yixin Lu at the National University of Singapore reported (Angew. Chem. Int. Ed. 2013, 52, 943) the Michael addition of oxindole 45 to methyl vinyl ketone with the phosphine catalysts 46, which represents the first example of a chiral phosphine promoting an asymmetric Michael reaction.

67  Construction of Alkylated Stereocenters

chloride 21 using a nickel complex with bisoxazoline ligand 22 and manganese(0) as reductant. Ilan Marek at the Technion-​Israel Institute of Technology reported (Angew. Chem. Int. Ed. 2013, 52, 5333) a method for the construction of all-​carbon quaternary stereocenters, such as the one present in aldehyde 25, using a diastereoselective carbometallation of cyclopropene 24 followed by oxidation and ring opening. Switching from methyl Grignard and copper iodide to MeCuCNLi reverses the diastereoselectivity of the carbometallation and allows access to the opposite enantiomer.

68

34. Enantioselective Construction of Alkylated Centers: The Rawal Synthesis of (+)-​Fornicin C Douglass F. Taber July 21, 2014

Kazuaki Kudo of the University of Tokyo showed (Angew. Chem. Int. Ed. 2013, 52, 11585) that the dienyl aldehyde 1 could be reduced to the saturated aldehyde 2 with high ee. Alexandre Alexakis of the University of Geneva effected (Angew. Chem. Int. Ed. 2013, 52, 12701) conjugate addition to the unsaturated amide 3 to give 4 in high ee. Professor Alexakis also carried out (Chem. Eur. J. 2013, 19, 11352) enantioselective conjugate addition to the alkynyl nitro alkene 5, leading to 6. Gerrit J. Poelarends of the University of Groningen found (Chem. Eur. J. 2013, 19, 14407) that the enzyme 4-​oxalocrotonate tautomerase mediated the conjugate addition of acetaldehyde to a nitroalkene 7 to deliver the aldehyde 8 in high ee.

Tohru Yamada of Keio University developed (Chem. Commun. 2013, 49, 8371) an enantioselective Cu catalyst for the Claisen rearrangement of 9 to 10. Shi-​Kai Tian of USTC Hefei made (Chem. Commun. 2013, 49, 8190) the primary amine of 11 a leaving group, coupling 11 with 12 to make 13. David W. C. MacMillan of Princeton University alkylated (J. Am. Chem. Soc. 2013, 135, 11756) the aldehyde 14 with the boronic acid 15, to give 16 in high ee. Paolo Melchiorre of ICIQ Tarragona effected (Nature Chem. 2013, 5, 750) the enantioselective construction of the quaternary center of 19 by alkylation of the aldehyde 17 with 18.

 69

(+)-​Fornicin C 32 was isolated from the traditional Chinese medicinal plant Ganoderma fornicatum. Viresh H. Rawal of the University of Chicago prepared (J. Am. Chem. Soc. 2013, 135, 16050) 32 by enantioselective conjugate addition of the CO2 surrogate 30 to the enone 29 to give 31.

69  Enantioselective Construction of Alkylated Centers

Other methods for the enantioselective construction of quaternary alkylated centers have also been put forward. Varinder K.  Aggarwal of the University of Bristol elaborated (J. Am. Chem. Soc. 2013, 135, 16054) the inexpensive secondary ester 20 into the alkylated product 21. Jianwei Sun of the Hong Kong University of Science and Technology cyclized (Angew. Chem. Int. Ed. 2013, 52, 13593) the prochiral diol 22 to 23 in high ee. Amir H. Hoveyda of Boston College effected (Angew. Chem. Int. Ed. 2013, 52, 8156)  enantioselective conjugate addition to the enone 24 to give 25. Xiaoming Feng of Sichuan University devised (Angew. Chem. Int. Ed. 2013, 52, 10883) a catalyst for the addition of the bulky α-​diazo ester 26 into the α-​keto ester 27, leading to 28.

70

35. Alkylated Stereogenic Centers: The Jia Synthesis of (−)-​Goniomitine Douglass F. Taber February 16, 2015

John W. Wong of Pfizer and Kurt Faber of the University of Graz used (Adv. Synth. Catal. 2014, 356, 1878)  a wild-​type enzyme to reduce the nitrile 1 to 2 in high ee. Takafumi Yamagami of Mitsubishi Tanabe Pharma described (Org. Process Res. Dev. 2014, 18, 437) the practical diastereoselective coupling of the racemic acid 3 with the inexpensive pantolactone 4 to give, via the ketene, the ester 5 in high de.

Takeshi Ohkuma of Hokkaido University devised (Org. Lett. 2014, 16, 808) a Ru/​Li catalyst for the enantioselective addition of in situ generated HCN to an N-​acyl pyrrole 6 to give 7 in high ee. Yujiro Hayashi of Tohoku University found (Chem. Lett. 2014, 43, 556) that an aldehyde 8 could be condensed with formalin, leading in high ee to the masked aldehyde 9. Stephen P. Fletcher of the University of Oxford prepared (Org. Lett. 2014, 16, 3288) the lactone 12 in high ee by adding an alkyl zirconocene, prepared from the alkene 11, to the unsaturated lactone 10.

In a remarkable display of catalyst control, Masakatsu Shibasaki of the Institute of Microbial Chemistry and Shigeki Matsunaga of the University of Tokyo opened (J. Am. Chem. Soc. 2014, 136, 9190) the racemic aziridine 13 with malonate 14 using a bimetallic catalyst. One enantiomer of the aziridine was converted specifically to the branched product 15 in high ee. The other enantiomer of the aziridine was converted to the regioisomeric opening product.

 71

James P. Morken of Boston College developed (Org. Lett. 2014, 16, 2096) conditions for the allylation of an allylic acetate such as 20 with 21, to deliver the coupled product 22 with high maintenance of ee. Hirohisa Ohmiya and Masaya Sawamura, also of Hokkaido University, described (Angew. Chem. Int. Ed. 2014, 53, 4954) the direct enantioselective coupling of 24, prepared in situ from the corresponding alkene, with the allylic chloride 23 to give 25. Amir H. Hoveyda, also of Boston College, assembled (Angew. Chem. Int. Ed. 2014, 53, 1910) 28 by adding 27, prepared in situ from the alkyne, to the enone 26. Matthew S. Sigman of the University of Utah constructed (Nature 2014, 508, 340) the quaternary center of 30 by the Pd-​mediated addition of phenyl boronic acid to the alkene 29.

The alkaloid (−)-​goniomitine 34, isolated from Gonioma malagasy, shows nanomolar antiproliferative activity against several human tumor cell lines. Yanxing Jia of Peking University prepared (Org. Lett. 2014, 16, 3416) the quaternary center of 34 by diastereoselective alkylation of the β-​hydroxy ester 31 with 32 to give 33.

71  Alkylated Stereogenic Centers

Kimberly S.  Peterson of the University of North Carolina at Greensboro used (J. Org. Chem. 2014, 79, 2303) an enantiomerically-​pure organophosphate to selectively deprotect the bis ester 16, leading to 17. Chunling Fu of Zhejiang University and Shengming Ma of the Shanghai Institute of Organic Chemistry showed (Chem. Commun. 2014, 50, 4445) that an organocatalyst could mediate the brominative oxidation of 18 to 19. The ee of the product was easily improved via selective crystallization of the derived dinitrophenylhydrazone.

72

36. Construction of Alkylated Stereogenic Centers: The Zhu Synthesis of (−)-​Rhazinilam Douglass F. Taber July 20, 2015

Zheng Huang of the Shanghai Institute of Organic Chemistry (J. Am. Chem. Soc. 2014, 136, 15501) and Zhan Lu of Zhejiang University (Org. Lett. 2014, 16, 6452) effected enantioselective hydroboration of α-​alkyl styrenes, as illustrated by the conversion of 1 to 2. Stephen L. Buchwald of MIT devised (J. Am. Chem. Soc. 2014, 136, 15913) a Cu catalyst for the anti-​Markovnikov hydroamination of 3 with 4 to give 5.

John F. Hartwig of the University of California, Berkeley developed (Angew. Chem. Int. Ed. 2014, 53, 8691, 12172) an Ir catalyst for the enantioselective coupling of 6 with 7 to give 8. Hirohisa Ohmiya and Masaya Sawamura of Hokkaido University established (J. Am. Chem. Soc. 2014, 136, 13932) conditions for the preparation of 11 by the SN2¢ displacement of the allylic phosphate 9 with the alkyne 10. Ying-​Chun Chen of Sichuan University added (Org. Lett. 2014, 16, 6000) the allyl ketone 12 to 13 to give 14. Huw M. L. Davies of Emory University showed (J. Am. Chem. Soc. 2014, 136, 9792) that the Rh carbene derived from 16 could insert into the C–​H bond of 15 to give 17 in high ee.

K. N. Houk of UCLA and Wen-​Hua Zheng of Nanjing University relied (J. Am. Chem. Soc. 2014, 136, 12249)  on a Brønsted acid to promote the enantioselective oxidation of the prochiral acetal 18 to the ester 19. Xinhao Zhang of Peking University Shenzhen Graduate School and Qian Cai of the Guangzhou Institutes of Biomedicine and Health cyclized (Angew. Chem. Int. Ed. 2014, 53, 9555)  the prochiral amine 20 to 21 using a Cu catalyst.

 73

​(−)-​Rhazinilam 33, isolated from the evergreen dwarf shrub Rhazya stricta Decaisne, has been shown to interfere with tubulin polymerization and dynamics. Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne secured (Angew. Chem. Int. Ed. 2014, 53, 9926) the absolute configuration of the quaternary center of the intermediate aldehyde 32 by the enantioselective opening of the prochiral bis-​lactone 31.

We note with sorrow the passing of Professor Tsutomu Katsuki of Kyushu University, whose insightful contributions to asymmetric catalysis have often been highlighted on these pages.

73  Construction of Alkylated Stereogenic Centers

Sanzhong Luo of the Institute of Chemistry, Chinese Academy of Sciences employed (J. Am. Chem. Soc. 2014, 136, 14642)  an organocatalyst to mediate the enantioselective alkylation of the acetoacetate 22 with the bromide 23 to give 24 under photoredox conditions. Takanori Shibata of Waseda University added (Chem. Eur. J. 2014, 20, 8893)  Me3Al to 25 in a conjugate sense to give, after cyclization, the enol lactone 26. Xingzhong Zeng of Boehringer Ingelheim showed (Angew. Chem. Int. Ed. 2014, 53, 12153)  that conjugate addition of Me2Zn to 27 gave 28 in high ee. Alexandre Alexakis of the University of Geneva devised (Chem. Eur. J. 2014, 20, 16694)  a two-​step protocol for the enantioselective construction of the α-​quaternary alkyne 30 by the sequential coupling of two different Grignard reagents with the dichloride 29.

74

37. Construction of Multiple Stereocenters Léa Benkoski and Tristan H. Lambert February 24, 2014

Erick M. Carreira at ETH Zürich reported (Science 2013, 340, 1065) the enantioselective α-​allylation of aldehyde 1 with alcohol 2 to produce 3 using a dual catalytic system involving a chiral iridium complex and amine 5. This stereodivergent method allows access to all of the possible stereoisomers of 3. In a conceptually related process, John F. Hartwig at the University of California, Berkeley reported (J. Am. Chem. Soc. 2013, 135, 2068) the highly stereoselective allylic alkylation of azlactone 6 with allylic carbonate 7 catalyzed by a combination of Ir(cod)Cl2, ligand 9, and racemic silver phosphate 10.

An enantioselective three-​component Mannich-​type reaction of tert-​butyl diazoacetate, aniline, and imine 11 to produce α,β-​bis(arylamino) acid derivative 13 under dual catalysis with Rh2(OAc)4 and acid 12 was developed (Synthesis 2013, 45, 452) by Wenhao Hu at the Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development. Keiji Maruoka at Kyoto University reported (Chem. Commun. 2013, 49, 1118)  a one-​pot cross double-​Mannich reaction of acetylaldehyde 14, and imines 16 and 17 using axially chiral amino sulfonamide 15 to obtain densely functionalized 1,3-​diamine 18 as a single stereoisomer.

Jeffrey S. Johnson at the University of North Carolina at Chapel Hill reported (Org. Lett. 2013, 15, 2446)  the asymmetric synthesis of enantioenriched anti-​α-​hydroxy-​ β-​amino acid derivative 21 from 19 by treatment with oxone followed by catalytic hydrogenation using Ru(II) complex 20. Naoya Kumagai and Masakatsu Shibasaki

 75

The enantioselective homocrotylation of octanal 26 with cyclopropylcarbinylboronate 27 to produce alcohol 28 with high ee was disclosed (J. Am. Chem. Soc. 2013, 135, 82)  by Isaac J.  Krauss at Brandeis University with computational studies provided by Kendall N.  Houk at UCLA. Benjamin List at the Max-​Planck-​Institut für Kohlenforschung reported (J. Am. Chem. Soc. 2013, 135, 6677) the enantioselective epoxidation of cyclohexenone 29 utilizing cinchona alkaloid-​derived catalyst 30.

Hao Xu at Georgia State University reported (J. Am. Chem. Soc. 2013, 135, 3343) a diastereoselective intramolecular aminohydroxylation of olefin 32 to produce 33 via catalysis by an iron (II) complex. A  highly stereoselective, three-​component direct Mannich reaction of ketone 34, benzaldehyde, and p-​toluenesulfonamide using bifunctional catalyst 36 was developed (Org. Lett. 2013, 15, 508) by John Cong-​Gui Zhao at the University of Texas, San Antonio.

Tomislav Rovis at Colorado State University reported (J. Am. Chem. Soc. 2013, 135, 8504) that the novel N-​heterocyclic carbene 39 catalyzed the asymmetric intermolecular reaction of enal 37 and nitroalkene 38 to yield δ-​nitroester 40. Last but not least, Yungui Peng at Southwest University in China reported (Chem. Commun. 2013, 49, 4561) that the chiral pyrrolidine 42 catalyzed the Michael reaction of aldehyde 41 with nitroolefin 43 to produce γ-​nitrocarbonyl 44 with high ee and dr.

75  Construction of Multiple Stereocenters

at the Institute of Microbial Chemistry found (Org. Lett. 2013, 15, 2632) that a silver complex of bisphosphine 24 effected a syn-​selective and highly enantioselective Mannich-​type reaction of aldimine 22 and α-​sulfanyl lactone 23 to furnish the stereodiad 25 with very high ee.

76

38. Arrays of Stereogenic Centers: The Yadav Synthesis of Nhatrangin A Douglass F. Taber July 28, 2014

Miquel Costas of the Universitat de Girona developed (J. Am. Chem. Soc. 2013, 135, 14871) an iron catalyst for the enantioselective epoxidation of the Z-​ester 1 to 2. Although the α-​chloro aldehyde derived from 3 epimerized under the reaction conditions, Robert Britton of Simon Fraser University showed (Org. Lett. 2013, 15, 3554) that the subsequent aldol condensation with 4 favored one enantiomer, leading to 5 in high ee. Other selective aldol condensations of 4 (not illustrated) have been reported by Zorona Ferjancic and Radomir N.  Saicic of the University of Belgrade (Eur. J.  Org. Chem. 2013, 5555)  and by Tomoya Machinami of Meisei University (Synlett 2013, 24, 1501). Motomu Kanai of the University of Tokyo condensed (Org. Lett. 2013, 15, 4130) D-​arabinose 6 with diallyl amine and the alkyne 7 to give the amine 8 as a mixture of diastereomers. Naoya Kumagai and Masakatsu Shibasaki of the Institute of Microbial Chemistry combined (Angew. Chem. Int. Ed. 2013, 52, 7310) 9 and 10 to prepare the α-​chiral amine 11.

Tomoya Miura and Masahiro Murakami of Kyoto University used (J. Am. Chem. Soc. 2013, 135, 11497) an Ir catalyst to migrate the alkene of 13 to the E allyl boronate, that then added to 12 to give 14. Gong Chen of Pennsylvania State University alkylated (J. Am. Chem. Soc. 2013, 135, 12135) the β-​H of 15 with 16 to give selectively the diastereomer 17. Geoffrey W. Coates of Cornell University devised (J. Am. Chem. Soc. 2013, 135, 10930)  catalysts for the carbonylation of the epoxide 18 to either regioisomer of the β-​lactone 19. Yujiro Hayashi of Tohoku University combined (Chem. Lett. 2013, 42, 1294) the inexpensive succinaldehyde 20 and ethyl glyoxylate 21 to give the versatile aldehyde 22.

 7

An aldehyde such as 34 is readily epimerizable. En route to nhatrangin A 36, Jhillu Singh Yadav of CSIR-​Indian Institute of Chemical Technology, Hyderabad found (J. Org. Chem. 2013, 78, 8524) that the asymmetric aldol condensation of 34 with propionaldehyde could be carried out without epimerization, to give 35.

77  Arrays of Stereogenic Centers

Nuno Maulide of the Max-​Planck-​Institut für Kohlenforschung Mülheim effected (J. Am. Chem. Soc. 2013, 135, 14968) Claisen rearrangement of 23 to give, after reduction and hydrolysis, the aldehyde 24. Stephen G. Davies of the University of Oxford reported (Chem. Commun. 2013, 49, 7037)  a related Claisen rearrangement (not illustrated). Ying-​Chun Chen of Sichuan University devised (Org. Lett. 2013, 15, 4786) the cascade combination of 25 and 26 to give 27. Helma Wennemers of ETH Zürich added (Angew. Chem. Int. Ed. 2013, 52, 7228) the aldehyde 29 to the nitro alkene 28 to give 30. Alessandra Lattanzi of the Università di Salerno combined (Org. Lett. 2013, 15, 3436) 31 with 32, leading to the thioether 33.

78

39. Arrays of Stereogenic Centers: The Thomson Synthesis of (−)-​Galactin Douglass F. Taber February 23, 2015

Hisashi Yamamoto of the University of Chicago and Chubu University developed (J. Am. Chem. Soc. 2014, 136, 1222) a tungsten catalyst for the enantioselective oxidation of allylic alcohols such as 1 to the epoxide 2. Homoallylic alcohols also worked well. Naoya Kumagai and Masakatsu Shibasaki of the Institute of Microbial Chemistry devised (Chem. Eur. J. 2014, 20, 68) a scalable Zn-​catalyzed protocol for the coupling of 3 with 4 to give 5. Professor Shibasaki and Takumi Watanabe, also of the Institute of Microbial Chemistry, established (Org. Lett. 2014, 16, 3364) a Nb catalyst for the preparation of 8 by the Henry addition of 7 to 6. Wenhao Hu of East China Normal University effected (Synthesis 2014, 46, 1348)  the coupling of 9 and 10 with two equivalents of aniline to give the diamine 10.

Sanzhong Luo of the Institute of Chemistry, Beijing showed (Angew. Chem. Int. Ed. 2014, 53, 4149) that the adduct between 11 and an in situ formed N-​nitroso could be reduced with high diastereoselectivity, leading to 12. Kumagai and Shibasaki also described (Angew. Chem. Int. Ed. 2014, 53, 5327) the assembly of 15 by the enantioselective addition 14 to 13. Bernhard Breit of the Albert-​Ludwigs-​Universität Freiburg effected (Synthesis 2014, 46, 1311) the carbonylation of the alkene 16 to give an aldehyde that underwent in situ condensation with the imine 17, leading, after a subsequent addition of vinyl magnesium chloride, to the lactone 18. Michael J. Krische of the University of Texas prepared (J. Am. Chem. Soc. 2014, 136, 8911) the diol 21 by adding the racemic epoxide 20 to the aldehyde 19.

 79

The nutmeg Pycanthus angolensis and the pepper plant Holostylis reniformis have traditionally been used, in Africa and Brazil respectively, to treat malaria. Tetralin lignans isolated from these sources have been shown to have significant antiplasmodial activity. Regan J. Thomson of Northwestern University devised (Angew. Chem. Int. Ed. 2014, 53, 1395) a general strategy for the preparation of this class of natural products, based on the oxidative rearrangement of a hydrazone such as 31. The intermediate carbocation from the rearrangement coupled with 32 to give 33 with remarkable stereocontrol. The product 33 was readily carried on to (−)-​galactin 34.

79  Arrays of Stereogenic Centers

Martin Hiersemann of the Technische Universität Dortmund achieved (J. Org. Chem. 2014, 79, 3040) high enantioselectivity in the rearrangement of the enol ether 22 to 23. Michael T. Crimmins also observed (Org. Lett. 2014, 16, 2458) high stereocontrol in the rearrangement of 24 to 25. Wannian Zhang and Chunquan Sheng of the Second Military Medical University and Wei Wang of the University of New Mexico and the East China University of Science and Technology added (Org. Lett. 2014, 16, 692) the diketone 26 to the aldehyde 6 to give an intermediate adduct, that further cyclized to 27. Helma Wennemers of ETH Zürich used (J. Org. Chem. 2014, 79, 3937) an organocatalyst to effect the coupling of 28 with 29 to give 30 in high ee.

80

40. Arrays of Stereogenic Centers: The Shin/​Chandrasekhar Synthesis of (+)-​Lactacystin Douglass F. Taber July 27, 2015

Kami L.  Hull of the University of Illinois established (J. Am. Chem. Soc. 2014, 136, 11256)  conditions for the diastereoselective hydroamination of 1 with 2 to give 3. Jon C. Antilla of the University of South Florida employed (Org. Lett. 2014, 16, 5548) an enantiomerically-​pure Li phosphate to direct the opening of the prochiral epoxide 4 to 5. Jordi Bujons and Pere Clapés of IQAC-​CSIC engineered (Chem. Eur. J. 2014, 20, 12572) an enzyme that mediated the enantioselective addition of glycolaldehyde 7 to an aldehyde 6, leading to 8. Takahiro Nishimura of Kyoto University set (J. Am. Chem. Soc. 2014, 136, 9284) the two stereogenic centers of 11 by adding 10 to the diene 9.

Amir H.  Hoveyda of Boston College added (J. Am. Chem. Soc. 2014, 136, 11304) the propargylic anion derived from 13 to the aldehyde 12 to give, after oxidation, the diol 14. Yujiro Hayashi of Tohoku University constructed (Adv. Synth. Catal. 2014, 356, 3106)  17 by the combination of 15 with 16. Yitzhak Apeloig and Ilan Marek of Technion-​Israel Institute of Technology prepared (J. Org. Chem. 2014, 79, 12122) the bromo diol 20 by rearranging the adduct between the alkyne 19 and the acyl silane 18. James P. Morken, also of Boston College, effected (J. Am. Chem. Soc. 2014, 136, 17918) enantioselective coupling of 22 with the bis-​borane 21. The product allyl borane added to benzaldehyde to give the alcohol 23.

 81

Jonathan W.  Burton of the University of Oxford showed (Org. Lett. 2014, 16, 4078) that, on oxidation, the α-​amido malonate 29 cyclized to 30. Yong Jian Zhang of Shanghai Jiao Tong University assembled (Angew. Chem. Int. Ed. 2014, 53, 11257) the adjacent alkylated quaternary stereogenic centers of 33 by adding the carbonate 32 to 31. María D. Díaz-​de-​Villegas of the University of Zaragoza wrote (Adv. Synth. Catal. 2014, 356, 3261)  a valuable review on the enantioselective α-​functionalization of such 2-​cyanoacetates. Lactacystin 36 promotes neurite outgrowth. En route to a formal synthesis of 36, Dong-​Soo Shin of Changwon National University and Srivari Chandrasekhar of the Indian Institute of Chemical Technology opened (Eur. J. Org. Chem. 2014, 6707) the epoxide 34 with azide, leading to 35.

81  Arrays of Stereogenic Centers

Sentaro Okamoto of Kanagawa University reduced (Org. Lett. 2014, 16, 6278) the aryl oxetane 24 to an intermediate that coupled with allyl bromide to give the alcohol 25. In the presence of catalytic CuCN, the alternative diastereomer was the major product. Erick M.  Carreira of ETH Zürich used (Angew. Chem. Int. Ed. 2014, 53, 13898) a combination of an Ir catalyst and an organocatalyst to couple the aldehyde 27 with the allylic alcohol 26. The four possible combinations of enantiomerically pure catalysts worked equally well, enabling the preparation of each of the four enantiomerically pure diastereomers of 28.

82

41. C–​O Ring Construction: The Martín and Martín Synthesis of Teurilene Tristan H. Lambert January 13, 2014

Benjamin List at the Max-​Planck-​Institute in Mülheim reported (Angew. Chem. Int. Ed. 2013, 52, 3490) that the chiral phosphoric acid TRIP catalyzed the asymmetric SN2-​type intramolecular etherification of 1 to produce tetrahydrofuran 2 with a selectivity factor of 82. The coupling of alkenol 3 with 4 to give the α-​arylated tetrahydropyran 5 via a method that combined gold catalysis and photoredox catalysis was disclosed (J. Am. Chem. Soc. 2013, 135, 5505) by Frank Glorius at Westfälische Wilhelms-​Universität Münster. Mark Lautens at the University of Toronto reported (Org. Lett. 2013, 15, 1148) the conversion of cyclohexanedione 6 and phenylboronic acid to bicyclic ether 8 using rhodium catalysis in the presence of dienyl ligand 7. Propargylic ether 9 was found (Org. Lett. 2013, 15, 2926) by John P. Wolfe at the University of Michigan to undergo conversion to furanone 10 upon treatment with dibutylboron triflate and Hünig’s base followed by oxidation with hydrogen peroxide.

Tomislav Rovis at Colorado State University demonstrated (Chem. Sci. 2013, 4, 1668) that the spirocyclic compound 13 could be prepared in enantioenriched form from 11 by a photoisomerization-​coupled Stetter reaction using carbene catalyst 12. Antonio C. B. Burtoloso at the University of São Paulo reported (Org. Lett. 2013, 15, 2434) the conversion of ketone 14 to lactone 15 using samarium(II) iodide and methyl acrylate.

The merger of diketone 16 and pyrone 17 in the presence of Amberlyst-​15 to produce (−)-​tenuipyrone 18 was disclosed (Org. Lett. 2013, 15, 6) by Rongbiao Tong at the Hong Kong University of Science and Technology. Joanne E. Harvey at Victoria

 83

Two rings and four stereocenters were generated in the construction of bicyclic ether 23 from dienol 21 and acetal 22 via a Lewis acid-​mediated cascade, as reported (Org. Lett. 2013, 15, 2046) by Christine L. Willis at the University of Bristol. Notably, 23 was carried forward to the natural product (−)-​blepharocalyxin D. Paul E. Floreancig at the University of Pittsburgh developed (Angew. Chem. Int. Ed. 2013, 52, 625) a rhenium-​ mediated cascade for the conversion of epoxide 24 to the bis(tetrahydro)pyran 25.

A method for the synthesis of medium ring lactone 28 involving the reaction of cyclic acetal 26 with alkynyl ether 27 in the presence of Lewis acid was developed (J. Am. Chem. Soc. 2013, 135, 4680) by Zigang Li at Peking University and Jianwei Sun at the Hong Kong University of Science and Technology. Nobutaka Fujii and Hiroaki Ohno at Kyoto University found (Org. Lett. 2013, 15, 3046) that medium ring ether 30 could be constructed by palladium-​catalyzed ring closure of alkynol 29.

Finally, Víctor S. Martín and Tomás Martín at the University of Laguna in Spain reported (Angew. Chem. Int. Ed. 2013, 52, 3659) the transformation of trisepoxide 31 to the tris(tetrahydro)furanyl polyether 32 via an epoxide-​opening cascade. The cascade was initiated with a Nicholas reaction by treatment with dicobalt octacarbonyl followed by silica gel. Although formed as a 1:1 mixture of diastereomers at the propargylic site, both isomers of 32 could be carried forward to the natural product teurilene 33, a triterpene polyether bearing eight stereocenters, which is nevertheless achiral due to its meso symmetry.

83  C–O Ring Construction

University of Wellington in New Zealand found (Org. Lett. 2013, 15, 2430) that tricyclic ether 20 could be generated efficiently from dihydropyran 19 and pyrone 17 via a palladium-​catalyzed double allylic alkylation cascade.

84

42. C–​O Ring Formation Tristan H. Lambert April 14, 2014

The enantioselective bromocyclization of dicarbonyl 1 to form dihydrofuran 3 using thiocarbamate catalyst 2 was developed (Angew. Chem. Int. Ed. 2013, 52, 8597) by Ying-​Yeung Yeung at the National University of Singapore. Access to dihydrofuran 5 from the cyclic boronic acid 4 and salicylaldehyde via a morpholine-​mediated Petasis borono-​Mannich reaction was reported (Org. Lett. 2013, 15, 5944) by Xian-​Jin Yang at East China University of Science and Technology and Jun Yang at the Shanghai Institute of Organic Chemistry. Chiral phosphoric acid 7 was shown (Angew. Chem. Int. Ed. 2013, 52, 13593) by Jianwei Sun at the Hong Kong University of Science and Technology to catalyze the enantioselective acetalization of diol 6 to form tetrahydrofuran 8 with high stereoselectivity. Jan Deska at the University of Cologne reported (Org. Lett. 2013, 15, 5998) the conversion of glutarate ether 9 to enantiopure tetrahydrofuranone 10 by way of an enzymatic desymmetrization/​oxonium ylide rearrangement sequence.

Perali Ramu Sridhar at the University of Hyderabad demonstrated (Org. Lett. 2013, 15, 4474) the ring-​contraction of spirocyclopropane tetrahydropyran 11 to produce tetrahydrofuran 12. Michael A. Kerr at the University of Western Ontario reported (Org. Lett. 2013, 15, 4838) that cyclopropane hemimalonate 13 underwent conversion to vinylbutanolide 14 in the presence of LiCl and Me3N•HCl under microwave irradiation.

Eric M. Ferreira at Colorado State University developed (J. Am. Chem. Soc. 2013, 135, 17266)  the platinum-​catalyzed bisheterocyclization of alkyne diol 15 to furnish the bisheterocycle 16. Chiral sulfur ylides such as 17, which can be synthesized easily and cheaply, were shown (J. Am. Chem. Soc. 2013, 135, 11951)  by Eoghan M. McGarrigle at the University of Bristol and University College Dublin and Varinder

 85

The amine 20-​catalyzed tandem heteroconjugate addition/​Michael reaction of quinol 19 and cinnamaldehyde to produce bicycle 21 with very high ee was reported (Chem. Sci. 2013, 4, 2828) by Jeffrey S. Johnson at the University of North Carolina, Chapel Hill. Quinol ether 22 underwent facile photorearrangement–​cycloaddition to 23 under irradiation, as reported (J. Am. Chem. Soc. 2013, 135, 17978) by John A. Porco, Jr. at Boston University and Corey R. J. Stephenson, now at the University of Michigan.

Scott D.  Rychnovsky at the University of California, Irvine demonstrated (Org. Lett. 2013, 15, 4536) that reaction of hydroxysilyl enol ether 24 and aldehyde 25 in the presence of Lewis acid led to the formation of the tetrahydropyranone 26 as a single isomer. Chiral diamine catalyst 28 was found (ACS Catal. 2013, 3, 1356) by Gang Zou at East China University of Science and Technology and Gang Zhao at the Shanhai Institute of Organic Chemistry to catalyze the transformation of alcohol 27 to enantioenriched tetrahydrofuran 29 via heteroconjugate addition.

Decarboxylative allylation technology was employed (Angew. Chem. Int. Ed. 2013, 52, 5134) by Xue-​Wei Liu at Nanyang Technological University for the transformation of glycan 30 to dihydropyran 31 with complete stereoselectivity. Finally, Sanzhong Luo at the Institute of Chemistry, Chinese Academy of Sciences utilized (Angew. Chem. Int. Ed. 2013, 52, 9786) the catalyst of a combination of indium(III) salt and chiral phosphoric acid 33 to achieve the enantioselective cycloaddition of 32 and 1,5-​hexadiene to produce the densely functionalized dihydropyran 34.

85  C–O Ring Formation

K. Aggarwal at the University of Bristol to stereoselectively epoxidize a variety of aldehydes, as exemplified by 18.

86

43. C–​O Ring Construction: The Tong Synthesis of (−)-​Aculeatin A Douglass F. Taber October 27, 2014

Oxetanes are both interesting structural elements and activated leaving groups. James A. Bull of Imperial College London cyclized (Chem. Commun. 2014, 50, 5203) the tosylate 1 to the oxetane with LiHMDS, then alkylated the product using the same base to give 2. J.  S. Yadav of CSIR-​Indian Institute of Chemical Technology established (Org. Lett. 2014, 16, 836) conditions for the cyclization of 3 to 4.

Hiroaki Sasai of Osaka University used (Chem. Commun. 2013, 49, 11224)  a Pd(II)–​Pd(IV) cycle to convert 5 to 6. Lauri Vares of the University of Tartu demonstrated (Tetrahedron Lett. 2014, 55, 3569) that the racemic epoxide 7, a mixture of diastereomers, could be cyclized to 8 as a single diastereomer in high ee. Alistair Boyer of the University of Glasgow converted (Org. Lett. 2014, 16, 1660) the triazole 9, prepared from the corresponding alkyne, to the intermediate 10, that could be hydrolyzed to the ketone or reduced to the amine. Subhas Chandra Roy of the Indian Association for the Cultivation of Science devised (Eur. J. Org. Chem. 2014, 2980) a Ti(III)-​mediated cascade conjugate addition–​cyclization for the assembly of 12 from 11.

Paul E. Floreancig of the University of Pittsburgh reported (Angew. Chem. Int. Ed. 2014, 53, 4926) the highly diastereoselective reductive cyclization of 13 to 14. Arun K. Ghosh of Purdue University prepared (J. Org. Chem. 2014, 79, 5697) the ketone 16 from the enantiomerically-​pure alcohol 15. Professor Ghosh also described (Org. Lett. 2014, 16, 3154) a complementary approach to tetrahydropyrans based on the hetero

 87

Jiyong Hong of Duke University showed (Org. Lett. 2014, 16, 2406) that an organocatalyst could be used to mediate the cyclization of 22 to the oxepane 23. Mingji Dai, also of Purdue University, reported (Angew. Chem. Int. Ed. 2014, 53, 6519) the carbonylative macrocyclization of the diol 24 to the lactone 25.

The Aculeatin family of natural products, isolated from the rhizomes of Amomum aculeatum that have long been used in Papua, New Guinea, to treat fever and malaria, indeed shows potent in vitro activity against Plasmodium falciparum. Rongbiao Tong of the Hong Kong University of Science and Technology prepared (J. Org. Chem. 2014, 79, 1498) aculeatin A 28 by the cyclization of 26 to 27, followed by selective reduction.

87  C–O Ring Construction

Diels–​Alder addition of the alkynyl aldehyde 18 to the diene 17 to give 19. Xin-​Shan Ye of Peking University found (J. Org. Chem. 2014, 79, 4676) that the alcohol 20 could be cyclized to 21 with NBS, and to the diastereomer with PhSeCl.

8

44. C–​O Ring Construction: The Smith Synthesis of (+)-​18-​epi-​Latrunculol A Douglass F. Taber April 13, 2015

James A. Bull of Imperial College London showed (Angew. Chem. Int. Ed. 2014, 53, 14230) that the malonate 1 could readily be cyclized to the oxetane 2. Davide Ravelli of the University of Pavia functionalized (Adv. Synth. Catal. 2014, 356, 2781) the α position of the oxetane 3 with 4, leading to 5.

Frank Glorius of the Westfälische Wilhelms-​Universität Münster hydrogenated (Angew. Chem. Int. Ed. 2014, 53, 8751) the furan 6 to give 7 in high ee. Jia-​Rong Chen and Wen-​Jing Xiao of Central China Normal University converted (Eur. J. Org. Chem. 2014, 4714) the initial Henry adduct from 8 into the cyclic ether 9. Anil K. Saikia of the Indian Institute of Technology, Guwahati cyclized (J. Org. Chem. 2014, 79, 8592) the ene–​yne 10 to the ketone 11. Richard C. D. Brown of the University of Southampton developed (Org. Lett. 2014, 16, 5104) a chiral auxiliary that effectively directed the oxidative cyclization of the diene 12 to 13. The chiral auxiliary could be recovered and reused.

K. A. Woerpel of New York University showed (Org. Lett. 2014, 16, 3684) that, depending on the solvent, 15 could be added to 14 to give either 16 or 17. Samuel J. Danishefsky of Columbia University and the Memorial Sloan-​Kettering Cancer Center also observed (Chem. Eur. J. 2014, 20, 8731)  a marked solvent effect on the diastereoselectivity of the reduction of 18 to 19. Xiaoming Feng of Sichuan University added (Chem. Eur. J. 2014, 20, 14493) the ketone 20 to Danishefsky’s

 89

Chun-​Yu Ho of the South University of Science and Technology, taking advantage (J. Org. Chem. 2014, 79, 11873)  of the superior chelating ability of the allyl ether, selectively cyclized 25 to 26. Xuegong She of Lanzhou University used (Angew. Chem. Int. Ed. 2014, 53, 10789) a gold catalyst to convert 27 into the eight-​ membered ring ether 28. Other medium rings could also be constructed using these strategies.

In the course of a synthesis of the selectively cytotoxic macrolide (+)-​18-​epi-​ latrunculol A  31, Amos B.  Smith III of the University of Pennsylvania employed (J. Org. Chem. 2014, 79, 9284) Mitsunobu conditions to cyclize 29 to 30, with inversion at the secondary center. The product was more easily purified after deprotection with ceric ammonium nitrate.

89  C–O Ring Construction

diene 21 to give 22 in high ee. Jhillu Singh Yadav of the Indian Institute of Chemical Technology effected (Tetrahedron Lett. 2014, 55, 3996) intramolecular opening of the oxetane of 23 to give, with clean inversion, the cyclic ether 24.

90

45. C–​O Ring Construction: The Oger/​Lee/​Galano Synthesis of 7(RS)-​ST-​∆8-​11-​dihomo-​Isofuran Douglass F. Taber November 9, 2015

Shaorong Yang and Huanfeng Jiang of the South China University of Technology assembled (Angew. Chem. Int. Ed. 2014, 53, 7219)  the β-​lactone 3 by the Pd-​ catalyzed addition of 2 to the alkyne 1. Jack R.  Norton of Columbia University observed (J. Am. Chem. Soc. 2015, 137, 1036) that the vanadium-​mediated reductive cyclization of 4 proceeded by a free radical mechanism, leading to the cis 3,4-​ disubstituted tetrahydrofuran 5. The cyclization of 6 to 7 developed (J. Org. Chem. 2015, 80, 965)  by Glenn M.  Sammis of the University of British Columbia also involved H atom transfer. Amy R. Howell of the University of Connecticut devised (J. Org. Chem. 2015, 80, 5196)  the ring expansion of the β-​lactone 8 to the tetrahydrofuran 9. Dmitri V. Filippov and Jeroen D. C. Codée of Leiden University showed (J. Org. Chem. 2015, 80, 4553) that the net reductive alkylation of the lactone 10 led to 11 with high diastereocontrol.

A. Stephen K.  Hashmi of the Ruprecht-​Karls-​Universität Heidelberg optimized (Chem. Eur. J. 2015, 21, 427) the gold-​mediated rearrangement of the ester 12 to the lactone 13. This reaction apparently proceeded by the coupling of the metalated lactone with a propargylic carbocationic species. Benjamin List of the Max-​Planck-​Institut für Kohlenforschung developed (Angew. Chem. Int. Ed. 2015, 54, 7703) an organocatalyst that mediated the addition of 15 to 14, leading to 16 in high ee. Scott E. Denmark of the University of Illinois published (Nature Chem. 2015, 6, 1056) a detailed study of the enantioselective

 91

Young-Ger Suh of Seoul National University used (Chem. Commun. 2015, 51, 9026)  a Pd catalyst to cyclize 23 to (−)-​deguelin 24. John Montgomery of the University of Michigan showed (Org. Lett. 2015, 17, 1493) that the Ni-​catalyzed reductive cyclization of 25 to 26 proceeded with high diastereoselectivity.

The neurofurans and dihomoisofurans, exemplified by 7(RS)-​ST-​∆8-​dihomo-​IsoF 29, are potential biomarkers of oxidative stress. Camille Oger and Jean-​Marie Galano of Université de Montpellier and Jetty Chung-​Yung Lee of the University of Hong Kong described (Chem. Eur. J. 2015, 21, 2442) a general route to the isofurans and neurofurans, based on the Borhan cyclization of 27 to 28.

91  C–O Ring Construction

cyclization of 17 to 18. Shunichi Hashimoto of Hokkaido University established (Tetrahedron Lett. 2015, 56, 1397)  that his catalyst was effective for the cyclization of 19 to 20. Debendra K.  Mohapatra of the Indian Institute of Chemical Technology showed (J. Org. Chem. 2015, 80, 1365)  that allyl trimethylsilane could trap the intermediate from the cyclization of 21, leading to 22 with high diastereocontrol.

92

46. C–​O Ring-​Containing Natural Products: Cyanolide A (Krische), Bisabosqual A (Parker), Iso-​ Eriobrucinol A (Hsung), Trichodermatide A (Hiroya), Batrachotoxin Core (Du Bois) Tristan H. Lambert January 20, 2014

Michael J. Krische at the University of Texas at Austin developed (Angew. Chem. Int. Ed. 2013, 52, 4470) a total synthesis of cyanolide A 7 in only seven steps, a sequence so short it is shown here in its entirety. Diol 1 was subjected to enantioselective catalytic bisallylation under iridium catalysis to furnish 2 with very high levels of stereocontrol. Cross metathesis using ruthenium catalyst 3 first with ethyl vinyl ketone and then with ethylene resulted in the production of pyran 4. Glycosylation of 4 with phenylthioglycoside 5, stereoselective reduction of the ketone function, and oxidative cleavage of the olefin then furnished the carboxylic acid 6. Finally, dimerization of 6 with 2-​methyl-​6-​nitrobenzoic anhydride (MBNA) yielded cyanolide A.

Kathlyn A.  Parker at Stony Brook University reported (J. Am. Chem. Soc. 2013, 135, 582) a tandem radical cyclization strategy for the total synthesis of bisabosqual A 11. The key substrate 9 was prepared in three steps from the diester 8. Treatment of 9 with tri-​s-​butylborane and TTMS in the presence of air induced the tandem 5-​exo, 6-​exo radical cyclization to produce the complete core 10 of the natural product as a mixture of diastereomers, which could be equilibrated. Some further redox maneuvers then led to bisabosqual A.

 93

A concise approach to trichodermatide A 19 was developed (Angew. Chem. Int. Ed. 2013, 52, 3546) by Kou Hiroya at Musashino University. Aldehyde 16, which was synthesized from L-​tartaric acid, was condensed with 1,3-​cyclohexanedione in the presence of piperidine, resulting in diketone 17. Compound 17 was treated under carefully selected acidic conditions to furnish the pentacyclic pyran ketal 18. The selective installation of three additional hydroxyl groups then completed the synthesis of trichodermatide A.

Justin Du Bois at Stanford University reported (Chem. Sci. 2013, 4, 1059) an efficient synthesis of the core structure of batrachotoxin (or BTX) 26, a selective and extremely potent sodium channel agonist. Addition of the anion of 3-​bromofuran to tricarbonyl 20 followed by MOM protection produced 21 as a 2:1 mixture of isomers. Lithium–​halogen exchange then converted the endo isomer to the tetracycle 22. Following some manipulation to 23, the ketone function was stereoselectively reduced under chelation control using DIBAL-​H to furnish alcohol 24. Some final transformations, particularly to forge the homomorpholine ring, then yielded 25, the core of batrachotoxin 26 and several related structures.

93  C–O Ring-Containing Natural Products

Richard P.  Hsung at the University of Wisconsin, Madison disclosed (Org. Lett. 2013, 15, 3130) a very brief synthesis of iso-​eriobrucinol A and related isomers using a unique cascade sequence. First, phloroglucinol 12 and citral 13 were condensed using piperidine and acetic anhydride. The product of this operation was the tetracyclic cyclobutane 14, the result of an oxa-​[3+3] annulation followed by a stepwise, cationic [2+2] cycloaddition. Treatment of 14 with methyl propiolate in the presence of catalytic indium(III) chloride under microwave irradiation furnished iso-​eriobrucinol A, as well as the isomeric natural product iso-​eriobrucinol B.

94

47. Total Synthesis of C–​O Natural Products Tristan H. Lambert April 21, 2014

Weiping Tang at the University of Wisconsin, Madison reported (J. Am. Chem. Soc. 2013, 135, 12434) the total synthesis of the tropone-​containing norditerpenes hainanolidol 6 and harringtonolide 7 by making use of a strategic [5+2] oxidopyrylium cycloaddition. First, the known ketone 1 was converted through a number of steps to cycloaddition precursor 2. Treatment with DBU then effected the key cycloaddition to furnish the complex polycyclic compound 3. Additional manipulations revealed structure 4 with the lactone ring in place. The tropone ring of the natural structures was constructed by reaction of the cycloheptadiene moiety of 4 with singlet oxygen followed by Kornblum-​DeLaMare rearrangement with DBU to afford ketone 5. Double elimination using TsOH then produced hainanolidol 6. The free hydroxyl of 6 was engaged in a C–​H-​functionalizing cyclization using Pd(OAc)4 to yield harringtonolide 7 as well.

Hanfeng Ding at Zhejiang University developed (Angew. Chem. Int. Ed. 2013, 52, 13256)  a concise route to indoxamycin F 12 (as well as the related indoxamycins A and C). The complex intermediate 9 was accessed in only four steps from the bicyclic ketone 8, which in turn was prepared by a route involving an Ireland–​Claisen rearrangement and a reductive 1,6-​enyne cyclization (not shown). An impressive oxa-​ conjugate addition/​methylenation reaction to produce 11 was accomplished by treatment of 9 with Grignard 10 followed by Eschenmoser’s salt. Some final decorative work then led to indoxamycin F 12.

The strained polycyclophane natural product cavicularin 18 was synthesized in enantioenriched form by an innovative strategy reported (Angew. Chem. Int. Ed. 2013,

 95

1. nBuLi, then

Armen Zakarian at the University of California, Santa Barbara disclosed (J. Am. Chem. Soc. 2013, 135, 14552) a route to the notoriously challenging maoecrystal V 25. The strategy was centered on creation of the core tetrahydrofuran ring of the natural product by way of a C–​H functionalizing cyclization of 19 to form 20 with 10:1 dr. This material was converted to the vinyl silane 21, which underwent intramolecular Diels–​Alder cycloaddition to produce the tricycle 22. After processing to selenocarbonate 23, the lactone ring-​containing 24 was forged by radical cyclization with TTMS and AIBN. Further manipulations and strategic use of ring-​closing metathesis (not shown) then completed the total synthesis of maoecrystal V 25.

95  Total Synthesis of C–O Natural Products

52, 10472) by Keisuke Suzuki at the Tokyo Institute of Technology. After assemblage of the polyaromatic 13, racemic cyclophane 14 was produced by SNAr cyclization induced by CsF and CaCO3. Deracemization of 14 was achieved by the unusual step of swapping of the racemic sulfoxide moiety for an enantioenriched one (using reagent 15), and a subsequent diastereoselective (41:1 dr) deprotection of one of the phenolic MOM ethers then furnished enantioenriched 16. A series of steps was used to convert 16 to aryl iodide 17 to set up the penultimate radical cyclization with TTMS and AIBN, which forged the final ring of the natural product. Global deprotection of 17 then yielded (+)-​cavicularin 18.

96

48. C–​O Natural Products: DihomoIsoF (Lee/​ Galano), Pyrenolide D (Gracza), Clavilactone A (Li), Psoracorylifol A (Tong), Bermudenynol (Kim), Aspercyclide C (Hirama) Douglass F. Taber November 10, 2014

Dihomo-​Isofurans, produced in vivo by oxidation of adrenic acid, are potential markers of neuronal oxidative damage. Jetty Chung-​Yung Lee of the University of Hong Kong and Jean-​Marie Galano of Université de Montpellier I and II described (Angew. Chem. Int. Ed. 2014, 53, 6249) the cyclization of 1 to 2, opening what should be a general route to these furans, exemplified by 10-​epi-​17(R,S)-​SC-​ ∆15-​11-​dihomo-​IsoF 3.

The cytotoxic lactone pyrenolide D 6 was isolated from the phytogenic fungus Pyrenophora teres. Tibor Gracza of the Slovak University of Technology prepared (Synthesis 2014, 46, 817) 6 by the Pd-​mediated cyclization of 4 to 5.

The clavilactones, isolated from cultures of the Basidomycetous fungus Clitocybe clavipes, are potent tyrosine kinase inhibitors. Zhiping Li of Renmin University of China assembled (Angew. Chem. Int. Ed. 2014, 53, 4164)  the epoxy lactone 10 by the oxidative combination of the aldehyde 7 with the unsaturated ester 8 to give 9. Cyclization led to clavilactone A 10.

 97

Bermudenynol 16 was isolated from the red algae Laurencia intricata. Deukjoon Kim of Seoul National University closed (Angew. Chem. Int. Ed. 2014, 53, 272) the eight-​membered ring of 16 by intramolecular alkylation, cyclizing 14 to 15.

The aspercyclides, isolated from Aspergillus sp., show potential against allergy disorders. Building on previous work from his group, Masahiro Hirama of Tohoku University devised (Chem. Lett. 2014, 43, 349) a route to aspercyclide C 19 based on the regioselective oxidative macrocyclization of 17 to 18.

97  C–O Natural Products

The psoracorylifols, isolated from the traditional Chinese medicinal herb Psorlea corylifolia, are potent inhibitors of Heliobacter pylori. Rongbiao Tong of the Hong Kong University of Science and Technology used (Org. Lett. 2014, 16, 2986)  the Achmatowicz oxidative rearrangement of 11 followed by acid treatment to construct 12, which was carried on to psoracorylifol B 13.

98

49. C–​O Ring Construction: Sauropus Hexoside (Xie/​Wu), (+)-​Ipomeamarone (Usuki), Decytospolide A (Fujioka), Cytospolide P (Goswami), (+)-​ Didemniserinolipid B (Tong), Gymnothelignan N (She) Douglass F. Taber April 20, 2015

A range of biological activity was observed for the group of 3,6-​anhydro-​2-​deoxy hexosides, of which 3 is representative, isolated from Sauropus rostratus. Wei-​Jia Xie and Xiao-​Ming Wu of China Pharmaceutical University prepared (Org. Lett. 2014, 16, 5004) 3 by the dealkylative cyclization of 1 to 2.

(+)-​Ipomeamarone 6 is a phytoalexin isolated from mold-​damaged sweet potatoes. Yoshinosuke Usuki of Osaka City University assembled (Chem. Lett. 2014, 43, 1882) 6 by the diastereoselective cyclization of 4 to 5.

Hiromichi Fujioka of Osaka University protected (Org. Lett. 2014, 16, 3680) the enone of 7 by the conjugate addition of triphenylphosphine. Diastereoselective reduction of the other ketone followed by deprotection of the enone and cyclization led to 8, that was hydrogenated to decytospolide A 9.

 9

Rongbiao Tong of the Hong Kong University of Science and Technology set (J. Org. Chem. 2014, 79, 6987) the absolute configuration of (+)-​didemniserinolipid B 15 by Sharpless asymmetric osmylation of the alkene 13. Oxidative Achmatowicz rearrangement/​bicycloketalization then delivered 14.

Xuegong She of Lanzhou University observed (Org. Lett. 2014, 16, 4440) remarkable diastereoselectivity in the reductive cyclization of 16 to 17. Oxidation of 17 led to regioselective cyclization to gymnothelignan N 18.

99  C–O Ring Construction

En route to cytospolide P 12, Rajib Kumar Goswami of the Indian Association for the Cultivation of Science had planned (J. Org. Chem. 2014, 79, 7689) the ring-​closing metathesis of 10. This failed, but cyclization of the corresponding silyl ether to 11 was successful with the second-​generation Hoveyda catalyst.

10

50. C–​O Ring-​Containing Natural Products: (+)-​Isatisine A (Panek), Cephalasporolide E (Sartillo-​ Piscil), (+)-​Xestodecalactone (Jennings), Colchilomycin B (Banwell), Lactimidomycin (Georg), 5,6-​Dihydrocineromycin B (Fürstner) Douglass F. Taber November 16, 2015

(+)-​Isatisine A 4 was isolated from Isatis indigotica, long used in traditional Asian medicine for the treatment of viral diseases. James S. Panek of Boston University set the stage (J. Org. Chem. 2015, 80, 2959) for the synthesis of 4 by the addition of the allyl silane 2 to the aldehyde 1 to give the highly substituted tetrahydrofuran 3.

Fernando Sartillo-​Piscil of Benemérita Universidad Autónoma de Puebla devised (J. Org. Chem. 2015, 80, 2601)  an H-​atom abstraction/​fragmentation/​cyclization cascade that converted 5 into the spiroketal cephalosporolide E 7. Cephalosporolide F, the unstable kinetic product from the cyclization, could be observed in the NMR spectrum of the crude product when a base was added.

(+)-​Xestodecalactone A  10 was isolated from the fungus Pencillium cf. montanese, that was secured from the marine sponge Xestospongia exigua. Michael P.  Jennings of the University of Alabama constructed (Eur. J.  Org. Chem. 2015, 3303) the macrolactone of 10 by cyclizing the carboxylic acid 8 to 9 under Friedel-​ Crafts conditions.

 10

Lactimidomycin 16 binds to and so blocks the tRNA E-​site of the 80S ribosome. Gunda I. Georg of the University of Minnesota assembled (Chem. Commun. 2015, 51, 8634) the macrolide triene of 16 by the cyclization of 14 to 15.

Alois Fürstner of the Max-​Planck-​Institut für Kohlenforschung, who developed effective catalysts for alkyne metathesis, has been exploring (Angew. Chem. Int. Ed. 2015, 54, 6241) the conversion of the product cyclic alkynes to trisubstituted alkenes. In the synthesis of 5,6-​dihydrocineromycin B 19, he took advantage of the directing propargylic alcohol for the conversion of 17 to 18.

101  C–O Ring-Containing Natural Products

Colchilomycin B 13, isolated (without acetone!) from the marine fungus Cochliobolus lunatus, is a naturally occurring acetonide. Martin G.  Banwell of the Australian National University showed (J. Org. Chem. 2015, 80, 460) that the Nozaki–​ Hiyama–​Kishi cyclization of 11 to 12 proceeded with high diastereoselectivity.

102

51. C–​N Ring Construction: The Waser Synthesis of Jerantinine E Douglass F. Taber April 28, 2014

James A. Bull of Imperial College London prepared (J. Org. Chem. 2013, 78, 6632) the aziridine 2 with high diastereocontrol by adding the anion of diiodomethane to the imine 1. Karl Anker Jørgensen of Aarhus University observed (Chem. Commun. 2013, 49, 6382) high ee in the distal aziridination of 3 to give 4. Benito Alcaide of the Universidad Complutense de Madrid and Pedro Almendros of ICOQ-​CSIC Madrid reduced (Adv. Synth. Catal. 2013, 355, 2089) the β-​lactam 5 to the azetidine 6. Hiroaki Sasai of Osaka University added (Org. Lett. 2013, 15, 4142) the allenoate 8 to the imine 7, delivering the azetidine 9 in high ee.

Tamio Hayashi of Kyoto University, the National University of Singapore, and A*STAR devised (J. Am. Chem. Soc. 2013, 135, 10990) a Pd catalyst for the enantioselective addition of the areneboronic acid 11 to the pyrroline 10 to give 12. Ryan A. Brawn of Pfizer (Org. Lett. 2013, 15, 3424) reported related results. Nicolai Cramer of the Ecole Polytechnique Fédérale de Lausanne developed (J. Am. Chem. Soc. 2013, 135, 11772) a Ni catalyst for the cyclization of the formamide 13 to the lactam 14. Andrew D. Smith of the University of St. Andrews used (Org. Lett. 2013, 15, 3472) an organocatalyst to cyclize 15 to 16. Jose L. Vicario of the Universidad del Pais Vasco effected (Synthesis 2013, 45, 2669) the multicomponent coupling of 17, 18, and 19, mediated by an organocatalyst, to construct 20 in high ee.

 103

Jérôme Waser, also of the Ecole Polytechnique Fédérale de Lausanne, rearranged (Angew. Chem. Int. Ed. 2013, 52, 13373) the cyclopropane 32 with Cu triflate to give the ketone 33. This was carried on over several steps to jerantinine E 34.

103  C–N Ring Construction

André Beauchemin of the University of Ottawa explored (J. Org. Chem. 2013, 78, 12735) the thermal cyclization of ω-​alkenyl hydroxyl amines such as 21. Abigail G. Doyle of Princeton University developed (Angew. Chem. Int. Ed. 2013, 52, 9153) a Ni catalyst for the enantioselective addition of aryl zinc bromides such as 24 to the prochiral 23, to give 25 in high ee. Dennis G. Hall of the University of Alberta developed (Angew. Chem. Int. Ed. 2013, 52, 8069) an in situ preparation of the allyl boronate 26 in high ee. Addition to the aldehyde 27 proceeded with high diasteroselectivity. Slawomir Jarosz of the Polish Academy of Science prepared (Org. Lett. 2013, 15, 6214) the piperidine 31 by the addition of allyl magnesium bromide to the nitrile 29 followed by reduction with NaBH4.

104

52. C–​N Ring Construction: The Glorius Synthesis of ent-​Monomorine Douglass F. Taber November 17, 2014

Ryan Gilmour of the Westfälische Wilhelms-​Universität Münster employed (Chem. Eur. J. 2014, 20, 794)  an organocatalyst to direct the enantioselective aziridination of 1 to 2. Vanessa Kar-​Yan Lo and Chi-​Ming Che of Hong Kong University devised (Angew. Chem. Int. Ed. 2014, 53, 2982) a Ru catalyst for the enantioselective aziridination (not illustrated) of terminal alkenes. Shu-​Li You of the Shanghai Institute of Organic Chemistry and Aiwen Lei of Wuhan University described (Angew. Chem. Int. Ed. 2014, 53, 2443) the Pd-​mediated carbonylation of 3 to the β-​lactam 4.

Professor You reported (J. Am. Chem. Soc. 2014, 136, 6590) the enantioselective allylation of a pyrrole 5 with 6 to give the imine 7. Maria-​Paz Cabal and Carlos Valdés of the University of Oviedo showed (Eur. J. Org. Chem. 2014, 1672) that the cyclization of 8 to 9 proceeded with predictable high diastereocontrol. In one pot, Darren J. Dixon of the University of Oxford combined (ACS Catal. 2014, 4, 634) 10 and 11 to give 12 in high ee. The addition of 13 to 14 to give 15 described (Nature Chem. 2014, 6, 47) by Takashi Ooi of Nagoya University set two adjacent quaternary centers with control of both relative and absolute configuration.

Scott E. Denmark of the University of Illinois devised (J. Am. Chem. Soc. 2014, 136, 8915) a catalyst for the enantioselective electrophilic cyclization of 16 to 17 with control of sidechain stereochemistry. Using commercial acetone cyanohydrin 19, Christian V. Stevens of Ghent University cyclized (Eur. J. Org. Chem. 2014, 1296) 18 to the nitrile 20. George W. J. Fleet, also of the University of Oxford, used (Eur. J. Org.

 105

In the course of a synthesis of syringolin A, Satoshi Ichikawa of Hokkaido University effected (Angew. Chem. Int. Ed. 2014, 53, 4836) intramolecular Ugi three-​ component coupling of the isonitrile 25, the acid 26, and the amine 27, leading to the macrolactam 28. Jennifer L. Stockdill of Wayne State University stitched together (Org. Lett. 2014, 16, 1072) two of the rings of 30 by the radical cascade cyclization of the alkyne 29.

The alkaloid monomorine, presumably derived from ants, is found in the skins of frogs. Frank Glorius, also of Westfälische Wilhelms-​Universität Münster, developed (Angew. Chem. Int. Ed. 2013, 52, 9500) a synthesis of ent-​monomorine 33 based on the enantioselective hydrogenation of the prochiral 31 to 32.

105  C–N Ring Construction

Chem. 2014, 2053)  similar conditions to convert the sugar-​derived acetonide 21 into 22. Michael B. Tropak of the University of Toronto and Dilip P. Dhavale of the University of Pune showed (J. Org. Chem. 2014, 79, 4398) that the nitrone derived from 21 added to an alkene 23 with high facial selectivity, leading to the piperidine 24.

106

53. C–​N Ring Construction: The Weinreb Synthesis of Myrioneurinol Douglass F. Taber April 27, 2015

Terminal epoxides such as 1 are readily available in high enantiomeric excess. Christopher D.  Bray of Queen Mary University of London observed (Tetrahedron Lett. 2014, 55, 5890) clean inversion in the conversion of 1 to the aziridine 3 with the reagent 2. Yong-​Chun Luo and Peng-​Fei Xu of Lanzhou University opened (Org. Lett. 2014, 16, 4896) the activated cyclopropane 4 with benzyl azide, then heated the adduct to expel N2, leading to the azetidine 5.

Zhenming Du of Roche Shanghai and Michelangelo Scalone of Roche Basel developed (Org. Process Res. Dev. 2014, 18, 1702) practical conditions for the asymmetric hydrogenation of 6 to the pyrrolidine 7. Young Ho Rhee of the Pohang University of Science and Technology showed (Chem. Eur. J. 2014, 20, 16391) that depending on the diol protecting group, addition of allyl silane to 8 could lead to either the cis product 9 or the trans diastereomer (not illustrated). Ohyun Kwon of UCLA used (J. Am. Chem. Soc. 2014, 136, 11890) an organocatalyst to add the racemic allene 10 to 11 to give 12 in high ee. Tom Livinghouse of Montana State University cyclized (Angew. Chem. Int. Ed. 2014, 53, 14352)  the hydrazine 13 into an intermediate organozinc species that was then coupled with allyl bromide to give 14.

Yonggang Chen of Merck Process and Xumu Zhang of Rutgers University devised (Angew. Chem. Int. Ed. 2014, 53, 12761) practical conditions for the reduction of 15 to the piperidine 16. Teck-​Peng Loh of the Nanyang Technological University and

 107

Sebastian Stecko and Bartlomiej Furman of the Polish Academy of Sciences reduced (J. Org. Chem. 2014, 79, 10487) the lactam 24 with the Schwartz reagent to give an intermediate that added to the Danishefsky diene 25 to give the bicyclic enamide 26. Xing-​Wen Sun and Guo-​Qiang Lin of Fudan University used (Chem. Commun. 2014, 50, 15913) an organocatalyst to add 27 to the nitroalkene 28, then condensed the product with the endocyclic ketimine 29 to give the bicyclic 30 in high ee.

Myrioneurinol 33, isolated from the Vietnamese tree Myrioneuron nutans, was shown to have significant anti-​malarial activity. A  key step in the total synthesis of 33 reported (Angew. Chem. Int. Ed. 2014, 53, 14162)  by Steven M.  Weinreb of Pennsylvania State University was the diastereoselective cyclization of 31 to 32.

107  C–N Ring Construction

the University of Science and Technology of China effected (Chem. Commun. 2014, 50, 8324)  asymmetric phenylation of biomass-​derived 17 to give an intermediate that was oxidatively rearranged, then reduced to 18. Robert R. Knowles of Princeton University showed (J. Am. Chem. Soc. 2014, 136, 12217) that the cyclization of 19 to 20 proceeded with high diastereoselectivity. Maria J. Alves of the Universidade do Minho osmylated (Synlett 2014, 25, 1751) the adduct from the Diels–​Alder cycloaddition of 22 to 21 to give 23 in high ee.

108

54. C–​N Ring Construction: The Hattori Synthesis of (+)-​Spectaline Douglass F. Taber November 23, 2015

Magnus Rueping of RWTH Aachen University found (Chem. Commun. 2015, 51, 2111) that under Fe catalysis, a Grignard reagent would couple with the iodoazetidine 1 to give the substituted azetidine 2. Timothy F. Jamison of MIT established (Chem. Eur. J. 2015, 21, 7379) a protocol for converting 3, readily available from commercial homoserine lactone, to the alkylated azetidine 4.

Long-​Wu Ye of Xiamen University used (Chem. Commun. 2015, 51, 2126) a gold catalyst to cyclize 5, readily prepared in high ee, to the versatile ene sulfonamide 6. Chang-​Hua Ding and Xue-​Long Hou of the Shanghai Institute of Organic Chemistry added (Angew. Chem. Int. Ed. 2015, 54, 1604) the racemic aziridine 7 to the enone 8 to give the pyrrolidine 9 in high ee. Arumugam Sudalai of the National Chemical Laboratory employed (J. Org. Chem. 2015, 80, 2024) proline as an organocatalyst to mediate the addition of 11 to 10, leading to the pyrrolidine 12. Aaron D. Sadow of Iowa State University developed (J. Am. Chem. Soc. 2015, 137, 425) a Zr catalyst for the enantioselective cyclization of the prochiral 13 to 14.

Masahiro Murakami of Kyoto University devised (Angew. Chem. Int. Ed. 2015, 54, 7418) a Rh catalyst for the enantioselective ring expansion of the photocyclization product of 15 to the enamine 16. Sebastian Stecko and Bartlomiej Furman of the Polish Academy of Sciences reduced (J. Org. Chem. 2015, 80, 3621) the carbohydrate-​derived lactam 17 with the Schwartz reagent to give an intermediate that could

 109

Carlos del Pozo and Santos Fustero of the Universidad de Valencia used (Org. Lett. 2015, 17, 960) a chiral auxiliary to direct the cyclization of 25 to the bicyclic amine 26. In another illustration of the use of microwave irradiation to activate amide bond rotation, G. Maayan of Technion showed (Org. Lett. 2015, 17, 2110) that 27 could be cyclized efficiently to the medium ring lactam 28.

The alkaloid (+)-​spectaline 31 was isolated from the leaves of Cassia spectabilis. Yasunao Hattori of Kyoto Pharmaceutical University constructed (Heterocycles 2015, 91, 959) the piperidine ring of 31 by the diastereoselective Pd-​catalyzed cyclization of 29 to 30.

109  C–N Ring Construction

be coupled with an isonitrile, leading to the amide 18. Lei Liu of Shandong University oxidized (Angew. Chem. Int. Ed. 2015, 54, 6012) the alkene 19 in the presence of 20 to give 21. Tomislav Rovis of Colorado State University optimized (J. Am. Chem. Soc. 2015, 137, 4445) a Zn catalyst for the addition of 22 to the nitro alkene 23, leading, after reduction, to the piperidine 24.

10

55. Alkaloid Synthesis: (−)-​ L-​Batzellaside A (Toyooka), Limazepine A (Zemribo), (+)-​Febrifugine (Pansare), Amathaspiramide F (Tambar), Allomatrine (Brown), Lyconadine C (Waters), Tabersonine (Andrade) Douglass F. Taber May 12, 2014

Naoki Toyooka of the University of Toyama prepared (Eur. J.  Org. Chem. 2013, 2841)  the lactam 1 from commercial tri-​O-​benzyl-​D-​glucal. Reduction with Dibal followed by coupling of the intermediate with allyltrimethylsilane delivered the piperidine 2, that was carried on to (−)-​L -​batzellaside A 3.

Ronalds Zemribo of the Latvian Institute of Organic Synthesis effected (Org. Lett. 2013, 15, 4406) Ireland–​Claisen rearrangement of the lactone 4 to give the pyrrolidine 5 with high geometric control. This was readily converted to limazepine E 6.

Sunil V. Pansare of Memorial University used (Synthesis 2013, 45, 1863) an organocatalyst to set the relative and absolute configuration in the addition of 7 to 8 to give 9. The acyclic stereogenic center of 9 was inverted twice en route to (+)-​febrifugine 10.

 1

Richard C. D. Brown of the University of Southampton used (Org. Lett. 2013, 15, 4596) the sulfinylimine of 15 to direct the stereochemical sense of the addition of 16. The product 17 was carried over several steps to the tetracyclic alkaloid allomatrine 18.

Stephen P.  Waters of the University of Vermont devised (Org. Lett. 2013, 15, 4226) what appears to be a general route to pyridones. On warming, the acyl azide derived from the acid 19 rearranged to the isocyanate, that cyclized to the pyridone 20. Deprotection led to the Lycopodium alkaloid lyconadin C 21.

Among the several creative routes to indole alkaloids that have been put forward in recent months, the synthesis of tabersonine 25 (J. Am. Chem. Soc. 2013, 135, 13334) by Rodrigo B. Andrade of Temple University stands out. Deprotonation of 22 led to an anion that was condensed with 23 to give 24, with the relative and absolute configuration directed by the pendant sulfinylimine. In addition to tabersonine, the intermediate 24 was carried on to vincadifformine and to aspidospermidine.

111  Alkaloid Synthesis

Uttam K.  Tambar of the University of Texas Southwestern Medical Center combined (Org. Lett. 2013, 15, 5138) 11 with 12 under Pd catalysis to set the relative configuration of 13. Late-​ stage bromination completed the synthesis of amathaspiramide F 14.

12

56. Alkaloid Synthesis: Penaresidin A (Subba Reddy), Allokainic Acid (Saicic), Sedacryptine (Rutjes), Lepistine (Yokoshima/​Fukuyama), Septicine (Hanessian), Lyconadin C (Dai) Douglass F. Taber November 24, 2014

Penaresidin A 3, isolated from the Okinawan marine sponge Penares sp., is a potent activator of actomyosin ATPase. B. V. Subba Reddy of the Indian Institute of Chemical Technology prepared (Tetrahedron Lett. 2014, 55, 49) the azetidine ring of 3 by mesylation of the hydroxy sulfonamide 2, derived from 1, followed by cyclization.

Allokainic acid 6 has become a useful tool for neurological studies. Radomir N. Saicic of the University of Belgrade found (Org. Lett. 2014, 16, 34) that the Tsuji–​ Trost cyclization of 4 to 5 proceeded with high diastereoselectivity, presumably by way of the enamine of the aldehyde.

Floris P. J. T. Rutjes of Radboud University Nijmegen prepared (Org. Lett. 2014, 16, 2038)  the starting material 7 for (−)-​sedacryptine 9 via an enantioselective Mannich addition. The reagent of choice for the Aza–​Achmatowicz rearrangement of 7 to 8 proved to be mCPBA.

 13

(+)-​Septicine 15 is the biogenetic precursor to the phenanthrene alkaloid (+)-​ tylophorine. Stephen Hanessian of the Université de Montréal prepared (Org. Lett. 2014, 16, 232) 15 by condensing the proline-​derived ketone 13 with the aldehyde 14.

Mingji Dai of Purdue University elaborated (Angew. Chem. Int. Ed. 2014, 53, 3922) the amine 16 to the enone 17 by intramolecular Mannich alkylation followed by methylenation and allylic oxidation. Condensation with the sulfoxide 18 then delivered lyconadin C 19.

113  Alkaloid Synthesis

The intriguing tricyclic alkaloid (−)-​lepistine 12 was isolated from the mushroom Clitocybe fasciculate. En route to the first-​ever synthesis of 12, Satoshi Yokoshima and Tohru Fukuyama of Nagoya University cyclized (Org. Lett. 2014, 16, 2862) the glycidol-​derived sulfonamide 10 to the azacycle 11.

14

57. Alkaloid Synthesis: Indolizidine 223AB (Cha), Lepadiformine (Kim), Kainic Acid (Fukuyama), Gephyrotoxin (Smith), Premarineosin A (Reynolds) Douglass F. Taber May 11, 2015

Jin Kun Cha of Wayne State University prepared (Org. Lett. 2014, 16, 6208) the allene 1 by SN2′ coupling of a cyclopropanol with a propargylic tosylate. Silver-​mediated cyclization converted 1 into 2, that was reduced with diimide to the Dendrobates alkaloid indolizidine 223AB 3.

Sanghee Kim of Seoul National University observed (Chem. Eur. J. 2014, 20, 17433)  high diastereoselectivity in the Ireland–​ Claisen rearrangement of 4 to 5. The acid 5 was the key intermediate for the synthesis of the tunicate alkaloid lepadiformine 6.

Tohru Fukuyama of Nagoya University also used (Eur. J. Org. Chem. 2014, 4823) an ester enolate Claisen rearrangement to set the relative and absolute configuration of 7. Pd-​catalyzed cyclization then led to 8, that was carried on to the excitatory amino acid receptor agonist kainic acid 9.

 15

Zhen Yang of the Peking University Shenzhen Graduate School showed (Chem. Eur. J. 2014, 20, 12881) that the Rh carbene derived from 13 readily cyclized to an imine. The facial selectivity of the addition of the Grignard reagent 14 to that imine depended on the temperature of the reaction. At room temperature, 15 was formed. At low temperature, the other diastereomer predominated. Ring-​closing metathesis was used for the elaboration of 15 to the Stemona alkaloid tuberostemospiroline 16.

Kevin A.  Reynolds of Portland State University prepared (J. Org. Chem. 2014, 79, 11674) 19 by condensation of the pyrrole 17 with the aldehyde 18. The biosynthetic enzyme, that they had overexpressed, oxidized 19 to the antimalarial alkaloid permarineosin A 20.

115  Alkaloid Synthesis

Gephyrotoxin 12 was so named because it incorporates structural elements from two different classes of the Dendrobates alkaloids. Martin D. Smith of the University of Oxford envisioned (Angew. Chem. Int. Ed. 2014, 53, 13826) the cascade cyclization of deprotected 10 to give, after reduction, the ketone 11.

16

58. Alkaloid Synthesis: (−)-​α-​Kainic Acid (Ohshima), Serpentine (Scheidt), (−)-​Galanthamine (Jia), (+)-​Trigolutes B (Gong), Sarain A (Yokoshima/​Fukuyama), DZ-​2384 (Harran) Douglass F. Taber November 30, 2015

(−)-​α-​Kainic acid 3 is widely used in neuropharmacological studies. En route to 3, Takashi Ohshima of Kyushu University found (Chem. Eur. J. 2015, 21, 3937) that the intramolecular ene cyclization of 1 delivered 2 with high diastereocontrol.

Karl A. Scheidt of Northwestern University set (Angew. Chem. Int. Ed. 2015, 54, 6900) the absolute configuration of 5 and so of serpentine 6 by the organocatalyzed cyclization of 4. This is the first total synthesis of that alkaloid.

Yanxing Jia of Peking University prepared (Angew. Chem. Int. Ed. 2015, 54, 6255) the benzofuran 8 by the Pd-​mediated cyclization of the alkyne 7. An organocatalyzed intermolecular Michael addition set the absolute configuration of (−)​galanthamine 9.

 17

Satoshi Yokoshima and Tohru Fukuyama of Nagoya University showed (Angew. Chem. Int. Ed. 2015, 54, 7367) that on deprotection, 14 was converted to an eight-​ membered cyclic nitrone, that further cyclized to 15. This set the stage for the synthesis of sarain A 16.

Patrick G.  Harran of UCLA has extensively studied the complex alkaloid (−)-​diazonamide A  (not illustrated). Structural simplification and optimization of antimitotic activity led to the macrolactam DZ-​2384 18. It is exciting that 18 could be prepared (Angew. Chem. Int. Ed. 2015, 54, 4818) on a multigram scale by selective electrochemical oxidation of the much simpler precursor 17.

117  Alkaloid Synthesis

Liu-​Zhu Gong of the University of Science and Technology of China assembled (Chem. Eur. J. 2015, 21, 8389)  (+)-​trigolutes B 13 by the organocatalyzed addition of 10 to 11 to give 12. Barry M.  Trost of Stanford University employed (Chem. Sci. 2015, 6, 349)  a similar strategy in a synthesis of (−)-​perophoramidine (not illustrated).

18

59. Preparation of Benzene Derivatives: The Yu/​Baran Synthesis of (+)-​Hongoquercin A Douglass F. Taber June 16, 2014

Lutz Ackermann of the Georg-​August-​Universität Göttingen oxidized (Org. Lett. 2013, 15, 3484) the anisole derivative 1 to the phenol 2. Melanie S. Sanford of the University of Michigan devised (Org. Lett. 2013, 15, 5428)  complementary conditions for either para acetoxylation of 3, illustrated, to give 4, or meta acetoxylation. Lukas J.  Goossen of the Technische Universität Kaiserlautern developed (Synthesis 2013, 45, 2387)  conditions for the cascade alkoxylation/​decarboxylation of 5 to give 6. Cheol-​Hong Cheon of Korea University showed (J. Org. Chem. 2013, 78, 12154) that the boronic acid of 7 could act as a blocking group during electrophilic aromatic substitution or, as illustrated, as an ortho directing group. It could then be removed by protodeboronation, leading to 8.

Jun Wu of Zhejiang University coupled (Synlett 2013, 24, 1448)  the phenol 9 with the bromo amide 10 to give an ether that, on exposure to KOH at elevated temperature, rearranged to the intermediate amide, that was then hydrolyzed to 11. Dong-​Shoo Shin of Changwon National University reported (Tetrahedron Lett. 2013, 54, 5151)  a similar protocol (not illustrated) to prepare unsubstituted anilines. Guangbin Dong of the University of Texas, Austin used (J. Am. Chem. Soc. 2013, 135, 18350) a variation on the Catellani reaction to add 13 to the ortho bromide 12 to give the meta amine 14. Kei Manabe of the University of Shizuoka found (Angew. Chem. Int. Ed. 2013, 52, 8611) that the crystalline N-​formyl saccharin 16 was a suitable CO donor for the carbonylation of the bromide 15 to the aldehyde 17. John F. Hartwig of the University of California, Berkeley described (J. Org. Chem. 2013, 78, 8250) the coupling of the zinc enolate of an ester (Reformatsky reagent), either preformed or generated in situ, with an aryl bromide 18 to give 19.

 19

Jin-​Quan Yu and Phil S. Baran of Scripps/​La Jolla combined forces (Angew. Chem. Int. Ed. 2013, 52, 7317) for the synthesis of (+)-​hongoquercin A 33. Directed regioselective ortho methylation of 31 followed by directed ortho acetoxylation led to 32, that was hydrolyzed to give 33.

119  Preparation of Benzene Derivatives

Olafs Daugulis of the University of Houston developed (Org. Lett. 2013, 15, 5842)  conditions for the directed ortho phenoxylation of 20 with 21 to give 22. Yao Fu of the University of Science and Technology of China effected (J. Am. Chem. Soc. 2013, 135, 10630)  directed ortho cyanation of 23 with 24 to give 25. Related results were reported (Org. Lett. 2013, 15, 4960)  by Pazhamalai Anbarasan of the Indian Institute of Technology Madras. Laura L.  Anderson of the University of Illinois, Chicago coupled (Org. Lett. 2013, 15, 3362)  26 with 27 to prepare the α-​aryl ketone 28. Kian L.  Tan, now at Novartis, optimized (J. Am. Chem. Soc. 2013, 135, 18778) the silyl tether of 29 to direct selective meta alkenylation, leading to 30.

120

60. Substituted Benzenes: The Garg Synthesis of Tubingensin A Douglass F. Taber October 13, 2014

John F.  Hartwig of the University of California, Berkeley devised (Science 2014, 343, 853)  conditions for the regioselective silylation of an arene 1 to give 2. The silyl group can directly be converted, inter alia, to halo, amino, alkyl, or hydroxyl. Jin-​Quan Yu of Scripps La Jolla effected (Angew. Chem. Int. Ed. 2014, 53, 2683) regioselective alkenylation of the arene 3 with 4 to give 5. Wei-​Liang Duan of the Shanghai Institute of Organic Chemistry described (Org. Lett. 2014, 16, 500) a related alkenylation protocol.

Deping Wang of Henyang Normal University developed (Eur. J. Org. Chem. 2014, 315)  inexpensive conditions for the conversion of an aryl bromide 6 to the corresponding phenol 7. Mamoru Tobisu and Naoto Chatani of Osaka University used (J. Am. Chem. Soc. 2014, 136, 5587) a Ni catalyst to convert the lactam 8 to the aryl boronate 9. Patrick J. Walsh of the University of Pennsylvania found (Adv. Synth. Catal. 2014, 356, 165) conditions for the clean monoarylation of the amide 11 with 10 to give 12. In an application of the Catellani approach, Zhi-​Yuan Chen of Jiangxi Normal University coupled (Chem. Eur. J. 2014, 20, 4237) the aryl iodide 13 with 14 to give the amino ester 15.

Frederic Fabis of the Université de Caen-​Basse-​Normandie used (Chem. Eur. J. 2014, 20, 7507)  Pd to catalyze the ortho halogenation (and alkoxylation) of the N-​sulfonylamide 16 to give 17. Wen Wan of Shanghai University and Jian Hao of Shanghai University and the Shanghai Institute of Organic Chemistry effected (Chem. Commun. 2014, 50, 5733) ortho azidination of the aniline 18 with 19, leading to 20.

 12

The development of arynes as reactive intermediates continues unabated. Xiaoming Zeng of Xi’an Jiaotong University developed (Org. Lett. 2014, 16, 314) the reagent 27 for the bis-​functionalization of the aryne derived from 26. As expected with the ortho methoxy aryne, 28 was produced as the dominant product. Daesung Lee of the University of Illinois, Chicago has been investigating the generation of arynes by the thermal rearrangement of poly alkynes. He observed (J. Am. Chem. Soc. 2013, 135, 4668)  that under Ag catalysis, the aryne generated by the cyclization of 29 underwent intramolecular C–​H insertion to give 30 with retention of absolute configuration. This reaction may be proceeding by rearrangement of the intermediate aryne to the Ag carbene.

An aryne was also a key intermediate in the synthesis of tubingensin A 33 reported (J. Am. Chem. Soc. 2014, 136, 3036)  by Neil K.  Garg of UCLA. On exposure to NaNH2, 31 underwent both desilylation and dehydrohalogenation. The resulting enolate added to the newly-​generated aryne to give the ketone 32.

121  Substituted Benzenes

Jianbo Wang of Peking University found (Angew. Chem. Int. Ed. 2014, 53, 1364) that the N-​aryloxy amide 21 could be combined with the α-​diazo ester 22 to give the ortho-​alkenyl phenol 23. Silas P.  Cook of Indiana University uncovered (Org. Lett. 2014, 16, 2026) remarkably simple conditions for the enantiospecific cyclization of 24 (65% ee) to 25 (63% ee).

12

61. Substituted Benzenes: The Li Synthesis of Rubriflordilactone A Douglass F. Taber June 15, 2015

Cheol-​Hong Cheon of Korea University (J. Org. Chem. 2014, 79, 7277) and Toshiyuki Kamei and Toyoshi Shimada of the Nara National College of Technology (Tetrahedron Lett. 2014, 55, 4245) described the ring bromination of arene boronates. The boronate can then be removed, enabling the conversion of 1 to 2. Yu Rao of Tsinghua University constructed (Chem. Commun. 2014, 50, 15037) the sulfone 5 by coupling the arenes 3 and 4 with K2S2O8.

Igor Larrosa of Queen Mary University of London assembled (Chem. Sci. 2014, 5, 3509) the biphenyl 8 by arylating 6 with the iodide 7. Guy Bertrand of the University of California, San Diego showed (J. Am. Chem. Soc. 2014, 136, 13594) that under Au catalysis, the aniline 9 was sufficiently nucleophilic to add in a conjugate sense to the enone 10 to give 11. Hideo Togo of Chiba University optimized (Eur. J. Org. Chem. 2014, 6077) conditions for the selective ortho formylation of a phenol 12. The crude reaction mixture could also be directly oxidized with I2/​NH3 to give the nitrile 13. Silas P.  Cook of Indiana University ortho metalated (J. Am. Chem. Soc. 2014, 136, 13130; Angew. Chem. Int. Ed. 2014, 53, 11065) the benzamide 14, then used an iron catalyst to couple that intermediate with a halide 15, leading to the alkylated product 16.

 123

Extracts of the magnolia vine Schisandra rubriflora have been widely used in Chinese herbal medicine. En route to rubriflordilactone A 34, Ang Li of the Shanghai Institute of Organic Chemistry assembled (J. Am. Chem. Soc. 2014, 136, 16477) the enantiomerically-​pure triene 32, that on warming in the presence of air cyclized to 33.

123  Substituted Benzenes

As with the phenol 12 and the benzamide 14, aromatic functionalization has usually been directed by a functional group directly attached to the ring. Daqin Shi and Yingsheng Zhao of Soochow University showed (Chem. Sci. 2014, 5, 4962)  that a longer tether can be effective, as illustrated by the conversion of 17 to 19. Debabrata Maiti of the Indian Institute of Technology Bombay also used (Org. Lett. 2014, 16, 5760) a longer tether for the selective meta functionalization of 20 to 22. Motohiro Sonoda of Osaka Prefecture University constructed (Tetrahedron Lett. 2014, 55, 5302) the phenol 25 by acid-​mediated rearrangement of the Diels–​Alder adduct of 24 with the furan 23. Anthony G. M. Barrett of Imperial College London devised (J. Org. Chem. 2014, 79, 8706) conditions for the iodinative cyclization of 26 to 27. Katsukiyo Miura of Saitama University found (Org. Lett. 2014, 16, 4762) that hydroalumination cyclized 28 to 29. P. Andrew Evans of Queens University observed (Org. Lett. 2014, 16, 4356) high regioselectivity in the cyclization of 30 to 31. Young Keun Chung of Seoul National University reported (Org. Lett. 2014, 16, 4352) a similar cyclocarbonylation (not illustrated).

124

62. Preparation of Substituted Benzenes: The Beaudry Synthesis of Arundamine Douglass F. Taber October 12, 2015

Stephen G. DiMagno of the University of Nebraska developed (Chem. Eur. J. 2015, 21, 6394) a protocol for the clean monoiodination of 1 to 2. The bromomethylation (or chloromethylation, with HCl) of a benzene derivative is straightforward with formaldehyde and HBr. Naofumi Tsukada of Shizuoka University designed (Organometallics 2015, 34, 1191) a Cu catalyst that mediated the coupling of an alkyne with the benzyl bromide so produced, effecting net propargylation of 3 with 4 to give 5.

Triazenes such as 7, versatile intermediates for organic synthesis, are usually prepared by diazotization of the corresponding aniline. Kay Severin of the Ecole Polytechnique Fédérale de Lausanne established (Angew. Chem. Int. Ed. 2015, 54, 302) an alternative route from the aryl Grignard reagent 6. Ping Lu and Yanguang Wang of Zhejiang University showed (Chem. Commun. 2015, 51, 2840)  that dimethylformamide could serve as the carbon source for the conversion of 8 to the nitrile 9. Junha Jeon of the University of Texas at Arlington effected (J. Org. Chem. 2015, 80, 4661; Chem. Commun. 2015, 51, 3778) the reductive ortho silylation of 10 to give 11. Vladimir Gevorgyan of the University of Illinois at Chicago found (Angew. Chem. Int. Ed. 2015, 54, 2255) that the phenol derivative 12 could be ortho carboxylated, leading to 13. Lutz Ackermann of the Georg-​August-​Universität Göttingen, starting (Chem. Eur. J. 2015, 21, 8812) with the designed amide 14, effected ortho metalation followed by coupling, to give the methylated product 15. Tetsuya Satoh and Masahiro Miura of Osaka University used (Org. Lett. 2015, 17, 704) the dithiane of 16 to direct ortho metalation. Coupling with acrylate followed by reductive desulfurization led to the ester 17.

 125

Several methods for the de novo assembly of benzene derivatives have recently been put forward. Rajeev S. Menon of the Indian Institute of Chemical Technology condensed (Org. Lett. 2015, 17, 1449) the unsaturated aldehyde 22 with the sulfonyl ester 23 to give 24. Joseph P. A. Harrity of the University of Sheffield observed (Chem. Eur. J. 2015, 21, 2701) substantial regioselectivity in the addition of the cyclobutenone 26 to the alkyne 25, leading to 27.

Arundamine 30 is representative of a family of alkaloids isolated from the roots of the Asian grass Arundo donax. Christopher M. Beaudry of Oregon State University assembled (Angew. Chem. Int. Ed. 2014, 53, 11931) 30 by the intramolecular Diels–​ Alder addition of the yneamine of 28 to the furan, followed by opening to 29.

125  Preparation of Substituted Benzenes

Jin-​Quan Yu of Scripps/​La Jolla designed (Angew. Chem. Int. Ed. 2015, 54, 888) the phenylacetamide 18 to direct selective meta metalation, leading to the unsaturated aldehyde 19. In an extension of the Catellani protocol, Guangbin Dong of the University of Texas prepared (J. Am. Chem. Soc. 2015, 137, 5887) the biphenyl 21 by net meta metalation of the benzylamine 20.

126

63. Preparation of Heterocycles: The Boukouvalas Synthesis of (−)-​Auxofuran Douglass F. Taber June 23, 2014

Nabyl Merbouh and Robert Britton of Simon Fraser University developed (Eur. J. Org. Chem. 2013, 3219) a general route to a 2,5-​disubstituted furan 3 by taking advantage of the ready α-​chlorination of an aldehyde 1, followed by coupling with a ketone enolate 2. Jérôme Waser of the Ecole Polytechnique Fédérale de Lausanne used (Angew. Chem. Int. Ed. 2013, 52, 6743) 5 to oxidize the allene 4 to the furan 6.

Qian Zhang and Xihe Bi of Northeast Normal University used (Angew. Chem. Int. Ed. 2013, 52, 6953) Ag catalysis to prepare the pyrrole 9 by coupling the alkyne 7 with the isonitrile 8. Aiwen Lei of Wuhan University reported (Angew. Chem. Int. Ed. 2013, 52, 6958)  similar results. Professor Lei also developed (Chem. Commun. 2013, 49, 5853) the Pd-​catalyzed oxidation of the allyl imine 10 to the pyrrole 11.

Kamal K. Kapoor of the University of Jammu reduced (Tetrahedron Lett. 2013, 54, 5699) the Michael adduct 12 to the pyrrole 13 with triethyl phosphite. Edgar Haak of the Otto-​von-​Guericke-​Universität, Magdeburg condensed (Eur. J. Org. Chem. 2013, 7354) the alkynyl carbinol 14 with aniline to give the N-​phenyl pyrrole 15. Jean Rodriguez and Thierry Constantieux of Aix-​Marseille Université prepared (Eur. J. Org. Chem. 2013, 4131) the pyridine 18 by combining the ketone 16 and the

 127

Two versatile approaches to substituted indoles were recently described. David F.  Wiemer of the University of Iowa cyclized (J. Org. Chem. 2013, 78, 9291)  the Stobbe product 27 to the 3-​bromo indole 28. Huw M. L. Davies of Emory University condensed (J. Am. Chem. Soc. 2013, 135, 11712) the alkyne 29 with tosyl azide to give an adduct that was further cyclized and oxidized to the indole 30.

There are many furan-​containing natural products. En route to (−)-​auxofuran 34, John Boukouvalas of the Université Laval took advantage (Org. Lett. 2013, 15, 4912) of the cycloaddition–​retrocycloaddition of 32 with the enantiomerically-​pure 31, leading to 33.

127  Preparation of Heterocycles

unsaturated aldehyde 17 with NH4OAc. Teck-​Peng Loh of the University of Sciences and Technology of China and Nanyang Technological University found (Angew. Chem. Int. Ed. 2013, 52, 8584) that TMEDA was an effective organocatalyst for the assembly of the pyridine 21 from 19 and 20. Andrew D. Smith of the University of St Andrews showed (Angew. Chem. Int. Ed. 2013, 52, 11642)  that the pyridyl tosylate 24, available by the combination of 22 and 23, readily coupled with both carbon and amine nucleophiles. In a related development, D. Tyler McQuade of Florida State University prepared (Org. Lett. 2013, 15, 5298)  the 2-​bromopyridine 26 from the alkylidene malononitrile 25.

128

64. Heteroaromatic Synthesis: The Tokuyama Synthesis of (−)-​Rhazinilam Douglass F. Taber October 20, 2014

Mei-​ Huey Lin of the National Changhua University of Education rearranged (J. Org. Chem. 2014, 79, 2751) the initial allene derived from 1 to the γ-​chloroenone. Displacement with acetate followed by hydrolysis led to the furan 2. A.  Stephen K. Hashmi of Ruprecht-​Karls-​Universität Heidelberg showed (Angew. Chem. Int. Ed. 2014, 53, 3715) that the Au-​catalyzed conversion of the bis alkyne 3, mediated by 4, proceeded selectively to give 5.

Tehshik P. Yoon of the University of Wisconsin used (Angew. Chem. Int. Ed. 2014, 53, 793)  visible light with a Ru catalyst to rearrange the azide 6 to the pyrrole 7. Cheol-​Min Park, now at UNIST, found (Chem. Sci. 2014, 5, 2347) that a Ni catalyst reorganized the methoxime 8 to the pyrrole 9. A Rh catalyst converted 8 to the corresponding pyridine (not illustrated).

In the course of a synthesis of opioid ligands, Kenner C.  Rice of the National Institute on Drug Abuse optimized (J. Org. Chem. 2014, 79, 5007) the preparation of the pyridine 11 from the alcohol 10. Vincent Tognetti and Cyrille Sabot of the University of Rouen heated (J. Org. Chem. 2014, 79, 1303) 12 and 13 under microwave irradiation to give the 3-​hydroxy pyridine 14.

 129

Matthias Beller of the Universität Rostock used (Chem. Eur. J. 2014, 20, 1818) a Zn catalyst to mediate the opening of the epoxide 21 with the aniline 20. A Rh catalyst effected the oxidation and cyclization of the product amino alcohol to the indole 22. Sreenivas Katukojvala of the Indian Institute of Science Education & Research showed (Angew. Chem. Int. Ed. 2014, 53, 4076) that the diazo ketone 23 could be used to anneal a benzene ring onto the pyrrole 24, leading to the 2,7-​disubstituted indole 25. Tomoya Miura and Masahiro Murakami of Kyoto University developed (J. Am. Chem. Soc. 2014, 136, 2272)  the one-​pot Cu-​catalyzed dipolar cycloaddition of tosyl azide to the alkyne of 26, followed by Rh-​mediated intramolecular addition to the benzene ring. That product could be oxidized directly to the indole 27. Edward A. Anderson of the University of Oxford observed (Chem. Commun. 2014, 50, 5187) that the sulfonamide 29, from Pd-​catalyzed cyclization of 28, could also be desulfonylated and oxidized to the indole.

(−)-​Rhazinilam 32, isolated from Rhazya stricta Decaisne, interferes with tubulin polymerization and dynamics. To assemble 32, Hidetoshi Tokuyama of Tohoku University devised (Angew. Chem. Int. Ed. 2013, 52, 7168) the intramolecular cyclization of 30 to give the pyrrole 31.

129  Heteroaromatic Synthesis

Tomislav Rovis of Colorado State University prepared (J. Am. Chem. Soc. 2014, 136, 2735) the pyridine 17 by the Rh-​catalyzed combination of 15 with 16. Fabien Gagosz of the Ecole Polytechnique rearranged (Angew. Chem. Int. Ed. 2014, 53, 4959)  the azirine 18, readily available from the oxime of the β-​keto ester, to the pyridine 19.

130

65. Heteroaromatics: The Zhou/​Li Synthesis of Goniomitine Douglass F. Taber June 22, 2015

Xin-​Yan Wu of East China University of Science and Technology and Jun Yang of the Shanghai Institute of Organic Chemistry added (Tetrahedron Lett. 2014, 55, 4071) the Grignard reagent 1 to propargyl alcohol 2 to give an intermediate that could be borylated, then coupled under Pd catalysis with an anhydride, leading to the furan 3. Fuwei Li of the Lanzhou Institute of Chemical Physics constructed (Org. Lett. 2014, 16, 5992) the furan 6 by oxidizing the keto ester 4 in the presence of the enamide 5.

Yuanhong Liu of the Shanghai Institute of Organic Chemistry prepared (Angew. Chem. Int. Ed. 2014, 53, 11596) the pyrrole 9 by reducing the azadiene 7 with the Negishi reagent, then adding the nitrile 8. Yefeng Tang of Tsinghua University found (Tetrahedron Lett. 2014, 55, 6455)  that the Rh carbene derived from 11 could be added to an enol silyl ether 10 to give the pyrrole 12. Pazhamalai Anbarasan of the Indian Institute of Technology Madras reported (J. Org. Chem. 2014, 79, 8428) related results.

Zheng Huang of the Shanghai Institute of Organic Chemistry established (Angew. Chem. Int. Ed. 2014, 53, 1390)  a connection between substituted piperidines and pyridines by dehydrogenating 13 to 15, with 14 as the acceptor. Joseph P. A. Harrity of the University of Sheffield conceived (Chem. Eur. J. 2014, 20, 12889) the cascade assembly of the pyridine 18 by cycloaddition of 16 with 17 followed by Pd-​catalyzed coupling. Teck-​Peng Loh of Nanyang Technological University converted (Org. Lett. 2014, 16, 3432) the keto ester 19 into the azirine, then eliminated it to form an azatriene that cyclized to the pyridine 20. En route to a cholesteryl ester transfer protein inhibitor, Zhengxu S. Han of Boehringer Ingelheim combined (Org. Lett. 2014, 16, 4142) 21 with 22 to give an intermediate that could be oxidized to 23.

 13

131  Heteroaromatics

Magnus Rueping of RWTH Aachen used (Angew. Chem. Int. Ed. 2014, 53, 13264)  an Ir photoredox catalyst in conjunction with a Pd catalyst to cyclize the enamine 24 to the indole 25. Yingming Yao and Yingsheng Zhao of Soochow University effected (Angew. Chem. Int. Ed. 2014, 53, 9884)  oxidative cyclization of 26 to 27. Cheon-​Gyu Cho of Hanyang University showed (Org. Lett. 2014, 16, 4492) that ZnCl2 cyclized the coupling product between 28 and 29 with high fidelity to give 30. Acid-​catalyzed cyclization led predominantly to the other regioisomer. Yanxing Jia of Peking University cyclized (Chem. Commun. 2014, 50, 7367) 31 to 32. Xianxiu Xu and Qun Liu of Northeast Normal University (Chem. Commun. 2014, 50, 7306) and Bing Zhou and Yuanchao Li of the Shanghai Institute of Materia Medica (Org. Lett. 2014, 16, 3900) reported similar results.

Professors Zhou and Li used (Chem. Eur. J. 2014, 20, 12768) a Rh catalyst followed by acid to cyclize the hydrazide 33. The product 34 was readily carried on to the alkaloid goniomitine 35.

132

66. Heteroaromatic Construction: The Li Synthesis of Mycoleptodiscin A Douglass F. Taber October 19, 2015

Kyungsoo Oh of Chung-​Ang University cyclized (Org. Lett. 2015, 17, 450) the chloro enone 1 with NBS to the furan 2. Hongwei Zhou of Zhejiang University acylated (Adv. Synth. Catal. 2015, 357, 389) the imine 3, leading to the furan 4.

H. Surya Prakash Rao of Pondicherry University found (Synlett 2014, 26, 1059) that under Blaise conditions, exposure of 5 to three equivalents of 6 led to the pyrrole 7. Yoshiaki Nishibayashi of the University of Tokyo and Yoshihiro Miyake, now at Nagoya University, prepared (Chem. Commun. 2014, 50, 8900) the pyrrole 10 by adding the silane 9 to the enone 8.

Barry M. Trost of Stanford University developed (Org. Lett. 2015, 17, 1433) the phosphine-​mediated cyclization of 11 to an intermediate that on brief exposure to a Pd catalyst was converted to the pyridine 12. Nagatoshi Nishiwaki of the Kochi University of Technology added (Chem. Lett. 2015, 44, 776) the dinitrolactam 14 to the enone 13 to give the pyridine 15. Metin Balci of the Middle East Technical University assembled (Org. Lett. 2015, 17, 964) the tricyclic pyridine 18 by adding propargyl amine 17 to the aldehyde 16. Chada Raji Reddy of the Indian Institute of Chemical Technology cyclized (Org. Lett. 2015, 17, 896) the azido enyne 19 to the pyridine 20 by simple exposure to I2.

 13

In the endgame of a synthesis (Angew. Chem. Int. Ed. 2015, 54, 6878) of the orthoquinone mycoleptodiscin A 34, Ang Li of the Shanghai Institute of Organic Chemistry was not able to cyclize 32 with Pd catalysis. Fortunately, the Cu-​mediated cyclization to 33 was successful.

133  Heteroaromatic Construction

Björn C.  G. Söderberg of West Virginia University used (J. Org. Chem. 2015, 80, 4783) a Pd catalyst to simultaneously reduce and cyclize 21 to the indole 22. Ranjan Jana of the Indian Institute of Chemical Biology effected (Org. Lett. 2015, 17, 672) sequential ortho C–​H activation and cyclization, adding 23 to 24 to give the 2-​substituted indole 25. In a complementary approach, Debabrata Maiti of the Indian Institute of Technology Bombay added (Chem. Eur. J. 2015, 21, 8723) 27 to 26 to give the 3-​substituted indole 28. In a Type 8 construction, Nobutaka Fujii and Hiroaki Ohno of Kyoto University employed (Chem. Eur. J. 2015, 21, 1463) a gold catalyst to add 30 to 29, leading to 31.

134

67. Organocatalyzed C–​C Ring Construction: The Carreira Synthesis of (+)-​Crotogoudin Douglass F. Taber August 11, 2014

Kazuaki Kudo of the University of Tokyo developed (Org. Lett. 2013, 15, 4964)  a peptide catalyst for the enantioselective construction of 3 by the addition of 2 to 1. Thorsten Bach of the Technische Universität München devised (Science 2013, 342, 840; J. Am. Chem. Soc. 2013, 135, 14948) a Lewis acid organocatalyst for the photocyclization of 4 to 5.

Albert Moyano of the Universitat de Barcelona effected (Eur. J. Org. Chem. 2013, 3103) enantioselective conjugate addition of 7 to 6 to give the cyclopentane 8. Daniel Romo of Texas A&M optimized (Nature Chem. 2013, 5, 1049) the addition of 9 to 10 to give the β-​lactone 11. Kamal Kumar and Herbert Waldmann of the Technische Universität Dortmund found (Angew. Chem. Int. Ed. 2013, 52, 9576) that the addition of 12 to 13 followed by Bayer–​Villiger oxidation and deacylation delivered 14 in high ee. David W. Lupton of Monash University opened (Angew. Chem. Int. Ed. 2013, 52, 9149) the cyclopropane of 15 in situ, leading to an ester enolate that added to 16 to give 17.

Jeffrey S. Johnson of the University of North Carolina used (Chem. Sci. 2013, 4, 2828)  an organocatalyst to mediate the addition of the prochiral 18 to 19, leading to 20. M. Belén Cid of the Universidad Autónoma de Madrid added (J. Org. Chem. 2013, 78, 10737) the nitroalkane 22 to the unsaturated aldehyde 21, leading, after

 135

Strategies have been developed for applying organocatalysis to the assembly of polycarbacyclic ring systems. Sanzhong Luo of the Beijing National Laboratory for Molecule Sciences uncovered (Synthesis 2013, 45, 1939)  a simple amine that efficiently catalyzed the Robinson annulation of 26 with 27 to give 28. Douglass F. Taber of the University of Delaware allylated (J. Org. Chem. 2013, 78, 8437)  29 with 30 to give, after methyl coupling and oxy-​Cope rearrangement, a ketone that condensed with methyl vinyl ketone 27 to give 31. Bor-​Cherng Hong of the National Chung Cheng University effected (Org. Lett. 2013, 15, 6258) coupling of 32, 19, and 33 to give 34.

En route to (+)-​crotogoudin 37, Erick M. Carreira of ETH Zürich reduced (Angew. Chem. Int. Ed. 2013, 52, 11168) the prochiral diketone 35 with baker’s yeast to give 36 in high ee. Following the precedent of Frejd (Tetrahedron: Asymm. 2010, 21, 1374), sugar was added for the reduction. Smallridge showed (Tetrahedron: Asymm. 1997, 8, 1049) some years ago that such reductions often proceed well in a heterogeneous mixture of solid yeast, petroleum ether, and water, without added sugar.

135  Organocatalyzed C–C Ring Construction

intramolecular Julia-​Kocienski addition, to the cyclohexene 23. Additions that proceed in high ee with cyclopentenone and cyclohexenone are often not as selective with cycloheptenone 24. Wei Wang of the University of New Mexico and Wenhu Duan of the Shanghai Institute of Materia Medica observed (Tetrahedron Lett. 2013, 54, 3791) that addition of nitromethane and of nitroethane to 24 were both highly effective.

136

68. Organocatalyzed C–​C Ring Construction: The Jørgenson Synthesis of (+)-​Estrone Douglass F. Taber December 8, 2014

Ana Maria Faísca Phillips and Maria Teresa Barros of the Universidade Nova de Lisboa added (Eur. J. Org. Chem. 2014, 152) the bromo ester 1 to cinnamaldehyde 2 to give the cyclopropyl phosphonate 3 in high ee. Mukund P. Sibi and Jayaraman Sivaguru of North Dakota State University used (Angew. Chem. Int. Ed. 2014, 53, 5604)  an organocatalyst to mediate the 2+2 photocycloaddition of 4, leading to 5.

Shu-​Li You of the Shanghai Institute of Organic Chemistry expanded (Org. Lett. 2014, 16, 1810) the four-​membered ring of 6 to create the cyclopentanone 7 in high ee. Damien Bonne and Jean Rodriguez of Aix-​Marseille Université condensed (Chem. Eur. J. 2014, 20, 410) the cyclopentanone 8 with 9 to give 10. Santanu Mukherjee of the Indian Institute of Science, Bangalore added (Chem. Sci. 2014, 5, 1627) the lactone 12 to the prochiral 11 to give 13 with remarkable diastereo-​and enantiocontrol. Yixin Lu of the National University of Singapore constructed (Angew. Chem. Int. Ed. 2014, 53, 5643) the cyclopentene 16 by adding 14 to the allene 15.

Efraim Reyes and Jose L. Vicario of the Universidad del País Vasco prepared (Chem. Eur. J. 2014, 20, 2145) the highly substituted cyclohexene 19 by combining 17 and 18. Maurizio Benaglia of the Università degli Studi di Milano added (Adv. Synth Catal. 2014, 356, 493) the ketone 20 to 21 to create the cyclohexanone 22. Ben W. Greatrex

 137

Eric N.  Jacobsen of Harvard University prepared (Angew. Chem. Int. Ed. 2014, 53, 5912)  the cycloheptenone 30 by the enantioselective intermolecular addition of the pyrylium salt derived from 29 to ethyl vinyl ether. Bor-​Cherng Hong of the National Chung Cheng University initiated (Org. Lett. 2014, 16, 2724) the assembly of the steroid derivative 33 by the enantioselective addition of 32 to the unsaturated aldehyde 31.

Karl Anker Jørgenson of Aarhus University assembled (Angew. Chem. Int. Ed. 2014, 53, 4137) the tetracyclic steroid skeleton 36 by the addition of 34 to the cyclopentenone 35. Over several steps, 36 was carried on to (+)-​estrone 37.

137  Organocatalyzed C–C Ring Construction

of the University of New England in Australia used (J. Org. Chem. 2014, 79, 5088) an organocatalyst to cyclize the symmetrical dialdehyde 23 to the α-​hydroxy ketone 24. Dieter Enders of RWTH Aachen added (Org. Lett. 2014, 16, 2954) the β-​keto ester 25 to 26 to give an intermediate that was further condensed with 27 to complete the preparation of 28.

138

69. Organocatalyzed C–​C Ring Construction: The Bradshaw/​Bonjoch Synthesis of (−)-​Cermizine B Douglass F. Taber August 17, 2015

In a continuation of his studies (OHL20141229, OHL20140811) of organocatalyzed 2+2 photocycloaddition, Thorsten Bach of the Technische Universität München assembled (Angew. Chem. Int. Ed. 2014, 53, 7661) 3 by adding 2 to 1. Li-​Xin Wang of the Chengdu Institute of Organic Chemistry also used (Org. Lett. 2014, 16, 6436) an organocatalyst to effect the addition of 5 to 4 to give 6.

Shuichi Nakamura of the Nagoya Institute of Technology devised (Org. Lett. 2014, 16, 4452)  an organocatalyst that mediated the enantioselective opening of the aziridine 7 to 8. Zhi Li of the National University of Singapore cloned (Chem. Commun. 2014, 50, 9729) an enzyme from Acinetobacter sp. RS1 that reduced 9 to 10. Gregory C. Fu of Caltech developed (Angew. Chem. Int. Ed. 2014, 53, 13183) a phosphine catalyst that directed the addition of 12 to 11 to give 13. Armido Studer of the Westfälische Wilhelms-​Universität Münster showed (Angew. Chem. Int. Ed. 2014, 53, 9622) that 15 could be added to 14 to give 16 in high ee. Akkattu T. Biju of CSIR-​ National Chemical Laboratory described (Chem. Commun. 2014, 50, 14539) related results.

The photostimulated enantioselective ketone alkylation developed (Chem. Sci. 2014, 5, 2438) by Paolo Melchiorre of ICIQ was powerful enough to enable the alkylation of 17 with 18 to give 19, overcoming the stereoelectronic preference for axial

 139

William P. Malachowski of Bryn Mawr College showed (Tetrahedron Lett. 2014, 55, 4616) that 28, readily prepared by a Birch reduction protocol, was converted by heating followed by exposure to catalytic Me3P to the angularly-​substituted octalone 29. In a striking example of catalysis for the 21st century, Benjamin List of the Max-​ Planck-​Institut für Kohlenforschung converted (Angew. Chem. Int. Ed. 2014, 53, 8765, 8770) 30 to the Torgov diene 31 using only 5 mol% of catalyst, 88% of which was recovered.

Ben Bradshaw and Josep Bonjoch of the University of Barcelona reported (Chem. Commun. 2014, 50, 7099) significant improvements on their process (OHL20131125) for the preparation of 34 by the addition of 32 to 33. Again, only 5 mol% catalyst was used, 93% of which was recovered. The ester 34, brought to 99% ee by recrystallization, was readily carried on to the Lycopodium alkaloid (−)-​cermizine B 35.

139  Organocatalyzed C–C Ring Construction

bond formation. David W. Lupton of Monash University established (J. Am. Chem. Soc. 2014, 136, 14397) the organocatalyzed transformation of the dienyl ester 20 to 21. James McNulty of McMaster University added (Angew. Chem. Int. Ed. 2014, 53, 8450) azido acetone 23 to 22 to give 24 in high ee. There are sixteen enantiomerically-​ pure diastereomers of the product 27. John C.-​G. Zhao of the University of Texas at San Antonio showed (Angew. Chem. Int. Ed. 2014, 53, 7619)  that with the proper choice of organocatalyst, with or without subsequent epimerization, it was possible to selectively prepare any one of eight of those diastereomers by the addition of 26 to 25.

140

70. Organocatalyzed C–​C Ring Construction: The Mihovilovic Synthesis of Piperenol B Douglass F. Taber December 21, 2015

M. Kevin Brown of Indiana University prepared (J. Am. Chem. Soc. 2015, 137, 3482) the cyclobutane 3 by the organocatalyzed addition of 2 to the alkene 1. Karl Anker Jørgensen of Aarhus University assembled (J. Am. Chem. Soc. 2015, 137, 1685) the complex cyclobutane 7 by the addition of 5 to the acceptor 4, followed by condensation with the phosphorane 6.

Zhi Li of the National University of Singapore balanced (ACS Catal. 2015, 5, 51)  three enzymes to effect enantioselective opening of the epoxide 8 followed by air oxidation to 9. Gang Zhao of the Shanghai Institute of Organic Chemistry and Zhong Li of the East China University of Science and Technology added (Org. Lett. 2015, 17, 688)  10 to 11 to give 12 in high ee. Akkattu T.  Biju of the National Chemical Laboratory combined (Chem. Commun. 2015, 51, 9559)  13 with 14 to give the β-​lactone 15. Paul Ha-​Yeon Cheong of Oregon State University and Karl A. Scheidt of Northwestern University reported (Chem. Commun. 2015, 51, 2690) related results. Dieter Enders of RWTH Aachen University constructed (Chem. Eur. J. 2015, 21, 1004) the complex cyclopentane 20 by the controlled combination of 16, 17, and 18, followed by addition of the phosphorane 19.

Derek R.  Boyd and Paul J.  Stevenson of Queen’s University Belfast showed (J. Org. Chem. 2015, 80, 3429) that the product from the microbial oxidation of 21

 14

Gloria Rassu of the Consiglio Nazionale delle Richerche and Franca Zanardi of the Università degli Studi di Parma combined (Angew. Chem. Int. Ed. 2015, 54, 7386) 31 and 32 to give the cyclohexadiene 33. Gregory C. Fu of the California Institute of Technology cyclized (J. Am. Chem. Soc. 2015, 137, 4587) the racemic allene 34 to the bicyclic diester 35 in high ee.

Marko D. Mihovilovic of the Vienna University of Technology effected (Eur. J. Org. Chem. 2015, 1464) microbial oxidation of sodium benzoate 36. The product was protected as the acetonide 37, that was carried over several steps to piperenol B 38.

141  Organocatalyzed C–C Ring Construction

could be protected as the acetonide 22. Ignacio Carrera of the Universidad de la República described (Org. Lett. 2015, 17, 684) the related oxidation of benzyl azide (not illustrated). Manfred T. Reetz of the Max-​Planck-​Institut für Kohlenforschung and the Philipps-​Universität Marburg found (Angew. Chem. Int. Ed. 2014, 53, 8659) that cytochrome P450 could oxidize the cyclohexane 23 to the cyclohexanol 24. F. Dean Toste of the University of California, Berkeley aminated (J. Am. Chem. Soc. 2015, 137, 3205) the ketone 25 with 26 to give 27. Benjamin List, also of the Max-​ Planck-​Institut für Kohlenforschung, reported (Synlett 2015, 26, 1413)  a parallel investigation. Philip Kraft of Givaudan Schweiz AG and Professor List added (Angew. Chem. Int. Ed. 2015, 54, 1960) 28 to 29 to give 30 in high ee.

142

71. Metal-​Mediated C–​C Ring Construction: The Carreira Synthesis of (+)-​Asperolide C Douglass F. Taber August 18, 2014

Djamaladdin G. Musaev and Huw M. L. Davies of Emory University effected (Chem. Sci. 2013, 4, 2844) enantioselective cyclopropanation of ethyl acrylate 2 with the α-​ diazo ester 1 to give 3 in high ee. Philippe Compain of the Université de Strasbourg used (J. Org. Chem. 2013, 78, 6751) SmI2 to cyclize 4 to the cyclobutanol 5.

Jianrong (Steve) Zhou of Nanyang Technological University effected (Chem. Commun. 2013, 49, 11758) enantioselective Heck addition of 7 to the prochiral ester 6 to give the cyclopentene 8. Liu-​Zhu Gong of USTC, Hefei added (Org. Lett. 2013, 15, 3958) the Rh enolate from the enantioselective ring expansion of the α-​diazo ester 9 to the nitroalkene 10, to give 11 in high de.

Stephen P. Fletcher of the University of Oxford set (Angew. Chem. Int. Ed. 2013, 52, 7995) the cyclic quaternary center of 14 by the enantioselective conjugate addition to 12 of the alkyl zirconocene derived from 13. Alexandre Alexakis of the University of Geneva reported (Chem. Eur. J. 2013, 19, 15226) high ee from the conjugate addition of alkenyl Al reagents (not illustrated) to 12. Paultheo von Zezschwitz of Philipps-​ Universität Marburg prepared (Adv. Synth. Catal. 2013, 355, 2651) the silyl enol ether 17 by trapping the intermediate from the conjugate addition of 16 to 15.

Stefan Bräse of the Karlsruhe Institute of Technology effected (Eur. J. Org. Chem. 2013, 7110) conjugate addition to the prochiral dienone 18 to give the highly substituted cyclohexenone 19. Ping Tian and Guo-​Qiang Lin of the Shanghai Institute of

 143

Rh-​mediated intramolecular C–​H insertion has been a powerful tool for the construction of cyclopentane derivatives. Douglass F. Taber of the University of Delaware found (J. Org. Chem. 2013, 78, 9772) that the Rh carbene derived from 22 was discriminating enough to target the more nucleophilic C–​H bond, leading to the cyclohexanone 23. Kozo Shishido of the University of Tokushima observed (Org. Lett. 2013, 15, 3666) high diastereoselectivity in the intramolecular Heck cyclization of 24 to 25. Two protocols for the titanocene-​mediated construction of polycarbacyclic systems have been developed. José Justicia and Juan M.  Cuerva of the University of Granada observed (Chem. Eur. J. 2013, 19, 14484) that only one of the two diastereomers of 26 cyclized, leading to the highly-​functionalized 27. A. Fernández-​Mateos of the Universidad de Salamanca found (J. Org. Chem. 2013, 78, 9571) that while the nitrile 28 cyclized to the 6/​4 cis fused cyclobutanone 29, the nitrile one carbon longer cyclized to give the complementary 6/​5 trans ring system (not illustrated).

Erick M. Carreira of ETH Zürich added (Angew. Chem. Int. Ed. 2013, 52, 12166) an allyl silane terminator to the enantioselective Ir catalysis he had developed. The triene 30 so designed cyclized cleanly to 31, that was carried on to (+)-​asperolide C 32.

143  Metal-Mediated C–C Ring Construction

Organic Chemistry cyclized (J. Am. Chem. Soc. 2013, 135, 11700) 20 to the kinetic, less stable epimer of the diketone 21.

14

72. Metal-​Mediated C–​C Ring Construction: The Sun/​Lin Synthesis of Huperzine A Douglass F. Taber December 15, 2014

Zachary T. Ball of Rice University found (Chem. Sci. 2014, 5, 1401) that the on-​bead performance of a designed Rh-​peptide complex was markedly superior to the corresponding solution catalysis for the addition of 2 to 1 to give 3. Jin-​Quan Yu of Scripps/​ La Jolla achieved (J. Am. Chem. Soc. 2014, 136, 8138) remarkable ee in the conversion of 4 to 5.

Adriaan J.  Minnaard of the University of Groningen developed (Adv. Synth. Catal. 2014, 356, 2061)  practical conditions for enantioselective conjugate addition–​enolate trapping, converting 6 to 8. Alexandre Alexakis of the University of Geneva had reported (Org. Lett. 2014, 16, 118) related results. Jérôme Waser of the Ecole Polytechnique Fédérale de Lausanne assembled (J. Am. Chem. Soc. 2014, 136, 6239) the amino cyclopentane 11 by adding 9 to 10. Jean-​Luc Vasse of the Université de Reims used (Org. Lett. 2014, 16, 1506) the Schwartz reagent to cyclize 12 to 13. Eric V.  Johnston and Armando Córdova of the University of Stockholm combined (Angew. Chem. Int. Ed. 2014, 53, 3447) Pd and organocatalysis in a cascade of first oxidation of 14, then conjugate addition by 15, then cyclization to 16.

Professor Alexakis found (Org. Lett. 2014, 16, 2006) that the enolate from conjugate addition to 17 could be trapped with a nitroalkene 18 to give, after in situ Nef reaction, the 1,4-​diketone 19. Fangzhi Peng and Zhihui Shao of Yunnan University

 145

In a remarkable cascade transformation, Joëlle Prunet of the University of Glasgow used (Org. Lett. 2014, 16, 3300)  the Zhang Ru catalyst to cyclize 26 to the taxol skeleton 27. In an even more remarkable transformation, Professor Nakada showed (Tetrahedron Lett. 2014, 55, 1597) that cascade conjugate addition–​conjugate addition converted 28 to 29, having the rare chair-​boat-​chair skeleton of the biologically potent fusidic acid and brasilicardin A.

En route to huperzine A 32, Bing-​Feng Sun and Guo-​Qiang Lin of the Shanghai Institute of Organic Chemistry cyclized (J. Org. Chem. 2014, 79, 240) 30 to 31. The ketone corresponding to 30 cyclized to a different regioisomer.

145  Metal-Mediated C–C Ring Construction

added (Chem. Eur. J. 2014, 20, 6112) malonate to the nitro alkene 20 to give an intermediate that could be carried to the cyclohexanone 21. Masahisa Nakada of Waseda University devised (Tetrahedron Lett. 2014, 55, 1100)  a cascade conjugate reduction—​intramolecular conjugate addition to cyclize 22 to 23. Hye-​Young Jang of Ajou University dimerized (Synthesis 2014, 46, 1329) cinnamaldehyde 24 with nitromethane to give the fully-​substituted cyclohexanol 25.

146

73. Metal-​Mediated C–​C Ring Construction: The Ding Synthesis of (−)-​Indoxamycin B Douglass F. Taber August 10, 2015

Shou-​Fei Zhu of Nankai University developed (Angew. Chem. Int. Ed. 2014, 53, 13188)  an iron catalyst that effected the enantioselective cyclization of 1 to 2. Bypassing diazo precursors, Junliang Zhang of East China Normal University used (Angew. Chem. Int. Ed. 2014, 53, 13751) a gold catalyst to cyclize 3 to 4.

Taking advantage of energy transfer from a catalytic Ir complex, Chuo Chen of University of Texas Southwestern carried out (Science 2014, 346, 219) intramolecular 2+2 cycloaddition of 5, leading, after dithiane formation, to the cyclobutane 6. Intramolecular ketene cycloaddition has been limited in scope. Liming Zhang of the University of California Santa Barbara found (Angew. Chem. Int. Ed. 2014, 53, 9572) that intramolecular oxidation of an intermediate Ru vinylidene led to a species that cyclized to the cyclobutanone 8. James D. White of Oregon State University devised (J. Am. Chem. Soc. 2014, 136, 13578) an iron catalyst that mediated the enantioselective Conia-​ene cyclization of 9 to 10. Xiaoming Feng of Sichuan University observed (Angew. Chem. Int. Ed. 2014, 53, 11579) that the Ni-​catalyzed Claisen rearrangement of 11 proceeded with high diastereo-​and enantiocontrol. The relative configuration of the product 12 was not reported. Robert H.  Grubbs of Caltech showed (J. Am. Chem. Soc. 2014, 136, 13029) that ring opening cross metathesis of 13 with 14 delivered the Z product 15.

 147

There is still much interest in the conversion of carbohydrates into enantiomerically-​pure carbocycles. Raquel G.  Soengas and Artur M.  S. Silva of the University of Aveiro added (Synlett 2014, 25, 2217) bromo nitromethane to the acetonide 25 under reductive conditions to give, after deprotection, the cyclohexanediol 26. In a continuation of his studies (OHL 20140421) in the series, Hanfeng Ding of Zhejiang University prepared (Chem. Eur. J. 2014, 20, 15053) indoxamycin B 29 by cyclizing racemic 27 to 28 and its separable enantiomerically-​enriched diastereomer. It is instructive to compare this work to the approach of Carreira (OHL 20121105).

147  Metal-Mediated C–C Ring Construction

Mn(III) cyclization has in the past required a stoichiometric amount of inorganic oxidant. Sangho Koo of Myong Ji University found (Adv. Synth. Catal. 2014, 356, 3059) that by adding a Co co-​catalyst, air could serve as the stoichiometric oxidant. Indeed, 16 could be cyclized to 17 using inexpensive Mn(II). Matthias Beller of the Leibniz-​Institüt für Katalyse prepared (Angew. Chem. Int. Ed. 2014, 53, 13049) the cyclohexene 20 by coupling the racemic alcohol 18 with the amine 19. Paultheo von Zezschwitz of Philipps-​Universität Marburg added (Chem. Commun. 2014, 50, 15897) diethyl zinc in a conjugate sense to 21, then reduced the product to give 22. Depending on the reduction method, either diastereomer of the product could be made dominant. Nuno Maulide of the University of Vienna displaced (Angew. Chem. Int. Ed. 2014, 53, 7068) the racemic chloride 23 with diethyl zinc to give 24 as a single diastereomer.

148

74. Metal-​Mediated C–​C Ring Construction: The Lei Synthesis of (−)-​Huperzine Q Douglass F. Taber December 14, 2015

Following the Szymoniak protocol, Morwenna S.  M. Pearson-​Long and Philippe Bertus of the Université du Maine added (Synthesis 2015, 47, 992) the Grignard reagent 2 to the nitrile 1 to give the cyclopropyl amine 3. Chen-​Guo Feng of the Shanghai Institute of Organic Chemistry prepared (Chem. Commun. 2015, 51, 8773)  the cyclobutane 6 by enantioselective conjugate addition of 5 to the unsaturated ester 4.

Martin Kotora of Charles University showed (Eur. J. Org. Chem. 2015, 2868) that the zirconacycle from the eneyne 7 reacted with the aldehyde 8 to give, after iodination, the alcohol 9. Xiaoming Feng of Sichuan University used (Angew. Chem. Int. Ed. 2015, 54, 1608) a scandium catalyst to effect the intramolecular Roskamp cyclization of 10 to 11. Celia Dominguez of CHDI observed (Org. Lett. 2015, 17, 1401) that the double alkylation of the ester 12 with the dibromide 13 proceeded with high diastereoselectivity, to give 14. Hirokazu Tsukamoto of Tohoku University cyclized (Chem. Commun. 2015, 51, 8027) 15 to 16 in high ee.

Daniel J. Weix of the University of Rochester found (J. Am. Chem. Soc. 2015, 137, 3237) that under the influence of an enantiomerically-​pure Ti catalyst, the organonickel species derived from 18 opened the prochiral epoxide 17 to give 19 in high ee. John F. Bower of the University of Bristol optimized (J. Am. Chem. Soc. 2015, 137, 463) conditions for the highly diastereoselective Rh-​mediated cyclocarbonylation of

 149

Yoshito Kishi of Harvard University demonstrated (Tetrahedron Lett. 2015, 56, 3220) that the carbenoid generated from the epoxide 27 cyclized to 28 with high diastereoselectivity. Wenjun Tang, also of the Shanghai Institute of Organic Chemistry, developed (Angew. Chem. Int. Ed. 2015, 54, 3033) a Pd catalyst for the diastereoselective (because it is enantioselective) cyclization of 29 to 30.

Carbonyl–​alkene metathesis has only rarely been used in target-​directed synthesis. A  key step in the assembly (Angew. Chem. Int. Ed. 2015, 54, 1011)  of (−)-​huperzine Q 33 by Xiaoguang Lei of Peking University was the selective cyclization of 31 to 32.

149  Metal-Mediated C–C Ring Construction

20 to 21. Margaret A. Brimble of the University of Auckland initiated (J. Org. Chem. 2015, 80, 2231) the construction of the cyclohexenone 24 by the diastereoselective addition of 23 to the unsaturated ester 22. Olivier Baslé and Marc Maduit of ENSC Rennes devised (Chem. Eur. J. 2015, 21, 993) conditions for the preparation of 26 by enantioselective conjugate addition to the cyclohexenone 25.

150

75. Diels–​Alder Cycloaddition: Pancratistatin (Cho), Nootkatone (Reddy), Platensimycin (Zhang/​ Lee), Scabronine G (Nakada), Isoglaziovianol (Trauner) Douglass F. Taber August 25, 2014

Samuel J. Danishefsky of Columbia University and the Memorial Sloan-​Kettering Cancer Center made (Proc. Natl. Acad. Sci. 2013, 110, 10904) the unexpected observation that methylation of the enolate derived from conjugate addition to the readily-​ prepared 1 followed by intramolecular alkene metathesis led to the trans fused ketone 2. This can be contrasted to the diastereo-​and regioisomer 3, the product from Diels-​ Alder cycloaddition of 2-​methylcyclohexenone to isoprene. The trans ring fusion of 2 is particularly significant because ozonolysis followed by aldol condensation would deliver the angularly-​methylated trans-​fused 6/​5 C–​D ring system of the steroids and related natural products.

Cheon-​Gyu Cho of Hanyang University added (Org. Lett. 2013, 15, 5806) the activated dienophile 4 to the dienyl lactone to give, after oxidation, the dibromide 5. Debromination followed by oxidation led to the antineoplastic lactam pancratistatin 6.

D. Srinivasa Reddy of CSIR-​ National Chemical Laboratory Pune devised (J. Org. Chem. 2013, 78, 8149) a cascade protocol of Diels-​Alder cycloaddition of 8 to the diene 7, followed by intramolecular aldol condensation, to give the enone 9. Oxidative manipulation followed by methylenation completed the synthesis of the commercially important grapefruit flavor nootkatone 10.

 15

Masahisa Nakada of Waseda University prepared (Angew. Chem. Int. Ed. 2013, 52, 7569) the enantiomerically-​pure allene 15. Oxidation of the phenol to the monoketal of the cyclohexadienone set the stage for intramolecular cycloaddition to give 16. Oxidative cleavage followed by intramolecular alkene metathesis led to (+)-​scabronine G 17.

Dirk Trauner of the University of Munich assembled (Org. Lett. 2013, 15, 4324) the enantiomerically-​pure alcohol 18. Oxidation gave the quinone, leading to intramolecular Diels–​Alder cycloaddition. The free alcohol then added to the exocyclic alkene of that product, to give, after further oxidation, the ether 19. Deprotection followed by reduction then completed the synthesis of (−)-​isoglaziovianol 20.

151  Diels-Alder Cycloaddition

Xinhao Zhang and Chi-​Sing Lee of the Peking University Shenzen Graduate School uncovered (J. Org. Chem. 2013, 78, 7912) another cascade transformation, intermolecular addition of 11 to 12 followed by intramolecular Conia-​ene cyclization, to give the tricyclic 13. Further manipulation led to an established intermediate for the total synthesis of platensimycin 14.

152

76. Diels–​Alder Cycloaddition: Fawcettimine (Zhai), Sculponeatin N (Zhai), Elansolid B1 (Kirschning), Frondosin A (Wright), Kingianin H (Parker), Rufescenolide (Snyder) Douglass F. Taber December 22, 2014

En route to fawcettimine 4, Hongbin Zhai of Lanzhou University found (Org. Lett. 2014, 16, 196) that microwave irradiation improved the efficiency of the cycloaddition of the enone 1 with butadiene 2 to give 3. Takuya Kurahashi and Seijiro Matsubara of Kyoto University developed (Org. Lett. 2014, 16, 2594) a Ru complex that promoted the cycloaddition of butadiene with cyclic enones.

In the course of a synthesis of sculponeatin N 7, Professor Zhai employed (Org. Lett. 2014, 16, 216) the silyl diene 5. After intramolecular cycloaddition, protonation of the resulting allyl silane with concomitant alkene migration led to the adduct 6.

On the way to elansolid B1 10, Andreas Kirschning of Leibnitz Universität Hannover oxidized (Org. Lett. 2014, 16, 568) the alcohol 8 to the enone, that cyclized to 9. Under the influence of MgBr2, the cyclization proceeded with remarkable diastereocontrol.

 153

Kathlyn A. Parker of Stony Brook University explored (J. Org. Chem. 2014, 79, 919) the amine radical cation-​promoted intermolecular Diels–​Alder cycloaddition of the bicyclooctadiene 14. Three readily-​separated diastereomeric dimers were observed. The diol 15, the precursor to kingianin H 16, was the major product.

Scott A. Synder of Scripps/​Florida described (J. Org. Chem. 2014, 79, 88) the interesting oxidative coupling of 17 with 18. The product 19 was readily carried on to rufescenolide 20.

153  Diels-Alder Cycloaddition

Dennis L. Wright of the University of Connecticut began (J. Am. Chem. Soc. 2014, 136, 4309) the synthesis of frondosin A 13 by preparing the secondary ether 11 in high ee. Diels–​Alder cycloaddition of tetrabromocyclopropene gave, after exposure of the initial adduct to water, the dibromoenone 12.

154

77. Diels–​Alder Cycloaddition: Nicolaioidesin B (Coster), Lycorine (Cho), Bucidirasin A (Nakada), Maoecrystal V (Thomson), Kuwanon J (Wulff/​Lei), Vinigrol (Kaliappan) Douglass F. Taber August 24, 2015

β-​Ocimene 2 is an inexpensive Diels–​Alder diene. En route to nicolaioidesin B 4, Mark J. Coster of Griffith University showed (Tetrahedron Lett. 2014, 55, 6864) that the Weinreb amide 1 added to the E isomer of 2 with high selectivity, to give 3.

The alkaloid lycorine 8 is found throughout the Amaryllidaceae. Cheon-​Gyu Cho of Hanyang University developed (Org. Lett. 2014, 16, 5718) a succinct route to 8 based on the use of the boryl styrene 5 as a Diels–​Alder dienophile.

Masahisa Nakada of Waseda University (Org. Lett. 2014, 16, 4734) prepared the enantiomerically-​pure enone 9 by way of a baker’s yeast reduction of a prochiral diketone. Diels–​Alder addition to 10 led to 11, that was carried on to bucidirasin A 12.

 15

William D. Wulff of Michigan State University and Xiaoguang Lei of Peking University optimized (Angew. Chem. Int. Ed. 2014, 53, 9257) the organocatalyzed Diels–​Alder cycloaddition of 17 to the diene 16. Deprotection then completed the synthesis of the prenylflavonoid kuwanon J 18.

In 2012, Barriault described (OHL 20121224) the conversion of 20 to the complex diterpene vinigrol 21. Krishna P. Paliappan of the Indian Institute of Technology Bombay showed (Org. Lett. 2014, 16, 5540) that the triene precursor to 20 could be prepared by ring-​closing metathesis of 19. In the absence of ethylene, a different product was formed.

155  Diels-Alder Cycloaddition

Regan J. Thomson of Northwestern University prepared (J. Am. Chem. Soc. 2014, 136, 17750) the triene 13 by asymmetric epoxidation of a prochiral enone. Diels–​ Alder addition of the very reactive nitroethylene to give 14 completed the carbon skeleton of maoecrystal V 15.

156

78. Diels–​Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (−)-​G-​J Aglycone (Paddon-​Row/​ Sherburn), IBIR-​22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone) Douglass F. Taber December 28, 2015

En route to sarcandralactone A 3, Scott A. Snyder of Scripps Florida effected (Angew. Chem. Int. Ed. 2015, 54, 7842) Diels–​Alder cycloaddition of the activated enone 1 to the Danishefsky diene. On exposure to trifluoroacetic acid, the adduct was unraveled to the ene dione 2.

Michael N. Paddon-​Row of the University of New South Wales and Michael S. Sherburn of the Australian National University prepared (Nature Chem. 2015, 7, 82) the allene 4 in enantiomerically-​pure form. Sequential cycloaddition with 5 followed by 6 gave an adduct that was decarbonylated to 7. Further cycloaddition with nitroethylene 8 led to the pseudopterosin (−)-​G-​J aglycone 9.

The protein–​protein interaction inhibitor JBIR-​22 12 contains a quaternary α-​ amino acid pendant to a bicyclic core. Nicholas J. Westwood of the University of St. Andrews set (Angew. Chem. Int. Ed. 2015, 54, 4046) the absolute configuration of the core 11 by using an organocatalyst to activate the cyclization of 10.

 157

Unactivated intramolecular Diels–​Alder cycloadditions have been carried out with more and more challenging substrates. A key step in the synthesis (Chem. Asian. J. 2015, 10, 427) of (−)-​platencin 18 by Martin G. Banwell, also of the Australian National University, was the cyclization of 16 to 17.

In another illustration of the power of the unactivated intramolecular Diels–​ Alder reaction, Thomas J. Maimone of the University of California, Berkeley cyclized (Angew. Chem. Int. Ed. 2015, 54, 1223) the tetraene 19 to the tricycle 20. Allylic chlorination followed by reductive cyclization converted 20 to chatancin 21.

157  Diels-Alder Cycloaddition

Metal catalysts can also be used to set the absolute configuration of a Diels–​Alder cycloaddition. In the course of establishing the structure of the marine natural product muironolide A 15, Armen Zakarian of the University of California, Santa Barbara cyclized (J. Am. Chem. Soc. 2015, 137, 5907) the enol form of 13 preferentially to the diastereomer 14.

158

79. Other Methods for C–​C Ring Construction: Pinolinone (Bach), Agelastatin A (Batey), Panaginsene (Lee), Salvileucalin D, Salvileucalin C (Ding), ent-​Codeine (Hudlicky), Walsucochin B (Xie/​Shi) Douglass F. Taber December 29, 2014

Thorsten Bach of the Technische Universität München used (Chem. Commun. 2014, 50, 3353) the chiral medium-​mediated photochemical 2+2 cycloaddition that he developed to prepare 3 by combining 1 with 2. Oxidative cleavage led to (−)-​pinolinone 4.

Robert A. Batey of the University of Toronto rearranged (Angew. Chem. Int. Ed. 2013, 52, 10862) furfural 5 in the presence of 6 to give the enone 7. Acylation followed by intramolecular conjugate addition delivered agelastatin A 8.

Hee-​Yoon Lee of KAIST prepared (Org. Lett. 2014, 16, 2466) the tosylhydrazone Na salt 9 from citronellal. Thermolysis led, via a dialkyl diazo intermediate, to the tricyclic 10. Direct comparison of synthetic material with the natural product panaginsene 11 enabled the assignment of the relative configuration of the pendant methyl group.

 159

In a recent chapter of his continuing work on the morphine alkaloids, Tomas Hudlicky of Brock University described (Adv. Synth. Catal. 2014, 356, 333) the intramolecular [3+2] cycloaddition of the nitrone derived from 15 to give 16. This was readily carried on to ent-​codeine 17.

Xingang Xie and Xuegong She of Lanzhou University used (Org. Lett. 2014, 16, 1996) Shi epoxidation and Itsuno–​Corey reduction to prepare 18 in enantiomerically-​ pure form. Cationic cyclization converted 18 to 19, that was oxidized to (−)-​walsucochin B 20.

159  Other Methods for C–C Ring Construction

Hanfeng Ding of Zhejiang University eliminated (Org. Lett. 2014, 16, 3376) HBr from 12 to give, after rearrangement, the cycloheptadiene salvileucalin D 13. Irradiation converted 13 to the cyclobutene salvileucalin C 14.

160

80. Carbocyclic Ring Construction: The Nicolaou Synthesis of Myceliothermophin E Douglass F. Taber August 31, 2015

Nan Zheng of the University of Arkansas developed (Adv. Synth. Catal. 2014, 356, 2831) a Ru catalyst for the addition of an amino cyclopropane 1 to an alkyne 2 to give 3. The reaction proceeded with high regiocontrol, but only modest stereocontrol.

Alain De Mesmaeker of Syngenta Crop Protection, Switzerland found (Tetrahedron Lett. 2014, 55, 6577) that the β,γ-​unsaturated amide 4 worked particularly well as a precursor to the keteniminium that cyclized to give, after hydrolysis, the cyclobutanone 5. Baeyer–​Villiger oxidation of 5 led to 5-​deoxystrigol 6.

David Tymann and Martin Hiersemann of the Technische Universität Dortmund have been exploring (Org. Lett. 2014, 16, 4062; Synthesis 2014, 46, 3110) the intramolecular carbonyl ene reaction as a tool for the assembly of highly substituted cyclopentanes, as in the conversion of 7 to 8. On oxidation, 8 was readily carried on to the alkene 9.

James L. Leighton of Columbia University conceived (J. Am. Chem. Soc. 2014, 136, 9878) the cascade transformation of 10 to 12. Deprotonation/​silylation set the stage for Claisen rearrangement to give 11. The subsequent Cope rearrangement is an equilibrium process, driven by the ring strain of 11.

 16

161  Carbocyclic Ring Construction

K. C. Nicolaou of Rice University described (Angew. Chem. Int. Ed. 2014, 53, 10970) the total synthesis of the cytotoxic tetramic acid derivative myceliothermophin E 15. A key step in the synthesis was the intramolecular Michael addition/​aldol condensation that converted 13 to 14.

162

81. The Inoue Synthesis of 19-​Hydroxysarmentogenin Douglass F. Taber January 6, 2014

With the continual improvement in synthetic methods, even highly oxidized steroids such as the cardenolide aglycone 19-​hydroxysarmentogenin 3 are accessible. A key step in the preparation of 3 described (Angew. Chem. Int. Ed. 2013, 52, 5300) by Masayuki Inoue of the University of Tokyo was the free radical cyclization of the acetal-​tethered bromo enone 1 to 2.

The cyclopentane component of 1 was prepared from the dione 4. Diastereoselective reduction followed by protection led to 5, that was carried on to the enol ether 6.

The preparation of 13 began with the Diels–​Alder addition of enantiomerically-​ pure perillaldehyde 7 to the diene 8. Hydrolysis gave the enone 9, that was converted to the enone 10. Oxidative cleavage of the isopropenyl group gave 11, that was carried on via 12 to 13.

 163

The intramolecular aldol condensation of the intermediate trione proceeded with a 8.6:1 preference for 15. The minor diastereomer was readily converted to an even more favorable 12:1 mixture on re-​exposure to KHMDS. After the unnecessary carbonyl was removed, leading to 16, oxidative cleavage exposed the C-​11 ketone. Selective protection, to 17, followed by reduction to 18 and iodination completed the preparation of 19. Pd-​mediated coupling with the known stannane 20 led to 21. Direct hydrogenation of 21 gave the wrong C-​17 diastereomer, but hydrogenation of the derived silyl ether was successful, leading to 19-​hydroxysarmentogenin 3.

The availability of such highly substituted steroids by total synthesis will reinvigorate structure–​activity studies.

163  The Inoue Synthesis of 19-Hydroxysarmentogenin

Addition of Br2 to 6 gave an unstable dibromide, that was coupled with 13 to give 1 as a mixture of diastereomers. Free radical cyclization proceeded with high diastereocontrol, delivering 14. Elimination of methanol followed by reprotection completed the preparation of 2.

164

82. The Nakada Synthesis of (+)-​Ophiobolin A Douglass F. Taber February 3, 2014

Ophiobolin A 3 shows nanomolar toxicity toward a range of cancer cell lines. A central feature of this sesterterpene, isolated from the rice fungus Ophiobolus miyabeanus, is the highly-​substituted eight-​membered ring. A key step in the synthesis of 3 described (Chem. Eur. J. 2013, 19, 5476; Angew. Chem. Int. Ed. 2011, 50, 9452) by Masahisa Nakada of Waseda University was the acid-​mediated cyclization of 1 to 2.

The preparation of 1 began with the enantioselective hydrolysis of 4 to the monoester 5. Selective reduction followed by protection gave 6, that was carried on via 7 to 8. The ethoxyethyl group was selectively removed, and the alcohol was converted to an iodide (not illustrated) that was condensed with the lactone 9 to give 1.

The cyclization of 1 could jeopardize the stereogenic center adjacent to the masked carbonyl, so eight diastereomers were possible. Careful optimization led to a preparatively useful yield of the desired product 2. Hydroboration gave 10, that was carried on to the aldehyde 11.

 165

Metathesis to close the eight-​membered ring was not trivial. Finally, it was found that 17 could be induced to cyclize to 18 at an elevated temperature using the second-​generation Hoyveda catalyst. Protecting group exchange gave 19. Routine functional group manipulation then completed the synthesis of (+)-​ophiobolin 3. Some years ago, Neil E. Schore of the University of California, Davis showed (Tetrahedron Lett. 1994, 35, 1153) that the opening of Sharpless-​derived epoxides such as 12 with vinyl nucleophiles was unexpectedly flexible. One set of conditions gave the expected inversion, but alternative conditions led to opening with clean retention (or double inversion) of absolute configuration.

165  The Nakada Synthesis of (+)-Ophiobolin A

The cyclopentanone 15 was prepared from the enantiomerically-​enriched epoxide 12. Opening with vinyl magnesium bromide followed by exposure to the second-​ generation Grubbs catalyst gave the diol 13, that was selectively protected, leading to 14. The derived bromohydrin was a mixture of regioisomers and diastereomers, from which, after oxidation, 15 dominated. Generation of the boron enolate from 15 in the presence of 11 gave the aldol product, that could be dehydrated with the Burgess reagent. Reduction with Raney nickel set the stereogenic center adjacent to the ketone, that was carried on to 16.

16

83. The Herzon Synthesis of (−)-​Acutumine Douglass F. Taber March 3, 2014

The alkaloid (−)-​acutumine 3, isolated from the roots of the Chinese moonseed Sinomenium acutum, improves object and social recognition in the Wistar rat model. With four rings and three adjacent, fully-​substituted stereogenic centers, 3 presents a significant synthetic challenge. Seth B. Herzon of Yale University assembled (Angew. Chem. Int. Ed. 2013, 52, 3642) 3 by the intramolecular Sakurai cyclization of 1 to 2.

The convergent preparation of 1 required the alkyne 10. The literature construction (Org. Lett. 2005, 7, 5075) by A. B. Smith III of the enone 7 from ribose 4 began with protection to 5. Conversion of the primary alcohol to the iodide followed by reduction delivered the aldehyde 6. Addition of vinyl magnesium bromide followed by exposure to the first-​generation Grubbs catalyst gave the cyclopentenol, that was oxidized to 7. Conjugate silylation led to the triflate 8, that was carried via coupling with 9 to 10.

In earlier work, Professor Herzon had shown (Angew. Chem. Int. Ed. 2011, 50, 8863) that the prochiral quinone from oxidation of 11 could be added to the diene 12 under enantioselective catalysis, to give 13 in high ee. Reduction of the azide gave the imine, that was quaternized with methyl triflate. Addition of the Li salt of 10 to

 167

The completion of the synthesis required extensive experimentation. Eventually, a protocol was established to oxidize 15 over several steps to the dienone 16. Selective reduction of the ketone (the other carbonyls are vinylogous esters) proceeded with the desired facial selectivity, to give 17. Selective hydrogenation using a Rh catalyst then delivered (−)-​acutumine 3. This is the second total synthesis of (−)-​acutumine 3. The first, by Steven L. Castle of Brigham Young University (OHL October 5, 2009), is quite different. It is instructive to compare the two side by side.

167  The Herzon Synthesis of (−)-Acutumine

that sensitive intermediate proceeded with high facial selectivity. With aromatization blocked, the product from the addition of 10 could be thermolyzed to yield 14. The stannylation of the alkyne proceeded with high regio-​and stereoselectivity, to give the alkene 1. Exposure of the allylic silane to tetrabutylammonium fluoride drove the desired cyclization to give 2. Chlorination followed by acetonide removal then completed the preparation of the diol 15.

168

84. The Njardarson Synthesis of Vinigrol Douglass F. Taber April 7, 2014

The diterpene vinigrol 3, isolated from Virgaria nigra F-​5408, is a tumor necrosis factor (TNF) inhibitor. Jon T. Njardarson of the University of Arizona envisioned (Angew. Chem. Int. Ed. 2013, 52, 8648) that Wharton fragmentation of 1 could deliver 2, suitably functionalized for elaboration to 3.

The tetracyclic 1 was prepared by the triply-​convergent assembly of the phenol 11. Addition of allyl magnesium bromide to 4 proceeded with high regio-​and geometric selectivity, to give an alcohol that was methylated, then iodinated with inversion to give 5. Condensation of the phosphonate 7 with the derived aldehyde 6 led to the alcohol 8, that was coupled under Mitsunobu conditions with the phenol 9 to give 10. Oxidation of 11 gave an intermediate that underwent intramolecular Diels–​ Alder cycloaddition to deliver 12. On exposure to the Pd catalyst, 12 cyclized to the diene 13.

 169

Subsequent transformations took advantage of the hindered nature of the trisubstituted alkene of 2. Hydrogenation of the disubstituted alkene proceeded selectively, to give an intermediate that was condensed with 14, leading to the enone 15. Two more selective hydrogenations, with the Wittig methylenation in between, completed the construction of the pendant isopropyl group. Once the isopropyl group was installed, what remained was the oxidation of 16 to 19. The epoxidation of 17 proceeded with high facial selectivity, to give an intermediate that was carried on by iodination and reduction to the alcohol 18. Allylic oxidation converted 18 into 19, that was deprotected to give Vinigrol 3. It is instructive to compare and contrast this approach to vinigrol 3 with the two that we have previously highlighted (OHL September 6, 2010; December 24, 2012). Each strategy offers its own advantages.

169  The Njardarson Synthesis of Vinigrol

On exposure to tBuOK/​tBuOH, the mesylate 1 smoothly fragmented to the hoped-​for ketone 2. Although this has been referred to as a Grob fragmentation, in fact this reaction was developed (J. Org. Chem. 1961, 26, 4781) by Peter S. Wharton, then at the University of Wisconsin, and would more properly bear his name.

170

85. The Gin Synthesis of Neofinaconitine Douglass F. Taber May 5, 2014

The hexacyclic norditerpenoid alkaloids, including neofinaconitine 4, isolated from traditional Chinese and Japanese antiarrhythmics and analgesics, have long offered a challenge to organic synthesis. The late David Y. Gin of the Memorial Sloan-​Kettering Cancer Center envisioned (J. Am. Chem. Soc. 2013, 135, 14313) an approach to 4 by way of the Diels–​Alder coupling of 1 and 2. This project was completed under the supervision of his colleague Derek S. Tan.

The cyclopropene 6 was prepared from the ester 5. Addition of 6 to the diene derived from 7 proceeded with modest regioselectivity to give, after enol ether hydrolysis, the ketone 8. After two-​carbon extension of the ketone with 9 to the ester 10, ionization with HBr led to 11, that was carried on the diene 1.

Opening of caprolactam 12 with ethylamine followed by oxidation delivered the aldehyde 13. Acid-​mediated cyclization to the enamide followed by bromination gave 14. Carbomethoxylation followed by selenylation and oxidation completed the preparation of the dienophile 2.

 17

There are two classes of the norditerpenoid alkaloids, having 18 and 19 carbons respectively. The ester 19 could be a versatile precursor to both classes. For 4, the carbon had to be removed. Reduction and protection followed by oxidative cleavage gave 20, that was carried on to neofinaconitine 4.

171  The Gin Synthesis of Neofinaconitine

With the sterically-​demanding Br blocking one face of the diene, Diels–​Alder cycloaddition of 2 to 1 proceeded with high diastereocontrol, leading after hydrolysis of the intermediate silyl enol ether to the ketone 15. Oxidative cleavage of the more accessible alkene followed by elimination led to the ketone 16, that on exposure to acid underwent Mannich cyclization. Oxidation followed by elimination completed the preparation of 17. Reductive cyclization to 18 established the sixth and last ring of 4, but the tertiary alcohol was lacking. This was installed by selenylation followed by oxidation, presumably by way of the transient anti-​Bredt enone.

172

86. The Li Synthesis of Daphenylline Douglass F. Taber June 2, 2014

The genus Daphniphyllum consists of 25–​30 species of evergreen trees and shrubs of south Asia. The leaves and roots are widely used in Chinese herbal medicine. About 250 alkaloids, many with complex polycyclic structures, have been isolated from these species. Of these, daphenylline 3 is unique in incorporating a benzene ring. Ang Li of the Shanghai Institute of Organic Chemistry envisioned (Nature Chem. 2013, 5, 679) a route to 3 based on the diastereoselective intramolecular Michael cyclization of 1 to 2.

Following the work of Piers (J. Org. Chem. 1996, 61, 8439), the preparation of 1 began with the Birch reduction of 4, followed by hydrolysis. Epoxidation followed by elimination and acetylation led to the racemic acetate 5. Hydrolysis with pig liver esterase left one enantiomer of the acetate, that was transesterified with methoxide to give 6 in high ee.

Mitsunobu coupling of 6 with the o-​nitrobenzenesulfonamide 7 gave 8. After some experimentation, selective α¢-​silylation was effected with TBDPSOTf, setting the stage for gold-​catalyzed Conia cyclization to 9. Deprotection of the amine followed by acylation with 10 gave 1, that cyclized smoothly to 2 as a 10:1 ratio of diastereomers.

 173

To close the last ring of 3, the ketone 13 was further oxidized to the enone 14. Desilylation of 14 followed by exposure to Ph3P/​I2 gave the iodide 15, that was cyclized under reductive free radical conditions to 16.

The hydrogenation of 16 under Pd catalysis delivered the incorrect diastereomer, perhaps because migration to the endocyclic alkene preceded reduction. This problem was solved by using the Crabtree Ir catalyst. Modified Krapcho decarbomethoxylation then gave 17, that was reduced to daphenylline 3.

173  The Li Synthesis of Daphenylline

The arene of 3 was constructed by converting 2 into the corresponding vinyl triflate. Pd-​mediated coupling with 11 gave 12. Under irradiation with strict exclusion of oxygen, 12 cyclized to the dihydro aromatic, that on warming with DBU in the presence of air was oxidized to 13.

174

87. The Baran Synthesis of Ingenol Douglass F. Taber July 7, 2014

The early promise for the biological activity of the derivatives of ingenol 3 has been borne out by the clinical efficacy of the derived angelate, recently approved by the US Food and Drug Administration for the treatment of actinic keratosis. Phil S. Baran of Scripps La Jolla envisioned (Science 2013, 341, 878) a route to 3 based on a rearrangement of 2, available by the Pauson–​Khand cyclization of the allenyl alkyne 1.

One of the partners for the preparation of 1 was available following the Sugai (Synlett 1997, 1297) procedure, by the Claisen rearrangement of triethyl orthopropionate 5 with the propargyl alcohol 4 to give 6. Reduction delivered a racemic mixture of alcohols. On exposure of the mixture to vinyl acetate and Pseudomonas cepacia lipase, the undesired enantiomer was selectively acetylated to 7, leaving residual 8 of high ee. IBX was found by the Scripps group to be effective at oxidizing 8 without racemization.

The other component of 1 was prepared from the inexpensive (+)-​3-​carene 10. Chlorination followed by ozonolysis delivered 11, that was reduced to the enolate, then alkylated with methyl iodide. Exposure to LiHMDS gave a new enolate, that was added to the aldehyde 9 to give 12. Addition of ethynyl magnesium bromide to the now more open face of 12 proceeded with high diastereoselectivity. Selective silylation of the secondary alcohol followed by silylation of the tertiary alcohol set the stage for the Pauson–​Khand cyclization.

 175

All that remained to complete the synthesis was selective oxidation. Allylic oxidation with stoichiometric SeO2 installed the secondary alcohol, that was acetylated to give 15. The other secondary alcohol was then freed, and dehydrated with the Martin sulfurane, to give 16. A last allylic oxidation completed the synthesis of ingenol 3. It is informative to compare the concise approach to ingenol 3 achieved in this work to the complementary total syntheses outlined in the Highlights for March 1, 2004, and for April 25, 2005. The three syntheses are quite different one from another.

175  The Baran Synthesis of Ingenol

Following the Brummond protocol, 1 was cyclized to 2. Methyl magnesium bromide was added, again to the more open face of the ketone, to give a new tertiary alcohol. Exposure to stoichiometric OsO4 converted the more available alkene to the cis diol, that was protected as its cyclic carbonate 13. A central challenge in the total synthesis of the ingenanes is the construction of the “inside–​outside” skeleton. This was achieved by the pinacol rearrangement of 13 with BF3•OEt2, to give 14.

176

88. The Fürstner Synthesis of Amphidinolide F Douglass F. Taber August 4, 2014

The amphidinolides, having zero, one, or (as exemplified by amphidinolide F 3) two tetrahydrofuran rings, have shown interesting antineoplastic activity. It is a tribute to his development of robust Mo catalysts for alkyne metathesis that Alois Fürstner of the Max-​Planck-​Institut für Kohlenforschung Mülheim could with confidence design (Angew. Chem. Int. Ed. 2013, 52, 9534) a route to 3 that relied on the ring-​closing metathesis of 1 to 2 very late in the synthesis.

Three components were prepared for the assembly of 1. Julia had already reported (J. Organomet. Chem. 1989, 379, 201) the preparation of the E bromodiene 5 from the sulfone 4. The alcohol 7 was available by the opening of the enantiomerically-​pure epoxide 6 with propynyl lithium, followed by oxidation following the Pagenkopf protocol. Amino alcohol-​directed addition of the organozinc derived from 5 to the aldehyde from oxidation of 7 completed the assembly of 8.

Addition of the enantiomer 10 of the Marshall butynyl reagent to 9 followed by protection, oxidation to 11, and addition of, conveniently, the other Marshall enantiomer 12 led to the protected diol 13. Silylcupration–​methylation of the free alkyne set the stage for selective desilylation and methylation of the other alkyne. Iodination then completed the trisubstituted alkene of 14.

 17

The plan from the beginning had been to selectively hydrate the alkyne of 2 by Pt-​ mediated intramolecular addition of the free alcohol. Inspection of models had led to the decision that the R diastereomer would cyclize more readily than the S, so that was the one prepared. In the event, cyclization followed by hydrolysis of the intermediate enol ether gave the desired ketone 23, that was carried on to amphidinolide F 3. It is instructive to compare the work described here with the complementary synthesis of 3 recently reported (Angew. Chem. Int. Ed. 2012, 51, 7948; J. Am. Chem. Soc. 2013, 135, 10792) by Rich G. Carter of Oregon State University. In both approaches, enantiomerically-​pure subunits were assembled to make 3.

177  The Fürstner Synthesis of Amphidinolide F

Methylation of the crystalline lactone 15, readily prepared from D-​glutamic acid, led to a mixture of diastereomers. Deprotonation of that product followed by an aqueous quench delivered 16. Reduction followed by reaction with the phosphorane 17 gave the unsaturated ester, that cyclized with TBAF to the crystalline 18. The last stereogenic center of 22 was established by proline-​mediated aldol condensation of the aldehyde 19 with the ketone 20. To assemble the three fragments, the ketone of 21 was converted to the enol triflate and thence to the alkenyl stannane. Saponification gave the free acid 22, that was activated, then esterified with the alcohol 18. Coupling of the stannane with the iodide 14 followed by removal of the TES group led to the desired diyne 1. It is noteworthy that the Mo metathesis catalyst is stable enough to tolerate the free alcohol of 1 in the cyclization to 2.

178

89. The Deslongchamps Synthesis of (+)-​Cassaine Douglass F. Taber September 1, 2014

Although the Na+-​K+-​ATPase inhibitor (+)-​cassaine 4 was isolated from the bark of Erythrophleum guineense in 1935, the structure was not established until 1959. Intriguing features of 4 include the unsaturated amide and the axial secondary methyl group, both pendant to the C ring. Pierre Deslongchamps, now at Université Laval, envisioned (Org. Lett. 2013, 15, 6270) that the relative stereochemistry of the secondary methyl could be established kinetically by intramolecular Michael addition of the enolate formed by the addition of the anion of 2 to the enone 1 to give 3.

The sulfoxide 2 was readily prepared by the addition (Tetrahedron Lett. 1990, 31, 3969) of the anion derived from methyl phenyl sulfoxide to methyl crotonate. The enone 1 was prepared from commercial dihydrocarvone 5. Robinson annulation with ethyl vinyl ketone 6 (Tetrahedron 2000, 56, 3409) led to 7, that was reductively methylated, reduced further, and protected to give 8. Oxidative cleavage of the pendant isopropenyl group followed by Baeyer–​Villiger oxidation, hydrolysis, and further oxidation gave the ketone 9, that was methoxycarbonylated, then oxidized further to 1.

The addition of the anion derived from 2 to 1 presumably gave initially the axial adduct. Subsequent intramolecular Michael addition then proceeded selectively to one face of the residual enone to give, after elimination of the sulfoxide, the enone 3.

 179

A series of protection, reduction, and oxidation steps led to the C-​ring ketone, that was methoxycarbonylated to give 14. Reduction followed by dehydration gave the unsaturated ester, that was reduced to the saturated ester with Mg in methanol. Reduction followed by oxidation then delivered the aldehyde 15. After some investigation, it was found that the aldehyde could be converted to the desired enol triflate by exposure to KHMDS and the Comins reagent. Deprotection and oxidation followed by Pd-​mediated carbonylation in the presence of 2-​dimethylaminoethanol and further deprotection then completed the synthesis of (+)-​cassaine 4. It is instructive to compare this synthesis to the complementary preparation of (+)-​ cassaine 4 previously reported (OHL August 24, 2009) by Professor Deslongchamps, that centered on a transannular intramolecular Diels–​Alder cycloaddition. In that case, the axial secondary methyl was installed by conjugate addition to a preformed C ring.

179  The Deslongchamps Synthesis of (+)-Cassaine

The anionic cascade annulation that formed the C ring having been accomplished, the ester of 3 was removed by exposure to ethoxide to give 10, having the alkene conjugated with the B-​ring ketone. Selective reduction followed by protection gave 11. In the course of the hydrogenolytic deprotection of the A-​ring alcohol, selective hydrogenation of the tetrasubstituted alkene was also observed. Increasing the H2 pressure and extending the reaction time gave complete conversion to the desired 12, the relative configuration of which was established by X-​ray crystallography.

180

90. The Kan Synthesis of the Streptomyces Alkaloid SB-​203207 Douglass F. Taber October 6, 2014

The alkaloid SB-​203207 3, isolated from a Streptomyces species by a SmithKline Beecham group, was shown to inhibit isoleucyl tRNA synthetase with an IC50 of less than 2 nM. Toshiyuki Kan of the University of Shizuoka envisioned (Org. Lett. 2014, 16, 1646) that the carbocyclic core of 3 could be assembled by the Rh-​mediated cyclization of 1 to 2.

The authors had already demonstrated (Org. Lett. 2008, 10, 169) the cyclization of 1 to 2. For the assembly of 3, they needed to scale up the preparation of 1. To this end, they required the mandelamide 5 and the aldehyde 8. To prepare 5, they devised a new preparation of diazoacetates, condensation with bromoacetyl bromide followed by exposure to the bis sulfonamide. The aldehyde 8 was prepared from the acid 6 (commercial, or Org. Synth. 2004, Coll. Vol. 10, 228). The preparation of the third component of 3, the acid 9, had been described earlier by Banwell and Easton (Bioorg. Med. Chem. 2003, 11, 2687).

The cyclization of 1 proceeded smoothly with 0.1% loading of the Rh catalyst, to give 2 in 72% de (85:15 ratio of enantiomers of the carbocyclic core). The enantiomeric excess could be upgraded by recrystallization of a later intermediate. The ester 2 was exchanged with allyl alcohol to give 10, presumably with recovery of the liberated chiral auxiliary 4. Formaldehyde added to the β-​keto ester 10 from the more open face. Hydride addition from that same face then delivered the diol 11. The allyl ester was removed,

 18

The oxime of 14 was dehydrated to the nitrile, that was readily carried on to the aldehyde 15. The aldehyde resisted oxidation to the corresponding carboxylic acid. Eventually, it was found that the derived cyanohydrin could be oxidized. The acid was protected as the benzhydryl ester to give 16. Both the Boc and the MOM group were removed by B-​bromocatechol borane, opening the way to acylation with the acid 9 to give 17. The nitrile was hydrated to the primary amide using the Parkins catalyst. In the last stage, the protecting groups were removed by hydrogenation, to give alkaloid SB-​203207 3.

181  The Kan Synthesis of the Streptomyces Alkaloid SB-203207

and the free acid was activated with SOCl2 then condensed with ammonia to give the primary amide. Ozonolysis followed by acidic methanol led to cyclization onto the amide, allowing ready differentiation of the two ends of the alkene. Reduction completed the preparation of the lactam 12. The nitrogen was sulfonylated, then the activated lactam was opened with assistance from the liberated primary alcohol. After acetal hydrolysis, the sulfonamide added to the aldehyde to give, after dehydration, the enamide 13. Inversion of the carboxyl converted the hydroxy acid to the urethane, that was formylated with the modified Vilsmeier reagent. Protection and deprotection followed by methylation then delivered the vinylogous amide 14.

182

91. The Trost Synthesis of (−)-​Lasonolide A Douglass F. Taber November 3, 2014

(−)-​Lasonolide A 4, isolated from the Caribbean sponge Forcepia sp., showed remarkable anticancer activity in the NIH 60-​cell screen. The central step in the synthesis of 4 reported (J. Am. Chem. Soc. 2014, 136, 88) by Barry M. Trost of Stanford University was the remarkably selective, convergent Ru-​mediated coupling of 1 with 2 to give 3.

To prepare 1, the authors took advantage of the underutilized Cu-​mediated addition of a Grignard reagent 6 to propargyl alcohol 5, to give 7. Coupling with the acetonide 8 followed by deprotection led to the phosphonium salt 9.

The other half of 1 was prepared from the acetonide 10 of the commodity chemical 1,1,1-​tris(hydroxymethyl)ethane. Oxidation followed by Zn-​catalyzed aldol addition of the ketone 11 led to the alcohol 12. Diastereoselective reduction followed by protection gave 13. Condensation with benzaldehyde proceeded with remarkable diastereoselection, setting the quaternary center of 14. Spontaneous intramolecular Michael addition proceeded under the conditions of the subsequent Horner-​Emmons reaction, leading to the aldehyde 15. Wittig reaction with the phosphonium salt 9 followed by deprotection completed the preparation of the alkyne 1.

 183

Acetone was the solvent of choice for the coupling of 1 with 2. This led to the acetonide 3, that was hydrolyzed and protected to give 25. Yamaguchi macrolactonization followed by deprotection then delivered (−)-​lasonolide A 4. It is instructive to compare this work to the four previous total syntheses of 4, one of which (Org. Highlights November 26, 2007) we have previously highlighted.

183  The Trost Synthesis of (−)- Lasonolide A

The β-​ketoester 18 prepared by the addition of 17 to 16 was prone to unwanted conjugation, and the terminal alkene was easily reduced under hydrogenation conditions. Enzymatic conditions were found to effect dynamic kinetic resolution and reduction, to give 19. The derived ketone 21, from coupling with 20 was reduced using the Corey organocatalyst, then hydrosilated, leading to 22. Under metathesis with 23, the product unsaturated aldehyde cyclized to 24. Homologation followed by allylation then completed the construction of 2.

184

92. The Fukuyama Synthesis of (−)-​Lepenine Douglass F. Taber December 1, 2014

The denudatine alkaloids, exemplified by (−)-​lepenine 3, have been converted chemically into the physiologically-​active aconitine alkaloids. Tohru Fukuyama of Nagoya University envisioned (J. Am. Chem. Soc. 2014, 136, 6598) an intramolecular Mannich condensation, the conversion of 1 to 2, that in a single step would assemble two of the six rings of 3.

The starting material for the synthesis was the ether 4, prepared by Mitsunobu coupling of the phenol with L-​lactic acid methyl ester. Reduction of the ester to the aldehyde followed by the addition of vinylmagnesium chloride led to the secondary allylic alcohol. Claisen rearrangement with triethyl orthoacetate delivered not the ether, but rather 5, the desired product of an additional Claisen rearrangement. The phenol of 5 was protected as the mesylate, that was then subjected to ozonolysis with a reductive workup to give the primary alcohol. This was protected as the pivalate, which was selectively saponified. The resulting carboxylic acid was cyclized to 6 using trifluoroacetic anhydride.

The triene 7 was prepared from 6 by the addition of vinylmagnesium chloride followed by dehydration. Prospective intramolecular Diels–​Alder cycloadditions that

 185

It is possible to protect tertiary amines, inter alia by formation of the adduct with a borane. In this case, transient protection as the hydrochloride was sufficient to allow oxidation of the alcohol derived from 2 to the diene 11. This was reactive enough to undergo the Diels–​Alder addition of ethylene, from the more open face, leading to 12. The now-​extraneous methoxy groups were then removed reductively to give 13, and the last stereogenic center of 3 was installed by hydroboration of the alkene. Methylenation of 14 followed by Luche reduction then completed the synthesis of (−)-​lepenine 3.

185  The Fukuyama Synthesis of (–)-Lepenine

would form five-​or six-​membered ring lactones often fail. In the event, the cyclization of 7 to the seven-​membered ring lactone 8 proceeded smoothly. The tetracyclic 8 could be brought to high ee by recrystallization. Hydroboration followed by reduction then delivered the diol aldehyde 9, that was converted to 1 by reductive amination followed by protection and oxidation. On deprotection, 1 cyclized to the iminium salt 10. Intramolecular Mannich addition of the enol form of the ketone then proceeded, to give 2.

186

93. The Smith Synthesis of (−)-​Calyciphylline N Douglass F. Taber January 5, 2015

The Daphniphyllum alkaloids are a diverse group, some of which exhibit potent biological activity. Amos B. Smith III of the University of Pennsylvania envisioned (J. Am. Chem. Soc. 2014, 136, 870) the preparation of the bicyclo[2.2.2] core of (−)-​ calyciphylline N 3 by the intramolecular Diels–​Alder cyclization of 1 to 2, with the silicon of 2 a surrogate for the secondary alcohol of 3.

Following the precedent of Mori (Tetrahedron Asymm. 2005, 16, 685), the requisite secondary center of 1 was set by methylation of the anion derived from the Evans acyl oxazolidinone 4. Reductive removal of the oxazolidinone led to the alcohol 5, that was reduced under Birch conditions, then isomerized with base to the desired conjugated diene 6. This was silylated with the alkenyl silane 7 to give the triene 1. Direct thermal cyclization of 1 gave a mixture of all four possible diastereomers of the cycloadduct. Fortunately, the Lewis acid-​activated cyclization delivered 2 as the dominant diastereomer.

To differentiate the two ends of the alkene, the ester of 2 was extended to the alcohol 8. Epoxidation occurred from the more open face of the alkene, setting the stage for intramolecular opening and oxidation to give 9. Reduction with SmI2 and protection then completed the preparation of the ketone 10.

 187

The alkene of 13 was converted to the primary alcohol, which was protected. The aryl lithium 14 then was used to selectively open the cyclic silyl ether, to give 15. Coupling with phthalimide followed by carbonylative vinylation of the derived vinyl triflate delivered the dienone 16. Exposure to HBF4 effected the desired Nazarov cyclization, and at the same time converted the aryl silane to the fluorosilane, set for the Tamao oxidation that revealed the secondary alcohol. The two alcohols were sequentially protected to give 17.

Direct oxidation of the primary silyl ether gave the aldehyde. Following the precedent of Carreira in the preparation of the closely related alkaloid (+)-​ daphmanidin E (Organic Highlights September 3, 2012), intramolecular aldol condensation followed by oxidation led to 18. Selective Ir-​catalyzed hydrogenation followed by deprotection and cyclization then completed the synthesis of (−)-​ calyciphylline N 3.

187  The Smith Synthesis of (−)-Calyciphylline N

The third quaternary center of 3 was constructed by acetylation of 10 followed by Pd-​catalyzed allylation, to give 11. On exposure to LDA, the derived iodide 12 smoothly cyclized to the cycloheptanone 13, the structure of which was confirmed by X-​ray analysis.

18

94. The Paterson Synthesis of (−)-​Leiodermatolide Douglass F. Taber February 2, 2015

(−)-​Leiodermatolide 4, isolated from the lithistid sponge Leiodermatium sp., showed 5.0-​nM activity against PANC-​1 pancreatic carcinoma cells, and reduced toxicity toward normal cells. Ian Paterson of the University of Cambridge established (Angew. Chem. Int. Ed. 2014, 53, 2692) a synthetic route to 4 based on sp2–​sp2 coupling, as exemplified by the combination of 1 with 2 to give 3.

Addition of the boron enolate of the enantiomerically-​pure benzoate 5 to the iodoaldehyde 6 gave 7, that was silylated, reduced, and deprotected to give 1. Addition of the boron enolate of ent-​5 to propanal gave 8. The α-​acyloxy ketone of 8 served as a masked acylating agent. The addition of allyl magnesium bromide followed by oxidative cleavage led to the ketone 9. The preparation of 2 was completed by diastereoselective Mukaiyama aldol condensation of 9 with the ketene silyl acetal 10.

The intramolecular Heck coupling of 1 with 2 presumably proceeded by way of the organo-​Pd intermediate 11. β-​Hydride elimination could have given one or more of four possible dienes, but in fact the E,E product 3 dominated, as expected. The allylic H’s are activated for elimination, while the H’s β to the silyl ether are deactivated both electronically and sterically.

 189

The diol 3 was oxidatively cleaved, and the resulting aldehyde was carried on to the iodide 18. This was coupled with the stannane 17 to give the diene 19. A sequence of deprotection, oxidation, and further deprotection yielded a tetraol, that was lactonized with high selectivity to give the 16-​membered ring of (−)-​leiodermatolide 4.

189  The Paterson Synthesis of (−)-Leiodermatolide

The third component of 4 was the stannane 17. Applying the same strategy, the addition of ent-​5 to the aldehyde 12 gave 13, that was protected and condensed with 14 to deliver, after oxidative cleavage, the alkynyl ketone 15. Conjugate addition of iodide proceeded with good geometric control to give 16, that was protected and stannylated to complete the preparation of 17.

190

95. The Fuwa Synthesis of Didemnaketal B Douglass F. Taber March 2, 2015

Didemnaketal B 3 may be an artifact of isolation, derived from didemnaketal C, in which one of the methyl esters is instead an ethylsulfonate. Nevertheless, it is B, not C, that is a potent inhibitor of HIV protease. Haruhiko Fuwa of Tohoku University has provided (Chem. Eur. J. 2014, 20, 1848) a detailed account of the synthesis of 3, including the necessary revision of the absolute configuration of seven of the stereogenic centers. A central feature of the modular synthesis of 3 was the cyclization of 1 to the thermodynamically most favorable diastereomer of the spiroketal 2.

Three components were combined for the synthesis of 3. The upper sidechain was prepared from commercial citronellal 4. Reduction followed by protection and ozonolysis delivered the aldehyde 5, that was carried on to the alkyne 6. Hydroiodination using the method previously reported by the authors (OHL May 30, 2011) gave 7, that was oxidized to 8 and then to the ester 9.

Lactone formation by ring-​closing metathesis is difficult because of the substantial preference for the extended conformation of the ester. As illustrated by the conversion of 10 to 11, this can be overcome by complexation with a Lewis acid. Conjugate addition followed by phosphorylation completed the preparation of the enol phosphate 12.

 19

Addition of the ketene silyl acetal 18 to the aldehyde derived from 2 proceeded to give the undesired diastereomer 19. This was overcome by oxidation to the ketone followed by enantioselective reduction. The iodide 9 was added to the aldehyde 20 to give a 1.8:1 mixture of diastereomers, the major one of which was didemnaketal B 3. This full paper is worth reading in detail. The work reported underlines the importance of powerful protocols for carbon–​carbon bond formation that maintain high diastereocontrol in stereochemically complex environments.

191  The Fuwa Synthesis of Didemnaketal B

The third component of 3 was the lactone 15, prepared by deprotonation/​kinetic protonation with 14 of 13. This was carried on to the sulfone 16, that was coupled with 17. Although the Julia–​Kocienski reaction usually strongly favors the E alkene, in this case it was necessary to optimize both the base and the solvent. Sharpless asymmetric dihydroxylation followed by coupling with the enol phosphate 12 then completed the preparation of the diol 1.

192

96. The Lee Synthesis of (−)-​Crinipellin A Douglass F. Taber April 6, 2015

The crinipellins are the only tetraquinane natural products. The enone crinipellins, including crinipellin A 3, have anticancer activity. Hee-​Yoon Lee of the Korea Advanced Institute of Science and Technology (KAIST) envisioned (J. Am. Chem. Soc. 2014, 136, 10274) the assembly of 2 and thus 3 by the intramolecular dipolar cycloaddition of the diazoalkane derived from the tosylhydrazone 1.

The initial cyclopentene was prepared from commercial 4 following the Williams procedure. Conjugate addition of the Grignard reagent 5 in the presence of TMS-​Cl led to the silyl enol ether 6. Regeneration of the enolate followed by allylation gave 7. The preparation of the racemic ketone was completed by ozonolysis followed by selective reduction and protection. Addition of hydride in an absolute sense led to separable 1:1 mixture of diastereomers. Reoxidation of one of the diastereomers delivered enantiomerically enriched 8. A few steps later, after coupling with 10, the sidechain stereocenter was set by Sharpless asymmetric epoxidation.

Oxidation of 11 gave the aldehyde, that was converted to the alkyne 12 by the Ohira protocol. Addition of the Grignard reagent 13 gave the allene 14 as an inconsequential 1:1 mixture of diastereomers. Deprotection then led to the tosylhydrazone 1.

 193

Direct α-​hydroxylation of the ketone derived from 2 gave the wrong diastereomer, and hydride addition to 18 reduced the wrong ketone. As an alternative, the enantiomerically-​pure sulfoximine anion was added to the more reactive ketone, and the product was reduced and protected to give 19. Allylic oxidation converted the alkene to the enone, and heating to reflux in toluene reversed the sulfoximine addition, leading to 20.

Epoxidation of 20 followed by α-​methylenation delivered the enone 21, that proved to be particularly sensitive. Eventually, success was found with TASF. With a similarly sensitive substrate, Douglass F. Taber of the University of Delaware observed (J. Am. Chem. Soc. 1998, 120, 13285) that TBAF in THF buffered with solid NH4Cl worked well.

193  The Lee Synthesis of (−)-Crinipellin A

The transformation of 1 to 2 proceeded by initial formation of the diazo alkane 15. Intramolecular dipolar cycloaddition gave 16, that lost N2 to give the trimethylene–​ methane diradical 17. The insertion into the distal alkene proceeded with remarkable stereocontrol, to give 2 as a single diastereomer—​in 87% yield from 1.

194

97. The Snyder Synthesis of Psylloborine A Douglass F. Taber May 4, 2015

In addition to the monomeric coccinellid alkaloids produced by the ladybug, some dimeric alkaloids, exemplified by psylloborine A 3, have been isolated. Scott A. Snyder of Scripps/​Florida initially attempted a direct dimerization strategy for the assembly of 3, but when that failed, he devised (J. Am. Chem. Soc. 2014, 136, 9743) a route to the tethered dimer 1, that could indeed be cyclized to 2, the immediate precursor to 3.

The starting material for both 9, the lower half of 1, and 13, the upper half of 1, was the commercial, enantiomerically-​pure piperidine 4. Metalation followed by allylation gave the desired trans diastereomer 5. Oxidative cleavage followed by condensation with 6 gave the ester 7, that was hydrogenated, then converted with 8 to the desired phosphonate 9.

To prepare 13, 4 was metalated and alkylated with methallyl bromide. The product 10 was carried on to the enone 12 by oxidative cleavage followed by the addition of 11, oxidative cleavage, and dehydration. Reduction to the desired diastereomer was achieved by conjugate addition of hydride in the presence of the sterically very demanding Yamamoto Lewis acid ATPH. Deprotection followed by oxidation then gave 13, that was condensed with 9 and deprotected to give 14. Selective deprotection followed by oxidation and condensation with 15 then led to 1.

 195

195  The Snyder Synthesis of Psylloborine A

A key element in the design of this synthesis was the ability to easily tune the sulfone activating group, to direct the proper order of bond formation. The vision was that regeneration of the enone and deprotection, with tetramethylguanidine, would lead to 16. The free amine would add to the saturated ketone to give an enamine, that would in turn add in a conjugate sense to the enone to give 17. Further deprotection of 17 under acid conditions would again generate an enamine that, it was hoped, would, after further cyclization, add to the unsaturated sulfone to give 2. As illustrated, the 3,5-​bis(trifluoromethyl)phenyl sulfone gave the best results. Desulfurization of 2 completed the synthesis of the complex dimeric alkaloid psylloborine A 3.

196

98. The Morken Synthesis of (+)-​Discodermolide Douglass F. Taber June 1, 2015

The anticancer properties of discodermolide 3 were exciting enough that Novartis undertook a commercial-​scale total synthesis. While initial clinical trials were not successful, it is still a very promising lead structure. James P. Morken of Boston College developed (Angew. Chem. Int. Ed. 2014, 53, 9632) a practical approach, based on the Still–​Gennari coupling of the phosphonate 1 with the aldehyde 2.

The preparation both of 1 and of 2 showed to advantage the diene borylations that have been developed by the Morken group over the past several years. The aldehyde 5 was prepared by enantioselective hydroformation of the protected acrolein 4. Borylation of pentadiene 6 followed by diastereoselective addition to 5 set, after oxidation, the three new stereogenic centers of 7. Ir-​catalyzed hydroboration led to the primary alcohol, that was carried through aldehyde deprotection and oxidation to the ester 8. Oxidation of the alcohol to the acid 9 followed by activation with 10 and coupling with the anion 11 then completed the synthesis of 1.

The preparation of the key Z-​trisubstituted alkene chiron 16 again began with enantioselective hydroformylation of the allyl silyl ether 12 to 13. The addition of 14

 197

Pt-​catalyzed enantioselective borylation of 6 followed by the addition of chloromethyl lithium led, after oxidation, to the diol 17. Exposure of the derived bis tosylate to potassium t-​butoxide led to facile elimination of the homoallylic tosylate. The remaining tosyl protecting group was then removed reductively to give 18. The Roush reductive aldol protocol using the enolate derived from 19 was applied to the derived aldehyde, leading to 20, that was carried on to 21. Under carefully defined conditions, the E-​enolate of 21 coupled efficiently with the allylic iodide 17 to give 2. Still–​Gennari coupling with 1 to give 22 followed by selective reduction, deprotection, and lactonization then completed the synthesis of (+)-​discodermolide 3.

197  The Morken Synthesis of (+)-Discodermolide

proceeded with high diastereoselectivity. Nickel-​catalyzed borylation of 15 was also highly diastereoselective, leading to an intermediate that was oxidized to the primary alcohol, then carried on the iodide 16.

198

99. The Trauner Synthesis of (−)-​Nitidasin Douglass F. Taber July 6, 2015

The sesterterpene (−)-​nitidasin 4 is a component of the Peruvian infusion “hercampuri,” prepared from the shrubs Gentianella nitida and Gentianella alborosea, that was used traditionally to treat hepatitis, diabetes, and hypertension. Dirk Trauner of Ludwig-​Maximilians-​Universität München envisioned (Angew. Chem. Int. Ed. 2014, 53, 8513) the assembly of 4 by the convergent coupling of 1 with 2 to give 3.

For this strategy to be effective, both 1 and 2 had to be prepared in enantiomerically-​enriched form. The skeleton of 1 was found in the enone 5, prepared by asymmetric Robinson annulation, that had already been carried on to the trans-​ fused ketone 6, and then to the enone 8 by way of 7. Following the authors earlier work (J. Org. Chem. 2012, 77, 5838), conjugate addition of 9 to the enone 8 gave 10. Hydrogenation of 10 had to be carried out with a Pt catalyst to avoid the undesired equilibration of the pendant group. Regioselectivity and diastereoselectivity in the hydroboration of the alkene 11 was optimized with the enantiomerically-​pure borane. Allylation of the derived ketone was best effected by way of the enol borinate. Reduction of 12 with K-​Selectride gave the cis alcohol, that was processed to the lactone. Kinetic alkylation then established the secondary methyl group.

 19

The preparation of 2 began with commercial, enantiomerically-​enriched citronellene 14. Oxidative cleavage of the more substituted alkene of 2 gave an aldehyde that was carried by the Corey–​Fuchs protocol to the volatile enyne 15. This was cyclized with the Negishi reagent to an intermediate zirconacycle, that was oxidized to the diiodide. Elimination gave a diene, that was hydroborated with good kinetic control to give the alcohol 16. Oxidation followed by methylenation then completed the preparation of 2. The addition of an excess of the alkenyl lithium derived from 2, a 4:1 mixture of enantiomers, to the ketone 1 proceeded with remarkable diastereoselectivity. The tetrasubstituted alkene of 17 intercepted the Grubbs intermediate, so epoxidation, that also proceeded with remarkable diastereoselectivity, was carried out before ring-​closing metathesis. The final steps were unusually delicate, but conditions were found for deprotection, hydrogenation, and oxidation to complete the synthesis of (−)-​nitidasin 4.

199  The Trauner Synthesis of (−)-Nitidasin

The lactone 13 was reduced to the diol, and protected as the bis TES ether. Selective oxidation of the primary TES ether generated the aldehyde, that could be methylenated without epimerization. Desilylation and oxidation then completed the synthesis of 1.

20

100. The Hoveyda Synthesis of Disorazole C1 Douglass F. Taber August 3, 2015

Disorazole C1 3, isolated from fermentation of the myxobacterium Sorangium cellulosum, shows antifungal and anticancer activity. Amir H. Hoveyda of Boston College applied (J. Am. Chem. Soc. 2014, 136, 16136) recent advances in alkene metathesis from his group to enable the efficient assembly of 2 and so of 3.

The ester 1 was assembled from the alcohol 11 and the acid 18. The preparation of 11 began with the enantioselective addition of 5 to 4 to give 6 and then 7, as described by Kalesse (Angew. Chem. Int. Ed. 2010, 49, 1619). Leighton allylation led to 8, that was then coupled with 9 to give 10 with high Z selectivity. Iodination of 10 followed by deprotection then completed the assembly of 11.

The starting material for the acid 18 was the allylic alcohol 13. As reported by Cramer (Angew. Chem. Int. Ed. 2008, 47, 6483), exposure of the racemic alcohol 12 to vinyl acetate in the presence of Amano lipase PS converted one enantiomer to the acetate, leaving 13. Methylation of the secondary alcohol followed by acid-​mediated removal of the t-​butyl ester led to the acid 14, that was converted to the corresponding acyl fluoride and coupled with serine Me ester 15 to give 16. After cyclization to the oxazole 17, cross metathesis with five equivalents of 4-​bromo-​1-​butene gave the homoallylic bromide, that was readily eliminated with DBU to give, after saponification, the acid 18.

 201

201  The Hoveyda Synthesis of Disorazole C 1

The cross metathesis of the coupled ester 1, a polyene, with 9 proceeded with remarkable selectivity to give 2, again as the Z geometric isomer. On exposure to the Heck catalyst Pd [(o-​tolyl)3P]2, 2 dimerized efficiently. The deprotection was not straightforward, but conditions (H2SiF6, CH3OH, 4°C, 72 h) were found that delivered 3 in 68% yield.

20

101. The Smith Synthesis of (−)-​Nodulisporic Acid D Douglass F. Taber September 7, 2015

The nodulisporic acids, isolated from the endophytic fungus Nodulisporium sp., show promising insecticidal activity. Amos B. Smith III of the University of Pennsylvania envisioned (J. Am. Chem. Soc. 2015, 137, 7095) the construction of the central indole of nodulisporic acid D 4 by the convergent coupling of the chloroaniline 1 with the enol triflate 2.

The preparation of 2 began (Org. Process Res. Dev. 2007, 11, 19) with the monoketal 5 of the Wieland–​Miescher ketone, available in enantiomerically-​pure form by organocatalyzed Robinson annulation. Condensation with thiophenol and formaldehyde gave 6, which, under dissolving metal conditions, was reduced to an enolate that was trapped as the silyl enol ether 7. Condensation again with formaldehyde gave 8, that was converted by reduction and protecting group exchange to the ketone 9. Pd-​catalyzed formylation of the derived enol triflate led to 10.

The Cu-​meditated conjugate addition of vinyl magnesium bromide to the unsaturated aldehyde 10 was carefully optimized to maximize equatorial addition, away from the angular methyl group. Subsequent C-​methylation of the aldehyde was achieved by generating the Li enolate and carrying out the alkylation in diglyme. With 11 in hand, the third carbocyclic ring was assembled by 1,2-​addition of vinylmagnesium bromide to the aldehyde followed by ring-​closing metathesis and

 203

The stereogenic center of 1 was established by Enders alkylation of 13 with the iodide 14. The ketone 15 was best liberated by ozonolysis under non-​epimerizing conditions. The critical Barluenga indole construction that formed 3 also required careful optimization in a model study, the key observation being the value of the Buchwald ligand RuPhos. The conditions developed were found, remarkably, to be compatible with the aldehyde functional group, so subsequent Horner–​Wadsworth–​ Emmons condensation with 16 could be carried out directly, to complete the synthesis of (−)-​nodulisporic acid D 4.

203  The Smith Synthesis of (−)-Nodulisporic Acid D

oxidation to give 12. Hydrogenation followed by functional group interconversion then completed the assembly of the enol triflate 2.

204

102. The Sato/​Chida Synthesis of Paclitaxel (Taxol®) Douglass F. Taber October 5, 2015

Paclitaxel (Taxol®) 3 is widely used in the clinical treatment of a variety of cancers. Takaaki Sato and Noritaka Chida of Keio University envisioned (Org. Lett. 2015, 17, 2570, 2574) establishing the central eight-​membered ring of 3 by the SmI2-​mediated cyclization of 1 to 2.

The starting point for the synthesis was the enantiomerically-​pure enone 5, prepared from the carbohydrate precursor 4. Conjugate addition to 5 proceeded anti to the benzyloxy substituent to give, after trapping with formaldehyde and protection, the ketone 6. Reduction and protection followed by hydroboration led to 7, that was, after protection and deprotection, oxidized to 8.

The second ring of 3 was added in the form of the alkenyl lithium derivative 9, prepared from the trisylhydrazone of the corresponding ketone. Hydroxyl-​directed epoxidation of 10 proceeded with high facial selectivity, leading, after reduction and protection, to the cyclic carbonate 11. Allylic oxidation converted the alkene into the enone, while at the same time oxidizing the benzyl protecting group to the benzoate, to give 12. Reduction of the ketone 12 led to a mixture of diastereomers. In practice, only one of the diastereomers of 1 cyclized cleanly to 2, as illustrated, so the undesired diastereomer from the NaBH4 reduction was oxidized back to the enone for recycling. For convenience, only one of the diastereomers of 2 was carried forward.

 205

It is a measure of the strength of the science of organic synthesis that Masahisa Nakada of Waseda University also reported (Chem. Eur. J. 2015, 21, 355) an elegant synthesis of 3 (not illustrated). These two approaches are well worth studying side by side for the complementary way they addressed the several challenges inherent in the structure of 3.

205  The Sato/Chida Synthesis of Paclitaxel (Taxol ®)

To establish the tetrasubstituted alkene of 3, the alkene of 2 was converted to the cis diol and on to the bis xanthate 13. Warming to 50°C led to the desired tetrasubstituted alkene, sparing the oxygenation that is eventually required for 3. For convenience, to intercept 16, the intermediate in the Takahashi total synthesis, both xanthates were eliminated to give 14. Hydrogenation removed the disubstituted alkene, and also deprotected the benzyl ether. Oxidation followed by Peterson alkene formation led to 15, that was carried on to the Takahashi intermediate 16 using the now-​standard protocol for oxetane construction.

206

103. The Johnson Synthesis of Paspaline Douglass F. Taber November 2, 2015

Paspaline 3, isolated from the ergot fungus Claviceps paspali, is a Maxi-​K channel antagonist, and so a potential lead for the treatment of Alzheimer’s disease. The selective C–​H functionalization that converted 1 to 2 was a key step in the synthesis of 3 reported (J. Am. Chem. Soc. 2015, 137, 4968; J. Org. Chem. 2015, 80, 9740) by Jeffrey S. Johnson of the University of North Carolina.

The prochiral diketone 4 was the starting point for the assembly of 1. Selective reduction with a commercial strain of yeast set both the relative and the absolute configuration of 5. The ketone interfered with the subsequent acid-​catalyzed cyclization of the epoxy alcohol, so it was protected as the tosylhydrazone 6. This set the stage for the direct Bamford–​Stevens conversion to the fully-​substituted alkene 7.

Ireland–​Claisen rearrangement of the isobutyrate derived from 7 proceeded with substantial preference for the equatorial diastereomer 8. This was carried on to the methyl ketone 9. Hydroboration of 9 showed substantial axial preference, to deliver, after oxidation, the equatorial aldehyde 10. Intramolecular aldol condensation to 11 followed by hydrogenation and benzyl oxime formation then completed the preparation of 1.

 207

At this point, the authors followed Smith (J. Am. Chem. Soc. 1985, 107, 1769) in using the Gassman protocol (J. Am. Chem. Soc. 1974, 96, 5495) to construct the indole. Amination of the sulfur of 15 with N-​chloroaniline gave the sulfonium salt, that on exposure to Et3N rearranged to 16. Reductive desulfurization followed by cyclization completed the synthesis of paspaline 3.

207  The Johnson Synthesis of Paspaline

Intramolecular Pd-​catalyzed acetoxylation has been extensively studied by Sanford (Org. Lett. 2010, 12, 532). The Sanford conditions, carried out on a gram scale, converted 1 into the equatorial diastereomer 2 with remarkable diastereoselectivity. The final carbocyclic ring was then added by vinyl Grignard addition to the derived keto aldehyde 12. Grubbs cyclization gave 13, that on exposure to acid rearranged to the enone 14. Reduction of the ketone occurred from the open face to give an alcohol that then directed hydrogenation from the opposite face, leading to the desired trans-​fused ketone. Sulfenylation then completed the synthesis of the ketone 15.

208

104. The Ding Synthesis of Steenkrotin A Douglass F. Taber December 7, 2015

Steenkrotin A 3 was isolated from Croton steenkampianus Gerstner, widely used in folk medicine for the treatment of coughs, fever, malaria, and rheumatism. Hanfeng Ding of Zhejiang University envisioned (Angew. Chem. Int. Ed. 2015, 54, 6905) that the intriguingly compact core of 3 could be assembled by reductive cyclization of the aldehyde 1 to 2, followed by intramolecular aldol condensation.

The diastereoselective assembly of 1 from the cycloheptenone core 4 depended on the conformational preferences of the seven-​membered ring. Enol ether formation followed by Rubottom oxidation led to the silyl ether 5. Oxidative rearrangement of the tertiary alcohol generated by 1,2-​addition to 5 of in situ generated allyl lithium established the enone 6. Again taking advantage of the conformational preference of the seven-​membered ring, cyclopropanation of the silyl enol ether derived from 6 proceeded across the open face of the electron-​rich alkene to give 7.

The other oxygenated quaternary center of 1 was constructed by O-​alkylation of 7 with diazo malonate followed by methylation and reduction. Acetylation of the diol 8 proceeded with 10:1 diastereoselectivity, to give, after oxidation, the aldehyde 9. In the first of a sequence of three intramolecular bond-​forming reactions, HF.py cyclized the aldehyde onto the endocyclic alkene, and also freed the alcohol, that was alkylated with the dibromide 10 to give 11 as a 1.5:1 mixture of diastereomers. On

 209

With 1 in hand, the stage was set for the second intramolecular cyclization. Even though 1 was predominantly in the lactol form, there was enough of an equilibrium concentration of aldehyde present for the SmI2-​mediated cyclization to proceed smoothly to 2. With 2 in hand, in addition to the last intramolecular cyclization, the two stereogenic centers (marked by an asterisk) had to be inverted. The methyl group adjacent to the ketone was readily equilibrated. The secondary alcohol could be inverted by late-​stage oxidation and reduction, and the authors did do that. However, they also observed a small amount of the desired epimeric alcohol 14 from the intramolecular aldol condensation of 12. Reasoning that the epimerization arose from the intermediacy of the aldehyde 13, the authors carefully optimized conditions to maximize the formation of 14. LiOH-​mediated elimination then completed the synthesis of steenkrotin A 3.

For convenience, this synthesis was carried out beginning with racemic 4, but the individual enantiomers of 4 are readily available (Tetrahedron Lett. 1999, 40, 4199).

209  The Ding Synthesis of Steenkrotin A

exposure to SmI2, the major diastereomer cyclized to give a intermediate that was carried on to 1. The minor diastereomer was merely reduced, to a product that could be recycled to 11.

210

 21

Author Index

Abad-​Somovilla, Antonio, 5: 154 Abe, Manabu, 5: 88 Abell, Andrew D., 4: 60, 5: 62 Ackermann, Lutz, 2: 82, 5: 125, 6: 118, 124 Adachi, Masaatsu, 5: 146 Adjiman, Claire S., 3: 48 Adolfsson, Hans, 6: 25 Adronov, Alex, 6: 14 Aggarwal, Varinder, 1: 82, 2: 136, 4: 82, 85, 104, 158, 5: 60, 141, 6: 69, 84–​85 Agustin, Dominique, 5: 56 Aitken, David J., 4: 160 Akai, Shuji, 4: 73, 126, 6: 21 Akamanchi, Krishnacharya G., 2: 190, 3: 7, 5: 54 Akhrem, Irena S., 3: 26, 4: 34, 5: 39 Akiyama, Takahiko, 5: 33 Alabugin, Igor V., 4: 124 Alajarín, Mateo, 2: 159 Alam, Mahbub, 5: 48 Albericio, Fernando, 3: 20, 5: 23, 6: 25 Albiniak, Philip A., 6: 24 Alcaide, Benito, 6: 102 Alcázar, Jesús, 5: 26 Alemán, José, 4: 77, 139 Alexakis, Alexandre, 1: 179, 204, 2: 5, 6, 73, 3: 73, 144, 146, 148, 4: 71, 79, 81, 85, 141, 143, 147, 5: 51, 79, 83, 6: 68, 73, 142, 144 Alexanian, Erik J., 4: 4, 5: 57 Alfonso, Carlos A. M., 1: 88 Alibés, Ramon, 3: 158 Alinezhad, Heshmatollah, 4: 12 Alonso, Diego A., 4: 77 Alonso-​Moreno, Carlos, 3: 16 Alper, Howard, 2: 178 Altmann, Karl-​Heinz, 3: 59

Alvarez-​Manzaneda, Enrique, 3: 127, 5: 123 Alves, Maria J., 6: 107 Amat, Mercedes, 1: 192 An, Duk Keun, 3: 8, 5: 44 An, Gwangil, 3: 3 Anabha, E. R., 3: 129 Anbarasan, Pazhamalai, 6: 119, 130 Anderson, Edward A., 5: 90, 6: 129 Anderson, James C., 2: 62, 3: 15 Anderson, Laura L., 4: 128, 5: 14, 6: 2, 119 Andersson, Pher G., 4: 74, 105, 149, 5: 162 Ando, Kaori, 4: 93 Andrade, Rodrigo B., 3: 46, 6: 111 Andrus, Merritt B., 2: 4 Annese, Cosimo, 5: 35 Antilla, Jon C., 3: 62, 6: 64, 80 Antonchick, Andrey P., 5: 124 Aouadi, Kaïss, 5: 84 Aoyama, Toyohiko, 3: 37 Apeloig, Yitzhak, 6: 80 Aponick, Aaron, 3: 88, 4: 126 Arai, Takayoshi, 3: 80 Arcadi, Antonio, 1: 49 Ardisson, Janick, 3: 166 Aribi-​Zouioueche, Louisa, 1: 34 Arimoto, Hirakazu, 1: 140, 4: 18, 6: 12 Ariza, Xavier, 5: 150 Armstrong, Alan, 6: 63 Arndt, Hans-​Dieter, 2: 187 Arndtsen, Bruce A., 3: 134, 4: 130 Aron, Zachary D., 4: 70 Arora, Paramjit, 2: 151, 3: 129 Arrayás, Ramón Gómez, 5: 66 Arseniyadis, Stellios, 3: 45 Asao, Naoki, 3: 22 Ashfeld, Brandon L., 4: 42, 5: 7 Asokan, C. V., 3: 129 Astashko, Dmitry A., 5: 57

Author Index  212

21

Aubé, Jeffrey, 1: 112, 139, 2: 37, 4: 111, 5: 107 Aubert, Corinne, 4: 130 Aucagne, Vincent, 3: 90 Audran, Gérard, 4: 160 Augé, Jacques, 3: 90 Augustine, John Kallikat, 5: 23 Aurrecoechea, José M., 3: 130 Avenoza, Alberto, 4: 57 Ávila-​Zárraga, José G., 4: 156 Ayad, Tahar, 6: 47 Azarifar, Davood, 6: 52 Baba, Akio, 1: 26, 3: 35, 5: 46, 6: 44 Baba, Toshihide, 4: 53 Babu, Srinivasarao Arulananda, 6: 35 Bach, Thorsten, 4: 36, 5: 160, 6: 134, 138, 158 Back, Thomas G., 4: 71 Bäckvall, Jan-​E., 2: 8, 3: 108 Badía, Dolores, 2: 122 Bagley, Mark C., 4: 90 Bahrami, Kiumars, 4: 17 Bailey, William F., 4: 17 Balci, Metin, 6: 132 Baldwin, Jack E., 2: 169 Ball, Zachary T., 6: 144 Ballini, Roberto, 5: 129 Balova, Irina A., 6: 26 Bandini, Marco, 5: 140 Bandyopadhyay, Debkumar, 2: 179 Bangdar, B. P., 3: 3 Banik, Bimal K., 4: 7 Bannwarth, Willi, 5: 18, 6: 23 Banwell, Martin G., 1: 170, 3: 155, 4: 101, 5: 158, 6: 101, 157, 180 Bao, Ming, 4: 145 Bao, Yong-​Sheng, 6: 6 Baran, Phil S., 2: 63, 3: 26, 29, 4: 32, 36, 130, 178, 5: 14, 36, 49, 149, 155, 6: 55, 57, 119, 174 Barbas, Carlos F. III, 1: 152, 2: 7, 121, 3: 63, 80, 82, 4: 84, 5: 15 Barbe, Guillaume, 5: 113 Barker, David, 5: 83 Barluenga, José, 2: 75, 3: 154, 4: 18, 5: 12, 147 Baroni, Adriano C. M., 4: 51 Barrero, Alejandro F., 4: 4

Barrett, Anthony G. M., 2: 156, 3: 125, 6: 123 Barriault, Louis, 5: 155, 6: 155 Barros, Maria Teresa, 6: 136 Barua, Nabin C., 3: 15 Baskaran, Sundarababu, 1: 8, 4: 4 Baslé, Olivier, 6: 148 Bassani, Dario M., 4: 24 Basset, Jean-​Marie, 4: 64 Basu, Amit, 1: 40 Bates, Roderick W., 3: 159, 4: 103 Batey, Robert A., 4: 70, 6: 158 Baudoin, Olivier, 5: 38, 39 Bauer, Eike B., 6: 11 Baumann, Marcus, 4: 19 Bavetsias, V., 1: 100 Bayón, Pau, 4: 111 Bazzi, Hassan S., 4: 56 Beau, Jean-​Marie, 4: 28 Beauchemin, André M., 4: 127, 5: 60, 6: 103 Beaudry, Christopher M., 6: 125 Bechara, William S., 3: 75 Becht, Jean-​Michel, 2: 185 Becker, Daniel P., 4: 54 Becker, James Y., 5: 44 Bedford, Robin B., 3: 124, 4: 124 Behr, Arno, 4: 53 Beier, Petr, 4: 124 Béland, François, 5: 59 Bélanger, Guillaume, 3: 107 Belder, Detlev, 6: 28 Bella, Marco, 5: 104, 137 Beller, Matthias, 3: 42, 126, 4: 3, 8, 16, 28, 5: 4, 16, 17, 135, 6: 16, 17, 19, 38, 56, 129, 147 Benaglia, Maurizio, 6: 29, 136 Bennasar, M.-​Lluïsa, 3: 117, 4: 117 Bera, Jitendra K., 6: 4, 56 Bergbreiter, David E., 4: 56 Berglund, Per, 6: 58 Bergman, Jan, 5: 45 Bergman, Robert G., 1: 122, 2: 41, 126, 178, 3: 19, 37, 133, 180, 4: 18, 130, 5: 2, 107 Bergmeier, Stephen C., 2: 192, 3: 160 Berkessel, Albrecht, 6: 60 Bernardi, Luca, 2: 58, 4: 69, 84 Bernini, Roberta, 1: 20

 213

Booker-​Milburn, Kevin I., 6: 32 Boons, Geert-​Jan, 4: 26 Bora, Utpal, 6: 14 Borhan, Babak, 2: 196, 3: 99, 5: 78 Bornscheuer, Uwe T., 2: 48 Bosch, Joan, 1: 192 Boto, Alicia, 4: 2 Boukouvalas, John, 2: 189, 6: 127 Bouzbouz, Samir, 4: 58, 61 Bowden, Ned B., 2: 151, 4: 57 Bower, John F., 6: 57, 148 Boyd, Derek R., 3: 148, 6: 140Boyer, Alistair, 6: 86 Braddock, D. Christopher, 6: 64 Bradshaw, Ben, 4: 190, 6: 139 Bräse, Stefan, 5: 123, 6: 23, 26, 142 Braun, Manifred, 1: 178 Brawn, Ryan A., 6: 102 Bray, Christopher D., 4: 156, 158, 6: 106 Breinbauer, Rolf, 4: 23 Breit, Bernhard, 1: 148, 2: 86, 3: 41, 80, 108, 159, 4: 50, 85, 5: 32, 59, 66, 6: 17, 78 Brenner-​Moyer, Stacey E., 5: 91 Breuning, Matthias, 6: 62 Brewer, Matthias, 3: 33, 6: 49 Brimble, Margaret A., 6: 148 Britton, Robert, 4: 92, 114, 6: 29, 76, 126 Brookhart, Maurice, 3: 25, 39, 4: 13, 5: 16, 6: 17 Broom, Toby, 6: 33 Brovetto, Margarita, 3: 90 Brown, M. Kevin, 6: 140 Brown, Richard C. D., 6: 88, 111 Browne, Duncan L., 5: 29 Brückner, Reinhard, 3: 64, 6: 8 Bruijnincx, Pieter C. A., 6: 52 Bryliakov, Konstantin P., 5: 38 Buchwald, Stephen L., 1: 164, 2: 187, 3: 32, 128, 129, 4: 31, 118, 122, 123, 5: 26, 27, 28, 30, 31, 95, 124, 6: 72 Buckley, Benjamin R., 6: 18 Buehler, Katja, 6: 33 Bujons, Jordi, 6: 80 Bull, James A., 6: 41, 86, 88, 102 Buono, Frederic G., 3: 125, 6: 33 Burés, Jordi, 4: 29 Burgess, Kevin, 4: 85 Burgos, Alain, 3: 60

213  Author Index

Berteina-​R aboin, Sabine, 4: 24 Bertozzi, Carolyn R., 3: 20 Bertrand, Guy, 6: 122 Bertrand, Michèle P., 3: 63 Bertus, Philippe, 6: 148 Betley, Theodore A., 5: 32, 6: 34, 54 Bettinger, Holger F., 3: 26 Betzer, Jean-​François, 3: 166 Bhanage, Balchandra M., 3: 12, 122 Bharate, Sandip P., 5: 124 Bhat, Ramakrishna G., 5: 108 Bhattacharyya, Ramgopal, 3: 42 Bi, Xihe, 4: 132, 6: 3, 126 Bieber, Lothar, 2: 55 Bielawski, Christopher W., 5: 52 Bielawski, Christopher W., 6: 6 Biffis, Andrea, 3: 18 Bihelovic, Filip, 5: 147 Bihlmeier, Angela, 5: 155 Biju, Akkattu T., 6: 138, 140 Bilodeau, François, 4: 128 Birman, Vladimir B., 4: 20 Bischoff, Laurent, 2: 159 Biscoe, Mark R., 4: 124, 5: 7 Bjørsvik, Hans-​René, 5: 26 Blagg, Brian S. J., 3: 33 Blakey, Simon, 3: 68 Blanc, Aurélien, 5: 22 Blanchet, Jérôme, 3: 82 Blay, Gonzalo, 3: 68 Blazejewski, Jean-​Claude, 2: 55 Blechert, Siegfried, 1: 134, 2: 109, 111, 152, 153, 205, 3: 51, 4: 62 Blond, Gadlle, 5: 144 Bobbitt, James M., 4: 17 Bochet, Christian, 3: 17, 5: 4 Bode, Jeffrey W., 1: 114, 2: 166, 3: 85, 142, 4: 89, 5: 5, 120 Bodnar, Brian S., 4: 12 Bodwell, Graham J., 5: 121, 156 Boeckman, Robert K., Jr., 4: 76 Boger, Dale L., 2: 45, 4: 132, 188, 200, 5: 58, 61, 128 Bolm, Carsten, 3: 5, 33, 76, 4: 133 Bommarius, Andreas S., 4: 80 Boncella, James M., 5: 19 Bonjoch, Josep, 4: 190, 5: 118, 6: 139 Bonne, Damien, 3: 141, 5: 85, 6: 136 Booker-​Milburn, Kevin I., 4: 23, 5: 4, 31

Author Index  214

214

Burke, Martin D., 4: 45, 119, 5: 22 Burke, Steven D., 2: 56, 3: 172 Burkett, Brendan A., 4: 22 Burkhardt, Elizabeth R., 3: 14 Burrell, Adam J. M., 3: 160 Burtoloso, Antonio C. B., 6: 82 Burton, Jonathan W., 3: 146, 152, 4: 156, 6: 81 Busto, Jesús H., 4: 57 Buszek, Keith R., 3: 38 Cabal, Maria-​Paz, 6: 104 Cabral, Shawn, 3: 9 Cacchi, Sandro, 3: 132, 4: 90 Caddick, Stephen, 4: 43, 5: 32 Caffyn, Andrew J. M., 3: 124 Cahiez, Gérard, 3: 31, 4: 43, 45, 5: 126 Cai, Qian, 6: 72 Cammidge, Andrew M., 1: 174 Campagne, Jean-​Marc, 3: 49, 4: 12, 6: 5 Campos, Kevin R., 2: 91, 4: 160 Canesi, Sylvain, 4: 159 Canney, Daniel J., 4: 90 Cantat, Thibault, 5: 20, 6: 14 Cao, Xiao-​Ping, 4: 140, 5: 146 Carbery, David R., 4: 12, 5: 15, 85 Carboni, Bertrand, 5: 134 Cárdenas, Diego J., 2: 125 Cardierno, Victoria, 2: 145 Carreira, Erick, 1: 98, 150, 2: 6, 17, 53, 118, 161, 181, 3: 9, 42, 4: 50, 68, 160, 5: 71, 107, 146, 149, 151, 180, 184, 192, 204, 6: 50, 74, 81, 135, 143, 147, 187 Carrera, Ignacio, 6: 141 Carretero, Juan C., 2: 92, 195, 3: 70, 72, 4: 83, 5: 66, 6: 35 Carter, Rich G., 3: 121, 142, 194, 4: 17, 6: 177 Casar, Zdenko, 5: 69 Casey, Charles P., 3: 2 Casiraghi, Giovanni, 1: 152, 5: 82 Castarlenas, Ricardo, 2: 110 Castillón Sergio, 2: 94, 3: 148 Castle, Steven L., 3: 204, 4: 5, 6: 167 Catellani, Marta, 3: 26 Çetinkaya, Bekir, 2: 22 Cha, Jin Kun, 4: 55, 142, 5: 50, 94, 6: 42, 114 Chae, Junghyun, 4: 26

Chai, Yonghai, 6: 27 Chain, William J., 5: 96 Chakraborti, Asit K., 4: 22 Chakraborty, Debashis, 4: 19 Chakraborty, Tushar Kanti, 2: 128, 3: 86, 108, 4: 146, 148 Challis, Gregory L., 5: 41 Chan, Albert S. C., 1: 65, 4: 67, 71 Chan, Johann, 3: 7 Chan, Philip Wau Hong, 5: 11 Chandra Roy, Subhas, 2: 93, 6: 86 Chandrasekaran, Srinivasan, 4: 3 Chandrasekhar, Srivari, 1: 86, 3: 64, 5: 26 Chang, Ching-​Yao, 3: 135 Chang, Ho Oh, 3: 150 Chang, Junbiao, 3: 131 Chang, Maosheng, 3: 22 Chang, Sukbok, 2: 43, 190, 3: 122, 133, 5: 120, 122, 6: 36, 38, 40 Charette, André B., 1: 192, 2: 58, 69, 3: 12, 34, 59, 72, 75, 150, 4: 18, 45, 5: 48, 51, 104, 6: 31 Chass, Gregory A., 4: 41 Chataigner, Isabelle, 4: 161, 5: 163 Chatani, Naoto, 3: 126, 4: 13, 5: 35, 6: 120 Chattopadhyay, Shital K., 5: 109 Chauvin, Remi, 2: 110 Chavan, Subhash P., 5: 22, 6: 65 Che, Chao, 4: 60 Che, Chi-​Ming, 1: 175, 2: 146, 3: 102, 104, 4: 54, 5: 11, 20, 56, 84, 87, 6: 41, 104 Chemler, Sherry R., 3: 106, 4: 106, 5: 106 Chen, Cheng-​Yi, 3: 131 Chen, Chien-​Tien, 2: 47, 127 Chen, Chuo, 4: 184, 185, 5: 145, 6: 146 Chen, David Y.-​K ., 5: 153 Chen, Fener, 6: 62 Chen, Gong, 4: 35, 36, 5: 33, 36, 107, 6: 35, 37, 76 Chen, Jia-​Hua, 5: 172 Chen, Jia-​Rong, 4: 140, 6: 88 Chen, Jian, 6: 13 Chen, Jihua, 1: 201, 2: 186 Chen, Kwunmin, 4: 74 Chen, Wanzhi, 4: 118 Chen, Ying-​Chun, 3: 107, 143, 4: 103, 135, 139, 141, 5: 104, 139, 141, 6: 72, 77 Chen, Yonggang, 6: 106 Chen, Zhi-​Yuan, 6: 120

 215

Colvin, Ernest W., 5: 47 Comins, Daniel, 5: 21 Compain, Philippe, 3: 14, 6: 142 Concellón, José M., 3: 31 Connell, Brian T., 4: 42 Connon, Stephen J., 5: 94, 6: 26 Constantieux, Thierry, 6:126Cook, James M., 4: 6 Cook, Matthew J., 5: 3 Cook, Silas P., 4: 149, 5: 103, 187, 6: 6, 121, 122 Coquerel, Yoann, 5: 81, 140 Cordes, David B., 4: 50 Córdova, Armando, 1: 118, 151, 2: 8, 68, 121, 3: 64, 78, 79, 82, 83, 84, 102, 136, 138, 143, 5: 82, 142, 6: 144 Corey, E. J., 1: 168, 196, 197, 2: 71, 100, 180, 208, 3: 136, 137, 139, 4: 157, 168, 5: 145, 163 Corma, Avelino, 4: 2 Correia, Carlos Roque Duarte, 4: 51 Cossy, Janine, 1: 109, 2: 10, 3: 31, 45, 4: 46, 58, 61, 62, 5: 8, 46, 148 Costa, Anna M., 5: 3 Costas, Miquel, 4: 48, 6: 34, 76 Coster, Mark J., 6: 154 Couturier, Michel, 4: 6 Cox, Liam R., 3: 23, 98 Cozzi, Pier Giorgio, 5: 74 Craig, Donald, 3: 110 Cramer, Nicolai, 4: 78, 5: 61, 6: 102, 200 Crich, David, 2: 33, 179, 191, 3: 17, 4: 10 Crimmins, Michael, 1: 134, 2: 30, 95, 115, 6: 79 Cronin, Leroy, 6: 28 Crooks, Peter A., 3: 12 Crudden, Cathleen M., 4: 52, 74 Csáky, Aurelio G., 5: 92 Csuk, René, 2: 144 Cuerva, Juan M., 2: 125, 174, 6: 143 Cuevas-​Yañez, Erick, 5: 21 Cui, Dong-​Mei, 4: 38 Cumpstey, Ian, 3: 88 Cunico, Robert, 1: 126 Curci, Ruggero, 1: 176, 3: 24, 28, 29 Curran, Dennis P., 1: 183, 2: 50, 3: 44, 4: 18, 5: 16 Cushman, Mark, 4: 4 Czekelius, Constantin, 5: 108

215  Author Index

Chen, Zili, 4: 94 Cheng, Jiang, 5: 122, 6: 24, 40 Cheng, Jin-​Pei, 3: 136 Cheng, Maosheng, 6: 27 Cheng, Xiaomin, 5: 51 Cheon, Cheol-​Hong, 6: 118, 122 Cheong, Paul Ha-​Yeon, 6: 140 Chetcuti, Michael J., 6: 46 Chi, Dae Yoon, 4: 2 Chiba, Kazuhiro, 5: 27 Chiba, Shunsuke, 3: 130, 4: 127, 132, 5: 128, 6: 34 Chida, Noritaka, 4: 89, 5: 111, 6: 204 Chien, Tun-​Cheng, 6: 13 Chiou, Wen-​Hua, 4: 109 Chirik, Paul J., 5: 58, 6: 14, 40 Chiu, Pauline, 3: 161 Chmielewski, Marcin K., 5: 21 Cho, Cheon-​Gyu, 6: 131, 150, 154 Cho, Eun Jin, 5: 60 Cho, Seung Hwan, 5: 120 Chong, J. Michael, 2: 140, 3: 72 Christie, Steven D. R., 4: 91 Christmann, Mathias, 3: 155, 4: 135, 5: 142 Chung, Keun, 6: 123 Cid, M. Belén, 6:134Ciufolini, Marco A., 1: 48, 3: 160 Clapés, Pere, 2: 165, 6: 80 Clark, J. Stephen, 2: 201, 3: 88, 5: 132 Clark, James H., 3: 17 Clarke, Matthew L., 5: 76, 6: 50 Clarke, Paul A., 5: 95 Clavier, Hervé, 3: 48, 50 Clayden, Jonathan, 2: 37, 3: 63, 133, 159, 5: 65, 6: 58 Clive, Derrick L. J., 1: 74, 3: 57, 4: 107 Coates, Geoffrey W., 2: 59, 3: 32, 6: 76 Cobb, Alexander J. A., 4: 134 Cobley, Christopher J., 5: 76 Codée, Jeroen D. C., 5: 24, 6: 90 Cohen, Theodore, 5: 112 Colby, David A., 4: 27, 5: 25 Coldham, Iain, 3: 161, 4: 104, 108, 5: 109 Cole, Kevin P., 3: 154 Cole, Thomas E., 4: 121 Cole-​Hamilton, David J., 1: 148, 6: 28 Coleman, Robert S., 2: 62 Collins, Shawn K., 4: 64, 6: 32 Coltart, Don M., 2: 147, 3: 31, 4: 43, 5: 72

Author Index  216

216

Da, Chao-​Shan, 4: 68 Dabdoub, Miguel J., 4: 51 Dai, Liyan, 4: 70 Dai, Mingji, 6: 87, 113 Dai, Wei-​Min, 3: 53 Dairi, Tohru, 5: 33 Dake, Gregory R., 2: 206, 3: 114 Daly, John W., 3: 113 Danheiser, Rick L., 2: 40, 4: 125, 160 Danishefsky, Samuel, 1: 73, 197, 2: 156, 4: 9, 5: 156, 6: 88, 150 Darcel, Christophe, 3: 16, 6: 10 Darses, Sylvain, 4: 49 Das, Biswanath, 3: 4, 4: 94 Das, Parthasarathi, 4: 7 Dauban, Philippe, 2: 179, 3: 67, 6: 39 Daugulis, Olafs, 3: 121, 4: 130, 5: 37, 6: 119 David, Michèle, 3: 43 Davies, Huw M. L., 1: 169, 2: 61, 105, 3: 28, 103, 208, 5: 135, 144, 148, 150, 6: 37, 40, 72, 127, 142 Davies, Stephen G., 4: 76, 5: 79, 6: 77 Davis, Benjamin G., 3: 50 Davis, Franklin A., 1: 188 Davis, Lindsey O., 6: 46 De Mesmaeker, Alain, 6: 160 de Souza, Rodrigo O. M. A., 6:32De Vos, Dirk E., 6: 15 de Vries, Johannes G., 3: 74, 4: 16 DeBoef, Brenton, 5: 120 Deiters, Alexander, 2: 83, 3: 23, 5: 128 del Pozo, Carlos, 6: 109 Delpech, Bernard, 4: 130 Dembinski, Roman, 3: 132 deMello, Andrew J., 6: 28 Demir, Ayhan S., 4: 130 Deng, Guo-​Jun, 5: 123 Deng, Li, 1: 153, 2: 4, 23, 101, 139, 164, 3: 62, 63, 71, 154, 4: 75, 155, 5: 66, 74, 81, 137 Deng, Xiaohu, 3: 130 Deng, Youquan, 1: 45 Denmark, Scott E., 1: 22, 154, 2: 117, 5: 69, 6: 90, 104 Denton, Ross, 5: 5, 6: 4, 6 Désaubry, Laurent, 3: 124 Deska, Jan, 5: 47, 6: 84 Deslongchamps, Pierre, 3: 155, 6: 178, 179

Desvergnes, Valérie, 6: 48 Deutsch, Jens, 6: 3 Dhavale, Dilip P., 6: 105 Diaz, Yolanda, 2: 94 Díaz-​de-​Villegas, María D., 6: 81 Dieter, R. Karl, 3: 85 DiMagno, Stephen G., 6: 124 Ding, Chang-​Hua, 6: 108 Ding, Hanfeng, 6: 94, 147, 159, 208 Diver, Steven T., 3: 45 Dixneuf, Pierre, 1: 182, 2: 110 Dixon, Darren J., 3: 21, 4: 142, 170, 5: 109, 196, 207, 6: 104 Doctorovich, Fabio, 3: 41 Dodd, Robert H., 2: 179, 3: 67, 4: 51 Doi, Takayuki, 2: 66, 6: 65 Doll, Kenneth M., 6: 7 Dolman, Sarah J., 4: 30 Dominguez, Celia, 6: 148 Dong, Dewen, 6: 2 Dong, Guangbin, 5: 52, 125, 6: 37, 55, 118, 125 Dong, Vy M., 5: 61 Donohoe, Timothy J., 4: 132, 5: 106 Donsbach, Kai, 2: 152 Dore, Timothy M., 2: 88 Dorta, Reto, 4: 60, 64 Doucet, Henri, 6: 12 Dougherty, Dennis A., 4: 18 Doye, Sven, 4: 48 Doyle, Abigail G., 6: 36, 103 Doyle, Michael P., 1: 177, 2: 127, 192, 3: 26, 6: 64 Dreher, Spencer D., 5: 71 Driver, Tom G., 3: 133, 5: 36 Du, Haifeng, 6: 58 Du, Yunfei, 5: 133 Du, Zhenming, 6: 106 Du Bois, Justin, 1: 8, 137, 153, 2: 118, 210, 3: 25, 28, 29, 4: 36, 108, 5: 34, 37, 6: 38, 56, 93 Duan, Wei-​Liang, 6: 120 Duan, Wenhu, 3: 20, 4: 74, 6: 135 Dudley, Gregory B., 2: 47, 87, 91, 3: 33, 4: 45, 6: 43 Dujardin, Gilles, 3: 43, 4: 135, 6: 63 Durek, Thomas, 5: 3 Dussault, Patrick H., 3: 41, 5: 56, 59 D’yakonov, Vladimir A., 4: 146, 6: 44

 217

Faber, Kurt, 1: 158, 6: 70 Fabis, Frederic, 5: 120, 6: 120 Fabris, Fabrizio, 5: 34 Fabrizi, Giancarlo, 3: 132 Fagnoni, Maurizio, 2: 181, 3: 25, 4: 32, 43, 5: 32, 6: 35, 40 Fagnou, Keith, 2: 25, 41, 156 Fairlamb, Ian J. S., 2: 104 Fairweather, Neil T., 6: 19 Faísca Phillips, Ana Maria, 6: 136 Falck, J. R., 2: 129, 3: 66, 68, 99, 4: 52, 78 Falvey, Daniel E., 4: 21 Fan, Chun-​An, 5: 104, 113 Fan, Renhua, 3: 25 Fan, Xiaohui, 6: 18 Fañanás, Francisco, 3: 100, 5: 100 Fandrick, Daniel R., 4: 71 Fandrick, Keith R., 5: 66 Fang, Jim-​Min, 1: 17 Fang, Shiyue, 4: 23 Farina, Vittorio, 2: 152 Farras, Jaume, 5: 150 Faucher, Anne-​Marie, 1: 132, 161 Favi, Gianfranco, 4: 132 Favre-​Réguillon, Alain, 6: 28 Feng, Chen-​Guo, 6: 148

Feng, Xiaoming, 2: 93, 3: 68, 4: 141, 5: 64, 94, 142, 6: 62, 64, 69, 88, 146, 148 Feng, Xiujuan, 4: 145 Feng, Yi-​Si, 5: 52, 6: 7 Fensterbank, Louis, 4: 46, 120, 5: 94, 6: 14 Feringa, Ben L., 1: 151, 164, 192, 204, 2: 6, 60, 100, 162, 3: 50, 71, 74, 77, 152, 4: 68, 80, 103, 146, 5: 77, 6: 66 Ferjancic, Zorona, 6: 76 Fernandes, Ana C., 4: 52 Fernandes, Rodney A., 6: 54 Fernández, Elena, 6: 60 Fernández, Roberto, 3: 96 Fernández-​Ibáñez, M. Angeles, 6: 35 Fernández-​Mateos, A., 4: 38, 6: 143 Ferraz, Helena M. C., 1: 202, 2: 198 Ferraz, Helena M. C., 6: 54 Ferreira, Eric M., 5: 128, 150, 6: 84 Ferroud, Clotilde, 3: 21 Fiaud, Jean-​Claude, 1: 34 Figueredo, Marta, 4: 111 Filippov, Dmitri V., 6: 90 Fillion, Eric, 3: 92 Fini, Francesco, 4: 84 Finn, M. G., 1: 145 Firouzabadi, Habib, 1: 106, 156, 3: 15 Fleet, George W. J., 3: 20, 6: 104 Fleming, Fraser F., 4: 86 Fletcher, Stephen P., 5: 80, 6: 70, 142 Fletcher, Steven, 6: 3 Floreancig, Paul, 1: 195, 2: 198, 3: 89, 4: 95, 155, 6: 83, 86 Flynn, Bernard L., 5: 138 Fogg, Deryn E., 2: 50, 3: 45 Fokin, Andrey A., 4: 94 Fokin, Valery V., 2: 86, 3: 132, 4: 142, 144, 5: 75 Forbes, David C., 1: 44, 4: 15 Forgione, Pat, 4: 128 Foss, Frank W. Jr, 5: 15 Foubelo, Francisco, 5: 68 Fox, David J., 6: 61 Fox, Joseph M., 2: 70, 3: 145, 154, 5: 112, 146, 150 Fox, Martin E., 1: 194 France, Stefan, 4: 159, 5: 131 Frantz, Doug E., 5: 2, 6: 43 Fréchet, Jean M. J., 4: 87 Frejd, T., 6: 135

217  Author Index

Earle, Martyn, 1: 21 Easton, C. J., 6: 180 Eberlin, Marcos N., 1: 202 Echavarren, Antonio M., 5: 150 El Kaïm, Laurent, 6: 7 Ellman, Jonathan A., 1: 122, 2: 41, 126, 178, 3: 80, 133, 180, 4: 18, 130, 5: 107, 6: 65 Elsevier, Cornelis J., 6: 18 Elvira, Katherine S., 6: 28 Enders, Dieter, 1: 185, 2: 7, 62, 171, 203, 3: 140, 6: 137, 140 Endo, Kohei, 4: 45 Ermolenko, Mikhail S., 1: 186 Eskici, Mustafa, 5: 47 Estévez, Ramon J., 1: 9 Esumi, Tomoyuki, 4: 145 Etzkorn, Felicia A., 4: 42 Eustache, Jacques, 3: 49 Evano, Gwilherm, 3: 110, 6: 6 Evans, David A., 2: 38, 3: 72, 5: 151, 206 Evans, P. Andrew, 1: 140, 2: 73, 6: 123

Author Index  218

218

Friestad, Gregory K., 4: 33 Fringuelli, Francesco, 2: 99 Frontier, Alison J., 3: 102 Frost, Christopher G., 4: 104 Fu, Chunling, 6: 71 Fu, Gregory C., 1: 38, 60, 61, 104, 2: 5, 24, 83, 101, 128, 3: 30, 37, 75, 76, 92, 4: 46, 71, 76, 78, 5: 7, 72, 77, 136, 6: 4, 58, 138 Fu, Gregory C., 6: 141 Fu, Hua, 3: 26 Fu, Xuefeng, 5: 15 Fu, Yao, 4: 8, 6: 48, 119 Fuchs, Philip L., 5: 18 Fügedi, Péter, 4: 20 Fujii, Nobutaka, 3: 117, 126, 4: 98, 5: 67, 109, 110, 6: 83, 133 Fujioka, Hiromichi, 2: 107, 3: 157, 4: 22, 161, 5: 18, 23, 90, 6: 98 Fujita, Ken-​ichi, 2: 55, 4: 6, 5: 14, 54, 6: 5 Fujiwara, Kenshu, 1: 195, 3: 93 Fukase, Koichi, 6: 32 Fukumoto, Yoshiya, 2: 146, 3: 5 Fukuyama, Takahide, 5: 30 Fukuyama, Tohru, 1: 142, 2: 141, 3: 14, 52, 98, 152, 4: 111, 131, 5: 75, 117, 178, 6: 4, 17, 113, 114, 117, 184 Fukuyama, Yoshiyasu, 4: 145 Funk, Raymond L., 2: 84, 136, 169, 4: 198 Funk, Timothy W., 4: 55, 61, 5: 46, 207 Furakawa, Shinya, 6: 18 Furket, Daniel P., 3: 103 Furman, Bartlomiej, 6: 107, 108 Fürstner, Alois, 1: 126, 2: 52, 3: 33, 35, 55, 144, 164, 4: 61, 65, 5: 90, 98, 101, 6: 14, 17, 101, 176 Fusco, Caterina, 6: 9 Fustero, Santos, 3: 23, 102, 6: 109 Futjes, Floris, 1: 92 Fuwa, Haruhiko, 3: 89, 4: 47, 5: 88, 6: 190 Gade, Lutz H., 5: 138 Gademann, Karl, 5: 158 Gaffney, Piers R. J., 3: 20 Gagné, Michel R., 2: 198, 3: 92, 98, 145, 149, 6: 18 Gagosz, Fabien, 2: 49, 173, 3: 130, 4: 93, 5: 88, 6: 129 Gaich, Tanja, 3: 161

Gais, Hans-​Joachim, 2: 128 Galano, Jean-​Marie, 6: 47, 91, 96 Gallagher, Timothy, 1: 106 Gallos, John K., 4: 155 Gamba-​Sánchez, Diego, 6: 23 Gandelman, Mark, 5: 2 Gandon, Vincent, 4: 130 Ganem, Bruce, 4: 29 Ganesan, A., 1: 174 Gangula, Srinivas, 6: 29 Gansäuer, Andreas, 4: 142 Gao, Shuanhu, 5: 102 Garcia Fernandez, José M., 2: 91 Garg, Neil K., 3: 127, 4: 208, 5: 174, 6: 121 Garner, Charles M., 2: 129 Gastaldi, Stéphane, 3: 63 Gathergood, Nicholas, 6: 26 Gau, Han-​Mou, 2: 162 Gaunt, Matthew J., 1: 167, 3: 114, 126, 139, 6: 39 Gauvin, Régis M., 4: 64 Gawley, Robert E., 4: 108, 5: 66 Ge, Haibo, 6: 39 Gellman, Samuel H., 2: 60, 119, 190, 3: 70, 75, 137, 4: 134, 5: 139 Gentili, Patrizia, 5: 13 Georg, Gunda, 1: 70, 5: 91, 6: 101 Georgiadis, Dimitris, 2: 66 Gervay-​Hague, Jacquelyn, 2: 133 Gevorgyan, Vladimir, 3: 130, 4: 128, 5: 88, 128, 6: 38, 48, 124 Gharpure, Santosh J., 4: 90 Ghelfi, Franco, 6: 25 Ghorai, Manas K., 4: 106, 5: 110 Ghorbani-​Vaghei, Ramin, 5: 122 Ghosh, Arun, 1: 50, 2: 199, 4: 96, 5: 42, 96, 6: 86 Ghosh, Subhash, 4: 98 Ghosh, Subrata, 2: 178 Gibb, Bruce C., 5: 18 Gil, Gérard, 3: 63 Gilmour, Ryan, 6: 104 Gilroy, Joe B., 6: 26 Gimeno, José, 2: 145 Gin, David Y., 2: 140, 6: 170 Girijavallabhan, Vinay, 5: 3 Gleason, James L., 1: 114, 2: 167 Glorius, Frank, 1: 18, 139, 2: 128, 5: 17, 24, 67, 136, 6: 82, 88, 105

 219

Gu, Zhenhua, 5: 127 Guan, Zheng-​Hui, 5: 123 Guerra, Francisco M., 6: 11 Guo, Cancheng, 6: 12 Guo, Chuangxing, 4: 25 Guo, Hai-​Ming, 5: 39 Guo, Kai, 6: 29 Guo, Lin, 4: 94 Guo, Qing-​Xiang, 3: 121, 4: 8 Gürtler, C., 1: 100 Haak, Edgar, 6: 126 Hajipour, Abdoul Reza, 2: 85 Hajra, Alakananda, 4: 25 Hajra, Saumen, 3: 88 Halcomb, Randall, 1: 32 Hale, Karl J., 5: 161, 6: 42 Hall, Dennis G., 1: 62, 2: 197, 3: 11, 65, 4: 63, 71, 122, 5: 7, 46, 6: 103 Hamada, Hiroki, 3: 79 Hamada, Yasumasa, 1: 78, 4: 41, 140, 5: 111, 112 Hamann, Mark T., 4: 16, 5: 13 Hamashima, Yoshitaka, 5: 141 Hammond, Gerald B., 3: 16, 36 Han, Hyunsoo, 3: 65, 6: 59 Han, Jianlin, 6: 12 Han, Li-​Biao, 3: 39, 4: 11, 5: 10 Han, Zhengxu S., 6: 130 Hanessian, Stephen, 2: 51, 177, 6: 113 Hansen, Karl B., 4: 66 Hansen, Tore, 4: 137 Hansen, Trond Vidar, 3: 124, 4: 118 Hanson, Paul, 1: 40, 2: 109 Hanson, Susan K., 5: 16, 6: 8 Hanzawa, Yuji, 2: 81, 188, 3: 129, 5: 128 Hao, Jian, 6: 120 Hao, Xiaojiang, 5: 53 Harada, Tadao, 3: 41 Harada, Toshiro, 1: 151, 3: 67, 4: 73, 6: 60 Harder, Sjoerd, 2: 125 Harman, W. D., 2: 65, 99 Harran, Patrick G., 5: 210, 6: 117 Harris, Thomas, 3: 125 Harrity, Joseph P. A., 1: 53, 193, 2: 205, 4: 121, 147, 5: 105, 132, 6: 125, 130 Harrowven, David C., 2: 26, 5: 10 Hartley, Richard C., 3: 91, 102, 4: 10

219  Author Index

Gnaim, Jallal M., 1: 174 Goddard, Jean-​Philippe, 6: 14 Godfrey, Christopher R. A., 4: 37 Goeke, Andreas, 3: 149, 5: 49, 145 Goel, Atul, 3: 127 Goess, Brian C., 4: 63, 5: 54 Goldsmith, Christian R., 4: 34 Gómez Arrayás, Ramón, 2: 195 Gong, Hegui, 6: 48 Gong, Liu-​Zhu, 2: 74, 3: 78, 86, 4: 84, 102, 5: 111, 6: 117, 142 Gonzáles-​Romero, Carlos, 6: 21 González-​Calderón, Davir, 6: 21 Goodman, Alan S., 6: 24 Goossen, Lukas. J., 1: 156, 2: 185, 4: 30, 6: 118 Gopalan, Aravamudan S., 5: 19 Gopi, Hosahudya N., 5: 6 Gorden, Anne E. V., 5: 13 Gorin, David J., 6: 20 Goswami, Rajib Kumar, 6: 99 Gotor, Vicente, 5: 66 Gouverneur, Véronique, 5: 9, 6: 51 Gracias, Vijaya, 2: 41 Gracza, Tibor, 6: 96 Graham, Andrew E., 4: 90 Grainger, Richard S., 3: 4, 6: 37 Greaney, Michael F., 3: 120 Greatrex, Ben W., 6: 136 Greck, Christine, 5: 84 Grée, René, 4: 14, 143 Greenberg, William E., 3: 103 Gregg, Brian T., 4: 40 Grela, Karol, 1: 126, 2: 110, 3: 47, 48, 4: 64 Griengl, Herfried, 3: 65 Grimaud, Laurence, 6: 7 Grimme, Stefan, 3: 38, 5: 16, 24 Grogan, Gideon, 3: 156 Gröger, Harald, 2: 143 Grotjahn, Douglas B., 3: 40, 5: 59 Groves, John T., 4: 36, 5: 38 Grubbs, Robert H., 1: 28, 2: 49, 110, 151, 3: 45, 47, 48, 50, 4: 56, 59, 5: 25, 26, 56, 62, 6: 46, 51, 52, 146 Grushin, Vladimir V., 5: 120 Grützmacher, Hansjörg, 3: 2 Gu, Hongwei, 6: 19 Gu, Peiming, 5: 126, 6: 64 Gu, Yonghong, 4: 120, 5: 122

Author Index  220

20

Hartwig, John F., 1: 157, 160, 2: 60, 92, 155, 3: 23, 39, 66, 120, 122, 123, 124, 4: 28, 129, 5: 17, 36, 38, 126, 150, 6: 38, 72, 74, 118, 120 Harvey, Joanne, 3: 101, 4: 12, 6: 82 Hasegawa, Masayuki, 3: 77 Hashimoto, Shunichi, 3: 100, 4: 146, 5: 144, 6: 91 Hashmi, A. Stephen K., 6: 90, 128 Hassner, Alfred, 5: 23 Hatakeyama, Susumi, 1: 196, 3: 94, 4: 116, 5: 37, 162 Hatanaka, Minoru, 3: 5, 4: 42 Hattori, Yasunao, 6: 109 Haufe, Günter, 5: 70 Hayashi, Masahiko, 5: 144 Hayashi, Tamio, 1: 64, 66, 2: 120, 129, 3: 33, 107, 152, 4: 2, 71, 72, 77, 81, 143, 144, 5: 74, 80, 6: 102 Hayashi, Yujiro, 1: 4, 2: 60, 68, 172, 3: 12, 58, 72, 74, 136, 137, 143, 4: 66, 107, 5: 78, 143, 6: 15, 70, 76, 80 He, Chuan, 1: 122, 175, 2: 17, 177, 3: 24 He, Ren, 3: 44 He, Weimin, 6: 5 Headley, Allan D., 5: 83 Heck, Richard F., 4: 41, 129 Heinrich, Markus R., 3: 125, 4: 53, 5: 122, 6: 57 Helmchen, Günter, 1: 138, 179, 202, 2: 113, 161, 4: 110, 112, 147, 5: 64, 154 Helquist, Paul, 3: 106, 4: 5, 122 Hemming, Karl, 5: 130 Heravi, Majid, 2: 75 Hernández, Rosendo, 4: 2 Herrera, Antonio J., 3: 27 Herrera, Raquel, 2: 58 Herrmann, Andreas, 5: 22 Herzon, Seth B., 4: 157, 5: 17, 113, 6: 6, 54, 166 Hiemstra, Henk, 1: 92 Hiersemann, Martin, 1: 96, 2: 61, 3: 81, 5: 144, 6: 79, 160 Hilinski, Michael K., 6: 40 Hiller, Michael C., 2: 41 Hilmersson, Göran, 3: 9, 4: 21 Hilt, Gerhard, 2: 156, 3: 25, 127, 4: 121, 144 Hilvert, Donald, 4: 93

Hinkle, Kevin, 1: 106 Hintermann, Lukas, 2: 146, 3: 5, 4: 11 Hirama, Masahiro, 2: 198, 4: 21, 5: 168, 6: 97 Hirano, Koji, 5: 70 Hiroya, Kuo, 2: 159, 4: 155, 6: 93 Hiyama, Tamejiro, 3: 116, 4: 41, 130, 5: 58 Ho, Chun-​Yu, 4: 55, 6: 89 Ho, Phil Lee, 4: 9 Hocek, Michal, 5: 90 Hodgson, David M., 1: 81, 149, 2: 137, 3: 36, 4: 47, 104, 5: 98, 110 Hoerrner, Scott, 1: 40 Hoffman, Reinhard W., 2: 135 Holland, Patrick L., 6: 54 Hollmann, Frank, 6: 67 Holmes, Andrew B., 3: 152 Hon, Yung-​Son, 2: 78 Honda, Toshio, 1: 75, 3: 161 Hong, Bor-​Cherng, 4: 135, 5: 137, 139, 143, 6: 135, 137 Hong, Fung-​E, 5: 56 Hong, Jiyong, 4: 108, 140, 5: 91, 100, 6: 87 Hong, Soon Hyeok, 5: 6, 6: 11, 14 Horni, Osmo E. O., 1: 88 Hosomi, Akira, 3: 88 Hosoya, Takamitsu, 6: 25, 26 Hosseini-​Sarvari, Mona, 2: 130 Hotha, Srinivas, 5: 82 Hou, Duen-​Ren, 2: 153, 4: 26, 6: 49 Hou, Xue-​Long, 3: 150, 4: 17, 126, 5: 132, 6: 108 Hou, Yuqing, 4: 118 Houk, K. N., 2: 198, 6: 72 Houpis, Joannis N., 3: 125 Hoveyda, Amir H., 1: 96, 141, 182, 2: 24, 29, 48, 50, 94, 164, 196, 207, 3: 71, 192, 193, 4: 56, 57, 61, 69, 73, 5: 62, 65, 73, 74, 92, 151, 6: 42, 47, 51, 62, 69, 71, 80, 200 Howell, Amy R., 6: 90 Hoye, Thomas, 1: 130, 2: 154, 5: 62, 111, 155, 6: 36 Hoz, Shmaryahu, 1: 18, 5: 12 Hsiao, Yi, 4: 66 Hsung, Richard P., 1: 187, 2: 101, 3: 154, 156, 4: 159, 5: 162, 6: 93 Hu, Jinbo, 5: 162 Hu, Longqin, 3: 18 Hu, Qiao-​Sheng, 1: 110

 21

Iadonisi, Alfonso, 5: 24 Ibrahem, Ismail, 5: 82, 142 Ichikawa, Junji, 5: 133 Ichikawa, Satoshi, 5: 19, 42, 6: 105 Ichikawa, Yoshiyasu, 5: 65 Iguchi, Kazuo, 1: 102 Ikariya, Takao, 2: 192, 4: 12, 146, 159 Ila, Hiriyakkanavar, 3: 33 Imada, Yasushi, 2: 77, 4: 52 Imagawa, Hiroshi, 4: 150 Imahori, Tatsushi, 3: 56 Ingleson, Michael J., 5: 126 Inomata, Katsuhiko, 4: 88 Inoue, Masayuki, 2: 198, 4: 19, 32, 5: 32, 34, 6: 40, 162 Inoue, Yoshio, 1: 98 Iqbal, Javed, 3: 46 Iranpoor, Nasser, 1: 106, 156, 3: 15 Ishibashi, Hiroyuki, 2: 145, 210, 3: 109, 117 Ishihara, Kazuaki, 2: 44, 65, 76, 100, 3: 156, 4: 14, 72, 5: 14, 6: 59

Ishii, Yasutaka, 1: 22, 3: 128, 4: 34, 42, 5: 11 Isobe, Minoru, 1: 136, 2: 130, 4: 154, 5: 148 Itami, Kenichiro, 5: 52 Ito, Hajime, 3: 65, 85, 4: 144 Ito, Hisanaka, 1: 102, 3: 22 Ito, Katsuji, 2: 58 Ito, Yukishige, 3: 22, 6: 21 Ivanova, Olga A., 4: 15 Iwabuchi, Yoshiharu, 2: 204, 3: 13, 4: 14, 177, 5: 13, 14, 42, 152, 6: 13 Iwao, Masatomo, 4: 128 Iwasa, Seiji, 4: 146, 5: 148 Iwasawa, Nobuharu, 4: 126, 5: 57 Jackson, James E., 3: 23 Jacobi, Peter A., 3: 85 Jacobsen, Eric N., 1: 84, 138, 150, 160, 177, 205, 2: 108, 3: 71, 74, 115, 147, 153, 4: 69, 137, 138, 5: 79, 119, 6: 65, 137 Jacquot, Roland, 6: 7 Jaekel, Christoph, 3: 148 Jafarpour, Maasoumeh, 6: 52 Jahn, Ullrich, 3: 160, 4: 156 Jain, Suman L., 4: 124 Jama, Umasish, 6: 44 James, Keith, 5: 30 Jamison, Timothy F., 1: 94, 2: 78, 126, 136, 198, 3: 39, 93, 112, 4: 52, 91, 5: 28, 29, 30, 31, 57, 6: 30, 33, 108 Jana, Ranjan, 6: 133 Jana, Umasish, 4: 128 Jang, Doo Ok, 2: 182, 4: 25, 72 Jang, Hye-​Young, 6: 145 Jarosz, Slawomir, 4: 154, 6: 103 Jarvo, Elizabeth R., 5: 80 Jenkins, David M., 5: 104 Jennings, Michael P., 1: 187, 3: 22, 58, 6: 100 Jensen, Klavs S., 4: 31, 5: 26, 6: 30 Jeon, Heung Bae, 1: 188 Jeon, Junha, 6: 124 Jeong, Nakcheol, 3: 148 Jew, Sang-​sup, 2: 163, 4: 78 Ji, Ya-​Fei, 5: 25 Jia, Guochen, 3: 132 Jia, Xueshun, 2: 189, 4: 26 Jia, Yanxing, 4: 109, 127, 5: 134, 6: 71, 116, 131

221  Author Index

Hu, Wenhao, 5: 87, 6: 74, 78 Hu, Xiang-​Ping, 4: 76 Hu, Xile, 5: 44, 47, 6: 47 Hu, Xinquan, 3: 3 Hu, Youhong, 5: 121 Hu, Yulai, 4: 3, 6: 5 Hua, Ruimao, 4: 4 Huang, Danfeng, 4: 3, 6: 5 Huang, Hanmin, 5: 60, 6: 36 Huang, Jianhui, 6: 34 Huang, Jing-​Mei, 4: 10, 5: 21 Huang, Kuo-​Wei, 5: 86 Huang, Pei-​Qiang, 4: 8, 18, 108, 5: 50, 110, 116 Huang, Xiaojun, 4: 105 Huang, Yong, 5: 9, 125 Huang, Zheng, 6: 42, 72, 130 Huang, Zhi-​Zhen, 4: 37, 53 Hudlicky, Tomas, 6: 159 Hudson, Richard A., 2: 15 Hue, Xue-​Long, 3: 84 Hull, Kami L., 6: 80 Hultzsch, Kai C., 2: 92, 5: 106 Hung, Shang-​Cheng, 1: 16 Hunson, Mo, 2: 13 Hwang, Geum-​Sook, 5: 136, 151 Hwang, Kuo Chu, 5: 125

Author Index  222

2

Jia, Yi-​Xia, 6: 66 Jian, Huanfeng, 4: 52 Jiang, Biao, 3: 33 Jiang, Biwang, 4: 60 Jiang, Huanfeng, 3: 130, 134, 4: 47, 50, 128, 5: 34, 90, 6: 8, 20, 49, 90 Jiang, Zhiyong, 5: 14, 86 Jiao, Ning, 4: 4, 32, 5: 9, 132, 133, 6: 3, 52 Jin, Myung-​Jong, 5: 120 Joglar, Jesús, 2: 165 Johnson, Jeffrey S., 2: 29, 3: 196, 4: 91, 107, 5: 63, 85, 5: 86, 6: 16, 74, 85, 134, 206 Johnson, Marc J. A., 2: 148, 3: 31 Johnston, Eric V., 6: 144 Johnston, Jeffrey N., 1: 38, 3: 119 Jones, Christopher, 3: 60 Jones, Paul B., 1: 176 Jørgensen, Karl Anker, 1: 119, 166, 205, 2: 4, 14, 23, 60, 102, 121, 172, 203, 3: 62, 64, 77, 85, 136, 137, 138, 139, 141, 178, 4: 77, 134, 141, 5: 136, 138, 6: 24, 67, 102, 137, 140 Joshi, N. N., 1: 64 Joullié, Madeleine M., 4: 88 Juhász, Zsuzsa, 3: 87 Julia, M., 6: 176 Jun, Chul-​Ho, 2: 178, 3: 42, 4: 53 Jung, Kyung Woon, 3: 112, 4: 39, 78, 118 Jung, Michael E., 2: 70, 3: 154, 5: 156 Jung, N., 6: 23 Jung, Young Hoon, 4: 10 Justicia, José, 6: 143 Jutand, Anny, 5: 94 Kadyrov, Renat, 4: 68 Kaeobamrung, Juthanat, 4: 89 Kakiuchi, Fumitoshi, 2: 209 Kalesse, Markus, 3: 65, 4: 82, 6: 200 Kallemeyn, Jeffrey M., 4: 160 Kambe, Nobuaki, 3: 36, 4: 40, 5: 46, 6: 46 Kamei, Toshiyuki, 6: 122 Kamijo, Shin, 6: 40 Kamimura, Akio, 3: 78 Kaminski, Zbigniew J., 2: 44 Kamitanaka, Takashi, 3: 41 Kan, Toshiyuki, 3: 98, 5: 141, 6: 180 Kanai, Motomu, 1: 98, 2: 3, 52, 87, 3: 61, 74, 4: 74, 81, 5: 87, 108, 6: 5, 9, 14, 39, 76

Kaneda, Kiyotomi, 1: 104, 107, 4: 18, 5: 10, 6: 8 Kanemasha, Shuji, 3: 77 Kang, Sung Ho, 5: 73 Kanger, Tönis, 4: 83, 156 Kanoh, Naoki, 5: 152, 6: 46 Kapoor, Kamal K., 6: 126 Kappe, C. Oliver, 2: 155, 187, 4: 30, 5: 29, 30, 6: 28, 30, 31, 33 Karoyan, Philippe, 3: 77, 106 Kato, Nobuo, 5: 33 Katoh, Tadashi, 5: 18 Katsuki, Tsutomu, 2: 13, 58, 3: 6, 40, 66, 148, 156, 4: 90, 148, 5: 108, 6: 35, 73 Katsumura, Shigeo, 2: 152, 3: 133, 5: 111 Katukojvala, Sreenivas, 6: 129 Kawabata, Takeo, 1: 38, 3: 105, 107, 5: 23 Kawatsura, Motoi, 2: 62 Kazmaier, Uli, 4: 38 Keck, Gary E., 2: 9, 32, 3: 198, 5: 89 Kelly, T. Ross, 1: 108 Kempe, Rhett, 2: 209, 5: 134, 135 Kerr, Michael A., 3: 119, 5: 53, 132, 6: 84 Kerr, William J., 2: 147 Kezuka, Satoko, 6: 62 Khaksar, Samad, 3: 21 Khodaei, Mohammad M., 4: 17 Kigoshi, Hideo, 1: 134 Kilic, Hamdullah, 4: 102 Kim, B. Moon, 5: 54 Kim, Deukjoon, 2: 32, 170, 6: 97 Kim, Dong-​Pyo, 4: 30, 5: 26, 31 Kim, Hee-​Doo, 6: 63 Kim, Hyoungsu, 5: 100 Kim, Ikyon, 3: 132 Kim, Jae Nyoung, 2: 41, 187 Kim, Jeung Gon, 6: 40 Kim, Kwan Soo, 1: 188 Kim, Mahn-​Joo, 1: 88 Kim, Sanghee, 2: 107, 6: 114 Kim, Sunggak, 3: 85, 4: 9, 36, 38, 81, 157, 5: 127 Kim, Tae-​Jeong, 3: 144, 146 Kim, Yong Hae, 5: 46 Kim, Young Gyu, 1: 108 Kimber, Marc C., 5: 143 Kimura, Yoshikazu, 6: 13 Kingsbury, Jason S., 4: 40, 6: 45 Kirihara, Masayuki, 6: 20

 23

Kraft, Philip, 6: 141 Krajnc, Matzaz, 5: 27 Kraus, George A., 4: 23, 5: 125 Krause, Norbert, 2: 197, 4: 85 Krauss, Isaac J., 6: 75 Krempner, Clemens, 6: 14 Krenske, Elizabeth H., 6: 48 Krische, Michael J., 2: 195, 3: 68, 82, 4: 84, 86, 5: 78, 82, 176, 6: 48, 78, 92 Krishna, Palakodety Radha, 5: 116 Krompiec, Stanislaw, 4: 21 Kroutil, Wolfgang, 1: 2, 3: 66, 69, 5: 16, 41, 108 Krska, Shane W., 4: 86 Kuang, Chunxiang, 5: 45 Kudo, Kazuaki, 3: 74, 5: 64, 6: 68, 134 Kuhakarn, Chutima, 3: 14 Kulkarni, Mukund G., 2: 127 Kumagai, Naoya, 4: 81, 5: 71, 78, 84, 144, 6: 74, 76, 78 Kumar, Kamal, 6: 134 Kumar, Pradeep, 4: 6 Kumaraswamy, Gullapalli, 4: 35 Kunai, Atsutaka, 2: 185 Kündig, E. Peter, 1: 137, 6: 41 Kuninobu, Yoichiro, 5: 44, 51, 121, 130, 6: 14, 39 Kunishima, Munetaka, 5: 22 Kuniyasu, Hitoshi, 5: 46 Kunz, Horst, 3: 109 Kurahashi, Takuya, 4: 47, 6: 152 Kurosu, Michio, 5: 6 Kurth, Mark J., 3: 141 Kusama, Hiroyuki, 5: 55 Kutsumura, Noriki, 4: 54, 5: 11 Kuwahara, Shigefumi, 1: 200, 3: 44, 5: 160, 200, 201, 6: 3 Kuwano, Ryoichi, 3: 104 Kwiatkowski, Piotr, 5: 136 Kwon, Ohyun, 5: 16, 117, 6: 106 Kwong, Fuk Yee, 3: 124 Lacôte, Emmanuel, 4: 120 Lakouraj, M. M., 1: 86 Lalic, Gojko, 5: 49, 58, 6: 4, 16, 18 Lam, Hon Wai, 4: 73, 76 Lambert, Tristan H., 3: 92, 150, 151, 4: 2, 5: 71, 88 Landais, Yannick, 3: 86, 6: 48

223  Author Index

Kirimura, Kohtaro, 4: 125 Kirkham, James D., 5: 132 Kirsch, Stefan F., 2: 206, 4: 123 Kirschning, Andreas, 1: 189, 2: 151, 3: 21, 177, 4: 30, 6: 28, 152 Kishi, Yoshito, 1: 178, 2: 191, 3: 68, 5: 5, 48, 6: 149 Kita, Yasuyuki, 2: 13, 18, 107, 3: 24, 157 Kitamura, Masato, 4: 20, 5: 106, 6: 26 Kitano, Yoshikazo, 6: 54 Kitazume, Tomoya, 2: 85 Klein Gebbink, Robertus J. M., 6: 52 Klopper, Wim, 5: 155 Klosin, Jerzy, 2: 59 Klumpp, Douglass A., 5: 124, 6: 20 Klussmann, Martin, 5: 37 Knight, David W., 2: 145, 3: 128, 4: 62 Knochel, Paul, 1: 81, 110, 127, 149, 2: 39, 3: 129, 4: 89 Knowles, Robert R., 6: 107 Kobayashi, Shu, 1: 111, 2: 39, 60, 162, 196, 3: 34, 83, 104, 4: 79, 5: 15 Kobayashi, Susumu, 3: 159, 206, 4: 143, 155, 5: 63 Kobayashi, Yoshihisa, 3: 19 Kobayashi, Yuichi, 3: 150 Kobayashi, Shoji, 5: 99 Kocevar, Marijan, 3: 131 Kocovsky, Pavel, 5: 78, 90, 6: 55 Koenig, Stefan G., 4: 20 Koert, Ulrich, 2: 135, 3: 54 Koide, Kazunori, 3: 33, 46, 5: 148 Kokotos, Christoforos G., 6: 54 Kokotos, George, 2: 48 Komatsu, Mitsuo, 2: 137 Komatsu, Takayuki, 6: 18 Kominami, Hiroshi, 6: 18 Kondo, Yoshinori, 1: 10 Koninobu, Yoichiro, 4: 51 Konopelski, Joseph P., 4: 106 Koo, Sangho, 5: 10, 6: 147 Kotaki, Yoshihiko, 3: 52 Kotora, Martin, 6: 148 Kotsuki, Hiyoshizo, 1: 153, 4: 136, 5: 140 Kouklovsky, Cyrille, 4: 63, 5: 163 Kowalski, Conrad, 1: 107 Kozlowski, Marisa C., 2: 185, 4: 89 Kozmin, Sergey A., 3: 174 Krafft, Marie E., 2: 173, 4: 158

Author Index  224

24

Landis, Clark R., 4: 80, 5: 72, 6: 51 Lapkin, Alexei A., 6: 32 LaPorte, Thomas L., 6: 33 Larhed, Mats, 4: 122 Larock, Richard C., 2: 82, 3: 128, 132 Larrosa, Igor, 6: 122 Larsen, David S., 5: 24 Lattanzi, Alessandra, 6: 77 Lau, Chak Po, 5: 2 Lau, Stephen Y. W., 4: 125 Lautens, Mark, 1: 74, 3: 129, 131, 4: 131, 144, 5: 117, 6: 82 Lavigne, Guy, 2: 151 Lawrence, Andrew L., 5: 102 Leadbeater, Nicholas, 1: 54, 2: 22, 4: 30 Lear, Martin J., 4: 22, 5: 97 Lebel, Hélène, 2: 43, 210, 4: 38, 5: 67 Lectka, Thomas, 1: 62, 119, 2: 161, 5: 38, 6: 40 Lee, Ai-​Lan, 5: 8 Lee, Chi-​Lik Ken, 5: 30 Lee, Chi-​Sing, 6: 151 Lee, Chulbom, 2: 138, 173, 6: 2 Lee, Daesung, 1: 132, 3: 56, 160, 4: 58, 63, 156, 5: 47, 148, 162, 6: 121 Lee, Eun, 1: 72, 2: 199, 4: 58 Lee, Hee-​Yoon, 1: 36, 6: 158, 192 Lee, Hyeon-​Kyu, 4: 70 Lee, Jetty Chung-​Yung, 6: 91, 96 Lee, Kieseung, 5: 46 Lee, Nathan K., 2: 152 Lee, Phil Ho, 4: 39, 128 Lee, Sang-​gi, 4: 46, 133 Lee, Sang-​Gyeong, 4: 24 Lee, Sang-​Hyeup, 6: 45 Lee, Seongmin, 5: 34 Lee, Su Seong, 3: 51 Lee, Sungyul, 4: 2 Lee, Sunwoo, 4: 119 Lee, Victor, 2: 169 Lee, Wen-​Cherng, 4: 4 Lee, Yoon-​Silk, 3: 3 Lefenfeld, Michael, 3: 23 Legault, Claude Y., 5: 162 Legzdins, Peter, 3: 24 Lei, Aiwen, 6: 2, 104, 126 Lei, Xiaoguang, 6: 149, 155 Leighton, James L., 2: 62, 89, 162, 4: 107, 5: 70, 6: 160

Leino, Reko, 6: 27 Leitner, Walter, 4: 30 Lemaire, Marc, 4: 5, 6: 19 Lendsell, W. Edward, 2: 43 Leonard, Nicholas M., 5: 3 Leow, Dasheng, 6: 56 Lepore, Salvatore D., 3: 15 Lesma, Giordano, 1: 70 Levacher, Vincent, 2: 44 Lewis, Yamamoto, 6: 194 Ley, Steven V., 2: 19, 67, 3: 176, 4: 19, 30, 5: 30, 6: 28, 32 Li, Ang, 5: 186, 190, 6: 123, 133, 172 Li, Bin, 5: 134 Li, Bryan, 2: 130 Li, Chao-​Jun, 2: 144, 3: 3, 28, 4: 37, 42, 122, 6: 10 Li, Chaozhong, 2: 173, 3: 43, 106, 4: 114, 130, 5: 4, 51 Li, Chuang-​Chuang, 4: 153, 196, 5: 145, 159 Li, Feng, 6: 6 Li, Fuwei, 6: 130 Li, Guigen, 5: 131 Li, Hongmei, 4: 20 Li, Jian, 5: 76 Li, Jianqing, 5: 4 Li, Jin-​Heng, 2: 155, 185 Li, Pingfan, 6: 56 Li, Shun-​Jun, 3: 72 Li, Wei-​Dong Z., 4: 116 Li, Xuechen, 4: 7 Li, Yahong, 4: 128 Li, Yuanchao, 6: 131 Li, Zhi, 5: 33, 6: 60, 138, 140 Li, Zhiping, 4: 129, 6: 96 Li, Zhong, 3: 114, 6: 140 Li, Zhong-​Jun, 5: 18 Li, Zigang, 5: 53, 6: 43, 83 Liang, Fushun, 3: 135 Liang, Guangxin, 5: 163 Liang, Xinmiao, 2: 144, 3: 140, 142 Liang, Yong-​Min, 3: 128, 4: 32, 42, 5: 49, 129 Liang, Yun, 6: 37 Liao, Chun-​Chen, 3: 158, 5: 158 Liao, Jian, 6: 66 Liao, Wei-​Wei, 5: 48 Lièvre, Catherine, 1: 75

 25

Lobo, Ana M., 3: 135 Loh, Teck-​Peng, 1: 150, 178, 2: 30, 96, 3: 69, 73, 140, 156, 4: 16, 36, 49, 138, 155, 159, 5: 72, 121, 6: 53, 106, 127, 130 Lombardo, Marco, 5: 140 Long, Timothy E., 4: 2 López, Fernando, 5: 49 López, Luis A., 5: 132 López, Núria, 6: 30 Lorenz, Jon C., 4: 71 Lou, Hui, 5: 12 Love, Jennifer, 3: 36 Lu, Liang-​Qiu, 5: 24 Lu, Ping, 6: 124 Lu, Yixin, 3: 140, 4: 67, 136, 140, 5: 64, 78, 107, 6: 67, 136 Lu, Zhan, 6: 72 Lubell, William D., 2: 87 Lubin-​Germain, Nadège, 3: 88 Luo, Sanzhong, 3: 136, 6: 73, 78, 85, 135 Luo, Shi-​Wei, 3: 86 Luo, Tuoping, 5: 94, 145 Luo, Yong-​Chun, 6: 106 Lupton, David W., 4: 90, 101, 6: 31, 134, 139 Luthra, Sajinder K., 5: 9 Lyapkalo, Ilya M., 2: 146, 3: 16 Lygo, Barry, 4: 152 Ma, Bin, 4: 4 Ma, Cheng, 5: 138 Ma, Dawei, 1: 143, 2: 164, 3: 83, 112, 141, 4: 88, 108, 138, 192, 5: 202 Ma, Jun-​An, 4: 79 Ma, Shengming, 1: 132, 2: 34, 4: 39, 132, 6: 45, 71 Macchi, Arturo, 6: 32 Machinami, Tomoya, 6: 76 Maciá, Beatriz, 6: 59 MacMillan, David W. C., 1: 4, 119, 124, 2: 1, 6, 3: 70, 75, 76, 143, 4: 68, 80, 137, 138, 139, 5: 76, 108, 115, 142, 6: 35, 38, 61, 68 Madabhushi, Sridhar, 5: 21 Maduit, Marc, 6: 148 Maehr, Hubert, 4: 39 Mäeorg, Uno, 3: 21 Maffioli, Sonia I., 2: 43

225  Author Index

Liguori, Angelo, 5: 50 Likhar, Pravin R., 5: 126 Lilly, Eli, 6: 26, 32 Limanto, John, 4: 86 Lin, Chung-​Cheng, 2: 47 Lin, Guo-​Qiang, 2: 62, 3: 63, 5: 74, 6: 107, 142, 145 Lin, Mei-​Huey, 6: 128 Lin, Rai-​Shung, 4: 146 Lin, Yun-​Ming, 4: 68 Lin, Zhenyang, 3: 132, 5: 71 Linclau, Bruno, 1: 156 Lindsay-​Scott, Peter J., 6: 26 Lindsley, Craig W., 4: 96, 106 Ling, Qing, 4: 131 Linker, Torsten, 3: 91, 5: 82 Liotta, Dennis C., 3: 83 Lipshutz, Bruce H., 3: 13, 48, 72, 149, 4: 70, 5: 46, 62 List, Benjamin, 1: 78, 166, 2: 68, 203, 3: 62, 73, 75, 76, 84, 139, 141, 143, 156, 4: 88, 136, 138, 5: 75, 81, 138, 6: 60, 62, 75, 82, 90, 139, 141 Little, R. Daniel, 1: 194 Liu, Bo, 5: 23, 25, 160 Liu, David R., 3: 39 Liu, Delong, 5: 142 Liu, Guoshen, 3: 29, 40 Liu, Hong, 3: 125 Liu, Kevin G., 2: 160 Liu, Lei, 3: 121, 4: 7, 125, 6: 48, 109 Liu, Pei Nian, 5: 2, 57 Liu, Qiang, 6: 10 Liu, Qingbin, 6: 2 Liu, Qun, 3: 135, 6: 3, 131 Liu, Rai-​Shung, 1: 171, 3: 145 Liu, Xiaohua, 4: 141, 5: 142, 6: 62 Liu, Xinyu, 6: 22 Liu, Xue-​Wei, 5: 86, 96, 6: 85 Liu, Xue-​Yuan, 5: 2 Liu, Yongxiang, 6: 27 Liu, Yuanhong, 6: 130 Liu, Yunkui, 5: 127 Liu, Zhong-​Quan, 5: 20, 52, 126 Livinghouse, Tom, 6: 106 Livingston, Andrew, 6: 28 Livinghouse, Tom, 2: 33, 4: 114, 152 Lloyd-​Jones, Guy C., 4: 23, 119, 5: 4, 124 Lo, Vanessa Kar-​Yan, 6: 104

Author Index  226

26

Maggini, Michele, 5: 29 Magnus, Nicholas A., 5: 110 Magnus, Philip, 4: 172 Maguire, Anita R., 4: 78 Maier, Martin E., 3: 122, 164, 4: 75 Maimone, Thomas J., 6: 39, 157 Mainolfi, Nello, 4: 31 Maiti, Debabrata, 5: 9, 12, 126, 6: 10, 57, 123, 133 Majee, Adinath, 4: 25 Majumdar, K. C., 4: 131 Makabe, Hidefumi, 6: 18 Makosza, Mieczyslaw, 2: 29 Makriyannis, Alexandros, 4: 3 Mal, Dipakranjan, 4: 129 Malachowski, William P., 2: 208, 6: 139 Malacria, Max, 4: 120, 130 Maldonado, Luis A., 5: 151 Maleczka, Robert E., Jr., 2: 160, 3: 8 Malkov, Andrew (Andrei) V., 5: 78, 90, 6: 55 Manabe, Kei, 3: 120, 6: 118 Manabe, Shino, 3: 22, 6: 21 Mancini, Pedro, 2: 188 Mandal, Bhubaneswar, 6: 5, 13 Mandal, Sisir K., 5: 126 Mander, Lewis N., 1: 12, 198 Mann, André, 3: 108 Mann, Enrique, 5: 162 Mans, Douglas M., 5: 130 Marcelli, Tommaso, 5: 126 Marcia de Figueiredo, Renata, 6: 5 Marciniec, Bogdan, 2: 17 Marco, J. Alberto, 1: 29 Marek, Ilan, 1: 47, 5: 81, 6: 67, 80 Maresh, Justin J., 6: 15 Margaretha, Paul, 4: 156 Mariano, Patrick, 1: 139 Marini, Francesca, 4: 75 Marion, Philippe, 6: 7 Markó, István, 2: 22, 93, 148, 3: 49, 74, 4: 16, 20, 5: 21 Marks, Tobin, 1: 30, 3: 13, 92 Marque, Sylvain, 3: 123 Marqués-​López, Eugenia, 5: 142 Marquis, Robert W., 1: 184 Marsden, Stephen P., 4: 17 Marshall, James A., 2: 122, 134, 3: 91 Martín, Angeles, 3: 90

Martín, M. Rosario, 3: 158 Martin, Rainer E., 6: 29, 30 Martin, Stephen, 1: 29, 83, 2: 34, 51, 70, 4: 65, 5: 95 Martín, Tomás, 6: 83 Martín, Victor S., 2: 96, 3: 104, 6: 83 Martín-​Matute, Belén, 6: 8 Martínez, Ana, 5: 61 Maruoka, Keiji, 1: 90, 152, 170, 2: 23, 117, 3: 78, 82, 85, 109, 4: 66, 72, 73, 77, 82, 104, 107, 5: 9, 75, 81, 82, 84, 6: 43, 61, 62, 74 Mascal, Mark, 4: 109 Mascareñas, José L., 5: 49 Mase, Nobuyuki, 4: 138 Mashima, Kazushi, 5: 5, 6: 2 Masson, Géraldine, 3: 69, 105, 4: 69, 5: 69 Mata, Ernesto G., 3: 48 Mateos, Carlos, 6: 30 Mati, Debabrata, 6: 51 Matsubara, Seijiro, 4: 47, 6: 152 Matsuda, Akira, 5: 19 Matsugi, Masato, 4: 64 Matsunaga, Shigeki, 4: 75, 86, 89, 142, 5: 78, 87, 6: 70 Matsuo, Jun-​ichi, 2: 14, 145, 210, 3: 155 Mauduit, Marc, 3: 47, 48 Maulide, Nuno, 4: 44, 5: 144, 6: 77, 147 May, Jeremy A., 5: 39, 114 May, Oliver, 2: 143 May, Scott A., 2: 82 Mazet, Clément, 4: 3, 5: 79, 6: 7 Mazurkiewicz, Roman, 2: 85 McCluskey, Adam, 3: 23 McDonald, Frank E., 1: 30, 70, 3: 93 McGarrigle, Eoghan M., 6: 84 McGuire, Michael A., 6: 31 McLeod, Malcolm D., 5: 89 McMurray, John S., 3: 9 McNulty, James, 6: 139 McNulty, LuAnne, 4: 65 McQuade, D. Tyler, 5: 64, 6: 28, 127 Meek, Graham, 1: 174 Mehta, Goverdhan, 2: 113, 5: 88 Melchiorre, Paolo, 3: 84, 6: 59, 68, 138 Meldal, Morten, 6: 26 Mellet, Carmen Ortiz, 2: 88, 91 Menche, Dirk, 4: 95, 99 Menon, Rajeev S., 6: 125

 27

Montgomery, John, 2: 30, 3: 31, 146, 5: 93, 6: 91 Moody, Christopher, 3: 121, 4: 127, 131, 133 Moore, Jeffrey S., 2: 110, 3: 49, 4: 41, 65 Moran, Wesley J., 4: 132, 160 Morgan, Jeremy B., 5: 56 Mori, Atsunori, 2: 25 Mori, Miwako, 1: 58, 83, 3: 145 Mori, Yuji, 4: 97 Morimoto, Hiroyuki, 6: 24 Morimoto, Yoshiki, 2: 93, 3: 94 Moriyama, Katsuhiko, 6: 15 Morken, James P., 1: 6, 2: 58, 119, 4: 46, 68, 80, 84, 100, 5: 70, 83, 6: 66, 71, 80, 196 Morris, Robert H., 1: 204 Mortier, Jacques, 2: 186 Mortreux, André, 3: 47 Morvan, François, 3: 10 Moses, John E., 6: 4 Moss, Thomas A., 5: 130 Mottaghinejad, Enayatollah, 1: 176 Moutevelis-​Minakakis, Panagiota, 3: 8 Movassaghi, Mohammad, 2: 79, 154, 188, 3: 14, 4: 150 Moyano, Albert, 3: 108, 5: 142, 6: 134 Mukai, Chisato, 2: 92, 5: 63 Mukaiyama, Teruaki, 3: 5, 12, 36, 70 Mukherjee, Debaraj, 5: 88 Mukherjee, Santanu, 6: 136 Müller, Paul, 1: 168, 2: 179, 3: 67 Müller, Thomas J. J., 2: 41, 3: 134, 4: 90 Mullins, Richard J., 4: 87 Mulzer, Johann, 1: 183, 2: 174, 3: 145, 161, 4: 150, 5: 100 Muñiz, Kilian, 5: 36, 38, 6: 64 Murahashi, Shun-​Ichi, 3: 10 Murai, Toshiaki, 4: 40, 5: 45 Murakami, Masahiro, 1: 123, 2: 69, 205, 4: 96, 5: 13, 52, 6: 42, 76, 108, 129 Muraleedharan, Kannoth Manheri, 4: 29 Murphree, S. Shaun, 5: 11 Murphy, John A., 1: 10, 3: 134, 4: 27, 5: 24, 6: 23 Murphy, Paul V., 3: 107 Murray, William V., 2: 49 Musaev, Djamaladdin G., 5: 144, 6: 142 Myers, Andrew G., 1: 87, 190, 2: 11, 3: 77, 4: 82, 5: 76 Myrboh, Bekington, 4: 24

227  Author Index

Menzel, Karsten, 3: 122 Merbouh, Nabyl, 6: 126 Metz, Peter, 2: 66, 4: 161 Meyer, Christophe, 4: 62, 5: 148 Mezzetti, Antonio, 6: 60 Miao, Chun-​Bao, 5: 90 Micalizio, Glenn C., 2: 122, 195, 3: 36, 4: 46, 93, 5: 85, 116, 130 Michael, Forrest E., 3: 108 Michelet, Véronique, 5: 120 Miel, Hugues, 4: 4 Mihara, Masatoshi, 4: 24 Mihovilovic, Marko D., 2: 134, 6: 141 Mikami, Koichi, 4: 69, 102, 5: 146 Militzer, H.-​Christian, 1: 191 Miller, Marvin J., 4: 34 Miller, Scott J., 5: 9, 14 Miller, Stephen A., 2: 143 Milne, Jacqueline E., 5: 120 Milstein, David, 2: 86, 3: 7, 4: 18, 5: 8, 19, 134, 6: 8, 10, 12, 22, 44 Minakata, Satoshi, 2: 137, 6: 15 Minehan, Thomas G., 4: 98 Minnaard, Adriaan J., 1: 164, 204, 2: 60, 3: 50, 94, 4: 103, 146, 6: 64, 144 Mioskowski, Charles, 2: 190, 3: 99 Misaka, Tomonori, 5: 64 Misaki, Tomonori, 5: 71, 6: 64 Miura, Katsukiyo, 3: 88, 4: 40, 6: 123 Miura, Masahiro, 1: 19, 3: 37, 4: 55, 5: 70, 6: 124 Miura, Tomoya, 6: 42, 76, 129 Miyake, Yoshihiro, 6: 44, 132 Miyaoka, Hiroaki, 5: 152 Miyashita, Masaaki, 1: 146, 2: 103, 4: 119, 204 Miyazawa, Masahiro, 6: 46 Miyoshi, Norikazu, 4: 118 Mizuno, Noritaka, 2: 77, 3: 7, 4: 34, 5: 11 Mlynarski, Jacek, 4: 138 Mobashery, Shahriar, 4: 13 Moberg, Christina, 1: 64 Moeller, Kevin, 1: 80, 4: 107 Mohan, Ram S., 4: 24 Mohapatra, Debendra K., 3: 45, 6: 91 Molander, Gary A., 1: 76, 3: 122, 4: 81, 119, 5: 5 Molinski, Tadeusz F., 5: 137 Mongin, Florence, 3: 130

Author Index  228

28

Nadeau, Christian, 4: 108 Nagao, Yoshimitsu, 2: 59 Nagaoka, Hiroto, 1: 36 Nagasawa, Kazuo, 4: 72 Nagashima, Hideo, 3: 8, 4: 12, 16, 5: 12 Nagorny, Pavel, 6: 21 Nain Singh, Kamal, 5: 142 Nájera, Carmen, 2: 56, 4: 77 Nakada, Masahisa, 1: 4, 52, 165, 2: 183, 4: 151, 164, 165, 5: 150, 6: 145, 151, 154, 164, 205 Nakagawa-​Goto, Kyoko, 5: 91 Nakamura, Eiichi, 3: 126 Nakamura, Itaru, 4: 9, 5: 5 Nakamura, Masaharu, 4: 41, 5: 47, 48 Nakamura, Shinji, 3: 38 Nakamura, Shuichi, 5: 64, 6: 138 Nakanishi, Koji, 2: 198 Nakanishi, Waro, 4: 19 Nakao, Yoshiaki, 3: 116, 4: 41, 130, 5: 58 Nakata, Masaya, 2: 186, 4: 121 Nakata, Tadashi, 4: 91 Nantz, Michael H., 5: 7 Naota, Takeshi, 2: 77, 4: 52 Narasaka, Koichi, 1: 128, 2: 188, 3: 130, 6: 64 Naso, Francesco, 3: 19 Nay, Bastien, 1: 186 Negishi, Ei-​chi, 3: 76, 4: 41, 129 Nelson, Scott G., 1: 116, 201, 2: 122, 140, 3: 80 Nettekoven, Matthias, 5: 28 Neumann, Ronny, 1: 86, 2: 77 Neuville, Luc, 6: 9 Nevado, Cristina, 3: 149, 4: 11, 149, 6: 50 Nguyen, SonBinh T., 2: 117, 143, 3: 51 Nguyen, Thanh Binh, 5: 15, 6: 7, 34 Ni, Bukuo, 4: 87, 5: 83 Ni, Raney, 3: 15, 67 Nicewicz, David A., 5: 60, 6: 52 Nicholas, Kenneth M., 4: 36, 5: 123, 6: 10 Nichols, Paul J., 2: 120 Nicolaou, K. C., 1: 120, 2: 44, 74, 76, 112, 131, 170, 3: 137, 4: 52, 88, 142, 174, 176, 5: 186, 6: 161 Nielsen, Thomas E., 5: 63 Nikas, Spyros P., 4: 3 Nikonov, Georgii I., 5: 12

Nishibayashi, Yoshiaki, 3: 151, 6: 44, 132 Nishikawa, Toshio, 2: 130, 5: 146, 6: 24 Nishimura, Takahiro, 3: 74, 4: 71, 77, 81, 144, 5: 74, 80, 6: 80 Nishiwaki, Nagatoshi, 6: 132 Nishiyama, Hisao, 2: 7 Nishiyama, Shigeru, 1: 145, 157 Nishiyama, Yutaka, 4: 26 Nishizawa, Mugio, 4: 2, 150 Njardarson, Jon T., 3: 106, 4: 92, 5: 12, 60, 92, 6: 168 Node, Manabu, 3: 69, 4: 157 Noël, Timothy, 6: 32 Nokami, Junzo, 1: 96, 2: 57 Nolan, Steven P., 2: 15, 3: 48, 50 Norton, Jack R., 6: 90 Notestein, Justin M., 5: 56 Novick, Scott J., 2: 162 Novikov, Alexei V., 2: 209, 4: 32, 5: 185 Nozaki, Kyoko, 2: 39, 4: 18 Nugent, Thomas C., 3: 67 Nugent, Willam A., 2: 122, 4: 143 Oba, Makoto, 4: 102 Obora, Yasushi, 4: 34, 5: 11, 46, 6: 46 O’Brien, Christopher J., 6: 42, 48 O’Brien, Peter, 1: 89, 5: 109 Ochiai, Masahito, 3: 38, 126, 4: 19, 48, 54, 5: 4 Ochima, Koichiro, 4: 102 Ochsenfeld, Christian, 6: 15 O’Doherty, George A., 3: 84, 89 Odom, Aaron L., 1: 170 Oelgemöller, Michael, 4: 31 Oestreich, Martin, 5: 21, 6: 22 Ogasawara, Masamichi, 4: 88 Ogawa, Akiya, 4: 46, 48 Oger, Camille, 6: 91 Ogilvie, William G., 5: 55 Ogoshi, Sensuke, 3: 116, 4: 51, 5: 128 Ogoshi, Tomoki, 6: 52 Ogura, Katsuyuki, 3: 123 Oguri, Hiroki, 3: 91 Oh, Kyungsoo, 4: 84, 102, 5: 78, 6: 132 Ohe, Kouichi, 5: 122 Ohira, Susumu, 1: 168, 2: 31 Ohki, Yasuhiro, 5: 21 Ohkuma, Takeshi, 5: 72, 6: 70 Ohmiya, Hirohisa, 5: 54, 55, 6: 66, 71, 72

 29

Paddon-​Row, Michael N., 6: 156 Padwa, Albert, 1: 22, 2: 100, 157, 3: 111, 115 Pagenkopf, Brian, 1: 5, 3: 81, 4: 90, 5: 88 Pagliaro, Mario, 5: 59

Pale, Patrick, 3: 18, 5: 22, 6: 45 Paliappan, Krishna P., 6: 155 Palmieri, Alessandro, 4: 130, 5: 129, 6: 30 Palomo, Claudio, 2: 57, 166, 3: 65, 72, 5: 76, 85, 6: 63 Panek, James, 1: 73, 4: 94, 96, 115, 5: 96, 6: 100 Pansare, Sunil V., 6: 110 Papini, Anna Maria, 2: 44 Paquette, Leo A., 1: 24, 2: 189, 3: 188 Paquin, Jean-​François, 5: 6, 6: 2 Paradies, Jan, 5: 16 Pardo, Domingo Gomez, 5: 8 Pariasamy, Mariappan, 5: 49 Park, Cheol-​Min, 5: 130, 6: 128 Park, Hyeung-​geun, 2: 163, 4: 78, 5: 73, 104 Park, Jaiwook, 1: 88, 2: 13, 3: 8 Park, Kwangyong, 4: 119 Parker, Kathlyn A., 2: 10, 3: 83, 6: 92, 153 Parkinson, Christopher J., 2: 185 Parsons, Andrew F., 2: 21 Parsons, Philip J., 3: 46 Partridge, Ashton C., 3: 36 Passchier, Jan, 5: 9 Patel, Bhisma K., 2: 75, 5: 38, 6: 38 Patel, Sejal, 4: 31 Paterson, Ian, 3: 97, 99, 6: 188 Pathak, Tanmaya, 2: 86, 3: 160, 4: 154 Pearson-​Long, Morwenna S. M., 6: 148 Pederson, Richard L., 4: 62 Pedro, José R., 3: 68 Peese, Kevin M., 6: 56 Pei, Tao, 3: 131 Pelletier, Jeffrey C., 3: 4 Peng, Fangzhi, 6: 144 Peng, Yungui, 6: 75 Percec, Virgil, 4: 118 Perchyonok, V. T., 3: 14 Pereira, Vera L. Patrocinio, 4: 4 Pérez, Pedro J., 6: 8 Pérez-​R amírez, Javier, 6: 30 Periasamy, Mariappan, 6: 49 Pericàs, Miquel A., 4: 31, 5: 28 Perlmutter, Patrick, 6: 44 Petasis, Nicos A., 2: 165 Peters, Jens-​Uwe, 4: 124 Peters, Jonas C., 6: 4 Peters, René, 3: 65, 84, 5: 84 Peterson, Kimberly S., 6: 71

229  Author Index

Ohmura, Toshimichi, 4: 85, 5: 106 Ohno, Hiroaki, 3: 117, 126, 4: 98, 5: 109, 110, 6: 83, 133 Ohshima, Takashi, 5: 5, 6: 22, 24, 116 Ohta, Hidetoshi, 6: 27 Ohta, Tetsuo, 4: 54 Oi, Shuichi, 1: 98 Oii, Takashi, 2: 118 Oikawa, Hideaki, 3: 91 Oisaki, Kounosuke, 6: 5 Ojima, Iwao, 2: 108 Okamoto, Sentaro, 2: 16, 4: 28, 5: 67, 6: 24, 81 Okimoto, Mitsuhiro, 6: 31 Olah, George A., 2: 86 Olivo, Horacio F., 2: 107 Ollivier, Cyril, 5: 94, 6: 14 Ollivier, Jean, 3: 102 Olofsson, Berit, 4: 29 Oltra, J. Enrique, 2: 125, 174 Ong, Tiow-​Gan, 6: 53 Ono, Yusuke, 5: 33 Onomura, Osamu, 4: 20 Ooi, Takashi, 3: 80, 4: 67, 72, 88, 5: 64, 68, 86, 6: 59, 65, 104 Opatz, Till, 4: 112 Orellana, Arturo, 5: 126 Organ, Michael G., 3: 41, 6: 31, 32 Orita, Akihiro, 5: 19, 6: 25 Oriyama, Takeshi, 3: 2 Oshima, Koichiro, 2: 88, 3: 38, 125, 4: 44 Otani, Yuko, 6: 61 Otera, Junzo, 5: 19 Otero, Antonio, 3: 16 Ouchi, Akihiko, 3: 23, 4: 22 Ouellet, Stéphane G., 3: 14 Ovaska, Timo V., 3: 161 Overhand, Mark, 1: 83 Overman, Larry E., 1: 56, 143, 160, 2: 27, 149, 174, 191, 3: 24, 200, 4: 180, 202, 5: 87, 6: 44 Ozerov, Oleg V., 2: 16, 56 Özkar, Saim, 4: 145

Author Index  230

230

Petrov, Ognyan I., 5: 47 Pettus, Thomas R. R., 2: 175 Petursson, Sigthur, 3: 20 Pfaltz, Andreas, 2: 69, 119, 4: 78 Phillips, Andrew J., 1: 180, 2: 121, 3: 41, 87, 4: 59 Phillips, Scott T., 5: 18 Phukan, Prodeep, 6: 14 Piers, Edward, 4: 125, 6: 172 Piers, Warren, 1: 131 Pietruszka, Jörg, 6: 30 Piettre, Serge R., 4: 161, 5: 163 Pihko, Petri M., 2: 99, 3: 90, 6: 65 Pineschi, Mauro, 1: 80 Pinto, Atahualpa, 6: 22 Pitchumani, Kasi, 5: 2 Pizzo, Fernando, 2: 99 Plattner, Dietmar A., 5: 53 Plietker, Bernd, 3: 82, 4: 33 Poelarends, Gerrit J., 6: 68 Pohl, Nicola L. B., 6: 27 Pohmakotr, Manat, 6: 18 Poiakoff, Martyn, 4: 30 Poirier, Donald, 5: 10 Polyzos, Anastatios, 6: 31 Pombeiro, Armando J. L., 4: 32 Popik, Vladimir, 2: 129 Poppe, László, 5: 26 Porco, John A., Jr., 1: 131, 4: 159, 5: 103, 6: 85 Porta, Ombretta, 3: 34 Pospísil, Jirí, 5: 51 Postema, aarten H. D., 1: 194 Potts, Barbara C. M., 1: 196 Poulsen, Sally-​Ann, 2: 49 Poupon, Erwan, 3: 118 Powell, David A., 2: 180, 4: 34 Prabhakar, Sundaresan, 3: 135 Praly, Jean-​Pierre, 5: 84 Prasad, Kavirayani R., 6: 24 Prashar, Sanjiv, 3: 124 Prati, Fabio, 1: 144 Preston, Peter N., 2: 43 Price, Kristin E., 6: 28 Prim, Damien, 3: 123 Pritchard, Gareth J., 4: 91 Procter, David J., 3: 12, 150, 4: 142, 148, 5: 12, 208, 6: 20 Protti, Stefano, 6: 30

Prunet, Joëlle, 4: 86, 6: 145 Pu, Lin, 4: 66 Puglisi, Alessandra, 6: 29 Punniyamurthy, T., 1: 26, 3: 2 Punta, Carlo, 3: 34 Purohit, Vikram C., 6: 9 Py, Sandrine, 6: 63 Pyne, Stephen G., 2: 165, 4: 105 Qi, Xiuxiang, 5: 129 Qin, Yong, 5: 182 Qin, Zhaohai, 6: 34 Qing, Feng-​Ling, 6: 50 Qu, Gui-​Rong, 5: 39 Quan, Junmin, 2: 186 Que, Lawrence, Jr., 3: 82 Quéléver, Gilles, 4: 22 Quideau, Stéphane, 3: 158 Quinn, Kevin J., 1: 186 Quintavalla, Arianna, 5: 142 Radivoy, Gabriel, 2: 15 Radosevich, Alexander T., 5: 16, 70 Raghavan, Sadagopan, 3: 32 Raines, Ronald T., 3: 47, 4: 15, 6: 3 Rainier, Jon D., 2: 50, 3: 46, 4: 143, 148 RajanBabu, T. V., 2: 120, 4: 44, 78, 143, 5: 55 Ram, N. Ram, 3: 34 Rama Rao, K., 2: 18 Ramachandran, P. Veeraghavan, 2: 33, 4: 4 Ramaiah, Kandikere, 4: 19, 5: 16 Ramana, C. V., 5: 121 Ramón, Diego J., 5: 3 Rangappa, K. S., 5: 13 Ranu, Brindaban C., 6: 4 Rao, H. Surya Prakash, 6: 132 Rao, J. Madhusudana, 2: 44 Rao, K. Rama, 4: 6 Rao, P. Shanthan, 4: 23 Rao, Yu, 5: 133, 6: 36, 122 Rassu, Gloria, 1: 52, 6: 141 Ratovelomanana-​Vidal, Virginie, 3: 148, 6: 47 Ravelli, Davide, 6: 88 Rawal, Viresh H., 2: 166, 4: 206, 6: 69 Ray, Jayanta K., 3: 27 Raymond, Kenneth N., 3: 19, 37, 5: 2 Read de Alaniz, Javier, 4: 158, 5: 70

 231

Rombouts, Frederik, 4: 27 Romo, Daniel, 1: 202, 3: 86, 4: 138, 5: 90, 94, 6: 134 Rosales, Antonio, 5: 48 Rota, Paola, 4: 25 Roth, Gregory P., 6: 29 Roush, William R., 1: 174, 2: 31, 62, 3: 152, 182 Rovis, Tomislav, 1: 78, 203, 2: 139, 3: 88, 105, 138, 4: 83, 5: 68, 86, 128, 135, 136, 6: 75, 82, 109, 129 Rowlands, Gareth, 1: 92 Rozen, Shlomo, 2: 13, 3: 4 Ruano, José Luis García, 3: 16, 76, 158, 4: 77, 139 Rueping, Magnus, 3: 82, 4: 68, 5: 5, 140, 6: 108, 131 Russell, Christopher A., 5: 124 Rutjes, Floris P. J. T., 2: 130, 3: 74, 5: 27, 6: 112 Rychnovsky, Scott D., 1: 162, 2: 30, 96, 191, 200, 3: 30, 87, 170, 4: 112, 5: 99, 6: 85 Ryu, Do Hyun, 4: 66, 84, 5: 21, 136, 151 Ryu, Ilhyong, 4: 42, 54, 5: 30, 32, 55, 6: 32, 35, 40, 46 Saá, Carlos, 2: 103 Sab, Carlos, 5: 37 Saba, Shahrokh, 5: 10 Sabitha, Gowravaram, 4: 10, 65 Sabot, Cyrille, 6: 128 Sadow, Aaron D., 6: 108 Saicic, Radomir N., 1: 74, 2: 153, 3: 144, 5: 147, 6: 76, 112 Saikawa, Yoko, 2: 186, 4: 121 Saikia, Anil K., 6: 88 Saito, Akio, 2: 81, 188, 3: 129, 5: 128 Saito, Nozomi, 5: 131 Saito, Susumu, 3: 16, 4: 10 Saito, Takao, 4: 54, 5: 11 Sajiki, Hironao, 2: 86, 3: 20 Sakai, Norio, 3: 8, 5: 6 Samant, Shriniwas D., 2: 39 Sames, Dalibor, 2: 25, 3: 29, 5: 38 Sammakia, Tarek, 1: 203, 2: 198, 3: 162 Sammis, Glenn M., 3: 90, 92, 4: 106, 5: 6, 6: 90 Sánchez, Adrián, 5: 25

231  Author Index

Ready, Joseph M., 2: 62, 97, 3: 67, 5: 55 Reddy, B.V. Subba, 5: 92, 120, 125, 6: 112 Reddy, Chada Raji, 6: 132 Reddy, D. Srinivasa, 4: 158, 5: 121, 159, 6: 26, 150 Reddy, K. Rajender, 4: 14, 15, 5: 19, 6: 20 Reddy, Leleti Rajender, 5: 69 Reddy, Maddi Sridar, 6: 7 Reek, Joost N. H., 5: 77, 6: 53 Reetz, Manfred T., 2: 91, 5: 33, 6: 16, 141 Reeves, Jonathan, 2: 187, 6: 58 Reiser, Oliver, 3: 55 Reisman, Sarah E., 5: 93, 164, 170, 6: 66 Reissig, Hans-​Ulrich, 3: 129, 4: 115, 6: 45 Renaud, Philippe, 2: 126, 3: 25, 40, 4: 17, 54, 5: 56, 57 Reuping, Magnus, 4: 141 Reyes, Efraim, 6: 136 Reymond, Sébastien, 4: 46 Reynolds, Kevin A., 6: 115 Rezaeifard, Abdolreza, 6: 52 Rhee, Hakjune, 3: 3 Rhee, Young Ho, 6: 106 Ribas, Xavi, 4: 48 Ribeiro, Nigel, 4: 9 Ricci, Alfredo, 4: 69 Rice, Kenner C., 6: 128 Richardson, David E., 3: 13 Richert, Clemens, 4: 26 Riera, Antoni, 1: 193, 5: 146 Riguet, Emmanuel, 4: 77 Rincón, Juan A., 5: 27 Rios, Ramon, 3: 108 Ritleng, Vincent, 6: 46 Ritter, Tobias, 4: 10, 5: 8 Robbins, Morris, 1: 175 Roberge, Dominique M., 6: 32 Roberts, Stanley, 1: 191 Robichaud, Joël, 2: 114 Robles, Rafael, 4: 29 Roche, Stéphane P., 6: 65 Rodríguez, Félix, 3: 100 Rodriguez, Jean, 3: 141, 5: 81, 85, 140, 6: 126, 136 Rodríguez-​García, Ignacio, 5: 48 Roelfes, Gerard, 2: 100, 3: 152 Roesky, Peter W., 2: 125 Rojas, Christian M., 3: 92 Rokach, Joshua, 3: 17

Author Index  232

23

Sanford, Melanie S., 1: 157, 2: 82, 3: 41, 124, 4: 34, 5: 55, 122, 6: 118, 207 Santelli, Maurice, 4: 40 Santillo-​Piscil, Fernando, 2: 48 Santoro, Francesco, 6: 60 Santra, Swadeshmukul, 4: 48 Sarandeses, Luis A., 2: 209 Sarkar, Tarun, 1: 140 Sarpong, Richmond, 2: 187, 4: 27, 113, 5: 131 Sartillo-​Piscil, Fernando, 6: 100 Sasai, Hiroaki, 4: 102, 5: 139, 6: 86, 102 Sasaki, Makato, 3: 89 Sasson, Yoel, 5: 13 Sataki, Masayuki, 3: 100 Sato, Fumie, 1: 44 Sato, Ken-​ichi, 2: 191, 6: 21 Sato, Takaaki, 4: 89, 5: 111, 6: 204 Sato, Yoshihiro, 5: 131 Sato, Yoshiro, 3: 145 Satoh, Tetsuya, 6: 124 Satoh, Tsuyoshi, 1: 110, 5: 45, 6: 42 Saudan, Lionel A., 3: 8 Sawamura, Masaya, 3: 65, 84, 4: 80, 5: 54, 55, 6: 66, 71, 72 Scalone, Michelangelo, 6: 106 Scammells, Peter J., 4: 8 Schafer, Laurel L., 1: 1, 2: 195, 3: 151, 4: 40, 5: 110, 6: 50, 53 Schaffner, Carl P., 4: 39 Schafmeister, Christian E., 3: 15 Schaus, Scott E., 1: 66, 2: 62, 133, 172, 3: 80, 5: 80 Scheidt, Karl A., 2: 117, 203, 3: 14, 4: 14, 136, 140, 5: 94, 99, 6: 116, 140 Schmalz, Hans-​Günther, 3: 72, 6: 50 Schmid, Andreas, 1: 35, 5: 26, 105 Schmidt, Bernd, 2: 109, 4: 61 Schnatter, Wayne F. K., 4: 121 Schneider, Christoph, 5: 81, 82, 108 Schomaker, Jennifer M., 5: 61 Schore, Neil E., 6: 165 Schreiner, Peter R., 4: 94, 5: 73 Schrekker, Henri S., 2: 181 Schrock, Richard R., 4: 61, 5: 92 Schrodi, Yann, 3: 45 Schwan, Adrian L., 5: 50 Scott, Colleen N., 4: 24 Seashore-​Ludlow, Brinton, 5: 86

Sedelmeier, Jörg, 4: 19 Seeberger, Peter H., 4: 30, 93, 5: 26, 28, 6: 30 Seeman, Jeffrey I., 5: 13 Seitz, Oliver, 2: 133 Sekar, Govindasamy, 3: 10, 13, 4: 124 Sello, Jason K., 4: 126 Selvakumar, N., 3: 54 Sestelo, José Pérez, 2: 209 Severin, Kay, 2: 178, 6: 124 Shair, Matthew D., 2: 7, 4: 182 Shao, Zhihui, 6: 144 Sharghi, Hashem, 2: 130 Sharma, G. V. M., 1: 144 Sharma, Pallavi, 6: 4 Sharma, Pawan K., 3: 10 Shaw, Jared T., 6: 41 She, Xuegong, 4: 93, 100, 6: 89, 99, 159 Shen, Zhengwu, 5: 125 Sheng, Chunquan, 6: 79 Shenvi, Ryan A., 5: 114, 157, 163, 6: 54 Sheppard, Tom D., 4: 11 Sherburn, Michael, 1: 68, 6: 156 Shi, Bing-​Feng, 6: 36, 37 Shi, Daqin, 6: 123 Shi, Min, 4: 64, 105, 126, 156, 5: 140 Shi, Xiaodong, 3: 108, 4: 44, 74, 5: 2, 5, 45 Shi, Yian, 1: 5, 158, 2: 77, 171, 210, 3: 80, 4: 110, 5: 32, 66, 104, 6: 50 Shi, Zhang-​Jie, 2: 81, 186, 3: 127, 148 Shibasaki, Masakatsu, 1: 56, 90, 98, 159, 2: 3, 52, 57, 74, 87, 111, 166, 3: 61, 74, 4: 74, 75, 81, 86, 89, 142, 5: 71, 78, 84, 144, 6: 70, 74, 76, 78 Shibata, Norio, 5: 70, 6: 9 Shibata, Takanori, 3: 147, 4: 45, 122, 6: 73 Shibatomi, Kazutaka, 5: 69 Shibuya, Masatoshi, 5: 14 Shih, Tzenge-​Lien, 1: 56 Shiina, Isamu, 2: 57, 136, 3: 99, 4: 80 Shimada, Kazuaki, 4: 127 Shimada, Toyoshi, 6: 122 Shin, Dong-​Soo, 6: 81, 118 Shin, Hyunik, 4: 46 Shin, Seunghoon, 3: 144, 5: 58 Shindo, Mitsuro, 2: 187, 4: 94 Shing, Tony K. M., 2: 177, 207, 3: 157, 159, 4: 116, 155, 161 Shintani, Ryo, 3: 107, 4: 72, 143

 23

Somfai, Peter, 3: 108, 123, 5: 86, 87 Somsák, László, 3: 87 Song, Choong Eui, 6: 60 Song, Gonghua, 4: 37 Song, Kwang Ho, 4: 119 Song, Ling, 5: 48 Song, Zhenlei, 5: 92 Song, Zhiguo J., 5: 105 Sonoda, Motohiro, 6: 123 Soós, Tibor, 3: 75 Sordo, José A., 2: 145 Sorenson, Erik J., 2: 65, 123 Sortais, Jean-​Baptiste, 6: 10 Spanevello, Rolando A., 3: 40 Speicher, Andreas, 5: 149 Sperry, Jonathan, 5: 129 Spicer, Mark D., 4: 27 Spino, Claude, 1: 46, 5: 162 Spivey, Alan C., 4: 99 Spring, David R., 3: 96, 5: 10 Sridhar, Perali Ramu, 6: 84 Srikrishna, A., 4: 64, 5: 35 Srogl, Jiri, 4: 15 Stahl, Shannon S., 2: 190, 3: 40, 4: 80, 125, 5: 11, 106, 6: 11 Standen, Michael C., 1: 44 Stark, Christian B. W., 4: 92 Stawinski, Jacek, 4: 47 Stecko, Sebastian, 6: 107, 108 Steel, Patrick, 1: 54 Steinke, Joachim H. G., 2: 49 Stephens, John C., 4: 141 Stephenson, Corey R. J., 4: 10, 28, 35, 5: 28, 30, 58, 6: 17, 85 Stevens, Christian V., 6: 104 Stevenson, Paul J., 6: 140 Stewart, Jon D., 4: 80 Stockdill, Jennifer L., 6: 105 Stocker, Bridget L., 5: 104 Stockman, Robert A., 4: 61 Stoltz, Brian M., 1: 164, 3: 57, 68, 113, 116, 151, 4: 148, 5: 152, 157, 6: 46 Stork, Gilbert, 2: 35, 3: 192, 4: 168 Stradiotto, Mark, 6: 7 Streicher, Hansjörg, 4: 7 Strukul, Giorgio, 2: 177 Studer, Armido, 3: 38, 67, 4: 17, 6: 138 Su, Weiping, 4: 49, 5: 126 Suárez, Alejandra G., 3: 154

233  Author Index

Shipman, Michael, 3: 104 Shiraishi, Yasuhiro, 3: 42, 4: 53 Shirakawa, Eiji, 3: 33, 4: 2 Shishido, Kozo, 3: 151, 5: 73, 118, 147, 163, 6: 143 Sibi, Mukund P., 1: 52, 116, 2: 9, 3: 60, 62, 65, 71, 152, 6: 136 Siciliano, Carlo, 5: 50 Sieburth, Scott McN., 5: 72 Siegel, Dionicio, 6: 33 Sierra, Miguel Á., 3: 154 Sigman, Matthew S., 4: 50, 54, 5: 80, 6: 67, 71 Silva, Artur M. S., 6: 147 Silvani, Alessandra, 1: 70 Silverman, Richard B., 5: 20, 6: 20 Simpkins, Nigel S., 3: 158, 159, 4: 147 Sina, Bu-​Ali, 6: 52 Singaram, Bakthan, 3: 40, 5: 12 Singer, Robert A., 2: 155 Singh, Vinod K., 3: 6, 5: 74 Sinha, Anil K., 4: 124 Sintim, Herman O., 4: 34 Sirkecioglu, Okan, 1: 16 Sivaguru, Jayaraman, 6: 136 Skrydstrup, Troels, 3: 31, 32, 4: 127, 5: 130 Slater, Martin J., 3: 104 Sliwka, Hans-​Richard, 5: 61 Smallridge, A. J., 6: 135 Smith, Amos B. III, 2: 48, 111, 114, 135, 3: 168, 4: 22, 6: 89, 166, 186, 202 Smith, Andrew D., 4: 69, 6: 67, 102, 127 Smith, Martin D., 6: 115 Smith, Milton R., 2: 40, 160 Snaith, John S., 4: 24 Snapper, Marc L., 2: 48, 178, 206, 3: 44, 57, 148, 5: 48, 65 Snider, Barry B., 2: 102, 169, 3: 101, 159, 4: 152 Snieckus, Victor, 6: 19 Snowden, Timothy S., 3: 34 Snyder, Scott A., 4: 155, 5: 102, 6: 37, 153, 156, 194 Söderberg, Björn C. G., 6: 133 Soengas, Raquel G., 6: 147 Sohtome, Yoshihiro, 4: 72 Solin, Olof, 5: 9 Solladié-​Cavallo, Arlette, 1: 92 Soltani, Mohammad Navid, 2: 189, 3: 30

Author Index  234

234

Suárez, Ernesto, 3: 27, 90 Suda, Kohji, 1: 159 Sudalai, Arumugam, 3: 28, 64, 78, 6: 56, 108 Suffert, Jean, 5: 144 Sugai, Takeshi, 3: 38 Sugimura, Takashi, 5: 64, 71, 6: 22, 64 Suginome, Michinori, 3: 126, 4: 85, 5: 106 Suh, Young-​Ger, 4: 67, 113, 5: 150, 6: 91 Sun, Bing-​Feng, 6: 145 Sun, Jianwei, 5: 71, 6: 43, 45, 69, 83, 84 Sun, Wei, 3: 37 Sun, Xing-​Wen, 6: 107 Sun, Zhaolin, 1: 20 Sureshbabu, Vommina, 5: 4 Surya Prakash, G. K., 2: 86 Suzuki, Akira, 4: 129 Suzuki, Keisuke, 2: 101, 4: 78, 6: 95 Suzuki, Ken, 3: 10 Sydora, Orson L., 6: 7 Szabó, Kálmán J., 3: 25, 34, 81, 4: 40, 52, 5: 32, 6: 49 Szostak, Michal, 6: 20 Szymczak, Nathaniel K., 6: 11 Szymoniak, Jan, 5: 57 Taber, Douglass F., 1: 28, 57, 141, 165, 2: 34, 84, 104, 207, 3: 33, 36, 69, 149, 156, 158, 4: 26, 38, 75, 96, 129, 130, 133, 147, 5: 107, 136, 6: 52, 135, 143, 193 Tachibana, Kazuo, 3: 100, 4: 96 Tadano, Kin-​ichi, 4: 75 Taddei, Maurizio, 3: 41, 5: 54 Tae, Jinsung, 4: 154 Taguchi, Takeo, 4: 94 Tajbakhsh, Mahmood, 4: 28 Takacs, James M., 3: 66, 4: 86 Takahashi, Takashi, 2: 66, 3: 145, 5: 26 Takahashi, Tamotsu, 4: 88 Takahata, Hiroki, 3: 56 Takai, Kazuhiko, 4: 49, 51, 5: 44, 51, 121, 130 Takamura, Norio, 2: 160 Takayama, Hiromitsu, 3: 184–​85, 4: 103, 5: 145, 6: 64 Takeda, Kei, 6: 61 Takeda, Takeshi, 1: 11, 2: 21, 205, 5: 87 Takemoto, Yoshiji, 1: 63, 2: 163, 3: 43, 142, 5: 37, 104

Talbakksh, M., 1: 86 Tambar, Uttam K., 5: 38, 70, 6: 55, 111 Tamm, Matthias, 5: 51 Tamooka, Katsuhiko, 2: 92 Tamura, Osamu, 3: 43, 109 Tan, Choon-​Hong, 3: 140, 5: 14, 86 Tan, Derek S., 2: 94, 6: 170 Tan, Kian L., 3: 42, 4: 49, 80, 5: 68, 6: 21, 119 Tanabe, Yoo, 2: 148 Tanaka, Fujie, 1: 152, 3: 63 Tanaka, Ken, 2: 73, 103, 3: 123, 146, 4: 76, 149, 5: 148 Tanaka, Masato, 2: 181 Tanaka, Tetsuaki, 1: 46, 166, 3: 24 Taneja, Subhash Chandra, 3: 86 Tang, Weiping, 3: 148, 4: 45, 149, 5: 98, 6: 94 Tang, Wenjun, 6: 16, 149 Tang, Yefeng, 5: 94, 172, 6: 130 Tang, Yong, 4: 41, 144 Tang, Yun, 2: 203 Taniguchi, Nobukazu, 5: 54 Taniguchi, Tsuyoshi, 4: 54, 5: 8 Tanino, Keiji, 1: 14, 2: 103, 4: 119, 186, 204, 6: 47 Tanner, David, 4: 102 Taoufik, Mostafa, 4: 64 Tatsumi, Kazuyuki, 5: 21 Tayama, Eiji, 4: 108, 5: 20, 124 Taylor, Mark S., 4: 28, 5: 20 Taylor, Paul C., 3: 48 Taylor, Richard E., 3: 87 Taylor, Richard J. K., 3: 96, 4: 100, 116, 5: 119, 161 Taylor, Scott D., 4: 21, 22 Tedrow, Jason S., 3: 8 Tellers, David M., 5: 105 Temelli, Baris, 6: 12 Teo, Peili, 6: 54 Teo, Yong-​Chua, 4: 122 Terada, Masahiro, 2: 120, 4: 67, 91, 92, 5: 78 Terao, Jun, 3: 36 Tevelkar, Vikas N., 3: 10 Theodorakis, Emmanuel A., 4: 95, 5: 157, 166 Theodorou, Vassiliki, 3: 20 Thierry, Josiane, 4: 51

 235

Tu, Yong-​Qiang, 2: 138, 5: 43, 52, 74, 94, 130, 146 Tuck, Kellie L., 3: 14 Tudge, Matthew, 3: Tulla-​Puche, Judit, 6: 25 Tunge, Jon A., 4: 16, 44 Turculet, Laura, 6: 7 Tymann, David, 6: 160 Uchiro, Hiromi, 5: 153, 159 Uchiyama, Masanobu, 1: 101, 2: 78, 3: 38, 130 Uedo, Ikao, 1: 34 Uenishi, Jun’ichi, 2: 130, 4: 101 Ukaji, Yutaka, 4: 88 Umemoto, Teruo, 4: 8 Underwood, Toby, 4: 30 Unverzagt, Carlo, 5: 18 Uozumi, Yasuhiro, 3: 2 Urabe, Hirokazu, 4: 8, 86, 91, 6: 21 Uriac, Philippe, 3: 120 Urlacher, Vlada B., 6: 62 Urpí, Fèlix, 3: 58 Usami, Yoshihide, 6: 57 Uskokovic, Milan, 4: 39 Usuki, Yoshinosuke, 6: 98 Uziel, Jacques, 3: 88 Vaccaro, Luigi, 6: 48 Vakulya, Benedek, 3: 75 Valdés, Carlos, 4: 18, 5: 12, 21, 6: 104 Vallribera, Adeline, 6: 58 van de Weghe, Pierre, 3: 120 van der Marel, Gijsbert A., 5: 24 Van Vranken, David L., 5: 107 Vanderwal, Christopher D., 3: 109, 4: 61, 117, 5: 194 Vankar, Yashwanl D., 2: 130 Varea, Teresa, 5: 53 Vares, Lauri, 6: 86 Vasse, Jean-​Luc, 5: 57, 6: 144 Vatèle, Jean-​Michel, 6: 12, 22 Vazquez, Alfredo, 5: 25 Vederas, John, 1: 54, 2: 38 Veisi, Hojat, 5: 3 Velezheva, Valeriya S., 3: 133 Venkateswarlu, Y., 4: 37 Verardo, Giancarlo, 4: 39 Verdaguer, Xavier, 5: 146

235  Author Index

Thomson, Regan J., 3: 35, 4: 44, 141, 5: 51, 6: 79, 155 Tian, Kian L., 5: 79 Tian, Ping, 5: 74, 6: 142 Tian, Shi-​Kai, 4: 18, 5: 44, 6: 68 Tiefenbacher, Konrad, 6: 20 Tietze, Lutz, 1: 142 Timmer, Mattie S. M., 4: 22, 5: 104 Tius, Marcus A., 3: 40, 4: 136, 5: 146 Tobisu, Mamoru, 3: 127, 4: 13, 5: 35, 6: 120 Tognetti, Vincent, 6: 128 Togo, Hideo, 4: 121, 6: 15, 122 Tokunaga, Makoto, 3: 6, 4: 50, 5: 140 Tokuyama, Hidetoshi, 6: 129 Tomioka, Kiyoshi, 1: 200, 2: 5, 3: 161, 4: 48 Tomioka, Takashi, 4: 44, 5: 46 Tomishige, Keiichi, 4: 13 Tomkinson, Nicholas C. O., 4: 123 Tomooka, Katsuhiko, 3: 116, 5: 3, 22 Tong, Rongbiao, 6: 82, 87, 97, 99 Tong, Shanghai Jiao, 6: 81 Tong, Xiaofeng, 4: 129 Tori, Motoo, 4: 57 Toshima, Kazunobu, 2: 47 Toste, F. Dean, 2: 41, 73, 84, 93, 159, 195, 3: 106, 178, 4: 53, 55, 142, 145, 5: 61, 6: 141 Toullec, Patrick Y., 5: 120 Toy, Patrick H., 4: 6, 47 Toyooka, Naoki, 6: 110 Trabanco, Andrés A., 4: 27 Trapp, Oliver, 6: 31 Trauner, Dirk, 1: 1, 2: 26, 3: 155, 157, 4: 153, 5: 114, 6: 15, 23, 151, 198 Trofimov, Boris A., 6: 49 Troisi, Luigino, 4: 42 Tropak, Michael B., 6: 105 Trost, Barry M., 2: 32, 108, 139, 146, 163, 193, 3: 82, 95, 103, 113, 146, 202, 4: 49, 82, 104, 108, 111, 148, 166, 194, 5: 84, 108, 144, 6: 117, 132, 182 Trudell, Mark, 1: 41, 6: 4 Tsai, Yeun-​Mi, 4: 154 Tsanaktsidis, John, 5: 10 Tsuji, Yasushi, 3: 6, 134, 6: 10 Tsukada, Naofumi, 6: 124 Tsukamoto, Hirokazu, 3: 18, 6: 148 Tu, Shu-​Jiang, 5: 131

Author Index  236

236

Verkade, John K., 2: 155 Vesely, Jan, 3: 108 Vicario, Jose L., 5: 104, 138, 6: 102, 136 Vicente, José, 6: 23 Vicente, Rubén, 5: 132 Vidal-​Ferran, A., 2: 77 Vidari, Giovanni, 4: 27 Vijaykumar, Pujari, 5: 23 Vilarrasa, Jaume, 3: 16, 58, 4: 2, 6, 29, 5: 3, 25 Villar, Ramón, 2: 49 Vincent, Guillaume, 4: 63, 5: 163 Vincent, Jean-​Marc, 3: 86 Vinod, Thottumakara K., 2: 76, 4: 54 Vishwakarma, Ram A., 5: 33, 124 Vogel, Pierre, 1: 60, 144 Vogt, Dieter, 3: 41, 4: 8 von Zezschwitz, Paultheo, 6: 142, 147 Wagener, Kenneth B., 6: 14 Waldmann, Herbert, 6: 134 Wallace, Debra J., 4: 60 Walsh, Patrick J., 1: 66, 152, 2: 3, 61, 69, 3: 130, 5: 71, 126, 6: 120 Walters, Iain A. S., 2: 83 Walton, John C., 5: 50 Wan, Boshun, 5: 134 Wan, Wen, 6: 120 Wang, Baiquan, 5: 134 Wang, Chun-​Jiang, 3: 108, 6: 59, 61 Wang, David Zhigang, 5: 53 Wang, Deping, 6: 120 Wang, Ge, 3: 6 Wang, Hong, 4: 140 Wang, Jeh-​Jeng, 5: 133 Wang, Jianbo, 3: 104, 4: 47, 120, 133, 5: 44, 51, 120, 6: 36, 121 Wang, Jianhui, 4: 62 Wang, Li-​Xin, 6: 61, 138 Wang, Limin, 4: 132 Wang, Mei-​Xiang, 3: 66 Wang, Pengfei, 3: 19, 4: 29, 5: 18 Wang, Quanri, 3: 148, 5: 49, 145 Wang, Shao-​Hua, 5: 130 Wang, Wei, 2: 9, 203, 3: 20, 79, 106, 4: 74, 5: 76, 108, 6: 79, 135 Wang, Xiaolai, 2: 75 Wang, Yanguang, 3: 135, 6: 124 Wang, Yong-​Qiang, 6: 54

Wang, Youming, 5: 72 Wang, Zhigang, 5: 53 Wang, Zhiyong, 6: 64 Wang, Zhong-​Xia, 4: 124 Wang, Zhongwen, 5: 93 Wardrop, Duncan J., 2: 135, 4: 108 Waser, Jérôme, 5: 122, 6: 103, 126, 144 Watanabe, Takumi, 6: 78 Watanabe, Yoshihito, 5: 33 Watanabe, Yutaka, 6: 27 Waters, Stephen P., 6: 111 Watson, Donald A., 5: 9, 36 Watson, Mary P., 5: 80 Watts, P., 5: 26 Waymouth, Robert M., 6: 8 Weck, Marcus, 3: 60 Wee, Andrew G. H., 2: 180, 5: 40 Wei, Xudong, 2: 152, 182 Wei, Yunyang, 6: 38 Weibel, Jean-​Marc, 6: 45 Weinreb, Steven M., 4: 27, 43, 6: 107 Weissman A., Steven, 2: 21 Weix, Daniel J., 4: 120, 5: 44, 48, 50, 6: 54, 148 Weller, Andrew S., 2: 178 Wendeborn, Sebastian, 2: 147 Wender, Paul A., 2: 104, 5: 161 Wennemers, Helma, 3: 75, 6: 77, 79 Werner, Michael, 6: 30 Werner, Thomas, 6: 48 Wessjohan, Ludger A., 2: 181 West, Frederick G., 3: 106 Westermann, Bernhard, 2: 62 Westwood, Nicholas J., 6: 156 Wharton, Peter S., 6: 169 Whitby, Richard J., 5: 147 White, James D., 3: 97, 6: 146 White, M. Christina, 2: 18, 134, 210, 3: 24, 40, 4: 33, 34, 84, 5: 36, 6: 34, 36, 55 White, Timothy D., 6: 32 Whitehead, Roger C., 1: 200 Whiting, Andrew, 5: 134, 6: 60 Wicha, Jerzy, 2: 102 Widenhoefer, Ross A., 2: 92, 137, 5: 106 Widlanski, Theodore S., 1: 144 Wiemer, David F., 5: 89, 6: 127 Wijayantha, K. G. Upul, 6: 18 Wiles, Charlotte, 4: 30, 5: 26

 237

Xi, Chanjuan, 6: 2 Xia, Chungu, 3: 37 Xia, Wujiong, 6: 3 Xiang, Jiannan, 6: 5, 11

Xiao, Jianliang, 3: 35, 4: 66, 6: 12 Xiao, Wen-​Jing, 1: 184, 2: 67, 4: 134, 140, 5: 24, 133, 6: 88 Xiao, Yumei, 6: 34 Xie, Jian-​Hua, 5: 147, 148 Xie, Jian-​Wu, 4: 94 Xie, Shiping, 3: 104 Xie, Wei-​Jia, 6: 98 Xie, Xingang, 4: 100, 6: 159 Xu, Bin, 4: 38 Xu, Bo, 3: 16, 5: 11 Xu, Feng, 4: 66, 105 Xu, Hao, 5: 138, 6: 56, 75 Xu, Hua-​Jian, 5: 120, 6: 7, 43 Xu, Jian-​He, 2: 161 Xu, Jiaxi, 6: 56 Xu, Ming-​Hua, 2: 62, 3: 63 Xu, Peng-​Fei, 5: 141, 142, 6: 106 Xu, Qing, 5: 8 Xu, Wei-​Ming, 4: 26 Xu, Xianxiu, 6: 131 Xu, Xiao-​Ying, 6: 61 Xu, Yun-​He, 6: 53 Xu, Zhen-​Jiang, 3: 104 Yadav, J. S., 2: 18, 197, 3: 1, 4, 11, 30, 31, 36, 92, 122, 123, 4: 143, 6: 77, 86, 89 Yadav, Lal Dhar S., 6: 17 Yamada, Hidetoshi, 5: 103 Yamada, Tohru, 4: 70, 6: 68 Yamagami, Takafumi, 6: 70 Yamaguchi, Junichiro, 5: 52 Yamaguchi, Masahiko, 2: 125 Yamaguchi, Ryohei, 2: 55, 4: 6, 5: 14–​15 Yamamoto, Hisashi, 1: 62, 118, 158, 2: 61, 76, 117, 165, 171, 198, 3: 61, 78, 152, 4: 82, 86, 135, 136, 6: 20, 58, 78 Yamamoto, Yoshinori, 2: 37, 40, 137 Yamamura, S., 4: 18 Yamashita, Makoto, 4: 18 Yamashita, Shuji, 5: 168 Yamazaki, Takashi, 4: 93 Yan, Ming, 4: 136 Yan, Tu-​Hsin, 1: 148 Yanagisawa, Akira, 3: 127, 5: 129 Yang, Dan, 2: 172, 4: 6, 16 Yang, Hai-​Tao, 5: 90 Yang, Hengquan, 4: 64 Yang, Jiong, 5: 137

237  Author Index

Williams, Craig M., 3: 208–​09, 4: 24, 5: 10, 198 Williams, David, 1: 42, 2: 208, 4: 162 Williams, Jonathan M. J., 1: 26, 156, 2: 189, 3: 2, 10, 16, 4: 3, 19, 5: 7 Williams, Lawrence J., 1: 172 Williams, Robert M., 4: 158, 5: 154 Williard, Paul G., 1: 176, 2: 210, 4: 9, 5: 35 Willis, Christine, 2: 135, 5: 60, 92, 6: 83 Willis, Michael C., 2: 178, 3: 76 Winssinger, Nicolas, 2: 112, 192 Wipf, Peter, 3: 135, 4: 133, 5: 134 Wirth, Thomas, 4: 30, 6: 31, 32 Wise, Christopher, 5: 48 Wishka, Donn G., 4: 109 Woehl, Pierre, 5: 29 Woerpel, Keith A., 3: 4, 5: 87, 6: 88 Wolf, Christian, 2: 144, 6: 62 Wolfe, John, 1: 138, 2: 134, 4: 92, 104, 106, 6: 82 Wong, Chi-​Huey, 3: 103 Wong, Henry N. C., 4: 151 Wong, John W., 6: 70 Wong, Man-​Kin, 2: 146, 5: 20 Wood, John L., 3: 186, 5: 53 Wood, Mark E., 3: 28 Woodward, R. B., 2: 35 Woodward, Simon, 1: 204, 2: 3 Workentin, Mark S., 6: 26 Wright, Dennis L., 5: 97, 6: 153 Wright, Stephen W., 4: 28 Wu, Bin, 6: 39 Wu, Jie, 3: 120, 4: 122 Wu, Jun, 6: 118 Wu, Li-​Zhu, 6: 10 Wu, Wenjun, 5: 58 Wu, Xiao-​Ming, 6: 98 Wu, Xiaoyu, 4: 82 Wu, Xin-​Yan, 6: 130 Wu, Yikang, 5: 43 Wu, Yun-​Dong, 1: 114, 3: 84 Wulff, Jeremy E., 4: 39, 158 Wulff, William D., 2: 195, 3: 147, 4: 106, 6: 155

Author Index  238

238

Yang, Jun, 6: 84, 130 Yang, Qing, 5: 45 Yang, Shang-​Dong, 6: 55 Yang, Shaorong, 6: 90 Yang, Xian-​Jin, 6: 84 Yang, Xiaodong, 6: 23 Yang, Zhen, 1: 201, 2: 186, 4: 60, 196, 5: 94, 145, 159, 172, 6: 115 Yao, Ching-​Fa, 1: 108 Yao, Qizheng, 4: 160 Yao, Xiaojun, 4: 42 Yao, Yingming, 6: 131 Yavari, Issa, 4: 11, 158 Yazaki, Ryo, 6: 22 Ye, Jinxing, 3: 140, 142, 4: 140, 5: 78, 79, 104 Ye, Long-​Wu, 6: 108 Ye, Song, 5: 67, 74 Ye, Xin-​Shan, 5: 90, 6: 87 Yeung, Ying-​Yeung, 4: 35, 5: 34, 95, 6: 84 Yi, Chae S., 6: 27 Yin, Biaolin, 5: 131 Yin, Dali, 3: 134 Yin, Shuang-​Feng, 5: 10, 6: 18 Ying, Jackie Y., 3: 51 Yinghuai, Zhu, 4: 60 Yokoshima, Satoshi, 6: 113, 117 Yonehara, Koji, 5: 57 Yoon, Tehshik P., 3: 38, 4: 52, 53, 154, 5: 70, 93, 6: 128 Yoon, Yong-​Jin, 4: 24 Yorimitsu, Hideki, 2: 88, 3: 15, 38, 125, 4: 44, 102 York, Mark, 5: 27 Yoshida, Hiroto, 2: 185 Yoshida, Hisao, 3: 124, 6: 28 Yoshida, Jun-​ichi, 2: 104, 5: 29, 31, 126, 6: 28, 30 Yoshida, Kazuhiro, 3: 127, 5: 129 Yoshida, Masanori, 3: 77, 5: 139 Yoshida, Mashiro, 3: 132, 4: 126 Yoshida, Suguru, 6: 25 Yoshikai, Naohiko, 5: 134, 135 Yoshimi, Yasuharu, 3: 5, 4: 42, 6: 44 Yoshimitsu, Takehiko, 3: 24, 5: 40 You, Shu-​Li, 4: 6, 157, 5: 137, 143, 6: 104, 136 Youn, So Won, 5: 53 Young, Damian W., 5: 63, 6: 42, 51

Yu, Biao, 3: 104 Yu, Chan-​Mo, 1: 150, 2: 95, 3: 89, 4: 110, 5: 64 Yu, Hongwei, 4: 70 Yu, Jin-​Quan, 1: 1, 3: 26, 121, 124, 4: 32, 36, 78, 118, 124, 125, 127, 129, 5: 39, 40, 123, 127, 6: 35, 39, 119, 120, 125, 144 Yu, Wing Yiu, 4: 67, 123 Yu, Xiao-​Qi, 2: 189 Yu, Zhengkun, 1: 184, 6: 13 Yu, Zhi-​Xiang, 3: 147, 4: 144, 148, 5: 58, 147, 6: 44 Yuan, Wei-​Cheng, 5: 83 Yuan, Yan-​qin, 6: 11 Yudin, Andrei K., 3: 160, 4: 104 Yun, Jaesook, 4: 74 Yus, Miguel, 2: 15, 5: 68, 6: 59 Zacuto, Michael J., 3: 18, 4: 93 Zakarian, Armen, 3: 81, 190, 4: 107, 5: 91, 6: 95, 157 Zaman, Shazia, 4: 60, 5: 62 Zanardi, Franca, 5: 82, 6: 141 Zanoni, Giuseppe, 4: 27 Zard, Samir, 1: 23, 3: 34, 39, 4: 161, 5: 58 Zarei, Amin, 4: 118 Zeitler, Kirsten, 2: 146, 5: 72 Zemribo, Ronalds, 6: 110 Zeng, Wei, 5: 20 Zeng, Xiaoming, 6: 121 Zeng, Xingzhong, 6: 73 Zercher, Charles K., 2: 207 Zhai, Hongbin, 3: 105, 114, 151, 6: 152 Zhang, Ao, 4: 160 Zhang, Chen, 4: 38 Zhang, Fu-​Ming, 5: 43, 52 Zhang, Hong-​Kui, 5: 116 Zhang, Hongbin, 4: 83, 6: 23 Zhang, Ji, 4: 83 Zhang, Junliang, 6: 45, 146 Zhang, Li, 3: 17 Zhang, Liming, 2: 103, 182, 206, 3: 11, 90, 118, 4: 94, 108, 6: 9, 146 Zhang, Qi, 6: 27 Zhang, Qian, 4: 132, 6: 126 Zhang, Quanxuan, 6: 22 Zhang, Song-​Lin, 6: 44 Zhang, Wanbin, 4: 72, 5: 142

 239

Zhong, Guofu, 1: 152, 3: 84, 138, 140, 4: 134 Zhou, Bing, 6: 131 Zhou, Gang, 3: 123 Zhou, Hongwei, 6: 132 Zhou, Jianrong (Steve), 5: 75, 151, 6: 53, 142 Zhou, Qi-​Lin, 2: 120, 3: 118, 4: 70, 73, 103, 5: 77, 111, 147, 148, 6: 16, 63, 67 Zhou, Xiang, 4: 73 Zhou, Xiangge, 5: 54 Zhou, Yong-​Gui, 1: 48, 2: 91, 3: 67, 4: 68, 5: 68 Zhou, Yongbo, 6: 18 Zhou, Zhenghong, 5: 72 Zhu, Chengjian, 4: 66, 5: 6, 6: 11 Zhu, Gangguo, 5: 44 Zhu, Jieping, 2: 21, 3: 66, 69, 105, 4: 69, 5: 118, 133, 6: 41, 43, 61, 73 Zhu, Shou-​Fei, 6: 63, 146 Zhuan, Zhuang-​ping, 3: 132 Zimmer, Reinhold, 6: 45 Zoghlami, H., 3: 40 Zou, Gang, 5: 82, 6: 85 Zou, Jian-​Ping, 4: 120 Zubia, Eva, 5: 114 Zutter, Ulrich, 3: 159

239  Author Index

Zhang, Wannian, 6: 79 Zhang, Wei, 4: 120 Zhang, Weige, 3: 22 Zhang, X. Peter, 3: 144, 150, 4: 36, 146, 5: 34, 110 Zhang, Xinhao, 6: 72, 151 Zhang, Xumu, 1: 88, 2: 59, 3: 42, 4: 78, 5: 58, 6: 61, 106 Zhang, Yan, 6: 36 Zhang, Yihua, 4: 89 Zhang, Yong Jian, 6: 81 Zhang, Yuhong, 4: 33, 5: 135 Zhang, Zhaoguo, 3: 64, 6: 47 Zhao, Gang, 4: 136, 5: 82, 6: 85, 140 Zhao, John Cong-​Gui, 3: 86, 5: 143, 6: 75, 139 Zhao, Kang, 2: 160, 3: 131, 135, 5: 129, 133, 6: 34 Zhao, Matthew M., 2: 56 Zhao, Yingsheng, 6: 123, 131 Zhaorigetu, Bao, 6: 6 Zhdankin, Viktor V., 1: 176, 2: 185, 3: 16 Zheng, Nan, 4: 131, 6: 160 Zheng, Wen-​Hua, 6: 72 Zheng, Xiao, 4: 108, 5: 110 Zheng, Zhuo, 2: 163, 4: 76

240

 241

Reaction Index

Acid (Amide, Ester) Aldol, intramolecular 1: 202 Aldol, with thioester 2: 147 α-​Alkenylation, enantioselective 5: 77 Alkylation Intermolecular, enantioselective 3: 77 4: 77, 79 6: 71, 73 Intramolecular 1: 14, 39, 201 6: 148 Alkynyl, reduction to alkenyl 5: 10 Amide ester, from amino acid 5: 19 Amide from acid 6: 2 Amide from acyltrifluoroborate 5: 5 Amide from alcohol 5: 6 Amide from aldehyde 2: 190 3: 14 5: 11 Amide from alkene, cleavage 6: 3 Amide from alkene, homologation 6: 50 Amide from amide 2: 76, 190 5: 4, 5, 7, 9 Amide from amine 6: 12 Amide from azide 3: 17 5: 6 Amide from ester 2: 190 Amide from isocyanate 4: 10 Amide to aldehyde 6: 17, 19 Amide to aldehyde 6: 17, 19 Amide to amine, reduction 6: 14, 16 Amide to enamine 4: 12 Amide to ester 6: 2 α-​Amination 5: 71 α-​Amino, to aldehyde, one carbon loss 6: 15 Anhydride, enantioselective opening 2: 59 4: 136 6: 62 α-​Arylation, enantioselective 5: 75 Conjugate addition to acceptor, enantioselective 3: 71, 104 4: 75 Ester from alcohol 3: 15 Ester from alcohol, homologation 3: 32 4: 42 Ester from alcohol, oxidation 6: 15

Esterification, enantioselective 6: 70, 71, 73 From alcohol 1: 26, 75, 76 4: 4, 91 5: 11 6: 8, 11, 12, 15 From aldehyde (one carbon addition) 2: 21 From aldehyde (oxidation) 1: 17 2: 21, 144 3: 4, 12, 15 4: 19 5: 15 6: 28 From aldehyde, α,β-​unsaturated 6: 5 From alkene (one carbon addition) 1: 148 3: 41 4: 55 6: 53 From alkene (two carbon addition) 1: 122 3: 41 4: 33, 51, 53, 55 From alkyne 2: 43, 86, 146, 190 3: 5 4: 11 6: 2, 7, 12 From amide 5: 4, 18 6: 2 From amine 2: 44 3: 11 4: 17 From amine, oxidation 5: 11 From amino alcohol, oxidative cleavage 6: 15 From aryl mesylate 3: 32 From C-​H 4: 32, 34, 36 From halide 4: 46 From ketone 1: 20, 113, 139 2: 76 4: 38 From nitrile 2: 43 6: 2 From sulfone 5: 11 From thioacid 5: 6 From unsaturated acid, enantioselective 6: 15 Halo, to alkyl amide, enantioselective 2: 6 α-​Halo, to α-​diazo 4: 15 Halogenation, enantioselective 1: 119 Halolactonization, selective 2: 97 Hydrolysis 5: 19 Hydrolysis, enzymatic 2: 48 4: 27, 70 6: 164, 172, 174, 201 α-​Hydroxylation 5: 166, 172 α-​Hydroxylation, enantioselective 2: 161

Reaction Index  242

24

Acid (Amide, Ester) (cont.) Protection (see Protection) Protonation, enantioselective 4: 72 5: 81 Resolution 4: 80 Sulfinylation 4: 15 Thioester from aldehyde 6: 11 To alcohol 2: 86 3: 8, 12, 14 4: 12, 18 6: 19 To alcohol, homologation 5: 12, 16, 29 To alcohol, one carbon lost 6: 15, 171 To aldehyde 2: 53, 189 3: 8 4: 5 5: 12, 16, 29 6: 2, 5 To alkene (loss of carbon) 1: 157 To alkyne (one carbon added) 1: 107 3: 31 To allyl silane 1: 195 To amide 3: 5, 11, 12, 15–​17 4: 3, 5, 9 5: 3, 4, 7, 9, 26 To amine 2: 21 4: 17, 18 5: 12, 50 To amine (loss of carbon) 1: 100, 184 2: 23, 27, 44 4: 5, 70 5: 4, 9, 179 6: 13, 111 To anhydride, mixed 5: 3 To epoxy ketone (homologation) 1: 149 To ester 5: 20 To ester, one carbon homologation 1: 106 To ester, two carbon homologation 5: 29 6: 44 To ether 3: 9 To hydride (one carbon loss) 2: 26, 29, 158 3: 5 5: 10, 12 6: 7, 173 To α-​hydroxy amide 5: 14 To ketone, homologation 1: 11, 109, 163 2: 117 4: 101 5: 48 6: 31, 197 To β-​keto ester 2: 148 5: 46 To nitrile 1: 12 2: 43 4: 3 6: 7, 28 To nitrile (one carbon loss) 2: 190 To nitrile (homologation) 3: 32 6: 44 To nitro alkene (loss of carbon) 2: 44 To sulfide 5: 6 To sulfide, loss of carbon 6: 7 To thioacid 5: 4 To trifluoromethyl 4: 8 Unsaturated, conjugate addition 1: 150, 166 2: 149, 163 4: 91 5: 48 6: 107, 111 Unsaturated, conjugate amination 6: 109

Unsaturated, enantioselective conjugate addition 3: 73, 74, 75, 77, 79, 83, 101, 138, 143, 192 4: 71, 74, 76, 79, 81, 83, 87 5: 79–​81, 86 6: 67, 70, 72, 77, 116, 136, 142, 149 Unsaturated, enantioselective nitrile addition 1: 150 5: 74 Unsaturated, enantioselective OH addition 1: 177 Unsaturated, from alkene 6: 55 Unsaturated, from alkynyl aldehyde 2: 146 Unsaturated, from propargyl alcohol 6: 7 Unsaturated, enantioselective reduction 3: 42, 72, 74 4: 70, 71, 85 5: 74, 77 6: 70 Unsaturated, to alkenyl halide 4: 7 Acyl anion (radical) 1: 23 2: 68 4: 43, 67, 76, 106 5: 5, 143 6: 30, 46, 48, 82, 109, 137 Alcohol Allylation, enantioselective 3: 68 4: 84 5: 82, 176 Allylic, from alkyne 5: 32 Allylic, from allylic alcohol, enantioselective 2: 162 4: 74 Allylic, from halide, enantioselective 2: 162 Allylic, hydrosilylation, enantioselective 5: 73 Allylic, to aldehyde 2: 146 4: 3, 11 Allylic, to alkene 3: 14, 36 4: 5 Allylic, to alkyl 4: 80 Allylic, to allylic alcohol 5: 47 Allylic, to allylic alcohol, enantioselective 2: 161 5: 64 Allylic, to allylic amine 6: 65 Allylic, to allylic ether 5: 8 Allylic, to amino alcohol 3: 134 Allylic, to enone 3: 13, 34 Allylic, to ketone 5: 2 Allylic, to unsaturated sulfone 4: 6 Benzylic, enantioselective allylation 1: 178 Dehydration 1: 25 5: 185 6: 3 From acid, loss of carbon 6: 15 From aldehyde 5: 16 6: 10 From alkene 2: 10 4: 50, 54

 243

To ketone 1: 26, 41, 86, 176 2: 13, 143 3: 2, 6 4: 14 5: 15 6: 8, 11, 13, 14 To ketone, C-​C cleavage 4: 79 To ketone, enantioselective 1: 89 To ketone, homologation 4: 42 To mercaptan 3: 12 4: 3 To nitrile 3: 30 5: 9, 46 To nitrile, homologation 6: 46 To phosphonium salt 2: 85 To sulfonate, inversion 5: 8 Unsaturated, to aldehyde, enantioselective 6: 67, 71 Aldehyde Aldol, enantioselective 3: 79, 81, 88, 104 44: 76 Alkylation, enantioselective 4: 80 5: 72, 74, 75 6: 68, 70 α-​Allylation 3: 35 α-​Allylation, enantioselective 3: 71, 73 α-​Amination 4: 127 α-​Amination, enantioselective 3: 65, 67, 78 5: 64 6: 61, 63 Conjugate addition to acceptor, enantioselective 3: 77, 86, 137 5: 72, 75, 79, 81, 83 Decarbonylation 3: 111 4: 68, 181 5: 11 From acid 2: 53, 189 5: 12, 16, 29 6: 10, 17, 31 From alcohol 1: 41 3: 3, 6 4: 14, 39 6: 15 From aldehyde, one carbon lost 5: 53 From alkene 1: 148 2: 78, 126 4: 50, 68 6: 53, 57, 79, 104, 196, 197 From alkene, enantioselective 2: 59 3: 42 4: 78 From alkyne 2: 86 3: 16 4: 11 6: 7 From allylic alcohol 2: 146 4: 3, 11 From allylic alcohol (one carbon homologation) 1: 148 From amide 6: 17, 19 From amine 5: 15 From α-​amino acid 6: 15 From epoxide 1: 159 6: 7, 129 From ether 4: 4 From halide 3: 14 From hydride, benzylic 5: 13 From nitrile 5: 26 6: 19 From nitro 4: 19 From silyl ether 6: 15

243  Reaction Index

From alkyne 5: 17 From allylic sulfide 2: 4 From amine 5: 8 From C-​H 4: 34, 36 From epoxide 3: 8 From ester 3: 12 From ester, homologation 5: 44 From ketone 3: 2 5: 18, 21, 30 From ketone, enantioselective 1: 2, 88 3: 60, 64 4: 68 5: 64, 66, 70, 85 6: 16, 59, 60, 63–​65, 82, 206 From nitro 3: 85 From oxazoline 3: 14 From silyl 6: 187 From sulfone 5: 5 Homologation 2: 55 Oxidative cleavage 2: 198 5: 15 Propargylic, to α-​acetoxy ketone 5: 5 Propargylic, to enone 2: 182 3: 114: 11, 44 5: 2 Propargylic, to epoxy imine 5: 5 Propargylic, to α,β-​unsaturated amide 6: 7 Protection (see Protection) To acid 1: 26 2: 2, 75, 76, 143, 144 3: 13 6: 8, 11, 12, 15 To acid, homologation 3: 32 4: 42 To alcohol, homologation 6: 48 To aldehyde 1: 41 2: 13, 75, 95 3: 3, 6 4: 14, 39 6: 15 To alkene 6: 3 To alkyl 6: 42 To alkyne 5: 47 To amide 3: 7 To amine 1: 56, 136, 156, 160, 161, 188 2: 34, 63, 145, 161, 189, 195 3: 4, 16 4: 6, 8 5: 3, 5 6: 3, 4, 6 To aryl ketone 3: 35 To azide 2: 189 3: 15 5: 5 To enone 4: 14 To ester 5: 11 6: 15 To ester, homologation 4: 42 To ester, inversion 5: 8 To ether 6: 3 To halide 1: 156 2: 85, 189 4: 2, 6, 166, 168 5: 5, 6, 8 6: 4, 6 To hydride 1: 195, 198 2: 16, 55, 133 3: 10 5: 30, 209 6: 14, 17

Reaction Index  244

24

Aldehyde (cont.) From telluride 4: 22 Halo, to epoxide, enantioselective 4: 71 α-​Halogenation, enantioselective 1: 119 3: 82 5: 69 Homologation 2: 178, 181 3: 34–​37 4: 43, 44, 47, 67, 69, 71–​74, 76 5: 47 6: 30, 31, 44, 85 Multiple centers, enantioselective 1: 6, 42, 47, 51, 55, 63, 64, 92, 95, 114, 116, 117, 124, 125, 152, 153, 163, 166, 189, 200 2: 2, 7, 8, 9, 10, 19, 20, 31, 61, 62, 67, 89, 121, 122, 165, 166, 196, 197, 199, 203, 204 3: 78, 89, 95 4: 82–​90, 92, 93, 97, 100, 145 5: 78, 82–​84, 86, 87 6: 49, 74–​81, 100, 103, 110, 176, 188, 189, 196, 197 Single center, enantioselective 1: 4, 62, 65, 66, 95, 96, 114, 150, 178 2: 56, 57, 59, 89, 117, 118, 119, 162, 197, 198 3: 30, 61–​71, 73–​78, 86, 95 4: 66, 67, 69, 71–​73, 76, 77, 79, 98, 194 5: 29, 65, 67–​69, 72, 74, 78, 79, 100, 164, 176 6: 59–​63, 65, 70, 92, 176, 200, 203 α-​Hydroxylation, enantioselective 1: 152 2: 1 3: 61, 64, 84 4: 66 5: 64, 84 α-​Methylenation 2: 99 5: 171 α-​Sulfinylation, enantioselective 2: 4 To acid 3: 3, 10 4: 19 5: 15 6: 28 To acid (one carbon addition) 2: 21 3: 34 To alcohol 5: 16 6: 10, 15 To alkene 2: 22, 56 4: 166 To alkyl 6: 125 To alkyne (homologation) 1: 82 2: 148 3: 37 4: 104, 166 6: 193 To alkyne (same carbon count) 2: 146 To allylic alcohol (two carbons added) 2: 147 To amide 2: 190 3: 7, 13, 14 5: 11, 15 To aminal 5: 9 To amine 3: 12 4: 199 6: 60 To amine, with homologation 1: 26 2: 8, 21, 58, 62, 118, 195, 196 4: 67, 69, 72, 82, 85 To amine, one carbon loss 3: 7 To amino alcohol, homologation 3: 34 5: 78

To α-​bromo unsaturated ester, homologation 3: 33 To 1,1-​dihalide 1: 87 4: 185 To enone 6: 46 To epoxide 1: 44 To ester 3: 11, 14 To ester, α,β-​unsaturated 6: 179 To ether 1: 16, 86 3: 2 To halide 3: 4 To haloalkene, homologation 3: 36 To α-​keto aldehyde 5: 13 To ketone 2: 56, 147 3: 34 4: 30, 40 To ketone, cleavage 6: 3 To nitrile 3: 7, 11 5: 7 To phenol (one carbon loss) 4: 19 5: 15 To unsaturated ester 3: 36 To unsaturated ketone 3: 31, 36 Unsaturated, conjugate addition 3: 57 6: 125, 127 Unsaturated, conjugate amination 3: 84 Unsaturated, enantioselective conjugate addition 3: 73, 77, 79, 109, 137, 138, 143, 178 4: 74, 77, 79, 89 5: 76, 81, 83 6: 60, 67, 79, 137–​141, 144, 145, 202 Unsaturated, enantioselective conjugate reduction 2: 6 4: 80 6: 68 Unsaturated, enantioselective epoxidation 2: 14, 121 Unsaturated, enantioselective homologation to epoxy alcohol 1: 152 Unsaturated, from alkene 6: 181 Unsaturated, from ketone 6: 202 Unsaturated, from propargylic alcohol 2: 146 Unsaturated, to ester 6: 5 Aldol, intermolecular, enantioselective 4: 136–​138, 142 5: 82 6: 60, 62, 65, 70, 76–​78, 80, 165, 175, 177, 183 Aldol, intramolecular 4: 135, 137, 141, 143, 148, 182, 187, 193 5: 159, 181, 205, 208, 211 6: 137, 151, 163, 187, 209 Aldol, intramolecular, enantioselective 4: 117, 136, 139, 141 5: 94, 137, 166 Alkaloid synthesis 1: 8, 9, 12, 58, 82, 84, 112, 134, 136, 146, 188, 190 2: 11, 26, 27, 35, 37, 38, 45, 48, 63, 74, 79, 91, 97, 100, 107, 108, 111, 139, 140,

 245

Alkene Acylation 3: 41 Aminoalkoxylation 3: 92, 98, 106 4: 53 Amino fluorination 6: 50 Arylation 3: 119, 120 4: 49, 51, 53, 55, 78 5: 120–​123, 125–​127 Arylation, enantioselective 4: 79 Carbonylation, enantioselective 6: 51 Diamination, enantioselective 3: 80 6: 50 Dihydroxylation 3: 113 4: 4, 50, 54, 57, 90, 92 5: 31, 54 Dihydroxylation, enantioselective 4: 68 5: 84 Epoxidation 1: 35 2: 77, 98 3: 38, 42, 60 4: 48 5: 14, 56 6: 29, 52–​54, 56 Epoxide, enantioselective 1: 59 3: 40, 60 4: 86, 168 6: 59, 60 Ethenylation, enantioselective 4: 78 5: 55 From acid, one carbon loss 1: 157 2: 44 6: 46 From alcohol 5: 185 6: 3 From alkene 2: 177 From alkyne 5: 26 6: 10, 17, 18 From diol 5: 61 From enol triflate 3: 32 6: 43 From epoxide 5: 10, 21 6: 18 From halide 3: 15 From hydride 5: 14 From keto amide 6: 43

From ketone 2: 16, 22, 150, 174 5: 189, 197 6: 198, 202, 206 Haloamination 2: 137 Haloarylation 3: 41 Homologation 2: 78, 120, 126, 178 3: 39, 41, 59 4: 33, 48–​51, 53, 55, 57–​66, 109 5: 55, 57–​59 6: 43, 49–​51, 53, 55, 57, 65, 67, 70, 85, 89, 90, 95, 96, 104, 117, 134, 136, 140, 143–​146, 148, 149, 160, 166, 168, 183, 190, 193, 199, 201 Homologation, branching, enantioselective 3: 76, 81 Hydroamination (see Hydroamination) Hydroboration 4: 53 6: 7, 164, 187, 196, 197, 203 Hydroboration, diastereoselective 2: 10 5: 56, 59, 180, 205 6: 184, 206 Hydroboration, enantioselective 3: 66, 72 4: 87 5: 74 6: 72 Hydrogenation 2: 77 3: 9, 20, 38, 42 4: 16, 52, 63 5: 17, 30, 56, 59 6: 14, 28, 54 Hydrogenation, enantioselective 1: 161, 164, 174 2: 59, 119 3: 70, 72, 74, 76, 79, 102, 104 4: 71, 74, 76, 78, 88 5: 85, 211 6: 15, 67 Hydrohalogenation 3: 42 5: 61 Hydrosilylation 3: 39 5: 58 6: 38 Hydrosilylation, enantioselective 5: 70 Hydroxyamination 3: 39 Metathesis (see Grubbs reaction) Metathesis with ester 2: 50 Migration 6: 2, 45 Oxidation, to allylic alcohol 1: 25, 137 2: 18, 168 Oxidation, to enone 1: 177 2: 177, 184 3: 115 4: 35 Oxidative cleavage 1: 77, 129 2: 194 3: 38, 41 4: 18, 30, 48, 52, 54 5: 56, 166, 171, 207 6: 53, 56, 162 -​164, 168, 178, 181, 190, 192, 194, 195, 198 Silyl, to alkene, halo 5: 2 To acid (one carbon homologation) 1: 122, 146 4: 55 6: 50, 53 To acid (two carbon homologation) 4: 51, 53, 55 To alcohol 4: 54 To aldehyde 5: 56

245  Reaction Index

141, 149, 153, 157, 159, 167, 169, 170, 188 3: 52, 56, 59, 94, 98, 109–​119, 121, 135, 155, 169, 170, 172, 178, 180, 190, 194, 198, 200, 204, 206 4: 5, 34, 57, 65, 89, 98, 103, 105, 107, 109–​117, 119, 127, 129, 131, 133, 141, 151, 152, 154, 160, 170, 172, 182, 188, 190, 194, 198, 200, 202, 208, 208 5: 37, 40–​42, 45, 65, 67, 75, 79, 85, 91, 96, 105, 107, 109, 112–​119, 127, 129, 131, 137, 139, 145, 151, 154, 168, 178, 180, 182, 186, 192, 196, 200, 202, 204, 206, 210 6: 37, 43, 45, 61, 65, 71, 73, 81, 89, 99, 100, 103, 105, 107, 109–​ 117, 125, 129, 131, 133, 139, 145, 149, 150, 152, 154, 157–​159, 161, 166, 170, 172, 178, 180, 184, 186, 194, 200, 202, 204, 206

Reaction Index  246

246

Alkene (cont.) To aldehyde (one carbon homologation) 2: 126 3: 42, 108 4: 50, 53, 109 5: 55 6: 53, 57, 79, 104, 196, 197 To aldehyde (one carbon homologation) enantioselective 2: 59 4: 78, 80 5: 72, 77, 79 6: 51 To alkane, homologation 6: 51 To alkene 6: 54 To alkenyl borane 4: 52 5: 57 6: 61 To alkenyl halide 4: 54 To alkenyl silane 3: 39 4: 52 To alkyne 5: 11, 13 To allyl silane 2: 78 5: 36 To allylic alcohol 6: 34 To allylic amine 2: 210 5: 38, 60 To allylic amine, enantioselective 5: 67 To amide, one carbon homologation 3: 41 5: 58 6: 50 To amine 5: 57, 58, 60 To amine, enantioselective 6: 72 To amine, one carbon homologation 3: 41 4: 40, 53 6: 50, 55 To amino alcohol 6: 56 To amino alkene 4: 35 To azide 2: 17 5: 57, 59 To diamine 6: 56 To diol 5: 56 To enone 6: 32 To ester (oxidation) 2: 144 To ether 2: 17 4: 50 5: 54 To halide, allylic 6: 36 To haloketone 5: 54 To hydroxy ketone 6: 56 To ketone 2: 178 3: 41, 43, 99 4: 55 5: 57, 61 6: 9, 13, 55 To methyl ketone (Wacker) 1: 120 2: 90 3: 209 4: 50 6: 9 To nitrile 4: 51 To nitrile, enantioselective 6: 50 To nitro alkene 3: 42 4: 54 6: 51 To organometallic 5: 59 To phosphine oxide 3: 39 4: 48 To phosphonium salt 5: 56 To silane 2: 125, 3: 39 To sulfide 4: 48 5: 3 To unsaturated acid, one carbon homologation 3: 41 6: 55

Alkylidene carbene C-​H insertion 6: 37 O-​H insertion 4: 93 Alkyne Addition to aldehyde 1: 47, 65 3: 31 Addition to epoxide 1: 5 Addition to unsaturated amide 1: 98 Amination, intramolecular 3: 106 From acid 3: 31 From aldehyde, one carbon homologation 1: 82 3: 37 5: 195 6: 190 From aldehyde (same carbon count) 2: 146 From aldehyde, homologation 1: 150 2: 126, 182 4: 104, 166 6: 193, 199 From alkene 5: 11, 13 From cyclic ketone, fragmentation 4: 45 From enol tosylate 6: 45 From enol triflate 6: 43 From epoxy ketone 1: 13 From halide, one carbon homologation 5: 51 From ketone 3: 16 5: 47, 51 6: 49 From ketone, homologation 3: 33, 37 From nitrile, homologation 2: 148 3: 31 Haloborylation 4: 41 Homologation 2: 90, 93, 101, 182 3: 25, 37, 39 4: 33, 39, 41, 45, 47, 49, 60, 63, 65–​67, 71, 73, 75, 77, 81, 88, 90–​93, 95, 103, 109, 112, 121, 123, 125–​127, 131, 132, 138, 143, 144, 145, 146, 148, 149, 154–​156, 158–​ 160, 164, 166, 167, 180, 181, 183, 194, 195, 198, 199 5: 31, 47, 49–​52, 55, 58, 65, 81 6: 2, 37, 43, 46–​49, 61, 63, 66, 72, 76, 82, 83, 86, 88–​91, 93, 101, 105, 117, 126, 127, 142–​ 148, 151, 155, 160, 166–​168, 172, 175–​177, 183, 189, 190, 193, 199 Hydroamination 1: 13 Hydroboration 4: 2 6: 2 Hydrohalogenation 4: 47 Hydrosilylation 6: 183 Hydrostannylation 1: 6 4: 38 Hydrozirconation 1: 32 Metathesis Intermolecular 1: 126 2: 110 3: 47

 247

Allene homologation 2: 13, 95 3: 37 4: 44 6: 43, 45 6: 43, 45 Allene homologation, enantioselective 3: 76 4: 76, 88, 95, 103 6: 43 Allyl silane From alkene 5: 36 From ester 1: 195 Allylic coupling 1: 46, 58, 60, 64, 66, 78, 97, 128, 129, 160, 179, 192, 193 2: 5, 12, 20, 24, 33, 60, 62, 70, 74, 97, 108, 122, 139, 140, 155, 161, 162, 163, 193, 194, 197, 198, 205 3: 4, 13, 14, 18, 19, 22, 25, 28, 29, 33–​36, 66–​69, 70, 73, 77, 78, 81, 83–​85, 88, 90, 92, 93, 98, 99, 101, 103, 106, 107, 144–​146, 150 4: 33, 35, 40, 41, 43, 44, 53, 75, 80, 81, 92, 101, 104, 105, 107, 110–​113, 117 5: 8, 59, 68, 71, 73, 75, 190, 209 6: 29, 34, 38–​40, 42, 45, 47–​50, 55, 57, 59, 63, 65, 66, 68, 71–​74, 77, 79–​81, 83, 84, 91, 92, 97, 98, 103, 104, 106, 108–​112, 114, 115, 117, 135, 143, 144, 146, 147, 149, 150, 160, 164, 167–​169, 172, 184, 187, 188, 192, 193, 194, 195, 200, 206, 208 Aminal synthesis 5: 69, 85 Amine Allylic, from allylic alcohol 4: 68 Allylic, from allylic alcohol, enantioselective 4: 70 Allylic, to chlorohydrin, enantioselective 5: 78 Allylic, to hydride 2: 65 From acid 5: 12 From acid (loss of one carbon) 1: 100, 184 2: 23, 27, 44 4: 5, 70 5: 4, 9, 179 6: 13 From alcohol 1: 156 2: 34, 64, 145, 189, 195 3: 4, 16 4: 6, 8, 10 6: 3, 4, 6 From aldehyde 3: 15 From aldehyde, enantioselective 3: 62, 67 4: 67 From alkene 4: 48, 51, 53 From alkene, homologation 4: 40, 48, 51, 53 From alkyl borane 5: 70 From alkyne 1: 1

247  Reaction Index

Intramolecular 1: 83, 126, 127 3: 49, 55 4: 58, 60–​65, 199 5: 51, 101 6: 47, 101, 177 Metathesis with aldehyde to alkene 2: 103 Reduction, to cis alkene 4: 5 5: 26 6: 18, 61 Reduction, to trans alkene 1: 127 6: 10, 17, 45 To acid 2: 43, 86, 146, 190 3: 5 4: 11 6: 2, 7, 12 To acid, homologation 5: 47 To alcohol 5: 17 To aldehyde 1: 1 2: 146 3: 5, 16 4: 11 6: 7 To alkene, homologation 3: 36, 39 5: 44, 45 To alkenyl phosphonate 4: 11 To alkyne, alkyne migration 1: 127 4: 198 To allylic alcohol 3: 31, 39 To amide, cleavage 6: 3 To amine 1: 1 To α-​amino acid 5: 2 To α-​amino aldehyde 6: 2 To α-​amino ketone 5: 13 To diene 1: 44 To 1,4-​diyne 2: 147 To enol ether 6: 83 To enol phosphate 4: 9 To enol tosylate 4: 38 To enone 3: 36 To haloenamine 5: 2 To α-​hydroxy ketone 6: 9 To iodoalkene 3: 33 To ketone 3: 16 4: 3, 9, 17, 38 6: 177 To ketone, homologation 3: 37, 39 To nitrile 2: 146 To nitrile, loss of carbon 5: 9 To silyl alkene 5: 2 Zirconation 2: 98 Allene Construction, enantioselective 6: 43, 45, 47, 49, 193 From enol triflate 6: 43 From enyne 6: 45 From propargyl alcohol 6: 45 Hydroamination, intramolecular 6: 114

Reaction Index  248

248

Amine (cont.) From allene, enantioselective 6: 58 From allylic alcohol 1: 136, 188 2: 161 5: 5 From allylic alcohol, enantioselective 1: 56, 160, 161 2: 161 3: 65 From allylic halide, enantioselective 2: 4 From amide 2: 158, 168 3: 9, 12 4: 12, 17, 18 6: 14 From amide, with homologation 2: 21 5: 50 From amine 4: 8 From aryl halide 1: 110 2: 87, 155 4: 31 From azide 5: 6 From enamide, enantioselective 6: 15 From ether, benzylic 4: 10 From halide 4: 10, 40 6: 4 From ketone 2: 16, 3: 14 4: 12, 16 5: 10 From ketone, enantioselective 2: 16, 117, 162, 204 3: 62, 67 4: 66, 68, 72 5: 15, 67, 68, 108, 109 6: 33, 58 From nitrile 2: 4, 15 4: 40 5: 12 6: 11, 13, 14, 16 From nitro 2: 15, 17 5: 13, 30 6: 18 From nitroalkene, enantioselective 5: 64 From unsaturated amide, enantioselective 3: 62, 65 Propargyl, to allenyl aldehyde 3: 37 Protection (see Protection) Reductive methylation 3: 108, 201 To acid 2: 76 4: 17 5: 15 To alcohol 4: 8 5: 8 To aldehyde 5: 15 To alkyl 6: 68 To amide 3: 5, 11–​13, 15 To amide, cleavage 6: 6 To amide, oxidation 6: 12 To amine 4: 3 To azide 4: 119 5: 11 To enamine 6: 12 To ether 4: 8 To hydride 4: 18 To ketone (oxime) 3: 10 4: 15 To nitrile 3: 14 4: 14 6: 11 To nitro 3: 4 4: 15 α-​Amino acid (nitrile) synthesis 1: 26, 40, 99 2: 23, 118, 162 3: 43, 62, 69 4: 69, 70–​72 5: 15, 71, 78, 85, 86 6: 2, 59, 61, 63, 64, 74

β-​Amino acid (nitrile) synthesis 3: 43, 62, 63 4: 36, 51, 71, 72, 75 6: 63, 65, 74, 75 Aromatic ring construction 1: 171, 191 2: 40, 81, 84, 105, 176, 186, 188 3: 121, 123, 125, 127, 131 4: 119, 121, 123, 125, 129 5: 121, 123, 125, 129, 187 6: 36, 57, 121, 123, 125, 129, 133, 156, 173 Aromatic ring substitution 1: 10, 18, 19, 21, 48, 54, 65, 69, 104, 108, 110, 111, 120, 122, 138, 149, 164, 171, 174, 175, 190, 205 2: 11, 12, 15, 22, 25, 26, 28, 39, 40, 58, 75, 81, 82, 84, 86, 87, 91, 108, 128, 132, 134, 141, 155, 156, 157, 160, 175, 176, 179, 180, 185, 186, 206, 208, 209 3: 25, 27, 32, 33, 35, 63, 110, 114, 116, 118, 120–​127, 129, 131–​134 4: 30, 49, 51, 74, 78–​80, 83, 90, 102, 104–​107, 109, 112–​114, 118–​125, 127–​129, 131, 133, 168, 196, 200 5: 30–​33, 37, 39–​41, 49, 52, 55, 61, 71, 73, 75, 80, 81, 120–​127, 151, 175, 200 6: 29–​33, 35–​37, 39, 41, 53, 57, 58, 67, 73, 93, 97, 117–​122, 124, 125, 129, 131, 133, 144, 145, 148, 149, 159, 184, 203, 207 Aza-​Claisen 4: 113, 203 Aza-​Cope: 2: 27 Azetidine construction 5: 107, 110, 179, 205 6: 102, 106, 108, 112 Azide Addition to epoxide 1: 8 Addition to ketone 1: 113, 139 2: 38 From alcohol 2: 189 3: 15 5: 5 From alkene 4: 55 5: 59 From amine 4: 119 5: 11 From cyclopropane 5: 53 From ketone 5: 12 To amide 3: 16 4: 20 5: 6 To amine 5: 28 6: 64 To diazo 4: 15 6: 3 To nitrile 2: 14 4: 19 5: 11 Aziridine Carbonylation 4: 104 From alkene 2: 18 4: 102 5: 31, 104, 108, 110, 112 From haloaziridine, homologation 1: 160 From imine 6: 102

 249

Baeyer-​Villiger 1: 20 2: 124, 133 3: 79 5: 14, 66, 94, 157 6: 134 Baeyer-​Villiger, enantioselective 6: 64 Baylis-​Hillman reaction, intramolecular 1: 196 Beckmann rearrangement 1: 20 2: 76 Benzofuran synthesis 3: 132 4: 139 6: 117, 127 Benzyne substitution 2: 185 3: 120, 125, 154 4: 122 5: 175 6: 121 Biotransformation. See Enzyme Biphenyl synthesis 1: 19, 54, 60, 110, 171 2: 39, 42 3: 25, 97, 120, 121, 123–​125, 127 4: 30, 119, 122, 124, 161, 172, 200 5: 103, 115, 131 6: 33, 95, 123 Birch reduction 1: 12 2: 168, 184, 208 3: 160 4: 149, 161, 186, 206 5: 125, 141, 184 6: 172, 186, 202 Blaise reaction 3: 94 4: 46 6: 132, 183 Borane from halide 6: 6 Carbene cyclization 3: 93 4: 157 5: 195 6: 159, 162, 193. See also C-​H insertion Carvone (starting material) 1: 33, 148 2: 62, 122, 186, 206 6: 159, 162, 178 Castro-​Stevens coupling 4: 31 5: 125 C-​H Functionalization 1: 59, 110, 122, 157, 175 2: 10, 18, 22, 25, 40, 78, 81, 82, 85, 105, 127, 134, 135, 140, 156, 180, 188, 210 3: 25–​30, 64, 68, 70, 71, 89, 94, 99, 101, 105, 122, 122, 124, 126, 133, 134, 149, 157, 160 4: 7, 10, 32–​37, 78, 84, 95, 104, 109, 120, 122–​125, 127–​129, 131, 133, 147, 148, 154, 183, 191, 197 5: 32–​43, 67, 70, 75 6: 30, 32, 34–​40, 55, 62, 72, 144, 146, 181, 207 C-​H Homologation 3: 25, 27–​29 4: 32–​37, 78, 90, 95, 104, 109, 118, 120,

122–​125, 127–​129, 147, 148, 154 5: 13, 14, 32–​35, 37, 39–​43, 46, 75, 120–​127, 151 6: 30–​32, 35–​41, 55, 72, 77, 91, 146, 181 C-​H Insertion Intermolecular 2: 61, 106, 210 3: 25 4: 32–​37, 90 5: 32–​44, 75 6: 72, 77, 144, 146 Intramolecular By carbene 1: 110, 142, 168 2: 31, 135, 180, 207 3: 25, 29, 88, 93, 98, 100, 104, 112, 149, 157, 160 4: 32, 34, 36, 78, 93, 146, 148, 154 5: 35, 37, 39, 40 6: 37, 41, 91, 181 By nitrene 1: 8, 153, 175 2: 10, 84, 118, 180, 189, 209 3: 25, 29, 133, 134 4: 36, 70 5: 32, 37, 175 6: 34 C-​H to alcohol 1: 157 2: 18, 134, 168, 179, 210 3: 24, 26, 28, 29 4: 7, 10, 32–​34, 36, 118, 120, 123, 124, 183, 191, 197 5: 26, 32–​36, 38 6: 8, 11, 12, 34, 36, 38, 40, 62, 207 C-​H to aldehyde 5: 13 6: 34 C-​H to alkene 3: 25, 26 4: 118 6: 37, 39 C-​H to amine 2: 10, 84, 118, 180, 210 3: 25, 26, 28, 29, 133, 134 4: 35, 36, 84, 120, 123, 125, 127, 129 5: 32, 37, 67, 70, 175 6: 37–​40, 65 C-​H to amine, enantioselective 3: 29, 67, 69, 70 4: 70 5: 67, 70 6: 34 C-​H to aryl 4: 32 5: 32, 33, 37, 39 6: 35, 37, 39, 41 C-​H to C-​borane 1: 157 2: 40 3: 121, 122 5: 38 C-​H to carboxylic acid 4: 32, 34 5: 32, 33, 35, 37, 39 C-​H to ether 5: 36, 43, 90 6: 36 C-​H to halide 3: 24, 28 4: 34, 36, 125 5: 38 6: 30, 36, 40 C-​H to ketone 2: 179 4: 34, 35, 123, 191 5: 32, 34, 37, 46 6: 8, 34, 55 C-​H to nitrile 4: 120 5: 15, 34, 35 C-​H to phosphorus 4: 120 C-​H to silyl 5: 36 C-​H to sulfide 6: 11 Claisen rearrangement 1: 27, 96, 195, 203 2: 62, 107, 122, 163, 182, 193, 194 3: 97, 121, 191, 209 4: 85, 107, 155, 163, 176 5: 27, 75, 79, 83, 149, 185, 180, 193, 199 6: 110, 174, 206

249  Reaction Index

Opening 1: 92, 193 2: 18, 34, 121, 140, 166, 188, 196 3: 105–​107, 110 4: 82, 88 5: 56, 79, 182 6: 70, 106, 108, 138 Synthesis, enantioselective 1: 92 3: 78, 105 4: 104, 106, 108 5: 108, 100, 182 6: 102, 106 To allylic amine 6: 65 Aziridine aldehyde to amino ester 1: 115 Azirine synthesis, enantioselective 5: 102, 112

Reaction Index  250

250

Claisen rearrangement, enantioselective 3: 81, 83, 85, 116, 159 4: 138 5: 45 6: 68, 74, 77, 79, 81, 85, 114, 146, 161, 184 Cleavage 5: 15, 28, 54, 126 6: 32, 37, 126, 162, 171, 178, 188, 189 C-​N ring > 6 5: 62, 73, 75, 81, 202, 207 6: 109, 110, 115, 117, 185. See also Macrolactam C-​O ring 4 construction 1: 116 2: 124 4: 94 5: 88, 90 6: 32, 77, 81, 86, 88, 89, 90, 134, 138, 139, 140, 205 C-​O ring 5 construction 1: 50, 51, 56, 69, 78, 95, 130, 140, 141, 142, 154, 168, 186, 189, 194 2: 29, 31, 32, 49, 66, 88, 95, 97, 111, 133, 134, 135, 154, 158, 184, 197, 200, 202 3: 24, 42–​44, 54, 55, 86–​101, 197 4: 51, 61, 90, 92, 94–​96, 98, 100 5: 43, 66, 83, 88, 90, 92, 94–​100, 102, 165–​167, 185, 186, 193, 201 6: 12, 14, 21, 30, 34, 37, 41, 48, 63, 69, 70, 71, 73, 75–​77, 79, 81–​88, 90, 91, 93–​100, 105, 113, 115, 117, 123, 135, 136, 137, 143, 146, 147, 151, 153, 155, 156, 159, 160, 162–​166, 168, 176, 177, 198, 209 C-​O ring 6 construction 1: 29, 33, 42, 43, 108, 124, 130, 140, 141, 142, 187, 189, 194, 195, 203 2: 10, 29, 30, 32, 50, 88, 93, 94, 96, 111, 114, 116, 133, 135, 136, 153, 156, 197, 198, 199, 200, 201 3: 11, 27, 29, 43, 46, 49, 51, 52, 54, 61, 86, 87, 89–​97, 99–​101, 197 4: 56, 61, 62, 91–​93, 95, 97, 98, 100, 101, 195 5: 42, 60, 63, 89, 91–​95, 100–​103, 166, 170, 176, 178, 183, 199, 201, 204 6: 16, 21, 22, 27, 30, 37, 48, 62–​65, 73, 76, 80, 83, 85, 86, 87, 89, 91–​95, 97, 99, 115, 119, 122, 123, 133–​137, 151–​155, 157, 162, 163, 183, 188–​191, 197, 203, 204, 206, 207 C-​O ring > 6 construction 1: 155, 195 2: 20, 133 3: 45, 49, 51, 53, 55, 58, 197 4: 23, 33, 62, 64, 196 5: 42, 49, 63, 73 6: 63, 70, 83, 87, 89, 94, 95, 97, 133. See also Macrolactone Conia alkyne cyclization 5: 144 6: 143, 146, 151, 172

Cope rearrangement 1: 24 2: 208 3: 127, 157, 204 4: 156, 159 5: 178 6: 135, 139 Cycloalkane > C7 synthesis: 1: 23, 24, 25, 33, 43, 45, 72, 73, 75, 77, 86, 135, 183 2: 16, 26, 71, 72, 98, 100, 114, 153, 156, 170, 193, 202, 208 3: 59, 105, 139, 147, 153, 157, 160, 193 4: 57, 61, 64, 111, 141, 163, 178, 181 5: 149, 173, 209, 211 6: 97, 145, 155, 165, 169, 199, 205 Cyclobutane cleavage 2: 113, 124 3: 57, 149 5: 118 6: 158 Cyclobutane synthesis 1: 76, 102 2: 64, 71, 113, 206 3: 27, 49, 136, 137, 145, 148, 156–​158, 181, 186, 189 4: 63, 136, 142, 144, 146, 148, 154, 156, 160, 204 5: 28, 118, 138, 140, 142, 144, 146, 148, 150, 160–​162 6: 93, 134, 136, 138, 140, 142–​144, 146, 148, 158, 159, 160 Cycloheptane synthesis 1: 53, 165, 169, 180, 204 2: 51, 70, 104, 124, 206 3: 45, 51, 55, 144, 161, 169 4: 63, 116, 139, 149, 153, 167, 205, 207 5: 68, 94, 161, 194, 205 6: 94, 135, 137, 151, 153, 159, 161, 170, 173, 175, 187 Cyclohexane synthesis 1: 12, 14, 22, 23, 25, 32, 37, 53, 57, 58, 66, 68, 75, 78, 80, 81, 128, 136, 143, 165, 166, 167, 180, 188, 190, 198, 200, 201, 202, 204, 205 2: 12, 20, 24, 27, 34, 35, 36, 52, 60, 63, 64, 65, 66, 67, 68, 70, 73, 74, 100, 102, 104, 124, 156, 158, 159, 164, 166, 167, 169, 171, 172, 173, 174, 184, 204, 206, 207, 208 3: 11, 57, 59, 109, 111, 115, 117–​ 119, 136–​149, 151–​157, 168, 169, 177, 183, 191, 194, 202, 201 4: 31, 58, 63, 65, 103, 108, 111, 115–​117, 134–​141, 143, 145, 147, 149–​155, 157, 159, 161, 165, 169, 172, 175–​178, 180, 182, 184, 186, 189, 190, 192, 193, 196, 197, 202, 204, 206, 208 5: 27, 29, 31, 81, 89, 94, 100, 113, 117, 118, 137, 139, 141, 143, 145, 147, 149, 151–​159, 161, 163, 165, 172, 184, 186, 188, 189,

 251

Diazo alkane from aldehyde 6: 193 Diazo alkane from ketone 6: 41

Diazo alkane to ketone 6: 45, 104 Diazo amide, from azido amide 6: 3 Diazo ester Aldol, enantioselective 4: 83, 90 5: 84 α-​Alkenylation 5: 151 α-​Arylation 5: 124 From α-​halo ester 6: 180 Intermolecular C-​H insertion 6: 41 Intramolecular C-​H insertion 4: 147 5: 43, 146 6: 39, 91, 95 Mannich reaction 5: 82, 87 To α-​alkoxy ester, enantioselective 4: 74 To α-​alkynyl ester 5: 45, 49 To α-​amino ester, enantioselective 6: 63 To cyclopropane 4: 146 5: 136 To cyclopropene 5: 144, 146 To epoxy amide, enantioselective 4: 84 To α-​halo unsaturated ester 4: 39 To α-​hydroxy ester 6: 75 Diazo ketone, from acid 5: 50 Dieckmann cyclization 1: 37 Diels-​Alder Catalyst 1: 52, 168 2: 100 3: 152–​155 5: 113 6: 29, 139 Diene 1: 189 2: 65, 99 5: 153 Dienophile 1: 112, 136, 189 2: 65, 99, 100 6: 150, 162 Hetero 2: 94, 165, 166, 188, 195 3: 105 4: 91, 97, 107 5: 163 6: 65, 85, 89, 107, 109, 127–​129, 131 Hetero, intramolecular 2: 2, 45 3: 106, 129 Intermolecular 1: 13, 52, 112, 136, 139, 168, 180, 198 2: 65, 99, 100, 123, 171, 176, 186, 188, 202, 208 3: 131, 152, 154, 155, 200 4: 121, 125, 147, 178, 208 5: 27, 113, 154, 156–​159, 172 6: 29, 123, 150, 152–​156, 162, 167, 170, 171, 185 Intramolecular 1: 22, 120, 135, 146, 191, 199, 203 2: 66, 79, 81, 101, 105, 168, 169, 170 3: 11, 109, 111, 115, 153–​155, 206 4: 117, 150–​153, 165, 175, 178, 184, 188–​189, 197, 205 5: 102, 152–​154, 157–​159, 190 6: 36, 95, 121, 125, 139, 151–​153, 155, 157, 168, 184, 186 Retro 1: 198 2: 186 5: 21 6: 167 Transannular 3: 155

251  Reaction Index

191, 193, 198, 199, 202 6: 79, 93–​95, 99, 103, 107, 115–​117, 121, 127, 135, 137, 139, 141, 143, 145, 147, 149, 150–​157, 161–​163, 167, 168, 170, 178, 184–​186, 206 Cyclopentane synthesis 1: 9, 12, 23, 24, 36, 37, 42, 43, 52, 66, 74, 77, 79, 80, 112, 128, 165, 166, 167, 168, 180, 183, 189, 198, 200, 201, 202, 203, 205 2: 1, 28, 68, 70, 72, 73, 97, 101, 102, 103, 104, 113, 123, 124, 159, 164, 167, 169, 170, 171, 172, 173, 174, 180, 183, 184, 193, 203, 205, 206, 207, 208 3: 27, 47, 48, 50, 109, 136–​138, 140–​143, 149, 150, 152–​155, 157–​161, 178, 181, 189, 204 4: 56, 60, 64, 103, 112, 116, 134–​136, 138–​148, 150–​154, 156–​158, 160, 165, 167, 171, 175–​177, 185, 187, 199, 204 5: 35, 39, 43, 53, 87, 91, 94, 97, 112, 118, 136, 138–​148, 150–​155, 157–​163, 165, 173, 181, 184, 191, 194, 195, 200, 203, 209 6: 31, 37, 39, 48, 85, 93, 94, 134, 136, 138, 140–​142, 144, 146–​149, 151, 152, 158–​160, 164–​167, 171, 175, 181, 187, 193, 199, 203, 207, 209 Cyclopropane cleavage 2: 10, 36, 70, 71, 104, 184 3: 102, 144–​145, 148, 149, 151, 160, 208 4: 55, 57, 62, 64, 85, 106, 134, 145, 147, 149, 156, 159, 167 5: 53, 92, 95, 150, 200 6: 33, 67, 84, 106, 123, 134, 140, 149, 159, 160, 170 Cyclopropane synthesis 1: 36, 52, 81, 167, 203 2: 69, 70, 184, 205 3: 102, 138, 142–​145, 147, 148, 150, 156–​158, 160, 208 4: 136, 140, 142, 144, 146, 148, 156, 158, 160, 166, 205 5: 136, 138, 140, 42, 144, 146, 148, 150, 160, 162, 163, 165, 178, 195, 200 6: 33, 134, 136, 142, 144, 146, 148, 208 Cyclozirconation, of diene 2: 104 5: 147 Cyclozirconation, of enyne 6: 148, 199

Reaction Index  252

25

1,1-​Dihalide, from halide, homologation 3: 34 Diimide generation 2: 77 3: 38 4: 13 6: 18, 56, 114 Diol cleavage 5: 15 Diol from epoxide 1: 160 2: 161 Diol to alkene 6: 11 Dipolar cycloaddition 2: 34, 53, 54, 140, 158, 199, 202 3: 39, 103, 107, 108, 132 4: 53, 67, 83, 85, 88, 95, 108, 116, 134, 179 5: 107, 116 6: 50, 63, 85, 94, 102, 104, 106, 108, 117, 126, 137, 159, 193 Diastereoselective cycloheptane construction 1: 76 2: 207 3: 161 4: 95, 116 6: 94, 137 Diastereoselective cyclohexane construction 1: 22, 23 2: 46, 158 3: 161 4: 108, 154, 161 5: 163 6: 117, 159 Diastereoselective cyclopentane construction 3: 47, 141, 158 4: 134, 147, 154 5: 163, 203 6: 85, 94, 193 Electrolysis 5: 27, 44 6: 29, 32, 117 Enamide, conjugate addition 4: 73 Enamine From alkene 6: 37 From amine 6: 9 Hydrogenation, enantioselective 6: 14 Ene reaction, intramolecular 1: 24 3: 157, 159, 177 4: 90 5: 112 6: 116 Ene reaction, intermolecular, enantioselective 3: 68 6: 65 Enolate, intramolecular coupling 4: 202 6: 42 Enone Allyl addition 3: 30 Conjugate addition 1: 43 3: 30, 96 4: 43, 46, 51, 75, 187, 204 5: 44, 46, 49, 194 6: 46, 48, 83, 167 Conjugate addition, enantioselective 1: 57, 98, 151, 164, 166, 167, 192, 204, 205 2: 24, 60, 67, 68, 73, 74, 101, 139, 203, 204, 207 3: 73, 74, 77, 81, 85, 137, 138, 140–​142, 144, 148, 192 4: 17, 73, 74, 77, 81, 83, 89, 105, 134, 136–​138, 143, 147, 149 5: 75, 79, 80 6: 62, 65, 68, 69, 71, 73, 85, 144, 145, 147, 149, 204

Conjugate addition of amine 4: 7 Conjugate addition of amine, enantioselective 3: 69 5: 67 Conjugate addition of silyl 6: 166 Conjugate reduction 1: 25 3: 13 4: 169, 191 Conjugate reduction, enantioselective 4: 157 5: 29 Cyanide addition 1: 199 Cyanide addition, enantioselective 3: 74 5: 72 Enantioselective reduction to allylic alcohol 1: 103 2: 12 4: 70 Epoxidation 5: 169, 179, 199 Epoxidation, enantioselective 3: 84, 156 5: 82, 138 From alcohol 4: 14 From alkene 3: 41, 115 5: 174 6: 32, 34 From ketone, homologation 6: 46 From propargyl alcohol 2: 182 3: 11 4: 11, 44 5: 2 Reduction, enantioselective 6: 138 Enzyme Akaloid synthesis 5: 41 Aldol condensation 2: 165 4: 89, 93 Alkene epoxidation 6: 60 Alkene reduction 6: 67, 70, 138 Allylic oxidation 5: 33 Amide formation 5: 105 Arene oxidation 1: 190 6: 141 Baeyer-​Villiger, enantioselective 5: 66 C-​H to alcohol 6: 62, 141 Conjugate addition to nitroalkene 6: 68 Epoxide hydrolysis, enantioselective 2: 161 Ester hydrolysis 2: 48 4: 27, 70 6: 84, 164, 172 Esterification 4: 70 6: 174, 201 Glucosidase 3: 23 5: 89 Henry reaction 3: 66 Reduction of ketone 1: 1, 34 2: 143, 183 4: 197 6: 16, 135, 183, 206 Reduction of unsaturated aldehyde 4: 80 Reduction of unsaturated lactone 3: 79 Reductive amination 2: 161 3: 69 5: 108, 109 6: 33, 58 Resolution of alcohol 1: 34, 88, 158 3: 66, 76, 108 4: 73, 177, 186, 204

 253

with amine 5: 169, 179 6: 113 with azide 1: 8, 173 6: 81 with dithiane 1: 51 with enolate 4: 92, 156, 158 with hydride 6: 203 with imide 4: 111 with organometallic 1: 46, 80, 165 2: 58, 63, 133 3: 81, 82, 164 4: 46, 86, 91, 177, 180 5: 48, 160 6: 149, 165, 176, 193 with selenide 4: 173 with selenide, enantioselective 4: 66 6: 80 with sulfoxide anion 4: 94 Reduction 2: 125, 178 Reductive condensation with nitrile 4: 38 Reductive cyclization 3: 87, 112, 130, 145 4: 91 To aldehyde 3: 162 4: 185 6: 7, 129 To alkene 4: 18 5: 10, 21 To allylic alcohol 1: 137 4: 173 To amino alcohol 1: 160 To carbene 6: 149 To diol 1: 160 2: 161 To propargylic alcohol 3: 33 Epoxy alcohol to silyloxy aldehyde 3: 162 Epoxy aldehyde to hydroxy ester 1: 115 3: 65 Epoxy amide to hydroxyamide 1: 159 Epoxy ether to ether aldehyde 1: 159 Eschenmoser cleavage 1: 13 Ether Allyl, to propenyl ether 4: 9 Allylic from allylic alcohol, enantioselective 3: 66 5: 90 Allylic, to hydride 5: 10, 12 Cleavage 2: 189 Fragmentation 3: 33 From alcohol 6: 3 From aldehyde or ketone 1: 16, 86 2: 15 3: 2 4: 19 From alkene 2: 17 4: 50, 55 5: 54 From ester 3: 9 5: 15 To acid 4: 4 To aldehyde 4: 4 6: 15 To amine 4: 10 5: 21 To hydride 4: 13 5: 17, 60 6: 19 To ketone 4: 17, 19 6: 15 To lactone 5: 165 6: 12 To phenol 5: 15

253  Reaction Index

Resolution of amine 3: 63 Ring cleavage, enantioselective 3: 156 Epoxidation. See also Sharpless Asymmetric Epoxidation Of enone, enantioselective 1: 90, 91 3: 84, 156 4: 155 6: 75 Of unsaturated aldehyde, enantioselective 2: 121 4: 88, 174 Of unsaturated amide, enantioselective 1: 90 Of unsaturated ester, enantioselective 6: 76 Epoxide Alkenyl, carbonylation 3: 175 Carbene donor 3: 150 Enantioselective, from halo ketone 1: 2 From aldehyde 1: 44 From aldehyde, enantioselective 4: 68, 84 6: 85 From alkene 1: 35 2: 77, 98 3: 38, 40 4: 48 5: 56 6: 29, 52–​54, 56 From alkene, enantioselective 1: 32, 159 2: 14, 58, 61, 77, 98, 112, 134, 156, 171, 177, 198 3: 40, 60, 84, 156 4: 86, 168 5: 67 6: 59, 60 From allylic alcohol (Sharpless) 1: 32, 46, 67, 115, 141, 168, 172, 193 2: 58, 61, 77, 112, 156, 197, 198 3: 94, 163, 175 From α, β-​unsaturated aldehyde, enantioselective 2: 14, 121 From α, β-​unsaturated amide, enantioselective 1: 90, 159 From α, β-​unsaturated sulfone, enantioselective 1: 91 Homologation, reductive 2: 128 Homologation (one carbon) to allylic alcohol 2: 95 Homologation to epoxy ketone 1: 149 Homologation to β-​lactone 2: 59 Homologation to δ-​lactone 6: 48 Hydrogenolysis 1: 1 2: 102 3: 8 Opening intramolecular 2: 173 3: 87, 90, 91, 93, 94, 99 4: 154, 158, 206 5: 160, 162, 166, 179, 184 6: 113 with alcohol 2: 93, 202 3: 54 4: 95–​97 5: 184 6: 140, 187 with alkyne 1: 5, 94 3: 3, 33, 81, 82, 164

Reaction Index  254

254

Flow 5: 26–​31 6: 28–​33 Fragmentation 2: 198 3: 139, 156 4: 45, 85, 91, 126, 127, 133, 134, 145, 147, 149, 156, 159, 167, 178 5: 46, 49, 50 6: 33, 43, 49 Furan synthesis 1: 175 2: 41 3: 19, 128, 130, 132, 134 4: 126, 128, 130, 132, 170, 198 5: 128, 130, 132, 135, 154, 164, 206 6: 126–​128, 130, 132 Gold catalysis Alcohol to alkyne 5: 17 Aldol condensation 2: 104, 173 Alkene activation 2: 17 5: 17 Alkene homologation 4: 53, 55 Alkene hydration 4: 50 Alkene hydroamination 2: 92, 137, 140, 196 3: 102 Alkyne activation 1: 122 3: 107, 118 6: 172 Alkyne hydroboration 4: 2 Alkyne to alkenyl tosylate 4: 38 Alkynyl alcohol to α-​halo enone 4: 44 Allylic coupling 5: 8 Allylic coupling, intramolecular 5: 140, 185 Allylic hydration 3: 8 Arene alkylation 1: 175 Claisen rearrangement, alkynyl 5: 185 Cyclohexane synthesis 3: 144 Cyclopentane synthesis 2: 206 3: 149, 150, 178 5: 140 Cyclopropanation 6: 146 Dihydrofuran formation 2: 197 Dihydropyrrole formation 6: 108 Enone from propargyl alcohol 2: 182 3: 11 4: 11 5: 2 Furan synthesis 3: 130 4: 126, 128, 132 5: 92, 130 Indole synthesis 4: 127 6: 133 Ketone from alkyne 5: 5, 17 6: 5 Ketone from nitro 4: 3 β-​Lactam synthesis 4: 108 Piperidine synthesis 4: 103 5: 109 Propargylic coupling 6: 90 Pyridine synthesis 6: 129 Pyrrole synthesis 2: 41 3: 130 4: 126, 130 6: 129 Pyrrolidine synthesis 4: 103 5: 106, 108 Spiroketal formation 3: 203

Grob (Wharton) fragmentation 4: 178 5: 53, 107 6: 169 Grubbs reaction (Rh, Mo, W) Ene-​yne 1: 75, 82, 83, 130 2: 154 3: 56, 200 6: 145, 155 Intermolecular 1: 28, 50, 70, 71, 74, 141 2: 17, 49, 51, 79, 95, 109, 110, 112, 132, 152, 154, 178, 196 3: 44, 46–​51, 53, 163, 173, 175, 180, 193, 194, 199 4: 56–​65, 171, 191 5: 26, 62, 63, 90, 92, 187, 200, 201, 211 6: 27, 51, 92, 99, 146, 200, 201 New catalysts 1: 131, 141, 182, 183 2: 49, 49 (Au), 50, 151 3: 44–​48, 50, 51 4: 56, 57, 59–​62, 64 5: 151 (W) 6: 31, 51, 200 Intramolecular 1: 29, 42, 70, 72, 73, 74, 93, 103, 112, 131, 132, 133, 139, 141, 154, 161, 181, 182, 183, 184, 185, 186, 187, 188, 189, 194, 195, 200 202 2: 20, 49, 51, 52, 90, 93, 94, 95, 96, 109, 110, 111, 113, 114, 116, 150, 151, 152, 153, 154, 193, 195 3: 45, 46, 48–​59, 89, 93, 95, 101, 103, 105, 170, 172, 189 4: 56–​58, 60–​63, 105, 199 5: 62, 90, 91, 100, 145, 148–​151 (W), 173, 207 6: 26, 31, 56, 99, 165, 166, 190, 199, 203, 207 Halide Alkyl, homologation 2: 19, 55, 56, 127, 128, 181 3: 30 4: 40, 42, 43, 46, 119, 120, 124 5: 44, 49 6: 46–​49 Alkyl, homologation, enantioselective 2: 6, 23 5: 73 Alkynyl, homologation 4: 45 Allylic, to aldehyde 1: 177 Allylic, homologation, enantioselective 3: 71 Benzylic, homologation 4: 41 From acid 4: 8 From alcohol 2: 85, 189 4: 2 4: 6, 10, 166, 168 5: 5, 6, 8, 170 6: 4, 6 From aldehyde 3: 4 From alkene 4: 54 From C-​H: 6: 30, 32 From ketone 1: 26 6: 17 Propargylic, homologation 3: 37

 25

Horner-​Emmons, intramolecular 3: 157 4: 161 Hydride From acid, loss of carbon 5: 10, 12 6: 7 From alcohol 3: 10 4: 16 5: 30 6: 10, 14, 17 From allylic ether 5: 10, 12 From amine 4: 18 From ether 4: 13 6: 19 From halide 4: 13, 16, 19 From nitrile 4: 13 6: 10 From sulfide 6: 207 From sulfone 6: 11 From sulfoxide 6: 18 To halide 6: 30, 32 Hydroamination Intermolecular Alkene 1: 30 2: 177 6: 72 Alkyne 1: 1 2: 37 Intramolecular Alkene 1: 30 2: 92, 137, 196 4: 114 Alkyne 1: 13, 170 2: 37 Allene 2: 137, 196 3: 102 Hydrogen peroxide Epoxidation 3: 40, 42 5: 179, 199 6: 60, 75, 76, 78, 193 Oxidation of alcohols 1: 26, 86 6: 11 Imidazole synthesis 6: 9 Indole synthesis 2: 25, 35, 36, 41, 42, 45, 63, 84, 91, 140, 157, 160 3: 106, 115–​118, 129, 131, 133, 134 4: 30, 109, 127, 129, 131, 133, 202, 206, 209 5: 118, 129, 131, 133, 134, 200 6: 43, 66, 71, 75, 103, 111, 117, 121, 125, 127, 129, 131, 203, 207 Indoline synthesis 1: 38, 48 143 2: 40, 45, 46, 108, 139 3: 109, 113, 115, 116, 209 6: 37, 41, 117, 125, 131, 133 Indolizidine synthesis 1: 8, 31, 182 2: 34, 37, 111 3: 25, 105–​107, 109, 111, 112, 114, 118, 119 4: 65, 109, 111, 112 5: 63, 112, 114 6: 105, 107, 113, 114, 115 Ionic Liquid Alkane nitration 2: 85 Aromatic substitution 1: 21 Baeyer-​Villiger 1: 20 Beckmann rearrangement 1: 20

255  Reaction Index

Propargylic, homologation, enantioselective 3: 76 To aldehyde 3: 14 To alkene 3: 15 4: 41 5: 7 To alkyne 4: 39 5: 45, 47 To amine 4: 10, 122, 124 6: 4 To amine (one carbon added) 2: 55 α to carbonyl, homologation, enantioselective 3: 75, 77 To amide (one carbon added) 4: 38, 119 To borane 5: 7 To ester (one carbon added) 2: 43 To ether (one carbon added) 4: 38 To hydride 2: 16 3: 14 4: 13, 16, 19 6: 19 To ketone 4: 120 6: 48 To nitrile (carbon count unchanged): 4: 4 To nitro (carbon count unchanged) 4: 119 To sulfide 6: 29 To sulfonic acid 4: 3 Haloalkene From aldehyde 3: 36 4: 174, 180 From alkene 4: 54 From alkenyl borane 6: 200 From alkenyl silane 6: 43, 48, 51 From alkenyl stannane 5: 175 From alkyne 4: 41, 181 5: 192, 194 6: 189, 190 From ketone 4: 177, 180 6: 163 From silyl alkene 6: 43, 51, 168 From stannyl alkene 6: 167 From sulfone 6: 176 From unsaturated acid 4: 5, 7 Homologation 1: 149, 157 4: 45 5: 47 Hydrogenation 6: 54, 167 To alkenyl sulfide 4: 7 To alkyl alkene 6: 46 To alkyne 5: 45 To enol ether 6: 5 To nitrile, α,β-​unsaturated 6: 5 To stannyl alkene 6: 189 Halolactonization, enantioselective 5: 95 Heck Reaction. See Palladium Henry reaction 4: 172 5: 180, 196 6: 45 Henry reaction, enantioselective 2: 57 3: 65, 68 5: 143 6: 62, 78, 147 Hetero Diels-​Alder. See Diels-​Alder: Hetero

Reaction Index  256

256

Ionic Liquid (cont.) Carbocyclization 2: 45 Friedel-​Crafts 1: 21 Heck reaction 1: 21 Henry reaction 1: 21 Osmylation 1: 89 Phenol ether cleavage 4: 26 Iridium Catalyst Alcohol allylation, enantioselective 3: 68 4: 84 Alcohol to alkyl 6: 42, 46 Alcohol to hydride 6: 11 Alcohol oxidation 3: 3 5: 15 Aldehyde from allylic alcohol 4: 3 Aldehyde from epoxide 6: 7 Aldehyde hydroxyallylation, enantioselective 4: 86 6: 79 Aldehyde hydroxymethylallylation, enantioselective 4: 87 Aldol condensation 2: 55 4: 42 Alkene hydroacylation 4: 55 Alkene hydroamination 6: 107 Alkene hydroboration 6: 196 Alkene reduction 5: 69 6: 173, 187, 207 Alkene reduction, enantioselective 1: 49 2: 91, 119 3: 76, 118 4: 70, 78, 85, 88, 105, 165 5: 77 6: 107 Alkene silylation 4: 52 Alkene to enamine 6: 37 Alkylation of C-​H 4: 90 6: 35 Allylation 1: 63 Allylic coupling 1: 138, 160, 179, 202 2: 113, 161 3: 65, 66 4: 68, 84, 86, 87, 110, 112 6: 59, 72, 81, 92, 104, 144 Amination of C-​H 6: 40 Amine from allylic alcohol, enantioselective 4: 68 Amine from amine 4: 3 Amine from ketone, enantioselective 4: 66 Aromatic ring substitution 6: 57 Borylation of C-​H 2: 40, 160 3: 25, 121, 122 4: 113 Claisen rearrangement 2: 122, 163 Cyclopropanation 3: 148 Dihydrofuran synthesis 3: 90 Ester aldol condensation, enantioselective 1: 6

Ester reduction, to aldehyde 5: 16 Ether cyclization 3: 88 Furan synthesis 3: 134 Haloketone from allylic alcohol 6: 8 Indole synthesis 6: 131 Photocatalysis 6: 44 Pyridine synthesis 5: 135 6: 131 Pyrrole synthesis 4: 129 5: 134 6: 132 Iron Catalyst Alcohol oxidation 6: 11 Aldehyde hydroxylation 3: 61 Aldehyde reductive amination 3: 12 Alkene acylation 3: 41 Alkene aziridination 5: 104 Alkene dihydroxylation, enantioselective 3: 82 Alkene epoxidation 6: 53 Alkene homologation 6: 55 Alkene hydrosilylation 5: 58 Alkene reduction 3: 2, 42 4: 16 Alkene to amino alcohol 6: 56 Alkyne alkylation 6: 47 Alkyne hydration 3: 16 Alkyne reduction 6: 10, 45 Allylic acetate carbonylation 3: 93 Allylic epoxide carbonylation 3: 176 Amide from nitrile 4: 3 Amine from amide 4: 17 Amine from nitro 5: 30 Arene coupling 3: 126 6: 122, 125 Borane from halide 6: 6 C-​H amination 5: 32 6: 55 C-​H arylation 5: 33 C-​H oxidation 2: 179, 210 Conia ene 6: 146 Cyclohexane synthesis 3: 149, 151 Cyclopropanation 5: 146 6: 144, 146 Diazo coupling 4: 73 Diene oxamination 5: 70 Enamine from amine 6: 9 Epoxide opening 4: 87 Ester to alcohol 6: 19 Ether oxidation 6: 12 Ether to hydride 6: 19 Grignard coupling 6: 108, 193 Halide coupling 3: 30, 35 4: 41, 46 5: 47, 49, 94 Haloarene amination 3: 125 Henry reaction 6: 45

 257

Julia synthesis 3: 95 5: 50, 196 6: 135, 191 Ketene cycloaddition 6: 160 Ketone α–​Acylation 3: 30 6: 42 Aldol, enantioselective 3: 79, 80, 83, 86, 103 α–​Alkenylation 2: 128 3: 115 Alkylation 6: 42 Alkylation with aldehyde 1: 107 Alkylation, enantioselective 1: 165 5: 72 6: 203 Alkylation, intramolecular 1: 134, 167 6: 187 α–​Allylation, enantioselective 3: 68, 151 4: 75 α–​Amination 5: 71 α-​Amination, enantioselective 6: 58, 79 α–​Arylation 1: 165 2: 156, 173 5: 175 6: 46 α–​Arylation, enantioselective, of α–​halo ketone 4: 79 Conjugate addition to acceptor, enantioselective 3: 140 5: 113 Enantioselective Mannich 1: 151 From acid 4: 122 5: 46 6: 197 From alcohol 1: 26, 41, 86, 176 2: 85 4: 14 5: 15 6: 8, 11, 13 From aldehyde 2: 56, 147 4: 30 6: 3 From alkene 1: 120 2: 90, 178 3: 41, 43, 99, 209 4: 30, 48, 50, 51, 53–​55 5: 185, 191 6: 9, 13 From alkyne 3: 16 4: 3, 9, 17 6: 5 From amide 1: 11, 109, 163 2: 117 4: 184

From amine 4: 15 From diazo alkane 6: 45 From ester 4: 11 From ether 4: 17, 19 6: 15 From halide 6: 48 From nitrile 2: 82 From nitro 4: 3, 4 From sulfone 4: 17 From thiol 3: 5 α-​Halo, from allylic alcohol 6: 8 α-​Halo, homologation 4: 43 α-​Hydroxy, from alkyne 6: 9 Halogenation, enantioselective 1: 158 Homologation 4: 45 Hydroxylation 4: 17 Hydroxylation, enantioselective 1: 4, 118 4: 141 Protection (see Protection) Reduction to alcohol 1: 86 2: 15, 16 3: 5 5: 17, 21, 30 6: 14 Reduction to alcohol, enantioselective 1: 2, 43, 162, 165 2: 42, 143 3: 60, 64, 85, 89, 102, 103, 166, 170, 202 4: 68, 86, 88, 103, 166, 184, 186, 194, 202 5: 64, 66, 70, 85, 147 6: 16, 63, 65, 82, 206 Reduction to alkene 2: 16, 22 Reduction to amine 1: 16, 117 3: 9, 14, 109 4: 12, 16 5: 10, 15 Reduction to amine, enantioselective 2: 162, 204 3: 62, 69 4: 66, 68, 72, 138 5: 67, 68, 108, 109 6: 33, 58, 61 Reduction to ether 1: 16 2: 15 4: 19 Silyl enol ether coupling 3: 35 To aldehyde, α,β-​unsaturated 6: 202 To alkene 2: 16, 158, 174 3: 31 6: 198 To alkyne 3: 16 5: 47 6: 49 To allylic alcohol 6: 206 To amide 1: 20, 113, 147 2: 38, 76 To amine, enantioselective (homologation) 4: 72 (see also Ketone: reduction to amine, enantioselective) To azide 5: 12 To 1,1-​bis allyl 4: 40 To diene 5: 2 To enone 3: 7, 11 4: 190, 193 5: 11, 13 6: 46 To halide 6: 17 To α-​hydroxy ketone 4: 10 5: 14, 209

257  Reaction Index

Indole synthesis 3: 131 4: 131, 133 Ketal deprotection 3: 200 Ketone to methylene 4: 12 Mitsunobu coupling 5: 8 Nitrile from amide 4: 3 Oxazole formation 5: 133 Oxetane formation 6: 81 Pyrrole formation 4: 129, 132 Sulfide to sulfoxide 3: 6 Isocyanate to amide 4: 10 Isonitrile from aldehyde (one carbon loss) 4: 207 Isoxazole synthesis 3: 128

Reaction Index  258

258

Ketone (cont.) To α-​thio ketone 4: 15 To iodoalkene 1: 87 To methylene 1: 87 2: 86 3: 9 4: 12, 18, 75 6: 163, 173, 179 To nitro 4: 4 To propargyl alcohol 6: 49 Unsaturated, conjugate addition (see Enone: Conjugate addition) Unsaturated, epoxidation, enantioselective 3: 84, 156 Unsaturated, from aldehyde 3: 31 Unsaturated, from nitroalkene 6: 15 Unsaturated, from propargylic alcohol 2: 173, 182 Kolbe coupling 5: 44, 50 Kulinkovich reaction 1: 197 2: 71 3: 102 4: 55, 142 5: 46, 50, 95, 127 Lactam hydroxylation 2: 46 Lactam to nitro acid 6: 9 Lactam synthesis 1: 10, 20, 22, 59, 113, 147, 182, 193, 196, 197 2: 11, 12, 26, 28, 33, 37, 38, 46, 100, 120, 210 3: 29, 106, 107 4: 102, 104–​106, 111, 115 5: 175, 178, 183, 189, 191, 197, 205, 206, 207 6: 37, 39, 50 Lactone from ether 6: 12 Lactone, to α,β-​unsaturated lactone 2: 14 β-​Lactone homologation 2: 59 4: 136 Macroether synthesis 1: 183 2: 26, 170, 202 4: 64 Macrolactam synthesis 1: 72, 74, 83, 124, 132, 133, 142, 161, 185 2: 20, 26, 38, 134, 138, 152 3: 98 4: 107, 109, 113, 115, 199, 201 5: 103, 113, 206 6: 65, 73, 105, 109, 110, 129 Macrolactone synthesis 1: 6, 51, 71, 72, 94, 126, 131, 163, 187, 195 2: 20, 30, 32, 51, 52, 54, 66, 90, 112, 116, 136, 153, 156, 198, 199 3: 59, 97, 99, 101, 196 4: 33, 59, 60, 65, 91, 93, 99–​101, 195 5: 91, 92, 98, 99, 101, 103, 177, 182 6: 43, 47, 51, 83, 89, 91, 92, 97, 99, 101, 157, 161, 177, 183, 189, 201 Mannich Intermolecular 2: 55, 127 3: 34, 35 4: 105 5: 82, 87, 171 6: 107

Intermolecular, enantioselective 1: 65 2: 58, 62, 92, 118, 119, 121 3: 63, 69, 70, 77, 79–​85, 142 6: 65, 74–​80, 104, 107, 108, 111, 115, 140 Intramolecular 2: 28, 34, 35, 142, 149 3: 110, 119, 195 4: 203 6: 79, 111, 113, 115, 147, 185, 198 McMurry coupling 1: 43 2: 71 Mercaptan from alcohol 3: 12 Mercaptan to hydride 6: 14 Mercury catalyst Ketone from alkyne 4: 3 Pyridine synthesis 5: 130 Metathesis, Alkene. See Grubbs Metathesis with alkene and amide 4: 143 Metathesis with alkene and ester 5: 89 Metathesis with alkene and ketone 3: 46 Metathesis, Alkyne. See Alkyne: Metathesis Michael addition Intermolecular 1: 57, 84, 153, 166, 204 2: 23, 38, 60, 67, 74, 92, 101, 108, 120, 163 3: 136, 137–​143, 178 6: 33, 48, 93, 111, 113, 135, 178 Intermolecular, enantioselective 4: 138–​ 141, 146 5: 118, 137–​142 6: 59, 61, 65–​69, 72, 75, 77, 79, 102, 107, 134, 135, 136, 137, 139, 140, 141, 144, 145 Intramolecular 1: 166, 166, 167, 201 2: 38, 68, 73, 101, 102 3: 47, 52, 79, 76, 119, 142 4: 100, 101, 134–​136, 138, 139, 141 5: 161, 163, 170, 182, 183, 189, 193, 198, 199 6: 88, 115, 137, 145, 172, 195 Intramolecular, enantioselective 4: 135–​137, 157, 192 5: 139, 142, 143, 188, 192 6: 85, 116, 135, 136, 138, 141, 143 Microwave acceleration (not heating) Amide bond rotation 2: 151 Enzyme activity 3: 22 Mitsunobu reaction, improved 2: 145 3: 70 4: 6, 177 5: 8, 73, 114 6: 3, 6, 22, 89, 168, 172, 187 Natural product synthesis AB3217-​A 4: 37 Abyssomycin C 2: 170 Acetylaranotin 5: 93

 259

Attenol A 2: 200 Aurantioclavine 3: 116 Aureonitol 3: 98 Auxofuran 6: 127 Avrainvillamide 2: 11 Basiliolide B 5: 153 Batzellaside A 6: 110 Berkelic Acid 3: 101 5: 100 Bermudenynol 6: 97 Bisabosqual A 6: 93 Bistellettadine A 4: 153 Biyouyanagin A 3: 137 Blepharocalyxin D 2: 199 Blumiolide C 3: 59 Boivinianin B 4: 96 Botcinin F 3: 99 Bourgeanic Acid 4: 85 Brasilenyne 1: 154 Brevipolide H 6: 48 Brevisamide 3: 102, 4: 97 Briarellin F 4: 180 Brombyin II 4: 152 Brombyin III 4: 152 Bruguierol A 3: 101 Bryostatin 1 5: 89 Bryostatin 7 5: 176 Bryostatin 16 4: 194 Bucidirasin A 6: 154 Calciphylline N 6: 187 Calvosolide A 2: 136 Cameroonan-​7α-​ol 5: 40 Caribenol A 4: 153 5: 159 Carissone 5: 156 Cassaine 3: 155 6: 179 Caulophyllumine B 5: 107 Cavicularin 6: 95 Celogentin C 4: 35 Centrolobine 2: 11 Cephalosporolide E 6: 100 Cephalosporolide F 6: 100 Cephalostatin 1 4: 182 Cephalotaxine 3: 117 4: 116 Cermizine A 3: 118 Cermizine B 6: 139 Cernunine 3: 184 Chatancin 6: 157 Chimonanthine 2: 188 Chinensiolide B 4: 63 Chloranthalactone A 5: 160

259  Reaction Index

Actinophyllic Acid 4: 202 Aculeatin A 6: 86 Acutiphycin 2: 136 Acutumine 3: 204 6: 167 Adaline 4: 111 Agelastatin A 5: 112 α-​Agorafuran 4: 145 Agelastatin 1: 188 Agelastatin A 6: 158 Ageliferin 5: 145 Aigialomycin D 2: 112 3: 101 Akaol A 5: 123 Akuammicine 5: 115 Alkaloid 205B 2: 111 Alkaloid 223A 4: 111 Alkaloid 223AB 3: 112 Alliacol 1: 80 Allokainic Acid 5: 40 6: 112 Allomatrine 6: 111 Amathaspiramide F 6: 111 Amphidinolide 1: 50, 94 Amphidinolide F 6: 177 Amphidinolide K 4: 59 Amphidinolide V 3: 55 Amphidinolide X 3: 58 Amphidinolide Y 3: 53 Anamarine 4: 65 Anatoxin 1: 82 Anominine 4: 190 Antasomycin 2: 19 Anthecotulide 5: 98 Apicularen A 4: 101 Apiosporic Acid 5: 154 Apratoxin C 6: 64 β-​Araneosene 2: 71 Arglabine 3: 55 Armillarivin 5: 158 Arnebinol 2: 186 Aromadendranediol 3: 143 Artimisin 5: 28, 43, 101 Arundamine 6: 125 Aspalathin 4: 98 Aspercyclide 4: 99 Aspercyclide C 6: 97 Asperolide C 6: 143 Asperpentyn 4: 58 Aspidophylline A 4: 208 Aspidophytidine 2: 157 Aspidospermidine 5: 115

Reaction Index  260

260

Natural product synthesis (cont.) Chromazonarol 5: 49 Citlalitrione 1: 24 (6E)-​Cladiella-​6,11-​dien-​3-​ol 2: 170 Cladospolide C 2: 153 Clausevatine D 4: 129 Clavicipitic Acid 4: 127 Clavilactone A 6: 97 Clavilactone B 2: 156 Clavirolide A 3: 192 Cleavamine 4: 117 Cocaine 4: 116 Cochliomycin B 6: 101 Codeine 4: 161, 172 6: 159 Colombiasin A synthesis 2: 105 Combretastatin A-​4 5: 47 Communiol A 5: 99 Complanadine A 4: 113 Complestatin 4: 200 β-​Conhydrine 3: 15 Conocarpan 3: 100 Coraxeniolide A 3: 139 Cortistatin A 5: 168 Coryantheidol 2: 140 CP-​99,994 4: 110 Crinine 5: 117 Crinipellin A 6: 193 Crispine A 3: 118 Crotogoudin 6: 135 Cruentaren A 3: 164 Cyanolide A 5: 99 6: 92 Cyanthiwigin 1: 180 Cyanthiwigin F 3: 151 Cybrodol 4: 123 Cycloclavine 4: 133 Cytospolide P 6: 99 Cytotrienin A 3: 59 Dactylolide 3: 59 5: 101 Daphenylline 6: 173 Daphmanidine E 5: 180 Dasycarpidone 3: 117 Davidiin 5: 103 Deacetoxyalcyonin acetate 1: 76 Decursivine 4: 109 Decytospolide A 6: 99 Defucogilvocarcin A 5: 156 Dendrobatid alkaloid 251F 1: 112 Dendrobine 5: 192 Deoxopaosopinine 5: 116

6-​Deoxyerythronolide B 4: 33 7-​Deoxyloganin 4: 101 Deoxyharringtonine 2: 140 Deoxyneodolabelline 1: 42 7-​Deoxypancriastatin 3: 111 5-​Deoxystrigol 6: 160 Desmethoxyfusarentin 5: 123 1-​Desoxyhypnophillin 3: 147 11, 12-​Diacetoxydrimane 3: 153 Dictyosphaeric Acid A 4: 100 Didemnaketal B 6: 191 Didemniserinolipid B 3: 172 6: 99 Digitoxigen 2: 183 Dihydroactinidiolide 4: 50 5,6-​Dihydrocineromycin B 6: 101 Dihydrocuscohygrine 6: 44 Dihydroxyeudesmane 3: 29 Dimethyl Gloiosiphone A 3: 145 Discodermolide 3: 166 6: 197 Disorazole C1 6: 201 Dolabelide D 2: 89 Dolabellane 1: 42 Dolabellatrienone 2: 100 Drupacine 3: 113 Dumetorine 2: 153 Dysiherbaine 3: 94 DZ-​2384 6: 117 Echinopine A 5: 153, 163, 194 Echinosporin 5: 161 Elansolid B1 6: 152 Elatol 3: 57 Elisapterosin B 2: 105 Englerin A 4: 95 5: 97 Ephedradine 1: 142 5-​epi-​Citreoviral 4: 61 8-​Epihalosilane 4: 63 Epothilone B 3: 198 Epoxomycin 1: 172 β-​Erythrodine 2: 169 Erythronolide A 2: 53 Esermethole 2: 108, 139 3: 116 5: 118 Estrone 6: 137 Ethyl Deoxymonate B 3: 96 Etnangien 4: 99 Eunicillin 1: 76, 135 D-​Fagoamine 2: 165 Fawcettidine 3: 115 Fawcettimine 3: 178 5: 154 6: 152 Febrifugine 6: 110

 261

Harringtonolide 6: 94 Harveynone 5: 161 Haterumalide NA 3: 100 Helianane 5: 73 Herbindole A 5: 131 Himandrine 4: 151 Hirsutellone B 4: 174 5: 153 Histrionicotoxin 5: 75 Hongoquercin A 6: 119 Huperzine A 4: 111 6: 145 Huperzine Q 6: 149 Hyacinthacine A2 5: 12 Hyacinthacine B3 4: 105 Hybridilactone 5: 98 (+)-​6'-​Hydroxyarenarol 3: 15 4-​Hydroxydictyolactone 4: 162 19-​Hydroxysarmentogenin 6: 163 Hyperibone K 4: 159 Ialibinone A 4: 147 Ialibinone B 4: 147 Ibophyllidine 5: 117 Incarviditone 5: 102 Incarvillateine 3: 180 Incarvilleatone 5: 102 Indolizidine 207A 5: 114 Indolizidine 223AB 6: 114 Indoxamycin B 5: 184 6: 147 Indoxamycin F 6: 94 Ingenol 1: 14, 134 6: 175 Ipomeamarone 6: 98 Isatisine A 6: 100 Iso-​Eriobrucinol A 6: 93 Isoglaziovianol 6: 151 5-​F2t-​Isoprostane 3: 57 Irofulven 2: 157 Isatisine A 5: 96 Isoborreverine 5: 114 7-​Isocyanoamphilecta-​11(20),15-​ diene 5: 152 7-​Isocyano-​11(20),14-​ epiamphilectadiene 5: 157 Isoedunol 2: 71 Isofagomine 3: 56 Isofregenedadiol 5: 121 7(RS)-​ST-​Δ8-​11-​dihomo-​Isofuran 6: 90 10-​epi-​17(RS)-​SC-​Δ15-​11-​dihomo-​ Isofuran 6: 96 Isohouamine B 5: 115 5-​F3t-​Isoprostane 6: 46

261  Reaction Index

Ferrugine 1: 82 Flinderole A 5: 114 Flinderole A 5: 114 Floriesolide B 2: 112 Fluvirucinine A2 4: 113 Fomannosin 3: 188 Fometellic Acid B 4: 143 Fornicin C 6: 68 FR182877 4: 164 FR901483 3: 119 5: 116 Frondosin A 4: 149 6: 153 Frondosin B 4: 139 Frontalin 6: 62 Frullanolide 5: 158 Fuligocandin B 5: 45 Fusicoauritone 2: 208 Fusiocca-​1,10 (14)-​diene-​8β, 16-​triol 5: 33 Galactin 6: 78 Galanthamine 6: 117 Galbelgin 5: 83 Galbulin 5: 139 Galubima alkaloid 1: 12 2: 79 Gamberiol 4: 97 Garsubellin A 2: 51 GB 13 4: 192 GB 175 5: 188 Gelsemine 5: 182 Gelsemiol 5: 158 Gelsemoxonine 5: 178, 204 Gephyrotoxin 6: 115 Geranullinaloisocyanide 5: 65 Gigantecin 2: 154 Gleenol 3: 159 Gloeosporone 4: 91 Glycinoeclepin A 4: 186 Goniomitine 5: 118 6: 42, 70, 131 Goniothalesdiol A 4: 100 1-​Gorgiacerol 5: 100 Gracilamine 5: 202 Grandisine G 5: 119 Grandisol 4: 63 Guanacastepene E 2: 123 Guanacastepene N 2: 174 Gymnothelignan N 6: 99 Hainanolidol 6: 94 Halenaquinone 3: 155 Hamigeran B 1: 120 3: 149 4: 125 Haouamine B 5: 115

Reaction Index  262

26

Natural product synthesis (cont.) Jatrophatrione 1: 24 JBIR-​22 6: 157 Jerangolid D 3: 95 Jerantinine E 6: 103 Jiadifenolide 5: 166 Jimenezin 2: 135 Juvabione 2: 204 Kainic Acid 3: 52, 112, 116 4: 89, 112 5: 112 6: 115, 116 Kaitocephalin 5: 37 KDN 4: 93 Kendomycin 2: 114 4: 121 Khayasin 5: 198 Kingianin H 6: 153 Kuwanon J 6: 155 Lactacystin 1: 196 2: 108 6: 80 Lactiflorin 5: 161 Lactimidomycin 4: 65 6: 101 Lactone L-​783,277 4: 101 Lasalocid A 3: 91 Lasiol 4: 87 Lasonolide A 2: 199 6: 183 Lasubine 1: 134 Lasubine II 2: 139 Latrunculin 2: 51 18-​epi-​Latrunculol A 6: 88 Laurefucin 5: 102 Leiodermatolide 6: 189 Lepadiformine 2: 107 6: 114 Lepadiformine 3: 111 Lepadin 1: 142 Lepadin B 3: 59 Lepenine 6: 185 Lepistine 6: 113 Leucascandrolide A 3: 170 Leuconolactam 5: 111 Limazepine E 6: 110 Lithospermic Acid 5: 41 Littoralisone 2: 1 Longicin 2: 51 Louisianin C 3: 135 Lucidulin 5: 113 Lunarin 5: 113 Lupeol 4: 168 Lyconadin A 3: 168 Lyconadin C 6: 111, 113 Lycoperine A 4: 112 Lycopladine A 2: 159

Lycopodine 3: 194 Lycoposerramine-​C 4: 103 Lycoposerramine-​S 5: 117 Lycoposerramine-​Z 5: 118 Lycoramine 2: 208 γ-​Lycorane 2: 108 Lycoricidine 2: 100 Lycorine 6: 154 Lysergic Acid 3: 117 5: 67 Macrolide RK 397 3: 163 Magnofargesin 2: 135 Majusculone 2: 207 Manzamine A 5: 196 Maoecrystal V 4: 196 6: 95, 155 Maoecrystal Z 5: 170 Marginatone 5: 154 Maribacanine 5: 41 Mearsine 4: 116 Merrilactone 2: 113 Mesembrine 5: 137 Metacycloprodigiosin 5: 41 Methyl 7-​Dihydro-​trioxaacarcinoside B 3: 54 Methyl N,O-​Diacetyl-​α-​L -​ acosaminide 5: 79 N-​Methylwelwitindolinone C 5: 174 N-​Methylwelwitindolinone D Isonitrile 4: 206 ent-​Monomorine 6: 105 Morphine 2: 141 Mucosin 5: 147 Muironolide A 6: 157 Muramycin D2 5: 42 Myceliothermophin A 5: 159 Myceliothermophin E 6: 161 Mycestercin G 5: 85 Mycoleptodiscin A 6: 133 Myrioneuroinol 6: 107 Nakadomarin A 4: 170, 200 5: 151, 206 Nakiterpiosin 4: 184 Nanakurines A and B 3: 200 Navenone B 4: 58 Nazlinine 6: 32 Neofinaconitine 6: 171 Neovibsanin B 4: 150 Nhatrangin A 6: 76 Nicolaloidesin B 6: 154 Nicotine 4: 110 Nigellamine A2 2: 97

 263

Poitediol 4: 63 Ponapensin 5: 103 Premarineosin A 6: 115 9β-​Presilphiperfolan-​1α-​ol 5: 157 Preussin 4: 114 Prostaglandin E1 5: 143 Prostaglandin F2α 5: 141 Przewalskin 5: 43 Pseudolaric Acid 4: 166 Pseudopterosin G-​J 5: 55 6: 156 Pseudotabersonine 4: 65 Psoracorylifol B 6: 97 Psylloborine A 6: 195 Ptilocaulin 4: 152 Pumiliotoxin 251D 3: 112 Pycnanthuquinone C 4: 153 Pyrenolide D 6: 96 Quebrachamine 4: 56 Quinidine 1: 84 Quinine 1: 84 4: 117 Quinocarcin 5: 109 Quinolizidine 217A 5: 105 Rapamycin 3: 176 Reserpine 5: 119 Rhazinal 5: 127 Rhazinicine 3: 114 Rhazinilam 2: 26, 140 4: 107 6: 72, 129 Rhishirilide B 2: 175 Ricciocarpin A 3: 143 Rimocidinolide 1: 162 Roseophilin 5: 113, 210 Rotundial 4: 135 Rubriflordilactone A 6: 123 Rufuscenolide 6: 153 Rumphellanone A 5: 160 Runanine 5: 113 Saliniketal B 3: 99 Salinosporamide 1: 196 Salmochelin SX 3: 99 Salvileucalin B 5: 164 Salvileucalin C 6: 159 Salvileucalin D 6: 159 Sanguline H-​5 3: 97 Sarain A 2: 149 6: 117 Sarcandralactone A 6: 156 Sauropus hexoside 6: 98 SB-​203207 6: 181 SC-​Δ9,13-​9-​IsoF 4: 96 Scabronine G 5: 152 6: 151

263  Reaction Index

Nitidasin 6: 199 Nodulisporic Acid D 6: 203 Nomine 2: 167 Nookatone 6: 151 Norfluorocarine 3: 109 Norhalichondrin B 4: 59 Norzoanthamine 1: 146 3: 206 NP25302 2: 139 Okilactomycin D 5: 155 Omaezakianol 3: 93 Omuralide 1: 196 Ophiobolin A 6: 165 Ophirin 1: 134 Ottelione B 3: 57 Oximidine II 5: 91 Pachastrissamine 4: 98 Paclitaxel 6: 205 Paeonilactone B 3: 96 Pallavicinolide A 4: 151 Panaxtriol 3: 56 Pancratistatin 6: 150 Paspaline 6: 207 Paspalinine 5: 200 Pasteurestin A 3: 145 Pauliurine F 3: 110 Penaresidin A 6: 112 Pentalenene 3: 145 9-​epi-​Pentazocine 3: 114 Penifulvin A 3: 161 Pentalenene 4: 157 Peribysin-​E 5: 159 Pericosine E 6: 56 Peridinin 4: 45 Periplanone C 2: 153 Phaseolinic Acid 3: 54 Phenserine 1: 142 Phomactin A 1: 32 Phomopsidin 4: 151 Pinnotoxin A 3: 190 Pinolinone 6: 158 Piperenol B 6: 141 Pladienolide D 3: 53 Plakotenin 5: 155 Platencin 4: 75 6: 157 Platensimycin 2: 131 5: 97 6: 151 Pleocarpenone 2: 206 Pleuromutilin 5: 208 Plicatic Acid 4: 155 Podophyllotoxin 1: 68 4: 83 6: 38

Reaction Index  264

264

Natural product synthesis (cont.) SCH 351448 2: 115 Schindilactone A 5: 172 Scholarisine A 6: 36 Sclerophytin A 4: 100 Sculpnoneatin N 6: 152 Securinine 4: 111 Sedacryptine 6: 113 Septicine 6: 113 Serotobenine 3: 98 Serpentine 6: 116 Serratezomine A 3: 119 Shimalactone A 3: 157 Shiromool 5: 149 Siamenol 3: 119 Solandelactone E 3: 97 Solanoeclepin A 4: 204 Sordaricin 1: 128, 198 Spectaline 6: 109 Spiculoic Acid A 2: 169 Spirastrellolide A Me Ester 3: 97 Spirofungin A 3: 174 Spirolaxine Methyl Ether 3: 95 Spirotryprostatin B 3: 113 Steenkrotin A 6: 209 Stemoamide 2: 107 Stephacidin B 2: 11 Streptorubin B 4: 141, 41 Strychnine 1: 58 3: 115 4: 115, 117 5: 115 Subincanadine F 4: 114 Sundiversifolide 5: 43 Superstolide A 3: 182 Symbioimine 2: 170 Tabersonine 6: 111 Taiwaniaquinone G 3: 127 Tangutorine 3: 118 Tanikolide 4: 73 Terpestacin 2: 193 Terreusinone 5: 129 Tetracyclin 1: 190 Tetrodotoxin 1: 136 Teurilene 6: 82 TMC-​151 C 5: 63 Tocopherol 1: 142 Tonantzitlolone 1: 188 Tremulenolide A 2: 70 Trichodermatide A 6: 93 Triclavulone 1: 102 Trigolutes B 6: 117

Trigonoliimine A 6: 60 Tryprostatin A 4: 131 Tuberostemospiroline 6: 115 Tubigensin A 5: 186 6: 121 Tylophorine 4: 112 Ushikulide A 3: 202 Valerenic Acid 4: 150 Valienamine 1: 188 Vannusal 4: 176 Varitriol 4: 98 5: 96 Vibralactone C 3: 159 Vigulariol 2: 201 Vincadifformine 5: 115 Vindoline 2: 45 4: 188 E-​δ-​Viniferin 6: 40 Vinigrol 4: 178 5: 155 6: 155, 169 Virginamycin M2 4: 115 Vitamin A1 6: 52 Walsucochin B 6: 159 Welwitindolinone A Isonitrile 3: 186 8-​epi Xanthatin 2: 51 Xenovenine 4: 114 Xestodecalactone A 2: 201 6: 101 Yangonine 3: 43 Yohimbine 3: 115 (6,7-​deoxy)-​Yuanhuapin 5: 161 Zampanolide 5: 42 Zaragozic Acid 3: 196 Zoanthenol 4: 119 Zoapatanol 1: 109 Nazarov cyclization 2: 208 5: 139, 146 Negishi coupling. See Palladium Nitrile Alkylation 1: 99 4: 87 6: 46 Alkylation, intramolecular 5: 160, 162 α-​Aryl, from α-​triflyl 4: 78 Alkylation 1: 199 4: 87 From acid 1: 12 2: 43 4: 3 6: 7 From alcohol 3: 30 5: 9, 46 6: 13 From alcohol, with inversion 1: 106 From aldehyde 1: 17 5: 7 From alkene 2: 181 4: 51 From alkenyl halide 6: 5, 6 From alkyne 2: 146 From alkyne, loss of carbon 5: 9 From amide 1: 12 2: 43 4: 3 From amine 3: 14 4: 14 6: 11 From aryl halide 2: 21 6: 36 From azide 2: 14 4: 19 5: 11 From halide (adding one carbon) 4: 38

 265

From unsaturated acid (one-​carbon loss) 2: 44 5: 9 Radical homologation 1: 108 Reduction to amine 3: 9 Reduction to nitroalkane 4: 173 To ketone 6: 15 Organocatalysis 1: 4, 62, 91, 114, 115, 116, 118, 119, 124, 125, 151–​153, 166, 167, 202, 205 2: 1, 2, 4, 6, 8, 9, 14, 60, 61, 67, 68, 100, 101, 102, 118, 119, 139, 166, 171–​173, 195, 203, 204 3: 61–​66, 68–​71, 73, 75–​86, 88, 136–​143, 154–​156 4: 66–​77, 79, 80, 82–​85, 87–​89, 91, 92, 94, 101, 103, 106, 107, 109, 116, 117, 134–​141, 157, 160, 171, 174, 192 5: 61, 66, 67, 72, 74, 75, 78, 79, 81–​84, 91, 104, 105, 108, 109, 111–​113, 115, 119, 136–​143 6: 45, 48, 52, 58–​65, 67–​77, 79–​85, 87, 91, 102, 104–​108, 110, 116, 117, 126, 134–​141, 155, 157, 192, 200, 206 Osmylation. See also Sharpless asymmetric dihydroxylation Of alkene 1: 8, 21 3: 78 4: 111, 168, 179 5: 31, 54 6: 168, 169, 171, 178, 194, 195, 198, 205 Of diene 1: 15 6: 175 Oxamination Of ketone, enantioselective 1: 4, 118 Oxazole synthesis 3: 128 5: 133 Oxetane opening 6: 81 Oxy-​Cope rearrangement 1: 24 3: 204 5: 136, 184 6: 35 Ozonolysis 1: 43, 77, 95, 113 2: 78 3: 41, 147, 161, 166, 167, 205, 207 4: 18, 160, 174, 202 5: 56, 59, 208 6: 53, 162, 164, 175, 190, 192, 203 Palladium catalysis Acid decarboxylation 6: 46 Alcohol oxidation 6: 11 Alcohol silylation 2: 130 Aldehyde arylation 4: 207 Aldehyde decarbonylation 5: 12, 126 Aldehyde from allylic alcohol 4: 11 Aldehyde homologation 4: 69 Alkene to alcohol 6: 55

265  Reaction Index

From halide (carbon count unchanged): 4: 4 From methyl arene 4: 32 From nitro alkane 2: 6 6: 13 From unsaturated amide, enantioselective 1: 150 Reductive cleavage 1: 13 4: 112 To aldehyde 5: 26 6: 19 To alkene 3: 33 To alkyl 2: 200 To alkyl amine 4: 40 5: 13 To alkyne, by metathesis 2: 148 3: 31 To amide 2: 43 4: 3 6: 2, 181 To amine 6: 11, 13, 14, 16 To hydride 4: 13 6: 10 To ketone 2: 82 6: 45 To methyl 5: 10 Unsaturated, enantioselective conjugate addition 6: 77 Unsaturated, reduction, enantioselective 4: 74 Nitro From amide 6: 9 From amine 3: 4 4: 15 From ketone 4: 4 To alcohol 3: 85 To aldehyde 4: 19 To amine 3: 4, 15, 17 5: 13, 30 6: 18 To hydride 3: 9 5: 4: 171 5: 192 To ketone 4: 3, 4 6: 155 To nitrile 6: 13 Nitro alkane Alkylation 5: 53 Enantioselective conjugate addition 4: 67, 135–​137 Nitro alkene Conjugate addition 5: 197 Diels-​Alder dienophile 6: 155, 156 Enantioselective conjugate addition 1: 153 2: 166 3: 73, 75, 77, 83, 85, 136, 141 4: 74, 77, 79, 81, 83–​85, 87, 94, 134, 135, 137, 140, 141, 171 5: 72, 75, 79, 86, 181 6: 65, 68, 73–​77, 79, 107, 137, 145 Enantioselective conjugate alkoxylation 3: 64 4: 95 Enantioselective conjugate amination 4: 67 5: 64 6: 63, 109 Enantioselective reduction 1: 150 From alkene 4: 54 6: 51

Reaction Index  266

26

Palladium catalysis (cont.) Alkene alkoxy arylation 1: 142 2: 134 Alkene alkylation 3: 39 Alkene amination 3: 40, 80, 108 Alkene amino arylation 2: 138 Alkene borylation 5: 57 Alkene carbonylation 1: 148, 178 3: 37, 41 5: 99, 173 6: 53, 87, 96, 104 Alkene chloroarylation 3: 41 Alkene diamination, enantioselective 3: 80 4: 110 6: 50 Alkene dihydroxylation 4: 50 Alkene dihydroxylation, enantioselective 6: 86 Alkene to enone 6: 34, 55 Alkene homologation 4: 55 5: 55, 57, 60 6: 50, 55 Alkene oxidative cleavage 4: 52 Alkene protection 5: 54 Alkene reduction 3: 9, 20 4: 40 5: 59, 170 6: 89, 105 Alkenyl phosphonate from alkyne 4: 11 Alkyne addition 2: 73 Alkyne to alkene 4: 5 6: 18, 83 Alkyne borylation/​stannylation 4: 45 Alkyne coupling 4: 195 5: 55, 144, 153 Alkyne coupling with acrolein 4: 39 5: 45 Alkyne stannylation 6: 67 Alkyne to ester 5: 47 Alkyne reduction 5: 10, 47 6: 31 Allene diborylation 2: 48 Allene formation 6: 43, 47 Allene stannylation 2: 95 Allyl ester reduction 5: 187 Allyl ether cleavage 3: 18 Allylic amination, enantioselective 6: 65 Allylic oxidation 5: 32 Allylic rearrangement/​coupling 1: 56, 58, 78, 128, 164, 165, 192, 193 2: 32, 62, 70, 97, 108, 122, 193, 194, 205 3: 14, 18, 25, 29, 34, 35, 103, 107, 113, 117, 144–​146, 150, 151 4: 44, 70, 75, 80, 84, 100, 101, 105, 111, 117 5: 20, 68, 75, 83, 100, 106, 144, 145, 166, 184, 187, 191 6: 47, 49, 66, 68, 71, 80, 81, 83, 85, 98, 104, 109, 111, 112, 115, 147, 148, 187 Amide reduction 3: 9 Amide to nitrile (reversible) 2: 43

Amine deprotection 6: 185 Amine from allylic alcohol, enantioselective 4: 70 Anion coupling 6: 42 Arene acylation 2: 82 4: 123 Arene amination 4: 123, 125 5: 126 Arene borylation 2: 40 Arene carboxylation 2: 40 Arene construction 5: 123 Arene halogenation 2: 81 3: 124, 125 4: 122, 125 5: 121, 122, 125 Arene homologation 4: 118–​120, 122–​ 125 5: 120, 123, 136, 151 Arene hydroxylation 4: 118 5: 121 Arene nitration 4: 119 Aryl mesylate carbonylation 3: 32 Aryl substitution 1: 19, 171 2: 22, 25, 26, 42, 156, 180, 185, 209 3: 27, 31, 123, 124, 125, 127, 134 4: 74, 102, 103, 118–​120, 122–​125, 207 5: 27, 55, 75, 107, 120–​123, 126, 136, 151, 201 6: 29, 31, 35, 36, 37, 39, 41, 53, 57, 67, 117–​122, 125, 131, 133, 142, 203 Aziridine formation 4: 102 Aziridine opening 6: 108 Benzylic coupling 6: 43 Borane coupling 3: 41 Borylation of allylic alcohol 4: 41 Carbonylation 2: 43 3: 120 5: 36 6: 45, 55 C-​H to amine: 4: 35 6: 39 C-​H to amine, enantioselective: 4: 84 C-​H to C-​C: 4: 32, 35, 36, 37 5: 33, 35, 37, 39, 41, 45 6: 35–​37, 39, 144 C-​H hydroxylation 1: 157 2: 18, 82, 134 4: 33, 34 5: 32 6: 207 Claisen rearrangement 5: 75 6: 85 Conjugate addition 2: 73 4: 46, 105 6: 144 Cope rearrangement 3: 116 Coupling with allenyl alcohol 4: 41 Coupling with allylic alcohol 4: 44 Coupling with allylic alcohol, enantioselective 4: 70, 80 Coupling with triflate 4: 78 Cyclobutane synthesis 3: 157 5: 144 Cyclohexane synthesis 3: 151, 157 Cyclooctane synthesis 3: 157

 267

Ketone to amide 4: 38 Ketone to diene 5: 2 Ketone to enone 2: 131, 142 3: 206 5: 11, 168, 208 6: 173, 198 Ketone hydrogenation 6: 99 Ketone α-​hydroxylation 4: 10 Kumada coupling 3: 120 β-​Lactam formation 4: 103 β-​Lactone formation 6: 90 Negishi coupling 1: 61, 164, 192 2: 91 3: 106 5: 47 6: 173 Nitrile from alkenyl halide 6: 5 Nitrile from aryl halide 2: 21 Nitrile homologation to ketone 2: 82 Nitrile to amine 6: 19 Nitrile to methyl 5: 10 Nitro to amine 6: 18 Organotin coupling 3: 31 Organozirconium coupling 1: 104 Oxidation of alcohol 2: 13, 122, 128 Phenol to hydride 2: 86 Piperidine synthesis 5: 107, 186, 188 Polycarbocyclic construction 3: 145, 157 Propargylic coupling 4: 47 5: 90 6: 176 Pyrazole synthesis 3: 131 Pyridine substitution 3: 133, 135 4: 113 Pyridine synthesis 6: 131, 133 Pyrrole synthesis 3: 134 5: 130 6: 126 Pyrrolidine synthesis 4: 103–​106 5: 106, 108, 112, 114 Reductive amination 3: 108 5: 16 Reductive amination, enantioselective 4: 68 Sonogashira coupling 1: 60, 175 2: 155, 185 (Cu only = Castro-​Stephens) 3: 33 (Fe only) 4: 41 5: 30, 31, 129, 161 6: 45, 166 Spiroketal from alkene 3: 99 Spiroketal from alkyne 3: 95 6: 87 Stille coupling 1: 7, 60, 155 2: 100, 150 3: 32, 111, 183 4: 45, 48, 65, 74, 81, 89, 174, 187 5: 55, 201 6: 163, 177, 187, 189, 201 Suzuki Intermolecular 1: 54, 85 2: 22, 39, 62, 79, 83, 126, 159, 188 3: 120, 122, 167, 179, 203 5: 21, 55, 136, 180 6: 101 202 Intramolecular 1: 33

267  Reaction Index

Cyclopentane synthesis 3: 145, 149 5: 144–​146 Cyclopropane synthesis 3: 150 Decarboxylation of acid to alkene 1: 157 Diazo to amino 6: 63 Enol phosphate coupling 3: 89 Enol triflate carbonylation 2: 28 Enol triflate coupling 5: 167, 180, 201 Enol triflate reduction 5: 189 6: 198 Enone conjugate addition 5: 49 Epoxide opening 4: 111 Ether oxidation 3: 89 Fluorination 5: 26 Furan synthesis 2: 41 3: 128, 130 6: 130 Halide to alkene 5: 7 Haloalkene coupling 5: 170 6: 46 Haloalkene to alkene 5: 179 6: 46 Haloarene amination 2: 87, 155 Haloarene cyanation 3: 120 Haloarene hydrolysis 3: 127 Heck Intermolecular 1: 18, 21, 20, 105, 122, 142, 174, 175 2: 39, 104, 178, 186 3: 35, 43, 120–​122, 175 4: 49, 51, 55, 78, 98 5: 41, 57, 120, 122, 123, 151, 172 6: 43, 53, 71, 102, 142 Intramolecular 1: 1, 18, 58, 59 2: 28, 114, 141, 157, 174 3: 109, 113, 114, 117, 151 4: 99, 107, 117, 165, 209 5: 127 6: 29, 31, 49, 57, 143, 145, 168, 189 Oxidative 4: 49, 55, 78 Oxidative, enantioselective 4: 79 Hydroamination of alkyne 2: 37 Hydrogenolysis of allylic ether 5: 10 Hydrogenolysis of benzyl ether 4: 8 6: 99, 101 Hydrogenolysis of benzylic amine 2: 186 Hydrogenolysis of benzylic nitro 3: 9 Hydrogenolysis of epoxide 1: 1 Imine reduction 3: 67 In ionic liquid 1: 21 Indole synthesis 3: 129, 131 5: 31, 129, 131, 201 6: 117, 129, 131, 133 Ketone α-​allylation 5: 166, 184, 191, 201 Ketone α-​allylation, enantioselective 3: 68, 73 4: 76 Ketone α-​arylation 1: 165 2: 156, 173 4: 102 6: 91

Reaction Index  268

268

Palladium catalysis (cont.) Tetrahydrofuran construction 5: 90 Wacker oxidation of alkene to aldehyde 4: 68 Wacker oxidation of alkene to ketone 1: 120 2: 90 3: 99, 209 4: 50 6: 9, 52, 55 Pauson-​Khand cyclization 1: 201 2: 70 4: 103, 112, 146 5: 31, 145, 147, 173 Petasis condensation 4: 105 Phosphine oxide, from alkene 3: 39 Phosphonate From acid 4: 18 6: 194, 196 From alkene 4: 48 Phosponium salt From alcohol 2: 85 From alkene 2: 125 5: 56 Pinacol coupling 1: 64 2: 71 Pinacol rearrangement 1: 15 4: 204 5: 74 Piperidine synthesis 1: 13, 30, 39, 49, 59, 70, 92, 93, 132, 134, 138, 139, 143, 164, 182, 192, 193 2: 33, 34, 65, 79, 80, 109, 111, 137, 138, 153, 165, 166, 168, 195, 196, 206 3: 56, 59, 160, 168, 169, 181, 184, 195, 201 4: 57, 60, 63, 103, 105, 107, 109–​117 5: 38, 103, 104, 107, 109, 111, 113, 116, 119, 182, 188, 197, 207 6: 16, 43, 52, 71, 103, 105, 107, 109–​111, 113–​117, 129, 131, 136, 139, 145, 152, 154, 172, 181, 185, 194, 195 Polyene synthesis 1: 162 2: 150, 153, 174, 199 3: 44, 47, 58, 123, 163, 176, 177, 182, 183 4: 9, 58, 59, 63, 65, 97, 99, 100, 101, 115, 139, 151, 153, 154, 164, 165, 167, 174, 175 5: 61, 190 6: 45, 46, 53, 66, 149, 157, 168, 183 Prins cyclization 2: 32, 96, 136, 197, 199 3: 88, 89 4: 91–​93, 95, 100, 180 5: 92, 99 6: 81, 85, 87, 91 Propargyl coupling 1: 53 3: 76, 83, 85, 104, 164 4: 47 5: 90 6: 83 Protection Of acid (ester, amide) 1: 46, 100, 144, 156, 172 2: 7, 43, 48, 59, 89 3: 17, 19, 20, 22, 23 4: 21, 22, 24, 27, 29 5: 20 6: 20, 23, 24, 27, 33, 79, 119, 168

Of alcohol 1: 4, 16, 34, 40, 86, 144, 145, 155, 156, 158, 177 2: 10, 47, 48, 87, 90, 91, 129, 130, 191 3: 18, 20, 21 4: 4, 8, 20, 23–​26, 28, 29, 58, 167, 175 5: 6, 18, 20–​24, 178 6: 21–​24, 27, 64, 96, 99, 101, 105, 147, 151, 162–​179, 181–​185, 187–​193, 195–​ 205, 208, 209 Of aldehyde 3: 23 4: 22, 29 5: 21, 23 6: 20, 23, 27, 146, 162, 192, 194, 196, 200 Of alkene 4: 18, 21, 208 5: 21, 54 6: 26 Of alkyne 2: 129 3: 23 5: 19 6: 25, 26 Of allylic alcohol 4: 26 6: 21 Of amide 5: 25 Of amine 1: 40, 56, 59, 100, 101, 144, 170, 193 2: 10, 48, 83, 130, 149 3: 19, 21–​23, 116 4: 20, 21, 23, 25, 27, 28, 193, 209 5: 19, 20, 23–​25, 27, 182 6: 21, 23, 25, 28, 30, 111, 113, 115, 133, 173, 181, 195 Of amino acid 5: 25 Of enone 6: 99 Of ketone 2: 80, 129 3: 19, 21 4: 22, 24, 27, 29, 190 5: 23, 25, 155, 189 6: 20, 23, 24, 163, 171, 173, 188, 189, 193, 198, 202, 203, 206, 207 Of nitrile 6: 27 Of phenol 1: 145 2: 112 3: 21 4: 21, 23, 26 5: 17, 19, 25 6: 32, 101, 119, 133, 184 Of sulfonic acid 4: 21 Of thiol 5: 23 Pyrazole synthesis 5: 133 Pyridine synthesis 1: 10, 49, 123, 139, 171 2: 25, 42, 159, 188, 209 3: 102, 103, 105, 107–​109, 111, 112, 114, 115, 117, 119, 129, 133, 135 4: 127, 129, 131, 133 5: 128–​131, 135 6: 29, 127–​129, 131, 133 Pyrrole synthesis 1: 170, 189 2: 41, 159, 187 3: 128, 130, 132, 134 4: 107, 126, 128-​130, 132 5: 27, 128, 130, 132, 134, 135, 139 6: 33, 73, 105, 115, 126, 128–​130, 132 Pyrrolidine synthesis 1: 11, 31, 48, 59, 82, 83, 84, 92, 106, 138, 139, 143, 182, 184, 196 2: 33, 34, 37, 73, 74, 91, 92, 107, 108, 110, 111, 137, 138, 168, 196

 269

Quaternary center, stereocontrolled Acylic, alkylated 1: 114, 196 2: 23, 24, 128, 164 3: 71, 73, 77, 81, 83, 85, 191 4: 32, 36, 75–​79, 81, 87, 138 5: 73–​76, 81, 83, 87, 95 6: 61, 66, 67–​69, 71, 73, 77, 79, 80, 81, 84, 86, 129, 164, 183 Acyclic, aminated 2: 23, 62, 69, 87, 107, 118, 163 3: 28, 63, 133 4: 36, 70, 72, 88 5: 64, 65, 67–​69, 85–​87, 104 6: 58, 59, 61, 63, 65, 74, 76, 79, 81 Acyclic, oxygenated 2: 53, 54, 61, 71, 72 3: 54, 61, 68, 203 4: 55, 70, 71, 73 5: 65, 66, 70, 71, 78, 84, 86, 87, 96, 160 6: 59, 60, 63, 65, 75, 80, 88, 208 Cyclic, alkylated 1: 1, 5, 13, 15, 23, 24, 33, 43, 46, 47, 58, 67, 68, 78, 80, 97, 102, 121, 128, 134, 153, 165, 169, 176, 181, 197, 199, 205 2: 24, 26, 27, 34, 38, 45, 52, 60, 63, 65, 67, 68, 70, 71, 73, 97, 100, 101, 102, 104, 105, 108, 113, 120, 123, 125, 128, 131, 157, 159, 164, 167, 169, 172, 174, 183, 184, 196, 199, 204, 205, 206, 207, 208 3: 136–​141, 143, 144, 148–​155, 157, 158, 159, 160, 161, 178, 183, 189, 192, 205, 206, 208 4: 43, 63, 65, 75, 85, 107, 115, 117, 119, 125, 133, 137–​151, 153, 155–​161, 168–​173, 176, 177, 182, 183, 186–​191, 196–​199, 202–​209 5: 39, 87, 88, 102, 108, 113, 115, 117, 118, 136–​138, 140–​142, 144–​150, 154–​158, 161, 163, 164, 166, 170, 171, 174, 178, 180, 183, 186, 191, 193, 195, 197, 199, 200, 203, 205, 207–​209 6: 3, 37, 38, 39, 97, 103, 104, 107, 108, 111, 117, 135-​149, 154, 157, 159, 161, 162, 167, 172, 175, 178, 181, 184, 187, 198, 202, 204, 206, 207

Cyclic, aminated 1: 136, 196 2: 46, 138, 139, 140, 149, 196 3: 25, 28, 195, 203 4: 57, 69, 106–​108, 111, 113, 116, 151, 158, 160, 161 5: 31, 68, 96, 100, 101, 104, 106, 107, 109–​111, 113, 115, 116, 140, 143, 152, 163, 175, 179, 203, 204 6: 100, 102, 107, 111, 114, 137, 141, 145, 167, 181, 195 Cyclic, oxygenated 1: 14, 24, 32, 33, 43, 67, 80, 102, 121, 135, 137, 196 2: 34, 46, 65, 66, 71, 80, 88, 93, 94, 98, 100, 102, 104, 113, 119, 132, 134, 138, 154, 156, 158, 170, 175, 176, 184, 196, 200, 202, 206, 208, 210 3: 27, 59, 61, 90, 138, 139, 140, 142–​144, 149, 156, 159, 161, 186, 188, 189, 193 4: 36, 51, 61, 63, 82, 91, 92, 95–​97, 100, 111, 115, 119, 140, 151, 153, 155, 157, 158, 161, 164–​167, 178–​185, 188, 189, 192, 193, 196, 197, 204–​207 5: 89, 90, 91, 94, 96, 97, 102, 103, 121, 136, 139, 143, 144, 148, 149, 154, 155, 159, 161, 163, 166–​169, 179, 197, 201 6: 37, 41, 75, 80, 82, 88, 93, 98, 109, 135, 137, 138, 140, 141, 143, 144-​146, 157, 158, 160, 164, 175, 188, 199, 204, 205, 208 Quinolizidine synthesis 3: 118, 185 5: 105 6: 107, 109, 111, 195 Radical coupling 1: 54 2: 56, 79, 127, 128, 188 4: 53–​55 6: 37 Radical cyclization 1: 10, 23, 36, 48, 69, 108, 196, 200 2: 12, 34, 172, 174, 201 3: 90, 92, 108, 117, 119, 160 4: 90, 97, 106, 112, 142, 143, 147, 148, 154, 157, 167, 176, 177, 193 5: 92, 151, 169, 171, 181, 186, 209 6: 37, 41, 81, 90, 100, 105, 146, 163, 171, 173, 209 Ramberg-​Bäcklund reaction 3: 101, 115 4: 175 5: 50 Resolution Of alcohols 1: 34, 88, 158 2: 124 3: 66 Of amines 3: 63 Rh catalysis Aldehyde homologation 2: 7 4: 76 5: 87, 177

269  Reaction Index

3: 25, 48, 52, 102–​113, 115–​119, 147, 159, 187 4: 57, 64, 102–​106, 108–​ 112, 114–​117 5: 15, 31, 39, 93, 104, 106–​108, 111, 112, 113, 117, 183, 193, 193, 203, 207 6: 6, 18, 31, 41, 45, 48, 50, 102, 103, 104, 106–​108, 110–​ 117, 149, 167, 172, 181 Pyrrolizidine synthesis 4: 106, 114

Reaction Index  270

270

Rh catalysis (cont.) Aldehyde to amide 1: 132 3: 7 Alkene acylation 3: 43 Alkene aminoalkylation 3: 41 Alkene aminohydroxylation 3: 92 Alkene borylation 3: 72 4: 52 Alkene carboxylation 3: 41 Alkene diamination 6: 56 Alkene epoxidation 1: 35 Alkene from alkane 6: 38 Alkene from diazo ester 6: 37 Alkene homologation 1: 122, 178 3: 39 6: 57 Alkene hydroamination 2: 92 6: 80 Alkene hydroboration 4: 53 Alkene hydroboration, enantioselective 4: 87 Alkene hydroformylation 1: 148 2: 59 3: 42, 108 4: 49, 50, 53 5: 55 6: 53, 57, 79, 196, 197 Alkene hydroformylation, enantioselective 4: 78, 80 5: 72, 79 6: 51 Alkene hydroformylation/​aldol, enantioselective 3: 81 Alkene hydrosilylation, enantioselective 5: 73 Alkyne addition 3: 105 5: 98 Alkyne to aldehyde 3: 5, 16 Alkyne to alkynyl thioether 3: 36 Alkyne to allylic alcohol 5: 32 Alkyne to amino ketone 5: 13 Alkyne cyclization 2: 138 3: 123 Alkyne to enamine 3: 5 Alkyne homologation 2: 90, 195 3: 37 Allene hydroacylation 4: 44 Allene hydroacylation, enantioselective 3: 76 Allylic amination, enantioselective 3: 67 Allylic coupling 1: 66, 141 2: 74, 198 3: 67 5: 66, 98 6: 42 Allylic oxidation 1: 177 5: 67 Amine from ketone, enantioselective 4: 72 Amine oxidation 2: 127 Arene coupling 3: 120 4: 122, 125 5: 87 Arene synthesis 5: 131 6: 123 Aromatic ring substitution 6: 119, 120, 125, 129, 131, 148

C-​C insertion 5: 52, 147 C-​H functionalization 2: 41 4: 32, 34 5: 67, 75, 87 6: 39, 41, 72, 84, 86, 91, 95 Conjugate addition 1: 98 2: 74, 120, 205 3: 72 5: 28 Conjugate addition, enantioselective 3: 74 4: 71, 76, 77, 81 6: 82, 142, 148 Conjugate borylation 3: 66 Cycloheptane synthesis 3: 144, 208 Cyclohexane synthesis 3: 147, 149, 153 5: 52, 147, 149 6: 143, 149 Cyclooctane synthesis 3: 147 Cyclopentane synthesis 3: 147, 149, 153, 181 5: 35, 39, 40, 43, 148, 151 Cyclopropane synthesis 3: 145 5: 144, 146 6: 142 Cyclopropene synthesis 5: 144, 146 Decarbonylation 3: 111 Diels-​Alder 2: 81 Dipolar cycloaddition 3: 103 Enantioselective hydrogenation 1: 161, 174 2: 59, 119, 163 3: 74 4: 66, 71, 72, 76 6: 61 Enyne cyclization 2: 70, 73, 74 139 Hydroacylation 2: 103, 178 4: 76 5: 61 Indole synthesis 2: 188 3: 133 5: 131 6: 127, 129, 131 Intermolecular C-​H insertion 2: 61, 106, 209 3: 29 5: 75 6: 41, 72 Intermolecular cyclopropanation 2: 106 3: 150, 208 Intermolecular O-​H insertion 6: 208 Intramolecular C-​H insertion 1: 8, 142, 15 2: 173, 188, 209 3: 25, 88, 98, 99, 112, 149 4: 70, 118 5: 35, 39–​43, 148, 151 6: 84, 86, 91, 95, 143, 181 Intramolecular cyclopropanation 2: 70 Intramolecular ene, enantioselective 6: 65 Intramolecular O-​H insertion 4: 196 Ketone methylenation 6: 113 Lactone formation 5: 43 Mannich 3: 63 6: 78, 79, 106 Nitrene insertion 1: 8 5: 42 Nitrene insertion, enantioselective 4: 70 Nitrile to hydride 4: 13 Pauson-​Khand cyclization 6: 175

 271

Alkyne hydration 2: 86, 103, 146 Alkyne to alcohol 5: 17 Alkyne silylation 6: 183 Alkyne stannylation 6: 101 Allene carbonylation 3: 159 Allylic alcohol to ketone 5: 2 Allylic coupling 5: 106 Amide reduction 3: 9 Amine to alcohol 5: 8 Amine deprotection 5: 19 Amine formylation 5: 24 Amine from ketone 6: 147 Amine from imine, enantioselective 4: 72 Arene amination 5: 126 Arene construction 2: 40 5: 121, 164 Arene coupling 2: 82 5: 28, 121 Arene hydrogenation 3: 159 Arene hydroxylation 5: 125 6: 118 Azide to amide 5: 6 Azide to nitrile 5: 28 Aziridine formation 5: 108 6: 104 Borylation 2: 17 Carbene insertion 3: 104 5: 37 C-​H functionalization 5: 37 6: 38 C-​H to ketone 5: 34 Conjugate addition 1: 204 4: 73 5: 72 6: 70 Cyclohexane synthesis 3: 145, 151 Cyclopentane synthesis 3: 145 5: 37 Cyclopropane synthesis 3: 144 5: 148 Decarbonylation 4: 68 Ester reduction 2: 86 3: 8 Ether oxidation 4: 4 5: 43 Heck reaction 5: 121 Hydride from acid 6: 7 Hydrogenation, enantioselective 3: 104 5: 68, 211 6: 60, 61, 88, 105, 106 Ketone allylation, enantioselective 6: 73 Ketone from alkene 2: 178 Ketone to silyl enol ether 5: 21 Nitrene insertion 3: 69 Nitrile from alkyne 2: 146 Nitrile to amine 6: 11, 17, 19 Oxidation 1: 88, 2: 13, 78 3: 3, 40 4: 4 Oxidative fragmentation 2: 198 Phthalimide reduction 2: 192 Polycarbocyclic construction 3: 145 Propargyl alcohol isomerization 2: 146 Pyridine synthesis 4: 132 5: 129

271  Reaction Index

Phthalimide reduction 2: 192 Piperidine synthesis 5: 106, 107 Polycarbocyclic construction 3: 147, 151 Propargylic oxidation 3: 26 Pyridine synthesis 3: 129, 132 5: 128, 135 6: 129 Pyrrole synthesis 4: 126 5: 128, 135 6: 130 Reductive aldol, enantioselective 3: 83 Ring expansion 3: 148, 149, 189 6: 142 Silylation 3: 18 5: 73 Sultam formation 5: 73 Ring contraction 1: 12 2: 72, 100 Ring expansion 5: 172, 194 6: 9, 136, 153, 175 Robinson annulation 5: 186 6: 178 Robinson annulation, enantioselective 4: 116, 135, 137, 139, 190 5: 118 Ru catalysis. See also Grubbs reaction Acid to aldehyde 5: 12 Acid to amine 5: 12 Acid to hydride 6: 7 Alcohol to acid 6: 8 Alcohol to amide 3: 7 Alcohol to amine 3: 16 5: 3 Alcohol oxidation, to aldehyde 4: 14 Alcohol oxidation, to ketone 6: 13 Aldehyde from alkyne 4: 11 Aldehyde allylation, enantioselective 3: 77 Aldehyde oxidation, to ester 3: 11 Aldol condensation 1: 107 Alkene addition 2: 178 Alkene aminohydroxylation 3: 92 Alkene carbonylation 6: 50 Alkene dihydroxylation, enantioselective 3: 82 Alkene homologation 4: 49 6: 50 Alkene hydration 4: 54 Alkene hydroboration, enantioselective 4: 74 Alkene to ketone 6: 13 Alkene oxidative cleavage 6: 56 Alkene migration 3: 42 Alkenyl halide from enol triflate 4: 2 Alkyne activation 1: 123 Alkyne cyclization 3: 127 5: 93 Alkyne homologation 4: 33, 49 5: 57 6: 48

Reaction Index  272

27

Ru catalysis. (cont.) Pyrrole synthesis 5: 134, 135 6: 126, 128 Pyrrolidine synthesis 5: 106 Pyrrolidone synthesis 4: 105 Reduction of alkene 3: 9 Reduction of ketone 1: 88, 162 3: 3 Reduction of ketone, enantioselective 3: 4, 85, 89, 202 4: 68, 103 6: 87 Ring construction 2: 103, 104 Triazole synthesis 3: 132 Sakurai reaction 5: 208 Schmidt reaction 5: 208 Schmidt reaction, intramolecular 1: 113, 147 2: 38 4: 111 5: 107 Selenide Alkylation 2: 112 Elimination to alkene 2: 112 4: 2, 6, 163 5: 183, 201 Oxidation, to aldehyde Sharpless asymmetric aminohydroxylation 4: 200 Sharpless asymmetric dihydroxylation 1: 84, 89, 141, 189 2: 54, 165, 194 3: 13, 67, 84, 97 4: 57, 73, 96, 105, 157 5: 201 6: 64, 99. See also Osmylation; Alkene: Dihydroxylation Sharpless asymmetric epoxidation 1: 32, 46, 67, 115, 141, 168, 172, 193 2: 58, 61, 77, 112, 156, 197, 198 3: 94, 162, 176 4: 95, 96, 185 5: 149, 160, 162 6: 78 (W), 192 Silane From alkene 2: 125 3: 39 From ether 3: 4 To alcohol 2: 36 Silane, allylic synthesis 1: 43 2: 78 5: 36 Silyl alkene to halo alkene 6: 51 Singlet oxygen 5: 26, 28 Sonogashira coupling with Cu. See Castro-​ Stevens coupling; Palladium Spiroketal construction 1: 187 2: 88, 94, 200, 204 3: 89, 91, 95, 97, 99, 101, 172, 174, 190, 202 4: 59, 93 5: 34, 100 6: 83, 87, 96, 100, 191 Stannane, α-​alkoxy, from aldehyde, enantioselective 3: 68 Stille coupling. See Palladium

Strecker synthesis 1: 26 6: 105 Strecker synthesis, enantioselective 1: 99 2: 118 3: 62 4: 69 Sulfide Alkenyl, homologation 2: 200 Alkenyl from alkenyl halide 4: 7 Allylic to alcohol 2: 4 From acid 5: 6 From acid, carbon loss 6: 7 From alkene 4: 48 6: 59 From halide 6: 29 From hydride 6: 11 To alkene 2: 145 4: 9 To amine 6: 108 To hydride 3: 15 6: 207 To ketone, homologation 3: 30 To sulfoxide 3: 6 Sulfonamide, vinylation 4: 8 Sulfonate, aryl to hydride 2: 86 Sulfone Alkylation, intramolecular 3: 87 Displacement 3: 87 To acid 5: 11 To alcohol 5: 5 To hydride 2: 86, 140, 193 To ketone 4: 17 Unsaturated, conjugate addition 6: 40, 41 Unsaturated, conjugate addition, enantioselective 3: 72 5: 66 Unsaturated from alkene 5: 54 Unsaturated from allylic alcohol 4: 6 Sulfonic acid from halide 4: 3 Sulfonyl chloride, from thiol 4: 17 Sulfoxide Homologation 3: 32 To alkene 2: 22 Suzuki reaction. See Palladium Tebbe reaction 1: 148 2: 50 3: 91, 97, 102 4: 11 5: 183, 205 Tetrazole synthesis 1: 17 Thermolysis (flow) 5: 29 Thioacid to amide 5: 6 Thiocyanate α to ketone 3: 5 Thioester from aldehyde 6: 11 Thioketal desulfurization 3: 18 Thiol To alcohol 3: 5 To hydride 6: 14

 273

Ullmann coupling 3: 110 Vinyl cyclopropane rearrangement 1: 203 3: 151 Vinylation, of sulfonamide 4: 8 Wacker reaction. See Palladium

Wharton fragmentation 4:178 6: 169. See Grob Wittig reaction 1: 108 5: 27, 44, 185, 195 6: 43, 140, 165, 169, 177, 183, 189, 192, 194, 195, 199 Wittig reaction intramolecular 3: 143 4: 94, 135 Wittig reaction, intramolecular, enantioselective 6: 48 Wolff rearrangement 4: 106 Wolff-​Kishner reduction. See Ketone: To methylene

273  Reaction Index

To ketone 3: 5 To sulfonyl halide 4: 17 5: 3 Triazine synthesis 1: 17 Triazole synthesis 3: 128, 132