Frustrated Lewis Pairs [1st ed.] 9783030588878, 9783030588885

Table of contents :
Front Matter ....Pages i-viii
Frustrated Lewis Pair Catalysis: An Introduction (Douglas W. Stephan)....Pages 1-28
Frustrated Lewis Pair Catalyzed Asymmetric Reactions (Xiangqing Feng, Wei Meng, Haifeng Du)....Pages 29-86
FLP Reduction of Carbon Monoxide and Related Reactions (Tongdao Wang, Constantin G. Daniliuc, Gerald Kehr, Gerhard Erker)....Pages 87-112
FLP-Mediated C–H-Activation (Yashar Soltani, Frédéric-Georges Fontaine)....Pages 113-166
Mechanistic Insight into the Hydrogen Activation by Frustrated Lewis Pairs (Mojgan Heshmat, Lei Liu, Bernd Ensing)....Pages 167-208
Lewis Acidic Boranes in Frustrated Lewis Pair Chemistry (Theodore A. Gazis, Darren Willcox, Rebecca L. Melen)....Pages 209-235
Heterogeneous Catalysis by Frustrated Lewis Pairs (Andrew R. Jupp)....Pages 237-281
Lewis Acid−Base Pairs for Polymerization Catalysis: Recent Progress and Perspectives (Miao Hong)....Pages 283-317
Frustrated Lewis Pairs Based on Transition Metals (Nereida Hidalgo, Macarena G. Alférez, Jesús Campos)....Pages 319-359
Radicals in Frustrated Lewis Pair Chemistry (Flip Holtrop, Andrew R. Jupp, J. Chris Slootweg)....Pages 361-385
Frustrated Lewis Pair Pedagogy: Expanding Core Undergraduate Curriculum and Reinforcing Fundamental Thermodynamic Concepts (Timothy C. Johnstone)....Pages 387-400
Back Matter ....Pages 401-404

Citation preview

Molecular Catalysis 2 Series Editors: Piet W. N. M. van Leeuwen · Carmen Claver · Nicholas Turner

J. Chris Slootweg Andrew R. Jupp Editors

Frustrated Lewis Pairs

Molecular Catalysis Volume 2

Series Editors Piet W. N. M. van Leeuwen, LPCNO, Institut National des Sciences Appliqué, Toulouse, France Carmen Claver, Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Tarragona, Spain Nicholas Turner, School of Chemistry, University of Manchester, Manchester, UK

This book series publishes monographs and edited books on all areas of molecular catalysis, including heterogeneous catalysis, nanocatalysis, biocatalysis, and homogeneous catalysis. The series also explores the interfaces between these areas. The individual volumes may discuss new developments in catalytic conversions, new catalysts, addressing existing reactions and new reactions regarded as desirable from a societal viewpoint. The focus on molecular insight requires an appropriate attention for synthesis of catalytic materials, their characterization by all spectroscopic and other means available, and theoretical studies of materials and reaction mechanisms, provided the topic is strongly interwoven with catalysis. Thus the series covers topics of interest to a wide range of academic and industrial chemists, and biochemists.

More information about this series at http://www.springer.com/series/15831

J. Chris Slootweg Andrew R. Jupp •

Editors

Frustrated Lewis Pairs

123

Editors J. Chris Slootweg Van ‘t Hoff Institute for Molecular Sciences University of Amsterdam Amsterdam, The Netherlands

Andrew R. Jupp School of Chemistry University of Birmingham Edgbaston, UK

ISSN 2522-5081 ISSN 2522-509X (electronic) Molecular Catalysis ISBN 978-3-030-58887-8 ISBN 978-3-030-58888-5 (eBook) https://doi.org/10.1007/978-3-030-58888-5 © Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

Frustrated Lewis pairs (FLPs) have been a key factor in the renaissance of main-group chemistry in the past few decades. Although it was known as early as the 1940s that steric hindrance could preclude Lewis adduct formation, it was in 2006 that Douglas Stephan and his team showed that combinations of unquenched Lewis acids and bases could be used to split the H–H bond in H2. This discovery paved the way for the FLP activation of a wide range of small molecules, including environmentally relevant gases such as carbon dioxide, sulfur dioxide and nitrogen oxides. More pertinent to the Molecular Catalysis series is their extraordinary ability to promote the catalytic hydrogenation of unsaturated organic substrates—a series of reactions that were previously thought to be limited to transition metal compounds. Perhaps one of the greatest contributors to the growing popularity of research into frustrated Lewis pairs is their simplicity. There are innumerable combinations of Lewis acids and bases that can be trialled, and these have unlocked a fantastic array of reactions. A Web of Science search for the topic frustrated Lewis pairs shows just how quickly this field has burgeoned. The very first citation to a published work containing this term was in 2007, and as we write this Preface on the 15 July 2020 there are almost 60,000 citations, with over 10,000 in 2019 alone. This book follows on from the two FLP titles that were published in 2013 (subtitled Uncovering and Understanding and Expanding the Scope), which were compiled and edited by the two forefathers of FLP chemistry: Douglas Stephan and Gerhard Erker. We have built on these foundations and attempted to collate and summarise the staggering progress made in the research area of FLP catalysis since those publications. We have by no means done this alone, and all the credit goes to the amazing researchers from around the globe who have contributed chapters to this book; we feel it really provides a summary of the state of the art in frustrated Lewis pair catalysis. Chapter 1 introduces the general topic of FLP catalysis and provides the context for the ensuing chapters. Chapter 2 outlines the phenomenal progress that has been made in recent years on asymmetric catalysis by FLPs. Chapters 3, 4 and 5 then cover specific transformations carried out by FLPs, specifically the reduction of carbon monoxide, the activation of C–H bonds and hydrogen activation, v

vi

Preface

respectively. Chapter 6 surveys the different and novel boranes that have been developed as Lewis acids within FLP systems, and the new reactivity they can unlock. Chapter 7 explores the recent development of heterogeneous catalysts in FLP chemistry, and Chapter 8 describes the practical application of using (frustrated) Lewis pairs to promote the polymerisation of a large range of monomer substrates. Chapter 9 then summarises the utilisation of transition metal complexes as one (or both) of the Lewis acidic or basic components in FLPs. The very recent developments in radical formation and reactivity in FLP systems are discussed in Chapter 10. We are delighted that the final chapter takes a different tack and rounds off all of the cutting-edge research of the rest of the book: Chapter 11 describes the effectiveness of the FLP framework as a pedagogical tool for helping students (re-) learn fundamental thermodynamic concepts. We hope that this book runs the gamut of catalysis by frustrated Lewis pairs, and will serve as both an inspiring read for those that are completely new to the field, and as a useful reference book for more experienced researchers. There is huge scope to expand on the work described in these chapters in the future, and there are undoubtedly many discoveries that could spawn completely new chapters in upcoming books! We would once again like to thank all the authors of the chapters for their immense contributions to this book, and we hope you enjoy reading it. Birmingham, UK Amsterdam, The Netherlands July 2020

Andrew R. Jupp J. Chris Slootweg

Contents

1

Frustrated Lewis Pair Catalysis: An Introduction . . . . . . . . . . . . . Douglas W. Stephan

1

2

Frustrated Lewis Pair Catalyzed Asymmetric Reactions . . . . . . . . . Xiangqing Feng, Wei Meng, and Haifeng Du

29

3

FLP Reduction of Carbon Monoxide and Related Reactions . . . . . Tongdao Wang, Constantin G. Daniliuc, Gerald Kehr, and Gerhard Erker

87

4

FLP-Mediated C–H-Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Yashar Soltani and Frédéric-Georges Fontaine

5

Mechanistic Insight into the Hydrogen Activation by Frustrated Lewis Pairs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Mojgan Heshmat, Lei Liu, and Bernd Ensing

6

Lewis Acidic Boranes in Frustrated Lewis Pair Chemistry . . . . . . . 209 Theodore A. Gazis, Darren Willcox, and Rebecca L. Melen

7

Heterogeneous Catalysis by Frustrated Lewis Pairs . . . . . . . . . . . . 237 Andrew R. Jupp

8

Lewis Acid−Base Pairs for Polymerization Catalysis: Recent Progress and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . 283 Miao Hong

9

Frustrated Lewis Pairs Based on Transition Metals . . . . . . . . . . . . 319 Nereida Hidalgo, Macarena G. Alférez, and Jesús Campos

10 Radicals in Frustrated Lewis Pair Chemistry . . . . . . . . . . . . . . . . . 361 Flip Holtrop, Andrew R. Jupp, and J. Chris Slootweg

vii

viii

Contents

11 Frustrated Lewis Pair Pedagogy: Expanding Core Undergraduate Curriculum and Reinforcing Fundamental Thermodynamic Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 Timothy C. Johnstone Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401

Chapter 1

Frustrated Lewis Pair Catalysis: An Introduction Douglas W. Stephan

Abstract This chapter provides a brief overview of the evolution of FLP catalysis. We begin with a description of the initial finding of reversible hydrogen activation and the development of FLP-mediated catalytic hydrogenations. Subsequently, the applications of FLPs in other catalytic processes involving other small molecules are considered. These include hydrosilylation, transfer hydrogenations, hydroboration, amination, hydroarylation, C–H borylation, polymerization, CO2 reduction, and C–F derivatization. The chapter concludes with a summary and short discussion of future potential. Keywords Frustrated lewis pairs · Hydrogenation · Hydrosilylation · Transfer hydrogenations · Hydroboration · Amination · Hydroarylation · C–H borylation · Polymerization · CO2 reduction · C–F derivatization

Abbreviations 9-BBN Ar atm bipy Bn Bu cat Cat. Cp Cy DABCO EPC

9-Borabicyclo[3.3.1]nonane Aryl Atmosphere Bipyridine Benzyl Butyl Catechol Catalyst Cyclopentadienide Cyclohexyl 1,4-Diazabicyclo[2.2.2]octane Electrophilic phosphonium cation

D. W. Stephan (B) Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M6S3H6, Canada e-mail: [email protected] © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_1

1

2

Et FLPs h Me Mes MIC MMA MOF NHC Ph Piers’ borane pin Pr rt terpy THF TMP

D. W. Stephan

Ethyl Frustrated Lewis pairs Hour(s) Methyl Mesityl; 2,4,6-trimethylphenyl Meso-ionic carbene Methyl methacrylate Metal-organic framework N-heterocyclic carbene Phenyl HB(C6 F5 )2 pinacol Propyl Room temperature Terpyridine Tetrahydrofuran Tetramethylpiperidine

1.1 Introduction In 2006, we described the first metal-free system capable of the reversible activation of H2 [1]. This finding was based on Mes2 PC6 F4 B(C6 F5 )2 (Mes = 2,4,6Me3 C6 H2 ), a molecule-containing sterically encumbered phosphine and borane sites. Subsequently, we further showed that such reactivity could be extended to simple combinations of sterically demanding boranes and donors [2]. Shortly, thereafter, Erker and coworkers reported the reaction of the intramolecular B/P system Mes2 PC2 H4 B(C6 F5 )2 with H2 [3]. These systems were shown to react with H2 to effect heterolytic cleavage as well as effect B/P addition to olefins, prompting the moniker “frustrated Lewis pairs (FLPs)” for such systems (Scheme 1.1) [4]. The ability to activate H2 immediately prompted questions regarding the possibility of metal-free catalysis. Moreover, studies probing the notion of FLPs have also led both to a broadened range of FLP catalysts as well as their application in a widening range of metal-free catalytic processes. Indeed, the emergence of the concept has provided a new strategy for synthetic chemists to develop new avenues for catalytic protocols in the last decade. It has been exploited for a broad range of applications in asymmetric reductions, metal-free organic synthesis, C–H bond activations, polymer synthesis, in addition to providing new perspectives on transition metal chemistry in biological systems and heterogeneous catalysis. Several reviews have appeared that detail specific aspects of FLP chemistry [5–17]. The ever-broadening applications of this remarkably simple concept are impressive, particularly in the context that the origin of this notion emerged from fundamental main group chemistry. In this chapter, we provide a brief account of the

1 Frustrated Lewis Pair Catalysis: An Introduction F

F

(Me3C6H2)2P

F

H2 B(C6F5)2

F

3

heat

(Me3C6H2)2P H

F

R3P / B(C6F5)3

H2

F

H B(C6F5)2

F

F

[R3PH] [HB(C6F5)3]

t

(R= Bu, Mes) Mes2P

B(C6F5)2

R3P / B(C6F5)3

H H2

B(C6F5)2

Mes2P H

R'

B(C6F5)3

R3P R'

Scheme 1.1 Reactions of sterically congested phosphine/borane systems with H2 and olefins

origins of the concept, a discussion of FLPs in hydrogenation and other applications of FLPs in catalysis. It is an overview and thus not comprehensive. Nonetheless, it does serve as an introduction to this exciting volume focused on this new area of chemistry.

1.2 FLP Hydrogenations 1.2.1 The Beginning In 2007, 5 mol% of the phosphonium–borate (Mes2 PH)(C6 F4 )BH(C6 F5 )2 was shown to affect the hydrogenation of sterically encumbered imines at 80–120 °C under 1– 5 atm of H2 , affording the corresponding amines in high yields [18]. Typical reaction times ranged from 1 to 24 h. The product amines were easily purified as filtration through a plug of silica gel removed the FLP catalyst. Similarly, Mes2 PC6 F4 B(C6 F5 )2 was used to catalyze the reduction of aziridines and nitriles (Scheme 1.2) [18]. In these reductions, delivery of proton and subsequent hydride transfer to the substrate was proposed to account for the reduction of imine substrates [18, 19]. This order of addition is consistent with reactivity trends as the electron-rich imine, tBuN CPh(H) was more readily reduced than electron-poor imines such as PhSO2 N CPh(H). In subsequent work, the order of addition was shown to be substrate dependent. For example, the reductions of ketones aldehydes [20, 21], or electron-deficient olefins [22, 23] proceed via initial hydride delivery followed by protonation. In these cases, the transient alkoxide and carbanion are basic and effect deprotonation of the protonated-base component of the FLP.

4

D. W. Stephan

Scheme 1.2 Early examples of FLP hydrogenations

5 mol% Ph N H

tBu (C6H2Me3)2PC6F4B(C6F5)2 Ph H2 5 mol% Ph B(C6F5)3

Ph N Ph

Ph

H2

tBu NH Ph N

B(C6F5)3

Ph

10 mol%

N

Mes2HP H

Ph

Me3Si

O

B(C6F5)2 H H2

N Ph

10 mol% Mes2HP H

Ph

B(C6F5)2 Me Si 3 O H Ph H2

10 mol% PPh2 PPh2 CHPh2

Ph

Ph

N H

B(C6F5)3

CHPh2 NH

In a further advance, we recognized that the substrate could act as the basic partner of the FLP. Thus, using only a catalytic amount of the Lewis acid, B(C6 F5 )3, the reduction of a range of sterically encumbered imines could be achieved [19]. In the case of electron-poor imines, the addition of a catalytic equivalent of Mes3 P accelerated hydrogenation, presumably because the imine/borane combination slowly activates H2 . In 2008, Erker et al. [3, 24] exploited 10 mol% of the ethylene linked phosphonium–borate Mes2 PH(C2 H4 )BH(C6 F5 )2 to affect the hydrogenation of imines and enamines under remarkably mild conditions (25 °C under 1.5 atm H2 ) (Scheme 1.2). While the diminished Lewis acidity of the boron center might be expected to slow H2 activation, it should also accelerate hydride delivery, thus affording enhanced catalytic activity. In other cases, the catalyst loadings could be reduced to as low as 3 mol% [25] while bulkier enamine PhC(NC5 H10 ) CH2 required more forcing conditions (50 atm H2 , 70 °C, 10 mol% catalyst). The Erker group also extended FLP reductions to silyl enol ethers [26], using the FLP derived from the bis-phosphine C10 H6 (PPh2 )2 and B(C6 F5 )3 as the catalyst. The following year, Berke and coworkers exploited bis-Lewis acid, 1,8-C10 H6 (B(C6 F5 )2 )2 under 15 atm H2 at 120 °C to hydrogenate imines, suggesting a “super Lewis acidic activation pathway” involving the action of both boron centers on H2 [27].

1 Frustrated Lewis Pair Catalysis: An Introduction

5

Following these early studies, there was a great deal of activity that focused on the development of a variety of aspects of FLP catalysis. The substrate scope has broadened, a variety of catalysts were developed, and functional-group tolerant catalysts were uncovered. Each of these key advancements has played a key role in the technology for metal-free hydrogenations that has emerged in the last decade. Some of the highlights of these aspects are discussed below.

1.2.2 Broadening the Substrate Scope The ability of FLPs to reduce imines was extended to diimines and pyridyl diimines using B(C6 F5 )3 in 2011 (Scheme 1.3) [28], and later by Du and coworkers to diimine reductions en route to cis-1,2-diaryl-1,2-diamines [29]. Similarly, more recent studies by Oestreich and coworkers53 have exploited B(C6 F5 )3 to catalyze the hydrogenation of O-alkyl and O-silyl oxime ethers providing a route to primary amines (Scheme 1.3) [30]. Similarly, B(C6 F5 )3 has also been exploited to reduce aldoximine ethers, ketone-, and aldehyde-derived hydrazones providing facile access to hydrazine hydrates or acetyl-substituted hydrazines (Scheme 1.3) [31]. 5 mol% B(C6F5)3 N iPr2C6H3

N

5 mol% OMe B(C6F5)3 Ph

Ph N Me

Ph

N

O

H R2

H2

H2 NH C6H3iPr2 iPr2C6H3

OMe NH

N HN

5 mol% NMe2 B(C6F5)3 Ph

Ph N

Me

H2

Me

5 mol% Pr2C=C(C6F5)B(C6F5)2 CPh DABCO Ph H2 H 10 mol% R2 B(C6F5)3 (C6F5)Ph2P

R1 CPh R2

80 C 102 Atm H2 5 mol% Me2NC6H4BH(C6F5)

R

R'

H2

H R

CO2Et

H

R1 H R'

Scheme 1.3 Examples of broadening the substrate scope

R1 R2

5 mol% B(C6F5)3 CO2Et DABCO Ph

o

R1

NMe2 NH

Me

5 mol% (C6F5)Ph2P B(C6F5)3 H2

O

Ph

C6H3iPr2

O R'

H2

H

CO2Et

H2 5 mol% B(C6F5)3

R

CH3

CO2Et R H R'

O H

6

D. W. Stephan

The description of FLP reductions of silyl-enol ethers by Erker was extended to a range of enone and ynone substrates using tBuCH C(Ph)B(C6 F5 )2 [32], CpFe(C5 H4 PMes2 )/B(C6 F5 )3 [33], MesB(C6 F5 )2 [34] and a series of alkenyl boranes with DABCO (Scheme 1.3) [35]. More recently, B(C6 F5 )3 has been used in a onepot Lewis acid-mediated generation of aza-Morita−Baylis−Hillman adducts and subsequent FLP hydrogenation [36]. In 2010, we extended FLP hydrogenations to substituted nitrogen-heterocycles, reducing substituted quinolines, phenanthroline, acridine as well as several indole derivatives using B(C6 F5 )3 under H2 [37]. Subsequently, the scope was extended to a series of pyridines, quinolines, and other N-heterocycles [38–43]. In 2012, a collaboration with Paradies [44] showed that the FLP (C6 F5 )Ph2 P/B(C6 F5 )3 effectively reduced 1,1-disubstituted olefins in the presence of H2 (Scheme 1.3). Similarly, dissociation of the adduct (Et2 O)B(C6 F5 )3 to the corresponding FLP was also capable of mediating the hydrogenation of 1,1-disubstituted olefins [45]. Similarly, B(C6 F5 )3 and Ph2 P(C6 F5 ) were shown to catalyze the FLP hydrogenation of polyaromatic compounds in 2012 [46]. For example, several anthracenes and tetracene derivatives were converted to the dihydro-analogs although 102 atm of H2 and 80 °C were required for 10–48 h (Scheme 1.3). Subsequently in 2012, electron-poor alkenes of the form RCH C(C(O)Et)2 were reduced by Alcarazo and coworkers using DABCO and B(C6 F5 )3 as the FLP catalyst (Scheme 1.3) [22]. A 2014 study described the reduction of a series of electronrich nitro-olefins and acrylates as well as silylated fulvenes [47] using (THF)B(2,6C6 F2 H3 )3 and lutidine or collidine under 4 bar H2 at room temperature. In more recent studies, vinylferrocene was reduced using the cyclopentane-based intramolecular FLP C5 H8 (PMes2 )B(C6 F5 )2 [48] while a series of terminal, di- and tri-substituted olefins were reduced using 20 mol% of HB(C6 F5 )2 as a catalyst by Wang and Li [49]. The latter system required 6 bar H2 and 140 °C, as it proceeds via initial hydroboration followed by hydrogenolysis which regenerates the borane and provides the reduced product. Also in 2012, an examination of the activation of H2 by the FLP derived from alkyl-aryl amines and B(C6 F5 )3 revealed the formation of expected ammonium hydridoborate at room temperature while heating to 110 °C afforded reduction of the corresponding cyclohexylammonium salts [50]. Indeed, a series of aromatic reductions were performed, although these reactions terminate by sequestration of the borane as the hydridoborate counterion. Interestingly, such reductions remain a challenge for transition metal-based catalysts. In a related 2015 study, Du and coworkers [51] showed that in contrast to the above aniline systems, reductions of tetrahydronaphthylamines could be catalyzed using 10 mol% of B(C6 F5 )3 under H2 at 60 °C. In 2013, Repo and coworkers [52] developed the intramolecular B/N FLP, C6 H4 NMe2 (BC6 F5 )H and exploited it to catalytically convert alkynes to cis-olefins (Scheme 1.3). These authors demonstrated that the reduction is initiated by hydroboration of the alkyne, followed by H2 cleavage and intramolecular protodeborylation liberates the alkene. These authors latter showed that C6 H4 (NMe2 )BCl2 [53] was also an effective catalyst for the production of cis-alkenes. In a related sense, Du et al.

1 Frustrated Lewis Pair Catalysis: An Introduction

7

[54] subsequently used HB(C6 F5 )2 in the presence of C6 F5 CH CH2 to hydrogenate alkynes to give cis-alkenes. In 2014, we [20] and the Ashley group [21] concurrently reported that ethereal solvents and B(C6 F5 )3 permitted the FLP hydrogenations of ketones and aldehydes (Scheme 1.3). While we used diethyl or di-isopropyl ether, Ashley employed tetrahydrofuran or 1,4-dioxane. Mechanistic studies and crystallographic data showed the reaction proceeds via activation of H2 which generates a hydrogen-bonded ketone/solvent pair cation with the anion [HB(C6 F5 )3 ]− . Subsequent hydride delivery affords the alcohol [20]. In a later study, Ashley et al. [55] showed that such reductions could be performed without rigorously dry conditions. We [56] subsequently showed that the use of B(C6 F5 )3 in toluene in the presence of either α-cyclodextrin (α-CD) or molecular sieves was also an effective protocol for ketone hydrogenation allowing facile separation of the product alcohol from the catalyst.

1.2.3 Functional-Group Tolerance The above catalysts, particularly those based on electrophilic fluorinated boranes, typically tolerate sterically encumbered functional groups [28]. However, it was the Soós group [57] that recognized that sterically encumbered Lewis acids could improve functional group tolerance and provide air stability. In early efforts, they reported the ability of MesB(C6 F5 )2 to hydrogenate sterically unencumbered imines that form classical Lewis acid–base adducts with less encumbered boranes (Scheme 1.4). Describing this as a “size exclusion” principle, Soós et al. [57] also showed that MesB(C6 F5 )2 [34] and one of the nitrogen-bases CH(CH2 CH2 )3 N or N(CH2 CH2 )3 N reduced a variety of quinolines and the conjugated olefinic bond in carvone, the latter of which highlights the tolerance of the carbonyl functionality. Cl

Cl

B(C6F5)2 Cl

B(C6F5)2 Cl

Cl

Cl

Cl

Cl

Cl

Cl Cl

B

C6F5 Cl Cl

Cl Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl Cl

B

Cl

B(C6F4H)2 Cl Cl

Cl

Cl

Scheme 1.4 Functional group tolerant FLP catalysts

C6F4H

Cl

Cl

8

D. W. Stephan

In a related approach, Ashley et al. [55] prepared the bulky Lewis acids, B(C6 Cl5 )2 (C6 F5 ) and B(C6 Cl5 )(C6 F5 )2 which proved to be air stable (Scheme 1.4). Moreover, these boranes mediated the reduction of N-tosyl imines and a quinoline in THF. At the same time, these authors found that the borane B(C6 Cl5 )3 carried the steric congestion too far, as this species was inactive. On the other hand, Soós [58] prepared the related boranes B(2,6-C6 Cl2 H3 )(2,3,5,6-C6 F4 H)2 and B(2,3,6C6 Cl3 H2 )(2,3,5,6-C6 F4 H)2 and demonstrated that these species are in fact superior catalysts for the reduction of acetals to ethers as well as in the tandem reductive etherification of carbonyl compounds (Scheme 1.4). A further study by Soós and coworkers [59] used the air-stable boranes such as (C6 H3 Cl2 )B(C6 F5 )2 , (C6 H3 Cl2 )B(C6 F4 H)2 , (C6 H2 Cl3 )B(C6 F5 )2 and (C6 H2 Cl3 )B(C6 F4 H)2 to catalyze a wide array of ketones and aldehydes (Scheme 1.4). In a clever innovation, Ashley showed that the group 14 Lewis acids (Bn3 SnOSO2 CF3 ) [60] and iPr3 Sn(OSO2 CF3 ) [61] mediated the hydrogenation of imines, with the latter catalyst offering a simple, inexpensive and effective catalyst that is moisture tolerant.

1.2.4 Catalyst Variation The range of catalysts for FLP reductions has been broadly explored. Initial studies focused on systems based on electrophilic boranes with various bases. For example, use of amines and various phosphines has drawn attention (Scheme 1.5) [10]. A detailed kinetic study of imine hydrogenation, reported by Paradies and coworkers [62, 63], examined the impact of catalyst variation, employing the fluorinated catalysts B(C6 F5 )3 , B(2,4,6-C6 F3 H2 )3 or B(2,6-C6 F2 H3 )3 (Scheme 1.5). While B(C6 F5 )3 and imine operate cooperatively to effect H2 -activation, the less Lewis-acidic boranes and imines proceed via a cycle in which the product amine and the borane activate H2 , consistent with the notion of a threshold of combined Lewis acidity and basicity is required for H–H bond cleavage. Interestingly, these auto-induced reduction cycles involving the generated amines were 8–10 times higher than those derived from the imine substrates. Alcarazo and coworkers also probed the impact of less-acidic fluorinated boranes in the hydrogenation of electron-deficient olefins [64]. These authors demonstrated that enhanced Lewis acidity accelerates H2 cleavage while slowing hydride delivery. These competing effects led to the finding that B(2,4,6-C6 H2 F3 )3 is the optimized catalyst for these reductions. The seminal work of Erker on intramolecular FLPs has also led to large number of variants that have proved to be effective catalysts. For example, Repo and coworkers [65]developed the intramolecular FLP catalyst, C5 H6 Me4 NH(CH2 C6 H4 )BH(C6 F5 )2 which was employed to reduce enamines (Scheme 1.5). Other intramolecular FLP catalysts have been developed based on cyclopentane-[48], ferrocene-[33], [2.2]paracyclophane-45 and a variety of alkyl- [48, 66–69], alkenyl- [70] and geminal linkers [33, 66].

1 Frustrated Lewis Pair Catalysis: An Introduction Ph

9 PMes2

PPh2

N

Fe

B(C6F5)2

B(C6F5)2

/ B(C6F5)3 PPh2

SiMe3

SiMe3 Mes2P B(C6F5)2

Mes2P H

Mes2P H

B(C6F5)2 H

B(C6F5)2 H

F FF

FF F F

B

F F

B(C6F5)2

F

Me

Ph

N

N B

Cl

N

F F

F F

Cl

F

B

N Me

[B(C6F5)4]

N

B N Ph [B(C6F5)4]

F C6F5 P C6F5

N Ph C6F5 / Me3Si Ph [B(C6F5)4]

B Ph 2 P Ru Cl PPh2

N

/

N

[B(C6H3Cl2)4]

Ph2P

K

(Me3Si)2N

K

B(C6F5)4

Scheme 1.5 Examples of FLP catalyst variants

While inter- and intramolecular FLP systems have drawn considerable attention, a range of other FLP catalysts have been explored, broadening the generality of the concept. For example, intermolecular FLPs derived from the gallane and indane Ga(C6 F5 )3 and In(C6 F5 )3 also catalyze the hydrogenation of imines [71]. An alternative class of FLP catalysts based on N-heterocyclic carbene (NHC)stabilized borenium cations has been reported. Salts of the form [(NHC)(9BBN)][B(C6 F5 )4 ] were readily prepared from the borane-NHC adducts and these

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D. W. Stephan

have proved to be highly effective catalysts for imine and enamine hydrogenation (Scheme 1.5) [72, 73]. Catalyst optimization found that the borenium cation [(Cl2 C3 (NMe)2 )(9-BBN)]+ to be most effective, affording a turnover frequency of ~ 1000 h−1 at 102 atm of H2 and 25 C. Subsequent work by Crudden et al. [74] has broadened the range of borenium cations to include those derived from triazole-derived meso-ionic N-heterocyclic carbenes (MIC). In 2013, we described the high Lewis acidity of electrophilic phosphonium cations. In contrast to boron-based systems, these derive their Lewis acidity from a low-lying σ ∗ orbital [75]. Moreover, we showed that [FP(C6 F5 )3 ][B(C6 F5 )4 ] in combination with a bulky amine affected FLP hydrogenation of olefins (Scheme 1.5) [76]. This proof of principle suggested that other potential catalysts could be derived from a wider variety of main group Lewis acids. In 2014, an innovative application of the concept of FLPs was reported by Ingleson and coworkers [77]. These researchers showed that N-methylacridinium salts are carbon-based Lewis acids (Scheme 1.5), which in the presence of 2,6lutidine generate a truly organic FLP. Such systems mediate the hydrogenation of bulky imines. The concept of FLPs has also been extended to unique pairs. For example, the complex [((Ph2 PC6 H4 )2 B(η6 -Ph))RuCl][B(C6 F5 )4 ] is Lewis acidic on the π bound arene ring (Scheme 1.5) [78]. This Lewis acid yields an FLP in combination with Mes3 P and also acts as Lewis acid catalyst for the catalytic hydrogenation of aldimines at room temperature. This system is a rather curious example of a catalyst containing an ancillary metal center. Extending the concept of FLPs, Wass among others have developed systems in which transition metal species are used as the Lewis acid component [79]. On the other hand, metals can also act as the basic component of an FLP. Examples of this latter situation are a series of Ni species described by Peters and coworkers [80]. The complexes (ArB(C6 H4 PPh2 )2 Ni Ar = Ph, Mes) activate H2 reversibly, whereby a boronhydride nickel(II) complex is generated. This species affects the hydrogenation of olefin substrates under mild conditions. While efforts to develop new FLPs derived from new, strong Lewis acids continue, an alternative approach exploited a weaker Lewis acid and a stronger base. Perhaps the most noteworthy examples of such systems are the salts, MPtBu2 (M = Li, Na, K), KH and KN(SiMe3 )2 (Scheme 1.5). In a 2018 report, we [81] showed that these systems, activate H2 to generate phosphine and MH reversibly and indeed these systems are capable of mediating imine and olefin hydrogenation.

1.2.5 Heterogeneous Hydrogenation Catalysis FLPs have also been exploited to advance the development of heterogeneous hydrogenation catalysts. The groups of Guo and Wang [82] demonstrated that while a clean gold surface is unreactive to H2 , its combination with an imine or nitrile in solution prompted the hydrogenation of C–N bonds. In this system, the Au surface

1 Frustrated Lewis Pair Catalysis: An Introduction

11

and soluble N-donor act as a rare example of a biphasic FLP which is able to activate H2 . In 2018, Ma and coworkers developed a clever strategy to install a Lewis pair in the pores of a metal-organic framework (MOF). These authors [83] then went on to employ this MOF–FLP material to affect the reduction of various imines. Moreover, these materials were shown to be recyclable in subsequent reduction runs. This strategy offers the advantages of air stability and recyclability of the catalyst while selectivity can be tuned via the manipulation of the MOF-FLP pore-size [83, 84]. In a subsequent study, Ma’s groups extended the utility of such MOF-FLP catalysts to affect the heterogeneous reduction of αβ-unsaturated organic compounds. For example, this catalyst was capable of selectively reducing the imine bond in αβunsaturated imine substrates en route to the allylic amines [85].

1.2.6 Asymmetric Hydrogenation The evolution from a broadening scope of substrates to more sophisticated catalyst systems capable of stereoselective reductions is a path that began for transition metal chemistry some 50 years ago. A similar evolution has occurred for FLP catalysts. Indeed, the potential of stereoselective, metal-free hydrogenations by FLPs was recognized very early on, as Klankermayer [86] reported such reduction in 2008, albeit with poor enantioselectivity. Nonetheless, efforts toward this end have continued, with contributions from our group as well as those of Erker [87] and Repo [88]. While Repo’s system was certainly the best of these, the indisputable leader in the development of asymmetric FLP reduction catalysts has been the research group of Du [89–92] while Wang and coworkers [93] have more recently made important contributions. Details of these systems are reviewed in a subsequent chapter and thus further discussion of these important advances is not present here.

1.3 Other Catalysis with FLPs The ability of FLPs to activate H2 also probed immediate questions about the possibility of the activation of other small molecules. Indeed, a great deal of work has been done based on this concept, and much of the stoichiometric chemistry has been reviewed previously. Here, we describe the key examples where such small molecule activation by FLPs can be applied in the catalysis.

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D. W. Stephan

1.3.1 Hydrosilylation The first description of hydrosilylation of ketones and aldehydes mediated by B(C6 F5 )3 was reported by Parks and Piers in 1996 [94]. While one might have proposed Lewis acid interaction with the carbonyl (Scheme 1.6) prompts reaction with silane, these authors demonstrated that these reactions proceeded by Lewis acid activation of the Si–H bond, prompting attack by the carbonyl. This finding was subsequently unambiguously confirmed by Oestreich and coworkers [95], who showed hydrosilylation of ketone proceeds with inversion of the silane. Thus, the initial finding by Piers was the first example in which a base (carbonyl) and Lewis acid act on a substrate. With the emergence of the concept of FLP chemistry, it is now clear that Piers’ work was ahead of its time, illustrating what is clearly now described as an FLP-type mechanism. In the intervening years since Piers work, borane mediated hydrosilylations have been exploited in a plethora of reactions affording a wide range of silicon derivatives. Much of the work in this area has been reviewed [96]. On the other hand, our work has focused on the use of other Lewis acids in hydrosilylations. In a series of papers, we showed that electrophilic phosphonium cations such as [(C6 F5 )3 PF]+ mediated the hydrosilylation of olefins [97] ketones, imines, nitriles [98] and amides [99] as well as the catalytic reductive deoxygenation of ketones (Scheme 1.6) [100]. More recently, we have described the use of the readily accessible air-stable Lewis acid [(terpy)PPh][B(C6 F5 )4 ]2 to mediate the hydrosilylation of aldehydes, ketones, and olefins (Scheme 1.6) [101]. All of these phosphorus cation-mediated reductions are thought to proceed via a mechanism analogous to the Piers-hydrosilylations [102]. This view is supported by a variety of observations including substrate selectivity. Nonetheless, the possibility that the P-cation acts as an initiator, prompting catalysis in which the silylium cation acts as the Lewis acid in a Piers-FLP mechanism cannot be unambiguously eliminated. Indeed, the marked difficulty in developing enantioselective analogs supports the latter proposition [103]. Scheme 1.6 Examples of FLP-mediated hydrosilylations

O R'

H

+ HSiR3

5 mol % cat

SiR3

O R'

H 2

Cat. = B(C6F5)3 or F C 6F 5 P C 6F 5 C 6F 5 [B(C6F5)4]

N N P

Ph

N

[B(C6F5)4]2

1 Frustrated Lewis Pair Catalysis: An Introduction

13

1.3.2 Transfer Hydrogenation The ability of strong Lewis acids to abstract hydride from carbons α to the N of amines has been known for some time. This was exploited to develop a strategy for a B(C6 F5 )3 -mediated catalytic transfer hydrogenation of imines, enamines, and N-heterocycles using iPr2 NH as the source of hydrogen (Scheme 1.7) [104]. Oestreich and coworkers [105] used cyclohexadienes and B(C6 F5 )3 , to reduce 1,1diarylolefins catalytically (Scheme 1.7). These reactions result in hydride abstraction generating the anion [HB(C6 F5 )3 ]− and a Wheland intermediate. The latter protonates the alkene, prompting hydride delivery. In a related sense, Chen et al. showed that Et3 N/B(C6 F5 )3 promotes transfer hydrogenation of methyl-methacrylate to give methylisobutyrate [106], while Melen et al. reduced silyl enol ethers using γ -terpinene as the hydrogen surrogate and TMP/B(C6 F5 )3 as the catalyst [107]. It is also interesting to consider the work of Radosevich et al. [108]. These authors showed that P(III) cations, which possess constrained T-shaped geometry, exhibited both Lewis acidity and basicity, allowing it to undergo oxidation to P(V) in reactions with ammonia–borane. The resulting dihydride then proved effective in catalytic transfer hydrogenation of diazobenzenes. While this is not strictly an FLP system, the conceptual relevance is intriguing. The Ingleson group [77] in developing the FLP chemistry of the Nmethylacridinium salt and lutidine mediated the transfer hydrogenation of imines, using Me2 NHBH3 as the reductant (Scheme 1.7). Du and coworkers [109] have achieved asymmetric transfer hydrogenation of imines using ammonia borane as hydrogen source, and a catalyst derived from the combination of HB(C6 F5 )2 with a chiral tert-butylsulfinamide, and a pyridine additive (Scheme 1.7). This led to the observation of good to excellent enantiomeric excesses of 84–95%. Further examples of asymmetric transfer hydrogenation have been reviewed [110] and are detailed in a subsequent chapter. Scheme 1.7 Examples of FLP-mediated transfer hydrogenations

Ph H

5 mol% tBu B(C6F5)3 Ph N iPr2NH 5 mol% B(C6F5)3

R1

N

Ph N

H

R1 R2

R2

Ph

tBu + Me2C=NiPr NH

[B(C6F5)4]

HMe2NBH3

CH3

+

H

N

/

Ph

Ph + (Me2NBH2)3 NH

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D. W. Stephan

1.3.3 Hydroboration In 2008, we showed that an FLP reacts stoichiometrically with HBcat [111], however, it was not until a 2015 study that this finding was extended to catalysis. Fan et al.showed the bulky borane ((CF)3 C6 H2 )2 BMe yields an FLP with pyridine. However, it is interesting that this borane could also be used as a catalyst to mediate 1,4-hydroboration of a series of pyridines with HBpin (Scheme 1.8) [112]. The subsequent year, while we reported the Piers’ borane (HB(C6 F5 )2 ) mediated hydroboration of alkynes [113]. Oestreich and colleagues described the use of B(3,5-(CF3 )2 C6 H3 )3 to hydroborate a series of alkenes with pinacolborane (HBpin) (Scheme 1.8). Interesting efforts to effect the corresponding reaction with B(C6 F5 )3 did not proceed. Hydroboration of styrene derivatives is shown to be selective for the cis-diastereomer [114]. In a subsequent study, these authors use this same borane to effect the hydroboration of imines [115]. In a similar vein, Melen and coworkers have used B(2,4,6-(CF3 )3 C6 H2 )3 to mediate the hydroboration of alkynes, aldehydes and imines, affording over 50 borylated products [116]. Ingleson’s group has pioneered the use of borenium cations in stoichiometric synthetic chemistry [117] and has also developed the process catalyzed by B(C6 F5 )3 affecting alkyne hydroboration using a borane-carbene adduct(Scheme 1.8) [118]. These reactions afford a selective avenue to trans-hydroboration. Crudden and coworkers [119] used B(C6 F5 )3 or [Ph3 C]+ and DABCO to generate related borenium salts by B−H bond abstraction from pinacolborane. This system proved effective in the hydroboration of imines. Scheme 1.8 Examples of FLP-mediated hydroborations

5 mol% CF3 CF3

2 CF3

+ HBpin

BMe

N

N

Bpin 5 mol% R' + HBpin

R

H

HB(C6F5)2 R

Bpin R'

F3C 5 mol% B 3 + HBpin

R

Bpin

F3C R

R

H

+ (NHC)-9-BBN

5 mol% B(C6F5)3

R

Bpin

H

H

1 Frustrated Lewis Pair Catalysis: An Introduction Scheme 1.9 Examples of FLP-mediated hydroaminations

R

15

10 mol% R N B(C6F5)3

NH R' + X

X

O EtO C 2 +

N

5mol% B(C6F5)3

N

10 mol% Brønsted acid

CO2Et O Boc +

N

5mol% B(C6F5)3 10 mol% Ph Brønsted acid

R'

O HN N

CO2Et CO2Et

Boc NH O Ph

1.3.4 Amination One of the first papers on FLP chemistry described the addition of phosphine and borane to olefins [4]. This work proved seminal in the development of a catalytic strategy to hydroamination. While stoichiometric addition of sterically encumbered amines and B(C6 F5 )3 to alkynes afforded the zwitterionic addition product of the form [R’2 NHC(R)=C(H)B(C6 F5 )3 ], use of a catalytic amount of borane with slow addition of the terminal alkyne gave the corresponding enamine product was prepared (Scheme 1.9) [120]. This metal-free route to hydroamination also proved to be amenable to tandem hydrogenation catalysis as subsequent addition of H2 effected the conversion of the enamines to the corresponding amines in a single pot. The hydroamination of alkynes was subsequently extended to intramolecular systems affording a catalytic route to a variety of heterocyclic derivatives [121]. Wasa and coworkers [122] have developed enantioselective α-aminations of ketones with dialkyl-azodicarboxylates catalyzed by FLPs derived from a Lewis acid and a Brønsted base (Scheme 1.9). These reactions afford an elegant route to α-aminocarbonyl compounds in high enantiomeric purity. In a conceptually related study, Wasa’s group also described the use of this same FLP to direct the Mannichtype reactions of a broad range of carbonyl compounds and aldimines with imines to afford both α- and β-amino esters (Scheme 1.9) [123].

1.3.5 Hydroarylation Electrophilic phosphonium cations have been exploited as Lewis acid catalysts to affect the hydroarylation of olefins by substituted anilines, bis-arylamines, phenol, furan, thiophene, pyrrole, and indole derivatives under mild conditions (Scheme 1.10) [124]. In a similar vein, the electrophilic dicationic [(PhO)P(2-(N-

16

D. W. Stephan

Scheme 1.10 Examples of FLP-mediated hydroarylations

1 mol% F C6F5 C6F5

Ph

Ph

P

H N Ph

C6F5

[B(C6F5)4]

+ HNPh2

Ph

Ph

(4-XC6H4)2E + RCCH

E

5 mol% O P

Ph

X

X R

Ph Ph

N [B(C6F5)4]2 tBu

R

+

tBu 10 mol% B(C6F5)3 N

N Me R

N tBu

Mepy))Ph2 ][B(C6 F5 )4 ]2 , catalyzed the double hydroarylation of alkynes with diarylamines to give a series of 9-methyl-9-aryl-9,10-dihydroacridine and 9,10-dimethyl9-aryl-9,10-dihydroacridine derivatives (Scheme 1.10) [125]. In a very recent report, we have described the hydroarylation of alkynes with N-substituted pyrroles catalyzed by B(C6 F5 )3 affording a family of dipyrrole alkanes (Scheme 1.10). Monohydroarylation was observed only for alkynes incorporating sterically congested substituents [126]. These reactions proceed via an initial zwitterionic intermediate in which the carbon-based nucleophile and the Lewis acid add to the alkyne, akin to the stoichiometric reactions of FLPs with alkynes [127].

1.3.6 C–H Borylation In a ground-breaking advance in 2015, Fontaine [128] and coworkers developed the intramolecularFLP (1-N(C5 H6 Me4 )-2-BH2 C6 H4 ) and demonstrated that this species could mediate the C–H borylation of furans, pyrroles, and electron-rich thiophenes (Scheme 1.11). The following year, Fontaine’s group showed that the use of the air-stable zwitterionic salt (1-HN(C5 H6 Me4 )-2-BF3 C6 H4 ) offered a convenient and efficient catalyst for such borylations [129]. That same year, Repo further expanded

1 Frustrated Lewis Pair Catalysis: An Introduction

17

Scheme 1.11 Examples of FLP-mediated C–H borylations

2.5 mol% BH2 N E

E

+ HBpin

Bpin + H 2

E + NR, O, S

the scope of such borylations to include arene and alkyne C–H bonds (Scheme 1.10) [130]. Fontaine went on to develop related amino-borane catalysts and to study the borylations experimentally and computationally, establishing the precatalysts contained BF3 units showed improved reactivity and could be used for multigram-scale syntheses (Scheme 1.11) [131]. In addition, Fontaine et al. extended such borylations to a series of 1-arylsulfonyl indoles affording borylation in 2 and 3-positions [132].

1.3.7 Polymerization As early as 2010, Chen began to develop an innovative application of FLP reactivity in polymerization. Indeed, FLPs derived from Al(C6 F5 )3 and phosphines or carbenes have been shown to affect the polymerization of a variety of species including methyl methacrylate (MMA), methylene butyrolactones, α-methylene-γ butyrolactone, γ -methyl-αmethylene-γ -butyrolactone [133–135], 2-vinyl pyridine and 2-isopropenyl-2-oxazoline (Scheme 1.12) [136]. In other innovations for polymerization, Würthwein described the use of Al/Nbased FLPs to oligomerize cyanamides [137]. In a distinct approach to polymerization, Erker, Studer, and Warren exploited radicals derived from the capture of NO with FLPs to effect the polymerization of acrylates and vinyl monomers (Scheme 1.12) [138]. In a more recent innovation, Xu and Xu have polymerized conjugated polar alkenes using rare-earth aryloxides with phosphines or N-heterocyclic carbenes. In Scheme 1.12 Examples of FLP-mediated polymerizations

N

n

B(C6F5)3 NHC (C6F5)2 B N O P Mes2

N

Ph

Mes2P N B(C F ) 6 5 2 n O

18 Scheme 1.13 Examples of FLP-mediated CO2 -reductions

D. W. Stephan

2 Et3P + CO2

CO2 + H2

4 mol% Et3P C PEt3 ZnBr2 (In2O3 x(OH)y)

Et3PO + CO

CO + H2O

this fashion, these authors prepared syndiotactic poly-methyl methacrylate. This rare-earth Lewis-based FLP was also effective for the polymerization of acrylates and acrylamide monomers [139].

1.3.8 CO2 Reduction The ability of FLPs to capture CO2 was demonstrated some time ago [140]. Since then, a series of efforts have focused on stoichiometric reduction reactions [12, 141], while more recent efforts have strived to effect the catalytic, metal-free reduction of CO2 . Conversion of CO2 to CO and phosphineoxide was mediated using in situ generated bis-phosphaylide as the base and Zn-halide as the Lewis acid (Scheme 1.13) [142]. Alternatively, several FLP systems have been shown to catalyze the hydroboration of CO2 provided methoxy boranes, ultimately a source of methanol (Scheme 1.13) [143–146]. In related heterogeneous work, Ozin and coworkers [147] have studied the catalytic conversion of CO2 and H2 to CO and H2 O using nanostructured hydroxylated indium oxide nanocrystals (In2 O3 x(OH)y ) (Scheme 1.13). Spectroscopic, kinetic, and computational data infer that this catalyst operates by the cooperative action of a Lewis basic hydroxide-oxygen atom and a Lewis acidic indium. A subsequent study [148] further supported this surface FLP mechanism where oxygen vacancies generate Lewis acidic indium and surface hydroxides basic sites.

1.3.9 C–F Derivatization The Lewis acid B(C6 F5 )3 was shown to mediate the conversion of alkyl fluorides to the corresponding alkanes in the presence of silane [149] affording the silylfluoride as the by-product (Scheme 1.14). Such reactions are thought to proceed by a mechanism analogous to the Piers’ mechanism for hydrosilylation, in which the Lewis acid activates the Si–H bond for attack by the alkylfluoride. In a similar sense, the more potent Lewis acids derived from EPCs have been exploited in hydrodefluorination. Moreover, performance of these reactions in the presence of electron-rich arenes provides an avenue for C–F arylation. Thus using benzyl fluorides [150] or CF3 -aryl

1 Frustrated Lewis Pair Catalysis: An Introduction

CF3

Rn

R3SiH

CF3

R2 + R3SiF + H2

Alkyl

cat.

R2 Et3SiH cat.

F

E

R1

n + R3SiF + H2

R2

E

Et3SiH cat.

t-Bu

R1

+ R3SiF + H2

E = O, S, NR F

F

Me3Si + R3

R1

+ R3SiF + H2

H2 C

R3SiH R2

F R2

R1

H2 C

Rn

cat.

R2

Alkyl

19

cat.

R2

R1 + Me3SiF R2 R3

cat. =

C6F5

P

C6F5 C6F5

[B(C6F5)4]

Scheme 1.14 Examples of FLP-mediated C-F derivatizations

[151] compounds as the fluoro precursors, provides catalytic routes to a wide range of diarylmethanes and alkylated-arenes (Scheme 1.14). In a more recent study, the P(III)-dications, [(terpy)PPh][B(C6 F5 )4 ]2 and [(bipy)PPh][B(C6 F5 )4 ]2 were used to catalyze the hydrodefluorination of nonactivated alkyl C–F bonds in the presence of silane as well as for the Csp3 –Csp3 coupling of benzyl fluorides with allyl silanes (Scheme 1.14) [152]. These latter coupling reactions proved tolerant of a number of functionalized additives and were selective for the benzyl fluorides in the presence of benzyl bromides or chlorides. As such these protocols are complementary to related metal-based cross-couplings.

1.4 Future Directions The emergence of FLP chemistry has provided a new approach to catalysis. The logical extension of the ability of FLPs to activate H2 resulted in the development of metal-free, main group-based hydrogenation catalysts. Subsequent developments have broadened the nature of FLP catalysts to include a range of main group homogeneous as well as heterogeneous systems. In addition, studies have improved activity, broadened the range of substrates, developed catalysts that offer functional-group tolerance and providing highly enantioselective catalysts. Moreover, the ability of

20

D. W. Stephan

FLPs to react with other small molecules led to the development of a range of other FLP catalyzed processes. The rapid development of FLP catalysis over the past decade has altered the landscape and provided new options for the evolution and greening of catalyst technologies. While commercial applications are certainly reasonable projections for future developments, FLPs also offer approaches to the development of new catalytic protocols for synthetic chemistry. This is certainly an area where advances are expected. FLP catalysis also offers new approaches to other persistent fundamental challenges. What is clear is that the future of FLP catalysis is bright. Acknowledgments The author would like to thank and acknowledge the excellent undergraduate and graduate students as well as postdoctoral fellows who have shared their enthusiasm for developing FLP chemistry. The author is also grateful to NSERC of Canada for research support and for the award of a Canada Research Chair as well as the 2019 J.C. Polanyi Award. In addition the author is grateful to the Guggenheim Foundation for the award of a 2020 fellowship.

References 1. Welch GC, Juan RRS, Masuda JD, Stephan DW (2006) Reversible, Metal-Free Hydrogen Activation. Science 314(5802):1124–1126. https://doi.org/10.1126/science.1134230 2. Welch GC, Stephan DW (2007) Facile Heterolytic Cleavage of Dihydrogen by Phosphines and Boranes. J Am Chem Soc 129(7):1880–1881. https://doi.org/10.1021/Ja067961j 3. Spies P, Erker G, Kehr G, Bergander K, Fröhlich R, Grimme S, Stephan DW (2007) Rapid Intramolecular Heterolytic Dihydrogen Activation by a Four-Bembered Heterocyclic Phosphane-Borane Adduct. Chem Commun 47:5072–5074 4. McCahill JSJ, Welch GC, Stephan DW (2007) Reactivity of “Frustrated Lewis Pairs”: Three-Component Reactions of Phosphines, a Borane, and Olefins. Angew Chem Int Ed 46(26):4968–4971. https://doi.org/10.1002/anie.200701215 5. Jupp AR, Stephan DW (2019) New Directions for Frustrated Lewis Pair Chemistry. Trends in Chemistry 1:35–48. https://doi.org/10.1016/j.trechm.2019.01.006 6. Stephan DW (2016) The Broadening Reach of Frustrated Lewis Pair Chemistry. Science 354:aaf7229. https://doi.org/10.1126/science.aaf7229 7. Stephan DW, Erker G (2015) Frustrated Lewis Pair Chemistry: Development and Perspectives. Angew Chem Int Ed 54(22):6400–6441. https://doi.org/10.1002/anie.201409800 8. Stephan DW (2015) Frustrated Lewis Pairs. J Am Chem Soc 137(32):10018–10032. https:// doi.org/10.1021/jacs.5b06794 9. Stephan DW (2015) Frustrated Lewis Pairs: From Concept to Catalysis. Acc Chem Res 48(2):306–316. https://doi.org/10.1021/ar500375j 10. Stephan DW, Erker G (2010) Frustrated Lewis Pairs: Metal-Free Hydrogen Activation and More. Angew Chem Int Ed 49(1):46–76. https://doi.org/10.1002/anie.200903708 11. Stephan DW (2012) Frustrated Lewis Pair Hydrogenations. Org Biomol Chem 10(48):5740– 5746. https://doi.org/10.1039/C2OB25339A 12. Stephan DW, Erker G (2014) Frustrated Lewis Pair Chemistry of Carbon, Nitrogen and Sulfur Oxides. Chem Sci 5(7):2625–2641. https://doi.org/10.1039/C4sc00395k 13. Stephan DW, Erker G (2013) Frustrated Lewis Pairs I: Uncovering and Understanding. Top Curr Chem 332:1–311. https://doi.org/10.1007/978-3-642-36697-0 14. Stephan DW, Erker G (2013b) Frustrated Lewis Pairs II: Expanding the Scope. Top Curr Chem 334:1–345. https://doi.org/10.1007/978-3-642-37759-4

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104. Farrell JM, Heiden ZM, Stephan DW (2011) Metal-Free Transfer Hydrogenation Catalysis by B(C6 F5 )3 . Organometallics 30(17):4497–4500. https://doi.org/10.1021/Om2005832 105. Yuan W, Orecchia P, Oestreich M (2017) Cyclohexa-1,3-diene-Based Dihydrogen and Hydrosilane Surrogates in B(C6 F5 )3 -Catalysed Transfer Processes. Chem Comm 53(75):10390–10393. https://doi.org/10.1039/c7cc06195a 106. Chen J, Chen EXY (2015) Reactivity of Amine/E(C6 F5 )3 (E = B, Al) Lewis Pairs Toward Linear and Cyclic Acrylic Monomers: Hydrogenation versus Polymerization. Molecules 20(6):9575–9590. doi: https://doi.org/10.3390/molecules20069575 107. Khan I, Reed-Berendt BG, Melen RL, Morrill LC (2018) FLP-Catalyzed Transfer Hydrogenation of Silyl Enol Ethers. Angew Chem Int Ed 57(38):12356–12359. https://doi.org/10. 1002/anie.201808800 108. Dunn NL, Ha MJ, Radosevich AT (2012) Main Group Redox Catalysis: Reversible P-III/P-V Redox Cycling at a Phosphorus Platform. J Am Chem Soc 134(28):11330–11333. https:// doi.org/10.1021/ja302963p 109. Li SL, Li G, Meng W, Du HF (2016) A Frustrated Lewis Pair Catalyzed Asymmetric Transfer Hydrogenation of Imines Using Ammonia Borane. J Am Chem Soc 138(39):12956–12962. https://doi.org/10.1021/jacs.6b07245 110. Meng W, Feng X, Du H (2018) Frustrated Lewis Pairs Catalyzed Asymmetric Metal-Free Hydrogenations and Hydrosilylations. Acc Chem Res 51(1):191–201. https://doi.org/10. 1021/acs.accounts.7b00530 111. Dureen MA, Lough A, Gilbert TM, Stephan DW (2008) B-H Activation by Frustrated Lewis Pairs: Borenium or Boryl Phosphonium Cation? Chem Commun 36:4303–4305. https://doi. org/10.1039/B808348g 112. Fan XT, Zheng JH, Li ZH, Wang HD (2015) Organoborane Catalyzed Regioselective 1,4Hydroboration of Pyridines. J Am Chem Soc 137(15):4916–4919. https://doi.org/10.1021/ jacs.5b03147 113. Fleige M, Mobus J, vom Stein T, Glorius F, Stephan DW (2016) Lewis Acid Catalysis: Catalytic Hydroboration of Alkynes Initiated by Piers’ Borane. Chem Commun 52(72):10830–10833. https://doi.org/10.1039/c6cc05360b 114. Yin Q, Kemper S, Klare HF, Oestreich M (2016) Boron Lewis Acid-Catalyzed Hydroboration of Alkenes with Pinacolborane: B(ArF )3 Does What B(C6 F5 )3 Cannot Do! Chem Eur J 22(39):13840–13844. https://doi.org/10.1002/chem.201603466 115. Yin Q, Soltani Y, Melen RL, Oestreich M (2017) BAr3 F -Catalyzed Imine Hydroboration with Pinacolborane not Requiring the Assistance of an Additional Lewis Base. Organometallics 36(13):2381–2384. https://doi.org/10.1021/acs.organomet.7b00381 116. Lawson JR, Wilkins LC, Melen RL (2017) Tris(2,4,6-trifluorophenyl)borane: An Efficient Hydroboration Catalyst. Chem Eur J 23(46):10997–11000. https://doi.org/10.1002/chem.201 703109 117. Cade IA, Ingleson MJ (2014) syn-1,2-Carboboration of Alkynes with Borenium Cations. Chem Eur J 20(40):12874–12880. https://doi.org/10.1002/chem.201403614 118. McGough JS, Butler SM, Cade IA, Ingleson MJ (2016) Highly Selective Catalytic transHydroboration of Alkynes Mediated by Borenium Cations and B(C6 F5 )3 . Chem Sci 7:3384– 3389. https://doi.org/10.1039/c5sc04798f 119. Eisenberger P, Bailey AM, Crudden CM (2012) Taking the F out of FLP: Simple Lewis AcidBase Pairs for Mild Reductions with Neutral Boranes via Borenium Ion Catalysis. J Am Chem Soc 134(42):17384–17387. https://doi.org/10.1021/Ja307374j 120. Mahdi T, Stephan DW (2013) Frustrated Lewis Pair Catalyzed Hydroamination of Terminal Alkynes. Angew Chem Int Ed 52(47):12418–12421. https://doi.org/10.1002/anie.201307254 121. Mahdi T, Stephan DW (2015b) Stoichiometric and Catalytic Inter- and Intramolecular Hydroamination of Terminal Alkynes by Frustrated Lewis Pairs. Chem Eur J 21(31):11134– 11142. https://doi.org/10.1002/chem.201501535 122. Shang M, Wang XX, Koo SM, Youn J, Chan JZ, Yao WZ, Hastings BT, Wasa M (2017) Frustrated Lewis Acid/Brønsted Base Catalysts for Direct Enantioselective alpha-Amination of Carbonyl Compounds. J Am Chem Soc 139(1):95–98. https://doi.org/10.1021/jacs.6b1 1908

1 Frustrated Lewis Pair Catalysis: An Introduction

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123. Chan JZ, Yao W, Hastings BT, Lok CK, Wasa M (2016) Direct Mannich-Type Reactions Promoted by Frustrated Lewis Acid/Brønsted Base Catalysts. Angew Chem Int Ed 55(44):13877–13881. https://doi.org/10.1002/anie.201608583 124. Pérez M, Mahdi T, Hounjet LJ, Stephan DW (2015) Electrophilic Phosphonium Cations (EPCs) Catalyzed Hydroarylation and Hydrosulfuration of Olefins. Chem Commun 51:11301–11304. https://doi.org/10.1039/C5CC03572D 125. LaFortune JHW, Bayne JM, Johnstone TC, Fan L, Stephan DW (2017) Catalytic Double Hydroarylation of Alkynes to 9,9-Disubstituted 9,10-Dihydroacridine Derivatives by an Electrophilic Phenoxyphosphonium Dication. Chem Commun 53:13312–13315. https://doi.org/ 10.1039/C7CC08037A 126. Guo J, Cheong O, Bamford KL, Zhou J, Stephan DW (2020) Frustrated Lewis Pair-Catalyzed Double Hydroarylation of Alkynes with N-Substituted Pyrroles. Chem Commun 56:18551858. https://doi.org/10.1039/C9CC08654D 127. Dureen MA, Stephan DW (2009) Terminal Alkyne Activation by Frustrated and Classical Lewis Acid/Phosphine Pairs. J Am Chem Soc 131(24):8396–8398. https://doi.org/10.1021/ ja903650w 128. Legare MA, Courtemanche MA, Rochette E, Fontaine FG (2015) Metal-Free Catalytic C-H Bond Activation and Borylation of Heteroarenes. Science 349(6247):513–516. https://doi. org/10.1126/science.aab3591 129. Legare MA, Rochette E, Legare Lavergne J, Bouchard N, Fontaine FG (2016) Bench-Stable Frustrated Lewis Pair Chemistry: Fluoroborate Salts as Precatalysts for the C-H Borylation of Heteroarenes. Chem Commun 52(31):5387–5390. https://doi.org/10.1039/c6cc01267a 130. Chernichenko K, Lindqvist M, Kotai B, Nieger M, Sorochkina K, Papai I, Repo T (2016) Metal-Free sp2 -C-H Borylation as a Common Reactivity Pattern of Frustrated 2Aminophenylboranes. J Am Chem Soc 138(14):4860–4868. https://doi.org/10.1021/jacs. 6b00819 131. Legare Lavergne J, Jayaraman A, Misal Castro LC, Rochette E, Fontaine F-G (2017) MetalFree Borylation of Heteroarenes Using Ambiphilic Aminoboranes: On the Importance of Sterics in Frustrated Lewis Pair C-H Bond Activation. J Am Chem Soc 139(41):14714–14723. https://doi.org/10.1021/jacs.7b08143 132. Jayaraman A, Misal Castro LC, Desrosiers V, Fontaine FG (2018) Metal-Free Borylative Dearomatization of Indoles: Exploring the Divergent Reactivity of Aminoborane C-H Borylation Catalysts. Chem Sci 9(22):5057–5063. https://doi.org/10.1039/c8sc01093e 133. Xu T, Chen EY (2014) Probing Site Cooperativity of Frustrated Phosphine/Borane Lewis Pairs by a Polymerization Study. J Am Chem Soc 136(5):1774–1777. https://doi.org/10. 1021/ja412445n 134. Zhang YT, Miyake GM, John MG, Falivene L, Caporaso L, Cavallo L, Chen EYX (2012) Lewis Pair Polymerization by Classical and Frustrated Lewis Pairs: Acid, Base and Monomer Scope and Polymerization Mechanism. Dalton Trans 41(30):9119–9134. https://doi.org/10. 1039/C2dt30427a 135. Zhang YT, Miyake GM, Chen EYX (2010) Alane-Based Classical and Frustrated Lewis Pairs in Polymer Synthesis: Rapid Polymerization of MMA and Naturally Renewable Methylene Butyrolactones into High-Molecular-Weight Polymers. Angew Chem Int Ed 49(52):10158– 10162. https://doi.org/10.1002/anie.201005534 136. He JH, Zhang YT, Chen EYX (2014) Synthesis of Pyridine- and 2-Oxazoline-Functionalized Vinyl Polymers by Alane-Based Frustrated Lewis Pairs. Synlett 25(11):1534–1538. https:// doi.org/10.1055/s-0033-1341248 137. Holtrichter-Rossmann T, Isermann J, Rosener C, Cramer B, Daniliuc CG, Kosters J, Letzel M, Wurthwein EU, Uhl W (2013) An Aluminum-Nitrogen Based Lewis Pair as an Effective Catalyst for the Oligomerization of Cyanamides: Formation of Acyclic C-N Oligomers Instead of Thermodynamically Favored Cyclic Aromatic Trimers. Angew Chem Int Ed 52(28):7135– 7138. https://doi.org/10.1002/anie.201301970 138. Sajid M, Stute A, Cardenas AJP, Culotta BJ, Hepperle JAM, Warren TH, Schirmer B, Grimme S, Studer A, Daniliuc CG, Frohlich R, Petersen JL, Kehr G, Erker G (2012) N,N-Addition

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139.

140.

141.

142.

143. 144.

145.

146.

147.

148.

149.

150.

151.

152.

D. W. Stephan of Frustrated Lewis Pairs to Nitric Oxide: An Easy Entry to a Unique Family of Aminoxyl Radicals. J Am Chem Soc 134(24):10156–10168. https://doi.org/10.1021/ja302652a Xu PF, Xu X (2018) Homoleptic Rare-Earth Aryloxide Based Lewis Pairs for Polymerization of Conjugated Polar Alkenes. ACS Catalysis 8(1):198–202. https://doi.org/10.1021/acscatal. 7b02875 Mömming CM, Otten E, Kehr G, Fröhlich R, Grimme S, Stephan DW, Erker G (2009) Reversible Metal-Free Carbon Dioxide Binding by Frustrated Lewis Pairs. Angew Chem Int Ed 48(36):6643–6646. https://doi.org/10.1002/anie.200901636 Ashley AE, Thompson AL, O’Hare D (2009) Non-Metal-Mediated Homogeneous Hydrogenation of CO2 to CH3 OH. Angew Chem Int Ed 48(52):9839–9843. https://doi.org/10. 1002/anie.200905466 Dobrovetsky R, Stephan DW (2013) Catalytic Reduction of CO2 to CO by Using Zinc(II) and In Situ Generated Carbodiphosphoranes. Angew Chem Int Ed 52(9):2516–2519. https:// doi.org/10.1002/anie.201208817 Wang T, Stephan DW (2014) Phosphine Catalyzed Reduction of CO2 with Boranes. Chem Commun 50(53):7007–7010. https://doi.org/10.1039/C4cc02103g Courtemanche MA, Legare MA, Maron L, Fontaine FG (2014) Reducing CO2 to Methanol Using Frustrated Lewis Pairs: On the Mechanism of Phosphine-Borane-Mediated Hydroboration of CO2 . J Am Chem Soc 136(30):10708–10717. https://doi.org/10.1021/ja5047846 Fontaine FG, Courtemanche MA, Legare MA (2014) Transition-Metal-Free Catalytic Reduction of Carbon Dioxide. Chem Eur J 20(11):2990–2996. https://doi.org/10.1002/chem.201 304376 Gomes CD, Blondiaux E, Thuery P, Cantat T (2014) Metal-Free Reduction of CO2 with Hydroboranes: Two Efficient Pathways at Play for the Reduction of CO2 to Methanol. Chem Eur J 20(23):7098–7106. https://doi.org/10.1002/chem.201400349 Ghuman KK, Wood TE, Hoch LB, Mims CA, Ozin GA, Singh CV (2015) Illuminating CO2 Reduction on Frustrated Lewis Pair Surfaces: Investigating the Role of Surface Hydroxides and Oxygen Vacancies on Nanocrystalline In2 O3-x (OH)y . Phys Chem Chem Phys 17(22):14623–14635. https://doi.org/10.1039/c5cp02613j Ghuman KK, Hoch LB, Szymanski P, Loh JY, Kherani NP, El-Sayed MA, Ozin GA, Singh CV (2016) Photoexcited Surface Frustrated Lewis Pairs for Heterogeneous Photocatalytic CO2 Reduction. J Am Chem Soc 138(4):1206–1214. https://doi.org/10.1021/jacs.5b10179 Caputo CB, Stephan DW (2012) Activation of Alkyl C-F Bonds by B(C6 F5 )3 : Stoichiometric and Catalytic Transformations. Organometallics 31(1):27–30. https://doi.org/10.1021/Om2 00885c Zhu JT, Pérez M, Stephan DW (2016) C-C Coupling of Benzyl Fluorides Catalyzed by an Electrophilic Phosphonium Cation. Angew Chem Int Ed 55(29):8448–8451. https://doi.org/ 10.1002/anie.201603627 Zhu J, Pérez M, Caputo CB, Stephan DW (2016) Use of Trifluoromethyl Groups for Catalytic Benzylation and Alkylation with Subsequent Hydrodefluorination. Angew Chem Int Ed 55(4):1417–1421. https://doi.org/10.1002/anie.201510494 Chitnis S, Kirscher F, Stephan DW (2018) Catalytic Hydrodefluorination of C-F Bonds by Air-Stable P(III) Lewis Acids. Chem Eur J 4:6543–6546. https://doi.org/10.1002/chem.201 801305

Chapter 2

Frustrated Lewis Pair Catalyzed Asymmetric Reactions Xiangqing Feng, Wei Meng, and Haifeng Du

Abstract As a lately emerging area, frustrated Lewis pair chemistry provides the most effective way for metal-free catalytic reductions, and a wide range of unsaturated compounds have been successfully reduced. However, the asymmetric catalytic reduction is still in its initial stage, and some formidable challenges still remain. The development of highly effective chiral FLP catalysts and their applications in asymmetric catalysis are two very important subjects in this field. This chapter will summarize the advances for chiral FLP catalysts and metal-free asymmetric reductions including hydrogenations, Piers-type hydrosilylations, and transfer hydrogenations in the past six years. Keywords Frustrated Lewis pairs · Asymmetric catalysis · Chiral boranes · Chiral Lewis bases · Asymmetric hydrogenation · Asymmetric hydrosilylation · Asymmetric transfer hydrogenation

Abbreviations Ac Ar Atm Barton’s base

Acetyl Aryl Atmosphere 2-tert-butyl-1,1,3,3-tetramethylguanidine

X. Feng · W. Meng · H. Du (B) Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China e-mail: [email protected] X. Feng e-mail: [email protected] W. Meng e-mail: [email protected] University of Chinese Academy of Sciences, Beijing 100049, China © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_2

29

30

Bn Boc Bu Cat. Cbz Conv. Cy DCM DFT DIBAL-H DMF DMS dr ee equiv. Et FLPs LA LB Me Mes NHC Np PCC Ph Piers’ Borane Pin PG PMHS PMP1 PMP2 Pr Rt TBAF Tf THF TMS Tol Ts

X. Feng et al.

Benzyl t-Butyloxy carbonyl Butyl Catalyst Benzyloxycarbonyl Conversion Cyclohexyl Dichloromethane Density Functional Theory Diisobutyl aluminium hydride Dimethylformamide Dimethyl sulfide Diastereomeric ratio Enantiomeric excess Equivalent(s) Ethyl Frustrated Lewis pairs Lewis acid Lewis base Methyl 2,4,6-Trimethylphenyl N-heterocyclic carbene Naphthyl Pyridinium chlorochromate Phenyl HB(C6 F5 )2 Pinacol Protecting group Polymethylhydrosiloxane p-Methoxyphenyl 1,2,2,6,6-Pentamethylpiperidine Propyl Room temperature Tetrabutylammonium fluoride Trifluoromethylsulfonate Tetrahydrofuran Trimethylsilyl Tolyl Tosyl

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

31

2.1 Introduction In 2006, Stephan and coworkers reported the first metal-free reversible activation of H2 by an intramolecular combination of sterically hindered Lewis acid and base (Scheme 2.1) [1], which opens a novel field of frustrated Lewis pair (FLP) chemistry [2–12]. Since then, the field of FLPs has witnessed extremely rapid growth, and numerous FLPs have been widely utilized as catalysts for hydrogenations, hydrosilylations, and transfer hydrogenations, which have previously been predominated by the transition-metal catalysts. The FLP-catalyzed metal-free hydrogenation of unsaturated compounds has been successfully realized. However, the asymmetric versions are still far less developed [13–18]. In 2008, Klankermayer and coworkers reported the first chiral FLPcatalyzed asymmetric hydrogenation of an imine 3a to furnish the desired amine in a quantitative conversion with 13% ee [19]. Chiral borane 4 was derived from Piers’ borane(HB(C6 F5 )2 ) and (+)-α-pinene (Scheme 2.2). Despite the low enantioselectivity, this study presents a promising possibility for the asymmetric hydrogenation with chiral FLP catalysts. Subsequently, several chiral FLPs were designed and synthesized for asymmetric hydrogenations [20–23] and hydrosilylations [24–26]. Enamines, imines and 2-phenylquinoline proved to be effective substrates but generally giving less than 90% ee (Fig. 2.1). The development of highly effective chiral FLP catalysts and their applications in asymmetric catalysis are therefore still two very important subjects in this field. The construction of chiral FLPs can be usually categorized into three types, (I) intramolecular FLPs [21, 22], (II) intermolecular FLPs of chiral acids, and achiral bases [19, 20], (III) intermolecular FLPs of achiral acids and chiral bases. For the reported chiral Lewis acids, two protocols were usually developed for their synthesis. One is the hydroboration of chiral alkenes or alkynes with Piers’ borane [27]. When an internal alkene was used, a mixture of diastereoisomers was often generated. The other is the substitution reaction of (C6 F5 )n BCl3−n with organometallic reagents. F

F

(Mes)2P H

F

H B(C6F5)2

F

1

>100 oC, -H2 (75%) H2 (1 atm), 25 oC (100%)

F

(Mes)2P

B(C6F5)2 F

F

2

F

Scheme 2.1 Reversible activation of H2 by frustrated Lewis pairs

Scheme 2.2 Asymmetric hydrogenation of imine catalyzed by chiral borane 4

N Ph

3a

Ph Me

4 (10 mol %) H2 (20 atm) toluene, 65 °C

HN

Ph

∗

Ph

Me 5a > 99% conv. 13% ee

C6F5

B 4

C6F5

32

X. Feng et al. B(C6F5)2

C6F5

B

C6F5

2008

Ph

P t Bu3

2010

B(C6F5)2

N

B(C6F5)2

B C6F5

P t Bu2 2012

Klankermayer J.

2011

2012

Repo T.

Oestreich M.

Fig. 2.1 Representative borane or FLP catalysts for asymmetric reductions

Some significant advances have been made in the past decade for type I and II chiral FLPs. In a sharp contrast, despite the vast number of chiral Lewis bases, type III chiral FLPs have rarely been disclosed. This chapter will summarize the advances for chiral FLP catalysts and the asymmetric reactions since 2013.

2.2 Asymmetric Hydrogenation 2.2.1 Asymmetric Hydrogenation of Imines and Related Substrates In 2013, Du and coworkers developed a novel strategy for preparing chiral FLP catalysts [28]. As shown in Scheme 2.3, chiral boranes were generated by the in situ hydroboration of chiral binaphthyl-based dienes with Piers’ borane. This strategy avoided the tedious isolation and purification process. Moreover, the terminal olefin also avoided to generate diastereoisomers. The in situ generation strategy makes the easy operation and the rapid evaluation beneficial for the discovery of highly effective chiral FLPs catalysts (Scheme 2.3). Chiral dienes 9 were prepared with readily available (S)-diisopropyl-3,3’dibromo-1,1’-binaphthyl-2,2’-dicarboxylate (6) as starting material. After a subsequent Suzuki coupling reaction, reduction with LiAlH4 , oxidation, and Wittig reaction, a variety of chiral dienes 9 bearing different aryl substituents at the 3,3’positions were afforded in reasonable yields [29] (Scheme 2.4). These in situ derived chiral boranes were investigated for the asymmetric hydrogenation of imine 3a, the

HB(C6F5)2 in situ generation easy operation rapid evaluation

Scheme 2.3 New strategy for the development of chiral FLP catalysts

B(C6F5)2 B(C6F5)2

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions Br

Ar

Ar

CO2iPr CO2iPr

6

33

CO2iPr CO2iPr

ArB(OH)2 Pd(OAc)2

Br

7 Ar

KOtBu

9

Ar

CHO CHO

2. PCC

Ar

9a: Ar = Ph 9b: Ar = 4-tBuC6H4 9c: Ar = 4-CF3C6H4 9d: Ar = 3-MeC6H4 9e: Ar = 3-MeOC6H4 9f: Ar = 2,4,6-Me3C6H2

MePPh3I

1. LiAlH4

8

Ar

i 9g: Ar = 2-MeO-4- PrC6H3 9h: Ar = 3,5-tBu2C6H3 9i: Ar = 3,5-(3,5-tBu2C6H3)2C6H3 9j: Ar = 2-MeO-5-tBuC6H3 9k: Ar = 2-EtO-5-tBuC6H3 9l: Ar = 2-iPrO-5-tBuC6H3

Scheme 2.4 New strategy for the development of chiral FLP catalysts

substituents on chiral dienes 9 had a significant impact on the enantioselectivities of the reactions. The bulkiest chiral diene 9i gave a relatively high 60% ee (Table 2.1). For imines 3, both electron-donating and electron-withdrawing substituents were well tolerated for this hydrogenation, giving the amine products 5 in 63–99% yields with 74–89% ee’s (Table 2.2) [28]. In 2015, an intramolecular chiral aminoborane FLP catalyst 13 with a binaphthyl backbone was developed by Pápai and Repo [30]. The catalyst was prepared from (R)-11 by lithiation and substitution with B(C6 F5 )2 Cl, and it could activate H2 rapidly and reversibly (Scheme 2.5). The asymmetric hydrogenation of unhindered imines and enamines furnished a variety of amine products in moderate to high yields with Table 2.1 Evaluation of chiral dienes 9 for asymmetric hydrogenation of imine 3a N Ph

Ph

Me 3a

HB(C6F5)2 10 (10 mol %) 9 (5 mol %) H2 (10 bar), 60 C

HN

Ph Me

Ph 5a

Entry

chiral diene 9

yield (%)

ee (%)

1

9b

100

16

2

9d

100

22

3

9f

100

25

4

9g

100

30

5

9h

100

40

6

9i

100

60

34

X. Feng et al.

Table 2.2 Catalytic asymmetric hydrogenation of imines N

Ph HB(C6F5)2 10 (2.5-10 mol %) 9i (1.25-5 mol %) H2 (20 bar), rt

R

Ar

HN

Entry 1

R

Ar

3

Ph

5

product NHPh Ph

Me

5a

yield (%)

ee (%)

98

78

91

89

97

85

91

80

95

85

96

79

63

88

93

78

NHPh

2

Me

5b

BnO

NHPh

3

Me

5c

F3C

NHPh

4

MeO

Me

5d NHPh ∗

5

Me

5e

O NHPh

6 5f PhHN

7 5g NHPh

8

Et i

Me Me N Me I

PrO

1. -78 °C to rt n BuLi 2. -78 °C to rt B(C6F5)2Cl

(R)-11

Scheme 2.5 Synthesis of Catalyst (S)-13

5h Me Me N Me B(C6F5)2

(S)-12

H2 (2 bar) toluene, rt, 1 min C6D6, 80 °C, 15 min

Me Me Me N H B(C6F5)2 H (S)-13

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

35

up to 99% ee (Table 2.3). DFT studies suggested that both the repulsive steric and stabilizing intermolecular noncovalent forces were very important in the stereodetermining hydride transfer step. A ferrocene-based phosphane/borane frustrated Lewis pair catalyst 15 was reported by Erker and coworkers [31], which was applied in the asymmetric hydrogenation of imines, giving the corresponding products in moderate yields and with up to 69% ee [32] (Table 2.4). With α-phosphanyl ferrocenecarbaldehydeas starting material, chiral alkene 14 was obtained after a Wittig–Horner olefination. The phosphonium/hydridoborate 15 was then obtained through the hydroboration with Piers’ borane and a following reaction with H2 , and the major stereoisomer (pS,R)-15 could easily be obtained in diastereomerically pure form by crystallization (Scheme 2.6). To shorten the synthetic steps for chiral alkenes, the Du group developed a novel type of chiral olefins 17, which were easily obtained by the reaction of chiral binaphthols 16 with 3-chloro-2-(chloromethyl)prop-1-ene in one step (Scheme 2.7). Chiral boron Lewis acids 18 generated in situ from these chiral alkenes were found to be effective for the asymmetric hydrogenation of imines, giving the corresponding optically active amines in 84–99% yields with 45–89% ee’s (Table 2.5) [33]. Very recently, Wang and coworkers developed a novel type of chiral C 2 -symmetric bisborane catalysts derived from chiral bicyclic[3.3.0] dienes 19 with HB(C6 F5 )2 or HB(p-C6 F4 H)2 [34]. Interestingly, tuning the reaction temperature could afford two diastereomeric catalysts from the same diene precursor (Scheme 2.8). At 25 °C, a kinetically controlled process predominated, and a thermodynamically controlled hydroboration occurred at 80 °C. These bisboranes exhibited both excellent catalytic activity (up to 200 TONs at −40 °C) and high enantioselectivity (up to 95% ee) for the hydrogenation of imines (Scheme 2.9 and Table 2.6). A variety of NHC–boranes and triazolium-based carbene–boranes were synthesized, the chirality is located either on the carbene or alternatively on the borane(Fig. 2.2) [35]. Some of these species were effective precursors for the asymmetric hydrogenation of imine, but only giving very low enantioselectivities (1–20% ee) (Table 2.7). In 2019, the Fuchter group developed a chiral N-heterocyclic carbene (NHC)stabilized borenium ions for the asymmetric reduction of N-alkyl ketimines [36]. The borenium catalysts could be prepared from hydride 25 by the treatment with HNTf2 to give 26 in 73% yield on Gram scale (Scheme 2.10). For the asymmetric hydrogenation of N-alkyl ketimines, moderate to good enantioselectivities were achieved (Table 2.8). Vicinal diamines widely exist in natural products and biologically active compounds, and are also very important building blocks in synthetic chemistry. Catalytic hydrogenation of vicinal diimines provides a straightforward way for the synthesis, the vicinal diamines. Du and coworkers reported the first metal-free hydrogenation of 1,2-diaryl-1,2-diimines using B(C6 F5 )3 as catalyst, a variety of cis-1,2-diaryl-1,2-diamines were afforded in 92–99% yields as single isomers [37] (Table 2.9). For the asymmetric reaction, only 10% ee was obtained with the diene 29-derived chiral borane catalyst (Scheme 2.11).

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X. Feng et al.

Table 2.3 Catalytic asymmetric hydrogenation of imines and enamines (S)-13 (2.5-10 mol %) H2 (2 bar)

imine or enamine

Entry 1

methyl tert-butyl ether or toluene

product HN

2

HN

ee (%)

80

83

92

75

79

34

72

32

34

36

95

99

81

95

42

85

Me Me 5j

Ph

yield (%)

Bn Me 5i

Ph

amine

HN

3

Bn Me

5k 4

HN

Me Me 5l

Bn

OMe

5

HN

5m

Me

Ph

N

6

5n 7

N Ph

8

Me 5o

N Me

5p

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

37

Table 2.4 Catalytic asymmetric hydrogenation of imines Ph

N

(pS,R)-15 (20 mol %) H2 (60 bar), rt

Me

Ar

5

product HN

1

Ph

yield (%)

ee (%)

46

52

61

69

40

58

41

42

55

52

Ph Me 5a

HN

Ph

2

Me

5q

MeO

HN

3

Ph Me

5r

Cl

HN

4

Ph Me

Ar

3

Entry

HN

Ph

MeO

Me

5d HN

5

Ph Me

5s Ph

Ph 1. HB(C6F5)2 10

PMes2 Fe (pS)-14

Ph

BH(C6F5)2 + PHMes2

2. H2 (1.5 bar)

Fe

Fe (pS, R)-15

(pS, S)-15 91% yield ca. 4:1

Scheme 2.6 Synthesis of C4-bridged FLP 15

BH(C6F5)2 PHMes2

38

X. Feng et al. Ar OH Cl OH

Ar 16 chiral diols readily available

Ar

Ar HB(C6F5)2

O O

Cl one step

in situ

Ar 17 chiral alkenes easily accessible 18a: Ar = 4-FC6H4 18b: Ar = 4-t BuC6H4 18c: Ar = 2-OMeC6H4 18d: Ar = 2-i PrOC6H4 18e: Ar = 2-OBnC6H4 18f: Ar = 3-OMeC6H4 t 18g: Ar = 3,5- Bu2C6H3

O O

B(C6F5)2

Ar 18 chiral boron Lewis acids

18h: Ar = 3,5-(CF3)2C6H3 18i: Ar = 3,5-(3,5-tBu2C6H3)2C6H3 18j: Ar = 2-OMe-5-tBuC6H3 18k: Ar = 2,4,6-Me3C6H2 18l: Ar = 2,4,6-Cy3C6H2 18m: Ar = 2-Np 18n: Ar = 9-Anthracene

Scheme 2.7 Synthesis of chiral alkenes 17

Cyclic imines 3-substituted 2H-1,4-benzoxazines 30 were also effective substrates for the FLP catalysis. Using B(C6 F5 )3 (2.5 mol %) as catalyst, a variety of 3,4dihydro-2H-1,4-benzoxazines 31 were successfully furnished in 93–99% yields (Table 2.10). With diene 9i-derived chiral borane, up to 42% ee was achieved for the asymmetric hydrogenation [38] (Table 2.11).

2.2.2 Asymmetric Hydrogenations of N-Heterocyclic Compounds Piperdines are important building blocks in synthetic and medicinal chemistry and exist widely in natural products and biologically active compounds. So far, the direct hydrogenation of simple pyridines for accessing piperidines remains a challenge due to the deactivation of catalysts and the dearomatization. Stephan and coworkers reported a stoichiometric hydrogenation of pyridines [39]. Recently, Du and coworkers applied borane catalysts generated in situ from commercially available alkenes with HB(C6 F5 )2 for the catalytic hydrogenation of pyridines. A variety of piperidines were obtained in high yields with excellent cis stereoselectivities [40]. For 2,6-diarylpyridines, the corresponding piperidines were afforded in 93–99% yields with 90/10 to >99/1 dr. 2-Aryl-6-methylpyridines were also efficient substrates to give the piperdine products in 80–99% yields with excellent cis selectivity (Table 2.12). 2,2’-Bipyridines were also suitable substrates. For 6,6’-dimethyl-2,2’-bipyridine, only one pyridine cycle was selectively hydrogenated to give the product in 59% yield. While for 6,6’-ditolyl-2,2’-bipyridine, two pyridine cycles were both reduced to afford the product in 75% yield with >99/1 dr. Several chiral dienes were evaluated for this asymmetric hydrogenation. Unfortunately, moderate conversion with < 10%

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

39

Table 2.5 Asymmetric hydrogenation of imines N

Ar' H2 (30 bar)

R

Ar

HN

18g (10 mol %)

Entry

5

product HN

1

Ph

Me 5a

Me

97

65

92

79

99

60

97

89

99

66

99

73

5t

Bu

HN

Ph

3

Me

5u

F

HN

Ph

Me

Me

5v

F

HN

5

ee (%)

Ph

2

4

yield (%)

Ph

HN

t

R

Ar

3

Ar'

Ph

Ph Et 5w

OMe HN

6

Me

5x

MeO

MeO HN

7

99

55

Me Ph

5y

ee were obtained. Alternatively, using L or D-tartaric acids a chiral resolution reagent, both enantioisomers of piperidine 33i could be easily accessed [40] (Scheme 2.12). 1,2,3,4-Tetrahydro-1,8-naphthyridine moieties usually exhibit good biological activities. Among numerous methodologies for the synthesis of 1,2,3,4tetrahydro-1,8-naphthyridines, the hydrogenation of 1,8-naphthyridines is undoubtedly a clean and straightforward approach. Du and coworkers utilized a

40

X. Feng et al. Ar

Ar

H HBAr F

BAr F2

Ar F2 B

Ar

H HBAr F

2

25 °C

2

H

BAr F2

Ar F2 B

80 °C

H Ar 20 kinetic predominantly one isomer

H

H Ar 21 thermodynamic predominantly one isomer

Ar

19

Scheme 2.8 Chiral boranes 20 and 21prepared by hydroboration with HB(C6 F5 )2

N Ph

Ph

bisborane 20 or 21 (2 mol %)

Me

H2 (50 bar), rt

HN Ph

Ar

H

(C6F5)2B

B(C6F5)2 H

Me 5a

3a Ar

Ph

Ar

20a: Ar = Ph, 100% (62% ee) 20b: Ar = 4-FC6H4, 63% (62% ee) 20c: Ar = 4-tBuC6H4, 100% (57% ee) 20d: Ar = 3,5-tBu2C6H3, 100% (81% ee)

H

(C6F5)2B

B(C6F5)2

H Ar 21a: Ar = 3,5-tBu2C6H3, 100% (78% ee) Ar (Hp-C6F4)2B

H B(p-C6F4H)2

H Ar 21b: Ar = 3,5-tBu2C6H3, 100% (84% ee) -40 °C, 17 h, 100% (94% ee)

Scheme 2.9 Investigation of chiral bisborane catalysts for imine hydrogenation

pentafluorostyrene-derived borane catalyst for the hydrogenation of 2,7-disubstituted 1,8-naphthyridines, giving the corresponding products in 83–98% yields. With the diene 9k-derived chiral borane, a variety of 1,2,3,4-tetrahydro-1,8-naphthyridine derivatives were furnished in 90–96% yields with up to 74% ee [41] (Table 2.13). The asymmetric hydrogenation of 2-substituted quinoxalines under transitionmetal catalysis is now a developed area. However, the highly stereoselective hydrogenations of 2,3-disubstituted quinoxalines, especially the asymmetric reactions, were still not well solved. Stephan and coworkers reported the hydrogenation of 2,3-quioxalines with one equivalent of B(C6 F5 )3 [39]. In 2014, Du group applied catalytic amount of B(C6 F5 )3 or B(p-HC6 F4 )3 for the hydrogenation of 2,3disubstituted quinoxalines to afford a wide range of cis-2,3-disubstituted 1,2,3,4tetrahydroquinoxalines in 80–99% yields with 92/8 –> 99/1 dr’s [42]. With the chiral borane catalysts derived from chiral dienes with HB(C6 F5 )2 , the corresponding tetrahydroquinoxalines were furnished with excellent cis-selectivities in 67–96% yields and up to 96% ee (Table 2.14).

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

41

Table 2.6 Asymmetric hydrogenation of imines (S)-13 (2.5-10 mol %) H2 (2 bar)

imine or enamine

Entry 1

methyl tert-butyl ether or toluene

product NHPh Me

Ph

5a

amine

yield (%)

ee (%)

99

94

94

91

99

90

98

92

93

94

87

91

96

93

83

93

98

83

94

71

NHPh

2

Me

5z

MeOOC NHPh

3

MeO

Me

5d Me

NHPh

4

Me

5a’ 5 6

NHPh Ph

Et

5w

NHPh Ph

Bn

5b’ NHPh

7

Me

Me

5c’

Me NHPh

8

Me

5d’ NHPh

9

Me

5e’

S

NHPh

10

Me Br

N

5f’

42

X. Feng et al. O N

O R

H B

O

O

N

R

N

iPr

R N

N

HB

iPr

N

22c

N

BH

HB

24a

23a: R = R' = Me 23b: R = R' = iPr 23c: R = Me, R' = Bn

22b: R = t Bu

N N Ph

N N Ph

H 3B 22a: R = i Pr

OMe

OMe

N R'

24b 10 : 1

Fig. 2.2 Chiral carbene–borane adducts Table 2.7 Hydrogenations of imines by catalysts derived from ref. [22–24] N Ph

Ph

[Ph3C][B(C6F5)4] (5 mol %) chiral carbene borane (5 mol %)

Me

H2 (102 atm), CH2Cl2

HN

Me

Ph

3a

Ph

5a

Entry

precatalyst

t (h)

T (ºC)

yield (%)

ee (%)

1

22a

3

25

50

12

2

22b

24

25

0

-

3

22c

3

50

6

7

4

23a

24

−30

5

20

5

23b

24

−30

99% conv. 10% ee

Ph 29

Scheme 2.11 Asymmetric hydrogenation of diamine 27j

spiro[4.4]dienes with HB(C6 F5 )2 or HB(p-C6 F4 H)2 (Scheme 2.14) [46]. These catalysts were applied in the asymmetric hydrogenation of 2-substituted quinolines to furnish the desired products in 63–99% yields with 87–99% ee’s (Table 2.18). These catalysts exhibited excellent functional-group tolerance. For example, a Bpin moiety, internal and terminal double and triple bonds, coordinative MeS and heterocyclic substituents were compatible, which makes this method complementary to the existing methods for quinoline hydrogenation.

2.2.3 Asymmetric Hydrogenations of Silyl Enol Ethers The direct hydrogenation of ketones with FLP catalysts is a challenging problem. The transformation of ketones to the corresponding silyl enol ethers represents a detour to access secondary alcohols for the FLP catalysis. In 2008, Erker and coworkers reported the hydrogenation of silyl enol ethers with an FLP of bisphosphine and B(C6 F5 )3 [47]. In 2014, using a combination of t Bu3 P and chiral boranes generated by the in situ hydroboration of chiral dienes with HB(C6 F5 )2 , Du and coworkers reported a highly enantioselective hydrogenation of silyl enol ethers [48]. A wide range of optically active secondary alcohols 51 were afforded in 93–99% yields with 88 −> 99% ee’s (Table 2.19). The readily available chiral boranes from chiral dienes and the diverse combination with Lewis bases make them a prospective class of FLP catalysts for the metal-free asymmetric hydrogenation. To develop more effective and versatile chiral FLP catalysts, chiral alkenyl boranes generated by the in situ hydroboration of chiral diynes 52 with HB(C6 F5 )2 were tentatively designed and prepared by Du group in 2015 (Scheme 2.15 and 2.16) [49]. The C=C double bonds in boranes were conjugated to the binaphthyl moieties, which makes the structures more rigid and easier to adjust the Lewis acidity of borane by introducing electron-donating or withdrawing substituents on chiral diynes. With the combination of chiral alkenyl boranes and t Bu3 P, an asymmetric hydrogenation of silyl enol ethers was realized to furnish a wide range of optically active secondary alcohols in high yields with up to 99% ee (Table 2.20).

46

X. Feng et al.

Table 2.10 Hydrogenation of 1,4-benzoxazines 30 O

R'

N

R''

B(C6F5)3 (2.5-5 mol %) H2 (20 bar), toluene

R 30

Entry

product

O

R'

N H 31

R''

R

cat. loading (mol %)

yield (%)

2.5

93

2.5

99

2.5

98

2.5

93

2.5

99

2.5

99

2.5

99

2.5

99

5

99

5

98

O

1

N H

Ph

31a

O

2

N H

OMe 31b

O

3

N H

Ph 31c

O

4

F

N H

31d

O

5

N H

31e

O

6

S

N H

31f O

7

Cl

N H

Ph

31g

Ph

31h

O

8

9

10

Me

N H O

Ph

N H

Ph

O

Me

N H

Ph

31i

31j

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

47

Table 2.11 Asymmetric hydrogenation of 1,4-benzoxazines 30 O N

Ar

chiral diene 9i (2.5 mol %) HB(C 6F5)2 (5 mol %)

O

H2 (20 bar), CH2Cl2 rt, 12 h

N H 31

30

Entry

product

Ar

yield (%)

ee (%)

95

33

90

40

90

42

92

31

92

33

97

30

O

1

N H

Ph

31a

O

2

N H

OMe 31b

O

3

N H

Ph 31c

O

4

N H

F

31d

O

5

N H

OMe

31k

O

6

N H

Cl

31l

2.2.4 Asymmetric Hydrogenations of Ketones and Enones Generally, the asymmetric induction for the FLP catalysis comes from the chiral Lewis acid component. As a two-component catalyst, chiral Lewis base is also likely to control the asymmetric process. However, very limited intermolecular FLPs with chiral Lewis bases have been developed. Chiral Lewis bases have been widely utilized as ligands or catalysts in the asymmetric catalysis. To combine chiral Lewis bases with achiral Lewis acids as FLP catalysts, would provide a novel and convenient direction toward the FLP construction. The asymmetric hydrogenation of ketones and electron-deficient unsaturated compounds have seldom been reported [50, 51]. Very recently, a novel type of chiral FLPs was developed by a combination of chiral oxazoline Lewis bases with

48

X. Feng et al.

Table 2.12 Hydrogenation of pyridines 32

entry 1

substrate

Ph 32a

N

Ph

product

2

Ph

O

N

32b

O

3

OMe 32c

5

Me

Me

Ph 32d

N

N

6

Me

N H MeO

N

8

Me

Br

9

Me 32g

N

Me 32h

N

N

N

Me 32i

Me

10

N

p-Tol

11

Me

N

N

p-Tol 32j

C11H23 32k

N

Me O

N O

Me Ph

NH

Me

90/10

92

99/1

96

95/5

99

97/3

96

94/6

51

--

68

--

59

96/4

75

>99/1

60

93/7

33e

OMe 33f

Me Ph

33g

33h N

Me 33i

NH HN

N H

93

33d

Me

p-Tol

98/2

OMe 33c

N H

OMe 32f

7

Ph

N H

98

33b N H

32e

MeO

O

F

Me

dr (%)

33a

N H

O

N F

4

Ph

N H

yield (%)

C11H23

p-Tol 33j

33k

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

NH Me

L-tartaric acid

N

49

liquid

crystal Ι

+

Me

33i

D-tartaric acid

NaOH

crystal ΙΙ

N

NH

N

NH

Me (R,R)-33i 74% (>99% ee)

Me

Me

Me

NaOH

(S,S)-33i 73% (>99% ee)

Scheme 2.12 Resolution of racemic piperidine 33i Table 2.13 Enantioselective metal-free hydrogenation of 1,8-naphthyridines 34 chiral diene 9k (5 mol %) HB(C6F5)2 10 (10 mol %) R

R'

N

N

H2 (30 atm)

R

34

Entry 1

product

Ph

N

Me

N H

N H

N

3

Me

N H

Me

N H

N

Ph

N

N H

Me

N

N H

93

47

96

52

93

74

92

33

96

17

94

48

35c

MeO

S

ee (%)

35b

N

4

yield (%)

35a

F

6

R'

35

2

5

N H

N

Me

35d

i

Bu

35e

Me

35f

50

X. Feng et al.

Table 2.14 Asymmetric hydrogenation of 2,3-disubstituted quinoxalines 36 H N

R'

R R" N H 37 92:8->99:1 d.r

entry

N

H2 organoborane

Me

N H

Ph

H N

Et

N H

Ph

N 36

H N

Me

N H

Ph

1

3

MeO

Me

N H

Ph

H N

Me

N H

Ph

H N

7

Me

N H

Ph

Me

Me

N H

Ph

yield (%)

cis/trans

ee (%)

82

>99/1

89

71

>99/1

77

72

99/1

67

87

>99/1

92

85

>99/1

94

85

98/2

86

93

>99/1

77

89

>99/1

92

37d

37e

6 H N

R" N H 37 98:2->99:1 dr 67-96% ee

37c

H N

5

Br

R'

R

37b

4

Cl

R"

chiral diene 9j HB(C6F5)2

H N

37a

2 Me

H2

R

product H N

R'

37f

37g

Me

H N

Me

Me

N H

Ph

8 37h

achiral boron Lewis acids, which was found highly effective for the asymmetric hydrogenations of ketones, enones, and chromones [52]. The corresponding products were afforded in high yields with up to 95% ee. Both aryl-alkyl and dialkyl ketones were applied in the hydrogenations to furnish the corresponding alcohols in 43–97% yields with 50–87% ee’s (Table 2.21). Simple ketones bearing electrondonating substituents at the aryl group and heteroaryl-substituted ketones were not effective substrates in the reactions. For enones and 3-substituted chromones, the

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

51

Table 2.15 Asymmetric hydrogenation of 2,3,4-trisubstituted quinolines 38 R'

R'

chiral diene 9l HB(C6F5)2

R" R N

R" R

H2

R"'

R"' N H 39 76->99% yields 82-99% ee's

38

entry

product

yield (%)

ee (%)

90

90

>99

92

76

85

86

93

91

93

86

89

87

93

78

96

Ph Me

1 N H

Ph

39a

Ph Me

2

N H

Me 39b

Ph Me

3

Br

N H

39c

F

4

Me N H

Ph

39d

Ph Et

5 N H

Ph

39e

Ph n-C6H13

6 N H

Ph

39f

Ph

7

Cl

Me Ph

N H

39g

Ph Me

8 N H

S

39h

52

X. Feng et al.

Table 2.16 Enantioselective hydrogenations of disubstituted quinolines R'

R'

N

R

40

H2

R' N

N H 41

chiral diene 9j HB(C6F5)2

R' N H 43

R

42

entry

R

product

R

75-98% yields 86-98% ee's 95/5-99/1 dr's

74-99% yields 45-80% ee's 95/5->99/1 dr's

yield (%)

cis/trans

ee (%)

91

97/3

91

94

98/2

94

93

98/2

94

98

>99/1

97

80

98/2

87

88

99/1

90

Ph

1 N H

Ph

41a

Ph

2

N H

Ph 41b

Ph

3

OMe

N H

41c

Ph

4

Cl N H

41d

Ph

5 N H

O

41e

Ph

6

N H

S

41f (continued)

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

53

Table 2.16 (continued) Br

7 N H

Ph

Ph

99/1

94

93

98/2

86

94

98/2

98

91

>99/1

69

94

>99/1

69

99

>95/5

72

96

>99/1

56

91

>99/1

80

74

>99/1

80

41g

8 N H

86

41h

Ph

9

Me Ph

N H

41i

Me

10

N H

Ph

43a

Me

11

N H

Me 43b Me

12

Cl

N H

43c Me

13

S

N H

43d Et

14

N H

Ph

43e

n-hex

15

N H

Ph

43f

54

X. Feng et al.

Table 2.17 Hydrogenation of 2-quinolinecarboxylates 44 B(C6F5)3

R

R

H2

COOR'

N

entry

product

1

COOR'

N H 45

44

yield (%)

COOMe

N H

94 45a

Me

2

N H

3

4

F

N H

F

5

COOMe

N H

F

COOMe

N H

99 45c

COOMe

COOiPr

99 45b

92 45d 99

45e

chiral diene 9e HB(C6F5)2 N

COOMe

Cy3P, H2

44a

∗

N COOMe H 45a 82% conv. 14% ee

Scheme 2.13 Asymmetric hydrogenation of 2-quinolinecarboxylate 44a Ph HB(p-C6F4H)2 Ph 46

(Hp-C6F4)2B

Ph B(p-C6F4H)2 Ph 47

Scheme 2.14 Synthesis of bisborane 47 from chiral spiro[4.4]diene 46

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

55

Table 2.18 Asymmetric hydrogenation reactions of 2-substituted quinolines 48 spiro-bicyclic bisborane 47

R N

R

H2 (20 or 50 bar)

R'

N H

48

entry

product

1

2

3

N H

Me

N H

n

yield (%)

ee (%)

97

91

98

92

90

95

90

90

98

91

63

91

94

98

95

98

94

96

86

96

98

96

91

98

49a

Bu

N H

49b

49c

PinB

4

N H

Me

49d

O

5 N H

Me

49e

N H

Me

49f

O

6

7

8

9

10

11

12

R'

49

N H

N H

N H

Ph

49g O

49h N

49i

Ph

N H

N H

N H

Me

49j

Ph 49k

Ph

49l

56

X. Feng et al.

Table 2.19 Asymmetric hydrogenation of enol ethers 50 1. chiral diene 9h (5 mol %) HB(C6F5)2 10 (10 mol %) t Bu3P (10 mol %) H2 (40 bar)

OTMS R

R''

2. TBAF

OH R

R' 50

entry 1

R'' R' 51

product OH Me 51a

Ph

yield (%)

ee (%)

98

98

97

97

93

95

97

>99

97

>99

97

88

97

97

98

99

98

99

OH

2

Me

51b

Et OH

3

Me

51c

F

OH

4

MeO

Me

51d OMe OH

5

Me

51e OH

6

Me O

51f

OH

7

Me

51g

S OH

8

Me

51h OH

9 51i

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions Ar

57 Ar

HB(C6F5)2

B(C6F5)2 B(C6F5)2

in situ Ar

Ar 52

more rigid structure easier adjustment of Lewis acidity

Scheme 2.15 The design for developing chiral boranes by hydroboration of chiral diynes

CHO CHO

8

Ar

Ar

Ar

CBr2

CBr4/PPh3 0 °C 84-96%

CBr2

Ar

53

Ar

Ar 1. n-BuLi, THF, -40 °C 2. CH3I, -40 °C to rt

1. n-BuLi, THF, -78 °C 2. NH4Cl (aq.) 50-60%

Me Me Ar 52k: Ar = 3,5-tBu2C6H3 52l: Ar = 4-MeOC 6H4

52 52a: Ar = 3,5-tBu2C6H3 52b: Ar = 4-MeC6H4 52c: Ar = 4-CF3C6H4 52d: Ar = 4-FC6H4 52e: Ar = 4-tBuC6H4

Ar

52f: Ar = 4-MeOC 6H4 52g: Ar = 4-PhC6H4 52h: Ar = 2-MeO-5- tBuC6H3 52i: Ar = 2,5-(MeO) 2C6H3 52j: Ar = 3,5-(CF3)2C6H3

Scheme 2.16 Synthesis of chiral diynes 52

desired products were obtained in 91–99% yields with 33–95% ee’s (Tables 2.22 and 2.23). To have a better understanding on the mechanism, a theoretical investigation was conducted. The FLP of chiral oxazoline 55a and B(p-HC6 F4 )3 splits dihydrogen heterolytically to give a thermodynamically favorable INT, which then undergoes a concerted H-transfer process (TS). A 5.5 kcal/mol energy difference indicates a preference of the R-isomer, which is in compliance with the experiment results. The background reaction catalyzed by B(p-HC6 F4 )3 is responsible for the difference in enantioselectivity between theoretical result and experimental one (Fig. 2.3).

2.3 Asymmetric Hydrosilylation In 1996, Piers and coworkers reported a B(C6 F5 )3 -catalyzed hydrosilylation of carbonyl compounds [53], in which the borane activates the hydrosilane reagent instead of the carbonyl substrate. The first chiral FLP catalyzed asymmetric hydrosilylation was developed by Klankermayer and coworkers in 2012 with camphorderived catalysts; several amines were obtained with up to 87% ee [24]. It was notable that a racemic product was obtained using chiral borane without the addition of phosphine.

58

X. Feng et al.

Table 2.20 Catalytic asymmetric hydrogenation of silyl enol ethers 48 1. HB(C6F5)2 10 chiral diyne 52a t Bu3P, H2 2. TBAF

OTMS R1

R

3

R2 50

entry 1

OH R1

R3 R2 51

product OH Me 51a

Ph

yield (%)

ee (%)

90

95

80

98

95

96

82

97

92

98

90

99

92

98

97

92

99

93

OH

2

Me

51c

F

OH

3

Me

51g

S OH

4

Me

51h OH

5 51i Cl

OH

6

Me

51j OH

7

Br

Me

51k OH

8

Me

51l 9

OH S

Me

51m

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

59

Table 2.21 Asymmetric hydrogenations of ketones B(p-HC6F4)3 (10 mol %) oxazoline 55a (20 mol %)

O R

H2 (40 bar)

R'

R

54

entry 1

OH

O Ph

R' 51

product OH Ph

Me 51a

N Ph 55a

yield (%)

ee (%)

54

68

78

71

74

87

91

77

95

76

95

64

95

50

OH

2

Me

51c

F Cl

OH

3

Me

51j OH

4

Br

Me

51k OH

5

Et

51n

F 3C

6 7

Ph

Me

51o

OH Ph

Me OH

51p

A chiral borane catalyzed asymmetric hydrosilylation of imines was successfully achieved to give the desired optically active amines 5 in 70 −> 99% yields with 44–82% ee’s (Table 2.24) [54]. The chiral dienes bearing bulky substituents ensured the relatively higher enantioselectivity. The chiral NHC-stabilized borenium ion 26a was also effective for hydrosilylation of N-alkyl ketimines to furnish the corresponding amines in moderate to excellent yields with up to 86% ee (Table 2.25) [36]. Comparative reactivity and mechanistic studies suggested that the improvements in enantioselectivity are due to better substrate/catalyst matching and the bulky alkyl substituent on the nitrogen atom of the substrates. Optically active α-hydroxy carbonyl compounds exist widely in biologically active natural products and are usually utilized as useful chiral building blocks in synthetic chemistry. Among various well-established methods, the asymmetric

60

X. Feng et al.

Table 2.22 Asymmetric hydrogenations of enones 56 O

O

B(p-HC6F4)3 (10 mol %) oxazoline 55b (20 mol %)

R

R'

O R

H2 (40 bar)

R'

56

entry

product

yield (%)

ee (%)

94

77

94

80

94

78

91

71

94

86

97

85

96

68

94

69

95

87

99

86

99

92

O

1

Ph

57a O

2 CF3 57b

O

3 57c

F Br

O

4 57d O

5

Me

Ph

57e O

6

Br

Ph

57f O

7

Ph

57g

Br O Ph

8

57h

Br

O

9

Br COOMe 57i O

10

Br

Me

57j O

11

Et

Br

57k

N Ph

57

55b

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

61

Table 2.23 Asymmetric hydrogenations of chromones 58 O R' R

B(3,4,5-H 3C6F2)(p-HC6F4)2 (5 mol %) oxazoline 55b (5 mol %)

O R'

H2 (40 bar)

O

N

O

58

Ph

59

entry

product O

1

i

Br

Pr

O

i

Pr

Ph

ee (%)

95

95

95

92

93

92

95

89

92

87

93

51

93

33

96

44

98

80

59b

O

O

i

3

Pr

59c

O

Br

yield (%)

55b

59a

O

2

O

R

O i

Pr

4 O

59d

Br

O

5

i

Pr

59e

O O Et

6

59f

O O

Me

7

59g

O O Ph

8 O

59h

O

9 O

Me

59i

reduction of vicinal dicarbonyl compounds such as 1,2-diketones and α-keto esters is one of the most powerful and straightforward approaches. In 2016, the Du group developed a highly enantioselective hydrosilylation of 1,2-dicarbonyl compounds using the combination of tricyclohexylphosphine and chiral alkenyl boranes as FLP catalyst. A variety of optically active α-hydroxy ketones and esters were furnished

62

X. Feng et al. B(C6F4H)3

H

t

Bu

O

+ O

Ph

N

Ph

H F3C H2

Ph

O

t Bu N H O

Ph

H B(C6F4H)3

F3C

Ph Ph

TS

O

t Bu N H O H B(C6F4H)3

Ph

F3C

t

Ph

Ph Substrate

Ph

O

O

Bu

N H H B(C6F4H)3

N H H B(C6F4H)3 Bu

t

INT

Fig. 2.3 A plausible mechanism for asymmetric hydrogenation of ketones

in 52–98% yields with up to 99% ee (Table 2.26) [55]. It is noteworthy that chiral diynes exhibited an obvious advantage over chiral dienes in this hydrosilylation. In 2016, Oestreich and coworkers developed an enantioselective hydrosilylation of acetophenone derivatives using a binaphthyl-based boron catalyst bearing a C6 F5 group at the boron atom and PhSiH3 as the stoichiometric reductant (Scheme 2.17) [56]. The corresponding alcohols were obtained in 17–87% yields with up to 99% ee (Table 2.27). Additional Lewis base is not necessary for this catalytic system. The steric 3,3 -disubstituted binaphthyl backbone of the borane catalyst and the use of reactive trihydrosilanes as stoichiometric reductant were crucial to the success. The chiral FLP catalysts composed of tri-tert-butylphosphine and chiral binaphthyl-based diene-derived boranes were also highly effective for the enantioselective hydrosilylations of simple ketones [57]. A variety of optically active alcohols were prepared in 80–99% yields with up to 97% ee (Table 2.28). The hydrosilylation

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

63

Table 2.24 Catalytic asymmetric hydrosilylation of imines N R

entry

PMP1

HB(C6F5)2 (2 mol %) 9i (1 mol %) PhMe2SiH

R' 3

product PMP 1

HN

1

5m

Me

Ph

HN

2

R

PMP1 R 5

yield (%)

ee (%)

>99

67

99

65

96

68

96

82

>99

50

86

44

70

60

PMP1 Me

5x

MeO

HN

3

HN

Br

PMP 1 Me

5j’ HN

4

MeO

PMP1 Me

MeO

5k’

OMe

5

PMP 1

HN Ph

5l’

Et

PMP1

HN

6

Me

5m’ 7

HN

PMP1 Me

5n’

was carried under mild conditions and exhibited good substrate tolerance. The chiral skeletons may influence the reactivity and enantioselectivity to a large extent. C 2 -Symmetric 1,1’-spirobiindane chiral dienes have been successfully developed by the Du group [58]. With chiral dicarboxylic acid 65 as starting material, ester

64

X. Feng et al.

Table 2.25 Hydrosilylation of imines R

N Ar

1

PhMe2SiH (1.1 equiv) then CH3OH workup

R'

3

entry

HN

26a (4 mol %)

product

HN Ph

R

Ar 5

R'

yield (%)

ee (%)

91

80

47

80

71

80

75

86

~100

64

79

58

62

28

5h’

Me

Me

2

HN Ph

3

Me

5o’

Me

HN Ph

5g’

Me

HN

4

Me

5p’ 5

6

HN Ph HN Ph

7

Ph Me

5i

Bu Me 5q’

HN Ph

Et

5i’

68 was obtained through a Pd-catalyzed directed ortho-C−H iodination and methylation. Various aryl substituents can be easily introduced through Suzuki coupling reactions. Followed by DIBAL-H reduction, PCC oxidation, and Wittig-reaction, chiral dienes 64a − e were afforded in 81–85% yields (Scheme 2.18). The Du group applied these chiral boranes derived from chiral spiro dienes in the asymmetric Pierstype hydrosilylation of simple ketones, giving the desired secondary alcohols in high yields with up to 90% ee (Table 2.29).

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

65

Table 2.26 Asymmetric hydrosilylation of 1,2-diketones 60 1. chiral diyne 52a (5 mol %) HB(C6F5)2 10 (10 mol %) Cy3P (10 mol %) PhMe2SiH (3.0 equiv)

O R

Ar

2. Py HF

O 60

entry

product

1

Ph

HO

HO

H

H

Ar

R

O 61

Ph

yield (%)

ee (%)

91

>99

89

99

98

99

96

96

96

98

82

96

90

98

82

>99

87

97

61a

O

F HO H

2 F

O

61b OMe

HO

H

3 O

61c

OMe

t

HO

4 t

O

Bu HO H

5

Bu

H

Ph

OEt

61e

O

HO

H

OEt

6 O Me

61f

HO H

7

61d

OEt

O

61g

Cl

HO

H

8

OEt

O

Me HO H

9 S

O

OEt

61i

61h

66

X. Feng et al. Ph

Sn

Ph

Ph TMS TMS

(C 6F5)BCl 2

B C 6F 5

94%

Ph 62

DMS 53%

B Ph

Ph 63

(S)-63⋅DMS

Scheme 2.17 Preparation of catalyst (S)-63·DMS Table 2.27 Enantioselective carbonyl hydrosilylation (S)-63 DMS (2.4 mol %) PhSiH3 (3.0 equiv)

O Ar

neat, rt

R

OH R

Ar

54

51

entry

product OH

1

Me 51a

Ph

yield (%)

ee (%)

62

93

78

99

57

82

67

85

45

73

40

74

24

62

77

80

OH

2

Br

Me

51k OH

3

Me

51q

F 3C OH

4

Me

51r

Me

Br

OH

5

Me

51s 6

OH Ph

Bn 51t

OH

7

Ph

51u OH

8

Me

51v

Me S Me C 6F 5

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

67

Table 2.28 Asymmetric Piers-type hydrosilylation of ketones 1. HB(C 6F5)2 10 (5 mol %) chiral diene 9h (2.5 mol %) OH t Bu3P (5 mol %) Ph2SiH2 (1.2 equiv) Ar R 51 2. TBAF, THF

O Ar

R 54

entry 1

product OH Me 51a

Ph

yield (%)

ee (%)

88

93

98

97

95

96

87

94

97

88

96

81

99

86

97

97

93

87

OH

2

Me

51c

F

OH

3

MeO

Me

51d Cl

OH

4

Me

51j OH

5

Me

51l OH

6 7 8

S

Me

OH Ph

Bn 51t OH

Ph

Et 51w

51m

OH

9 51x

Chromanones and flavanones are important moieties contained in a variety of biologically and medicinally active compounds. With 0.1 mol % of borane catalyst derived from pentafluorostyrene and HB(C6 F5 )2 , a Piers-type hydrosilylation of chromones and flavones was realized to afford various chromanones and flavanones in 60–99% yields [59]. The asymmetric hydrosilylation was performed using chiral

68

X. Feng et al. I COOH COOH

Pd(OAc)2, I2 PhI(OAc)2, NaOAc

COOH COOH

DMF, 100°C, 36 h 42%

SOCl2, MeOH reflux, 12 h 83%

I 65

66 1. DIBAL-H toluene, -78 °C-rt,12 h COOMe COOMe 2. PCC, Celite DCM, rt, 4 h 65-72% Ar 68

I COOMe COOMe

Ar

ArB(OH)2, Pd(OAc)2 PPh3, K2CO3 DMF, 90 °C, 12 h 68-82%

I 67 Ar CHO CHO

Ar

Ph3PMeI t

BuOK

THF, 0 °C-rt 81-85%

Ar 69

64

Ar

64a: Ar = Ph 64b: Ar = 3,5-tBu2C6H3 64c: Ar = 3,5-(CF3)2C6H3 64d: Ar = 4-iPrOC6H4 64e: Ar = 2-naphthyl

Scheme 2.18 Synthesis of the chiral spiro dienes 64

diyne and HB(C6 F5 )2 , giving chromanones and flavanones in 91–99% yields with 11–32% ee’s (Table 2.30). Recently, Xu and coworkers reported a one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and α-ketoesters to construct 1,2,3,4tetrahydroquinoxalines (Scheme 2.19).With B(C6 F5 )3 as catalyst and polymethyl hydrosiloxane (PMHS) as silane reagent, a variety of 1,2,3,4-tetrahydroquinoxalines were obtained in good to excellent yields with good functional group tolerance even to reduction-sensitive moieties [60] (Table 2.31). The choice of hydrosilanes is crucial for a high catalytic activity and selectivity, and PMHS has proven to be optimal. Meanwhile, 3-substituted-3,4-dihydroquinoxalin-2(1H)-ones could also be efficiently and conveniently prepared by reducing the amount of PMHS. The asymmetric reaction was performed with chiral binaphthyl-diene-derived bisborane catalysts to afford the desired products in 83 − 91% yields with up to 87% ee (Table 2.32).

2.4 Asymmetric Transfer Hydrogenation Zwitterion species composed of proton and hydride were involved in the classical FLP catalysis. Inspired by these species, a novel type of FLP containing acidic and hydridic hydrogen atoms was developed by the Du group [61]. This FLP could provide Hδ− and Hδ+ which are originally incorporated in Lewis acid and Lewis

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

69

Table 2.29 Asymmetric hydrosilylation of ketones 1. HB(C6F5)2 10 (10 mol %) chiral diene 64b (5 mol %) t Bu3P (10 mol %) Ph2SiH2 (1.5 equiv) 2. TBAF, THF

O Ar

Me 54

entry product 1

Me

Ar

Me 51

yield (%) ee (%)

OH Ph

OH

51a

67

80

87

90

91

75

95

86

86

84

OH

2

Me

51c

F

OH

3

Me

51r

Me

OH

4

Me

51y

Ph OH

5

O

Me

51z

base, and the active species could be regenerated from the bonding Lewis acid and base with suitable hydrogen sources (Fig. 2.4). It is notable that the use of a chiral Lewis base would allow the control of asymmetric induction. Ammonia borane is an ideal hydrogen source for transfer hydrogenation with several advantages, such as low molecular weight, high hydrogen storage capacity, good stability, and easy handling. However, only a few successful examples have been reported for the asymmetric reduction with ammonia borane. Chiral tert-butane sulfinamide as an important and inexpensive reagent has been widely applied as chiral auxiliaries or coordinating moieties in chiral ligands. The adjacent N, O, and S Lewis base centers, appropriate steric hindrance, and weak N−H acidity, make it suitable as the Lewis base in the FLP. A stoichiometric asymmetric transfer hydrogenation of imines was successfully performed using a combination of Piers’ borane (1.1 equiv) and (R)-tert-butyl sulfinamide (1.1 equiv) with ammonia borane as the hydrogen source. A variety of amines were obtained in 78–96% yields with 73–96% ee’s (Table 2.33) [61]. The protecting groups on the nitrogen atoms were investigated, and 4-CNC6 H4 protecting group gave the best 96% ee. The catalytic transformation was also carried out to afford the desired products in 78–99% yields with 84–95% ee’s

70

X. Feng et al.

Table 2.30 Asymmetric hydrosilylation of chromones and flavones 70 O

O 70

entry

HB(C6F5)2 10 pentafluorostyrene or chiral diyne 52a

O

PhMe2SiH

O

R

R

71

product

yield (%)

ee (%)

98

21

91

17

95

32

99

11

O

1 O

Me 71a

O

2 O

Et 71b

O

3 O

t

Bu 71c

O

4 O

O

NH2 R

+ NH2

OR'

Ar

Ph 71d

H N

PMHS, B(C6F5)3

R

one-pot tandem process OR'

72

73

74

O

hydrosilylation

R N

R'

deoxygentive hydrosilylation

cyclization

H N

N H

R'

Scheme 2.19 Catalytic synthesis of 1,2,3,4-tetrahydroquinoxalines

H N

O

N H

R'

R

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

71

Table 2.31 Synthesis of tetrahydroquinoxalines 74 and 3,4-dihydroquinoxalin-2(1H)-ones 75 entry

product

yield (%)

H N

90

1 N H

Me

74a

H N

2 N H

t

84 Bu

74b

H N

3 N H

n

87 C6H13

74c

H N

4

88 N H

Ph

74d

H N

5

84 Ph

N H

Me N

6

N H

7

78 Me

74f

78

N N H

Me

H N

O

N H

Me

H N

O

N H

Ph

74g

8

93 75a

9

86 75b

H N

O

N H

Me 75c

NC

H N

O

NC

N H

Me

O

O

N H

Me

10

85

11

12

74e

82 75d 88 75e

72

X. Feng et al.

Table 2.32 Asymmetric synthesis of 1,2,3,4-tetrahydroquinoxalines and 3,4-dihydroquinoxalin2(1H)-ones O

NH2 + NH2

OEt

R

Ph2SiH 2 (1.5 or 4.0 equiv)

O

72

73

entry

H N

HB(C 6F5)2 10 chiral diene 9f

product

O

N R H 74 or 75

yield (%)

ee (%)

87

47

83

76

88

58

89

58

85

87

90

70

H N

1 N H

Me

74a

H N

2 Ph

74d

N H

Bn

74h

H N

O

N H

Me

H N

O

N H

Ph

H N

O

N H

Bn

N H

H N

3

4 75a

5 75b

6

product

LA

75c

LB

LA

LB

product

LA

δ H

substrate

LB

δ H

hydrogen source substrate

H

LA

H

LB

Classic FLPs

Fig. 2.4 Novel FLPs designed for asymmetric catalysis

novel FLP

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

73

Table 2.33 Stoichiometric asymmetric transfer hydrogenation of imines

N

Ar'

H 2N

t

76 (1.1 equiv.) Bu

HB(C6F5)2 10 (1.1 equiv.)

Me

Ar

O S

HN

Entry

Me

Ar

3

Ar'

5

product HN

1

Ph

ee (%)

91

90

93

91

96

92

92

93

78

96

Ph Me 5a

HN

Ph

2

Me t

yield (%)

5t

Bu NHPh

3

Cl

Me

5r’ 4

HN Ph

PMP Me

5m CN

5

HN Ph

Me

5s’

(Table 2.34). Pyridine was used as an additive to prevent the Piers’ borane-catalyzed racemic reaction of imines with ammonia borane. Based on the experimental and theoretical mechanistic studies, a plausible catalytic cycle for this transfer hydrogenation was proposed. Piers’ borane and sulfinamide form an FLP, which binds with imines. The hydrogen transfer occurs via an 8-membered ring transition state to generate amine products. The FLP catalyst can be regenerated with ammonia borane to complete a catalytic cycle (Fig. 2.5). The above catalytic system was also effective for the transfer hydrogenation of 2,3-disubstituted quinoxalines with ammonia borane. High yields and cis selectivities with 77–86% ee’s were afforded for 2-alkyl-3-arylquinoxalines (Table 2.35, entries 1–3). For 2,3-dialkylquinoxalines, trans-tetrahydroquinoxalines

74

X. Feng et al.

Table 2.34 Catalytic asymmetric transfer hydrogenation of imines HB(C6F5)2 10 (10 mol %) O S t 76 (10 mol %) H 2N Bu pyridine (10 mol %) NH3·BH 3 73 (1.0 equiv.)

CN N Ar

Me 3

Entry

product

CN HN Ar

Me 5

yield (%)

ee (%)

99

89

96

95

92

92

90

90

98

94

99

86

CN

1

HN Ph

5s’

Me

CN HN

2

Me

5t’

EtO CN HN

3

Me

5u’ CN

4

HN O

Me

5v’

O CN

5

HN Br

Me

5w’ CN HN

6

Me O Me

5x’

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions O S

NH 2

75

+ HB(C 6F5)2

NH 2 H S B C 6F5 O C 6F 5 NAr'

NH 3·BH 3 Ar O S

N

B(C 6F5)2

NHAr' Ar

Me

Me

t

Bu

H N H S O

C 6F5

B H C 6F 5

N C

Ar' Me

Ar

Fig. 2.5 Plausible catalytic pathway

were obtained predominantly in 58–93% yields with 28/72–75/25 dr (trans:cis) and up to 99% ee (Table 2.35, entries 4–8) [62]. Optically active β-amino acids and their derivatives are very useful building blocks in synthetic and medicinal chemistry. The FLP of Piers’ borane and (R)tert-butylsulfinamide was also effective for the asymmetric transfer hydrogenation of β-N-substituted enamino esters. The desired products were afforded in moderate to good yields with up to 91% ee (Table 2.36) [63]. Enantio-pure β-lactam could be easily constructed via a single-step Grignard reaction. Hantzsch esters are one of the most widely utilized hydrogen transfer reagents for transfer hydrogenation. A highly efficient transfer hydrogenation of imines with Hantzsch esters as hydrogen source was successfully realized in a FLP manner. Only with 0.1 mol % of B(C6 F5 )3 as catalyst, the desired products could be afforded in 80–99% yields. Moreover, using chiral boranes derived from chiral dienes and Piers’ borane HB(C6 F5 )2 , the asymmetric reaction was realized to give the amine products with up to 38% ee (Table 2.37) [64]. The reaction may involve an activation of Hantzsch esters by borane catalysts instead of substrate-activation.

2.5 Miscellaneous A frustrated Lewis acid/Brønsted base complex catalyzed α-amination of unactivated carbonyl compounds was developed by Wasa and coworkers [65]. B(C6 F5 )3 ,

76

X. Feng et al.

Table 2.35 Asymmetric transfer hydrogenation of 2,3-disubstituted-quinoxalines 72

N

HB(C6F5)2 10 O S t 76 H 2N Bu

R'

R N

NH3·BH 3 77

R"

H N N H 37

36

entry

product H N

Me

N H

Ph

H N

Et

N H

Ph

H N

Me

1

cis/trans

ee (%) (trans)

ee (%) (cis)

78

94/6

--

78

72

94/6

--

84

95

96/4

--

77

84

28/72

99

--

72

42/58

98

39

76

35/65

97

35

72

50/50

99

--

78

72/28

93

--

37i

H N

Me

N H

Me

H N

Me

4

N H

yield (%)

37b

S

N H

5

R"

37a

2

3

R'

R

n

Pr

H N

Me

N H

Bn

H N

Et

N H

Et

37j

37k

6 37l

7 37m

H N

8 N H

37n

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

77

Table 2.36 Asymmetric transfer hydrogenations of β-enamino esters 78 Ar'

HB(C6F5)2 10 O S t 76 H 2N Bu

NH COOR

Ar

NH3·BH 3 77

Ar'

78

entry

Ph

NH COOEt

Ph

COOR 79

product

1

NH

Ar

79a

yield (%)

ee (%)

67

72

72

85

76

54

79

80

83

78

82

83

85

85

80

84

83

91

83

80

N

2 NH COOEt

Ph Bn

3

79b

NH

Ph

COOEt

79c

MeO

4

NH COOEt

Ph

79d

MeO

5

NH COOMe

Ph

79e

MeO

6

NH Ph

COOnBu

79f

MeO

7

NH Ph

COOiPr

79g

MeO

8

NH Ph

O

79h

O

MeO

9

NH Ph

COOtBu

79i

MeO NH

10 S

COOtBu

79j

78

X. Feng et al.

Table 2.37 Asymmetric transfer hydrogenations of imines N Ar

Ar'

HB(C6F5)2 10 (10 mol %) 9h (5 mol %)

Me

EtOOC

COOEt

HN 5

N H 80

Me

entry

product HN

1

Me

Ar

3

Ar'

yield (%)

ee (%)

89

38

95

24

98

37

98

33

95

16

Ph Me 5a

Ph

Me

Ph

HN

2

Me

5q

MeO

HN

3

Ph Me

5u

F

HN

4

Ph Me

5c

F3C

Me

5

HN Ph

Me

5y’

in combination with several different bases, such as 1,2,2,6,6-pentamethyl piperidine and Barton’s base, the aminocarbonyl products were afforded in 35–98% yields (Table 2.38). Both acyclic and cyclic ketones, esters, amides, thioesters and thioamides could serve as suitable nucleophiles. With N-trifluoroacetyl-substituted (1R,2R)-(+)-1,2-diphenylethylenediamine derivative 84 as chiral base, the enantioselective variant of the reaction was also efficiently processed to furnish the desired products in 47–95% yields with up to 98% ee (Table 2.39). The catalytic reaction may function through the following process: the boron Lewis acid coordinated to carbonyl pro-nucleophiles to increase the acidity of the

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

79

Table 2.38 Catalytic amination of different pro-nucleophiles O O H

X

+

N N

MeO

B(C6F5)3

OMe

amine

R

X

R

O 82a

81

entry

83

product

yield (%) HN N

O

1

COOMe

97

COOMe

83a 2

3

HN N

O

COOMe COOMe

O HN N

Ph

89 83b

COOMe COOMe

Me

4

O HN N

Ph

98 83c

COOMe

70

COOMe

83d O

5

HN N

O

COOMe

88

COOMe

83e O

6

7

8

N

O

HN N

S

S Me N

O HN N

HN N

COOMe

65

COOMe

83f

COOMe COOMe

HN N

97 83g

COOMe COOMe

98 83h

COOMe COOMe

80

X. Feng et al.

Table 2.39 Direct enantioselective α-amination reactions O O H

X R 81

+

RO

B(C6F5)3

OR

N N

Ph Ph

O 82

N

Me

entry

N H Me 84

product HN N

O

1

X

O CF3

O HN N

COOR COOR

R 83

yield (%)

ee (%)

85

36

86

94

87

88

47

70

78

86

COOMe COOMe

83a O

2

HN N

COOMe COOMe

83i O

3

HN N

COOMe COOMe

83j

O

4

O HN N

COOMe COOMe

83k O

5

HN N H

COOEt COOEt

83l

α-C− H bond, the deprotonation was promoted by the hindered amine to form a tight ionic pair consisting of a boron enolate and an ammonium cation. The ammonium cation served as hydrogen bond donor to activate dialkyl azodicarboxylates to afford aminocarbonyl products. It was facile to independently modify the Lewis acid and Brønsted base for higher reaction efficiency and/or enantioselectivity (Fig. 2.6).

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

81

B(C6F5)3 +

X

O HN N ∗

Ph

COOR Ph COOR

R'

Me

N

N H Me

O

O CF3

R'

O

Ph

Ph

O Me2N H

N H

R'OOC N N (C6F5)3B O δ+ X

H

X

B(C6F5)3

R' CF3

O

Me Ph N

H

X

Me HN F3C

Ph

O

OR'

R O

O

Me Ph HN R' Me Ph HN

OR

F3C

X RO

N N

O

B(C6F5)3

O

Fig. 2.6 A proposed catalytic pathway

An enantioselective direct Mannich-type reaction catalyzed by a chiral frustrated Lewis acid/Brønsted base complex was developed by Wasa and coworkers in 2017 [66, 67]. A broad range of carbonyl compounds and aldimines were subjected in the transformations, and the corresponding β-aminocarbonyl compounds were furnished in high yields with up to 20/1 dr and up to 96% ee (Table 2.40). The combination of the chiral Lewis acid and achiral Brønsted base gives rise to in situ enolate generation, subsequently the enolates react with hydrogen bond-activated aldimines to furnish the β-aminocarbonyl compounds 86.

2.6 Summary FLP chemistry provides a promising approach for the metal-free asymmetric reduction of unsaturated compounds, and great progress has been made for enantioselective hydrogenation, hydrosilylation and transfer hydrogenation in the past decade. Moreover, the concept of FLPs has been successfully applied to other types of asymmetric reactions. Significantly, the FLP catalysts have exhibited some advantages over the transition metal catalysts in some cases. Despite these achievements, there

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Table 2.40 Mannich-type reaction with different pronucleophiles and electrophiles O R1

entry

N

H + R2 81

chiral diene 9 (10 mol %) HB(C6F5)2 10 (10 mol %) base (20 mol %)

PG

Ar

HN

catalyst 9c+PMP2

PG Ar

R1 86

85

product O

1

O R2

yield (%)

anti/syn

ee (%)

98

>20/1

92

99

>20/1

90

99

10/1

84

97

--

72

87

>20/1

84

96

>20/1

96

98

>20/1

74

99

>20/1

94

63

7/1

70

98

10/1

54

73

3/1

Boc

HN

F

Ph

86a O

2

Boc

HN

9c+PMP2

Ph

86b

O O

3

Boc

HN

9c+PMP2

Ph

86c 4

O

9c+PMP2

HN

86d

Ph

Ph

O HN

5

Boc

9a+PMP2

Boc Ph

86e O

6

HN

Boc

9c+PMP2 F 86f

O

7

HN

Boc

9c+PMP2

O

86g O

8

HN

9c+PMP2

Cbz Ph

86h 9

10

9c+Barton’s base

9h+Barton’s base

O HN S

Me O HN

O

Me

O

11

Boc Ph

86i

Boc Ph

HN

86j Ts

anti: 16

9a+PMP2 86k

syn: 66

2 Frustrated Lewis Pair Catalyzed Asymmetric Reactions

83

still remain some problems and challenges for this emerging area, such as the difficulty for the catalyst synthesis, the relatively narrow substrate scope, the efficiency, and the selectivity. To develop novel catalysts as well as novel strategies for the catalyst synthesis and expanding their application for asymmetric reduction of other unsaturated compounds are undoubtedly very important tasks to ensure the wide acceptance and application of FLPs in synthetic chemistry.

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Chapter 3

FLP Reduction of Carbon Monoxide and Related Reactions Tongdao Wang, Constantin G. Daniliuc, Gerald Kehr, and Gerhard Erker

Abstract Frustrated Lewis pairs (FLPs) show some small molecule binding features that are remotely reminiscent of metal/ligand coordination. This is illustrated by examples of synergic binding of carbon monoxide (CO) or nitric oxide (NO) to the Lewis acid/Lewis base pairs of some intramolecular FLP systems. Various pathways of carbon monoxide reduction at FLP frameworks leading to the formyl stage and beyond are described. CO reactions at extended FLP systems containing multiple Lewis acid/Lewis base combinations lead to unusually structured products. The formation of macrocyclic oligomers upon treatment of some P/B/B FLPs with carbon monoxide are typical examples. Some carbon monoxide reactions of specifically substituted d0 -configurated Group 4 bent metallocene complexes show remarkable similarities to typical reactions of the metal-free main group element FLPs. Keywords Frustrated Lewis pairs · Carbon monoxide · CO reduction and coupling · Macrocyclic oligomers · d0 -metallocene cations

Abbreviations 9-BBN CP MAS Cp Cp* DFT Dmesp ESR

9-borabicyclo[3.3.1]nonane cross-polarization magic-angle spinning cyclopentadienyl 1,2,3,4,5-pentamethylcyclopentadienyl density functional theory 2,6-dimesitylphenyl electron spin resonance

T. Wang Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning 116024, China C. G. Daniliuc · G. Kehr · G. Erker (B) Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany e-mail: [email protected] © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_3

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88

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frustrated Lewis pair 2,4,6-tris(trifluoromethyl)phenyl mesityl 2,4,6-tri(tert-butyl)phenyl nuclear magnetic resonance phthalimide-N-oxyl 2,2,6,6-tetramethylpiperidinyloxyl 2,4,6-tri(iso-propyl)phenyl

3.1 Introduction Coordination of carbon monoxide to most transition metals can be described by a synergic bonding scheme: the CO molecule serves as a donor and forms a σ-bond with an empty metal acceptor d-orbital. This is then substantially strengthened by metal to ligand back bonding [1–4]. The dative interaction of a filled metal d-orbital with the CO π*-orbital (see Scheme 3.1) leads to the typical structural and chemical features of the M–C≡O moiety, namely weakening of the CO bond and making it amenable to nucleophilic attack, a feature that is, e.g., made use of in the classical Fischer carbene complex synthesis [5]. We note an increasing use of main group element-based systems for efficient small molecule activation. Frustrated Lewis pair (FLP) chemistry plays a significant role in this current development [6–19]. The interaction of a donor/acceptor pair with a small molecule Y≡X can in principle follow two alternative schemes: Addition of the Y≡X substrate only to the acceptor leads to a simple Lewis adduct. Alternatively, both the acceptor and the donor sites could interact with the Y≡X molecule. This type of an interaction would be remotely reminiscent of metal–CO bonding, only that the acceptor and donor orbitals of the template would be located at a pair of sites instead at a single atom. A number of main group element systems featuring linked donor/acceptor components had previously been described. Many of them bind to transition metal centers Scheme 3.1 Metal reminiscent FLP bonding scheme

Synergic metal ligand bonding Ln M C X M

M

C X

C X Ln M C X

back bonding

X: O or CR

Metal reminiscent FLP coordination behavior? D A

D Y X

A

X Y

D Y X A

3 FLP Reduction of Carbon Monoxide and Related Reactions Scheme 3.2 Donor/acceptor behavior of FLPs

R2 P

89 R2 P

MLn B R2 ambiphilic ligands

≠ H

B R2

R2 P C O

H

B R2

FLP small molecule activation

as ambiphilic ligands [20–22]. But there has been increasing evidence that some such systems might take up a metal reminiscent role themselves in the reaction with small molecules. This has been proposed for the activation of the dihydrogen molecule at main group element derived frustrated Lewis pairs (see Scheme 3.2) [23–25]. A similar bonding situation has been found to prevail in FLP reactions of nitric oxide (NO) and carbon monoxide (CO) [14]. Some such systems and their consequences on the reaction pathways taken by NO and CO molecules will be presented and discussed in this brief account.

3.2 Synergic FLP Binding to NO, CO, and Related Molecules We observed metal reminiscent synergic P/B FLP bonding upon exposure of compound 1 to alkyl isocyanides [26]. The unsaturated P/B FLP 1 had been prepared conveniently in a single step by 1,1-carboboration (“Wrackmeyer Reaction”) [27– 30] of p-tolyl(diphenylphosphino)acetylene with the strongly Lewis acidic B(C6 F5 )3 borane. Treatment with tert-butyl isocyanide gave the Lewis adduct 3, which was characterized by X-ray diffraction. When 3 was dissolved, the NMR spectra showed a complex behavior. Compound 3 equilibrated with the starting materials and with the P/B bonded FLP addition product 4 formed by cooperative FLP addition. At low temperature (193 K), compound 4 was by far the predominant species. The reaction of the FLP 1 with the less sterically encumbered n-butyl isocyanide reagent gave the five-membered ring product 2 directly at r.t. as a mixture of E- and Z-“imine” isomers. The major E-isomer was characterized by X-ray diffraction (see Scheme 3.3). This behavior is not limited to the use of the reactive isonitrile reagents: we observed the analogous dichotomy in the reaction of the norbornane-based P/B FLP 6 with carbon monoxide [31]. Exposure of 6 to CO in a softened argon matrix at 35 K gave rise to the formation of the borane carbonyl product 5 [˜v (CO) = 2196 cm−1 vs 2138 cm−1 for free CO under these conditions]. At r.t. in solution compound 6 cleanly formed the cooperative P/B FLP CO addition product 7 (characterized by X-ray diffraction). A number of similar heterocyclic CO addition products were subsequently found and described, e.g., compound 8 or the N/B FLP CO product 10 (see Scheme 3.4) [31–35]. 1,1-Carboboration of acetylenes has become an important tool for preparing reactive alkenyl boranes [27–30]. We recently described a rare example of the B–H

90

T. Wang et al. B(C6F5)3 + Ph2P 1,1-carboboration p-tol

C6 F 5 (C6F5)2B

PPh2

n

Bu

(C6F5)2B 2

1 C N

(C6F5)2B 3

t

N

PPh2

NnBu p-tol

C6F 5 (C6F5)2B

PPh2

C

C

Bu

p-tol

C6 F 5

p-tol

C6F 5 C N

4 t

Bu

C

PPh2

NtBu

Scheme 3.3 Cooperative alkyl isonitrile addition to the unsaturated vicinal P/B FLP 1

(C6F5)2 B CO Mes2P 5

B(C6F5)2

CO 35 K (argon matrix)

B(C6F5)2 O 8

B(C6F5)2

Mes2P

O

Mes2P 7

6 Dipp

Mes2P

CO r.t.

NH N Ar

H B(C6F5)2 9

Dipp CO 105 oC - H2

O N N Ar

B(C6F5)2 10

Scheme 3.4 Cooperative FLP addition reactions to carbon monoxide

analog of that reaction, namely the 1,1-hydroboration reaction of a suitably substituted alkyne [36]. The unsaturated P/B FLP 11 was obtained by the unusual reaction between the Mes2 P/Me3 Si-substituted alkyne with Piers’ borane [HB(C6 F5 )2 ] [37– 40]. Compound 11 was found to actively split dihydrogen and it reacted with carbon monoxide to form the product 12 (see Scheme 3.5). Metal nitrosyls are the NO relatives of the metal carbonyls [41, 42]. Not unexpectedly a variety of intramolecular P/B FLPs reacted cooperatively with nitric oxide (NO) to form the respective P/B NO addition products [43, 44]. These behaved as persistent nitroxide radicals, similar to the often used organic radical reagents TEMPO or PINO. Scheme 3.6 shows a few recent examples. Most of the P/B FLPs

3 FLP Reduction of Carbon Monoxide and Related Reactions

91

used for the NO reactions were prepared by convenient hydroboration routes [45– 47]. This is illustrated by the special example of HB(C6 F5 )2 hydroboration of the Me3 Si-substituted propargyl phosphane 16 and its reaction with nitrogen monoxide to yield the persistent FLP NO radical 18 [48]. Some FLP precursors were prepared in a slightly more complex way using alternatives to the hydroboration entry. The formation of the P/B FLP 21 is such an example. It was formed by the reaction of the bis-acetylene 19 with B(C6 F5 )3 . The sequence was initiated by a 1,1-carboboration reaction. Subsequent two-fold aryl migration was thought to take place to give 21, which then reacted with NO to yield the persistent FLP NO radical 22 (see Scheme 3.7) [49]. Many of the FLP NO radicals were characterized by X-ray diffraction and by ESR spectroscopy [43, 45, 46, 48–50]. They were shown to undergo typical nitroxide radical reactions. In contrast to these intramolecular P/B FLPs, some geminal P/Ge and P/Si pairs reacted with NO to give phosphane oxides [51]. Scheme 3.5 Reaction of the vicinal P/B FLP 11 with carbon monoxide

SiMe3 + HB(C6F5)2

Mes2P

1,1-hydroboration Me3Si

H

Mes2P

B(C6F5)2

CO

Me3Si

H

Mes2P

B(C6F5)2

11

Mes2P

N

BArF2

Mes2P

O 13 ArF: C6F5 (a), Fxyl (b)

O

B(C6F5)2

B(C6F5)2

N

Mes2P

O 14

Mes2P 16

N

O

15 Me3Si

Me3Si SiMe3

12

H

HB(C6F5)2 Mes2P

B(C6F5)2 17

H

NO Mes2P

N O

Scheme 3.6 Examples of persistent FLPNO radicals

B(C6F5)2 18

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T. Wang et al.

Scheme 3.7 A pathway to P/B FLP 21 and its reaction with NO

SiMe3

SiMe3 C6F 5

o

80 C

B(C6F5)2

B(C6F5)3 PMes2

19

SiMe3 C 6F 5 B

C 6F 5

20

SiMe3 C6F 5 C6F 5 B N O Mes P C6 F 5 Mes 22

NO r.t.

P Mes C 6F 5

Mes

PMes2

21

3.3 Metal-Free FLP Reduction and Coupling of Carbon Monoxide It has long been known that diborane does not reduce carbon monoxide unless catalyzed. It forms borane carbonyl 23 instead [52, 53]. The [BH4 – ] catalyzed reaction gives trimethylboroxine (see Scheme 3.8) [54]. A while ago we had shown that Piers’ borane [HB(C6 F5 )2 ] behaves similarly, with CO it forms “Piers’ borane carbonyl” 25 [55]. It was characterized by an X-ray crystal structure analysis. Aside from the above mentioned borane Lewis acids, some electron-deficient boron species (e.g. boroles [56], borocations [57], borylenes [58, 59], diborane(4) [60], azaborinine [61]) and other analogues (e.g. silylium ion [62–64] and bismuth cations [65]) have also shown to facilitate CO activation. P/B FLPs seem to show some special features toward understanding pathways in stoichiometric CO reduction chemistry. Piers’ borane reduces CO to the formyl stage in the presence of the FLP 6 [66]. The resulting [(η2 -formyl)B(C6 F5 )2 ] moiety is found attached at the FLP framework in the product 26. Several reactions of 26 were performed. It reacts with H2 via a frustrated Lewis pair pathway to eventually reduce the CO molecule to CH2 found bonded between boron and phosphorus in the product 28 (see Scheme 3.9) [55]. Treatment of 26 with excess pyridine results in removal of the FLP template (as its pyridine adduct) and liberation of the genuine

1

/ 2 B2 H 6

(C6F5)2BH

CO

CO

H3 B

C O 23

(C6F5)2B 25

cat. [BH4-]

/3 H3C

H C

1

O

Scheme 3.8 Formation of borane carbonyl examples

O B

CH3 B O B O CH3 24

3 FLP Reduction of Carbon Monoxide and Related Reactions

93 O

B(C6F5)2

CO

B(C6F5)2

(C6F5)2B

O Mes2P C B(C6F5)2

HB(C6F5)2

Mes2P

pyridine

6

N

H

26

27

H2

K2Cr2O7 O

H B(C6F5)2

B(C6F5)2

O H Mes2P C

Mes2P

C B(C6F5)2 28 H2

H

29

H

(C6F5)2B

OH

H O

2

N

B(C6F5)2

30

Scheme 3.9 Formation and reactions of the η2 -formylborane FLP 26

formylborane, isolated as its pyridine-stabilized adduct 27. Without the pyridine donor, this should not be stable but decompose to Piers’ borane and CO [55]. The stable pyridine adduct 27 was shown to undergo a variety of typical organic carbonyl reactions, e.g. imine formation or Wittig olefination reactions [32]. It could even be oxidized to the respective borane carboxylic acid (isolated as a typical dimer) by means of dichromate oxidation [19]. The reaction of the analogous (η2 -formyl)B(C6 F5 )2 compound 32, derived from the parent FLP Mes2 P–CH2 CH2 –B(C6 F5 )2 , with pyridine and its derivatives takes a somewhat different course (see Scheme 3.10). The reaction of 32 with, e.g., 4-methyl pyridine resulted in a hydroxymethylation reaction to give 31. Similarly, isoquinoline was hydroxymethylated selectively in the 1-position. The reaction of 32 with R

R

N

N (C6F5)2B

Mes2P H

O

B(C6F5)2 C O

N

N B(C6F5)2

B(C6F5)2 N

32

31 R: H, Me

O 33

N

N

(C6F5)2 B H

N (C6F5)2B

O H

(C6F5)2B

N N

Mes2P PMes2 35

C H O B(C6F5)2

34

Scheme 3.10 Reactions of the η2 -formylborane FLP 32 with pyridine derivatives

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T. Wang et al.

pyrimidine gave the compounds 34 and 35, respectively. Both were characterized by X-ray diffraction [67]. The new FmesBH2 reagents (employed as a donor-free dimer or as dimethyl sulfide-stabilized reagent FmesBH2 ·SMe2 ) reacted with Mes2 P–vinyl to give the FLP 36. This contains an active B–H functionality. Compound 36 reacts with carbon monoxide to form the internal η2 -formyl borane type product 38. We assume that activation of CO for reduction by the B–H functionality may occur by means of synergic P/B addition generating the intermediate 37 (see Scheme 3.11) [68]. The FLP formylborane species 32 reacts with sulfur dioxide by insertion into the three-membered ring substructure to form the product 39. The SO2 insertion can be made reversible. Treatment of 39 with Mes2 P–CH2 CH2 –B(C6 F5 )2 (40) traps sulfur dioxide with re-formation of 32 to finally give the product 41 (Scheme 3.12) [69]. The trimethylene-bridged N/B FLP 42 is apparently in a hidden equilibrium situation with the iminium/hydridoborate zwitterion that serves as a reactive intermediate in the reaction with the Piers’ borane/CO system. The reaction probably takes place by means of borohydride attack on Piers’ borane carbonyl to eventually give the template bonded borata-oxirane derivative 44. This is further reduced by reacting it with dihydrogen to give 45. Overall, the reactive sequence results in a cleavage of the C≡O carbon oxygen triple bond with reduction to a boron bonded methyl group (Scheme 3.13) [70]. The related zwitterionic iminium/hydridoborate compound 46 reacts with CO and B(C6 F5 )3 to give the coupling product of two carbon monoxide molecules 48 [71]. The reaction probably proceeds through a three-membered BCO heterocycle 47. Compound 46 couples two NO molecules with formation of the five-membered heterocyclic substructure in 49 [71] (Scheme 3.14). The product 49 is formed by head CF3 Mes2P

BH2 (FmesBH2)

+ CF3

CF3

Mes2P

B

Fmes CO H

Mes2P

36

37

C O

B

Fmes

B Fmes C H O

Mes2P

H

38

Scheme 3.11 Formation of P/BH FLP 36 and its reaction with carbon monoxide

Mes2P H

B(C6F5)2 C O B(C6F5)2 32

SO2

Mes2P Mes2P

B(C6F5)2

O C O S

H (C6F5)2B

O

40

- 32

39

Scheme 3.12 Reaction of the η2 -formylborane FLP 32 with SO2

B(C6F5)2 Mes2P

B(C6F5)2 S O O 41

3 FLP Reduction of Carbon Monoxide and Related Reactions

N

B(C6F5)2

N

B(C6F5)2

43

42

95

H

H2 N (C6F5)2B 25

B(C6F5)2

H C

O

44

B(C6F5)2

N

O H2C B(C6F5)2

45

O H H3C B(C6F5)2

(C6F5)2BH + CO

Scheme 3.13 Carbon monoxide reduction with the N/B FLP 42

Scheme 3.14 CO/CO coupling and NO/NO coupling by the masked FLP

CO

H

N

B(C6F5)2

B(C6F5)2

N

C O H 47

46 NO

CO

N

N

N

O

B(C6F5)3

N

B(C6F5)2

C

O

49

48

H

(C6F5)2 B O O

C

B(C6F5)3

to head coupling of two NO molecules and topologically related to diazeniumdiolate [72] or azodioxide formation [73]. We found that the η2 -formylborane system 32 reacted with nitric oxide (NO) to yield the diamagnetic CO/NO coupling product 51. We assume a reaction scheme (supported by DFT computational analysis) that involves the P/B FLP attached heterocyclic radical intermediate 50 (see Scheme 3.15) [74]. Hydrogen atom abstraction by NO is thought to directly lead to the observed and isolated product 51 with in situ

Mes2P

B(C6F5)2 NO C O H B(C F ) 6 5 2 32

Mes2P B(C6F5)2 H C N O O B(C6F5)2 50

B(C6F5)2 Mes2P C N O O HNO B(C6F5)2 51 NO

follow-up products

Scheme 3.15 Reaction of the η2 -formylborane FLP 32 with NO

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T. Wang et al.

Me2Si PhN Sc B Ar N 52

Cl

Li(THF)3

2 CO

N Ar Ar: 2,6-diisopropyl phenyl

Me2Si

PhN THF O C Sc THF C O

Ar

B

N

N Ar

CO

CO

Ar

Me2Si PhN

Sc

THF 53

C O

54

B

N

N Ar

Ar Me2Si PhN

:C

Sc

THF

O 53'

B

N

N Ar

Scheme 3.16 Reactions of the borylscandium complex 52 with CO

formation of nitroxyl (HNO) [75]. That is known to be prone to disproportionation to N2 O and H2 O. The two products lead to some observed side products of this reaction. Interestingly, Hou and coworkers found that the borylscandium complex 52 reacted with two CO molecules by selective head to head coupling to give a fivemembered NC2 OSc metallacycle 54 [76, 77]. A pathway for the formation of 54 is given in Scheme 3.16. Insertion of one molecule of CO into the Sc–B bond of 52 gives a complex, which is described by a resonance hybrid of η2 -CO(boryl) scandium 53 and boryl oxycarbene scandium 53’. Further reaction of this compound with CO yields the phenylamido- and boryl-substituted enediolate complex 54 through C–C bond formation between CO and the carbene unit in 53’ and cleavage and rearrangement of the Si–N bond in the silylene-linked Cp–amido ligand. Kinjo et al. had shown that the boryl lithium system 55 reacts with carbon monoxide. The reaction of 55 with CO generates the 1,2-diborylalkene species 58. Putatively, compound 58 is formed via formation the equilibrating 56/57 intermediates followed by dimerization. Compound 58 is sensitive to air and moisture, and its chemical trapping with Me3 SiCl yielded the stabilized product 59 (see Scheme 3.17) [78]. Stephan et al. found a remotely related behavior in the reaction of the phosphide anion (tBu2 P)K(18-crown-6) with carbon monoxide [79].

3.4 Reaction of P/B/B FLPs with Carbon Monoxide: Formation of Macrocyclic Oligomers The phosphane Mes*P(vinyl)2 60a reacts with HB(C6 F5 )2 by twofold hydroboration to give the P/B/B system 61a [80]. This contains a phosphane/borane contact and

3 FLP Reduction of Carbon Monoxide and Related Reactions Bu

Bu

Bu

55

t

t

t

Ar N

97

B

N CO N Ph

Ar N

Li

56

O

B

N N Ph

C

Ar N LiO

Li

B

N N Ph

C

57

Ar: 2,6-diisopropylphenyl t

t

Bu

Bu

Ar N B

N N Ph

Me3SiO C C Ph OSiMe3 B N N Ar N 59 t Bu

Ar N B

2 Me3SiCl - 2 LiCl

Ph

N N

LiO C C OLi B N Ar

N N Ph

58

t

Bu

Scheme 3.17 A pathway to the 1,2-diborylalkene 59

a pendent free borane Lewis acid. The internal exchange between the free and Pcoordinated borane is fast. It can readily be followed by temperature dependent dynamic NMR spectroscopy. The combination of the phosphorus nucleophile and the pair of strongly electrophilic boranes is such that it readily accommodates a molecule of carbon dioxide to form compound 62 (see Scheme 3.18) [80]. We had previously shown that treatment of R–B(C6 F5 )2 systems with 9-BBN can lead to selective replacement of one C6 F5 group at boron by hydride [81–83]. The stoichiometric coproduct F5 C6 –BBN can easily be removed. Consequently, the reaction between 61a and 9-BBN generated the –B(H)C6 F5 containing P/B/B system 64 [80]. However, this rapidly underwent a σ-bond metathesis reaction to give 63, which we isolated. This reaction was apparently reversible, so that treatment of 63 (or in situ generated 64) with carbon monoxide resulted in the formation of compound 65.

Mes*P

2 HB(C6F2)2

60a

Mes*P 61a

Mes*: 2,4,6-tri-tert.butylphenyl

+ 9-BBN

B(C6F5)2

Mes*

CO2 (C6F5)2B

B(C6F5)2

O

P C

O

B(C6F2)2 62

- F5C6-BBN Mes*

Mes*P

BC6F5

HB(C6F5)2 63

Mes*P 64

B

C 6F 5

CO

H

B(C6F5)2

Scheme 3.18 Formation and reactions of the P/B/B FLP 61a

P C

(C6F5)2B H

O

B

C6F5

65 (two isomers)

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T. Wang et al.

HB(C6 F5 )2 hydroboration of the aryl(divinyl)phosphanes 60b and 60c, which feature the bulky 2,6-dimesitylphenyl (Dmesp) or 2,4,6-tri(iso-propyl)phenyl (Tipp) ligands at phosphorus instead of Mes*, gave the P/B/B FLP systems 61b and 61c, respectively [84]. Each of these compounds reacted rapidly with carbon monoxide (1.5 bar) at room temperature. It is well known, that alkylboranes can insert CO into the B–C bond under somewhat forcing conditions. In our case, the active combination of a phosphane with a pair of strongly electrophilic alkyl–B(C6 F5 )2 boranes apparently accelerated this reaction type. We assume the generation of the CO insertion products 66b and 66c as reactive intermediates. These contain each a pair of B(C6 F5 )2 groups. One of them is occupied by interaction with the phosphane, the other is a strong pendent Lewis acid. The carbonyl oxygen is a suited Lewis base for binding, but that cannot be reached by the boron Lewis acid intramolecularly. Consequently, intermolecular C=O···B(C6 F5 )2 contact formation was observed and we isolated the respective macrocyclic dimers 67b and 67c (see Scheme 3.19) [84]. Figure 3.1 shows two views of the core of the molecular structure of the Tipp-substituted dimer 67c (top and side views). In the crystal, the macrocycle is close to C2 -symmetric (but not exactly crystallographically). In solution, it features a single 31 P NMR resonance. The Mes* containing P/B/B system 61a also reacts with carbon monoxide under these conditions. We assume a similar reaction course with initial generation of the CO insertion product 66a. This then undergoes a cyclo-oligomerization using its C=O/B FLP reactivity. However, in this case, this does not lead to a dimer but we observed cyclotrimer formation. The product 68 was isolated (see Scheme 3.20). In the cyclooligomers, the phosphonium moieties are chiral. In the dimer, we consequently might observe a meso and a rac isomer (only the rac 67b and 67c structures were found in the crystal). In the cyclotrimer the Mes* substituents at phosphorus could all be oriented toward one face of the macrocycle (all cis-isomer), leading to a chiral C3 -symmetric overall structure, or two could be cis- and the third transoriented. In that case, the system is also chiral (C1 ) and all three P centers should be O Ar P 61b,c

B(C6F5)2 B(C6F5)2

CO

(C6F5)2B Ar

P B(C6F5)2

66b,c

dimerization

Mes Ar:

(b)

O

[B]

Ar P [B]

Mes

[B] P Ar (c)

[B]

O

67b,c [B]: B(C6F5)2

Scheme 3.19 Formation of macrocyclic dimers by P/B/B FLP carbonylation

3 FLP Reduction of Carbon Monoxide and Related Reactions

99

Fig. 3.1 Top and side views of the molecular structure of the macrocyclic dimer 67c (only the ipso-carbon atoms of the aryl substituents at phosphorus and boron are shown for clarity)

Mes*P

B(C6F5)2 B(C6F5)2

61a

[B]

O

[B] Mes*

Mes* P

P

CO [B]

O

Mes* 66a

O O

(C6F5)2B

[B]

P B(C6F5)2

[B]

P

[B]

Mes*

[B]: B(C6F5)2 68

Scheme 3.20 Formation of the cyclotrimeric carbonylation product 68

different. Inspection of the molecular structure in the crystal by X-ray diffraction revealed the nonsymmetric trans-, cis-arrangement (see Fig. 3.2). Consequently, compound 68 showed three 31 P NMR features in the solid-state CP MAS NMR spectrum. Remarkably, this cyclotrimeric structure was retained in the solution. We observed three well-separated equal intensity 31 P NMR resonances of compound 68 at low temperature in solution (CD2 Cl2 , 203 K) [84]. A similar CO insertion into a B–C bond was also found upon treatment of the α-borylated phosphorus ylide 69 with CO [85]. The reaction proceeds through the intermediate 70 and finally results in the formation of the dimeric product 71 (see Scheme 3.21). A Lewis basic Pt(0)-ethene complex 72 supported by a diphosphine ligand reacts with B(C6 F5 )3 to generate a β-agostic compound 73 in a manner reminiscent of a frustrated Lewis pair reaction. This then reacts with carbon monoxide to give a single product 75 [86], namely a five-membered metallacycle with the borane bonded to the carbon adjacent to oxygen. The metallacyclobutanone adduct 74 was proposed as an intermediate (see Scheme 3.21).

100

T. Wang et al.

Fig. 3.2 Top and side views of the molecular structure of the cyclotrimer 68 in the crystal (for clarity only the ipso-carbon atoms of the Mes* substituents at phosphorus and of the C6 F5 groups at boron are depicted)

69

P

O

CO

Ph3P

Ph3P

BEt2

P

P

Ph3P Et2B

BEt2 PPh3 O

71 P

P

H Pt

CO

Pt

P O

B(C6F5)3

P 72

P

BEt2 70

B(C6F5)3 Pt

O

74

73 PtBu2

P

PtBu2

P

:

B(C6F5)3

Pt O

B(C6F5)3

75

Scheme 3.21 Examples of CO insertion into the B–C bond

3.5 Reaction of Carbon Monoxide at d0 -Metallocene Cations Transition metal complexes of d0 electron configuration are special as they lack electron density for back donation. The group 4 bent metallocene cations Cp2 M(IV)R+ with d0 electron configuration are Lewis acidic [87, 88]. Group 4 bent metallocene cations have found extensive use in homogeneous Ziegler-Natta olefin polymerization catalysis [89–91]. Selected examples have also been used as bulky Lewis acid components in FLP chemistry. Stephan et al. [92] and Wass et al. [12, 93–101] have described a variety of intra- and intermolecular Cp2 ZrR+ combinations with bulky Lewis bases, usually bulky phosphanes, that showed typical FLP behavior, e.g., in the

3 FLP Reduction of Carbon Monoxide and Related Reactions

101

reaction with dihydrogen. The system 76 in Scheme 3.22 is a typical example [93]. We had prepared a variety of related titanocene or zirconocene complexes (e.g. 77) that also showed some typical FLP behavior, e.g. in the reaction with CO2 [102–104]. We have recently developed some CO-reduction chemistry of suitably functionalized zirconocene cations that bears some relation to the reduction chemistry of carbon monoxide at frustrated Lewis pairs (vide supra), although the majority of these reactions are strictly speaking not general frustrated Lewis pair reactions. Mostly, in these systems, activation of the CO molecule occurs by the action of the metallocene cation or a strongly Lewis acidic borane reagent or even by their joint action without the specific influence of a Lewis base. However, because of the similarity of the product formation, these systems are included in this short account. The intramolecular Zr+ /P pair 78 undergoes a variety of typical FLP reactions. Its capture of carbon dioxide to give 79 is an example. We subsequently reduced the CO2 moiety at the Zr+ /P template by treatment with Piers’ borane. The reaction of 78 with carbon monoxide took a different course [105]. Here the typical σ-aryl zirconocene reactivity prevailed. CO was inserted into the Zr+ – C(sp2 ) bond to give 81, although in that compound, the Zr+ Lewis acid might have benefitted from some stabilizing interaction with the pendent –PPh2 Lewis base. Subsequent treatment with phenylacetylene gave 82 (see Scheme 3.23), similar to a related reaction sequence previously described by Jordan et al. [106–108]. According to the X-ray crystal structure analysis and the NMR spectra, there is no P···Zr+ interaction in 82. Even neutral d0 -configurated 16 electron Cp*2 Zr(H)X complexes can be Lewis acidic enough to promote the reduction of carbon monoxide by the HB(C6 F5 )2 Scheme 3.22 Typical examples of intramolecular M+ /P FLPs (M = Ti, Zr)

Ph

O CpR2Zr

PtBu2

76 (Wass et al.)

Cp2Zr

PPh2

Cp2Zr 79

78

PPh2

PPh2 81

PPh2 O 80 H O B(C6F5)2

O Ph2P

PhC CH

Cp2Zr

77 (Normand et al.)

Cp2Zr

O

CO O

Cp2M PCy2 M: Zr,Ti

HB(C6F5)2

CO2

cations with [B(C6F5)4]counter anions

O Cp2Zr Ph

Ph

82

Scheme 3.23 FLP addition versus metal-carbon σ-bond insertion in reactions of 78

102

T. Wang et al.

reagent. We prepared the Zr-hydride 83 by treatment of J. Bercaw’s zirconocene dihydride complex 84 [109, 110] with HO–Mes (see Scheme 3.24). Compound 83 reacted rapidly with HB(C6 F5 )2 /CO, presumably via (C6 F5 )2 B(H)CO, to give the zirconocene-stabilized formylborate product 85 [111]. Compound 85 was characterized by an X-ray crystal structure analysis and by 1 H Hahn echo MAS solid state NMR spectroscopy (at 20.0 T), in which the typical formyl O=CH-resonance (δ 11.3 ppm) and even the B–H signal could be located [111]. In solution, compound 85 shows dynamic temperature dependent 1 H NMR spectra, indicating rapid exchange of the hydrogen positions Ha and Hb via the not directly observed symmetrical – O–CH2 –[B] intermediate 86. We assume that this reactive intermediate determines some of the chemistry of the Zr+ -formyl(hydrido)borate system 85. It seems to act as an oxygen/boron FLP towards carbon monoxide. The CO reaction produces the borata-β-lactone-like four-membered ring product at the zirconocene template. A rearrangement to the preferred Zr+ Lewis acid adduct of the lactone carbonyl oxygen then eventually forms the final observed product 89. Compound 85 is an analog of our pyridine-stabilized formyl borane 27, of Stephan’s Pt Bu3 /B(C6 F5 )3 /H2 derived borane-stabilized formylborate 90 [112] or Piers’ Cp*2 Sc coordinated formylborate complexes 92 [113]. Both the latter compounds reacted further by internal C6 F5 shift from boron to carbon (see Scheme 3.25). It should be noted that the zirconoxymethylborane intermediate 86 underwent a variety of additional FLP like reactions. It was trapped by CO2 or by N-sulfinylaniline to give the five-membered ring products 94 and 95 at the zirconocene framework (see Scheme 3.26) [111].

OMes

Cp*2Zr

Cp*2Zr

H

83

84

H H

+ HO

HB(C6F5)2 CO (1.5 bar) C6H5Br, r.t. OMes

Cp*2Zr 85

O Ha

Cp*2Zr 87

B(C6F5)2 H

OMes

Cp*2Zr 86

b

OMes O C O B(C6F5)2 H H

O H

Cp*2Zr 88

a

O

O

B(C6F5)2 85'

Hb

OMes

H 2C

OMes

Cp*2Zr

O

B(C6F5)2

Cp*2Zr 89

Hb

B(C6F5)2 Ha

OMes O

B(C6F5)2 O CH2

Scheme 3.24 Reaction scheme of the formation of the borata-lactone complex 89

3 FLP Reduction of Carbon Monoxide and Related Reactions

O (C6F5)2B

O C

(C6F5)3B

ScCp*2

B(C6F5)3

t

Bu3PH

103

H

O C

(C6F5)3B

90

H

92

H

N Bu3PH B(C6F5)3 O C 6F 5 (C6F5)2B H 91

ScCp*2

t

27

O

C 6F 5

(C6F5)2B

H

93

Scheme 3.25 Examples of a formylborane and formylborates

Scheme 3.26 Structures of complexes 94 and 95

OMes

Cp*2Zr

O

94

OMes

Cp*2Zr

C O B(C6F5)2 O C H2

O

S O

PhN

95

CH2 B(C6F5)2

Complex 85 splits dihydrogen via its FLP isomer 86. Under mild conditions, it reacted rapidly with H2 (1 h, r.t.) to give a mixture of the hydroxy zirconocene complex 97 (characterized by X-ray diffraction) and the methylborane 98. In the course of the whole reaction sequence, the CO molecule has thus been reduced to the methyl substituent at boron, but the reaction can still go further. Exposure to H2 under similar conditions (r.t., 1.5 bar H2 , 8 d) resulted in H2 splitting by the intermolecular O/B FLP (97/98) to probably generate the salt 99 as an intermediate. Subsequent internal protonolysis then apparently liberated methane and the zwitterionic Zr+ /B– -product 100 (see Scheme 3.27). Its structure was confirmed by its independent synthesis from 97 and HB(C6 F5 )2 . The reaction sequence was also carried out starting from 85 over both FLP reaction steps with dideuterium to give CH2 D2 [111].

Cp*2Zr 85

OMes

Cp*2Zr

O B(C6F5)2 H

86

H

Cp*2Zr 97

OMes OH

+

H3C B(C6F5)2 98

OMes O H

H2 slow

Cp*2Zr

B(C6F5)2 H

Cp*2Zr

H2

96

OMes

O H H H H3C B(C6F5)2 99

Scheme 3.27 Reduction of complex 85 with dihydrogen

Cp*2Zr

OMes H O H H 2C

B(C6F5)2

OMes O H

H B(C6F5)2 100

+ CH4

104

T. Wang et al. HB(C6F5)2 + Cp*2Zr 101

OMes

H3C B(C6F5)2 + Cp*2Zr

CH3

83

98

OMes H CO

Cp*2Zr

OMes

102 H C 3

Cp*2Zr

B(C6F5)2 H

O H

OMes O

103 H

Cp*2Zr

B(C6F5)2 CH3

104

OMes O B(C6F5)2 H

CO

OMes

H 3C 105

Cp*2Zr

O

O

Cp*2Zr

C B(C6F5)2

OMes O

H3 C 106

C

O

Cp*2Zr

B(C6F5)2 H

CH3

OMes O

B(C6F5)2 O

107

CH3 H

Scheme 3.28 A pathway to complex 107

We also tried to react the corresponding methyl zirconocene complex 101 with HB(C6 F5 )2 and CO. However, we noticed that the 101/HB(C6 F5 )2 mixture rapidly equilibrated with 83/H3 C–B(C6 F5 )2 (98) by hydride/methyl exchange. Subsequent reaction with CO then gave a mixture of the initially expected formyl(methyl)borate complex 104 with its rearrangement product, the acetyl(hydrido)borate system 102 [114]. The latter was by far the favored product (> 10:1). The rearrangement was thought to proceed via the intermediate 103. This could be trapped with additional carbon monoxide. In a rather slow reaction (3d at r.t.), the four-membered ring product 107 was formed (see Scheme 3.28). We entered into some related chemistry starting from Cp*2 ZrMe2 (108). Its reaction with the TEMPO radical (two molar equiv.) [115–118] proceeded by means of methyl radical abstraction to eventually yield complex 110. This was converted to the zirconocene cation by treatment with B(C6 F5 )3 . The cation of 113 served as an active intramolecular frustrated Lewis pair using the TEMPO-derived internal nitrogen base. With Pt Bu3 , it formed an intermolecular P/Zr FLP. The reaction of 110 with HB(C6 F5 )2 also proceeded by means of formal methyl anion transfer from zirconium to boron. In this case, the hydride bridged product 111 was obtained (characterized by X-ray diffraction). Compound 111 reacted with carbon monoxide to give the three-membered reduction product 112 (see Scheme 3.29) [119].

3.6 Conclusions We have found several pathways to overcome the reluctance of the carbon monoxide molecule to become reduced by B–H boranes. Since the B–H boranes alone form

3 FLP Reduction of Carbon Monoxide and Related Reactions

Cp*2Zr 108

CH3 CH3

+

Cp*2Zr

N O

HB(C6F5)2

O

111

N

CH3 N O

CH3 Cp*2Zr

O

N

O

N

110 B(C6F5)3

CO

Cp*2Zr

(C6F5)2B O Cp*2Zr

+

TEMPO

B(C6F5)2

H Cp*2Zr

CH3

109 TEMPO

H3 C

105

O

CH3 H

H3C B(C6F5)3 113

N 112

FLP reactions

Scheme 3.29 Formation and reactions of Cp2 Zr(Me)OTMP 110

borane carbonyls [B](H)–CO, they need the help of auxiliary reagents in order to proceed to CH containing carbon monoxide follow-up products. The action of frustrated Lewis pairs is one solution. The B–C≡O unit can interact with a suitable P/B FLP by means of side-on CO bonding to generate intermediates that are activated for reduction by internal hydride. Several such systems were prepared and their specific chemistry was reported. CO activation can also take place by, e.g., the formation of bridged carbonyl structures by synergic interaction of both the P/B functionalities with the CO carbon atom. This activates the CO molecule for hydride attack. We have also presented a variety of examples where activation of the CO molecule occurs through the combined action of a pair of suitably functionalized Lewis acids, be they both boron Lewis acids or a combination of a boron Lewis acid with a transition metal derived Lewis acid, e.g., a d0 configurated group 4 metallocene cation. So far, the presented reactions are stoichiometric, but they may provide a sound synthetic and mechanistic basis for a future development of novel catalytic utilizations of the carbon monoxide molecule through some of the reactive species that were disclosed in these studies. Acknowledgments G.E. thanks his many coworkers and collaborators who were involved in these studies for their dedicated work and their invaluable contributions. Financial support of the studies carried out in his group at Münster by the Deutsche Forschungsgemeinschaft, the European Research Council, and the Alexander von Humboldt-Stiftung is gratefully acknowledged.

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Chapter 4

FLP-Mediated C–H-Activation Yashar Soltani and Frédéric-Georges Fontaine

Abstract The C–H functionalization of aromatic molecules is a green approach that allows creating complex molecules from simple reagents. While these transformations are mainly catalysed using transition metal complexes, the main group molecules, including frustrated Lewis pairs, have been shown to be efficient species to functionalize C–H bonds. This chapter describes the different approaches and mechanisms that are used to activate C–H bonds using Lewis acidic boron and silicon species. On the one hand, highly electrophilic cationic boron and silicon species can activate C–H bonds by an electrophilic addition pathway that generates a Wheland intermediate that is further deprotonated by a Lewis base. On the other hand, frustrated Lewis pairs act in a concerted way where the Lewis acid activation and the deprotonation by a base occur simultaneously. In both systems, the nature of the Lewis acid and Lewis base plays an important role on the activity and the selectivity of the functionalization reaction. Keywords C–H activation · Electrophilic addition · Borylation · Silylation · Frustrated lewis pairs

Abbreviations HBPin HBCat Pin Cat 9-BBN 3c-2e AIBN Ar

4,4,5,5-Tetramethyl-1,3,2-dioxaborolane Catecholborane Pinacolate Catecholate 9-Borabicyclo[3.3.1]nonane Three-centre two-electron Azobisisobutyronitrile Aryl-

Y. Soltani · F.-G. Fontaine (B) Département de Chimie, Université Laval, 1045 Avenue de la Médecine, Québec City, Québec G1V 0A6, Canada e-mail: [email protected] © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_4

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Bn BOC bpy COD Cy DMF DMSO DTBMP dTBP EAS Et exp FDA FLP fur HOMO Int LUMO m Me NMR NTf2 − o p PAH Ph PMP Pip tBu TfO− THF THT TIPS TM TMP TMS Tol Ts TS tTBP

Y. Soltani and F. G. Fontaine

Benzyltert-Butyloxycarbonyl 2,2 -Bipyridine 1,5-Cyclooctadiene CyclohexylDimethylformamide Dimethyl sulfoxide 2,6-Di-tert-butyl-4-methylpyridine 2,6-Di-tert-butylpyridine Electrophilic aromatic substitution EthylExperimental Food and Drug Administration Frustrated Lewis pair FurylHighest occupied molecular orbital Intermediate Lowest unoccupied molecular orbital metaMethylNuclear magnetic resonance Bistriflimide anion, [(CF3 SO2 )2 N]− OrthoParaPolycyclic aromatic hydrocarbons Phenyl1,2,2,6,6-Pentamethylpiperidine PiperidylTert-ButylTriflate anion, (CF3 SO3 − ) Tetrahydrofuran Tetrahydrothiophene TriisopropylsilylTransition metal 2,2,6,6-Tetramethylpiperidine Trimethylsilyl TolylTosylTransition state 2,4,6-Tri-tert-butylpyridine

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4.1 Introduction Following many important discoveries since the beginning of the century, C–H functionalization has become a cornerstone in green chemistry. The ability to cleave selectively C–H bonds in inactivated molecules to install active functional groups and create complex architectures can prove both atomically and economically efficient. It is indeed a great tool for late-stage functionalization, an attractive property in pharmaceutical and medicinal chemistry [1, 2]. It also limits the amount of waste since it does not require the presence of functional groups on the starting materials. One key component of the C–H functionalization reaction by transition metals (TM) is the C–H activation step, which can be separated into three mechanistically distinct processes: oxidative addition, σ-bond metathesis and electrophilic activation, even though the dividing line between these classes is sometimes rather blurred (Fig. 4.1) [3]. The oxidative addition involves the cleavage of the desired carbon–hydrogen bond to generate M–C and M–H bonds. This activation step increases the oxidation state of the metal centre by two units and increases the metal coordination number by two. The sigma-bond metathesis reaction proceeds via a concerted transition state where Oxidative Addition H

H

H [LnM]

[LnM]

[LnM]

σ-bond Metathesis R

H

[LnM]

R

H

[LnM]

[LnM] +

R H

+

Hbase

Electrophilic Activation H [LnM]

[LnM]

[LnM] H base

Fig. 4.1 Main C–H activation pathways for C–H functionalization

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the C–H bond is cleaved at the same time as the M–C and R–H bonds are formed. The R group can be part of the coordination sphere or an outside Lewis base and this transformation does not involve a change in oxidation state. Although similar in concept, the electrophilic activation reaction is a two-step mechanism. A Wheland intermediate is first formed after the initial electrophilic attack of a Lewis acid to an unsaturated organic compound [4]. The now positively charged arenium cation is deprotonated by a base to rearomatize the system and generate the final product. As seen in Fig. 4.2, the C–H activation step is similar in both the processes and only differs by the presence of a stable intermediate in the electrophilic activation mechanism. Reporting the full extent of TM catalysed C–H functionalization reactions is outside the scope of this work, but some examples bear analogies to frustrated Lewis pair (FLP) processes and will be briefly introduced.

O

Me C

L Pd L

O

O

H

L Pd L

TS1

Me C

O H

TS2

Int1 AcOH

AcOH

Me

+

C O

PdL2

O L Pd L

+ PdL2

H

PdL2(OAc) + H

σ-bond Metathesis

Electrophilic Addition

Fig. 4.2 Potential energy profile of the σ-bond metathesis and electrophilic addition reactions

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4.2 C–H Functionalization by Transition Metal Complexes One of the most powerful methodologies to functionalize aromatic molecules is the C–H borylation using iridium-based catalysts. The first observation of such a process was reported by Marder and co-workers in 1993 [5], but was only optimized few years later by the groups of Smith, Hartwig and Miyaura [6–12] (Scheme 4.1). Mechanistic investigations conclude that the most likely process for the C–H activation step is an oxidative addition at Ir(III) to generate Ir(V) [13, 14]. Smith and co-workers[15] showed that a key component of the C–H activation step in this system involves a proton transfer from the Ar–H to a nucleophilic boryl ligand (Scheme 4.2), demonstrating the importance of the concerted action between the metal and the ligand in reducing the transition state (TS) energy of this system. Smith (1999) Cp*Ir(PMe3)(H)(BPin) (17 mol%) HBPin (5 equiv.) 150 °C, 120 h -H2

BPin

53 %

Miyaura (2002) [IrCl(COD)]2/bpy (1.5 mol%) HBPin (1 equiv.) 80 °C, 16 h -H2

excess

BPin

80 %

Scheme 4.1 Catalytic borylation of benzene with iridium catalysts

Smith (2010) B(OR)2 B(OR)2 L Ir B(OR)2 L

PhH

B(OR)2 B(OR)2 L Ir B(OR)2 L H

boryl-assisted TS3

B(OR)2 B(OR)2 L Ir B(OR)2 L H

Int2

Scheme 4.2 Transition state and intermediate of a boryl-assisted C–H activation

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Ryabov (1985) R1 Pd(OAc)2 R2 Me

N

CHCl3 Me

OAc

N Pd

1/2

O H

O

Me

R1 R2

OAc Pd

+

NMe2

AcOH

2

TS4 (falsely suspected arenium species)

Scheme 4.3 Stoichiometric reaction of N,N-dimethyl benzylamine and Pd(II) acetate

In another relevant study published a decade earlier, Ryabov and co-workers probed the nature of a stoichiometric C–H activation at palladium (Scheme 4.3) [16]. They falsely concluded that this reaction proceeds via a positively charged arenium transition state (TS4), which is in line with an electrophilic substitution activation. Equipped with more powerful and elaborate computational methods, Macgregor and co-workers reported 20 years later that this reaction rather proceeds via a concerted σ-bond metathesis pathway [3]. This type of activation proved to be a powerful synthetic tool that was exploited by Echavarren [17, 18] and Fagnou [19, 20] to perform elaborate C–C-bond formation reactions. The mechanistic investigations supported a concerted σ-bond metathesis pathway for the C–H-activation process, where a carboxylate moiety (usually a pivalate group) can act as a Lewis base to abstract a hydrogen atom, while the palladium centre acts as a Lewis acid interacting with the carbon. While the range of transformations and the selectivity obtained using TM catalysts are impressive, there are some advantages in investigating the metal-free activation of C–H bonds, outside possible cost-saving. Indeed, ruling bodies like the Food and Drug Administration (FDA) strictly regulate trace metals in products made for human consumption, and the presence of residual catalysts in late-stage functionalization reactions can prove problematic [21]. In addition, residual metal catalysts can act as charge carrier traps or photoquenchers, strongly affecting the intrinsic properties in products for the modern electronics industry, making metal-free approaches highly desirable [22]. Since there are several similarities between the H–H bond and the C–H bond, it is possible to imagine that the typical FLP reactivity for the activation of dihydrogen and the catalytic hydrogenation can be adapted to C–H activation [23].

4.3 FLP Transformations: A Kinetic Concept To better define the use of FLPs in C–H activation and functionalization processes, it is important to define the concept of FLPs, since the typical definition based on sterics and “frustration” does not encompass all the chemistry observed, especially when it comes to C–H activation processes. We prefer to define a FLP as “a Lewis

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pair that can access a TS where the Lewis acid and the Lewis base are not neutralized and can cooperate for the activation of a bond”. According to this definition, a FLP is defined by its reactivity, and therefore is a kinetic concept [24]. It also correctly describes processes where FLP reactivity is observed with Lewis pairs that do not have accessible Lewis acidic and/or Lewis basic sites at the resting state. Looking back at the three main mechanisms proposed for TM catalysed transformations (Fig. 4.1), it is evident that most FLPs (especially the boron-based ones) cannot easily operate through oxidative addition since most main group elements cannot access readily more than one oxidation state. However, the σ-bond metathesis and the electrophilic activation TS are accessible, with the Lewis acid acting as the LUMO orbital (electrophile) and the Lewis base as the HOMO orbital (nucleophile). Looking back at Fig. 4.2, we can see analogies in the σ-bond metathesis step, which is typical of FLP activation processes, and the electrophilic activation. The main difference between these two processes is the formation of an arenium ion (Wheland intermediate) prior to the release of a proton in the electrophilic activation mechanism, whereas the corresponding structure is instead a TS in FLP chemistry. Since we know that H+ does not exist freely and requires stabilization, can we preclude the necessity of the Lewis base, as weakly as it might be, to abstract the proton and for this reaction to proceed? If so, where is the defining line between electrophilic and FLP processes in systems where the Wheland is high in energy and doubtfully exist? We are not claiming that electrophilic activation is a FLP process, but there is a grey zone between a FLP activation and an electrophilic activation and one cannot review one process without writing about the other.

4.4 Functionalization of C–H Bonds Through Electrophilic Activation 4.4.1 Electrophilic Borylation Starting from Haloboranes The electrophilic pathway makes use of the reactivity of positively charged ions towards aromatic C–H-bonds via a Wheland intermediate (Fig. 4.2). While several examples of electrophilic addition have been reported, the electrophilic borylation is the most pertinent reaction in line with FLP-type reactivity. The first mention of metal-free borylation of arenes was reported by Muetterties et al. using BCl3 and AlCl3 [25–28]. It was proposed by Ingleson [29] that this combination of reactants under the harsh conditions described by Muetterties might form an unobserved boron species related to [BCl2 ][AlCl4 ], which would be the active species responsible for this reactivity. In 1960, Dewar reacted a thiophenol with BCl3 and AlCl3 to form a cationic boron species (Int2) that carries on to react with the C2 -atom of the thiophenol molecule to form an arenium intermediate (Int3) [30]. After proton abstraction, the system rearomatizes to form a thiaborin derivative (Scheme 4.4).

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Dewar (1960) [AlCl4] SBCl2

AlCl3

SBCl

Int2

Shubin (2000) R1

S BCl AlCl3 H Cl

- HCl, AlCl3

S BCl

not isolated

Int3

Murakami (2010) Ph

B

Br2 N B

R1

N Me

R2

R1 R2 2 examples

R3 5 examples

Scheme 4.4 Formation of a thiaborin derivative via a borenium cation Int3 (top). Other examples exploiting this reactivity (bottom)

Using a similar strategy, several B–N containing heterocycles were synthesized, notably by Shubin [31] or Murakami, [32] as shown in Scheme 4.4. Revisiting the reactivity of boronium ions and other positively charged boron species led to a renaissance in electrophilic borylation. In a benchmark study, Ingleson and co-workers showed that BBr3 was not electrophilic enough for the electrophilic aromatic substitution (EAS) of unactivated arenes to take place [33]. When using neutral borane Lewis acids, only directed intramolecular arene C–H-borylations proved successful. Ingleson considered this transformation occurring through an electrophilic aromatic substitution or a C–H insertion, which are similar to TM C–H activation mechanisms. However, the selectivity of the borylation of toluene, giving mainly the thermodynamic C4 rather than the kinetic C3 derivative (C4:C3 is 2.1:1 and 5.4:1 at 20 and 110 °C, respectively) is consistent with an electrophilic mechanism where the methyl group can stabilize the cationic charge resulting from the Wheland intermediate (Scheme 4.5). In the following years, Ingleson [34–37] and Vedejs [38] showed a variety of electrophilic borylation systems using active borocations that were either generated in situ, via halide abstractions using AlCl3 , or by using stable and isolated borocations. These highly active boron species were shown to react stoichiometrically with (hetero-)arenes to give the borylated species (Scheme 4.6). The scope was extended to other heteroaromatic groups, like pyrroles and indoles. In all cases, a base is required to deprotonate the Wheland intermediate generated by the electrophilic attack of the borocation. The counterions – OTf and – NTf2 , or the amine stabilizing the borenium ion, are responsible for the deprotonation of the arenium intermediate. In 2013, Ingleson and collaborators [29] demonstrated that the borylation of NTIPS-pyrrole by the borenium cation [CatB(NEt3 )]+ could readily operate in the

4 FLP-Mediated C–H-Activation

121 EAS Mechanism CatB H Int5

+ Et 3Si[CbBr6 ] CatB Cl

PhBCat + H

[CatB][CbBr6]

- Et 3SiCl

Int4 H

[CbBr6] = [closo-1-H-CB11H5Br6] CatB

L = a weak nucleophile e.g. CatBH, Et3SiCl

PhBCat + HL

L

Int6 C-H Insertion Mechanism

Scheme 4.5 Possible mechanistic pathways for the borylation of benzene using in situ generated borenium cation Int4 Vedejs (2011) R1 N

R2

+

Me2N

[BBN] NMe2

R1

CH2Cl2

Tf2N

N

- Tf2NH 50 °C

R2 BBN

4 examples Ingleson (2011)

Ar-H

+

1) 20 °C, CH2Cl2 CatB NEt3 [AlCl4]

2) pinacol, Et 3N

Ar BPin 10 examples

Ingleson (2012)

S S

Cl B NEt3

1) Me2NTol, Al2Cl6 2) 2-Methylthiophene

Me

S

B

S

S +

+

Me H [AlCl4] N Me S B S

[Me2N(H)tol][AlCl4]

Scheme 4.6 Examples of stoichiometric borylation of various (hetero-)arenes using different boron cations

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presence of AlCl4 – but was inactive with weakly coordinating anions [CbBr6 ]– or [BArCl ]– (Scheme 4.7), even in the presence of 2,6-di-tert-butylpyridine (dTBP) to sequester the adventitious H+ in solution. It was proposed that a small amount of NEt3 in solution was required to promote the deprotonation of the arenium ion. To confirm the necessity of the Lewis base, a catalytic amount of PPh3 was added, which improved significantly the reaction when using [CbBr6 ]– or [BArCl ]– as counterions. The need for a phosphine, which is less basic than NEt3 but with similar steric constraints, puts in evidence the requirement of a Lewis base for this transformation to operate, once again showcasing the importance of the Lewis pair in the transformation (Scheme 4.7). When the reaction is carried out with neutral BCl3 or CatBCl in the presence of AlCl3 and of non-coordinating Lewis bases (Me2 NTol, dTBP or 2,4,6-tri-tert-butylpyridine (tTBP)), the formation of the borenium ion is disfavoured and the borylation of less active substrates such as toluene does not operate at ambient temperature. The borylation of pyrene at higher temperature is possible, and a significant change in selectivity is observed according to the Lewis base (Scheme 4.8). It is proposed that the addition at the 1-position is kinetically favoured, whereas the thermodynamic product is borylated at the 2-position. The great difference in the 1:2 ratio can be explained by the concentration of free base in solution available to deprotonate the borylated arenium ion. Spectroscopic evidences show that the smaller amine (Me2 NTol) forms stronger Lewis adducts with AlCl3 and BCl3 , thus leaving enough time for the migration of the boryl group from the 1-position to the 2-position. With more hindered Lewis bases, a more “frustrated” character is present, leaving enough base in solution to favour deprotonation and generate the kinetic product. These [CbBr6] = [closo-1-H-CB11H5Br6] [BArCl] = [B(3,5-C6H3Cl2)4]

TIPS N

[Y] = [AlCl4] 72 h

CatB >95 %

TIPS N

+

TIPS N

[Y] = [CbBr6] or [BArCl] CatB NEt3 Y

24 h with or without dTBP

CatB 5% TIPS N

[Y] = [CbBr6] or [BArCl] 1h PPh3 (0.2 equiv.)

CatB >95 %

Scheme 4.7 Borylation reactions of N-TIPS-pyrrole by borenium cations (dTBP-2,6-di-tertbutylpyridine)

4 FLP-Mediated C–H-Activation

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Ingleson (2013) [B]Cl (1 equiv.) amine (1 equiv.) AlCl3 (1 equiv.)

[B] H

2 1

[B]

>100 °C

[B] amine T (°C) 1:2 ratio 1 : 12 BCl2 Me2NTol2 1202 BCl2 tTBP2 1202 6 : 12 BCat dTBP 100 12 : 1

Scheme 4.8 Stoichiometric borylation of pyrene

results clearly show that unquenched Lewis acid and base reactivity is key in these intermolecular systems, thus encompassing the kinetic aspects of FLP chemistry. These borylation methodologies were exploited to make B–N-fused polycyclic aromatics, [39] by replacing C–C units with isoelectronic B–N units, with interesting electronic and optical properties. These units can be introduced into polycyclic aromatic hydrocarbons (PAH), [40–44] which can be further processed to give B– N embedded graphene sheets with wide applications in catalysis, electronics, and energy conversion and storage [45, 46].

4.4.2 Electrophilic Borylation Starting from Hydroboranes Another approach to generate cationic boron species is using hydroboranes rather than haloboranes. The former reagents are more readily available and easier to handle. The B–H bond can be readily activated by a strong Lewis acid (Z) such as B(C6 F5 )3 to generate active borenium-like molecules [47]. In a typical mechanism, the Z will interact with the B–H and form the activated species Int7 that is reminiscent of the activation of silanes by Lewis acids, as first proposed by Piers for the hydrosilation reaction using B(C6 F5 )3 [48] and later supported by Oestreich[49] (Scheme 4.9). The electrophilic borane in Int7 will then interact with the most accessible nucleophilic site of the (hetero)arene to generate a Wheland intermediate Int8. This transformation Scheme 4.9 Activation of triphenylsilane using B(C6 F5 )3

Piers (1996)

Ph3Si H

+

B(C6F5)3

δ δ Ph3Si H B(C6F5)3

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leads to the borylated product after the deprotonation/activation of the C–H bond with concomitant release of H2 and regeneration of the catalyst Z (Fig. 4.3). There have been early reports on stoichiometric intramolecular C–H borylation reactions that were possible using hydroboranes activated by strong electrophiles, such as trityl ions (Scheme 4.10) [50, 51]. In a comprehensive mechanistic study, Vedejs and collaborators demonstrated that the borylation of deuterated species 1D (Scheme 4.10), once promoted by B– H hydride abstraction using the trityl salt [Ph3 C][B(C6 F5 )4 ], had a kH /kD value of 2.8, which is unexpected for electrophilic addition that have usually kH /kD values close to 1 [50]. Indeed, the rate limiting step in these processes is normally the formation of the Wheland intermediate and does not involve C–H bond cleavage. The authors rationalized this observation by the fact that no base is present in the system, making the release of H2 rate determining. According to DFT calculations, the Wheland complex Int10 is not the intermediate leading to C–H bond cleavage and C–B formation. It is rather borane π-complex Int9 that proceeds through 3c-2e interaction transition state TS5 where the boron interacts with the C–H bond to be cleaved, releasing dihydrogen concomitant with the C–B bond formation (Fig. 4.4). Ingleson demonstrated that CatBH can act as a stoichiometric reagent in the electrophilic borylation of arenes, using [CatB]+ ion as catalyst, generated from the reaction of CatBX (X = Cl or Br) and [Et3 Si][CbBr6 ] [33]. The choice of catecholborane in this transformation over the pinacolborane is critical since the cleavage of the C–O bond in the pinacol backbone can occur under highly electrophilic conditions. However, the use of B(C6 F5 )3 as a Lewis acid catalyst proved much more convenient, as demonstrated independently by Oestreich and Takita in 2017 [52, 53]. Takita and co-workers looked at the borylation of dimethylaniline using HBCat in the presence of 10 mol% B(C6 F5 )3 and a Lewis base (Scheme 4.11) [53]. They noticed the significant role of the Lewis base during catalysis, since oxygen-containing THF, DMF, DMSO and OPPh3 all inhibited catalysis. However, sulphur-containing molecules did prove favourable for catalysis, obtaining good yields when used in PhBCat, H-H

HBCat Z

BCat H H Z

δ δ CatB H Z Int7

Int8

Fig. 4.3 General mechanism of the electrophilic borylation using hydroboranes catalysed by Lewis acid Z

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Vedejs (2009)

n

R

NMe2 BH3

1) [Ph3C][B(C6F5)4] 2) NBu4BH4

D n

R

NMe2

B H2

1 n=1,2,3

Me

14 examples

H

BH2 NMe2

1D kH /kD=2.8

Vedejs (2013)

H3B Et N

a) or b)

Et

N

Et +

B H2

a) 52%, b) 69%

H 3B

N

a) or b)

H2B N

a) 30%, b) 29%

+

N

BH2

a+b) P > As > Sb) causes later transition states with shorter Y… H distances and thus higher barriers of H2 activation. This means that the deformation (strain) in the transitions state with respect to the initial reactant state, which increases in the same order as the activation barrier (N < P < As < Sb), is the reason for this trend. The influence of the Lewis acidity of the elements of Group 13 shows the opposite trend, with the barrier decreasing from B to In, with the exception of Al, which displayed the lowest H2 activation barrier. The geminal N/Al FLP was identified as the most active system for H2 activation. The lowest barrier for H2 activation with Al correlates with the strongest interaction energy and the lowest Pauli repulsion between FLP and H… H fragments at the transition state. The Pauli repulsion originates from the repulsion between the occupied orbitals of the two fragments [49]. Recent investigations have shown that intramolecular FLPs can be more catalytically active than their intermolecular counterparts [50]. Heiden and coworkers investigated the thermodynamics of hydrogen, hydride, and proton transfer from P/B intramolecular and intermolecular FLPs. The aim was to determine whether intramolecular or intermolecular FLPs are preferred in FLP-catalyzed hydrogenation reactions. Thermodynamic investigation of 22 intramolecular phosphoniumborohydrides and their corresponding intermolecular counterparts indicated that an intramolecular phosphonium-borohydride is the preferred catalyst for reduction of imines and enamines. On the other hand, an intermolecular phosphoniumborohydride is the preferred catalyst for the reduction of ketones and aldehydes [50].

5.3.2 Transition State and Reaction Kinetics The mechanistic mode causing the polarization of the H–H bond has been investigated in a number of theoretical studies leading initially to various proposed hypotheses. The present consensus mechanism involves the heterolytic splitting of the H–H bond, and two viable models have been proposed in the literature that aim to explain the catalytic mode of action of the FLP, namely, the electron transfer (ET) and the electric field (EF) models. In the ET model, which was proposed by Pápai and coworkers [51–53], the HOMO of the Lewis base interacts with the σ* orbital of the H–H bond and the LUMO of the Lewis acid interacts with the σ orbital of the H–H bond. As a result, the H2 bond is cleaved into H+ and H− . At the molecular scale, the activation process is based on the interactions between the LB, H2 , and LA molecules. Thus, the electronic characteristics of the Lewis base and Lewis acid play crucial roles in the reaction process. In the EF model, suggested by Grimme and coworkers [54], the core principle is the polarization of the H2 molecule by the electric field that is created by the Lewis base and Lewis acid, causing an almost barrierless H2 splitting.

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Hence, the structural characteristics of the LA and LB play important roles in the cleavage. These mechanistic details of the H–H bond polarization are still a subject of debate and the number of theoretical studies in the literature focused on this topic continues to grow. In a recent study by Privalov’s group, the authors characterized, by means of the fragment-based Energy Decomposition Analysis (EDA) and the Frontier Molecular Orbital (FMO) analysis, the interplay of electrostatic and orbital interactions in the Transition State (TS) structures of a series of FLPs in heterolytic H2 activation [55], where B(C6 F5 )3 was used as the Lewis acid together with a selection of Lewis bases including tBu3 P, (o-C6 H4 Me)3 P, 2,6-lutidine, 2,4,6-collidine, MeN=C(Ph)Me imine, MeN(H)-C(H)PhMe amine, THF, 1,4-dioxane and acetone. The authors showed that both orbital interactions (electron transfer between HOMO/LUMO) and electrostatic interactions (classical Coulomb interactions between negative and positive charges) are essential to compensate the Pauli repulsion between fragments in the TS structures, and neither the electrostatic nor the orbital interactions dominate (see Fig. 5.1). Furthermore, the Frontier Molecular Orbitals (FMOs) of the TS structures can arise not only from the “push–pull” molecular orbital scheme (case 1 in Fig. 5.1), but also from more intricate but energetically more fitting orbital interactions (case 2 and case 3 in Fig. 5.1). Cases 2 and 3 depicted in Fig. 5.1 have escaped notice thus far. In the “push–pull” molecular scheme, pure occupied σ and empty σ* MOs of H2 are involved. However, the reported results indicate that a combination of HOMO [LB + H2 ] interacting with LUMO [BCF] and LUMO [H2 + BCF] interacting with HOMO [LB] is viable. A recent AIMD study by Liu et al. revealed that these two models (i.e., ET and EF) are somehow complementary to each other [56]. Based on their metadynamics simulations, the authors demonstrated that when H2 is far from the LA/LB centers, the case 1

case 2

H-H Fragment 2

LB

Fragment 1 FLP

LA

LB

H-H LA

Fragment 1

Fragment 2 case 3

LB Fragment 2

case 4

H-H

LB LA Fragment 1

Fragment 2

LA Fragment 1

Fig. 5.1 The [LB… H… H… LA]TS transition state from the viewpoint of the EDA method: possible fragmentation schemes of LB, H… H and BCF interactions

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H–H bond is polarized mainly through the electric field created by the FLP. However, when H2 is closer than 2.5 Å to the LA/LB centers, the electron transfer from H− to B and from P to H+ could be visualized by the electron density difference. This means that the ET model plays a role in the short distance region and the EF model is relevant at longer distances (details are discussed in Sect. 5.4.1). In a few recent studies of geminal FLPs, Fernandez et al. investigated the influence of the nature of the acid/base pairs on the H2 activation process. Activation barriers and geometries of transition state structures were computationally explored and it turned out that they are strongly dependent on the electronic nature of the substituents directly attached to either the acidic or the basic center of the FLP. The energy decomposition analysis and activation strain model indicated a highly orbital-controlled mechanism in which asynchronous orbital interactions lead to a more kinetically favored activation [57, 58].

5.3.3 Engineering FLP Reactivity DFT calculations showed that increasing the strength of both the LA and the LB components in an FLP decreases the energy barrier for H2 activation, which confirms that the LA and LB act synergistically [59]. Furthermore, the reaction thermodynamics of H2 activation is strongly affected by the cumulative strength of the LA/LB parts, which can be quantified by the proton affinity and hydride affinity [60, 61]. However, the individual roles of the LA and the LB are still unclear. To this end, in a very recent study of FLP reactivity toward H2 activation by Heshmat et al., a series of experimentally investigated LAs, with two prototypical sets of LBs, including P(tBu3 P and Me3 P) and O-(dioxane, THF, Et2 O, and Ph2 O) based LBs, were compared (Fig. 5.2). The main question addressed was on the electronic and structural impact of the LAs and the individual roles of the LA and the LB in the entire reaction path of H2 activation, starting from a LA/LB complex and ending with the product-ion pairs (reaction 1). The authors analyzed the electronic and structural effects on the LA–LB complexation by systematically reducing the number of electronegative F atoms and by adding bulky groups that increase the pyramidalization strain of the flat borane molecules. The LA/LB binding/complexation energies in the initial molecular complex were investigated. The effects and outcomes of variation in electronic and structural properties of the Lewis acids are discussed below. L A · · · L B + H2 ↔ (L A · · · H · · · H · · · L B)T S ↔ L A − H − ↔+ H − L B (5.1) As shown in Fig. 5.3, two categories of initial LA/LB complexes are distinguished based on the LA… LB distances. The ones with a dative LA–LB bond, with distances from 1.6 to 2.3 Å, and the ones forming Van der Waals complexes, with distances from 3.8 to 6.0 Å. For dative-bond complexes, the more pronounced

5 Mechanistic Insight into the Hydrogen Activation by Frustrated Lewis Pairs F

F F F

F F

B

F3C

F

F

B

F F

F

F

F

F

F

B F Cl Cl

F

F

2 B(p-C6F4CF3)3

F F

F

F

F F

F

F

B F

F

F3C

CF3

CF3

1 BCF F

F

F

F

F

CF3

F

F

F

F

F F

F

F

F

F

F

181

Cl

F

F

F

F

F

B F Cl

Cl

Cl

Cl

Cl

F Cl

F Cl

3 B(C6F5)2{3,5-(CF3)2C6H3}

Cl

Cl

Cl

Cl

Cl Cl

Cl Cl

Cl

Cl

B Cl Cl

Cl Cl

Cl

Cl

Cl

Cl

Cl

Cl

4 B(C6F5)2(C6Cl5)

5 B(C6F5)(C6Cl5)2

6 B(C6Cl5)3

F

F

F

F

F F F

F F

F

F

B

F

B

F Cl

F Cl

F

F

F F

B

F Cl

F Cl

F Cl

F Cl

Cl

7 B(C6F4H)2(C6Cl2H3)

F

8 B(C6F4H)2(C6Cl3H2)

B F Cl

F

F

F F F

F

F

F

F

F

F

F

F

F F Cl

Cl

F3C

F

HC

CH

F

B

F

F F

F

F

F

B

CF3

CF3

F F F F

F F F

F

F

HC

F

10 B(C6F3H2)2(C6Cl3H2)

9 B(C6F3H2)2(C6Cl2H3)

F

11 B(CH(C6F5)2)3

12 B(CF3)3

Fig. 5.2 Considered Lewis acids (LA). The electronic and structural properties of the BCFderivatives are altered by varying the number of F atoms in the aryl rings or substitution of the F atoms by bulkier groups. All the BCF-derivatives have a flat geometry in the free molecule Figure adapted from Ref. [102].

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Fig. 5.3 Complexation energies (in kcal mol−1 ) of the initial molecular complexes formed between LA and LB versus the LA… LB distances (in Å). Two groups can be distinguished: those forming a dative LA–LB bond (left) and those forming a VdW complex (right) Figure adapted from Ref. [102].

attractive interactions are the orbital/electrostatic interactions between LA and LB fragments. For VdW complexes, the more pronounced attractive interactions are the dispersion/electrostatic interactions. The substantial variation in E complex in dativebond formers is due to the large differences in the structural deformation needed to form the compact molecular complexes, resulting in a steep and near-linear correlation between the LA–LB distances and the complexation energies. Instead, the VdW complexes, mainly containing tBu3 P and Ph2 O, are distributed horizontally. Specifically, their complexation energies are near the average of 14 kcal mol−1 , but the LA–LB distances show large variations, illustrating large flexibility of these molecular complexes but with little variation of the VdW interaction energies. The complexation energies, E complex , (in kcal mol−1 ) of the initial molecular complexes formed between each LA and tBu3 P, Me3 P, THF, and Ph2 O are reported in Table 5.1. In addition, the second column in Table 5.1 shows the hydride affinity of each LA relative to that of BCF, which is calculated as the reaction energy of the reaction: BCF − H− + LA → BCF + LA − H− . These H− affinities may be compared to experimentally determined LA electrophilicities. Taking the prototypical BCF structure (1) as our reference, replacement of the F atoms in the para position with CF3 groups (2) has a significant effect on the H− affinity (note that a negative number means a stronger affinity than that of BCF). Since the deformation in the LAs 1 and 2 is similar, the stronger complexation energy between 2 and Me3 P or THF is due to electronic effects. On the other hand, removing the F atoms from one ring and

5 Mechanistic Insight into the Hydrogen Activation by Frustrated Lewis Pairs

183

Table 5.1 The H− affinity of the LAs and their complexation energies with tBu3 P, Me3 P, THF, and Ph2 O. All values are in kcal mol−1 . The hydride affinity is defined relative to that of BCF. We quantify the Lewis acidity here as the complexation energy of the LA with Me3 P (column four). The numbers in parentheses show the deformation energy in the LA structure due to complexation to Me3 P. Table adapted from Ref. [102]. LA

H− affinity

tBu3 P

Me3 P (Estrain-LA )

THF

Ph2 O

1

0.0

−19.9

−31.7 (24.5)

−20.0

−17.9

2

−12.6

−20.8

−36.9 (24.6)

−26.7

−17.0

3

0.5

−19.7

−28.3 (31.7)

−21.8

−19.0

4

1.2

−15.9

−21.7 (31.5)

−14.1

−16.2

5

−0.4

−12.5

−16.0 (34.4)

−10.4

−16.0

6

−1.1

−13.3

−7.5 (40.6)

−8.9

−16.8

7

10.8

−12.1

−22.8 (28.8)

−13.2

−12.8

8

8.3

−12.3

−22.8 (29.9)

−12.8

−12.9

9

17.4

−12.3

−20.9 (28.6)

−12.7

−14.2

10

14.5

−14.8

−20.9 (29.7)

−10.6

−11.9

11

4.9

−12.5

−7.65 (5.5)

−9.23

−15.77

12

−26.9

−53.2

−66.13 (23.0)

−52.43

−36.53

adding two CF3 groups on the meta positions (3) weakens the H− affinity somewhat and, due to the increased LA structure deformation in complex formation, it is less Lewis acidic than 1. Replacing F atoms by Cl atoms on one ring (4), two rings (5), and three rings (6), decreases the strength of the dative adduct with Me3 P with each additional ring due to the increasing deformation energy. The opposite trend is seen for the H− affinity, although the affinity first decreases with structure 4. By varying the amount and type of substitution, it is possible to tune the strength of the dative adduct from –36.9 to –7.5 kcal mol−1 . Instead, in the case of Van der Waals complexes, the differences in complexation energy are not so large. In the Van der Waals complexes with tBu3 P and Ph2 O, the stabilization is largely due to dispersion interaction, while deformation and repulsion are less important because of the larger distance between the LA and LB centers compared to those with Me3 P and THF.

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These dominant attractive dispersion interactions are similar for tBu3 P and Ph2 O regardless that one is a P-bearing LB and the other is an O-bearing LB. The interaction between a solvent (ethereal) LB with an LA is seen to be rather strong. Hence, the preparation (reorganization) energy of the LA and LB pair for H2 activation in Van der Waals adducts of tBu3 P and Ph2 O is similar. LAs 7–10 were derived from BCF by replacing F atoms with H and Cl atoms to measure the effect of front strain (positions 2 and 6 in the aryl rings) and back strain (position 5). The H− affinity of all four LAs is much decreased compared to that of the original BCF structure and the Lewis acidity to form a dative-bond with Me3 P is decreased by up to ca. 35% (also with THF a dative-bond is formed). The complexation energy with tBu3 P and Ph2 O, with which the LAs form a Van der Waals complex, is similar to that of THF. Addition of one Cl atom at position 5 to increase back strain (see structures 8 and 10 versus 7 and 9) results in a stronger H− affinity by 2.5–3 kcal mol−1 . Moreover, LAs 9 and 10 are weak H− acceptors and their corresponding LA-H(−)…(+) H-LB ion pairs are supposed to release an H2 molecule. On the other hand, the back strain results in a larger deformation in the LA structure; its effect on decreasing the complexation energy is more visible with less donating LBs such as THF. In 11 (the bulkiest alkylated LA), the congestion around the boron atom is large. The C–H bonds are almost perpendicular to the BCCC plane so that the hydrogens shield the boron. According to previous experimental investigations, considerable steric shielding of the boron center imparted by the large CH(C6 F5 )2 ligands hinders access to the Lewis base and results in a weak borane LA. The H− affinity of 11 is nevertheless stronger than that of the LAs 7 to 10. This means that the C6 F5 rings can induce their electronegativity to the B atom despite the extra C–H groups, and make it more electrophilic than the LAs 7 to 10. None of the LBs form a dative-bond with 11. Instead, 12 (the strongest alkylated LA) forms a dative-bond with all LBs, showing the strongest interaction with Me3 P. The Lewis basicity of the LBs can be estimated from the strength of the dative-bond to 12. The influence of electronic and structural factors on the G‡ of the H2 activation (i.e., on the reaction kinetics) and on the overall G (i.e., the thermodynamics of the reaction) were also examined. Figure 5.4 shows the calculated free energy profile for the tBu3 P and THF (two typical examples of P- and O-based LBs) with LAs 1 to 11 depicted in Fig. 5.2. For tBu3 P, three extra LAs have been included that were obtained by gradually replacing C6 F5 rings with C6 H5 , i.e., B(C6 F5 )2 C6 H5 , B(C6 F5 )(C6 H5 )2 , and B(C6 H5 )3 , I-III. In this way, the electrophilicity of the LAs systematically decreases by removing the F atoms. For stronger LAs, which means a lower LUMO level of the LA, the free energy profile is strongly exergonic, e.g., G of the ion-pair is –10.19 kcal mol−1 for LA 1 and –18.60 kcal mol−1 for LA 2. However, the free energy profile gradually shifts toward endergonic with FLPs including weaker LAs, e.g., G is around 0.30 kcal mol−1 for B(C6 F5 )2 C6 H5 and 14 kcal mol−1 for B(C6 H5 )3 . The lower panel of Fig. 5.4 shows calculated free energy profiles of THF and LAs 1 to 11. For THF, all H2 splitting reactions are endergonic, and altering the electronic structure of the LA by removing the F atoms changes the G to more positive values. This is important when the activation of H2 is followed by hydrogenation and proton transfer to another LB in the system (e.g., O of C = O

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185

BCF B(p-C6F4CF3)3 B(C6F5)2{3,5-(CF3)2C6H3} B(C6F5)2(C6Cl5) B(C6F5)(C6Cl5)2 B(C6Cl5)3 B(C6F4H)2(C6Cl2H3) B(C6F4H)2(C6Cl3H2) B(C6F3H2)2(C6Cl2H3) B(C6F3H2)2(C6Cl3H2) B(CH(C6F5)2)3 B(C6F5)2(C6H5) B(C6F5)(C6H5)2 B(C6H5)3

tBu3P

THF

LA/LB complex

TS

Ion pair

Fig. 5.4 Calculated free energy profiles of the tBu3 P and THF with LAs 1 to 11 depicted in Fig. 5.2. For tBu3 P, three extra LAs are included that were obtained by gradually replacing C6 F5 rings with C6 H5 , i.e., B(C6 F5 )2 C6 H5 , B(C6 F5 )(C6 H5 )2 , and B(C6 H5 )3 , I-III. The less electronegative LA corresponds to a higher minimum energy path Figure adapted from Ref. [102].

group), according to the literature [28–30]. It is also illustrated that Lewis acidity and electrophilicity of the LA can have opposite effects. This means that for LAs with strong electrophilicity (H− affinity), the Lewis acidity (e.g., dative complexation to a small LB like Me3 P) is weak due to the bulkiness and strain in the structure of the LA. Previous studies showed that Lewis acidity is more crucial for decreasing the barrier and G [60]. Since the Brønsted basicity of the ethereal solvents (e.g., THF in Fig. 5.4) is substantially lower compared to the typical amine or phosphine Lewis bases, the hydride affinity of the LA has to be strong enough to activate H2 with a moderate activation barrier. This is in agreement with the experimental result that borane LAs with a smaller number of F atoms are less reactive toward H2 activation. Therefore, for an efficient H2 splitting process and hydrogenation reaction, a balance between electrophilicity (H− affinity) and Lewis acidity is necessary. As examples, in Table 5.1 LA 7 and LA 8 with weaker H− affinity versus LA 4 to 6, but stronger

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Lewis acidity, experimentally proved to be more suitable for hydrogenation of the C = O group due to easier delivery of the hydride to the C(C = O). On the other hand, LA 2 with stronger H− affinity and Lewis acidity than BCF is not a good candidate for hydrogenation of the C = O group because of the lower tendency for hydride release. The thermodynamics of the H2 activation by strong LA and LB fragments, leading to a highly polar product-ion pair (LA—H(−)…(+) H—LB), is strongly affected by condensed phase interactions, being solvation or crystal field effects. Solvent effects can cancel the entropic penalty of the ion-pair formation and strongly stabilize the product complex [62]. Although, in case of weak LBs (such as ethereal solvent molecules), in which the product-ion pair is not highly polar, solvation does not provide a large reduction of G [61, 63]. The crystal fields of solid FLPs can provide an extra stabilization of the zwitterionic products of H2 activation. Theoretical studies showed that reaction energies are more negative in the solid state than in the gas and solution phases for several H2 activation reactions [64].

5.3.4 Ethereal Solvents as Lewis Bases Recent experiments have shown that ethereal solvents are able to activate H2 and catalyze hydrogenation of C = O compounds in combination with boron LAs [28– 30]. The proposed FLP mechanism for activation of H2 and hydrogenation of the C = O group is depicted in Scheme 5.8, in which the borane and ketone or ethereal solvent act as an FLP to activate H2 . The major advantage of O-based LBs is the possibility of proton-delivery to another O-based LB that can be used in the hydrogenation of ketones, which does not happen with strong N- or P-bearing LBs. An alternative mechanism for the splitting of H2 and subsequent facile hydrogenation of carbonyl compounds has been proposed in a series of studies by Privalov et al. The mechanism starts with the activation of the C = O group by complexation of a Lewis or Brønsted acid to the oxygen of the C = O (Scheme 5.9 and 5.10) [65–68]. According to TS calculations and electronic structure analyses, the carbon atom in the activated carbonyl is electron-deficient enough so that it can function as a secondary Lewis acid center. The secondary Lewis acid center is capable of splitting H2 with the assistance of an ethereal solvent molecule acting as the Lewis base (panel !-

H2 + LB R C6H 5

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Scheme 5.9 Proposal of a plausible reaction path starting from a BCF-ketone adduct, i.e., Lewis acid activation of C = O, involving a BCF-alkoxide intermediate

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Scheme 5.10 Proposed mechanism of proton-catalyzed H2 splitting: a Brønsted acid activates the carbonyl carbon of a ketone, and the H2 splitting takes place by the assistance of the Lewis basic solvent molecule (LB˝). In the [LB´-(+) H… acetone + LB˝] molecular complex, LB´and LB˝ do not necessarily have to be the same. The typically dominant contribution of C(carbonyl) to the π*-type LUMO of the carbonyl group is also schematically shown

2 in Scheme 5.9). The formation of alcohol products from carbonyl compounds takes, therefore, place in a smaller number of steps than with a standard FLP mechanism because the hydride-transfer step is omitted. TS calculations show that energetically the activated carbonyl route resembles the FLP mechanism [65]. The activated C = O can be produced either via Lewis/Brønsted acid complexation or by hydrogen bond formation between the oxygen atom of a carbonyl group and a hydrogen bond donor. Calculated energy profiles showed that only activation of C(C = O) is not enough for heterolytic H2 splitting and assistance of a mildly basic ethereal solvent (e.g., 1,4-dioxane, THF, or Et2 O) is essential. A ketone sharing a proton with a solvent molecule is a common feature of present FLP mechanistic proposals for C=O hydrogenation. Thus, the FLP mechanism of carbonyl hydrogenation reactions in Lewis basic solvents might actually include a route that is fundamentally different. The mechanism of a one-step transformation of a ketone to the corresponding alcohol with complete recovery of the solvent-bound proton that induces Lewis acid character of the carbonyl carbon of the substrate (ketone) is depicted in Scheme 5.10. The novelty of the results presented above is in the solvent-assisted hydride-type attack of the polarized H2 molecule on the activated carbonyl carbon atom. The polarization of H2 occurs due to a combination of interactions between the electrophilic carbonyl carbon atom and the Lewis basic solvent. We note that hydrogen bond activation of the C = O group is a weak type of activation that polarizes the C = O bond less than other types of activation (Lewis and Brønsted acid complexation), and thus the transition state barrier is higher in this case [67].

5.3.5 The Role of Water Molecules Although FLP-catalysis has the advantage of exploiting main-group elements instead of toxic, rare or expensive transition metals, the strong Lewis acidity of boron in BCF and its LA analogs can be seen as an obstacle. In particular, boron’s oxophilicity and strong interaction with water and other coordinating substances in the reaction medium has thus far limited the majority of FLP-catalysis to anhydrous reaction

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conditions. Water-tolerant FLP catalysis is an emerging and developing direction in FLP chemistry [69–82]. There have been significant and (partially) successful efforts aiming to reduce the water-sensitivity by modifying the functional groups that coordinate the boron LA-center. For example, Soós et al. have developed new derivatives of BCF by tuning the electron-deficiency of the boron center and increasing the strain in the Lewis acid structure to reduce the complexation propensity with water [61, 71, 78]. Ashley and coworkers have used higher H2 pressures and reaction temperatures in hydrogenation reactions [79, 80]. Repo et al. have shown that sterically hindered phosphinoborane could be stable in water [81]. Recent experimental studies have shown that ethereal solvents (e.g., dioxane, THF, and Et2 O) act as LB for hydrogen activation in the hydrogenation of carbonyl compounds due to their large excess in solution. The Lewis base role as an electrondonor can also be performed by water. In a recent theoretical study, water has been considered as an active Lewis base (LB) in the H2 splitting and subsequent hydrogenation of the C = O group in wet ethereal solutions [82]. A strongly stabilized borohydride/hydronium intermediate in the hydrogenation mechanism was indicated computationally. The proposed borohydride/hydronium intermediate with the hydronium cation having three OH… ether hydrogen bonds or a combination of the OH… ether/OH… ketone hydrogen bonds (Fig. 5.5), appears to be as valid as the previously considered borohydride/oxonium (BCF-H(−)… ether-H(+) -ether) or borohydride/oxocarbenium (BCF-H(-)… ether-H(+) -ketone) intermediates (Scheme 5.8). This study showed that (1) the minimum energy path of H2 splitting via a borohydride/hydronium intermediate changes to exergonic in comparison to the routes via a borohydride/oxonium or borohydride/oxocarbenium intermediate, which are highly endergonic; (2) the proton-coupled hydride transfer from the borohydride/hydronium to a ketone has a reasonably low barrier. It is noteworthy to mention that strong LBs, such as amine or phosphine, can grab the acidic proton of the activated water molecule (throughout complexation of water to the BCF) and form the deactivated BCF-OH− anion. However, this is not the case when the LB is an ethereal solvent molecule with rather small pK a of protonated LB, e.g., for 1,4-dioxane pK a has been measured − 2.92 in aqueous solution [80]. Hence, the possibility of strong hydrogen bonding with ethereal solvent is more dominant than deprotonation of water. Figure 5.6 shows the calculated transition states structures of the H2 splitting (TSHH ) in panel a, and hydride transfer (TSHT ), panel b, with water as the active LB in the hydrogenation reaction of acetone in wet dioxane solvent.

5.4 Mechanistic Studies Using AIMD Simulation The first dynamics investigation of intermolecular FLPs was reported in 2012 by Pápai and coworkers, who investigated the association of the intermolecular tBu3 P/BCF FLP in toluene. Using classical molecular dynamics simulations with explicit solvent, they found a fast dynamic equilibrium between the separated donor and acceptor states and the paired donor… acceptor state. No significant free energy

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Fig. 5.5 The calculated free energy profile for the wet-ether FLP-mechanism of carbonyl hydrogenation (see also Scheme 5.8) with water as the main active Lewis base (LB) instead of the ether. The TSHH and TSHT are the transition states of the heterolytic H2 activation and the hydride transfer to the protonactivated C(carbonyl), respectively. The zero-energy reference is the sum of the free reactant molecules; “Product” denotes the product complex including the non-coordinated BCF and the alcohol with the alcohol… water… ethers hydrogen-bonds; “SM” stands for “solvent molecule” (ether). All relative free energies are in kcal mol−1

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a)

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TSHT with the active water

Fig. 5.6 Calculated transition states structures of the H2 splitting, TSHH (a), and the hydride transfer, TSHT (b), with water as the LB in the hydrogenation reaction of acetone in wet dioxane

barrier separated these two states [38]. Later, Ab Initio (DFT) Molecular Dynamics (AIMD) and metadynamics simulation techniques have been applied to model FLPcatalyzed H2 activation by the groups of Privalov and Ensing. In the next section, we will briefly summarize these studies.

5.4.1 Transition State Characterization by Ab Initio Molecular Dynamics Simulations H2 cleavage by the prototypical Bu3 P/B(C6 F5 )3 FLP was studied by Privalov et al. using AIMD simulations at room temperature [83]. Their results showed that the VdW complex of the solvent-caged [tBu3 P + H2 + B(C6 F5 )3 ] system initiated activation of H2 at a larger phosphine-borane separation than previously thought, i.e., ca. 6 Å rather than less than 5 Å. The VdW-state of the LB/LA + H2 systems was typically classified as “non-active” in static gas-phase models. However, these AIMD simulations showed that there are configurations with P… B distances larger than 5 Å providing suitable conditions for H2 activation. The solvent-caged tBu3 P and B(C6 F5 )3 have no molecular partners to interact with other than H2 . This indicated that the solvent-cage allows for a larger effective mobility of H2 inside the FLP pocket that causes more effective collisions between H2 ↔ tBu3 P and H2 ↔ B(C6 F5 )3 than would be the case without a solvent-cage. Another remarkable result of this study was a trajectory of the system trapped in the TS-region for a sub-picosecond period of time. This insight could be helpful for reaction rate measurements and attempts to detect the transient LB… H2 … LA states with ultrafast spectroscopic techniques in solution. The reaction dynamics of the reaction tBu3 P + H2 + B(C6 F5 )3 → tBu3 P-H(+) (−) + H-B(C6 F5 )3 at room temperature has been the subject of a detailed AIMD

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analysis [84]. The dynamical picture of this reaction resembles a three-body reactive system. Starting from configurations at the transition state of the reaction, the authors observed trajectories in which the system remained in the transition state region for an average period of 350 fs. The authors concluded that the reaction rate of H2 activation is influenced by a conformational inertia of the LA… LB pocket at the transition state. This conformational inertia is affected by the overall molecular masses of the LB and LA molecules. Hence, isotopically heavier Lewis base/Lewis acid pairs (in comparison to normal counterparts) may give measurably slower reaction rates. Thus, the predicted quasi-bound (TS) state could be verified by experimental femtosecond spectroscopy. The mechanism of H2 liberation from the LB—H(+) + H(–) —LA ion pair has been investigated in another reaction dynamics study by Pu and coworkers [85]. According to experiment, the frustrated Lewis pair (o-C6 H4 Me)3 P and B(p-C6 F4 H)3 heterolytically splits H2 at 25 °C, after which an (o-C6 H4 Me)3 P—H(+) + H(–) — B(p-C6 F4 H)3 ion-pair intermediate liberates H2 under static vacuum and 25 °C [86]. The FLP (o-C6 H4 Me)3 P/B(p-C6 F4 H)3 is a rare example, since the majority of FLPs efficiently cleaves H2 . AIMD simulations, starting from an (o-C6 H4 Me)3 P— H(+) + H(–) —B(p-C6 F4 H)3 ion-pair configuration, showed a short-lived transient LB… H2 … LA species. This species structurally resembles the calculated transition state (TS) in the minimum energy path of the reversible reaction between FLP (oC6 H4 Me)3 P/B(p-C6 F4 H)3 and H2 . Using an Energy Decomposition Analysis (EDA) on the structure of the transition state, (o-C6 H4 Me)3 P… H… H… B(p-C6 F4 H)3 ), a rather strong interaction between LB—H(+) and H(–) —LA (cationic and anionic) fragments was detected that promotes the H… H recombination process. This interaction between the cationic/anionic fragments is much reduced in case of the more standard tBu3 P/BCF FLP. Furthermore, the EDA results showed that in the TS-structure, the interplay of orbital interactions and electrostatic interactions between H… H and LA/LB fragments cancels the Pauli repulsion and stabilizes the TS-structure.

5.4.2 AIMD Simulation of Solvated Ion-Pairs The mechanism of FLP-catalyzed C=O hydrogenation, depicted in Scheme 5.7, passes through a [solvent-H(+) -O(solvent)][BCF-H(–) ] complex and a [solvent-H(+) ketone][BCF-H(–) ] complex, which are intermediate precursors for the hydride transfer. The dynamic behavior of these ion pairs at finite temperature was recently investigated using unbiased AIMD simulations [87, 88]. These simulations were aimed at, among other things, unraveling the possible locations of the solvated proton with respect to the hydride in these [solvent-H(+) -O(solvent)][BCF-H(–) ] and [solvent-H(+) -ketone][BCF-H(–) ] intermediates. The distance between H(–) and H(+) in these intermediates controls the mechanism of hydrogenation of the C = O group. In particular, the authors uncovered a new configuration with a cationic fragment, [BCF-H(–) ], docked from behind with respect to the direction of the B → H vector, i.e., a face-to-back configuration with a proton… hydride distance of

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Fig. 5.7 Optimized geometry of face-to-face (a) and face-to-back (b) configurations for [dioxaneH(+) -dioxane][BCF-H(–) ]. All distances are in Å. The dashed line shows the distance in each case

about 6 Å. Figure 5.7 shows the optimized geometry of a face-to-face (proposed previously in literature) and a face-to-back (reported in this study) configuration for [dioxane-H(+) -dioxane][BCF-H(–) ]. Since energetically there is no preference between the two configurations of the cation/anion complexes, the interconversion between the configurations is likely at finite temperature. This is in line with the observed face-to-back isomer of the ionpair composed of Cy3 P-H(+) and LA-H(–) fragments using X-ray crystallography, reported by Stephan et al. [86]. The possibility of the face-to-back configuration of the intermediate ion pairs and long distance between the hydride and carbonyl carbon paves the way for the alternative pathway of splitting of H2 at the activated carbonyl carbon by a proton (Scheme 5.10) [66]. AIMD simulations at the finite temperature of the [solvent-H(+) -ketone][BCF(−) H ] ion-pair showed that, starting from a face-to-face configuration, the cation/anion fragments initially remain at a relatively large H(–)… C(C = O) separation, for a period of time in the range between 10 and 100 ps. After several initial large amplitude motions between the fragments, ranging from 2.5 to 6.5 Å, the hydride transfer from [BCF-H(−) ] to the C(C = O) in [solvent-H(+) -ketone] takes place and the product-alcohol is formed, in which the H(−)… C(C = O) reduces to a typical C–H bond distance. For the formation of the product-alcohol, the [BCF-H(−) ] has to come into the proximity of the [solvent-H(+) -ketone] cation, with a proper H(−)… C(C = O) distance (less than 2.5 Å) and a BH(−) C(C = O) angle (i.e., a so-called Bürgi–Dunitz angle between 90° and 110° for nucleophilic attack on the ketone C(C = O)).

5.4.3 Free Energy Landscape of the FLP Catalyzed H2 Activation Liu et al. explored the H2 activation reaction using DFT-based metadynamics simulations [56]. On the basis of the calculated free energy surface, they concluded that

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the H2 activation by tBu3 P and B(C6 F5 )3 is a multiple-step process consisting of (1) polarization of H2 , (2) hydride transfer, and (3) proton transfer. Furthermore, they found different roles taken by the Lewis acid and Lewis base centers in the H2 activation. The authors found that first the hydride transfer step to the Lewis acid center takes place. This is followed by a proton transfer to the Lewis base center. The former step is the rate-limiting step in the H2 activation process (Fig. 5.8). They also confirmed that the ET and EF models are complementary to each other, i.e., at a larger distance of H2 from the Lewis pair centers the Electrostatic Field (EF) of the LA/LB polarizes H2 . When the H2 molecule is closer to the LA/LB centers, an electron transfer from H– to LA and from LB to H+ takes place. In a very recent work by Pápai and coworkers, static and dynamic models of H2 splitting were compared by employing DFT-based metadynamics simulations [89]. The authors considered three H2 activation reactions that involved three intramolecular Frustrated Lewis Pairs (FLPs), which have been well-studied both experimentally and computationally. The three selected systems are shown in Scheme 5.11. The set of covalently linked FLPs were the ethylene-linked phosphine-borane 1 developed by Erker et al. [54], the molecular tweezer amino-borane 2 introduced by Repo et al. [90], and geminal P/B pair 3 reported by Slootweg et al. [91]. With this selection of intramolecular FLPs, they focused on the H2 activation process (thus excluding the preorganization and encounter complex formation steps). Based on the computed free energy surfaces, the authors concluded that the heterolytic H2 splitting process is a single, concerted, step as described by static-DFT models. They also performed a statistical analysis of a large number of reaction trajectories initiated from the transition state region. This demonstrated a notable asynchronicity in the formation of donor-H and acceptor-H bonds, in which the acceptor-H bond is formed first. Pápai and coworkers concluded that the important consequence of asynchronicity is that

a

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) d HH (angstrom

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Fig. 5.8 a The minimum free energy path in the 3D space spanned by the H–H distance and the B-H and P–H coordination numbers. b The free-energy profile of H2 activation by the tBu3 P/B(C6 F5 )3 Lewis pair calculated with path-metadynamics simulation. The values of the free energies are shown in parentheses in kcal mol−1 . Points a–d show the reactant complex (A), the first intermediate after hydride transfer to boron (B), and the hydrogenated products with two orientations of the charged fragments, (c and d), respectively

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Scheme 5.11 The intramolecular FLPs studied by Pápai et al. with metadynamics simulations for H2 activation

most of the excess kinetic energy (reaction heat) due to H2 activation is accumulated in donor-H-bond vibrations. This results in enhanced reactivity of the donor-H site in a subsequent catalytic proton transfer step. Furthermore, the authors assessed the validity of the reactivity model proposed by static DFT [53] on the basis of AIMD simulations.

5.4.4 Participation of Multiple Solvent Molecules AIMD simulations allow for investigation of the role of solvent, by sampling explicitly the solvent molecular configurations in a canonical ensemble. Heshmat and Privalov used AIMD to study a molecular cluster consisting of a Me2 C = O–-BCF complex (i.e., a carbonyl group activated by the BCF Lewis acid), an H2 molecule and 13 solvent (dioxane) molecules explicitly solvating the Me2 C = O-BCF and H2 reactants [92]. Starting from an optimized geometry of the system, the H2 is seen to stay at the Van der Waals-range from C(carbonyl) and O(dioxane). The authors

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reported continuing perturbations of the H–H bond length due to concerted interactions between O(dioxane)↔ H2 and H2 ↔ C(C = O). Consequently, the H–H bond was elongated up to 0.88 Å. In Fig. 5.9, AIMD-snapshots of the encounter complexes are shown that represent distinct phases of the VdW-interactions between O(dioxane) with H–H and C(C = O) with H–H. For simplicity, only a few solvent molecules are shown. In Fig. 5.10, the distances of the four O(dioxane)… C(C = O) versus simulation time is plotted. This figure shows at various simulation times, a different O(dioxane) is close to the C(C = O). The main conclusion is that the multi-molecular nature of the solvent-involvement takes part in the reaction coordinate, which is hidden in static calculations. This is due to the omnipresence of the solvent molecules in solution, which continuously move and interact with H2 . This is not the case in comparison to the P-based LBs (tBu3 P). The interaction of various dioxane molecules with H2 throughout the AIMD simulations indicated that the reaction coordinate is more complicated than in the case of a singly interacting LB, such as tBu3 P.

Fig. 5.9 AIMD-snapshots representing distinct phases of VdW-interactions between different solvent molecules, O (dioxane), with H–H and C(C = O) with H–H. Distances are in Å

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t (fs) Fig. 5.10 Plots of C(C = O)… O(dioxane) distances versus time for the four dioxane molecules that are in the closets proximity of H2 . The labeling of the dioxane oxygen atoms is the same as in Fig. 5.9

5.5 Lewis-Pair-Functionalized Metal–Organic Frameworks (MOFs) and Their Applications Implementation of metal-free FLP catalysts faces the same concerns as other homogeneous catalysts: stability, recyclability, and catalyst-product separation. Recent calorimetric and kinetics experiments have shown that entropic effects play an essential role in the formation of the complex between the Lewis acid, H2 , and the Lewis base in solution. This means that entropic penalties strongly affect the thermodynamics and the rate of the H2 activation in solution [93]. It is for these reasons that the notion of exploiting FLPs in the solid phase to support heterogeneous FLP catalysts is an attractive topic that has been proposed and examined recently [64, 94–96]. To this end, employing Lewis-pair-functionalized Metal–Organic Frameworks (MOFs) in which the Lewis pairs are covalently bonded to the MOF as a solid platform to fix Lewis pair centers have been recently proposed computationally and utilized in experiments to capture, convert, and reduce multiple bonds of small molecules [97–99].

5.5.1 Computationally Proposed LP-Functionalized UiO-66 for CO2 Hydrogenation Lewis pair-functionalized UiO-66 has been proposed for the first time in 2015 by Johnson and coworkers in a computational study to develop novel nanoporous materials for CO2 capture and conversion from flue gas (Fig. 5.11) [97]. They focused

5 Mechanistic Insight into the Hydrogen Activation by Frustrated Lewis Pairs Fig. 5.11 The Lewis-pair-functionalized UiO-66 MOF for the capture and conversion of CO2 as proposed by Johnson and coworkers in a computational study in 2015

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on the UiO-66 MOF because it is chemically and thermally stable, selective toward CO2 adsorption over N2 , and can be readily functionalized via various approaches. The LP moiety is covalently attached to the 1,4-benzenedicarboxylate (BDC) linkers of the UiO-66 framework. Static-DFT calculations provided design strategies for efficient catalysts for CO2 reduction. The resulting functionalized MOFs were very stable and could have enhanced catalytic activity due to stabilization or protection of the catalytic complexes. Johnson and coworkers designed and screened many LPs for their aim to heterolytically dissociate H2 into hydridic and protic species. They computed energetics and barriers for hydrogenation of CO2 through a concerted 2-H addition to making formic acid [98]. They also computed reaction pathways for CO2 to methanol through a series of 2-H addition steps. Johnson and coworkers screened five different classes of functional groups, to test the hypothesis that changing the acidity or basicity of the LP moieties tunes the relative binding energies of CO2 and H2 . They found that the binding energies could be tuned by changing the acidity and the geometry of the LP functional groups. However, the functional groups that had strong H2 binding energies showed prohibitively large barriers for CO2 hydrogenation. In another work by Johnson and coworkers, a Lewis-pair (LP)-functionalized MOF was proposed as a heterogeneous porous catalyst for direct hydrogenation of CO to CH2 O from a mixture of CO and H2 , followed by condensation of CH2 O [99]. CH2 O formation is not equilibrium limited because the barrier for desorption from MOFs is much lower than that for the reverse reaction. Hence, CH2 O is continuously removed from the process, rendering high overall conversion rates. The computed reaction pathways and barriers for CO hydrogenation predicted that the thermodynamics of CH2 O synthesis was enhanced relative to gas-phase synthesis. Their calculations indicated that CO hydrogenation is more favorable inside MOF pores

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Fig. 5.12 Schematic representation of the LP-functionalized MOF for activation and conversion of small molecules

due to entropic considerations. The entropy for the conversion of CO to CH2 O is very negative in the gas phase (–109 J mol−1 K−1 at standard conditions). However, the entropy change in LP-functionalized MOF due to the confinement of the adsorbed substrate molecules on the LP centers is less negative than in the gas phase and this increases the entropy of conversion to 4 J mol−1 K−1 . In addition, the authors showed that the LP catalyst incorporated into the MOF is able to reduce the hydrogenation barrier by ca. 46 kcal mol−1 with respect to the non-catalytic pathway. After the predictions from the computational studies on LP-functionalized MOFs, the first experimental proof that MOFs can be successfully used to covalently bind LPs (classical and frustrated) came from Ma and coworkers (Fig. 5.12) [100, 101]. Furthermore, the catalytic performance of the MOF-LP was demonstrated to be excellent with good size and steric selectivity. Ma et al. grafted DABCO and B(C6 F5 )3 as the Lewis base and acid, respectively, into MIL-101 (Cr). The MIL-101(Cr)-LP efficiently catalyzed the imine reduction with high size and steric selectivity. Moreover, MIL-101(Cr)-LP directly hydrogenated alkylidene malonates under H2 environment. Excellent stability, recyclability, size, and steric selectivity were reported because of the confinement imposed by the porous MOF structure.

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5.5.2 AIMD Simulations on LP-Functionalized MOFs Unraveling the reaction path was the aim of a recent metadynamics/AIMD study, in which Heshmat and coworkers studied the reaction of CO2 + H2 → HCOOH, inside the cavity of a Lewis-pair (LP)-functionalized UiO-66 MOF. Figure 5.13 shows the optimized structure of the unit cell of UiO-66 with a singled out BDC linker (I) and its LP-functionalized primitive cell (II). The MOF functions as a periodic scaffold to fix the Lewis pairs at the solid–solvent interface. We note that the MOF atoms do not take part in the reaction mechanism. The LPs are covalently bound to the MOF at specific sites in a manner that access to the Lewis pairs is without steric hindrance and mutual quenching of LP moieties is prevented. Utilizing MOFs as a solid substrate for Lewis pairs is a practical way to apply the catalytic functionality of LP centers in a heterogeneous setting to overcome the usual drawbacks of homogeneous Frustrated Lewis Pair (FLP) catalysis related to stability, recyclability, and catalyst-product separation. In the current example, binding the LP centers to the BDC linkers of UiO-66 by a methyl group prevents migration and association of the LP centers. The Free Energy Surface (FES) of the entire formic acid formation reaction, catalyzed by the LP-functionalized UiO-66, shows a more eventful reaction mechanism than previously proposed from static-DFT calculations. The conformational flexibility around the Lewis pair centers, incorporated into the UiO-66 MOF, allows for different pathways of hydrogenation of CO2 , which were not seen in previous static-DFT calculations.

a

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Fig. 5.13 Optimized structure of the unit cell of UiO-66 with the BDC linker indicated by a circle (a), and the LP-functionalized primitive (b). Panel (c) shows the structure of the intramolecular Lewis pair covalently bound to the BDC linker via a CH2 group

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Trans conformation of HNBH

Cis conformation of HNBH

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LA LB

Fig. 5.14 Two conformations of the LP-functionalized BDC linker (other UiO-66 framework atoms not shown for clarity) with different HNBH dihedral angles. In the trans conformation, the H… H distance is too long for H2 formation. The LA and LB centers are indicated with “B” and “N”, respectively

The AIMD simulations start from a free H2 molecule nearby the Lewis pair (LP) centers, i.e., the N and B atoms, covalently bonded to the UiO-66 BDC linker. In the dissociated H2 state, with the N–H and B–H bonds formed at the LP, the HNBH dihedral angle is very flexible and the H–B bond rotates freely around the NB bond (Fig. 5.14). By rotation around this dihedral, the conformation changes from cis (N– H and B–H in the same direction) to trans (N–H and B–H in the opposite direction) and vice versa. Figure 5.15 shows the calculated FESs starting from both trans and cis conformations. The trans conformation leads to an alternative stepwise mechanism for the hydrogenation of CO2 . The stepwise mechanism starts with hydride transfer to the carbon of CO2 and is then followed by proton transfer to the oxygen of CO2 . In the concerted mechanism, which starts from the cis conformation, hydride transfer to the CO2 carbon and proton transfer to CO2 oxygen take place simultaneously. Comparison of the energetics of the stepwise and concerted mechanisms indicates that the stepwise mechanism has a slightly lower barrier than the concerted mechanism, by 0.5 kcal mol−1 . The CO2 hydrogenation is endergonic in both mechanisms. Furthermore, the FES is rather flat around the reactant state in the cis conformation. To summarize this section, we note that the instability of most FLP catalysts upon recycling unavoidably leads to the loss in catalytic activity. This restricts the industrial applications of FLP catalysts. Introducing the catalysts into porous materials is a straightforward method to gain better recycling performance and catalytic efficiency. Metal–organic frameworks, which are porous crystalline materials, have demonstrated outstanding potential in catalysis since they have tunable pores and walls that can be functionalized. MOFs are, therefore, promising materials to support LP centers and provide scaffolds to stabilize them.

5 Mechanistic Insight into the Hydrogen Activation by Frustrated Lewis Pairs

H

B -33.1

H

a

b

C -48.0

D -50.4

H

C(CO2) Å

A -54.0

E -29.0

F -43.5

H

BÅ

c

0.0 -5.0 -10.0 -15.0 -20.0 -25.0 -30.0 -35.0 -40.0 -45.0 -50.0

C(CO2) Å

0.0 -5.5 -11.0 -16.5 -22.0 -27.5 -33.0 -38.5 -44.0 -49.5 -55.0

201

d

O(CO2) Å

e

f

Fig. 5.15 Left panel: FES of the CO2 hydrogenation following the stepwise mechanism starting from the HNBH dihedral in the trans conformation. Right panel: FES of the concerted mechanism of hydrogenation of CO2 , starting from the cis conformation. The energy values are in kcal mol−1 . Contour lines are spaced at 1.5 kcal mol−1 . Structures a–c show the reactant complex, transition state, and product complex, respectively, starting from the trans conformation. Structures d–f show the reactant complex, transition state, and product complex, respectively, starting from the cis conformation

5.6 Summary and Outlook During the past decade, commercial interest in FLP reactivity has been triggered by its lower toxicity, distinct functional group tolerances, and reduced catalyst and product purification costs. Practical applications of FLP catalysis in synthetic organic and inorganic chemistry are now developing and new mechanistic insights are emerging. In this chapter, both inter- and intramolecular FLPs are considered and various mechanistic pathways of H2 activation are discussed. PES calculations of intermolecular FLPs showed that stabilization due to formation of the encounter FLP complex is ca. 15 kcal mol−1 . However, the entropic penalty lowers the possibility of a LA… LB molecular complex in solution. The endergonic encounter complex formation of the Lewis acid and base points to a low probability of the associated complex in solution. The initial encounter complex of LA/LB, can be a VdW-adduct or a Lewis-adduct. The interaction energies between the two LA/LB fragments in Lewis- and VdWadducts are typically within the same order of magnitude. However, the distance between the reactive centers can vary dramatically from 1.6 Å to 6.0 Å. On the other hand, for intramolecular FLPs in particular, the energy required to weaken the interaction between the LA and LB centers, the geometrical bulkiness, and the conformational flexibility of the LA and LB centers play a role in the formation of an efficient intramolecular FLP.

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EDA and FMO analysis of the TSs of H2 activation by FLPs indicated that both electrostatic interactions and orbital interactions are essential to compensate the Pauli repulsions and form a stable TS molecular complex. Moreover, it turned out that a combination of HOMO [LB + H2 ] interacting with LUMO [BCF] and LUMO [H2 + BCF] interacting with HOMO [LB] is more favorable (energetically) than pure occupied σ and empty σ* MOs of H2 interacting with the HOMO and LUMO of FLP. DFT-based metadynamics simulations demonstrated that when H2 is far from the LA/LB centers, the H–H bond is polarized mainly through the electric field created by the FLP. However, when H2 is closer than 2.5 Å to the LA/LB centers, the electron transfer between FMOs of H2 and FLP dominates. Splitting the H2 molecule by an activated carbonyl carbon as a Lewis acidic center has been examined with TS calculations and it was indicated that the solvent-assisted hydride-type attack of the polarized H2 molecule on the activated carbonyl carbon atom can be considered as an alternative reaction route. Activated (polarized) carbonyl carbon is formed by complexation of the C = O group to a Lewis or Brønsted acid or through the formation of H-bond with an H-bond donor in solution. It is computationally demonstrated that considering water as an active Lewis base in the FLP mechanism in wet ethereal solutions produces a strongly stabilized borohydride/hydronium intermediate in the hydrogenation mechanism of ketones. The minimum energy path of H2 splitting via this borohydride/hydronium intermediate changes to exergonic in comparison to the routes via a borohydride/oxonium or borohydride/oxocarbenium intermediates, which are highly endergonic. Various aspects of dynamical behavior of FLP + H2 system, by employing AIMD simulations, were investigated. For example, the flexibility of the [solventH(+) -ketone][BCF-H(−) ] intermediate ion-pair and large amplitude motions of the cationic/anionic fragments with respect to each other is a factor that can change the pathway of H2 activation followed by hydrogenation of the C = O group. Overall, AIMD simulations shed more light on some mechanistic aspects of the H2 activation and hydrogenation reactions that remained unnoticed in static-DFT calculations. For example, the multi-molecular nature of the solvent-involved hydrogenation of ketones in ethereal solutions was observed through AIMD simulations. Presently, most of the FLP catalysis is performed in the solution phase, and most often in organic solvents. This can cause environmental issues due to the volatility of the aromatic organic solvents. Recent experimental support for the generation of higher concentrations of encounter complexes of the FLPs in ionic liquids can lead to potential employment of FLP catalysis in solution with the advantage of using green solvents. On the other hand, transfer of the homogenous catalytic systems into heterogeneous states would overcome the drawbacks in catalyst-product separation, recyclability, and stability. As an example, grafted Lewis pair centers into MOF structures and solid surface materials such as carbon nanotubes may indeed become “game-changers” in the field of FLP-catalysis, and overcoming the gaps and drawbacks of homogeneous FLPs. This means that grafting these catalysts to heterogeneous supports enhances catalyst stability and product-catalyst separation and recyclability and adapts such molecular catalysts for commercial processes. This new paradigm offers enormous potential for further developments in the field of FLP catalysis.

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Chapter 6

Lewis Acidic Boranes in Frustrated Lewis Pair Chemistry Theodore A. Gazis, Darren Willcox, and Rebecca L. Melen

Abstract From their inception, boron-based frustrated Lewis pairs have garnered significant scientific attention thanks to the multitude of potential applications they can be employed in. The ever-expanding library of halogenated triarylboranes has enabled this interest to flourish. In this chapter, we explore the significant breakthroughs that have been achieved in the use of triarylboranes in frustrated Lewis pair chemistry including borane synthesis, water tolerance and chirality. Keywords Borane · Frustrated Lewis pair · Lewis acid

Abbreviations 1

H NMR P NMR 9-BBN AN Ar BPh3 BTPP DIPP DMAP Et Et2 O Et3 PO FLP

31

Proton Nuclear Magnetic Resonance spectroscopy Phosphorus-31 Nuclear Magnetic Resonance spectroscopy 9-borabicyclo[3.3.1]nonane Acceptor Number Aromatic Triphenylborane tert-Butylimino-tri(pyrrolidino)phosphorane Diisopropylphenyl (Dimethylamino) pyridine Ethyl Diethyl ether Triethylphosphine oxide Frustrated Lewis Pair

T. A. Gazis · D. Willcox · R. L. Melen (B) School of Chemistry, Cardiff Catalysis Institute, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK e-mail: [email protected] D. Willcox (B) Department of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK e-mail: [email protected] © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_6

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Methanol Mesityl N-bromosuccinimide Phenyl Benzene Phenyl dimethylsilane Tetrahydrofuran Tetramethylethylenediamine Tosyl

6.1 Introduction The seminal work in the field of frustrated Lewis pair (FLP) chemistry was reported by Stephan in 2006, where it was observed that a borane-based strong Lewis acid and a phosphine-derived Lewis base did not form the corresponding classical Lewis adduct. This work detailed the synthesis of a rigid tetrafluorophenylene-bridged phosphoniumfluoroborate, which was subsequently transformed into the corresponding borohydride (Fig. 6.1a) [1]. Upon heating of the zwitterionic species, molecular hydrogen (H2 ) was liberated, generating a phosphinoborane. The highly rigid linker and the steric bulk of the substituents on the phosphorus and boron moiety precluded the formation of the classical Lewis adduct. Very soon after Stephan’s seminal report,

Fig. 6.1 Seminal reports of FLPs reported by Stephan and Erker

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the Erker group developed a flexible intramolecular ethylidene-bridged phosphinoborane (Fig. 6.1b). Again, this species was capable of activating H2 at room temperature [2]. It became obvious that the combination of steric hindrance of the Lewis pair, coupled with high Lewis acidity and basicity of the FLP components, was responsible for the activation of H2 . Based on these observations, intermolecular FLPs were reported in 2007 together with their catalytic applications in H2 activation [3]. These major breakthroughs have laid the foundation for a field that has garnered much attention over recent years and has inspired chemists to search for new applications [4, 5]. The high importance of this in advancing synthetic main group chemistry is reflected by a large number of reviews and even books published on FLP chemistry [6–15]. This chapter will give an overview of the synthesis and application of Lewis acidic boranes, which have been utilized in FLP-based chemistry. Indeed, the Lewis acidity of the borane used in the FLP is central to the reactivity of the FLP in terms of small molecule activation and catalytic activity. At this point, it is poignant to recap how the Lewis acidity of boranes can be measured. Lewis acidity determination can be classified into three main categories: effective, global and intrinsic metrics (Fig. 6.2) [16]. Effective metrics typically consist of spectroscopic approaches, measuring the effect of the Lewis acid on a probe molecule [17, 18]. Gutmann–Beckett and the Childs methods both fall into this category [19–21]. The Gutmann–Beckett method involves the coordination of triethylphosphine oxide (Et3 PO) to a Lewis acid and recording the change in 31 P NMR resonance. The Lewis basic oxygen in Et3 PO forms an adduct with the borane, thus causing a deshielding of the adjacent phosphorus atom. This perturbation can be measured to ascertain the Lewis acidity by attributing an acceptor number (AN) to the borane. The Childs method correlates the Lewis acidity by measuring the change in the 1 H NMR resonance of the H3 proton in crotonaldehyde upon its complexation to a Lewis acid. From this method, it is possible to measure the relative acidity of the borane compared with boron tribromide (set to 1.0). Global metrics, on the other hand, are computationally derived and consider the whole process of adduct formation. These techniques enable extrapolation of thermodynamic outputs such as intramolecular coordination in the initial Lewis acid (Eintra ), deformation energies and preorganization (Eprep ) in addition to the immediate interaction energy (Einter ). The common examples of this technique are the fluoride ion affinities (FIA) method and the hydride ion affinity (HIA) [22, 23]. FIA calculates the change in enthalpy upon coordination of a fluoride anion (generated from a fluorophosgene precursor) to a free gaseous Lewis acid. HIA, on the other hand, utilizes the isodesmic reaction between superhydride and the borane in question. The final class is intrinsic metrics; these enable the electronic structure of the free Lewis acid to be probed through a combination of quantum-theoretical numbers or spectroscopy in a non-invasive fashion. The main approach utilized for this technique is the Global Electrophilicity Index (GEI) [24], which is based on the propensity of a molecule to take up electron density and as such the ranking of Lewis acidities is not defined with respect to a specific base.

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O P Et Et Et

+

ArF Et Et B ArF P O Et ArF

AN = 2.21 x (δsample − 41.0) Childs Method

Me F

Ar

B

ArF

+

ArF

O

H H

Relative acidity =

H

H Me

ArF B ArF O ArF

ΔH LA→crotonaldehyde ΔH BBr3→crotonaldehyde

Fluoride Ion Affinity (FIA)

COF2 + F COF3 + (LA) (LA) +

COF3 (experimentally observed) (LA)F + COF2 (DFT calculation) (LA)F

F

(overall FIA calculation)

Hydride Ion Affinity (HIA)

H B Et Et Et

F + ArF B ArF Ar

H B ArF ArF ArF

+

Et B Et Et

Fig. 6.2 Common methods for determining the Lewis acidity of boranes

Having established methods to determine the Lewis acidity of a borane, we will now look at how they are synthesized and how this correlates with the catalytic activity of frustrated Lewis pairs.

6.2 Synthetic Routes to Boranes 6.2.1 Homoleptic Halogenated Triaryl Boranes The archetypical borane utilized in FLP chemistry is B(C6 F5 )3 [25] and has prompted the synthesis of numerous other homoleptic boranes with small variations in the number and position of fluorine atoms on the aryl ring. These alterations heavily influence the Lewis acidity of the triarylborane. Generally, these derivatives can easily be synthesized in much the same way as B(C6 F5 )3 , by either using a Grignard or lithiation reaction with the appropriate bromobenzene substrate [26]. Consequently, as shown in Fig. 6.3, boranes B(4-FC6 H4 )3 , B(2,6-F2 C6 H3 )3 , B(2,4,6-

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Fig. 6.3 Synthetic routes to halogenated triarylboranes

F3 C6 H2 )3 , B(3,4,5-F3 C6 H2 )3 and B(3,5-(CF3 )2 C6 H3 )3 were synthesized from the corresponding Grignard reagents with BX3 (X = F, Cl, Br) [27–32], whereas boranes B(2,4-(CF3 )2 C6 H3 )3 , B(2,5-(CF3 )2 C6 H3 )3 and B(2-(CF3 )C6 H4 )3 [33–35] relied upon the reaction of the organolithium reagent with BX3 (X = F, Cl, Br). The organolithium route can also be applied to the synthesis of bulkier analogs possessing perfluorinated naphthyl or biphenyl groups such as B(C10 F7 )3 [36] and B(2-(C6 F5 )C6 F4 )3 [37]. Typically purification is achieved by sublimation. Of note are two boranes that required additional synthetic steps. Firstly, B(2,3,5,6F4 C6 H)3 required an additional purification step with Me2 SiHCl after the Grignard reaction to remove residual solvent [38]. Secondly, B(2,6-(OMe)2 C6 H3 )3 was selectively brominated by N-bromosuccinimide (NBS) at the meta-position to the boron to afford B(3-Br-2,6-(OMe)2 C6 H2 )3 (Fig. 6.4) [39]. Other halogenated boranes including B(4-ClC6 H4 )3 [40] and B(2-F-6-ClC6 H3 )3 [41] have also been synthesized using the appropriate Grignard reagent, whereas B(C6 Cl5 )3 could be made by either of the organometallic intermediates [42, 43]. An exception is encountered with B(3,5-Cl2 C6 H3 )3 , which could not be isolated by conventional methods. Instead, wet solvents were required to decompose the Na[B(3-5-Cl2 C6 H3 )4 ] salt to generate the desired borane in situ [44]. The search for triarylboranes with higher acidity than B(C6 F5 )3 led to the isolation of Lewis super acid B(4-(CF3 )C6 F4 )3 . A slightly modified synthetic approach was applied, whereupon, an aryl copper intermediate, generated from the addition of the Grignard reagent with excess cuprous bromide was reacted with BBr3 in a salt metathesis reaction to generate the desired borane (Fig. 6.5) [45].

Fig. 6.4 Synthesis of B(2,6-(OMe)2 C6 H3 )3 and B(3-Br-2,6-(OMe)2 C6 H2 )3

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Fig. 6.5 Synthesis of B(4-(CF3 )C6 F4 )3 using an aryl copper intermediate

6.2.2 Heteroleptic Halogenated Triaryl Boranes The high reactivity that characterizes the Grignard and lithiation reaction makes the formation of heteroleptic boranes challenging, as limited control can be exerted on the degree of substitution. Therefore, alternative approaches such as the use of metalbased aryl transfer reagents are often used for the synthesis of heteroleptic boranes. O’Hare employed perchloro- or perfluoro- aryl copper reagents to functionalize mono- or di-perchlorophenylboranes to give heteroleptic boranes B(C6 Cl5 )(C6 F5 )2 and B(C6 Cl5 )2 (C6 F5 ) (Fig. 6.6) [41]. A similar methodology was employed to prepare a range of heteroleptic boranes containing the 3,5-(CF3 )2 C6 H3 -functionality (Fig. 6.7) using transmetallation from zinc, copper or lithium to boron. Electrochemical studies undertaken using these boranes allowed the authors to compare the electrophilicity of the boranes with spectroscopic measurements (Gutmann–Beckett) of Lewis acidity. Structural studies showed a twist of the aryl rings away from the trigonal planar boron atom, which is thought to be significant when investigating the Lewis acidity of boranes [42]. An alternate route to heteroleptic boranes involves the use of potassium aryltrifluoroborate salts with the appropriate Grignard reagents (Fig. 6.8). This method-

Fig. 6.6 Synthesis of heteroleptic boranes with the general formula B(C6 Cl5 )x (C6 F5 )3-x (X = 1, 2)

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Fig. 6.7 Formation of heteroleptic boranes containing the 3,5-(CF3 )2 C6 H3 group

Fig. 6.8 Synthetic routes to heteroleptic boranes utilizing potassium trifluoroborate precursors (top and center) and the synthesis of B(C6 F5 )(C6 Cl5 )(3,5-(CF3 )2 C6 H3 ) (bottom)

ology facilitates the isolation of a series of ArB(2,3,5,6-F4 C6 H)2 and ArB(2,3,6F3 C6 H2 )2 boranes, where Ar = (2,6-Cl2 C6 H3 ) or (2,3,6-Cl3 C6 H2 ), respectively (Fig. 6.8 top) [46]. The same methods also enable a range of methylated variants to be synthesized (Fig. 6.8 center) [47]. The first halogenated triarylborane-bearing three completely different aryl rings, B(C6 F5 )(C6 Cl5 )(3,5-(CF3 )2 C6 H3 ), were reported by

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Fig. 6.9 Decomposition pathways

Wildgoose in 2016 and were synthesized from the perchlorophenylborane by treatment with the corresponding Li[3,5-(CF3 )2 C6 H3 ] followed by trimethylsilyl chloride. Methanolysis followed by anion exchange with BBr3 yields the diaryl boron bromide. This species undergoes salt metathesis with 0.5 equivalents of Zn(C6 Cl5 )2 to furnish this unique borane (Fig. 6.8 bottom) [48]. Finally, degradation of BAr3 precursors has led to the isolation of novel heteroleptic boranes. Understanding the decomposition pathways may lead to new borane formation in the future. Piers explored the reaction of chelating diboranes with cumyl chloride to further understand the mechanism of isobutene polymerization catalysts, which used diboranes as coinitiators. The diborane was observed to decompose in the presence of cumyl methyl ether via a protodeboronation route (Fig. 6.9, left) [49]. Decomposition of B(C6 F5 )3 has also been shown to form a methylated triarylborane, as demonstrated by Ziegler (Fig. 6.9, right) [50].

6.3 Boranes with Reduced Lewis Acidity Compared with B(C6 F5 )3 To date, the archetypical borane for FLP-catalysis is the commercially available tris(pentafluorophenyl)borane, B(C6 F5 )3 . Unfortunately, due to the strong Lewis acidity of B(C6 F5 )3 , there are sometimes drawbacks in its applications, namely its incompatibility with sterically uncongested, strong donor-containing functional groups such as ketones, amines and nitriles. In hydrogenation reactions using FLPs, the borane gains the hydride generating a borohydride and the Lewis base gains the proton. If the borane is highly Lewis acidic, such as B(C6 F5 )3 , the activation of hydrogen is more facile, however, the subsequent hydride delivery step will be much slower. This can account for the reduced catalytic activity for some substrates. To overcome the incompatibility of B(C6 F5 )3 with strongly Lewis basic functional groups, several research groups have focused on attenuating the Lewis acidity of the borane through synthesizing fluorinated triarylboranes possessing fewer fluorine substituents. Generally, the reduction in the number of fluorine atoms can ultimately lead to boranes exhibiting reduced Lewis acidity compared with B(C6 F5 )3 (Fig. 6.10). Removal of a single fluorine atom from each of the perfluorinated aryl rings has led to the formation of two different isomeric products, tris(2,3,5,6tetrafluorophenyl)borane [B(p-HC6 F4 )3 ] and tris(2,3,4,5-tetrafluorophenyl)borane

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Fig. 6.10 Borane Lewis acidity. Values in parentheses represent the Lewis acidity compared with B(C6 F5 )3 according to the Gutmann–Beckett test

[B(o-HC6 F4 )3 ] [37, 51]. It was found that both compounds were still highly Lewis acidic. B(p-HC6 F4 )3 exhibited 98% of the Lewis acidity of B(C6 F5 )3 , whereas B(oHC6 F4 )3 was 97% the Lewis acidity based on the Gutmann–Beckett Lewis acidity test. In comparison to B(C6 F5 )3 that underwent nucleophilic aromatic substitution (SN Ar) at the para-position of the C6 F5 ring when less sterically demanding phosphines were employed, B(p-HC6 F4 )3 was more stable toward SN Ar due to the absence of fluorine in the para-position [37]. Through the removal of two fluorine substituents from each of the aryl rings, five isomeric homoleptic boranes are possible, however, only three of them have been reported including tris(3,4,5-trifluorophenyl)borane [B(3,4,5F3 C6 H2 )3 ] [27], tris(2,4,6-trifluorophenyl)borane [B(2,4,6-F3 C6 H2 )3 ] and tris(2,4,5trifluorophenyl)borane [B(2,4,5-F3 C6 H2 )3 ] [52]. Of these B(2,4,6-F3 C6 H2 )3 and B(2,4,5-F3 C6 H2 )3 are less Lewis acidic than B(C6 F5 )3 and have been utilized in FLPcatalyzed hydrogenation of alkylidenemalonates and Aza-Morita–Baylis–Hillman adducts [51, 53] (Fig. 6.11). From these three boranes, it was found that the Lewis acidity of B(3,4,5-F3 C6 H2 )3 was slightly higher than that of B(C6 F5 )3 due to reduced sterics around the boron center, with B(2,4,6-F3 C6 H2 )3 being 70% as Lewis acidic and B(2,4,5-F3 C6 H2 )3 having a Lewis acidity of 73% of B(C6 F5 )3 [51, 54].

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Fig. 6.11 FLP catalysis using B(2,4,6-F3 C6 H2 )3 as Lewis acid component

Further reduction of the number of fluorine substituents on the aromatic ring has furnished two boranes tris(2,6-difluorophenyl)borane [B(2,6-F2 C6 H3 )3 ] and tris(2,4difluorophenyl)borane [B(2,4-F2 C6 H3 )3 ], which exhibits a reduced Lewis acidity with respect to B(C6 F5 )3 (79% and 67%, respectively) [51]. These boranes have been employed for catalytic screening in the FLP-catalyzed hydrogenation of electrondeficient olefins. It was found that B(2,4-F2 C6 H3 )3 led to no observable hydrogenation products even at 30 bar H2 and 80 °C. On the other hand, B(2,6-F2 C6 H3 )3 delivered the hydrogenated products in 98% conversion at 10 bar H2 and 50 °C, whereas B(C6 F5 )3 furnished the product in the same conversion (98%) but at higher H2 pressure and temperature (30 bar and 80 °C). Despite three isomers of monofluoroarylboranes being possible, only tris(ortho-fluorophenyl)borane B(o-FC6 H4 )3 and tris(para-fluorophenyl)borane B(p-FC6 H4 )3 have been reported [31, 53]. Interestingly, Lewis acidity data is only reported on B(p-FC6 H4 )3 and is analogous to other boranes with a reduced number of fluorine substituents, this compound exhibits reduced Lewis acidity in comparison to B(C6 F5 )3 . As is seen from the relative Lewis acidities in Fig. 6.10, a relationship can be deduced, where the Lewis acidity is related to both the number and position of the fluorine atom substitution on the aryl rings. Another approach to modulate the Lewis acidity of boranes is through the exchange of the perfluorophenylgroup(s) with chloro-analogs. Exchanging one or two of the perfluoroaryl rings to perchloroaryl rings results in the formation of two new heteroleptic boranes that exhibit slightly reduced Lewis acidity than B(C6 F5 )3 [42]. A newly developed approach utilizing boranes with reduced Lewis acidity is that of ‘inverse’ frustrated Lewis pairs. This concept uses weakly Lewis acidic boranes as the acid component combined with strong and sterically encumbered Brønsted bases. Inverse FLPs have been developed, which employ bench stable/easily handleable boranes such as triphenylborane, dimesitylborane and 9-BBN derivatives in combination with strong organosuperbases such as carbeniums and phosphazenes (Fig. 6.12) [55–57]. Inverse FLPs have been demonstrated to be capable of reversibly cleaving H2 and catalyzing the hydrogenation of imines and ketones. Hydrogenation of ketones to produce alcohol products was demonstrated to occur in a facile manner under inverse FLP conditions as the weakly acidic borane upon H2 activation forms borohydrides exhibiting enhanced hydricity, therefore accelerating the hydride transfer step [58–60].

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Fig. 6.12 a components for inverse FLPs and b inverse FLP-catalyzed hydrogenations

6.4 Water-Tolerant Boranes As seen previously, B(C6 F5 )3 exhibits a high oxophilicity due to the strong inherent Lewis acidity. As a result, the presence of water can be problematic for B(C6 F5 )3 /Lewis base-catalyzed transformations. The presence of water in the reaction mixture leads to the formation of a [Ar3 B-OH2 ] adduct, which precludes the binding of other small molecules. In addition, coordination of water generates a very strong Brønsted acid that is comparable to HCl (pKa = 8.4 in MeCN) [61]. Thus, conventional Lewis bases employed in FLP catalysis lead to deprotonation of the B(C6 F5 )3 -OH2 adduct (Fig. 6.13, right). But even in the absence of such bases, forcing conditions can favor degradation of the borane through elimination of C6 F5 H (Fig. 6.13, left). In both cases, catalyst poisoning is usually irreversible [60, 62, 63]. Attempts to ameliorate FLP water sensitivity can be broadly classified into two categories, (i) careful fine-tuning of the reaction parameters to allow for the use of conventional boranes and ii) design of novel boranes with altered steric (size exclusion principle) and electronic (limiting the electron deficiency of the boron center) properties [64].

6.4.1 Modifying Reaction Conditions A disadvantageous side effect of B(C6 F5 )3 exhibiting high oxophilicity is its strong coordination to carbonyl and alcohol-containing compounds. Akin to the water

Fig. 6.13 The possible water-promoted decomposition pathways of B(C6 F5 )3

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adducts, protodeboronation of the analogous alcohol borane adduct also results in C6 F5 H elimination. Consequently, the borane catalyst is poisoned and destroyed. For a long time, the FLP-catalyzed reduction of carbonyl compounds seemed impossible. Initial attempts with stoichiometric reactions were met with limited success, with only a few examples in non-donor solvents reported prior to 2014 [65, 66]. Intramolecular FLP systems have met with much the same fate, due to the irreversible capture of the carbonyl by the FLP [2]. Thus, aldehydes and ketones were noticeably missing from the long list of functional groups B(C6 F5 )3 could hydrogenate catalytically. The solution to this quandary took the form of ethereal solvents such as dioxane or diethyl ether, which was simultaneously reported by the groups of Ashley and Stephan (Fig. 6.14) [67–69]. Introduction of H2 to B(C6 F5 )3 in ethereal solvents enabled these solvents to act as the Lewis base and participate in hydrogen bonding [70]. Importantly, the acidity of these protonated ethers is significantly higher than any of the classical Lewis bases used in FLP chemistry (pK a Et2 OH+ = 0.2 in MeCN) [71] thus allowing for carbonyl activation and hydride transfer from [H–B(C6 F5 )3 ]− . Interestingly, analytically pure solvents or moisture excluding conditions were not required, as demonstrated by Ashley. Indeed, the catalyst stability was high enough to allow the presence of excess H2 O (1 or 5 equivalents) [72]. However, more forcing conditions or longer reaction periods were required to maintain high turnovers. For example, acetone hydrogenation [2.5 mol% B(C6 F5 )3 loading, 100 °C, H2 (50 bar)] achieved 92% conversion in 39 or 108 h, when exposed to 1 or 5 equivalents of water, respectively. Air- and moisture-sensitive manipulation allowed for quantitative conversion at 13 bar H2 in 6 h, albeit with a 5 mol% B(C6 F5 )3 loading. In order to examine the reversibility of the deprotonation of the H2 O–B(C6 F5 )3 adduct, the Subhani group investigated the reaction of formaldehyde with the B(C6 F5 )3 /Pt Bu3 FLP in the presence of water (Fig. 6.15, left top) [73, 74]. The major product obtained upon mixing was the FLP–water–formaldehyde adduct. Interestingly, the same result was obtained when adding formaldehyde to [HO– B(C6 F5 )3 ][H–Pt Bu3 ] (Fig. 6.15, left bottom). This highlights that proton abstraction from H2 O–B(C6 F5 )3 by the Lewis base is not always permanent. The FLP–water– formaldehyde adduct released water when heated to 100 °C leading to the isolation

Fig. 6.14 An example of FLP-mediated carbonyl hydrogenation

Fig. 6.15 B(C6 F5 )3 /Pt Bu3 FLP promotes formaldehyde activation

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Fig. 6.16 The reactivity of selected boranes toward reductive amination

of the product from FLP addition to the aldehyde (Fig. 6.15, right). Thus, conclusive evidence was obtained, supporting the stipulation that entropic release of water from B(C6 F5 )3 is achievable when suitably forcing conditions are used. Water-tolerant reductive amination of carbonyls using borane catalysts constitutes another area where significant progress has been made. Through the use of hydrosilanes as the terminal reductant, Ingleson demonstrated that the in situ generated water from imine condensation could be tolerated in the reaction [75]. Hydrogenation of imines catalyzed by B(C6 F5 )3 has been extensively studied, however, prior purification of the imine has always been a necessity to exclude the presence of water. The reaction shown in Fig. 6.16 follows this general rule, with the desired amine not observed and [HO–B(C6 F5 )3 ]- the major component when performed at room temperature with 1 equivalent of carbonyl compound, 1.2 equivalents of hydrosilane and 1 mol% B(C6 F5 )3 . Nevertheless, by heating the reaction to 100 °C, B(C6 F5 )3 could be liberated to catalyze imine hydrogenation. A control experiment using strong Brønsted acids, such as HCl, showed no reactivity, thus proving that the Brønsted acid H2 O–B(C6 F5 )3 is not responsible for the catalysis [76]. It is worthwhile to note that the presence of moderate Brønsted bases in the reaction mixture proved deleterious toward the progress of the reaction. This effect is attributed to competition for the hydrosilane, thus impeding H2 O–B(C6 F5 )3 formation. A limitation of this methodology was encountered when trying to expand the substrate scope to the more nucleophilic primary and secondary aliphatic amines. These aliphatic substrates would inevitably deprotonate the H2 O–B(C6 F5 )3 adduct. Conveniently, reduction of the Lewis acidity of the borane enabled the synthetically useful transformation to proceed [43]. By this means, the use of BPh3 proved effective in catalyzing the reaction even though 3.5 equivalents of hydrosilane was required to obtain synthetically meaningful yields. The increased demand for hydrosilane can be justified due to competition between the reduced electrophilic nature of N-alkylamines and water/silanol-dehydrogenation. Thus, when considering carbonyl reductive amination, B(C6 F5 )3 and BPh3 work in a complementary fashion. Owing to its high Lewis

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acidity, B(C6 F5 )3 is able to exclusively catalyze the reductive amination of arylamines but not alkylamines due to irreversible deprotonation of the H2 O–B(C6 F5 )3 adduct. Conversely, BPh3 is efficient at catalyzing reductive amination with alkylamines but not arylamines since protodeboronation of H2 O–BPh3 (catalyst decomposition) is more rapid than arylamine amination. The chlorinated borane of intermediate Lewis acidity, namely, B(3,5-Cl2 C6 H3 )3 (generated in situ) has also proven an effective catalyst for a broad range of reductive aminations using ambient conditions thanks to the increased stability of the catalyst in the presence of water. The convenience of a one-pot borane-catalyzed amination procedure has been the impetus behind efforts to expand this methodology to other substrates. The group of Xiao demonstrated the synthesis of tetrahydroquinoxalines via a sequential cyclization/hydrosilylation [77]. whereas the Otte group focused on amination of epoxides via a successive Meinwald rearrangement/reductive amination (Fig. 6.17) [78]. Finally, this methodology has also been adapted to work in a continuous-flow setup [79].

6.4.2 Design of Novel Boranes As mentioned in the introduction, targeted alteration of the ubiquitous Lewis acid B(C6 F5 )3 has been a focus of several research groups in order to improve water tolerance. An increase in steric crowding around the boron center allows for a decrease in the steric hindrance around the Lewis base, therefore leading to improved functional group and water tolerance. Replacing the ortho-fluorine atoms of B(C6 F5 )3 with more sterically demanding chloro substituents can prevent water (and other small molecules) access to the borane center while still enabling the activation of hydrogen and subsequent hydrogenation of substrates. Taking this approach further, substitution of the ortho-fluorine atoms of B(C6 F5 )3 with more sterically demanding chlorine can prevent the formation of [H2 O–BAr3 ] while still allowing hydrogenation reactions to occur. This is known as the size exclusion principle [80]. Soós

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Fig. 6.18 The use of H2 as the reductant for borane catalyzed aminations

took these factors into consideration when designing a catalyst for the hydrogenation of sterically unimpeded quinolines, a class of challenging substrates due to their propensity to bind strongly to B(C6 F5 )3 through N → B adduct formation (Fig. 6.18, left). While B(C6 F5 )3 is unable to hydrogenate quinoline under anhydrous conditions [105 °C, H2 (4 bar)], bis(2,3,5,6-tetrafluorophenyl)mesitylborane [B(4-HC6 F4 )2 (Mes)] is able to promote quinoline hydrogenation to 24%, thanks to the increased steric hindrance imparted by the mesityl substituents (Fig. 6.18, right) [81]. The difference in reactivity between B(C6 F5 )3 and B(4-HC6 F4 )2 (Mes) becomes even starker when 2-methylquinoline was exposed to air for 30 min prior to hydrogenation giving conversions of 3% and 35% conversion, respectively, under identical conditions [60 °C, H2 (4 bar)]. In order to elucidate the steric effect on the reactivity of the borane center, the Soós group conducted a comprehensive study in water, looking at the complexation of boranes B(2-Cl-6-FC6 H3 )3 , B(2-F,6-ClC6 H3 )2 (2,6-Cl2 C6 H3 ) and B(2-F,6ClC6 H3 )(2,6-Cl2 C6 H3 )2 with the Lewis base DABCO [40]. Gradual replacement of the fluorine atoms to chlorine significantly altered the reactivity profile of the boranes. Albeit all boranes formed the expected BAr3 -OH2 -DABCO compound at low temperatures (−30 °C), only the adduct of B(2-F,6-ClC6 H3 )3 was stable at higher temperatures (45 °C). Water dissociation was observed for the other two borane– water adducts back to the free boranes B(2-F,6-ClC6 H3 )2 (2,6-Cl2 C6 H3 ) and B(2-F,6ClC6 H3 )(2,6-Cl2 C6 H3 )2 (45% and 60%, respectively) with an exchange rate approximately 20 times higher for B(2-F,6-ClC6 H3 )(2,6-Cl2 C6 H3 )2 . Thus, by applying the size exclusion principle, novel and efficient catalysts for the reductive amination of both aryl- and alkyl-amines under ambient conditions were discovered (Fig. 6.19). The Soós group has also expanded the applicability of these chlorinated triarylboranes to catalytic hydrogenation of carbonyls. In this example, borane B(4HC6 F4 )2 (2,6-Cl2 C6 H3 ) in technical grade THF was able to promote the reaction even when saturated with 1.5 equivalents of water and continuous exposure to air. However, it is important to note that, for the water-saturated system, increased H2 pressure was required from 20 bar to 100 bar of H2 for the reduction of benzaldehyde under otherwise identical conditions (Fig. 6.20). Furthermore, the reaction exhibited excellent selectivity, showing a preference for hydrogenating carbonyls over any nitro or ester groups present in the molecule [82]. The introduction of a chlorine atom to the meta position on one of the aryl rings led to borane B(4-HC6 F4 )2 (2,3,6-Cl2 C6 H3 ), which was capable of promoting a reductive etherification in which THF acts as the solvent and the Lewis base component of the

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Fig. 6.19 Reductive amination of aryl- and alkyl-amines facilitated by boranes containing chlorine atoms

Fig. 6.20 Borane-catalyzed hydrogenation of various carbonyls

FLP (Fig. 6.21). Upon H2 activation, the protonated solvent adopts Brønsted acid behavior converting the intermediate oxocarbenium species into the desired ether [81]. A direct analog of B(C6 F5 )3 is the heavier halogenated derivative, B(C6 Cl5 )3 where the size exclusion principle is responsible for a remarkably stable borane toward hydrolysis [83]. This was showcased by refluxing B(C6 Cl5 )3 in a 1:1 H2 O/toluene mixture for a prolonged period of time (days) with no observable degradation (Fig. 6.22a). Indeed, such is the steric crowding around the boron center its Lewis acidity could not be determined by the Gutmann–Beckett method. Interestingly, this borane was still able to react with small molecules such as DMAP (dimethylamino pyridine) and fluoride despite the high degree of steric crowding

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Fig. 6.21 Reductive etherification of carbonyls with THF acting as solvent and Lewis base

Fig. 6.22 Examples of the reactivity of C6 Cl5 -containing boranes

around the boron center (Fig. 6.22b). To gain an insight into its Lewis acidity, Density Functional Theory was used giving an intermediate value between B(C6 F5 )3 and BPh3 . The slightly less bulky borane B(C6 F5 )2 (C6 Cl5 ) was able to perform hydrogenations under ambient conditions, as any water present could easily be removed by exposure to high vacuum or the presence of molecular sieves in the reaction mixture (Fig. 6.22c) [41, 84].

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Fig. 6.23 Methods for the synthesis of chiral boranes applied in FLP chemistry

6.5 Chiral Boranes in FLP Catalysis Chiral boranes, in which one or two of the fluorinated aryl groups have been exchanged, represent another class of boranes, which exhibit reduced Lewis acidity compared with B(C6 F5 )3 . In order to compensate for the decreased electronwithdrawing character of the substituent, it was observed that the steric demand of the substituent must increase significantly [41]. These chiral boranes, akin to B(C6 F5 )3 , demonstrate catalytic activity toward small molecule activation and have predominantly been used in asymmetric hydrogenation chemistry [85].

6.5.1 Synthesis The synthesis of this class of boranes can be achieved via two methods 1) salt metathesis with chiral organolithium or Grignard reagents and 2) hydroboration of alkenes or alkynes bearing chiral substituents (Fig. 6.23). Boranes synthesized by these methods will be outlined in detail in the next section.

6.5.2 Salt Metathesis The salt metathesis approach has been extensively utilized for the synthesis of achiral highly Lewis acidic boranes, however, the corresponding application toward the synthesis of chiral boranes is less explored. The Paradies group developed a chiral borane in which one of the C6 F5 groups was exchanged for an enantiopure planar [2.2]paracyclophane moiety [86]. The enantiopure 4-bromo [2.2]paracyclophane (obtained from the racemic analog) underwent Li/halogen exchange and was subsequently trapped with ClB(C6 F5 )2 to provide the enantiopure borane in 65% yield (Fig. 6.24a). This borane was found to exhibit about 92% Lewis acidity in comparison with B(C6 F5 )3 . The Repo group synthesized intramolecular chiral FLPs based on a tetrahydroquinoline or indoline scaffold. These boranes could be readily synthesized by treatment of the corresponding N-benzylated heterocycles with t BuLi followed by trapping with ClB(C6 F5 )2 (Fig. 6.24b) [87]. It was found that substituents

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Fig. 6.24 Synthesis of chiral boranes and FLPS via salt metathesis

in the 2-position of the quinoline or indoline core were crucial for obtaining configurationally stable FLPs as unsubstituted variants underwent epimerization at the 2position. A related N/B-containing FLP system based upon the (R)-1,1’-dinaphthyl core was synthesized by the same group. Sequential alkylation of (R)-2-iodo-2’-1,1’bisnaphthalene afforded the corresponding tertiary amine. Lithium/iodine exchange followed by trapping with ClB(C6 F5 )2 furnished the desired FLP, which was isolated as the corresponding zwitterion after H2 activation in 52% yield (Fig. 6.24c) [88].

6.5.3 Hydroboration One of the most synthetically practical methods for the synthesis of chiral boranes for FLP chemistry is through the hydroboration of olefins using Piers’ borane [HB(C6 F5 )2 ] [89]. The group of Erker demonstrated the possibility of synthesizing chiral intramolecular FLPs by hydroboration. They exploited the planar chirality of 1,2-substituted ferrocenes. These FLPs were synthesized via the hydroboration of the ferrocenylphosphino-olefin in excellent yield with excellent selectivity for the anti-Markovnikov product. The hydroboration of other heteroalkenyl moieties, such as cyclohexenyl phosphines or enamines, also led to the formation of FLPs, however, these novel B/P and B/N FLP systems are racemic [90, 91]. The synthesis of chiral boranes and FLPs by hydroboration is also possible. The hydroboration of monoterpenes with HB(C6 F5 )2 enables easy access to chiral boranes, which possess strong Lewis acidity. The Piers group demonstrated that hydroboration of α-pinene led to a 1:1 mixture of regioisomers [92]. This mixture was attributed to the formation of kinetic and thermodynamic products. The kinetic product arose from direct hydroboration of the olefin, whereas the thermodynamic product occurs via an isomerization through a retrohydroboration/rehydroboration sequence (Fig. 6.25a). The Klankermayer group demonstrated that chiral boranes could be accessed from camphor derivatives, which underwent hydroboration with HB(C6 F5 )2 . When the olefin was substituted with a phenyl group, a 4:1 mixture of diastereoisomers was observed. However, these could be resolved once converted into the corresponding phosphonium hydridoborate species by addition of t Bu3 P and H2 (Fig. 6.25b) [93]. When

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Fig. 6.25 Synthesis of monoterpene-derived FLPs and boranes

the steric hindrance of the phenyl group was increased, by changing to a 2-naphthyl group, the hydroboration proceeded with complete diastereoselectivity (Fig. 6.25c). Akin to the phenyl analog, this species was highly efficient at activating molecular hydrogen in the presence of t Bu3 P [94]. An intramolecular variant could also be furnished using this scaffold when the phenyl ring contained a bromide in the para position (Fig. 6.25d) [95]. Another class of boranes that have been synthesized by hydroboration are those which contain the axially chiral rigid 1,1-bisnaphthyl backbone. The Du group demonstrated that it was possible to achieve double hydroboration using HB(C6 F5 )2 on the atropisomeric bis(olefins) (Fig. 6.26a) and bis(alkynes) (Fig. 6.26b) [96, 97]. Modification of the 3 and 3’-positions of the scaffold was essential for obtaining high enantioselectivity in FLP catalysis. These catalysts have found widespread use for enantioselective hydrogenations and hydrosilylation of imines, enamines, quinolines, quinoxalines and silylenol ethers [95, 96, 98–106]. More recently, the Du group has demonstrated that another class of chiral boranes could be obtained from using 3,3’-substituted BINOL derivatives (Fig. 6.26c). These boranes were synthesized via an allylation of the alcohols resulting in the formation of a nine-membered ring bearing an exocyclic olefin. This 1,1’-disubstituted olefin underwent regioselective

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Fig. 6.26 Du’s in situ generated chiral boranes

Fig. 6.27 Chiral boranes developed by Wang

hydroboration using Piers’ borane to furnish the desired catalyst [107]. All these boranes were made and used in situ negating the isolation, storage and handling of the sensitive boranes. Very recently the group of Wang has developed a couple of bis-boranes that are highly selective in metal-free hydrogenations. The first series that was developed was based on a C 2 -symmetric bicyclic diene scaffold. This scaffold was chosen as syn addition of Piers’ borane to the α-aryl-substituted cyclic olefin delivered the B(C6 F5 )2 moiety selectively to the less hindered position and trans to the aryl group, thus only generating a single regioisomer. This bicyclic diene underwent hydroboration as predicted and furnished the bisborane, which was stabilized by addition of isoquinoline, generating a stable Lewis pair (Fig. 6.27a) [108]. The same group also developed a series of sterically hindered spiro-cyclic bisboranes based on the same hydroboration strategy they previously utilized (Fig. 6.27b) [109].

6.6 Summary Even within this short review, it is clearly seen that there has been a large push in developing novel boranes for applications in FLP chemistry. The steric and electronic properties as well as the stability of the boranes can be readily attenuated to either enhance or decrease the Lewis acidity of the borane compared with the

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archetypical B(C6 F5 )3 . Despite the fact that the chemistry of these boranes is still in its infancy, these new boranes have already found widespread application in synthetic transformations including enantioselective reactions.

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Chapter 7

Heterogeneous Catalysis by Frustrated Lewis Pairs Andrew R. Jupp

Abstract Frustrated Lewis pairs (FLPs), featuring reactive Lewis acid and Lewis base sites that can cooperatively activate small molecules, have been exploited in a wide range of homogeneous catalytic reactions since their inception in 2006. However, it is only recently that the tenets of FLP chemistry have been used to develop heterogeneous catalysts, which are advantageous due to their ease of separation from reaction mixtures and the recyclability of the catalyst. This chapter outlines the many different approaches that research groups around the world have taken to synthesise and utilise semi-immobilised or fully immobilised (solid-state) FLP catalysts. This includes supporting the Lewis acid and/or base components on or within a whole host of different materials, including silica, zeolites, metal-organic frameworks (MOFs), polyoxometalate clusters, metal oxides, graphene and hexagonal boron nitride. Keywords Heterogeneous catalysis · Frustrated lewis pairs · Solid-state · MOFs · Surfaces

Abbreviations AIBN atm. ATR BDC BPDC COD CP CQD

Azabisisobutyronitrile Atmosphere(s) Attenuated total reflectance Benzenedicarboxylate 4,4 -biphenyldicarboxylate 1,5-cyclooctadiene Cross polarisation Carbon quantum dot

A. R. Jupp (B) School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK e-mail: [email protected] Van ’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1090 GD Amsterdam, The Netherlands © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_7

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Cy DABCO DCM DMF DRIFT EDX FLP FTIR h HAADF-STEM h-BN IR MD MOF Mes MS NHO NMR NP OAc Pd/CN PDOS pin POM PXRD py r.t. RWGS SDS SIP TBHP TCPP TCTB TEM TGA THF TMP XPS α-CD

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Cyclohexyl 1,4-diazabicyclo[2.2.2]octane Dichloromethane N,N-dimethylformamide Diffuse reflectance infrared Fourier transform Energy-dispersive X-ray Frustrated Lewis pair Fourier transform infrared Hour(s) High-angle annular dark-field scanning tunnelling electron microscopy Hexagonal boron nitride Infrared Molecular dynamics Metal-organic framework Mesityl, 2,4,6-trimethylphenyl Molecular sieves N-heterocyclic olefin Nuclear magnetic resonance Nanoparticle Acetate Palladium on nitrogen-doped carbon material Projected density of states Pinacol Polyoxometalate Powder X-ray diffraction Pyridine Room temperature Reverse water gas shift Sodium dodecyl sulfate Surface-initiated polymerisation Tert-butyl hydroperoxide Tetrakis(4-carboxyphenyl)porphyrin Tris(para-carboxylate)tridurylborane Transmission electron microscopy Thermogravimetric analysis Tetrahydrofuran 2,2,6,6-tetramethylpiperidine X-ray photoelectron spectroscopy α-cyclodextrin

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7.1 Introduction Catalysis underpins the vast majority of industrially important reactions. In particular, hydrogenation is employed in upgrading crude oil, as well as in the synthesis of agrochemicals, pharmaceuticals and materials [1]. Historically, this has been carried out with transition metal complexes; however, in 2006 Stephan et al. articulated the concept of frustrated Lewis pairs (FLPs), and showed that unquenched combinations of bulky Lewis acids and Lewis bases could synergistically and reversibly activate dihydrogen, H2 (Fig. 7.1a) [2]. Even more importantly, the protic and hydridic species derived from the heterolytic cleavage of H2 could be used to effect the metal-free hydrogenation of unsaturated organic substrates (Fig. 7.1b) [3–7]. Since the initial discovery, a huge variety of FLP systems have been explored, most commonly with

a)

b)

c)

Fig. 7.1 a First reversible activation of dihydrogen by an FLP; b general catalytic cycle for FLPcatalysed hydrogenation of an imine (LB = Lewis base; LA = Lewis acid); c selected examples of intermolecular, intramolecular and chiral FLPs

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phosphine or amine Lewis bases in combination with borane Lewis acids. Both intermolecular and intramolecular systems have been developed, and chiral systems can be used for asymmetric hydrogenation (Fig. 7.1c) [8, 9]. In addition to hydrogenation catalysis, FLPs have been shown to activate a wide range of small molecules, including CO2 , CO, alkenes, alkynes, N2 O and SO2 . They have also found application in polymer synthesis, and providing perspective on biological systems. All of these applications have been reviewed previously [10–24]. Across all of the varied and intensive research of FLPs to date, the vast majority involve homogeneous systems, where the FLP components are dissolved in a solvent and react with the dissolved substrate in the same medium. The molecular nature of the Lewis acid and base within the FLP affords advantages for studying and developing novel reactions in a laboratory setting. The electronic and steric nature of the two components can be readily tuned, and the reactions can be easily monitored in situ using a range of solution-phase techniques, of which NMR spectroscopy is the most common and convenient. However, the majority of catalysts used in industry are heterogeneous in nature, typically with a solid-state catalyst and liquid or gaseous reagents [25]. Over 90% (by volume) of the chemicals manufactured worldwide are synthesised using solid catalysts [26]. For example, the Haber–Bosch process relies on a heterogeneous iron catalyst for the formation of NH3 from N2 and H2 , and zeolites are widely used in the refining of crude oil [27]. The benefits of heterogeneous catalysts are manifold, and include the ease of separation of the products, catalyst recycling and translating scale-up by working under flow conditions instead of batch reactors. There has been growing interest, therefore, in developing solid-state FLP systems as heterogeneous catalysts, which may well be part of the missing puzzle piece in transforming FLPs from academic curiosities to industrially relevant compounds. A Tutorial Review by Qu et al. gave an excellent introduction to the topic of semi-solid and solid FLP systems, and described the state-of-the-art at the end of 2017, with a particular focus on two-dimensional materials and metal oxide surfaces [28]. This chapter will therefore build on these early examples in a rapidly developing field, and give an overview of the diverse and creative approaches that researchers are exploring to accomplish heterogeneous reactivity and catalysis with FLPs. The account does not give the discoveries in chronological order, but they are instead grouped according to the type of heterogeneous system.

7.2 Semi-Immobilised Frustrated Lewis Pairs One approach to carrying out heterogeneous catalysis with FLP systems is to immobilise either the Lewis acid or the Lewis base, and combine this insoluble species with the complementary FLP component in solution. The solid acid or base can then be easily separated from the product and the rest of the reaction mixture and recycled in subsequent reactions. This approach is relatively simple to carry out, but the obvious downside is that the soluble acid or base component still needs to be separated from

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the product, and will need to be refreshed for subsequent recycling experiments. The examples of semi-immobilised FLP systems described in this section are divided into those where the Lewis base is the solid component, and those where the Lewis acid is the solid.

7.2.1 Solid Lewis Base with a Soluble Lewis Acid The approach of Taoufik et al. was to mimic the well-studied homogeneous FLP systems, but generate a heterogeneous catalyst by grafting the Lewis basic component to a solid support [29]. They first synthesised a hybrid organic/inorganic support by grafting tri-isobutyl aluminium on dehydroxylated silica at 700 °C, which consumed all of the reactive silanol groups [30]. Treatment with a slight excess of (4-hydroxyphenyl)diphenylphosphine afforded the solid-supported Lewis base [(≡SiO)2 (AlO–C6 H4 –PPh2 (Et2 O))] (1, Fig. 7.2a), as evidenced by solid-state 1 H, 13 C and 31 P NMR spectroscopy. Addition of the Lewis acids B(C6 F5 )3 or Piers’

a)

b)

Fig. 7.2 a Synthesis of solid-supported Lewis adducts 2 and 3; b catalytic hydrogenation of 3hexyne by 3 as a heterogeneous catalyst

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borane (HB(C6 F5 )2 ) to 1 yielded the Lewis adducts 2 and 3, respectively (Fig. 7.2a). A range of solid-state NMR techniques confirmed the presence of the P–B bond in both compounds, and diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy showed the diagnostic bands from the C6 F5 rings in both products, as well as the B–H stretching frequency at 2405 cm−1 in 3. Although the original FLP systems precluded formation of the Lewis adduct through sterics, it has since been shown that the same FLP reactivity can be observed if an equilibrium can be established between the “free” and “bound” acid and base components [31]. 2 and 3 were therefore explored as heterogeneous catalysts for the selective hydrogenation of 3-hexyne to Z-3-hexene (Fig. 7.2b). Although 2 gave rather poor conversion under the conditions tried, 3 was an efficient catalyst for this reduction, giving quantitative conversion and high selectivity towards Z-3-hexene (approximately 84%), with small amounts of E-3-hexene, Z-2-hexene, E-2-hexene and hexane also produced. The significantly enhanced catalytic ability of 3 over 2 led the authors to propose that the mechanism proceeds by initial hydroboration of the alkyne, followed by hydrogen splitting and protonation, as previously suggested by Pápai and Repo for a different FLP system [32]. Recycling studies of 3 as a catalyst were also carried out, leading to a drastic drop in conversion, but when the Piers’ borane was refreshed in between runs then the high conversion was maintained. Finally, the catalytic activity of 3 was also studied in the hydrogenation of other alkynes, namely diphenylacetylene, (hex-2-yn-1-yloxy)trimethylsilane and methyl octadec-9-ynoate, but in all cases the conversion was low (5–25%). Thomas et al. employed a different approach to obtain a solid Lewis base [33]. Instead of grafting the phosphine to a solid support, they synthesised porous polymer networks based on two different triarylphosphine moieties with varying degrees of steric hindrance close to the phosphorus centre. Accordingly, a Yamamoto polymerisation process was used to afford 4 and 5 (Fig. 7.3a) [34]. Suspension of the polymer networks with B(C6 F5 )3 in DCM led to rapid swelling of the polymer and impregnation of the Lewis acidic borane into each porous network, to afford adducts 6 and 7. The formation of an adduct is observed in the solid state in each case by MASNMR (MAS: magic angle spinning) spectroscopy. This may be initially surprising, as the “molecular” counterpart to 7, modelled as a combination of P(2,6-Me2 -C6 H3 )3 and B(C6 F5 )3 , is fully frustrated in solution, that is the NMR chemical shifts of the individual components are unchanged on mixing. But on removal of the solvent, the “dry” solid mixture of the acid and the base has a non-negligible interaction, and this is shown in the solid-state NMR spectrum of the dry mixture, which is distinct from each separate component. Although the P–B interaction is present in 6 and 7, the coordinating solvents (such as Et2 O, THF, methanol or acetone) preferentially bind to the borane, and thus simple washing of 6 and 7 with such solvents restores the free networks 4 and 5, respectively. The ability of these heterogeneous systems to activate dihydrogen was subsequently explored. A combination of either 4 or 5 with equimolar B(C6 F5 )3 in cyclohexane-d 12 under a pressure (6 bar) of 1:1 H2 /D2 led to the reversible activation of dihydrogen, as observed by the emergence of a 1:1:1 triplet signal attributable to HD in the 1 H NMR spectrum at 4.54 ppm (Fig. 7.3b). The isotopic scrambling indicates that these species could be promising candidates

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Fig. 7.3 a Synthesis of semi-immobilised FLPs 6 and 7 featuring B(C6 F5 )3 impregnated in a phosphine polymer network; b isotopic scrambling as evidence for H2 activation by these systems

to act as heterogeneous catalysts for subsequent hydrogenation reactions, although this remains currently untested. Rose et al. extended this concept and synthesised an organic polymer network based on an amine Lewis base [35]. The polymer 8 was synthesised by N-alkylation of p-xylylenediamine with 1,4-bis(bromoethyl)benzene (Fig. 7.4a). Impregnation with B(C6 F5 )3 in toluene afforded the Lewis adduct 9, and the N–B interaction

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Fig. 7.4 a Synthesis of polyamine organic framework 8 and impregnated FLP 9; b catalytic reduction of diethyl benzylidenemalonate

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was demonstrated using ATR-IR spectroscopy, where a new absorption band corresponding to the N–B stretching mode was observed at 1276 cm−1 . The FLP combination was successfully used as a heterogeneous catalyst for the hydrogenation of diethyl benzylidenemalonate, achieving 100% yield after 24 h with a H2 pressure of 20 bar (Fig. 7.4b). This is by direct analogy with the homogeneous FLP system comprising 1,4-diazabicyclo[2.2.2]octane (DABCO) and B(C6 F5 )3 [36]. An impressive result in the realm of homogeneous FLP catalysis was the hydrogenation of ketones and aldehydes to the corresponding alcohols, discovered independently by the groups of Stephan and Ashley [37, 38]. In both cases, the success was due to the weakly basic ethereal solvent being employed as the Lewis base, which served to stabilise the protonated carbonyl intermediate, and also meant that the resulting alcohol was not subsequently deprotonated by the Lewis base component of the FLP. Mahdi and Stephan furthered their finding by employing oxygen-containing materials, specifically 4 Å molecular sieves (MS) and α-cyclodextrin (α-CD), as weak heterogeneous Lewis bases to carry out analogous reactivity [39]. These two materials have very different structures. 4 Å MS are zeolites, which are porous aluminosilicate materials that are commonly used in the laboratory as adsorbents, usually to remove unwanted water. α-CD is a cyclic hexamer of glucose, usually studied for its host– guest interactions. Despite these structural differences, the presence of the weakly basic oxygen centres enabled both of these materials to function as a solid component along with molecular B(C6 F5 )3 in an FLP. As a representative example, Fig. 7.5a shows the reduction of 3-methyl-2-pentanone to 3-methyl-2-pentanol in quantitative yields for both systems. The reaction resulted in good yields for a range of alkyl ketones, and aryl ketones featuring electron-withdrawing substituents, whereas aldehydes typically gave poorer conversions. The solid Lewis bases could be recycled in successive hydrogenation experiments, but addition of B(C6 F5 )3 was required in between each run. Interestingly, for electron-rich aryl ketones, a tandem reduction and dehydration occurs, resulting in an overall reductive deoxygenation, as typified

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Fig. 7.5 a Reduction of 3-methyl-2-pentanone to the corresponding alcohol; b reductive deoxygenation of acetophenone by semi-solid FLPs involving B(C6 F5 )3 and either 4 Å MS or α-CD

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by acetophenone in Fig. 7.5b. This reaction was more selective when 4 Å MS were used as the Lewis base instead of α-CD, presumably because the former could trap the water by-product to drive the reaction to the styrene product. Finally, applying the same reaction conditions to diaryl ketones, such as benzophenone, resulted in reductive deoxygenation to give diphenylmethane. These reactions demonstrate the wide scope of Lewis bases that can be used in FLP reactions, and highlights the ease in some cases of transitioning from homogeneous to heterogeneous catalysis. The examples so far have all targeted the synthesis of heterogeneous FLP systems as catalysts, but, for completeness, solid-supported bases in combination with Lewis acids have also been used in polymerisation chemistry, specifically for modifying the surface of the material. The cooperative action of Lewis acids and bases to promote the efficient and controlled polymerisation of a range of monomer substrates has been well-studied, most notably by the group of Chen [40]. This approach was extended to surface-initiated polymerisation (SIP) by Zhang and Zhang [41]. A selfassembled monolayer containing N-heterocyclic olefin (NHO) moieties supported on a silica wafer was prepared, and used as a Lewis base in conjunction with Al(C6 F5 )3 to promote the polymerisation of lactones, giving rise to linear polymer brushes (Fig. 7.6a). A different surface modification could be achieved by using a grafted polymer chain bearing NHO functionalities in combination with Al(C6 F5 )3 , as in this case bottle-brush brushes were formed (Fig. 7.6b). This novel and conceptually simple application of solid-supported FLP reactivity highlights the growing utility of such systems in diverse fields. Understanding the interactions of Lewis acids and bases at heterogeneous interfaces is crucial for controlling such surface reactions. The “frustration” of these FLP systems, that is the reason that Lewis adduct formation does not inhibit reactivity, is often not related to steric hindrance, which is the common cause in typical homogeneous systems. To assess this phenomenon, Dawlaty et al. used a solid Lewis base consisting of 4-mercaptobenzonitrile bound to gold, and B(C6 F5 )3 as a Lewis acid, and used vibrational spectroscopy to measure the stretching frequency of the nitrile as a probe for the strength of adduct formation [42]. They showed that the surface adducts were weaker than those in the bulk. Three different origins for this frustration were proposed: surface steric frustration; solvation electric field differences between the surface and the bulk; and the alignment of energy levels between the frontier molecular orbitals of the acid and the base. It was concluded that multiple factors affect the observed surface interactions, and the relative importance of each effect will almost certainly be dependent on the system in question.

7.2.2 Solid Lewis Acid with a Soluble Lewis Base There are also several examples in the literature of solid Lewis acids used in conjunction with soluble Lewis bases for FLP reactivity, where the former can be a solidsupported Lewis acid or a transition metal surface. O’Hare et al. adopted a conceptually similar approach to the aforementioned work of Taoufik [29], in that they adapted

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Fig. 7.6 Schematic representation for the preparation of a linear polymer brushes and b bottlebrush brushes from the polymerisation of lactones by surfaces containing NHO functionalities and Al(C6 F5 )3

a prototypical homogeneous FLP system, but grafted the Lewis acid component instead of the Lewis base [43]. They devised a simple synthesis for [≡ SiOB(C6 F5 )2 ] (10) by adding HB(C6 F5 )2 to silica that had been pre-treated at 500 °C under vacuum for 4 h (Fig. 7.7a). Note that this solid Lewis acid had been previously synthesised and used as a co-catalyst for olefin polymerisation [44, 45], but this was the first time it had been employed in FLP chemistry. Addition of Pt Bu3 afforded the FLP 11 featuring a weak P–B interaction, which was confirmed by solid-state NMR spectroscopy. 11 was able to heterolytically split H2 to yield the stable salt [HPt Bu3 ][≡ SiOBH(C6 F5 )2 ] (12), and also activate polar O–D bonds, such as deuterated methanol to give [DPt Bu3 ][≡ SiOB(OMe)(C6 F5 )2 ] (13; Fig. 7.7b). This reactivity is in accord with standard homogeneous FLP reactivity, but this was further corroborated by the synthesis of a soluble analogue of 11 derived from a silicon-based cluster, which gave similar results to the heterogeneous system. One of the major appeals of FLPs is that reactivity that was once the sole domain of transition metal complexes can be achieved by combinations of cheap and abundant main-group elements, enabling a range of metal-free catalytic protocols. However,

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C6F5

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Fig. 7.7 a Synthesis of solid-supported Lewis acid 10 and semi-immobilised FLP 11; b activation of H2 and MeOD by 11

it was quickly realised that incorporating transition metal centres as either the acidic or basic site (or both) within FLPs opened up exciting new possibilities for reactivity [46–48]. In these cases, the line between transition metal-based FLP systems and more traditional metal–ligand cooperativity is blurred, and is arguably an unnecessary distinction [47, 49, 50]. Moving towards the heterogeneous systems, there have been a number of studies exploring metal surfaces as solid Lewis acids in combination with soluble bases. Wang et al. showed in their experimental and computational study that a clean gold surface could act as a Lewis acid within an FLP system [51]. In this case, they proposed the frustration is due to electronic repulsion between the lone pair on the Lewis base and the filled d-orbitals (band) of the gold, instead of typical FLP systems that rely on steric repulsion. The heterolytic cleavage of H2 by a combination of the gold surface and NH3 was first studied computationally, and analysis of the transition state for H2 splitting showed that it was theoretically similar to those seen in typical main-group FLP systems such as Pt Bu3 /B(C6 F5 )3 . A projected density of states (PDOS) analysis showed that the σ-bond of H–H can donate into the partially filled s- and p-bands of gold, while there is concomitant donation from both the Au d2z -band and the lone pair on NH3 into the H–H σ* orbital. Although Au acts as both a Lewis acid and a Lewis base towards H2 , the former effect dominates, as shown by the increase in negative charge on the gold surface during the reaction. Furthermore, the computed barrier for H2 splitting on the gold surface alone is significantly higher than in combination with NH3 (27.6 vs. 14.9 kcal/mol, respectively), highlighting the cooperative nature of the Au/NH3 system.

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Fig. 7.8 Gold surface as a heterogeneous catalyst for the FLP hydrogenation of a imines and b nitriles

In this particular case, the H2 activation is kinetically feasible but thermodynamically disfavoured. By switching the Lewis base to an imine, the initial H2 splitting would be followed by hydrogenation of the imine to the corresponding amine. The analogous homogeneous reactivity has been explored previously with B(C6 F5 )3 as the Lewis acid [52]. The viability of this reaction was initially examined computationally using propan-2-imine (Me2 C=NH) as a model substrate. It was subsequently experimentally validated using N-methyl-1-phenylmethanimine, affording 38% conversion to N-benzylmethylamine after 24 h (Fig. 7.8a). Furthermore, benzonitrile was doubly hydrogenated to benzylamine, via the imine intermediate, in 25% yield (Fig. 7.8b). The successful hydrogenation of these small imines and nitriles, which are challenging for typical homogeneous systems due to coordination of the substrate/product to the Lewis acid, can be attributed to the fact that the Au-derived FLP system relies on electronic frustration instead of steric frustration. This result has led to a growing interest in gold surfaces as a catalyst, particularly with respect to considering the reactivity as a Lewis acid within an FLP system [53]. For example, Fachinetti et al. previously reported the hydrogenation of carbon dioxide to formic acid by a gold surface in the presence of triethylamine [54], which was subsequently shown by theoretical methods to proceed by such an FLP mechanism [55]. Furthermore, in a conceptually similar approach, gold nanoparticles (Au-NPs) ligated with secondary phosphine oxides have been shown to promote the hydrogenation of α,β-unsaturated aldehydes to allyl alcohols via an FLP mechanism, although in this case the nanoparticles were soluble and thus not applicable in heterogeneous catalysis [56, 57]. Rossi et al. showed that Au-NPs supported on silica are inactive towards the hydrogenation of alkynes, but become highly active in the presence of amine Lewis bases [58]. A wide range of amines were tested for the reduction of phenylacetylene, of which piperazine proved to be the best, as it gave quantitative conversion and 100% selectivity towards the alkene product. The scope of the reaction for the AuNP/piperazine FLP was explored, and it was shown to be a very efficient system for the reduction of a wide range of terminal alkynes to alkenes in high yields, and for internal alkynes was selective to the Z-alkene product (Fig. 7.9a). This was rationalised by the mechanism shown in Fig. 7.9b, where one nitrogen centre of the piperazine binds to the gold surface, and the other basic centre can heterolytically cleave H2 in combination with the metal surface. The resulting hydride and proton can be transferred to the alkyne, which is also coordinated to the gold surface, in a stepwise manner to afford the Z-alkene. In order to examine the recyclability of

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Fig. 7.9 a Z-selective reduction of alkynes to alkenes by a silica-supported Au-NP/piperazine FLP; b proposed mechanism for the reduction

the heterogeneous catalyst, a magnetic variant of the silica support was used to aid separation; it was shown that the magnetic Au-NPs could be recycled five times but that fresh portions of piperazine were also required. A follow-up paper explored the influence of the capping ligands that are used in the synthesis of the Au-NPs [59]. It was demonstrated that the removal of these capping ligands by calcination at 400 °C gave a cleaner gold surface that resulted in significantly enhanced catalytic activity.

7.3 Fully Immobilised FLPs The majority of the semi-immobilised FLP systems discussed so far can act as heterogeneous catalysts, but suffer from recyclability issues due to the presence of a soluble component, namely either the Lewis acid or base. There have been many different approaches to develop fully immobilised FLP systems to overcome this problem,

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including solid-supported intramolecular FLPs, combinations of solid Lewis acids and bases, metal-organic frameworks, mesoporous silica, zeolites, polyoxometalate clusters, metal oxide surfaces and graphene. These will be discussed in the remainder of this chapter.

7.3.1 Solid-Supported Intramolecular FLPs Semi-immobilised FLP systems were based on either the Lewis acid or the Lewis base being bound to a solid support. Therefore, arguably the simplest conceptual approach to bridge the gap between semi-immobilised FLP systems and fully immobilised systems is to attach both the acid and base to the support. Intramolecular FLP systems contain both the acidic and basic component in the same molecule; a few examples are shown in Fig. 7.1. These have been explored since the very start of the FLP movement [2, 60], and it is therefore somewhat surprising that the first solid-supported intramolecular FLP was first described very recently by Fontaine et al. in 2019, in a continuation of their work on metal-free C–H activation chemistry [61]. It is worth noting that a polymer-supported Wulff-type amino-boronic acid was reported ten years prior, featuring a Lewis acidic boron and a Lewis basic nitrogen centre [62]. However, in this case, the intramolecular N–B interaction was exploited to lower the pK a of the boronic acid moiety, enabling the efficient binding of monosaccharides, but no FLP-type reactivity was explored. To understand the context of the heterogeneous catalyst reported by Fontaine et al., it is worth first describing the preceding homogeneous catalyst development. In a breakthrough discovery in 2015, it was shown that homogeneous FLPs can mediate the activation of C–H bonds [63]. The intramolecular FLP 14 was able to catalyse the borylation of heteroarenes such as furans, pyrroles and electron-rich thiophenes (Fig. 7.10a), giving complementary selectivity to transition metal catalysts. This system, like many other FLPs, is highly sensitive towards moisture, and specialist handling using dry solvents and inert atmospheres is required, which reduces their utility in synthetic applications. In recent years, great efforts have been made to generate water-tolerant FLP systems [64]. The group of Fontaine broadened the applicability of the C–H borylation catalyst 14 by synthesising air- and moisturestable precatalysts (15–17) that could be handled on the benchtop (Fig. 7.10b) [65]. It is proposed that after an induction period, these precatalysts are converted to the active catalyst 14 under the reaction conditions, and they could catalyse the same borylation reactions as before. This methodology could even be used to carry out the borylation of 1-methylindole on a kilogram scale [66]. The ease of synthesis and manipulation of these precatalysts prompted the authors to explore solid-state analogues for heterogeneous catalysis. Alkylammoniotrifluoroborate-functionalised polystyrene derivatives 18–20 (Fig. 7.10c) were synthesised from the functionalised styrene monomers via a radical polymerisation process, initiated by azabisisobutyronitrile (AIBN) in hot cyclohexanol [61]. 18, 19 and 20 could be obtained on gram scales in respectable

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Fig. 7.10 a Metal-free borylation of heteroarenes by intramolecular FLP 14; b benchtop-stable precatalysts for the same reaction; c polymeric precatalysts for heterogeneous borylation catalysis

yields of 73, 72 and 83%, respectively, although residual cyclohexanol could not be removed from 20, even after multiple purification attempts. 18 showed the lowest molecular weight with 26.6 kDa, whereas 19 and 20 exhibited molecular weights of 72.3 and 77.2 kDa, respectively. The polydispersity index of 1.6 for 18 was lower than expected for radical polymerisation, but the values of 2.5 and 3.2 for 19 and 20, respectively, are within the typical range. The polymers were tested in their ability to catalyse the borylation of 1methylpyrrole, either in CDCl3 or with no additional solvent. 18 was the least active in all cases, but 19 and 20 showed good conversions (87 and 89%, respectively) under neat conditions. It is important to note that the polymers remained insoluble before and during catalysis, and were therefore acting as heterogeneous catalysts. This was affirmed by testing the reactivity of the molecular monomeric species, all of which exhibited poor catalytic properties. The optimal conditions (16 h at 90 °C with no solvent) were used to explore a substrate scope incorporating a range of heteroarenes. In all cases, 19 and 20 gave the best conversions, but they were uniformly low in comparison to the previously reported homogeneous systems [66]. This is proposed to be due to poor accessibility of the active sites by the substrates. However, the advantage of the heterogeneous systems is that they could be successfully recycled for three successive runs. 18 and 19 are durable and their catalytic ability remained almost unaltered, whereas 20 was more erratic and the conversions dropped significantly in the third run, which was attributed to the residual cyclohexanol present in the catalyst. These results are an excellent proof-of-concept for heterogeneous FLP catalysts, and in particular 19 exhibited good conversions and recyclability, but

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further optimisation is required to increase the catalytic activity to be competitive with the homogeneous systems.

7.3.2 Solid Lewis Acid and Base A lot of bulky Lewis acids and bases used in FLP chemistry are solids at ambient temperatures and pressures, which are then normally dissolved in a suitable solvent for homogeneous reactivity. Erker et al. took an innovative approach to exploring heterogeneous catalysis by exploring the reactivity of solid acids and bases without any solvent [67]. This is beneficial as certain combinations of acids and bases can react with each other in solution, and be deactivated for further chemistry. For example, PCy3 and B(C6 F5 )3 in DCM solution will react rapidly via nucleophilic attack of the para position of B(C6 F5 )3 by the phosphine to ultimately afford the zwitterionic salt 21 (Fig. 7.11a). 21 is then unreactive towards H2 and other conventional substrates used in FLP chemistry. The same PCy3 and B(C6 F5 )3 compounds were combined as solids and continuously stirred under high pressures (50 bar) of H2 in an autoclave. After a prolonged period of time (10 days), the H2 -activation product [Cy3 PH][HB(C6 F5 )3 ] (22) was isolated in up to 81% yield (Fig. 7.11b). The identity of this product could be confirmed using conventional solution-phase NMR spectroscopy by dissolving the product in CD2 Cl2 , but also by directly analysing the solid using solid-state MAS-NMR spectroscopy. The same solid FLP system could also activate gaseous SO2 to afford the zwitterionic Cy3 PS(O)OB(C6 F5 )3 (23), again in contrast to the solution-phase reaction, which only yielded 21. The analogous hydrogen activation reactions were carried out using either PPhCy2 or PPht2 Bu as the Lewis base in combination with B(C6 F5 )3 . In each case the deactivation pathway in DCM was slowed relative to PCy3 on account of the reduced nucleophilicity of the phosphine, resulting in minor amounts of the corresponding

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Fig. 7.11 The difference in reactivity between the PCy3 /B(C6 F5 )3 FLP with H2 or SO2 in a DCM solution and b the solid state

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H2 -activation product being observed. However, in all cases, the deactivation pathway was effectively suppressed using the solid-state methodology, allowing for greater selectivity towards the desired H2 -activation product. The mechanism was explored with a suite of computational techniques, but it still remains somewhat speculative. The hydrogen activation reaction must initially take place at the interface between neighbouring particles of Lewis acid and Lewis base. Molecular dynamics (MD) simulations show that these components are relatively mobile at the surface, and can adopt molecular conformations akin to those typically observed in solution. MD simulations also show that H2 can diffuse through the lattice of the crystals. The activation of hydrogen thus gives rise to localised [P–H]+ and [B–H]– moieties at the surface of the particles, which somewhat resemble an ionic liquid. The authors propose that it is the combination of the molecular flexibility at the surface and the gas permeability through the lattice that leads to a “molten” system. This allows the initially distinct Lewis acid and Lewis base particles to ultimately be converted to a uniform salt of the activation product, instead of only observing salt formation at the surface of the solids. The authors subsequently exploited the properties of fluorous solvents to reduce the need for such harsh reaction conditions (50 bar H2 , 3–10 days reaction time). Fluorous solvents have a high solubility towards non-polar gases such as H2 , but do not mix well with common organic solvents. The solid B(C6 F5 )3 and PCy3 were suspended in perfluoromethylcyclohexane (C6 F11 –CF3 ) and stirred under 1.5 bar H2 , leading to 60% conversion to 22 in 10 h. Analogous experiments with PPhCy2 and PPht2 Bu as the Lewis base led to over 95% conversion to the respective H2 activation products under the same conditions. The fluorous solvent thus enhances the reactivity significantly, and allows the reactions to be carried out conveniently under near-ambient conditions. The product 22 was shown to be an effective reducing agent for converting the bulky imine N-phenyl-1-(p-tolyl)ethan-1-imine to the corresponding secondary amine. It is worth noting, however, that this reaction was carried out by combining the imine with stoichiometric quantities of the isolated 22 in DCM. It would be interesting to see whether the solid-state methodology can be extended and employed directly in heterogeneous catalysis, that is by reducing the substrate in the presence of the solid FLP without the prior need for isolation and dissolution in a solvent.

7.3.3 Metal-Organic Frameworks (MOFs) Metal-organic frameworks (MOFs) are porous materials consisting of metal ions or fragments bridged by organic linkers, often based on carboxylate moieties. The systems are easily tuneable by varying the identity of the metal centre or the size and topicity of the organic ligand, and this has given rise to a huge number of crystalline structures containing pores of different shapes and sizes [68]. Initial applications focused on the storage of fuels such as H2 and CH4 and the capture of CO2 , but more recent work has explored their utility in catalysis, gas separation and biomedical

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Fig. 7.12 Traditional linkers and Lewis pair-functionalised linkers in a UiO-66; b UiO-67 and MIL-140C and c MIL-140B

imaging. The highly tuneable nature of MOFs combined with their large internal surface area make these frameworks ideal supports in heterogeneous catalysis. Johnson et al. were the first to explore the conceptual merging of FLPs and MOFs in a series of computational papers from 2015 onwards. They proposed that incorporating Lewis acid and base moieties in specific sites in the pores of MOFs would enable FLP-type reactivity without the need for large steric bulk on either fragment, as the geometric constraint would prevent quenching. They used DFT (density functional theory) methods to design a system that could promote the hydrogenation of CO2 to formic acid (HCO2 H) [69]. The MOF UiO-66, which consists of [Zr6 O4 (OH)4 ] clusters bridged by 1,4-benzenedicarboxylate (BDC; terephthalate; Fig. 7.12a) linkers, was selected as the starting point, as it is chemically and thermally stable, selective towards CO2 adsorption, and amenable to further functionalisation. The MOF was functionalised by incorporating one intramolecular FLP per UiO-66 primitive cell; one of the BDC linkers was covalently bonded to a pyrazole framework with a BF2 moiety (24, Fig. 7.12a). They theoretically showed that this species could catalyse the reduction of CO2 to formic acid via a low-energy barrier pathway, which consists of the heterolytic cleavage of H2 (on the bold N and B centres in Fig. 7.12a) followed by concerted transfer of the proton and hydride to CO2 . However, the practical utility of this system is severely limited by the fact that CO2 binds much more strongly to the FLP than H2 , and thus CO2 effectively poisons the catalyst, which means successful implementation of this process would require initial exposure of the functionalised MOF to H2 , followed by exposure to CO2 . This issue was tackled in a follow-up paper, where the relative binding energies of H2 and CO2 were compared for a series of FLP systems in which the Lewis acid was varied [70]. They showed that the mechanism remains the same as before, but when the F atoms in 24 were replaced with Cl, Br, CN, CF3 or NO2 , then the system preferentially binds H2 over CO2 , and thus the CO2 poisoning is circumvented. However, the systems with a binding preference for H2 have a prohibitively large energy barrier for the subsequent hydrogen transfer to CO2 , rendering them ineffective as catalysts. Thus, of the FLP systems that were tested, the functionalised 24-UiO-66 remains the best candidate in terms of successfully catalysing the formation of formic acid,

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as long as the reaction is carried out sequentially with H2 then CO2 . A wider range of Lewis acid and base moieties that could be incorporated in MOFs for the hydrogenation of CO2 were subsequently explored, with phenylene-bridged amine-borane FLPs being the most promising class of catalyst [71]. Ye and Johnson subsequently targeted the formation of methanol from the reduction of CO2 via multiple successive hydrogenation steps [72]. To achieve this, they designed a new catalyst based on UiO-67; this is isostructural to the previously described UiO-66 and has similar stability and functionality, but has a larger pore volume due to the larger 4,4 -biphenyldicarboxylate (BPDC; Fig. 7.12b) linker. In this study, the functionalised linker 25 was used (Fig. 7.12b), and the large pore size combined with the relatively small FLP moiety enabled the researchers to model four functionalised linkers per primitive cell (as opposed to 24-UiO-66 that was limited to one functionalised linker per primitive cell). It was shown that the functionalised 254 -UiO-67 featuring four equivalents of 25 per primitive cell provided an energetically feasible pathway for the formation of methanol, with the key step being the intramolecular release of water from the methanediol (CH2 (OH)2 ) intermediate to afford formaldehyde. Furthermore, in this system, the heterolytic dissociation of H2 was preferred over the chemisorption of CO2 , meaning the catalyst is not poisoned by the latter. The group also explored the effect of topology on the catalytic ability of the systems [73]. The class of MOFs denoted as MIL-140 are porous zirconium dicarboxylate structures with triangular channels along the z-axis, composed of zirconium oxide chains connected with different dicarboxylate linkers. They examined functionalised versions of MIL-140B (featuring the previously described linker 25) and MIL-140C (featuring linker 26; Fig. 7.12c), and compared them to the aforementioned functionalised 24-UiO-66 and 25-UiO-67 systems. This series of MOFs differ by both the topology of the pores (triangular channels for MIL-140 and octahedral cavities for UiO-66 and UiO-67); the size of the pores (pore size: MIL-140B < UiO-66 < MIL-140C < UiO-67); and the orientation of the FLP site within the pore (thus the steric hindrance within does not necessarily scale with pore size). As in their previous studies, the authors showed that these systems can catalyse the hydrogenation of CO2 . They also showed that the heterolytic dissociation of H2 is strongly favoured over chemisorption of CO2 in the functionalised 25-MIL-140B and 25-UiO-67 MOFs due to the confinement effects and topological constraints, providing a route to avoid catalyst poisoning. Furthermore, the small pore size of functionalised 25-MIL-140B stabilises the formation of a pre-activated CO2 species, enabling a mechanistic pathway to formic acid with a lower overall energy barrier, and highlighting the importance of considering the local environment of the FLP system. Finally, from a theoretical standpoint at least, Johnson et al. used the previously described 25-UiO-67 to probe the possibility of synthesising formaldehyde directly from H2 and CO [74]. They determined that this system can selectively form formaldehyde instead of methanol, and do so with significantly lower energy barriers compared to the gas-phase system. If this reaction can be experimentally

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realised, it would reflect a significantly more sustainable approach than the established industrial process, which relies on the partial oxidation or dehydrogenation of methanol derived from Fischer-Tropsch processes. The authors propose that the formaldehyde can be continuously and readily desorbed from the MOF and collected via condensation, due to the difference in boiling points between the product and the gaseous reactants. The unreacted starting materials can then be recycled back over the heterogeneous catalyst, leading to high overall conversions for the reaction. This study shows the versatility of the functionalised MOFs, as the same system can theoretically catalyse a number of different reactions. All of the previously discussed examples of incorporating Lewis acids and bases in the pores of MOFs were studied in silico. The first group to experimentally realise this concept in a laboratory setting was that of Ma [75, 76]. They used the common MOF MIL-101(Cr), which features trimeric CrIII clusters bridged by BDC linkers, and was chosen based on its stability, large pore size and abundance of open metal sites. Whereas Johnson et al. targeted (computationally) the covalent functionalisation of the bridging ligands, Ma et al. simply used the MOF as a support by impregnating the structure with Lewis acids and bases. Specifically, the dehydrated MIL-101(Cr) was exposed to toluene solutions of the strong Lewis base DABCO, which bound to the free metal sites within the pores, leaving the second nitrogen centre of the base exposed for further functionalisation. The subsequent addition of B(C6 F5 )3 resulted in the formation of the Lewis adduct anchored within the cavities, giving rise to the functionalised MOF 27 (Fig. 7.13a). The sample was washed with copious amounts of toluene to remove any residual Lewis acid or base remaining in solution, to ensure that any observed reactivity was due to the heterogeneous catalyst 27. 27 was characterised by a range of techniques. The phase purity of the compound was confirmed using powder X-ray diffraction (PXRD), and N2 sorption studies at 77 K showed that the surface area of 27 was significantly smaller than the starting MIL-101(Cr), consistent with grafting of the Lewis pairs to the metal sites. Fourier transform infrared (FTIR) spectroscopy also showed stretching bands attributable to

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Fig. 7.13 a Schematic representation of sequential grafting of DABCO and B(C6 F5 )3 into a pore within MIL-101(Cr); reduction of b imines and c alkylidene malonates catalysed by 27

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the Lewis pair within the MOF. To probe the distribution of the DABCO/B(C6 F5 )3 moieties within the porous framework, they used high-angle annular dark-field scanning tunnelling electron microscopy (HAADF-STEM) and EDX spectroscopy. These techniques revealed that the Lewis pairs were evenly distributed throughout the structure, with no localised accumulation in particular regions. The catalytic performance of 27 towards the hydroboration of imines was subsequently tested, and compared with the homogeneous DABCO/B(C6 F5 )3 FLP combination previously reported by Crudden et al. [77]. 27 was effective at catalysing the reduction of N-tert-butyl-1-phenylmethanimine with HBpin, giving quantitative conversion to the corresponding pinacolboramide after 2 h (Fig. 7.13b). A small substrate scope for this reaction was examined, and revealed an interesting size selectivity. The smaller imines, such as N-benzylidene-1-phenylmethanamine, were reduced as effectively (in some cases more effectively) by 27 compared to the homogeneous system. However, for larger substrates, such as acridine, the catalytic activity of 27 was significantly worse than the homogeneous FLP, and this was attributed to the large substrates not being able to enter the pores of the MOF and interact with the catalyst. In a similar fashion, 27 was also a proficient catalyst for the hydrogenation of alkylidene malonates directly with H2 gas (Fig. 7.13c). The long-term stability of 27 was explored. No leaching of the FLP from the MOF into solution was observed at any point before or after catalysis, as measured by NMR spectroscopy of the supernatant. Furthermore, PXRD and N2 sorption studies performed on 27 showed that the material maintained crystallinity and pore structure after catalysis. These findings prompted the authors to assess the recyclability of the heterogeneous catalyst, and they showed that 27 could catalyse the reduction reaction in Fig. 7.13b for seven successive cycles with quantitative conversion achieved after 2 h in all cases. In a follow-up paper, Ma et al. functionalised the same MIL-101(Cr) MOF with a slightly modified FLP combination, specifically DABCO and BMes(C6 F5 )2 [78]. The synthesis and analysis were analogous to 27 described above. The new MOF-FLP could activate H2 at room temperature to afford the [H–DABCO]+ [H–BMes(C6 F5 )2 ]– ion pair impregnated within the pores of the MOF, which could then be used for effective hydrogenation of imines. Interestingly, the system could carry out the chemoselective reduction of α,β-unsaturated imines to afford the unsaturated amines. This selectivity is in contrast to the homogeneous FLP combination, which catalyses the reduction of both the imine and alkene double bonds. The authors propose that the chemoselectivity of the heterogeneous MOF-FLP system arises from an interaction of the imine nitrogen lone pair with either an OH group on the chromium cluster or one of the remaining open metal sites, which activates the C=N bond over the C=C bond. These results highlight the exciting possibilities for tuning reactivity by exploiting secondary interactions within the pores of MOFs that is not possible in simple homogeneous systems. In a different approach, Stylianou et al. designed a new water-tolerant MOF with a Lewis acid site in the bridging organic linker [79]. The MOF, named SION105, consists of EuIII dimers bridged by two water molecules and two tris(paracarboxylate)tridurylborane (TCTB) linkers (Fig. 7.14a). The MOF features zigzagshaped voids that comprise 36.6% of the total unit cell volume. The steric bulk around

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Fig. 7.14 a TCTB ligand used as a linker in SION-105; b conversion of ortho-phenylenediamine to benzimidazole catalysed by heterogeneous MOF SION-105

the boron centre prevents irreversible deactivation of the Lewis acid by donors such as water. PXRD confirmed the purity of SION-105, which was stable after immersion in water for 24 h. Furthermore, the MOF selectively adsorbs CO2 over N2 . Therefore, the potential of SION-105 in FLP catalysis was explored, in particular with respect to using CO2 as a C1-source. The reaction of aryl ortho-diamines with CO2 and silanes to afford benzimidazoles was chosen for the study, which has been previously shown to be catalysed by B(C6 F5 )3 [80]. After optimisation of the reaction conditions, SION-105 was shown to quantitatively convert ortho-phenylenediamine to benzimidazole in 24 h (Fig. 7.14b). Recycling experiments showed that the catalyst could be separated from the mixture by filtration, washed with methanol and then reused with no apparent loss of activity after five cycles. A substrate scope of different aromatic ortho-diamines was explored, with excellent yields for substrates containing electron-donating groups, and reduced yields for those with electron-withdrawing groups. The question of whether the reaction occurs within the pores or on the surface was explored. The X-ray crystal structure revealed that the pore window of SION-105 is smaller than even the smallest diamine substrate. Furthermore, thermogravimetric analysis (TGA) on samples of the MOF after being immersed in solution with the selection of amines gave very similar profiles to that of the starting MOF. This evidence indicates that the reactivity occurs at the surface of the MOF. Therefore, the majority of the boron centres are inaccessible to the substrate, and it is reasonable to assume that the activity of this catalyst could be significantly improved by incorporating a similar functional group within a more porous MOF. The same authors subsequently explored an inverse approach, where the framework of the MOF contained a Lewis basic site, and an external Lewis acid was added [81]. MOF-545 is a well-known MOF comprising Zr6 O8 clusters linked with tetrakis(4-carboxyphenyl)porphyrin (TCPP) ligands. The porphyrin moiety provides the Lewis basic centre, and the large pore size allows for impregnation with bulky Lewis acids, in this case B(C6 F5 )3 . This FLP combination was able to promote the hydrogenation of CO2 to methoxyborate, which can be readily hydrolysed to

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methanol, by direct analogy with the homogeneous system explored by O’Hare et al. [82]. Note that this impregnation of a porous polymer network containing Lewis basic sites with the strong Lewis acid B(C6 F5 )3 is conceptually similar to the previously discussed examples from Thomas and Rose (Figs. 3 and 4) [33, 35]. However, in the case of MOF-545/B(C6 F5 )3 combination, the acid–base interaction is sufficiently strong enough to enable recycling of the heterogeneous catalyst for at least three cycles without the need to add additional Lewis acid for each run. PXRD characterisation of the MOF after these reaction cycles is essentially unchanged relative to the starting material, which highlights the stability of the system under relatively harsh conditions (40 bar H2 /CO2 , 100 °C, 20 h). This section has highlighted the benefits that can be achieved by combining the metal-free reactivity of FLPs with the vast structural diversity of MOFs. There are many different approaches that can be taken, whether that is incorporating either a Lewis acidic site or a Lewis basic site in the framework of the MOF, or both, or by impregnating/grafting Lewis pairs into the pores of MOFs. The research on this topic is very much in its infancy, and there are innumerable opportunities for exploiting the topology and size of pores to achieve selectivities in FLP-mediated reactions that are unattainable in solution; for example, carrying out reactions in a chiral cavity to effect asymmetric catalysis by an FLP.

7.3.4 Mesoporous Silica In addition to MOFs, other porous structures have been explored as hosts for FLP reactivity. Kleitz et al. designed mesoporous solid-supported Lewis acid–base pairs and studied their adsorption behaviour towards CO2 [83]. The solid Lewis acids were synthesised by the metalation of silica SBA-15 with appropriate precursors to afford Ti4+ -, Zr4+ - and Al3+ -deposited mesoporous materials M-SBA-15 (M=Ti, Zr, Al), according to a previously reported protocol [84]. These were then impregnated with a range of Lewis bases, including 2,2,6,6-tetramethylpiperidine (TMP), triethylamine and tris(tert-butyl)phosphine to yield 28, 29 and 30, respectively (Fig. 7.15a), although certain combinations could not be fully characterised. For comparison purposes, systems were also developed where the amine or phosphine Lewis base was grafted onto the surface of the silica (31 and 32 in Fig. 7.15b). The porosity of the materials was measured by low temperature N2 physisorption, and as expected the surface area for each system decreases after impregnation/grafting of the Lewis base; and the compounds were further characterised using solid-state NMR spectroscopy and EDX (energy-dispersive X-ray) spectroscopy. The Lewis acidity of the systems was probed by adsorption of pyridine, and it was shown that the Lewis acidity of the metal surfaces was preserved even in the presence of the other Lewis bases. CO2 binding was quantified by measuring the low-pressure adsorption isotherms at three different temperatures, and it was shown that generally the systems with the grafted Lewis base (31 and 32) had a higher CO2 sorption ability than the impregnated systems (28-30). The Ti Lewis acid sites interact too strongly

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Fig. 7.15 Solid Lewis acid–base systems involving metalated mesoporous silica and a impregnated or b grafted Lewis bases

with the Lewis bases, which inhibits the reactivity of these systems towards CO2 . The best systems were 31-Zr and 32-Zr, both in terms of the adsorption capacity and strength of adsorption. These results show that the mesoporous FLP systems can capture CO2 , albeit not as effectively as other reported systems, and it would be interesting in the future to explore the possibility of exploiting the ambiphilic sites within these structures for CO2 functionalisation.

7.3.5 Zeolites NaY zeolites are porous sodium aluminosilicate clusters with a high silica/alumina ratio. They have been widely explored as supports for metal catalysts and used in the catalytic cracking of hydrocarbons in the petrochemical industry [85, 86]. Choi et al. probed the use of NaY zeolites loaded with platinum nanoparticles, Ptx /NaY, as potential FLP systems [87]. They showed that the addition of hydrogen gas resulted in the heterolytic cleavage of the H–H bond, and formation of a protic O(H+ ) site and a hydridic Na+ (H– ) site. The formulation of H2 -Ptx /NaY was supported by neutron powder diffraction measurements, solid-state NMR spectroscopy, FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS). The hydridic Na+ (H– ) site was demonstrated to be an effective catalyst for the coupling of two aldehyde moieties to form the corresponding ester via the Tischenko reaction. A toluene solution of acetaldehyde and the heterogeneous H2 -Ptx /NaY catalyst afforded ethyl acetate after 12 h at room temperature, in accord with the same reaction catalysed by NaH powder (Fig. 7.16a). Interestingly, H2 -Ptx /NaY

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Fig. 7.16 Comparison of the ability of H2 -Ptx /NaY and NaH to catalyse the esterification of a acetaldehyde and b benzaldehyde, highlighting the size selectivity of the zeolite system

was unable to promote the esterification of the larger benzaldehyde (in contrast to NaH powder, which readily produced benzyl benzoate; Fig. 7.16b), highlighting the size selectivity of the catalyst towards small aldehydes that can access the interior cavities of the zeolite. It remains to be seen whether H2 -Ptx /NaY can be exploited as a heterogeneous catalyst in more typical FLP reduction chemistry, where both the activated H+ and H– moieties are transferred to the substrate.

7.3.6 Polyoxometalate Clusters Recent efforts have been dedicated to exploring the use of polyoxometalate (POM) clusters in FLP chemistry. POMs have a huge structural diversity, and have found applications in catalysis, medicine and materials [88]. They typically contain transition metal centres in high oxidation states bridged by oxygen atoms. Hybrid POMs containing reduced metal centres can also be prepared, giving rise to unusual electronic structures and bonding modes [89]. The presence of both oxidising and reducing metal centres within the same cluster also allow the possibility for bifunctional catalysis, akin to FLPs. Xu et al. prepared a series of hybrid polyoxomolybdates containing Mo–Mobonded triangular (Mo4+ )3 centres [90, 91]. These were proposed to act as Lewis acidic sites, which could act in combination with surrounding basic O–MoVI =O groups to carry out FLP reactivity, with the acidity and basicity of each site potentially boosted by MoIV → MoVI electron transfer [92]. The fact that there are multiple adjacent sites in each cluster allows for the possibility of simultaneous and potentially cooperative activation of small molecules. As such, it was shown that the MoIV -γ-Keggin-like cluster H2 [(py3 MoIV 3 )2 MoVI 7 O32 (OH)4 )] could act as an effective heterogeneous catalyst for the transfer hydrogenation of nitroarenes to aniline derivatives with hydrazine hydrate at 80 °C in 2 h [92]. The structure dependence of related systems was subsequently explored for the same catalytic transformation [93]. To enhance the catalytic ability of the systems further, the relatively weak Lewis basic oxygen centres were conceptually replaced with antimony centres, to give the cluster H[(SbIII 3 MoIV 3 MoVI 15 O55 (OH)2 py3 ] (33) [94]. The structure contains

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Fig. 7.17 a Schematic representation of active site of POM 33 featuring SbIII and MoIV 3 centres, and the proposed FLP activation of hydrazine; b reduction of nitrobenzene catalysed by 33

chain-like SbIII …MoIV 3 interactions, where the Mo3 triangles are capped by an antimony centre with separations of 4.6–5.0 Å, which is pre-organised for cooperatively cleaving small molecules (schematically depicted in Fig. 7.17a). This enables the transfer hydrogenation of nitroarenes to be carried out at room temperature (in contrast to the analogues without an antimony centre), and at lower catalyst loadings. The proposed intermediate is shown in Fig. 7.17, although whether or not the system can accommodate two sets of protons and hydrides (as shown) or just one is still not clear. The heterogeneous catalyst could also be recycled effectively for ten cycles.

7.3.7 Surface (Interfacial) FLPs Arguably the fastest-growing area in heterogeneous FLP catalysis is exploiting active surface sites in a range of different materials. As will be seen below, these sites can be due to defects, for example oxygen vacancies, or due to intrinsically acidic or basic atoms or moieties embedded within the surface. In these cases, the “frustration” of the acids and bases arises from their fixed location on the surface, which prevents the quenching of the reactive sites, by direct analogy with molecular FLPs. These systems are often referred to as surface FLPs or interfacial FLPs, and there are now many examples in the literature that can promote a wide array of chemical transformations. The most commonly explored surfaces are those of metal oxides, and these will be examined first, followed by graphene and other p-block-based two-dimensional materials. In the majority of cases, the interfacial FLP comprises a metal-bound hydroxyl group as the Lewis base, and a nearby coordinatively unsaturated metal centre (or centres) as the Lewis acid. The coordinative unsaturation of the metal centre is typically due to oxygen vacancies. A general and simple model for the interfacial FLP splitting of H2 is shown in Fig. 7.18.

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Fig. 7.18 General simplified model of interfacial FLP made up of a Lewis basic hydroxyl site and Lewis acidic metal (M) site next to an oxygen vacancy [O] (in red). FLP acid and base sites in bold

7.3.7.1

Al2 O3

The first references to rationalising the reactivity of metal oxide surfaces using the tenets of FLP chemistry were from the groups of Copéret and Sautet. They initially showed that the observed C–H activation of methane on the surface of γ-alumina (γAl2 O3 ) could be explained by the presence of Al/O Lewis acid/base pairs [95]. The reactivity occurs at the metastable (110) termination, which can be stabilised by an optimum coverage of water molecules. The water increases the basicity of the O sites, and counterintuitively also allows the presence of metastable and highly Lewis acidic Al(III) sites, and after the activation of methane affords Al–CH3 and O–H species. This heterogeneous FLP reactivity is impressive, as the C–H activation of methane is one of the few examples of small molecule activation that homogeneous FLP systems have so far been unable to carry out, either catalytically or stoichiometrically. The role of water was explored in more detail in a subsequent publication, and it was demonstrated that the optimised partially dehydroxylated γ-Al2 O3 surface could activate methane and dihydrogen at low temperatures, and also bind N2 at the active Al(III) sites [96].

7.3.7.2

In2 O3

Since this discovery, other metal oxides surfaces have been thoroughly explored in relation to FLP chemistry, most notably indium oxide (In2 O3 ) and ceria (CeO2 ). Ozin et al. demonstrated that hydroxylated indium oxide nanocrystals, denoted by In2 O3–x (OH)y , could catalyse the reduction of CO2 with H2 to form CO and H2 O, known as the reverse water gas shift (RWGS) reaction [97, 98]. The reactivity was shown to arise from a Lewis basic hydroxide moiety (InOH) and an adjacent Lewis acidic indium site proximal to an oxygen vacancy (Figs. 7.18 and 7.19). These sites could function in an analogous manner to an FLP and heterolytically dissociate H2 to afford a bound proton and hydride, which could then be delivered to CO2 to afford CO and an equivalent of H2 O, followed by desorption of the products to regenerate the active catalytic sites (Fig. 7.19). The mechanism was explored in more detail by metadynamics-based computations, and revealed that the reduction of CO2 is the rate-limiting step [99]. It also showed that the desorption of the water is disfavoured, which could prevent sustained catalytic activity by blocking the active sites. The importance of surface defects, which give rise to the acidic and basic sites, was

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Fig. 7.19 The proposed mechanism for the RWGS reaction catalysed by the heterogeneous FLP In2 O3–x (OH)y

highlighted by studying different starting materials for the synthesis of In2 O3–x (OH)y [100]. The oxidising nature of the precursor anion had a substantial impact on defect formation in the material, and gave rise to markedly different catalytic activity for the different samples. Interestingly, the rate of RWGS reaction could be enhanced using photochemical conditions [98]. In the dark, measurable CO production was not observed until 1 −1 at 190 °C. Under irradiation by a Xe 165 °C, and was measured at 35.7 μmol g− cat h 1 −1 at 150 °C, increasing lamp, the same reaction was measured at 15.4 μmol g− cat h −1 −1 to 153 μmol gcat h at 190 °C, which represents a fourfold increase in rate due to photoactivation. A subsequent theoretical and experimental investigation showed that this effect is due to the fact that the hydroxide and indium sites become more Lewis basic and acidic, respectively, in the excited state relative to the ground state [101]. The defects on the surface were also directly related to the photocatalytic activity, as higher defect concentrations resulted in longer excited-state lifetimes, which were attributed to improved charge separation and higher catalytic activity [102]. Furthermore, the development of rod-like nanocrystal superstructures (nanorods) further enhanced the catalytic activity over the more simple nanocrystals; transient absorption studies showed that this is the result of prolonged photoexcited charge carrier lifetimes within the nanocrystal network comprising the nanorods [103]. The effect of doping on the catalytic activity of the defected indium oxide was also probed. The isomorphous substitution of In3+ by Bi3+ afforded a range of new metal oxides with the formula Biz In2–z O3–x (OH)y , and the best catalyst for the RWGS reaction was found when z = 0.0003, with slower rates at both higher and lower z values [104]. DFT studies suggested that Bi could slightly enhance the basicity of

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Fig. 7.20 Selectivity for formation of CO versus methanol under various conditions catalysed by various indium oxide heterogeneous FLPs. Note this just shows the product selectivity, and does not reflect the relative rates between different conditions

neighbouring In–OH groups relative to In, and the coordinatively unsaturated Bi3+ atoms could also act as more acidic sites to help cleave the H–H bond. However, at higher Bi loadings, there is the greater possibility of forming Bi–OH groups, which significantly decreases the basicity of the hydroxyl groups and thus the efficacy of the FLP. The previous results show that CO and H2 O are the sole products from the reduction of CO2 by H2 below 200 °C when catalysed by In2 O3–x (OH)y . However, on raising the temperature of the reaction to 250 °C and using the nanorods of In2 O3–x (OH)y as the catalyst, methanol can also be generated (Fig. 7.20, upper 1 −1 under dataset) [105, 106]. Methanol is produced at a rate of 97.3 μmol g− cat h irradiation, with a selectivity of over 50%, which is a significant result, as at the time of publishing this was over 200 times faster than the next best methanol production rate by simulated solar irradiation. It is worth noting that at 300 °C, both the rate and selectivity of the methanol-forming reaction decreased significantly, both in the light and in the dark. Another approach to alter the reactivity of materials is to vary the polymorph, where the composition is maintained but the structure is different. All of the previously mentioned studies were carried out on the cubic defected indium oxide polymorph, c-In2 O3–x (OH)y , but Yan et al. showed that the rhombohedral polymorph, rh-In2 O3–x (OH)y , exhibits higher activity, better stability and a higher selectivity for the generation of methanol over CO in the hydrogenation of CO2 (Fig. 7.20, lower dataset) [107]. It is worth noting that the c-In2 O3–x (OH)y used as the reference in this study were the nanocrystals first described in 2014 [97], and not the more active nanorods that were studied subsequently [103, 105, 106]. At 270 °C, 1 −1 under the rh-In2 O3–x (OH)y , produced methanol at a record rate of 180 μmol g− cat h irradiation, which is almost twice as fast as the aforementioned nanorods [105, 106],

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although at a much lower MeOH/CO selectivity than previously observed (50%). The optimum rh-In2 O3–x (OH)y also exhibited excellent stability, with no significant change in production rate or selectivity over more than 100 h of continuous testing, and no obvious oxidation state or structural changes were observed by PXRD, XPS or transmission electron microscopy (TEM) after the run. The rhIn2 O3–x (OH)y nanocrystals outperformed the c-In2 O3–x (OH)y material in all of the experiments in this study, which was attributed to the increased acidity and basicity of surface FLP sites on the defected (110) surface of the rhombohedral polymorph over those on the (111) surface of the cubic structure. The authors subsequently showed that rh-In2 O3–x (OH)y can split H2 at room temperature, and propose that this activation proceeds via heterolysis of the H–H bond instead of homolysis [108].

7.3.7.3

CeO2

The ability of defect-laden CeO2 to enable heterolytic FLP catalysis has been explored by Chang et al.; they demonstrated that porous nanorods of ceria with high concentrations of surface oxygen vacancies can catalyse the hydrogenation of alkenes and alkynes [109, 110]. The reactivity arises from an interfacial FLP site consisting of two adjacent Ce3+ centres and a lattice O atom, which are held together on the rigid surface at a distance of approximately 4 Å (Fig. 7.21). These acidic and basic sites can heterolytically cleave the H–H bond with a low activation energy, and subsequently deliver the hydride and proton to the unsaturated substrates. The oxygen vacancies are crucial for rationalising this reactivity, and DFT computations show that the (110) surface (depicted schematically in Fig. 7.21) is more effective at catalysing the reduction of acetylene than the (100) surface [110]. The scope of alkene hydrogenation catalysed by defected CeO2 was explored, and it was shown that styrene could be effectively reduced under mild conditions. Substrates containing Lewis basic moieties, such as ketones or alcohols, gave much poorer conversion due

Fig. 7.21 Schematic representation of heterolytic cleavage of H2 by (110) surface of defect-laden CeO2 . FLP acid and base sites in bold

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to the strong adsorption of the substrate to the Lewis acidic surface defects. The catalyst could also promote the reduction of alkynes to alkenes and alkanes, although with limited ability at controlling conversion and/or selectivity. A more detailed computational analysis of the formation and behaviour of the surface FLP sites on defected ceria was carried out using ab initio MD simulations and static DFT studies [111]. The principal conclusion is that the formation of stable FLP sites on the (110) surface is dependent on the number of oxygen vacancies, where FLP sites featuring three or more oxygen vacancies are thermodynamically stable. The FLP sites with fewer vacancies are less stable under vacuum, but can be accessed dynamically under experimentally relevant conditions. It was also predicted that the active CeO2 surface FLPs are capable of coupling methane to ethane and ethylene via relatively low activation energies, although this was not validated experimentally. The defect-enriched CeO2 surface is also capable of binding and activating CO2 [112]. The Lewis basic O site on the surface can interact with the electrophilic C atom of CO2 , and the two O atoms of CO2 interact with two adjacent Lewis acidic Ce centres, as modelled by DFT computations. Several geometries for the adsorption of CO2 were calculated, but in all cases the bound substrate is activated, with elongated C=O bond distances and an O=C=O bond angle that deviates significantly from linearity. The ability of defected CeO2 nanorods to activate and transform CO2 was demonstrated by carrying out the tandem conversion of alkenes and CO2 into cyclic carbonates, where an oxidant first converts the alkene into an epoxide, which subsequently reacts with the activated CO2 to afford the product (Fig. 7.22). As such, styrene could be converted into phenylethylene carbonate with moderate conversions and good selectivity (>80%) with tert-butyl hydroperoxide (TBHP) as the oxidant. The catalyst could be improved by using the porous nanorods, which have a greater defect concentration, and could enable the same conversion with higher yields and selectivity (up to 94%). After recovery by centrifugation, the porous nanorods could be recycled, and maintained activity and selectivity for at least three cycles.

Fig. 7.22 Tandem conversion of styrene, CO2 and an oxidant to afford phenylethylene carbonate, promoted by heterogeneous CeO2 FLP catalyst

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Fig. 7.23 FLP versus Lewis acid catalysis in the conversion of glycerol

7.3.7.4

Other Metal Oxide Surfaces

Cobalt borate nanosheets (CoBOx ) have also been explored as interfacial FLPs by Chang et al. [113]. The FLP reactivity arises from metal-bound hydroxyl groups acting as the Lewis base, and adjacent metal ions acting as the Lewis acid (Fig. 7.18). The heterolysis of the H–H bond was probed computationally and shown to proceed with a low-energy barrier of 8.5 kcal/mol (0.37 eV), enabling the efficient hydrogenation of alkenes into alkanes. Wang et al. have shown that Pt deposited on mesoporous WOx can promote the hydrogenolysis of glycerol under relatively low hydrogen pressures (10 bar), albeit with only moderate selectivity towards 1,3-propanediol [114]. Experimental evidence supports the heterolytic dissociation of H2 between the Pt and WOx sites, consistent with an FLP mechanism, which gives rise to the desired 1,3-propanediol product (Fig. 7.23). However, the acidic WOx sites can also independently catalyse the traditional dehydration–hydrogenation pathways to afford 1,2-propanediol or 1propanol. To overcome this issue, Au was also dispersed along with the Pt on the WOx surface, yielding the catalyst AuPt/WOx , which had a superior selectivity for the formation of 1,3-propanediol in the same reaction [115]. The modulating effect of the Au was attributed to the decrease in the number of Lewis acidic WOx sites, and an increase in the number of FLP sites; the latter was determined by an increase in the number of in-situ generated Brønsted acid sites in the presence of H2 .

7.3.7.5

Graphene and Other p-Block Supports

Metal oxides are not the only surfaces that have been exploited as sites for interfacial FLP chemistry. Graphene and other nanocarbon structures have been explored as alternatives to transition metals in a range of applications, including catalysis [116]. Parvulescu et al. have experimentally shown that graphene derived from the pyrolysis of alginate can act as a hydrogenation catalyst, both for the selective reduction of acetylene in the presence of ethylene [117], and for the reduction of nitro compounds

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Fig. 7.24 a Schematic representation of activation of H2 on acidic (blue triangle) and basic (orange hexagon) of graphene. b Selective hydrogenation of acetylene catalysed by graphene. c Lightmediated N-alkylation of aniline catalysed by CQD/ZnIn2 S4

[118]. In the former study, the conversion of the acetylene hydrogenation is significantly reduced when using graphene oxide or graphene doped with heteroatoms (N, P or S) as the catalyst, which suggests that the activity does not arise from the presence of these dopants. The authors propose a mechanism based on FLP reactivity, featuring discrete acidic and basic sites that can dissociate H2 on the surface (Fig. 7.24a, b), although the precise nature of these sites is still unclear [119, 120]. There are many possibilities, including carboxylate groups as the basic sites (due to the presence of residual oxygen – roughly 8 wt% O content – of the alginate precursor in graphene), and the acidic sites could be carbon vacancies or even carboxylic acid groups [118]. To support this notion, it was shown that adding small amounts of additional acid or base can have a deleterious effect on the catalytic activity, and adding CO2 can actually enhance the reactivity. Graphene was subsequently shown to be able to enable isotopic H/D exchange in dihydrogen at room temperature, and a computational study suggested that the reactivity can occur at carbon vacancies in the graphene surface [121]. A very recent report from Lin et al. demonstrated the use of carbon quantum dots (CQDs), which also feature a hexagonal arrangement of sp2 carbon centres as metal-free catalysts [122]. They explored the use of a CQD/ZnIn2 S4 nanocomposite as a direct replacement for that containing palladium, that is Pd/ZnIn2 S4 , and showed that the carbon analogue could promote the hydrogenation of imines, and the photocatalytic coupling of primary amines with alcohols to afford a range of secondary amines (Fig. 7.24c). By direct analogy with the previous studies, the mechanism was proposed to occur at acidic and basic defect (and carboxylate) sites on the carbon surface, but in this case the reactivity is enhanced by transfer of photo-generated electrons from the ZnIn2 S4 to the CQD to afford an electron-rich carbon surface. Despite the aforementioned finding that doping the graphene with heteroatoms reduces its catalytic activity [117], there are many other reports that have found a positive influence on catalysis due to the presence of dopants. Zhang et al. showed that N-doped carbon materials derived from the calcination of chitosan and melamine can catalyse the reduction of nitro compounds, using hydrazine hydrate as the reductant (Fig. 7.25) [123]. As the reactivity is not affected by the presence of butylated

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Fig. 7.25 Reduction of nitrobenzene to aniline catalysed by N-doped graphene (showing the graphitic nitrogen sites)

hydroxytoluene (BHT), which is an established radical scavenger, it is proposed that the mechanism proceeds via the transfer hydrogenation of a proton and a hydride to the surface. A graphitic nitrogen centre, that is, a three-coordinate nitrogen that has replaced a carbon in the hexagonal framework (shown in Fig. 7.25), is proposed to act as the Lewis base, while an electropositive neighbouring carbon acts as the Lewis acid. However, a previous computational report suggests that graphitic nitrogen is no more basic than undoped graphene, and instead pyridinic or pyrrolic sites are required for a substantial doping effect on catalytic activity [124]. FLP sites have also been invoked to explain the reactivity of N-doped reduced graphene oxide in promoting the hydrogenation of acetylene and ethylene [125]. Similarly, Chen et al. showed that P-doped carbon nanotubes can enable the hydrogenation (and transfer hydrogenation) of nitrobenzene to aniline under mild conditions [126]. This is in contrast to the pristine carbon nanotubes, which were unable to catalyse the reduction under analogous conditions, and highlights the effect of heteroatom doping. The dopant induces surface charge delocalisation, forming FLP sites that are spatially separated (to avoid neutralisation), and that can enable the heterolysis of H2 . Once again, the activity of the catalyst is diminished if acetic acid or triethylamine are added to the reaction mixture, as these species quench the basic or acidic sites of the FLP, respectively. Su et al. have designed systems more reminiscent of conventional FLPs, and have explored the co-doping of carbon nanostructures with both Lewis acidic boron centres and Lewis basic nitrogen centres. The initial design was explored computationally, and featured bilayers of graphene, where one layer contained the B sites, and the other layer contained the N sites [127]. The distinct layers are inherently separated due to electron repulsion, giving rise to B/N separations of 3.4–3.6 Å, depending on the nature of the stacking of the layers. These FLP sites are predicted to heterolytically cleave the H–H bond with an energy barrier as low as 22.8 kcal/mol (0.99 eV), which is significantly lower than the analogous barrier between pristine graphene bilayers (53.0 kcal/mol, 2.3 eV). The importance of keeping the B- and N-doped sites separate is emphasised in this study; however, when Su et al. subsequently explored this

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topic experimentally, they took a different approach [128]. Ultra-dispersed nanodiamond was thermally treated with a boron- and nitrogen-containing ionic liquid, and the nature of the product depended on the temperature (400 vs. 600 °C), but both materials featured a carbon lattice doped with adjacent B and N centres. The sample treated at 600 °C contained the active site shown in Fig. 7.26, and the B–N bond could be identified by its stretching frequency at 1401 cm−1 , as measured by ATR-IR spectroscopy. Despite this B–N interaction, the reactive sites are still accessible to substrates, as demonstrated by the changes in NMR chemical shifts of PMe3 and pyrrole on coordination to the Lewis acidic and basic sites, respectively. Furthermore, the material could catalyse the hydrogenation of cyclooctene to cyclooctane (Fig. 7.26), and of nitrobenzene to aniline, with a much higher efficiency than the undoped carbon analogue. Nitrogen-doped mesoporous carbon materials have also been used as supports for transition metals. Zhang et al. synthesised a nitrogen-doped carbon material by the pyrolysis of glucose and melamine using eutectic salts of KCl and ZnCl2 , and used it to support low concentrations of palladium nanoparticles, abbreviated as Pd/CN [129]. The heterogeneous catalyst could promote the hydrogenation of a range of quinolines to 1,2,3,4-tetrahydroquinolines (Fig. 7.27) at 50 °C and under 20 bar of H2 , with yields up to 98%. The nitrogen dopant was proposed to have two key roles. First, the lone pair electrons should have a strong interaction with the Pd nanoparticles, resulting in a more uniform dispersion of the nanoparticles on the surface. Furthermore, the nitrogen was proposed to act as the Lewis base in conjunction with

Fig. 7.26 Reduction of cyclooctene catalysed by B,N-doped carbon lattice (proposed active site shown)

a)

b)

Fig. 7.27 a Schematic representation of H2 activation by Pd/CN; b reduction of quinolines catalysed by Pd/CN heterogeneous FLP

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Pd as the Lewis acid to heterolytically cleave the H–H bond, resulting in a FLP-type mechanism. The heterogeneous catalyst could easily be recycled and reused without loss of activity over multiple cycles. Related Pd/CN materials, albeit prepared in a different manner, were also shown to be effective catalysts for the deoxygenation of aryl aldehydes and ketones compounds under mild conditions (25 °C, 1 bar H2 ) [130]. A similar mechanism was proposed by Rossi et al. for a gold-containing analogue [131]. Pyrolysis of Au(OAc)3 in the presence of 1,10-phenanthroline over TiO2 afforded a highly active and selective Au-NP catalyst embedded in a nitrogendoped carbon support, labelled as Au@N-doped carbon/TiO2 . The catalyst was able to promote the selective hydrogenation of alkynes to Z-alkenes in high yields under mild conditions, by analogy with the gold surfaces and nanoparticles discussed earlier in the chapter. The mechanism was proposed to involve the heterolytic cleavage of H2 by the Au and N sites, which was supported by a Hammett plot of various substituted alkynes: a strong substituent effect was observed for the Au@N-doped carbon/TiO2 catalyst, with a rate enhancement for the substrates containing electron-withdrawing groups, suggesting a charge build-up on the substrate during the catalytic cycle. This result is in contrast to the established Lindlar catalyst, which had a ρ-value of close to 0 for the same experiments, and is consistent with a homolytic H2 dissociation pathway. Once again, the catalyst exhibited excellent stability and recyclability, and was able to catalyse the alkyne reduction selectively even in the presence of other reducible organic functional groups. There are other surfaces that have been invoked in FLP chemistry, either directly or used as supports for additional elements. Hexagonal boron nitride (h-BN) is isoelectronic with the graphite/graphene carbon surfaces discussed above, and has high chemical and thermal stability [132]. Blair et al. studied defect-laden h-BN as a heterogeneous catalyst for the hydrogenation of a range of alkenes, and demonstrated rates that are significantly faster than other metal-free FLP systems and graphene catalysts [133]. Mechanochemistry, and specifically a reactor based on a ball mill, was used to ensure a large number of defects on the h-BN surface, and to prevent cluster formation. DFT was used to computationally study the different types of defects and their significance in the reaction mechanism of the hydrogenation of the simple alkene, propene. The defects that were studied were boron vacancies (VB ), nitrogen vacancies (VN ), Stone-Wales defects and boron substitution for nitrogen (BN ), and it was shown that the hydrogenation most likely occurs at VN sites, as supported by solid-state NMR spectroscopic measurements. In this case, the authors noted that although there are similarities between the hydrogenation mechanism on the h-BN surface and that for FLPs, ultimately their mechanism is closer to the Horiuti–Polanyi mechanism normally seen for transition metals, which involves hydrogen transfer from the surface to the β carbon of the alkene, and subsequent reductive elimination of the free alkane from the surface [134]. Phosphorene, a two-dimensional allotrope of phosphorus, is a single layer of the stable black phosphorus, and was isolated for the first time in 2014 by multiple independent research groups [135–137]. Chen et al. subsequently computationally designed a catalyst based on phosphorene doped with B or Al, where the P and Al/B sites can function as an FLP [138]. Both materials were predicted to heterolytically

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split H2 with low-energy barriers, and be able to promote the reduction of acetone, HCN and ethylene. Given the findings that it is possible to experimentally access certain doped phosphorene materials [139], it will be interesting to see whether these materials can be synthesised in the future, and whether they can act as effective heterogeneous FLP catalysts.

7.4 Concluding Remarks This chapter has showcased the myriad possibilities of developing heterogeneous FLP systems. Semi-immobilised FLPs consist of either a solid Lewis acid or base paired with a complementary soluble molecular Lewis base or acid, respectively. The semi-immobilised systems are typically easy to access, and can effectively carry out heterogeneous catalysis, but due to one of the FLP components being soluble they often still suffer from issues involving work-up of the product and catalyst recyclability. The fully immobilised systems feature both the Lewis acid and base on (or within) the same solid support, and therefore tend to exhibit enhanced catalyst stability and recyclability. The solid supports have taken a wide range of guises, including silica, zeolites, MOFs, polyoxometalate clusters, metal oxides and graphene. As well as the usual advantages of heterogeneous over homogeneous catalysis, there are often added benefits to these systems over simple molecular FLPs. For example, carrying out the FLP reactions inside the porous cavity of a zeolite or MOF enables an additional level of control over selectivity, as larger substrates cannot access the reactive site. It will be interesting to see in the future how far this concept can be extended; can chiral cavities be used as hosts for FLPs to promote asymmetric catalysis? This chapter has also highlighted how far the definition of FLPs has evolved since the original discovery in 2006, which involved the preclusion of Lewis acid/base adduct formation due to sterics [2, 140]. The contemporary chemical literature demonstrates that a wide array of reactions and interactions can be related to FLP chemistry, including transition metal reactivity, metal–ligand cooperativity and cooperative surface–ligand interactions. The example of surface chemistry is an interesting one, as the importance of the acidic and basic properties of surface sites (due to defects, dopants, vacancies, etc.) had been known and studied for decades before the advent of FLP chemistry [141]. It is arguably unnecessary to invoke FLPs to explain the catalytic activity of graphene, for example; however, that completely misses the point. By drawing parallels between the two fields, and in fact between FLPs and any other fields mentioned in this chapter and elsewhere, it allows the coming together of two otherwise separate research communities to share knowledge and advance both areas of study. The detailed mechanistic knowledge of molecular FLPs can be used to tailor the reactive sites in metal oxide surfaces, and to fine-tune their ability to promote small-molecule activation or catalysis. Alternatively, the heterogeneous materials that are capable of promoting reactivity that is currently unattainable by homogeneous FLPs, such as methane activation, can serve as inspiration for the

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design of new molecular systems. It is clear that the impact of FLP reactivity has extended well beyond the realm of bulky Lewis acids and bases in solution, and will continue to be a guiding principle in many fields in the coming years.

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Chapter 8

Lewis Acid−Base Pairs for Polymerization Catalysis: Recent Progress and Perspectives Miao Hong

Abstract Lewis pair polymerization (LPP), catalyzed by frustrated Lewis pairs (FLPs), interacting LPs (ILPs), or classical Lewis adducts (CLAs), has become a very powerful tool for efficient, controlled, and selective polymerizations of heteroatom-containing polar monomers since its inception in 2010. The unique cooperative/synergetic monomer activation by both Lewis acid (LA) and Lewis base (LB) sites of LP catalysts not only gives this new polymerization methodology a high visibility from the beginning, but also brings about a variety of novel polymeric materials that cannot be efficiently realized by traditional polymerization techniques. This chapter highlights the very recent progress made in this rapidly expanding field since the last comprehensive review in 2018, with a special emphasis on the LP-mediated polymerization of polar vinyl monomers and ring-opening (co)polymerization of cyclic esters and epoxides. Keywords Lewis pair polymerization · Frustrated Lewis pair · Classical Lewis adduct · Ring-opening polymerization · Polar vinyl monomer

Abbreviations β-AL AGE AMA BDM BHT BO n BA t BA Conv.%

β-angelica lactone (Scheme 8.12) Allyl glycidyl ether (Scheme 8.15) Allyl methacrylate (Scheme 8.1) 1,4-benzenedimethanol (Scheme 8.16) Butylated hydroxytoluene 1,2-Butylene oxide (Scheme 8.15) n-Butyl acrylate (Scheme 8.8) tert-Butyl acrylate (Scheme 8.8) Conversion

M. Hong (B) State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China e-mail: [email protected] © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_8

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CLA ε-CL DCM DHDM DMAA Ð EO EMA FLP 3-F-Py IN LPP l-LA MC ILP LB LA MBL MS NHC NHO OCA PO PDL PT RO(C)P RT SFMA Tg Td Tm THF TBD TBGE VBMA VMA δ-VL MMA DBU It Bu I* γ MMBL MTBD

M. Hong

Classical Lewis adduct ε-Caprolactone (Scheme 8.1) Dichloromethane Double high and double multiple N,N-Dimethyl acrylamide (Scheme 8.1) Molecular weight distribution/dispersity Ethylene oxide (Schemes 8.15) Ethyl methacrylate Frustrated Lewis pairs 3-Fluoropyridine (Scheme 8.14) Indenone (Scheme 8.11) Lewis pair polymerization l-Lactide (Scheme 8.1) Methyl crotonate (Scheme 8.10) Interacting Lewis pairs Lewis base Lewis acid α-Methylene-γ -butyrolactone (Scheme 8.1) (E,E)-Methyl sorbate (Scheme 8.1) N-Heterocyclic carbene N-Heterocyclic olefin O-Carboxyanhydrides (Scheme 8.13, 8.14) Propylene oxide (Scheme 8.15) ω-Pentadecalactone (Scheme 8.1) Pentaerythritol (Scheme 8.16) Ring-opening (co)polymerization Room temperature Semifluorinated methacrylate Glass transition temperature Onset degradation temperature Melting temperature Tetrahydrofuran 1,5,7-Triazabicyclododecene (Scheme 8.16) tert-Butyl glycidyl ether (Scheme 8.15) 4-Vinylbenzyl methacrylate (Scheme 8.1) Vinyl methacrylate (Scheme 8.1) δ-Valerolactone (Scheme 8.1) Methyl methacrylate (Scheme 8.1) 1,8-Diazabicyclo[5.4.0]undec-7-ene (Scheme 8.16) 1,3-Di-tert-butylimidazolin-2-ylidene (Scheme 8.6) Initiation efficiency = M n (calcd)/M n (exptl), where M n (calcd) = MW(monomer) × [monomer]0 /[initiator(catalyst)]0 × conversion (%) + MW(end groups) γ -Methyl-α-methylene-γ -butyrolactone (Scheme 8.1) 7-Methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (Scheme 8.16)

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Mg(HMDS)2 Magnesium bis(hexamethyldisilazide) (Scheme 8.15) TOF Turnover frequency = moles of substrate (monomer) consumed per mole of catalyst (initiator) per hour

8.1 Introduction The development of powerful catalysis or methodologies for new or more sustainable, efficient, controlled, and selective polymerizations is a long-standing scientific challenge in the field of polymer synthesis, which brings about the advanced polymeric materials with notable properties and specific functions [1–5]. Lewis pair polymerization (LPP), a recently emerged polymerization methodology, has attracted an increasing level of interest and achieved remarkable successes in polymerizing heteroatom-containing polar monomers [6–9]. Inspired by the seminal work of Stephan and Erker on “frustrated Lewis pair (FLP)” chemistry for the cooperative activation of small molecules, [10–14] Chen and co-workers reported the first application of FLP chemistry for polymer synthesis in 2010 through uncovering highly efficient polymerization of polar vinyl monomers, such as methyl methacrylate (MMA), α-methylene-γ -butyrolactone (MBL), and γ -methyl-α-methylene-γ butyrolactone (γ MMBL), by a Lewis pair (LP) catalyst comprising a superacidic and sterically encumbered Al(C6 F5 )3 Lewis acid (LA) and a sterically encumbered Lewis base (LB) [e.g., Pt Bu3 , N-heterocyclic carbenes (NHC)] [15]. According to the degree of interaction between LA and LB, LP catalysts utilized in LPPs can be classified into FLPs, interacting LPs (ILPs), and classical Lewis (acid−base) adducts (CLAs) (Scheme 8.1a). It should be noted that only those CLAs and ILPs, which can dissociate into the “frustrated” free LA + LB form in the presence of a suitable solvent or monomer, are capable of providing sufficient unquenched reactivity for promoting efficient polymerization. In a typical LPP, both LB and LA sites of the LP catalyst synergistically/cooperatively participate in the chain initiation process to generate active zwitterionic intermediates for the following chain-growth process that consists of the repeating fundamental steps of nucleophilic attack of zwitterionic intermediates with LA-activated monomers and the recapture of the LA from the growing polymer chain by incoming monomer via coordination (Schemes 8.1b, c). Compared to conventional polymerization techniques, LPP has shown several unique advantages or intriguing opportunities: (1) the synergy and cooperativity of both LA and LB, which makes the LPPs significantly different from the classic anionic [16, 17] and zwitterionic [18–20] polymerizations that are typically initiated by a negative charge (Nu– ) and an LB or an LA, respectively, can render the polymerization with enhanced activity or allow the polymerization that would be generally inaccessible by an LA or LB alone. (2) Readily available LAs and LBs, as well as easily adjustable Lewis acidity, basicity, and steric effects of LPs afford a straightforward approach to

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LB

a

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LB

ILP (active)

CLA (dormant)

LA X

b

LB

LB

LA

nM M

LB

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FLP (active)

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X

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LA

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R

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n

R

FG R

FG

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O

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O O

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O t

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Bu

O

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n+1

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O Bu

O

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Propagation

Zwitterion

x

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nM M

COOMe MS

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O

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N

O N

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VBMA

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O

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NH

O

O

MMBL

NCA

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O S

VL

CL

O

S

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R MBL

DMAA O

O

O O

4-VP

L-LA

O PDL

Scheme 8.1 An equilibrium between CLAs, ILPs, and FLPs (a); A generic chain initiation step to generate the zwitterionic active species and subsequent propagation steps to produce polymer products in LPP of polar vinyl monomers (b) and in LP-mediated ROP of cyclic esters (c); A list of selected monomers investigated in the previous LPPs (d)

construct LP catalysts without time-consuming multistep syntheses which are typically required for delicate organometallic catalysts in classic coordination polymerization [21–23]. (3) The ability to stabilize the propagating active species which can enable the polymerization to proceed in a controlled/living manner by suppressing chain transfer and termination side reactions.

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Since the concept of LPP was first introduced in 2010, it opens up an unprecedented pathway to effectively polymerizing polar vinyl monomers (Scheme 8.1b), and ring-opening (co)polymerizing [RO(C)P] cyclic esters and epoxides (Scheme 8.1c), as demonstrated by its relatively broad monomer scope (Scheme 8.1d), high activity, control or livingness, and complete chemo- or regioselectivity. In the area of LPP of polar vinyl monomers, Chen et al. developed metal-free phosphine/borane-based LP catalysts in 2014 for exceptionally active polymerization of biomass-derived γ MMBL [24]. In the same year, the chemoselective polymerization of divinyl acrylic monomers, such as vinyl methacrylate (VMA), allyl methacrylate (AMA), and 4-vinylbenzyl methacrylate (VBMA), has been achieved by Lu and co-workers through using Al(C6 F5 )3 /N-heterocyclic olefin (NHO) CLAs, which led to soluble polymers bearing pendant vinyl groups for the subsequent postfunctionalization [25]. In 2016, Rieger et al. realized the relatively controlled polymerization of sterically demanding methacrylates and functionalized monomers, such as furfuryl methacrylate (FMA), n-butyl methacrylate (n BuMA), tert-butyl methacrylate (t BuMA), 4-vinylpyridine (4-VP), N,N-dimethyl acrylamide (DMAA), by employing CLAs comprising weaker acidic LAs (e.g., AlMe3 , AlEt3 , AlPh3 ) and weaker LBs (e.g., PMe3 , PEt3 ) with less steric hindrance [26]. In 2017, Takasu et al. utilized the 1,3-di-tert-butylimidazolin-2-ylidene (It Bu) LB and a sterically encumbered methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) [MeAl(BHT)2 ] LA for the exclusive 1,4-addition polymerization of (E,E)-methyl sorbate (MS) to produce a cyclic polymer [27]. Recently, Zhang, Chen, and coworkers established the first living LPP of MMA via the development of a noninteracting FLP catalyst based on MeAl(BHT)2 LA and NHO LB [28]. The successful extension from main-group LA to rare-earth LA for LPP has also been achieved by Xu and co-workers [29, 30]. Moreover, in the area of LP-mediated RO(C)P, the controlled ROP of L-lactide (L-LA) and ε-caprolactone (ε-CL) to cyclic poly(co)esters was reported by Amgoune and Bourissou et al. in 2013 through combining Zn(C6 F5 )2 LA with an organic base (e.g., 1,2,2,6,6-pentamethylpiperidine), [31] while in 2015, Dove, Naumann et al. developed a simple LP based on a metal halide [MgX2 (X = Cl, Br, I), YCl3 , AlCl3 , etc.] LA and an organic base [NHCs, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.] for the ROP of macrolactone ω-pentadecalactone (PDL) [32]. In 2017, Zhang and Chen et al. disclosed that Al(C6 F5 )3 /NHO CLA can promote the living ROP of δ-valerolactone (δ-VL) or ε-CL, [33] while Yang et al. reported the utilization of the borane/amine LPs for the controlled ROP of N-carboxy anhydrides (NCAs) [34]. LP catalyst based on BEt3 /LB or Zn(C6 F5 )2 /LB was also successfully employed for alternating/regioselective copolymerization of CO2 (COS and anhydrides) with epoxides [35–37]. The above achievements and breakthroughs have already been comprehensively reviewed in our 2018 Chemical Reviews [9]. Nevertheless, over the past 2 years, a number of creative and insightful contributions to this area continued to emerge, bringing about the expanding applications of LP in polymerization catalysis. Accordingly, these recent advances in this time frame are highlighted in this chapter, which

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is organized into two main sections. The first section focuses on LPP of polar vinyl monomers, including petroleum-based monomers and novel biomass-derived monomers developed recently, while the second section covers the progress in LPmediated RO(C)P of cyclic esters, epoxides, and cyclic anhydrides. The attempt to provide a perspective for the future developments of this exciting area is also presented.

8.2 Lewis Pair Polymerization of Polar Vinyl Monomers 8.2.1 Petroleum-Based Polar Vinyl Monomers Shortly after that the first living LPP of MMA based on MeAl(BHT)2 /NHO1–3 (Scheme 8.2) FLP catalytic system was reported by Zhang, Chen, and co-workers in 2018, [28] Zhang et al. developed an another highly active FLP catalytic system, through combining diisobutyl (2,6-di-tert-butyl4-methylphenoxy)aluminum [(BHT)Ali Bu2 ] LA with a novel imidazolin-2ylidenamino substituted phosphine LB (IAP-1, Scheme 8.2), for promoting living polymerization of MMA to address the current challenge in the synthesis of ultrahigh-molecular-weight (UHMW) PMMAs with low dispersities [38]. Varying [MMA]0 :[IAP-1]0 :[(BHT)Ali Bu2 ]0 ratio from 400:1:2 to 20000:1:2, a linear growth of PMMA M n with very low dispersities (Ð: 1.06–1.10), high to quantitative monomer conversions (Conv.% = 89–100%, TOF: 371–36000 h−1 ), and near quantitative initiation efficiencies (I * : 86–108%) can be achieved at room temperature (RT). In the end, UHMW PMMA with a M n up to 1927 kg/mol and a low Ð of 1.10 was successfully prepared upon treating with an exceptionally low catalyst loading (20000:1:2). In sharp contrast, the control runs using the IAP-1 or (BHT)Ali Bu2 alone for the polymerization of MMA yielded no polymer formation for up to 24 h, revealing the importance of a bimolecular cooperative activation for efficient polymerization. Moreover, this FLP catalyst also exhibited good control over the polymerization of ethyl methacrylate ([EMA]0 :[IAP-1]0 :[(BHT)Ali Bu2 ]0 = 400:1:2, TOF = 12000 h−1 , M n = 49.7 kg/mol, Ð = 1.16, I * = 90%), thus enabling the synthesis of well-defined diblock copolymer PMMA-b-PEMA and triblock copolymer PMMA-b-PEMA-b-PMMA via the sequential addition method.

R1 N

R2 N

NHO-1: R1 = Ph, R2 = Ph N

NHO-2: R1 = Me, R2 = Me NHO-3: R1 = H, R2 = Me

i

Pr N

R P

IAP-1: R = Ph R i

N Pr

NHO-4: R1 = Me, R2 = Ph

Scheme 8.2 Structures of NHO-1–4 LBs (left) and IAP-1–5 LBs (right)

IAP-2: R = tBu IAP-3: R = iPr IAP-4: R = Mes IAP-5: R = C6F5

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The livingness of (BHT)Ali Bu2 /IAP-1 FLP-mediated polymerization is proposed to originate from exclusive zwitterionic initiating species, and no problematic side reactions. However, this FLP catalyst was less active and became sluggish toward γ MMBL ([γ MMBL]0 :[IAP-1]0 :[(BHT)Ali Bu2 ]0 = 800:1:2, TOF = 141 h−1 , M n = 85.6 kg/mol, Ð = 1.12, I * = 105%) and MS polymerization ([MS]0 :[IAP1]0 :[(BHT)Ali Bu2 ]0 = 400:1:2, TOF = 2.67 h−1 ), respectively, and lost the controlled ability in DMAA polymerization by producing polymers with a bimodal distribution. In addition, compared with (BHT)Ali Bu2 /IAP-1 FLP, other FLP catalytic systems comprising sterically more demanding LA and IAP-1 LB resulted in either less effective polymerization ([MMA]0 :[IAP-1]0 :[(BHT)2 Ali Bu]0 = 800:1:2, TOF = 141 h−1 , M n = 72.0 kg/mol, Ð = 1.13, I * = 112%) or uncontrolled/nonliving polymerization [MeAl(BHT)2 /IAP-1] accompanied by backbiting chain termination [39, 40]. The combination of strong acidic Al(C6 F5 )3 with IAP-1 also led to a uncontrolled polymerization due to the existence of the backbiting termination, though Al(C6 F5 )3 /IAP1–4 (Scheme 8.2) CLAs all showed high-speed polymerizations (TOF: 96000 h−1 , [MMA]0 :[LB]0 :[LA]0 = 800:1:2) with moderate to high initiation efficiencies (I * : 52–92%) and produced PMMAs with narrow dispersities (Ð: 1.11–1.21). Low polymerization activity was observed under the same conditions when switching to less nucleophilic IAP-5 (Scheme 8.2) LB to pair with Al(C6 F5 )3 (TOF = 13.7 h−1 ). The screening of LA and LB scope indicated that matched Lewis acidity, basicity, and steric effect are critical for achieving efficient and controlled polymerization. The livingness and robustness of (BHT)Ali Bu2 /IAP-1 FLP provided a practical approach for rapid and scalable synthesis of sequence-controlled methacrylic multiblock copolymers at RT with double high [molecular weight and degree of polymerization per block value (dpn )] and double multiple [monomers (k) and block numbers (n)] (DHDM) features as reported by Zhang et al. very recently [41]. At the outset, the authors tested the multiply chain-extension polymerization of MMA. Even after adding 10 batches of 400 equiv. of MMA or 1 batch of 400 equiv. of MMA followed by 28 batches of 100 equiv. of MMA (the initial addition of 400 equiv. of MMA was to ensure quantitative I * value), all of monomers can be rapidly and quantitatively converted by (BHT)Ali Bu2 /IAP-1 FLP (2 min per block), and a high degree of control over MW still maintained, which resulted in a high-MW decablock or nonacosablock PMMA (274–374 kg/mol, Scheme 8.3a, b) with a relatively low Ð (1.18–1.26) and a near quantitative I * value (107–117%). Based on the successful multiply chain-extension polymerization, (BHT)Ali Bu2 /IAP-1-mediated multiblock copolymerizations were then performed by choosing four different monomers, including MMA, EMA, 2-methoxyethyl mechacrylate (MEMA), and 2-ethyoxyethyl mechacrylate (EEMA). Through sequential addition of monomers, a pentablock copolymer (n = 5, k = 4, dpn = 400, Scheme 8.3c) with a high M n of 146 kg/mol and a low Ð of 1.18 was achieved. Noteworthy is that scaling up this multiblock copolymerization was also feasible, and multigram quantity of pentablock copolymer can be obtained (114.6 g, 98%) with full conversion accomplished within 2 min for each batch monomer. Moreover, block numbers (n) were further extended to 25 with dpn value of 100, and even to 53 with dpn value of 50 for the multiblock copolymerizations (k = 4). Remarkably, it took only 25 min (1 min per block) to

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a Decablock PMMA

O

O

O

O

400

400

400

400

O

O

O

O

O

O

b Nonacosablock PMMA

100

400

O

O

O

O

O

400

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400

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O

O

O

O

400

400

O

O

O

100

100

O

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100 7

O

O

d Pentacosablock Copolymer

O

O

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400

O

O

O

O

O

O

O

O

O

O

O

O

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O

O

O

e Tripentacontablock Copolymer 100 6

100

100

100

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c Pentablock Copolymer

O

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400

O

O

O

O

O O

O

O

O

O

O

O

50 13

50

50

50

400

O

O

O

O

O

Scheme 8.3 Structures of multiblock copolymers with different monomer types, block numbers, and the degrees of polymerization per block

accomplish full conversion for the former copolymerization, while the latter one only required 28 min (30 s per block). Accordingly, a pentacosablock with a high M n of 225 kg/mol and a low Ð of 1.23 as well as a tripentacontablock copolymer with a high M n of 310 kg/mol and a low Ð of 1.22 (Scheme 8.3d, e) can be successfully synthesized, thus affording an unparalleled opportunity for the facile preparation of DHDM multiblock copolymers without the addition of extra initiator/catalyst or time-consuming/complex synthetic procedure which was indispensable in the previous synthetic strategies. Meanwhile, (BHT)Ali Bu2 /IAP-1 FLP also have the ability to incorporate random block into multiblock copolymers, affording random heteropolymers with tailored properties [MMA400 -b-EEMA400 -b-(MMA360 -rEEMA40 )-b-(MMA40 -r-EEMA360 ), MMA400 -b-(MMA360 -r-EEMA40 )-b-(MMA40 r-EEMA360 )-b-EEMA400 , and MMA400 -b-(MMA360 -r-EEMA40 )-b-(MMA280 r-EEMA120 )-b-(MMA200 -r-EEMA200 )-b-(MMA120 -r-EEMA280 )-b-(MMA40 -rEEMA360 )-b-EEMA400 ]. In 2019, Zhang and co-workers found that MeAl(BHT)2 /NHO-5–7 (Scheme 8.4) CLAs are also capable of promoting living polymerization of MMA at a low

8 Lewis Acid−Base Pairs for Polymerization Catalysis … R1 N

R2

291

NHO-5: R1 = Ph, R2 = Ph, R3 = Me

N

NHO-6: R1 = Ph, R2 = Me, R3 = Me

R3

NHO-7: R1 = H, R2 = Me, R3 = Me

Scheme 8.4 Structures of NHO-5–7 LBs

catalyst loading ([MMA]0 :[LB]0 :[LA]0 ≥ 400:1:2), [42] which exhibited comparable polymerization activity (TOF = 229–4800 h−1 ), I * values (82–125%), and controllability to MeAl(BHT)2 /NHO-1–3 (Scheme 8.2) FLP catalysts [28]. However, these polymerizations performed at a high catalyst loading showed moderate I * values (47–72%, [MMA]0 :[LB]0 :[LA]0 = 200:1:2), leading to the deviation from a living polymerization. Moreover, different from the generation of clean zwitterionic enolaluminate intermediates from the stoichiometric reaction of NHO-1–3 with MeAl(BHT)2 ·MMA, [28] the reactions of NHO-5–7 with MeAl(BHT)2 ·MMA yielded zwitterionic enolaluminate intermediates accompanied by unidentified species. Apart from methacrylates, LPP has also proven to be an effective strategy toward completely chemoselective polymerization of divinyl acrylic monomers via exclusively enchainment of methylacrylic vinyl group while leaving the nonconjugated vinyl group intact (Scheme 8.5a) [25, 43–45]. However, this method was hampered by low I * value and chain termination side reaction. In 2019, Lu and co-workers reported living and chemoselective polymerization of divinyl acrylic monomers, as represented by VBMA (Scheme 8.1d), at RT by utilizing bulky LP catalysts to minimize the interaction strength between LA and LB for achieving high or even quantitative I * value [46]. Despite that MeAl(BHT)2 /PR3 (R = Me, Et, Cy) LP can bring about moderate to high I * values (39–74%), the employment of sterically hindered NHO-1 (Scheme 8.2) as LB to pair with MeAl(BHT)2 can further increase I * to near quantitative value (103%), affording a PVBMA with a relatively low Ð value

a

O

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LB

X

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LA

X

(n-1 ) M

LB O

n

b

LA O

Ph

X

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Ph N

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X

NHO-8

c Ph N

Ph N

Ph MeAl(BHT)2·AMA

N Ph

N

O

Ph

AlMe(BHT)2 Claisen O

Rearrangement

N Ph

N

O

AlMe(BHT)2 O

Scheme 8.5 a Chemoselective polymerization of divinyl acrylic monomers; b The structure of NHO-8; c Deactivated side reaction of active zwitterionic intermediates in LPP of AMA

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of 1.19 ([VBMA]0 :[LB]0 :[LA]0 = 200:1:2, TOF = 1200 h−1 , M n = 39.1 kg/mol). When switching to EtAl(BHT)2 LA and NHO-8 (Scheme 8.5b) LB to construct sterically more demanding LP catalysts [MeAl(BHT)2 /NHO-8, et al. (BHT)2 /NHO-8], near quantitative I * values (93–102%) and relatively low Ð values of the resulting PVBMAs (1.23–1.27) were maintained, but the polymerization activity decreased (TOF = 120–600 h−1 ). In the same year, Zhang et al. utilized MeAl(BHT)2 /NHO-1 and MeAl(BHT)2 /NHO-3 FLPs as well as MeAl(BHT)2 /NHO-7 CLA (Schemes 8.2 and 8.4) for the successful chemoselective polymerization of AMA and VMA (Scheme 8.1d) [42]. The living characteristics of MeAl(BHT)2 /NHO-1 FLPmediated polymerizations of AMA and VMA were clearly verified. For all [M]0 :[NHO-1]0 :[MeAl(BHT)2 ]0 ratios from 200:1:2 to 800:1:2, monomers can be fully polymerized into the corresponding polymers (TOF = 800–6000 h−1 ) with predicted M n s, relatively low Ð values (1.10–1.39), and high to near quantitative I * values (81–103%). The stoichiometric reaction of NHO-1 with MeAl(BHT)2 ·AMA indicated that the formed zwitterionic active species gradually transformed into a deactivated intermediate through the Claisen rearrangement (Scheme 8.5c). Therefore, during the sequential block copolymerizations, the subsequent batch of comonomers after AMA block must be added in time to avoid the formation of this deactivated intermediate. Accordingly, the well-defined diblock copolymers (PMMA-b-PAMA, PAMA-b-PMMA and PAMA-b-PVMA) and triblock copolymers (PMMA-b-PAMA-b-PMMA, PAMA-b-PMMA-b-PAMA and PAMA-b-PVMA-bPAMA), as well as random PMMA-co-PAMA copolymer bearing pendant vinyl groups, can be successfully prepared. Different from MeAl(BHT)2 /NHO-1 FLP catalyst, decreasing the catalyst loading ([AMA]0 :[LB]0 :[LA]0 = 800:1:2) in the polymerizations by MeAl(BHT)2 /NHO-3 FLP and MeAl(BHT)2 /NHO-7 CLA broadened the dispersities of the resultant polymers (Ð: 1.78–1.81). To overcome the issue of poor control that is generally encountered in LPP of acrylamides, [26, 30, 38, 39, 47] in 2019, Zhang et al. investigated LPP of DMAA at RT catalyzed by NHO-based (Scheme 8.2) LPs using a series of organoaluminums as LAs [48], including Al(C6 F5 )3 (100) > AlPh3 ·OEt2 (88) ≈ MeAl(BHT)2 (86) > AlMe3 (71) ≈ AlEt3 (70) = Ali Bu3 (70), the Lewis acidities of which were measured by the Gutmann-Beckett method [49, 50]. Fixing a [DMAA]0 :[LB]0 :[LA]0 ratio of 800:1:2, when weakly acidic AlMe3 or AlEt3 was employed as an LA to pair with NHO-1 LB, the polymerization occurred rapidly with quantitative monomer conversion accomplished within 30 s (TOF = 96000 h−1 , M n = 281–303 kg/mol, Ð = 1.13), but I * values of these polymerizations were low rather low (26–28%) and backbiting chain termination was observed in AlMe3 /NHO-1-mediated polymerization. Switching to a sterically more demanding Ali Bu3 , a PDMAA with a bimodal distribution was produced, which should be caused by Ali Bu3 -initiated background polymerization. Remarkably, CLAs comprising relatively stronger acidic AlPh3 ·OEt2 LA and NHO-1–4 LB not only exhibited exceedingly high activity but also showed living characterization toward DMAA LPP (TOF = 96000 h−1 , M n = 104–116 kg/mol, Ð = 1.06–1.07, I * = 69–76%). Good controllability can also be extended to N,Ndiethylacrylamide (TOF = 96000 h−1 , M n = 90 kg/mol, Ð = 1.12, I * = 113%), and

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well-defined diblock and triblock copolymers with narrow Ð values were thereby successfully synthesized through the sequential addition method regardless of the monomer addition order. In contrast, fixing NHO-1 as an LB, the utilization of superacidic and sterically encumbered Al(C6 F5 )3 led to a rapid polymerization with a high I * value (TOF = 96000 h−1 , M n = 101 kg/mol, Ð = 1.08, I * = 78%) but it was not a living process due to the existence of backbiting termination, while the employment of the most sterically encumbered but less acidic MeAl(BHT)2 [relative to Al(C6 F5 )3 ] as an LA resulted in a slow (TOF = 80 h−1 ) and uncontrolled LPP by producing polymers with a bimodal distribution. Unlike the other methacrylates, the efficient and precise polymerization of semifluorinated methacrylates (SFMAs) by conventional anionic or coordination polymerization has remained an unmet challenge, despite the unique and intriguing characteristics of the resulting semifluorinated polymethacrylates (SFPMA), such as high hydrophobicity, tunable lipophilic character, low surface energy, and low refractive indices. In 2020, Wang and Hong developed the first LPP of SFMAs, as represented by trifluoroethyl methacrylate (TFEMA) and hexafluorobutyl methacrylate (HFBMA), which provides a viable strategy for the efficient synthesis of SFPMA with precise control of MW and stereospecificity (Scheme 8.6, top) [51]. Among different LAs [MeAl(BHT)2 , Al(C6 F5 )3 , B(C6 F5 )3 , AlMe3 , AlMe2 Cl] and LBs [It Bu, IMes, Ii Pr, IMe(Me), TPT, NHO-3, PPh3 (Scheme 8.6, bottom)], MeAl(BHT)2 /It Bu stood out as the best catalyst for SFMA LPP in terms of promoting the most active polymerization at RT ([SFMA]0 :[LB]0 :[LA]0 = 300–4500:1:2, TOF: 333–4500 h−1 ) and showing a high degree of control over the polymerization with high to near quantitative I * values (60.0–96.6%) and low dispersities (Ð ≤ 1.10). At an exceptionally large excess of monomer ([SFMA]0 :[LB]0 :[LA]0 = 4500/1/2), quantitative

n

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O F

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O

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N

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Al

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O

TFEMA

[rr] = 92% (-78oC)

Lewis Pair Catalyst

it-PMMA

O

F F

F

F F

O

n

F

O

F or

O F

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HFBMA F

Living Polymerization Stereocomplex

Mn up to 1300 kg/mol

Tm up to 175 °C

Ð = 1.01~1.10

F

Ph N

N ItBu

N

N

IMes

N

N IiPr

N

N

IMe(Me)

Ph N

N N Ph TPT

Scheme 8.6 (Top) Precise control of MW and syndiotacticity in LPP of SFMAs and subsequent stereocomplex formation; (Bottom) the structures of NHC LBs

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monomer conversion can be accomplished by this LP catalyst within 60–180 min, affording UHMW SFPMAs with very low Ðs (PHFBMA: M n = 1300 kg/mol, Ð = 1.03, I * = 87.0%; PTFEMA: M n = 919.2 kg/mol, Ð = 1.05, I * = 82.2%). The livingness of MeAl(BHT)2 /It Bu-mediated polymerizations of HFBMA or TFEMA at RT has been unequivocally established, which relies on the fast chain initiation without induction period, the stability of imidazolium enolaluminate active species, and complete suppression of detrimental side reaction [e.g., proton abstraction of –C(H)F– group by LB]. Despite the fact that NHO-3/MeAl(BHT)2 FLP has proven to promote a living polymerization of MMA with high to quantitative I * value, [28] the activity and I * value of HFBMA polymerization by such LP catalytic system were about one half of that by It Bu/MeAl(BHT)2 , which is presumably caused by the instability of NHO-3 in HFBMA monomer. Noteworthily, at –78 °C, the polymerization of TFEMA by MeAl(BHT)2 /It Bu not only showed good control over the MW (M n = 46.7 kg/mol, Ð = 1.16), but was also highly syndiospecific ([rr] = 92.0%). The resulting highly syndioregular PTFEMA (st-PTFEMA) can readily form supramolecular stereocomplex with isotactic poly(methyl methacrylate) (itPMMA), thus converting amorphous st-PTFEMA (glass transition temperature: T g = 85.2 °C) and it-PMMA (T g = 59.8 °C) into a robust fluorinated crystalline material with a high melting temperature (T m ) up to 175 °C (Scheme 8.6, top). In 2019, the controlled LPP of vinyl phosphonates [diethyl vinyl phosphonate (DEVP), diisopropyl vinylphosphonate (DIVP), Scheme 8.7] has also been achieved via the development of Al/P-based bridged Lewis pair catalysts (BLP-1: R1 = R2 = Me; BLP-2: R1 = Me, R2 = i Pr; BLP-3: R1 = Me, R2 = t Bu; BLP-4: R1 = i Bu, R2 = t Bu; BLP-5: R1 = i Bu, R2 = Me, Scheme 8.7) as reported by Rieger et al. [52]. Because of the coexistence of multiple initiation mechanisms, LPP of DEVP in previous reports generally resulted in broad dispersities of the resultant polymers. For example, PDEVP produced by Al(C6 F5 )3 /Pt Bu3 and Al(C6 F5 )3 /IMes CLAs at RT had a broad Ð of 2.11, [47] while the utilization of AlPh3 /PEt3 CLA for the

R2

P

a

R2 Al

H

b

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R1 -R2PMe

R1 Al

2

Al R 1 O P OR OR

1

-ylene

R1 R2 P R2

R1 O P OR OR

O P OR . OR

R1 R2 P R2

Al R 1 O P OR OR

O

R1 Al

(n-1) M

R2

n

O

P O

O R

R

DEVP: R = Et; DIVP: R = iPr

-ylid

c

H

O P R O R

P R1

R2

R2

P

Al R1 O P OR OR

R2 Al R1

R1

O P OR OR

Scheme 8.7 Possible initiation pathways for the BLP-mediated polymerization of vinylphosphonate: a deprotonation; b conjugate addition; c nucleophilic transfer

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

295

polymerization of DEVP at –30 °C led to a PDEVP with a relatively broad Ð of 1.33 [26]. In contrast to these intermolecular LP catalysts, intramolecular Al-P BLP-1 not only exhibited high activity toward DEVP and DIVP polymerizations at RT, but also afforded high-MW polymers with narrow to extremely narrow dispersities, though I * values of these polymerizations were relatively low ([monomer]0 :[BLP-1]0 = 500, DEVP: TOF = 3700 h−1 , M n = 250 kg/mol, Ð = 1.19, I * = 33%; DIVP: TOF = 450 h−1 , M n = 250 kg/mol, Ð = 1.05, I * = 38%). Moreover, living characteristics of their LPPs has been confirmed by the increase of polymer M n versus monomer conversion and monomer-to-initiator ratio with low Ðs maintained. Accordingly, the preparation of poly(DEVP-b-DIVP) diblock copolymer was accessible with BLP1, whereas the combination with reverse monomer order was unsuccessful. ESI-MS analysis revealed that no methyl or any other end group was detectable in the obtained PDEVP oligomer, and in the 31 P NMR spectrum of unquenched polymerization mixture, the appearance of the signal of free phosphine MePi Pr2 and the disappearance of the signal of BLP-1 can be observed. These results indicated that the polymerization is most likely initiated via the deprotonation of the acidic α-position of the monomer by the methylene bridge of BLP-1 followed by its cleavage and release of the free MePi Pr2 (Scheme 8.7a), thus ruling out the possible conjugate addition (Scheme 8.7b) and nucleophilic transfer pathways (Scheme 8.7c). The exclusive deprotonation initiation mechanism should be responsible for the good control of the polymerization process. Theoretical calculations provided further evidence for a deprotonation mechanism, as the natural bonding orbital charges for the bridging methylene showed negative values (ca. –1e) for BLP-1 as well as the other BLPs 2–5. In comparison to BLP-1, more sterically demanding BLPs 2–5 were less active or ineffective toward DEVP polymerization ([DEVP]0 :[BLP]0 = 500, BLP-2: TOF = 900 h−1 , M n = 290 kg/mol, Ð = 1.12, I * = 28%; BLP-3 and BLP-4: TOF = 0 h−1 ; BLP-5 (neat): TOF = 1200 h−1 ). The observed higher TOF for BLP-1 is presumably attributed to its low Gibbs free reaction enthalpies because of the formation of a neutral, thermodynamically favorable η2 -ylene deprotonation intermediate over a zwitterionic η1 -ylide intermediate (Scheme 8.7a). Different from efficient and controlled polymerization of DEVP by BLP-1, this BLP was unable to polymerize MMA, and the control for DMAA polymerization (Ð = 1.52) was lost, despite its remarkable activity ([DMAA]0 :[BLP-1]0 = 500, TOF = 10000 h−1 ). In place of conventionally sequential addition method, in 2020, Chen et al. established LPP as a unique and convenient methodology to synthesize well-defined block copolymers from one-pot comonomer mixture (mixed addition) [53]. The authors found that the combination of sterically unhindered PMe3 LB with MeAl(BHT)2 LA can differentiate n-butyl acrylate (n BA) and tert-butyl acrylate (t BA) (Scheme 8.8, top), where n BA was depleted first which then followed by the consumption of t BA, thus affording Pn BA-b-Pt BA diblock copolymer with a M n of 127 kg/mol and a unimodal distribution (Ð = 1.02) from one-pot comonomer mixture within 15 s ([t BA]0 :[n BA]0 :[LA]0 :[LB]0 = 100:900:2:1). This achievement was proposed to originate from three distinctive features of LPP. First, zeroth-order kinetics dependence on monomer concentration in LPP substantially suppresses the tapering effect that commonly presents in conventional polymerizations due to the first-order

296

M. Hong [Al]

O

O O

+

O BA

n

Keq = 16

O

RT

t

[Al] O O

BA

+

O

Scheme 8.8 (Top) Prior equilibrium differentiation between n BA and t BA biased by MeAl(BHT)2 [Al]; (bottom) COPASI (complex pathway simulator) simulations of typical chain-growth polymerization and LPP, illustrating the significant prior equilibrium differentiation effect in LPP (A = more reactive monomer, B = less reactive monomer, K eq = 16) Copyright 2020 American Chemical Society

kinetics with respect to monomer concentration (Scheme 8.8, bottom). Second, preferential coordination of MeAl(BHT)2 to n BA over t BA imposes the significant prior equilibrium differentiation effect (K eq = 16, Scheme 8.8, top). Third, the k p for n BA is ~30 times greater than that of t BA, which further diminishes the probability for misincorporation errors. Unlike the unimodal distributions of the block copolymers obtained by mixed addition, both Pt BA-b-Pn BA and Pt BA-b-Pn BA-b-Pt BA produced by sequential addition method exhibited bimodal distributions with low molecular weight shoulders due to uncontrolled polymerizations of n BA and t BA by MeAl(BHT)2 /PMe3 . These results reveal that mixed addition method can prevent LA-activated chain termination by occupying the free LA with a comonomer at all block constructing stages.

8.2.2 Biomass-Derived Polar Vinyl Monomers At present, synthetic polymers are predominantly based on nonrenewable petroleum resources which are being rapidly depleted by our surging energy demand and bringing about the detrimental environmental effects (e.g., CO2 emissions). Therefore, there is a pressing need to gradually replace petroleum-based polymers with

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

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those derived from naturally abundant and renewable feedstocks (e.g., biomass) [54– 57]. As a robust polymerization technology, the application of a LP catalyst system for the synthesis of novel bio-based polymers with notable properties has emerged recently, and showed a great potential in polymerizing challenging biomass-derived monomers that cannot be efficiently realized by traditional polymerization techniques. Accordingly, this section highlights the selected progresses made recently in the LPPs of biomass-derived polar vinyl monomers. In 2017, Xu and co-workers reported the first application of rare-earth metalbased LA for the LPPs of polar vinyl monomers [29]. In that study, a cationic scandium aryloxide complex containing phosphorus-tethered β-diketiminate ligand (Sc1, Scheme 8.9), which acted as the intramolecular interacting rare-earth/phosphorus (RE/P) LP, can mediate the polymerization of biomass-derived γ MMBL monomer ([γ MMBL]0 :[Sc-1]0 = 100, TOF = 100 h−1 ), albeit with low I * value of 32%. In 2019, Xu et al. modified the structure of Sc-1 by introducing a bulky benzyl substituent at the γ position and increasing the tether length, thus leading to the novel cationic scandium aryloxide complex (Sc-2, Scheme 8.9) [58]. Interestingly, in comparison to Sc-1, Sc-2 turned out to be a better LP catalyst in terms of promoting a more active γ MMBL polymerization (TOF = 1200 h−1 ) and giving rise to a higher I * value of 53%. Methyl crotonate (MC) is a biorenewable monomer which can be derived from biopolymer poly(3-hydroxybutyrate) via pyrolysis and subsequent transesterification. However, compared to its constitutional isomer of MMA, MC is less susceptible to nucleophilic attack due to the increased steric hindrance of internal double bond. In 2018, Chen and co-workers reported the effective polymerization of MC by utilizing LP catalyst consisting of MeAl(BHT)2 LA and NHC (It Bu, TPT, Scheme 8.6) or NHO-1 (Scheme 8.2) LB under RT and solvent free conditions [59]. When the ratio of LA:LB is fixed at 2:1, the commonly employed strategy to enhance the polymer MW by the increase of monomer loadings was infeasible in MC polymerizations, especially those mediated by MeAl(BHT)2 /It Bu or NHO-1, because of intensified chain transfer to MeAl(BHT)2 -activated monomer (Scheme 8.10) ([MC]0 :[MeAl(BHT)2 ]0 :[LB]0 = 100:2:1, It Bu: M n = 3.63 kg/mol, Ð = 1.35, I * = 276%, NHO-1: M n = 15.9 kg/mol, Ð = 1.10, I * = 65%; [MC]0 :[MeAl(BHT)2 ]0 :[LB]0 = 500:2:1: It Bu: M n = 3.25 kg/mol, Ð = 1.43, I * = 1140%, NHO-1: M n = 11.0 kg/mol, Ð = 1.90, I * = 432%). In this context, it was found that decreasing the initial concentration of LB while keeping the LA Scheme 8.9 Structures of cationic scandium aryloxide complexes Sc-1 and Sc-2 (Ar = 2,6-t Bu2 C6 H3 , DiPP = 2,6-i Pr2 C6 H3 )

Ph N

N

Sc P

DiPP

N

O [B(C6F5)4]

Ph Ph Ar

Sc-1

N

Sc P

DiPP

O [B(C6F5)4]

Ph Ph Ar

Sc-2

298

M. Hong t

Bu

N : t

O

H

N

[Al]

OMe

Bu

Initiation Deprotonation H MeO2C

t

CO2Me

Bu N

t N Bu

O [Al]

n

Propagation

MeO2C [Al]

[Al]

OMe

Chain Transfer to MC

O

O

OMe

CO2Me

H

CO2Me t n

Catalyst Recapture

Bu N

[Al]

t N Bu

MC

OMe

OMe O

[Al]

Scheme 8.10 Proposed chain initiation, propagation, It Bu/MeAl(BHT)2 -mediated polymerization of MC

and

transfer

mechanism

for

concentration constant around 2 mol% was an effective strategy for synthesizing high-MW polymers at increased monomer loadings. A high M n up to 161 kg/mol with a Ð of 1.62 and an I * of 62% can be achieved by MeAl(BHT)2 /TPT LP at a [MC]0 :[LA]0 :[LB]0 ratio of 1000:20:1. Depending on the nature of the LB, the polymerizations are initiated through two different mechanisms: NHO-1 and TPT prefer the nucleophilic initiation pathway through the formation of zwitterionic active species which is commonly observed in LPPs, whereas It Bu prefers the unique basic initiation pathway via the deprotonation of MeAl(BHT)2 -activated monomer by It Bu which led to vinyl-end functionalized PMC (Scheme 8.10). The uncovered basic initiation pathway was also exploited to the facile synthesis of a high-MW PMC (M n = 97.1 kg/mol) by simply using KOt Bu as initiator in combination with MeAl(BHT)2 . The obtained PMCs exhibited similar stereochemistry with approximately 70% disyndiotacticity regardless of the LP catalysts employed. PMC materials were also demonstrated to possess high heat resistance and high thermal stability as indicated by no obvious T g up to 280 °C, and a high onset degradation temperature of ~354 °C (T d , defined by the temperatures of 5% weight loss). Unlike less reactive MC, the challenge of polymerizing indenone (IN), derived from biorenewable cinnamic acid, lies in its high reactivity which is susceptible to undergo autopolymerization because of the unstable anti-aromatic structure (Scheme 8.11, top). In 2019, Chen et al. reported the successful preparation and storage of IN and realized its first effective polymerization without autopolymerization side reactions by using LP catalysts [60]. The storage of IN in a diluted

8 Lewis Acid−Base Pairs for Polymerization Catalysis … O

O

OLA

O

OSiMe3

O

OSiMe3

LB:

LB: NHO-1

n

299

n

OMe

LA

LA

IN

NHO

O

anti-aromatic

OMe O

O

O

O

O

O

O

O

n

Erythro-diisotactic

O

n

Threo-diisotactic

O

O

O

O

O

O

O

n

n

Erythro-disyndiotactic

Threo-disyndiotactic

Scheme 8.11 (top) LPP of IN to PIN by LA/SKA and LA/NHO-1 LPs; (bottom) four possible diastereoregular structures of PIN

dichloromethane (DCM) solution (0.77 M) at −30 °C enabled the elimination of autopolymer contaminants within 7 days, and IN was also stable within 24 h when stirring its storage solution at RT under dark conditions. In contrast, an autopolymerized polyindenone (PIN) (yield = 87%, M n = 205 kg/mol, Ð = 1.91) was formed when stirring bulk monomer at RT for 72 h. After the establishment of a storage method, B(C6 F5 )3 or MeAl(BHT)2 /silyl ketene acetal (SKA) LP, and MeAl(BHT)2 /NHO-1 FLP were employed for group transfer polymerization and LPP of IN (Scheme 8.11, top). At RT, these LPs were all active toward IN polymerizations, where the latter FLP ([IN]0 :[LA]0 :[LB]0 = 500–1000:2:1, TOF = 500 h−1 ) showed higher activity than the former LPs ([IN]0 :[LA]0 :[LB]0 = 300–500:2:1, TOF = 25–42 h−1 ). Intriguingly, B(C6 F5 )3 /SKA led to soluble PINs with high M n s of 81–172 kg/mol and low Ð values of 1.13–1.23, while PINs produced by MeAl(BHT)2 /NHO-1 or SKA were insoluble in common solvents. The different diastereoregularity of PINs is responsible for their different solubility. Relatively high diastereoregularity of 71–75% can be achieved by steric bulky LPs based on MeAl(BHT)2 due to the chain-end control mechanism, whereas B(C6 F5 )3 /SKA led to a PIN sample with diastereoregularity of 57% and autopolymerized PIN was completely amorphous. Among four possible diastereoregular strucures, including threo-diisotactic, erythro-diisotactic, threo-disyndiotactic, and erythro-disyndiotactic (Scheme 8.11, bottom), erythroditacticitic units seemed the most reasonable arrangements as indicated by Newman projections. Noteworthily, due to an increase of crystallinity, PIN samples with erythro content between 57 and 75% exhibited significantly enhanced T g and T d values of 307 and 356 °C, relative to the amorphous autopolymerized PIN (T g = 269 °C, T d = 329 °C). Controlled pyrolysis of PIN upconverted it into versatile graphite oxide with up to 54% conversion, offering a valuable upcycling avenue for PIN at the end of its life. Currently, the vast majority of biomass-derived monomers are derived from edible resources (e.g., starch, sugar crops, plant oils) which will arouse a competition for food with the growing global population in future. In this context, monomers based on lignocellulosic biomass (e.g., forestry, agricultural residues) would be the most

300

M. Hong

ideal biomass resource because of its wide availability at a low cost. In 2020, Hong and Wang established a versatile bio-refinery platform to a high-quality gasolinelike biofuel and a heat- and solvent-resistant acrylic bioplastic (T g = 263.7 °C, T d = 364.0 °C) via LP-mediated selective dimerization and polymerization of lignocellulose-based β-angelica lactone (β-AL, Scheme 8.12a) [61]. Because of inert cyclic double bond of β-AL compared to its analogues (reactivity: β-AL < MC < MMA < γ MMBL) as well as the acidity of γ -H of β-AL which is susceptible to form the dimer or oligomer via chain transfer to monomer, β-AL has remained an unexploited bio-based monomer for polymerization. In this study, when RAl(BHT)2 (R = Me, Et, i Bu)/Ii Pr CLA was utilized as the catalyst, the first successful polymerization of β-AL can be achieved. A noticeable increase of activity and PβAL M n were observed with enhancing the steric hindrance of LA, and increasing LA/Ii Pr ratio from 2/1 to 4/1 was also proved to be an effective way to enhance M n of PβAL. With a [β-AL]0 :[i BuAl(BHT)2 ]0 :[Ii Pr]0 ratio of 300:4:1, quantitative β-AL conversion was accomplished within 5 min (TOF = 3600 h−1 ), affording exclusively PβAL with relatively high M n up to 26.0 kg/mol (Ð = 1.61). Unlike the commonly observed nucleophilic initiation pathway in LPP, this polymerization is initiated via basic pathway via the formation of [Ii Pr-H]+ –enolaluminate ion pair active species through the deprotonation of γ -H of MeAl(BHT)2 -activated β-AL by Ii Pr (Scheme 8.12b). The catalytic cycle of RAl(BHT)2 /Ii Pr CLA-mediated polymerization is proposed to consist of basic initiation-conjugate addition-MeAl(BHT)2 release-chain transfer to monomer fundamental steps (Scheme 8.12b). The keys to successful polymerization by RAl(BHT)2 (R = Me, Et, i Bu)/Ii Pr CLA have mainly relied on (1) the balanced Lewis acidity of RAl(BHT)2 which is sufficient for monomer activation but the lowest possible to suppress the LA-activated chain transfer to monomer; (2) the utilization of strongly Lewis basic Ii Pr to shut down chain transfer to [Ii Pr-H]+ . Intriguingly, when switching from Ii Pr to weakly basic Et3 N to construct FLP with MeAl(BHT)2 , the resultant product shifted from exclusive polymer to the dimer without any detectable PβAL formation. It is noteworthy that MeAl(BHT)2 /Et3 N is highly active toward the selective dimerization of β-AL (TOF: 200–1000 h−1 ). Even though 4000 equiv. of β-AL were employed, quantitative β-AL conversion can be accomplished within 810 min. The exquisite selectivity of MeAl(BHT)2 /Et3 N FLP toward dimerization has the relationship with the unique H-shuttling chain transfer to [Et3 N-H]+ [Scheme 8.12c (top)], besides chain transfer to monomer [Scheme 8.12c (bottom)]. Most remarkably, the obtained dimer can further act as a practical precursor for hydrodeoxygenation to generate gasoline-like alkanes. Upon treatment with Pt/C + TaOPO4 metal-acidic solid catalyst at 300 °C under 200 psi H2 for 3 h, high-quality biofuel in the gasoline volatility range was yielded with high alkane selectivity of 87% (C8: 72.6%, C9: 14.4%).

O

O

O

O

O

O

n

O

n

O

O

+

O

O

[Al]

[Al]

O

O

O

O

O

O

Propagation

[H-LB]

Initiation Deprotonation

[Al]

Dimer

Catalyst recapture

[H-LB]

O

O

O [Al]

H Me

Chain transfer

O

O

O

LB

Biofuel

O

O

O

[Al]

O

[Al]

(n+1) O

n

O

O

FLP

O

[H-LB]

[Al] O

Dimerization

c

O

O

O

-AL

O CLA

O

O

O

O

O

H

Et3N +

H

O

O

O

O

O

O

Polymerization

[Al]

n

O [Al]

Acrylic Bioplastic

O

[Al]

O

O

O

O

O

[Al]

O [Al]

[Et3N-H]

Chain transfer to monomer

[Et3N-H]

O [Al]

H-shuttling chain transfer

O

O

[Et3N-H]

O

Et3N + O

O

O

O

O

O

[Al]

[Al]

H

[Al]

Scheme 8.12 LP-mediated selective dimerization and polymerization of β-AL to biofuel and acrylic bioplastic (a); proposed mechanistic scenario of β-AL polymerization by MeAl(BHT)2 /Ii Pr CLA (b); and β-AL dimerization by MeAl(BHT)2 /Et3 N FLP (c)

O

b

a

H2

8 Lewis Acid−Base Pairs for Polymerization Catalysis … 301

302

M. Hong

8.3 Lewis Pair-Mediated Ring-Opening (Co)Polymerization Ring-opening (co)polymerization [RO(C)P] of cyclic esters or epoxides generally affords biodegradable and/or biocompatible polymers that have been recognized as greener or more sustainable polymeric materials relative to the conventionally nondegradable petroleum-based polymers [18, 19, 23, 62–68]. To achieve competitive physical and mechanical performance with petroleum-based polymers, one of the critical and practical approaches is to control the microstructure (e.g., MW, chemo-, regio-, and stereoselectivity) of ring-opened polymers via the development of powerful polymerization catalysis. The recent advances in the employment of LP catalysts for furnishing a high degree of control over RO(C)Ps are updated in this section of the chapter. O-Carboxyanhydrides (OCAs) can be prepared with a rich variety of side-chain functionalities from natural α-hydroxy acids or amino acids, thus considered as an alternative class of the monomers to lactide and its derivatives for ROP to produce poly(α-hydroxy acids) with diverse physical properties. In 2018, Yang, Meng, and co-workers found that the CLA comprising Zn(C6 F5 )2 and organic amines can efficiently initiate the controlled/living ROP of OCAs [69]. Screening the polymerization solvents [DCM, CHCl3 , dioxane, tetrahydrofuran (THF)] and temperatures (25–50 °C) by using Zn(C6 F5 )2 /1-hexanamine as the catalyst indicated that performing the polymerization in THF at 50 °C represented the optimized conditions for Phe-OCA (Scheme 8.13) ROP, because of the favored dissociation of CLA under these conditions. Increasing [Phe-OCA]0 :[Zn(C6 F5 )2 ]0 :[1-hexanamine]0 ratio from 25:1:1 to 200:1:1, complete monomer consumption can be accomplished with 1–24 h (TOF: 7–40 h−1 ), affording well-defined poly(Phe-OCA)s with M n values Ph H R N Zn(C6F5)2 H + Phe-OCA

O

O O

O

O

R N Zn(C6F5)2 H H

-CO2

O

O n

H

RNH

OH

Initiation

O RNH

Zn(C6F5)2

Coordination-insertion RNH

Zn O

C6F5 -C6F5H

Propagation Zn-alkoxide

Scheme 8.13 Proposed mechanism for ROP of Phe-OCA by Zn(C6 F5 )2 /RNH2 CLA

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

303

close to the calculated ones (M n up to 26.8 kg/mol) and low Ð values below 1.10. As a control, no polymer or only oligomer was obtained when the polymerization was initiated by 1-hexanamine or Zn(C6 F5 )2 alone. Switching to manOCA (Scheme 8.14), the controlled ROP was also achieved by Zn(C6 F5 )2 /1-hexanamine ([man-OCA]0 :[Zn(C6 F5 )2 ]0 :[1-hexanamine]0 = 50:5:1, M n = 8.1 kg/mol, Ð = 1.10, TOF = 17 h−1 ), thus giving access to the preparation of poly(Phe-OCA-b-man-OCA) diblock copolymer via sequential addition. The combination of Zn(C6 F5 )2 with the other primary amines (e.g., cyclohexamine, benzylamine, phenylamine) or secondary amine (diethylamine) all exhibited good control over MW for Phe-OCA ROP with identical activities. Experimental mechanistic studies and the theoretical calculations reveal that both amine and Zn(C6 F5 )2 are involved in the cooperative catalysis of initiation, which is followed by the ring opening and decarboxylation to give an intermediate with a hydroxyl group that can react with Zn(C6 F5 )2 to generate a Zn-alkoxide terminus for subsequent coordination–insertion chain propagation (Scheme 8.13). Correspondingly, poly(Phe-OCA) with an amide group at the α-terminus of the polymer chain was yielded. In addition, ROPs of enantiomerically pure Phe-OCA and manOCA by Zn(C6 F5 )2 /1-hexanamine were also attempted, which resulted in polymers with moderate isotacticities (66–77%) caused by the epimerization side reaction due to high C–H acidity at chiral center. To avoid the epimerization side reaction in manOCA ROP, in 2020, Wu et al. developed a selective catalyst system based on a weak LP composing of 3-fluoropyridine (3-F-Py) LB and aminobisphenolate zinc complex LA (Zn-1: R1 = R2 = t Bu, R3 = Me; Zn-2: R1 = R2 = t Bu, R3 = Et; Zn-3: R1 = Ad, R2 = t Bu, R3 = Me; Zn4: R1 = t Bu, R2 = OMe, R3 = Me, Scheme 8.14), which can smoothly convert enantiomerically pure L-manOCA into poly(L-manOCA) in presence of L-methyl lactate (L-ML) initiator at RT in toluene with Zn-1/3-F-Py as the most selective LP F N

R1 O

Zn

R1 O

N

R2

R2

R3

O

Ph O

Ph O

x

O

O y

O Ph Isotactic poly(rac-manOCA)

O O R1

O

Ph O

O

Ph

O

O R2 O

O

Ph

manOCA

O

O

F

O O

O

n

Ph poly(L-manOCA)

N

O

-CO2

O H R R1 O O Zn O

N R3

O

Ph R2

O

O

poly(D-manOCA) O O n

O

Ph

Scheme 8.14 Synthesis of enantiopure poly(L-manOCA) and poly(D-manOCA) as well as isotactic poly(rac-manOCA) via the ROP of L-manOCA, D-manOCA, and rac-manOCA, respectively, by 3-F-Py/aminobisphenolate zinc complex

304

M. Hong

of the series (Zn-1: Pm = 0.99, Zn-2–4: Pm = 0.95–0.96, [L-manOCA]0 :[Zn]0 :[3F-Py]0 :[L-ML]0 = 50:1:1:1, TOF = 77–100 h−1 ) [70]. However, when switching to Zn-5 (R1 = R2 = t Bu, R3 = H), the ROP occurred accompanied by serious epimerization (Pm = 0.54), presumably attributed to the more open environment of the zinc center because of the small R3 (hydrogen atom) that makes the inversion of the chiral center of manOCA easier. In all cases, M n s (4.2–24.2 kg/mol) of the obtained polymers are close to the calculated values with low Ð values (1.08–1.10), indicative of good controllability of these LPs over MW. In contrast, the polymerization by Zn-1 or 3-F-Py alone only led to negligible or sluggish activity. The most selective Zn-1/3-FPy LP was also exploited for stereoselective ROP of rac-manOCA (Scheme 8.14), but it produced atactic poly(rac-manOCA) at RT (Pm = 0.60). Remarkably, decreasing the polymerization temperature from RT to –50 °C can significantly enhance the isoselectivity, generating a highly isotactic poly(rac-manOCA) with Pm up to 0.92 (M n = 5.3 kg/mol, Ð = 1.12) due to the chain-end control mechanism, which represents the first stereoselective ROP of rac-manOCA. A noticeable increase in the T g value from 84 to 92 °C was observed when the isotacticity of poly(rac-manOCA) increased from Pm = 0.60 to 0.92. A T m peak at 116 °C appeared for isothermally crystallized isotactic poly(rac-manOCA) (Pm = 0.92) on account of stereocomplex formation, in comparison to no obvious T m for atactic poly(rac-manOCA) (Pm = 0.60). When enantiopure poly(L-manOCA) and poly(D-manOCA) were mixed at 1:1 ratio, T m value of the resulting stereocomplex material can reach 173 °C after isothermal crystallization. LP catalysts have also been applied for the preparation of high-MW poly(propylene oxide) (PPO) via ROP of propylene oxide (PO) as reported by Naumann et al. in 2019 [71]. Due to the existence of chain transfer to monomer side reaction (Scheme 8.15, top), the synthesis of high-MW PPO via conventional anionic polymerization still remains a challenge. It was found that a cooperative LP catalyst based on NHO-9 LB and novel magnesium bis(hexamethyldisilazide) [Mg(HMDS)2 ] LA can address this challenge (Scheme 8.15, middle). A PPO with a M n of 520 kg/mol and a relatively low Ð of 1.24 was produced within 81 h through performing the polymerization in pentane at –36 °C with a [PO]0 :[Mg(HMDS)2 ]0 :[NHO-9]0 ratio of 5000:10:1. A zwitterionic polymerization mechanism has been confirmed, where the polymerization is initiated by the nucleophilic attack of NHO-9 to Mg(HMDS)2 activited PO and propagated via a bimolecular, activated monomer mechanism (Scheme 8.15, bottom). The role of Mg(HMDS)2 , which is critical for obtaining high-MW PPO, is trifold: (1) activating PO to render the formation of zwitterionic initiated species and the occurrence of propagation, since neither NHO-9 nor Mg(HMDS)2 alone was able to initiate polymerization; (2) forming stable CLA with NHO to enable a high ratio of monomer to initiator (i.e., low I * ) for high-MW product; (3) stabilizing the oxyanion species to suppress transfer-to-monomer side reaction for high-MW product. Compared with NHO-9, pairing Mg(HMDS)2 with a more basic NHO-1 (Scheme 8.2) led to a UHMW PPO with a M n up to 1400 kg/mol and a Ð of 1.55 in 144 h ([PO]0 :[Mg(HMDS)2 ]0 :[NHO-1]0 = 5000:20:1), probably due to even lower I * . Besides, the combination of Mg(HMDS)2 with the other NHOs [NHO-10 and NHO-11 (Scheme 8.15, middle)] can all promote a smooth

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

305

O O

N

O M

H

O

N

N

NHO-9

N

N

NHO-10

R'

O

O

EO

PO

BO

O

N

NHO-11 Ph

Cl O

M

+

OH

O

O

O

ECH

CHO

SO

=

O

NBGE

N

O

Me3Si

N

O

AGE

O

O

SiMe3 N SiMe3 Mg

N

O

TBGE

O

N N

+ Me3Si

SiMe3

SiMe3 N Mg SiMe3 N

Mg(HMDS)2 O

N

O

N SiMe3 Initiation

N N

O

O

Mg(HMDS)2

Propagation

N N

O Mg(HMDS)2

Scheme 8.15 (Top) The side reaction of chain transfer to monomer generally encountered in anionic polymerization; (Middle) Structures of NHOs and epoxides; (Bottom) Proposed mechanism for chain initiation and propagation

ROP of PO despite lower activity relative to Mg(HMDS)2 /NHO-9, while the utilization of the other LAs together with NHO-9 failed to polymerize PO (LiCl, MgCl2 , MgI2 , ZnI2 , YCl3 , KHMDS) or only produced PPO oligomer (LiHMDS). Moreover, Mg(HMDS)2 /NHO-9 was also suitable for the ROP of allyl glycidyl ether (AGE, Scheme 8.15, middle) to synthesize a vinyl-functionalized aliphatic polyether with a high M n of 880 kg/mol (Ð = 1.65, 72 h, [AGE]0 :[Mg(HMDS)2 ]0 :[NHO-9]0 = 1000:5:1). However, in Mg(HMDS)2 /NHO-9-mediated ROP of 1,2-butylene oxide (BO, Scheme 8.15, middle), the resulting M n was almost an order of magnitude lower than that received for PO under the same conditions. The wide applications of aliphatic polyethers in biomedicine, pharmaceuticals and cosmetics call for the development of the noncytotoxic metal-free catalysis for epoxide ROP. In 2018, Zhao and co-workers reported the combination of mild organobase LB with weak acidic triethylborane (BEt3 ), which has succeeded in promoting alternating copolymerization of CO2 (COS) with epoxides previously, [35, 36] led to the establishment of efficient, living, and metal-free ROP of epoxides at RT [72]. To decrease cytotoxicity of resulting poly(ethylene oxide) (PEO)

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M. Hong

products, water was used as the simple initiator and phosphazene superbase t BuP1 was selected as the LB to pair with BEt3 for ROP of ethylene oxide (EO) (Schemes 8.15 and 8.16). At a relatively high initiator loading ([EO]0 :[H2 O]0 :[t BuP1 ]0 :[BEt3 ]0 = 24000:10:1:3), t Bu-P1 /BEt3 exhibited controlled bulk polymerization toward EO with a predictable M n of 96.6 kg/mol and a low Ð value of 1.26. Reducing the initiator loading to a very low level ([EO]0 :[H2 O]0 :[t BuP1 ]0 :[BEt3 ]0 = 24000:1:1:3) can provide PEOs with high M n up to 632.5 kg/mol after 7 h polymerization, despite broad MW distribution (Ð = 2.98). The utilization of THF as the solvent rendered more controlled polymerization (Ð = 1.06– 1.12). Importantly, after removal of THF solvent, these unquenched PEO products are noncytotoxic toward a variety of cell lines regardless of the amount of t BuP1 used. A short α-allyl-ω-hydroxyl bifunctional PEO (M n = 1.4 kg/mol, Ð = 1.12) and 4-arm hydroxyl-terminated PEO (M n = 18.8 kg/mol, Ð = 1.15) were also synthesized in the presence of 2-allyloxyethanol (AOE) and pentaerythritol (PT) initiators (Scheme 8.16), respectively. Compared with EO, t Bu-P1 /BEt3 was much less active toward PO polymerization when 1,4-benzenedimethanol (BDM, Scheme 8.16) was used as initiator, though its good control over MW was maintained (Ð = 1.07). The screening of the LB scope showed that t Bu-P2 constructed a better LP with BEt3 relative to DBU, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec5-ene (MTBD) and 1,5,7-triazabicyclododecene (TBD) (Scheme 8.16) in terms of higher activity and better control without detrimental transfer reaction to PO ([PO]0 :[H2 O or BDM]0 = 80–1600:1, 4–12 h, Conv. = 89–100%, M n = 4.8– 106.4 kg/mol, Ð = 1.06–1.14). However, a deviation of M n from the calculated OH R-OH

=

Base

=

O

OH

N

t

Bu-P1

HO

OH

HO

OH

BDM

HO

N N N P N P N N N

N N P N

t

AOE

PT

N

N

N

Bu-P2

N

DBU

R-OH

+ Base + Et3B

N

MTBD R'

Et3B

Et3 B R-O

N N

H- Base

TBD Et3 B R-O

O Et3B

N H

H- Base

O R'

R' R

O

R' O n

Dormant Chain

OH R'

Et3B

+ Base

R

O

Et3B O

O n R' Active Chain

H- Base

Initiation

Propagation R

O

Et3B O

H- Base

R'

Scheme 8.16 (Top) Structures of bases and ROH employed in this LPP study; (Bottom) Proposed mechanism for chain initiation and propagation

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

307

value was also observed when the polymerization was performed at a relatively low initiator loading ([PO]0 :[BDM]0 :[t Bu-P2 ]0 :[BEt3 ]0 = 16000:1:10:30, M nGPC = 210.3 kg/mol, Ð = 1.07, M nCal = 902.1 kg/mol). t Bu-P2 /BEt3 can also mediate controlled ROP of BO, tert-butyl glycidyl ether (TBGE), and AGE, but was ineffective for the polymerizations of styrene oxide (SO) and cyclohexene oxide (CHO) (Scheme 8.15). PEO-b-PPO-b-PEO, PPO-b-PEO-b-PPO, PAGE-b-PTBGE-b-PAGE triblock, PTBGE-b-PBO-b-PPO-b-PBO-b-PTBGE pentablock, as well as one-pot one-catalyst to PPO-based polyurethane, were successfully synthesized by t Bu-P2 (or t Bu-P1 )/BEt3 . The formation of both three-component base-H+ –O(R)–BEt–3 complex and BEt3 -activated epoxide enabled the occurrence of cooperative initiation, while the fast activity exchange between dormant and active hydroxy species has been proven essential for controlled polymerization (Scheme 8.16, bottom). Meanwhile, Zhang et al. also reported the living and efficient ROP of epoxides (e.g., PO, EO, BO) at 0 °C by using the same BEt3 /organic base LP catalytic system [73].Among the alcohol initiators [e.g., BnOH, MeOH, EtOH, BDM, HO(CH2 )3 OH] and organic bases (e.g., t Bu-P1 , t Bu-P2 , DBU, MTBD) evaluated, BEt3 /t Bu-P2 /BnOH was found to be the most active catalyst for PO ROP, in which rapid monomer consumption was observed within 2 min (TOF = 7500 h−1 , [PO]0 :[BnOH]0 :[BEt3 ]0 :[t Bu-P2 ]0 = 250:1:3:1). A PPO with a high M n up to 80.5 kg/mol and a very low Ð of 1.03 was obtained. Regioselectivity in the ROPs of rac-PO, S-PO and R-PO can be achieved by this catalytic system, showing the presence of head-to-tail structure without any detectable head-tohead or tail-to-tail linkage as a result of the selective attack at the methylene site of PO by the growing active species. Taking advantage of the living nature of this catalyst, a triblock copolymer poly(COS-alt-PO)-b-PPO-b-poly(COS-alt-PO) as well as diblock copolymers PEO-b-PPO and poly(styrene-b-PO) starting from αmethoxy/ω-OH PEO and hydroxyl-end functionalized polystyrene macroinitiators were synthesized accordingly. When BEt3 was added in excess of the t Bu-P2 (e.g., BEt3 :t Bu-P2 = 3:1) to the mixed monomers of epoxide and cyclic ester, only ROP of epoxide occured selectively with cyclic ester remained unreacted, while t Bu-P2 alone or t Bu-P2 in excess of BEt3 allowed the selective ROP of cyclic ester. On the basis of this disclosure, in 2019, Zhang, Ling, and co-workers established a switchable polymerization to ether-ester-type multiblock copolymer by switching the monomer selectivity in the copolymerization of epoxide and cyclic ester through varying the amount of BEt3 or t Bu-P2 during the polymerization [74]. For example, t Bu-P2 was first added to a mixture of δ-VL, PO, and BDM to turn “on” selective ROP of δ-VL ([δ-VL]0 :[PO]0 :[BDM]0 :[t Bu-P2 ]0 = 110:150:1:0.1, Scheme 8.17, top). When near quantitative conversion of δ-VL (94%) was accomplished after 30 min, BEt3 was added to the mixture ([BEt3 ]0 :[t Bu-P2 ]0 = 3:1) to turn “off” ROP of δ-VL and turn “on” selective ROP of PO for [12 h, Conv. (PO) = 84%]. Correspondingly, well-defined PPO-b-PVL-b-PPO triblock copolymer (M n = 19.0 kg/mol, Ð = 1.09) was successfully produced without random or tapered sequence (simultaneous enchainment of two monomers). The PVL-b-PPO-b-PVL triblock copolymer (M n = 30.7 kg/mol, Ð = 1.10) with ether-first order was also feasible (Scheme 8.17, top),

308

M. Hong xtBu-P2 + yBEt3 x>y

R(OH)2

+n

= cyclic ester/carbonate

m4

H

O R O

m'

y>x>0

H

O R O

H

n'

y' BEt3

H

(y' + y) > x

m'

O R O

n'

n'

H

m'

+m xtBu-P2 + yBEt3

R(OH)2

H

n'

0

+n

n4

2n'

x' tBu-P2

H

(x' + x) > y n, 2m'

n'

O R O

m'

m, (x' + x) 0.6, (y' + y)

m'

H

n'

1.0

0.1 tBu-P2 0.4 BEt3 0.5 tBu-P2 0.6 BEt3 0.7 tBu-P2 0.8 BEt3 1.0 tBu-P2 1.2 BEt3

+m

m3

= epoxide

H

m'

n3

= -VL

m2

n2

m1

= PO

n1

O R O

n1

2(n1+ n2 + n3 + n4)

m1

n2

m2

n3

n4

m3

n, 2(m1+ m2 + m3 + m4)

H

m4

m

Scheme 8.17 (Top) General scheme for triblock copolymers in both ester-first and ether-first orders; (Bottom) Multiple switches for multiblock copolymer

which can be readily realized by adding both BEt3 and t Bu-P2 to the mixed δ-VL and PO at the beginning to turn “on” selective ROP of PO ([PO]0 :[δ-VL]0 :[BDM]0 :[t BuP2 ]0 :[BEt3 ]0 = 160:150:1:0.1:0.3, 48 h, Conv. (PO) = 91%) and then subsequently adding excess t Bu-P2 to switch the monomer selectivity from PO to δ-VL ([t BuP2 ]0 :[BEt3 ]0 = 1.5, 0.5 h, Conv. (δ-VL) = 99%). This switchable polymerization was successfully expanded to a variety of cyclic esters (ε-CL, rac-lactide, L-LA, trimethylene carbonate), epoxides (EO, BO, AGE, TBGE), and alcohol initiators (benzyl alcohol, 5-norbornene-2- methanol, HO(CH2 )3 OH, PT), leading to a rich catalog of block copolymers with variable compositions and architectures. Remarkably, continuous back-and-forth switches of monomer selectivity can be achieved up to seven times, thus giving access to a pentadecablock copolymer from a mixture of δ-VL and PO (Scheme 8.17, bottom). In 2019, Li, Wang, and co-workers reported the facile synthesis of sequencecontrolled poly(ether-b-ester-b-ether) triblock copolymers in a one-pot manner from the monomer mixture of anhydride and excess epoxide by utilizing BEt3 /t Bu-P2 LP catalytic system [75]. It was found that loading 2 equiv. of BEt3 versus t Bu-P2 in the presence of BDM initiator was critical for achieving living polymerization with controlled monomer sequence, where alternating copolymerization of anhydride and epoxide proceeded selectively until the fully conversion of anhydride to afford ester block at first which then followed by sequential ROP of epoxide to accomplish ether blocks (Scheme 8.18), thus yielding the desired well-defined poly(ether-bester-b-ether) triblock copolymers. Various anhydrides [phthalic anhydride (PA), exo-norbornene anhydride (exo-NA), tetrahydrophthalic anhydride (THPA), caronic anhydride (CA), succinic anhydride (SA), (Scheme 8.18) and epoxides [BO, PO, nbutyl glycidyl ether (NBGE), AGE, epichlorohydrin (ECH), Scheme 8.15, middle] were demonstrated as good candidates for this one-pot block copolymerization. The broad monomer scope thereby allowed fabricating a library of structurally diverse triblock copolymers with M n s in the range of 8.6–113.1 kg/mol, low Ð values

8 Lewis Acid−Base Pairs for Polymerization Catalysis … O

+ R1

O

O R2

O

O

O

=

O

R2

R2

O

O

t

O Bu-P2/BEt3 BDM

O

O

Ar

309 R2

R2

O

O H

H

O

O

exo-NA

THPA

O

O

O H

H

R2 PA

R1 O

O

O

O

O n

R1

O

H

m

O

2

O

O

H

H

CA

SA

Scheme 8.18 One-pot synthesis of poly(ester-b-ether) block copolymer via alternating copolymerization of anhydride with epoxide and sequential ROP of epoxide

(1.05–1.16), and 24–67 mol% ether block. When enantiomerically pure S-PO was employed, highly regioselective ring opening of S-PO (head-to-tail structure) can be realized by BEt3 /t Bu-P2 LP, producing crystalline poly[SPO-b-(SPO-alt-PA)-b-SPO) triblock copolymer with high isotacticity ([mm] = 96.2%). Moreover, BEt3 /t Bu-P2 LP was also capable of suppressing epimerization of tricyclic and bicyclic anhydrides (exo-NA, THPA, CA) during the polymerization. Interestingly, recognizing the fact that ROP of L-LA was dramatically faster than the ROP of BO, the preparation of poly[LLA-b-BO-b-(BO-alt-PA)-b-BO-b-LLA) pentablock was feasible by adding L-LA during the process of BO ROP which acted as an external trigger to switch the selective ROP from BO to L-LA. In 2017, Zhang, Darensbourg, and co-workers reported alternating and regioselective copolymerization of COS with PO by BEt3 /organic base (e.g., DBU, TBD) LP catalytic system, thus establishing a new metal-free approach to poly(monothiocarbonate) [36]. However, this copolymerization proceeded in an uncontrolled manner (Ð: 1.6–1.9). Recently, living, alternating, and regioselective copolymerization of COS with PO without oxygen–sulfur exchange reaction was realized by the employment of highly active BEt3 /N,N,N’,N’tetraethylethylenediamine (TEED, Scheme 8.19, top) LP catalyst as reported by the same group [76]. Compared with triethylamine ([BEt3 ]0 :[TEA]0 = 1:1, Conv. (PO) = 12%), the combination of BEt3 with diamine TEED can significantly enhance the activity for bulk copolymerization under the similar conditions (Conv. (PO) = 94%, [COS]0 :[PO]0 :[BEt3 ]0 :[TEED]0 = 1000:500:1:0.5, 60 °C, 0.1 h), yielding an alternating copolymer product (88% vs cyclic thiocarbonate, Scheme 8.19, top) with high chemoselectivity (> 99%, without a detectable ether linkage) and high regioselectivity (> 99% tail-to-head linkage). The copolymerization carried out in THF became more controlled, in which the Ð value of the resulting copolymer decreased from 1.34 (M n = 79.8 kg/mol) to 1.10 (M n = 62.0 kg/mol) and the copolymer selectivity increased from 88% to > 99%. The screening of the diamine scope showed that TEED is unique for efficient copolymerization, while the other diamines with BEt3 were either low active [N,N,N,N-tetraethyl-1,3-propanediamine

310

M. Hong

O

N

+

O C S

N

N

N TEA

TEED

BEt3 O

S

N

N

TEPD

N

TEMD

N

TMDM

O

+O C S Initiation

N

+ O n

N

N

TMED

N

S

O

N

O

O

BEt3/LB

N

O

S

BEt3 2

Et3B Propagation

O 2

Cl

O

S

OH n

NH

Cl

+

HN Cl

HCl/Ethanol Termination

O N

O

S

OBEt3 n

2

Scheme 8.19 (Top) Copolymerization of COS with PO by BEt3 /tertiary diamine LP catalytic system; (Bottom) Proposed mechanism for COS/PO copolymerization by BEt3 /TEED LP

(TEPD), N,N,N,N-tetramethylethylenediamine (TMED)] or ineffective [N,N,N,Ntetraethylmethylenediamine (TEMD), N,N,N,N-tetramethyldiaminomethane (TMDM)] (Scheme 8.19, top). The living feature of BEt3 /TEED-mediated copolymerization as well as no further PO homopolymerization after completion allowed the authors to infer that copolymerization occurs via a zwitterionic mechanism, where both amine sites of consumption of COS rendered an interesting on/off character depending on the loading of COS. The TEED can initiate the copolymerization with preferential insertion of COS at the beginning (Scheme 8.19, bottom). After quenching by HCl/ethanol, the quaternary ammonium initiation chain-end converted into Cl chain-end, and the polymer chain that originated from one TEED molecule broke into two (Scheme 8.19, bottom). In 2019, Naumann, Buchmeiser et al. utilized a LP catalytic system based on thermally labile 5u-Me-CO2 adduct and simple metal halide (LiCl) for the practical synthesis of poly(oxazolidine-2-one)s (POxas), a class of engineering thermoplastic materials with good chemical inertness and insulation abilities as well as considerable thermal stability, via the polyaddition reaction of diisocyanates and diepoxides (Scheme 8.20a–c) [77]. Upon using 2,3,4,5tetrahydrothiophene-1,1-dioxide (sulfolane, Scheme 8.20b) as the solvent and a monomer-starved setup with dropwise addition of monomers to the catalyst solution at 200 °C ([diisocyanate]0 :[diepoxide]:[LiCl]0 :[5u-Me-CO2 ]0 = 100:100:2:1), various aliphatic and aromatic diisocyanates, including 2,4-toluene diisocyanate (TDI), 4,4’-methylene diphenyl diisocyanate (MDI), 4,4’-methylene dicyclohexyl diisocyanate (H12MDI), and isophorone diisocyanate (IPDI), and hexamethylene diisocyanate (HDI), and diepoxides [bisphenol A diglycidyl ether (BADGE), 1,4butanediol diglycidyl ether (BDE)] (Scheme 8.20c) can convert into linear, soluble

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

311 O

O

a

O

O

+ OCN

R'

LP

NCO

R

Sulfolane

O

O

R N

O

b

N

N

O

O

O

O

R N

Sulfolane

NCO

Diisocyanates: NCO HDI

4-Oxa

OCN

R N

R N

R'

O

O N R

Isocyanurate

OCN

NCO

OCN

NCO

NCO H12MDI

MDI

O

O

BDE

IPDI O

O

O Diepoxides:

O O

5-Oxa

NCO

TDIH

c

n

O R N

O

R'

5u-Me-CO2

OCN

S

N

R'

O

BADGE

O

O

d

N

O ClLi

LiCl

R

N N

R'

N

N R

C O

ClLi

LiCl LiCl

O C N

N

C

O O

LiCl

R'

R'

R'

O O

N R

R N

N

R

:

ClLi

LiCl

O LiCl

N

N N

C

N R O

N

N

O

:

N

N R'

O

R'

O

R N C O

O

LiCl R'

Scheme 8.20 a General preparation of POxa via polyaddition of isocyanates and epoxides; b The structures of 5u-Me-CO2 adduct and sulfolane solvent as well as isocyanurate side product and regioisomers; c The structures of monomers employed in this study; d Proposed catalytic cycle for the formation of oxazolidinones initiated via NHC-mediated nucleophilic attack either on the epoxide functionality or on the isocyanate group

POxas with isolated yields of 60–90% within 3–8 h (M n : 9.0–51.0 kg/mol, Ð: 1.4– 1.9). Mechanistically, CO2 in 5u-Me-CO2 is lost at the polymerization temperature of 200 °C and the free, active IMe NHC is generated, which reacts with LiCl-activated epoxide or isocyanate via nucleophilic attack to form a zwitterionic species for initiating polymerization (Scheme 8.20d). Worth noting is that such a cooperative, dual catalytic approach plays a critical role on the selective formation of oxazolidinone over side reactions, as it is demonstrated that either 5uMe-CO2 or LiCl alone entailed the formation of significant amounts of trimerized isocyanurate (Scheme 8.20b) and concomitant cross-linked material. Interestingly, the monomers are enchained exclusively via 5-Oxa formation rather than 4-Oxa formation, highlighting the regioselective polyaddition reaction (Scheme 8.20b).

312

M. Hong

8.4 Summary and Outlook The development of LPP not only brings about a renaissance in polymerization catalysis with main-group elements but also provides an efficient, controlled, and selective strategy for the synthesis of a variety of novel polymeric materials that cannot be efficiently realized by traditional polymerization techniques. The past two years have witnessed the unprecedented achievements made to this rapidly expanding field. In this chapter, these recent advances have been highlighted, with a special emphasis on the LP-mediated polymerization of polar vinyl monomers and RO(C)P of cyclic esters, epoxides, and anhydrides. Compared to the research work reported previously, the current LPPs exhibit several impressive advantages and also open up a new opportunity for the applications of LP catalysis: (1) Pushing the limits on accessible monomers, such as the first effective LPPs of SFMAs, [51] epoxides, [71–73] as well as those notable monomers derived from renewable biomass or natural products (e.g., MC [59], IN [60], β-AL [61], OCA [69, 70]). (2) Realizing the controlled or even living polymerizations of divinyl acrylic monomers, [42, 46] acrylamides, [48] vinyl phosphonates, [52] epoxides, [72, 73] whose LPPs generally suffered from poor control previously, via the development of LP catalyst with matched Lewis acidity, basicity, and steric effects. (3) Enabling the synthesis of UHMW polymers with relatively low dispersities, as seen in examples of UHMW PMMA by (BHT)Ali Bu2 /IAP-1 FLP, [38] SFPMAs by MeAl(BHT)2 /It Bu LP, [51] PPO by Mg(HMDS)2 /NHO-9 CLA [71]. (4) Establishing robust LP catalysts or convenient methodology for the facile preparation of well-defined block copolymers, as demonstrated by the utilization of robust (BHT)Ali Bu2 /IAP-1 FLP for methacrylic multiblock copolymers with DHDM features via sequential addition method, [41] one-pot manner to Pn BA-bPt BA diblock [53] and poly(ether-b-ester-b-ether) triblock copolymers [75] from n BA/t BA and anhydride/excess epoxide monomer mixture using MeAl(BHT)2 /PMe3 and BEt3 /t Bu-P2 LP, respectively, and a switchable polymerization to ether-estertype multiblock copolymer by switching the monomer selectivity through varying the amount of BEt3 and t Bu-P2 [74]. The accomplishments made in this time frame also points out several key challenges which are still in need of a solution in the field of LPPs. Currently, successful LPPs are only limited to heteroatom-containing polar monomers. To the best of our knowledge, less activated nonpolar monomers, such as conjugated dienes or styrenes still remain unexplored. Therefore, extending the monomer scope and thus further broadening the applications of LPPs will undoubtedly continue to be a major focus in the future research. It would be also of great interest to develop novel LPPs capable of constructing complex macromolecular structures with controlled topology or highorder sequence, which will be used to create polymeric materials with advanced properties and specific functions. Moreover, at present, highly stereoselective LPP can only be achieved at low polymerization temperature (e.g., −78 °C) with compromised activity. The design of new LP catalysts that allow highly stereoselective polymerization under mild conditions could become one of the next challenges to be addressed.

8 Lewis Acid−Base Pairs for Polymerization Catalysis …

313

More importantly, some of the recent examples have shown the exciting potential of LPP technique for the large-scale synthesis of functional polymeric materials in an industrial setting, such as multiblock copolymer-based thermoplastic elastomers. To compete with the current industrial production, the challenge associated with it should be the design and development of cost-efficient and environmental-friendly LPP processes with high availability, strong tolerance, and easy recyclability. Acknowledgments This work was supported by the National Natural Science Foundation of China (Y8502112G0, E0502112G0, 21821002), the Thousand Talents Plan for Young Scholars of China, and K. C. Wong Education Foundation.

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Chapter 9

Frustrated Lewis Pairs Based on Transition Metals Nereida Hidalgo, Macarena G. Alférez, and Jesús Campos

Abstract The concept of frustration and its application to bond activation and catalysis over the last decade has paved the way to a new era in the field of main group chemistry. In terms of catalysis, the introduction of transition metals as integrating components of frustrated designs has emerged as a promising approach to overcome the main limitations of main group FLP systems. Herein we have tried to summarize the most relevant results in this flourishing field, particularly those described over the last five years (187 references are included). It is our aim to provide a Chapter that will serve as an illustrative outline to those already working in the area of frustrated Lewis pairs and also as an inspiring guide to newcomers. After a general introduction covering the main goals associated to the idea of designing metallic FLPs, a subsequent section deals with transition metal frustrated Lewis pairs that incorporate a single transition metal center. A wide variety of recent examples based on early, mid- and late transition metals, as well as rare-earth elements is presented. The next topic involves the rather limited and exotic examples in which the two components of the FLP are based on transition metals. The connection of these systems to polarized heterobimetallic species is examined in detail. Bond activation processes and catalytic applications are discussed along the text, with particular emphasis on mechanistic aspects. Keywords Frustrated Lewis pairs · Transition metal frustrated Lewis pairs · Metal–ligand cooperation · Bimetallic compounds · Cooperative chemistry · Metal–metal bond

Nereida Hidalgo and Macarena G. Alférez contributed equally. N. Hidalgo · M. G. Alférez · J. Campos (B) Instituto de Investigaciones Químicas (IIQ). Consejo Superior de Investigaciones Científicas (CSIC), University of Sevilla, Avenida Américo Vespucio 49, 41092 Sevilla, Spain e-mail: [email protected] © Springer Nature Switzerland AG 2021 J. Chris Slootweg and A. R. Jupp (eds.), Frustrated Lewis Pairs, Molecular Catalysis 2, https://doi.org/10.1007/978-3-030-58888-5_9

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9.1 Introduction The concept of ‘frustrated Lewis pair’ (FLP) represented a landmark discovery in the chemistry of main group elements when Stephan demonstrated in 2006 that the cooperative action of a phosphine and a borane was capable of the heterolytic cleavage of dihydrogen [1]. This achievement parallels in time the independent work of Power [2] and Bertrand [3] on multiply bonded and sub-valent main group compounds that also accomplished dihydrogen splitting. Altogether, these and related findings have revolutionized the way by which chemists look at the P-block. It has now become clear that main group elements can behave as transition metals under certain conditions, and this also applies to their reactivity toward small molecules [4]. In fact, the mechanism followed by transition metals, sub-valent and multiply bonded main group systems, or FLPs to activate small molecules is the result of a precise orbital cooperation. Oxidative addition of dihydrogen over transition metals can be rationalized by the Dewar–Chatt–Duncanson model in terms of σ-donation from H2 to an empty metallic d-orbital and metal-to-ligand π-backbonding [5]. Related to this, the addition of H2 over multiply bonded and sub-valent main group systems also entails a synergistic interaction of frontier orbitals [6]. In the case of FLPs, although dihydrogen splitting is heterolytic (i.e., R3 P–H+ / Ar3 B–H− ), the initial step likewise involves the synergic donation from the lone pair of the (phosphine) base to the H2 σ*-orbital along with donation from the σ-H2 to the empty (borane) acid orbital (Fig. 9.1). Thus, a connection between the three modes of dihydrogen cleavage can be clearly delineated. Much of the widespread interest in FLP systems derives from their proved proficiency as metal-free hydrogenation catalysts [7, 8]. This has led to a frenetic development of the field over the last decade that continuously expands to a range of related areas. The development of transition metal frustrated Lewis pairs (TMFLPs), the crux of this Chapter, is one of such nascent approaches. As already mentioned, main group elements can behave as transition metals. Introducing the concept of TMFLPs somehow implies reversing this statement. The simplest case scenario would entail using a transition metal to render the same cooperative chemistry as a main group element in a traditional FLP. However, the incorporation of transition metal centers as (a)

(b)

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H R M = transition metal

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E = C, Si, Ge, Sn

Fig. 9.1 Frontier molecular orbital interactions for the splitting of dihydrogen by a transition metals; b sub-valent group-14 elements (tetrylenes); and c P/B frustrated Lewis pairs

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integrating components of FLP systems goes far beyond this simple assumption and provides a whole range of new chemical possibilities, as will be discussed throughout the Chapter. The use of transition metals either as the acid or basic site (or both) in the design of TM-based FLPs has attracted continuous attention since the pioneering work of the groups of Wass [9–11] and Erker [12, 13] on zirconium/phosphine pairs. This emerging field of research has already been reviewed in a reference book Chapter [14] that precedes the current contribution and in an inspiring perspective reported by Wass [15]. As such, this Chapter will mainly concentrate on the more recent achievements accumulated over the last five years. Besides, it will focus on FLP architectures where the transition metal functions as one (or both) of the active sites of the cooperative moiety, while those in which it merely acts as a structural pillar will not be covered [16–18]. The application of intramolecular FLPs as ambiphilic ligands to tune the reactivity and catalytic behavior of transition metals has already been reviewed elsewhere [19], and will not be further discussed. Highly informative recent perspectives have also focused on the analogy between FLPs and metallic cooperative catalysts in the context of dihydrogen cleavage [20], as well as on systems containing multiple metal–ligand bonds as masked TMFLPs [21]. The role of gold as the acidic fragment of TMFLPs has been lately revised [22], including gold nanoparticles. The latter and other heterogeneous catalysts that seem to operate through FLP-like mechanisms will not be covered either [23–25]. There is a clear analogy between TMFLPs and other cooperative systems, particularly in the context of hydrogenation/dehydrogenation catalysis. Thus, many of the most remarkable catalysts in the field, and even the active site of several metalloenzymes such as hydrogenases [26–28], could be described in terms of FLP-like reactivity. This analogy was rapidly noticed by Wass and others and has been thoroughly discussed before [15]. With this in mind, this Chapter will only cover cooperative designs in which the authors specifically state their intention to prepare TMFLPs or where their investigations on reactivity and mechanisms prompted them to identify those as FLP-like systems. Other cooperative entities that could in principle be understood in terms of FLP-like reactivity, but where the authors have restricted themselves to the broader term of ‘metal-ligand cooperation’, with no specific claim of frustration, will not generally be discussed [29–31], as they have been reviewed and highlighted on several occasions [32–35]. Introducing transition metals into FLP architectures might seem to arguably undermine the utmost benefit of the original systems, namely, their capacity to mediate catalytic transformations in the absence of transition metals. However, there are a number of rewards that largely justify intense research in this direction, apart from the obvious enormous rise of combinatorial possibilities derived from introducing three series of transition metals (even more if lanthanides and actinides are to be considered). Among the main advantages of introducing transition metals into FLP structures, the following should be had in mind: – Rich reactivity. The rich chemistry of transition metals results from the presence of partly occupied d orbitals with energies that make them amenable to

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participate in elementary reactions (e.g., oxidative addition, migratory insertion, reductive elimination…). The reluctance of main group systems to mediate these types of transformations has precluded their broader implementation into catalytic systems. Thus, incorporating transition metals into FLPs could offer a whole range of elementary reactions that could increase the catalytic usefulness of FLPs far beyond their current use as (mainly) hydrogenation catalysts. Structural diversity. The structural diversity of transition metal organometallic and coordination complexes largely exceeds that of main group systems. Coordination numbers typically range from two to six for the d-block, though they can reach up to nine (e.g., [ReH9 ]2− ) [36]. This leads to a wide variety of structures and geometries around the metal center that finds no parallel in the main group. Tunable properties. The vast amount of ligands with tunable stereoelectronic properties enables the synthesis of virtually any desired transition metal complex with precisely defined steric and electronic features, something unattainable for the main group. Moreover, a precise transition metal element (particularly midTMs) can behave as an acid or a base depending on its oxidation state and ligand environment, which also contrasts with the main group series, where the same behavior, though being well-known, is less versatile. Synthetic amenability. The methods to prepare transition metal complexes have been developed over the last decades and in many occasions synthetic protocols are relatively simple and expeditious. Similarly, the most common basic partners in traditional FLPs, namely phosphines, are readily prepared and their commercial catalogue is comprehensive. However, accessing the type of fluorinated boranes that are typically used as the acid fragment in FLPs is challenging [37], contrasting with the synthetic amenability of transition metal Lewis acids. Broad spectra of affinities. Transition metals exhibit a broader diversity of affinities toward specific elements and interactions than main group compounds. For instance, while the lighter main group elements are highly oxophilic and even metalloids such as germanium or tin present medium oxophilicity, the wider degree of oxophilicity found in the transition metal series is evidenced by the very high oxophilicity of elements such as titanium or hafnium and the practically inexistent tendency to bind oxygen of gold or palladium [38]. Other examples include carbophilicity [39], thiophilicity [38], metallophilicity [40], the propensity to form hydrogen bonding, and other types of interactions [41, 42]. Modulating these attributes can be essential for the activation of small molecules, to trap reactive intermediates or for the development of more efficient catalysts. For instance, a highly oxophilic element will favour the activation of an oxygencontaining species but if the resulting product becomes a thermodynamic sink, catalytic turnover may be hampered. Controlling the degree of affinity may thus be key for enhancing catalytic efficiency.

This Chapter is divided into two Sections. The first covers TMFLPs in which only one of the two components (acid or basic) is a transition metal, which comprises the majority of the reported systems. These designs are further categorized into those constructed around early transition metals and those incorporating mid and

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late counterparts. In addition, we have revisited recent systems based on rare-earth elements. In the second section, we describe transition metal-only frustrated Lewis pairs (TMOFLP), in which the two components are based on transition metal fragments. Explicit mention to polarized heterobimetallic systems whose behavior could be understood in terms of FLP-like reactivity will also be covered. These sections are followed by a summary and outlook of the current state of the field and potential research avenues for the near future.

9.2 TMFLPs with One Transition Metal Center 9.2.1 Early and Mid-Transition Metals Electron deficient early transition metal complexes, particularly those in high oxidation states, have been widely used as Lewis acid catalysts for a number of transformations [43]. In an early example, prior to coining the term ‘Frustrated Lewis Pair’[44], Stephan demonstrated that combining the acidic titanium compound [CpTi(N Pt Bu3 )][B(C6 F5 )4 ], with the sterically demanding P(o-MeC6 H4 )3 phosphine, did not lead to ligand coordination due to steric clash providing instead cooperative cleavage of a C–Cl bond of a dichloromethane solvent molecule. In a later study, the group of Wass investigated an intramolecular titanocene–phosphinoaryloxy complex capable of heterolytically activating dihydrogen [45]. This system is analogous to a zirconium-based counterpart that the same group explored in detail in previous years [9, 10]. Other intramolecular Ti-based TMFLPs were later reported by Erker. In their first strategy, the synthesis of a functionalized cyclopentadienyl ligand allowed access to a series of cationic titanium complexes with a pendant phosphine of general formula [CpCpP TiOAr][BPh4 ] (1) (Cp = ï5 -C5 H5 ; CpP = ï5 -C5 H4 (CMe2 )PCy2 ) (Scheme 9.1a) [46]. Although this species was completely unreactive toward gaseous substrates as H2 , CO2 , CO, or C2 H2 , it readily reacted with benzaldehyde to yield the corresponding addition product (2). Interestingly, compound 1 slowly reacts (9 days) with trans-chalcone to produce a 10-membered titanium macrocyle (3). More recently, the same group described an intramolecular phosphidotitanocene cation (4) that revealed FLP reactivity with ferrocene carboxaldehyde to yield the expected addition product 5 (Scheme 9.1b) [47]. Beckhaus described a series of electrophilic cationic d 0 titanium complexes with a single ligand framework, more precisely a novel tridentate Cp,N,P system (Scheme 9.2a) [48]. This design allowed the authors to explore the competence between the nitrogen termini and the phosphine ligand to cooperate with the acidic titanium center to activate the C–H bonds in phenylacetylene and acetone (toward 7 and 8, respectively). Although the overall reaction takes place at the Ti–N bond, as expected for the higher basicity of the nitrogen, a related compound missing the phosphine group (9) revealed no activity even under harsher conditions, which

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(a)

BPh4

BPh4 PCy2 Ti

O

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PhCHO

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Ph

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Ph Ph

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O

Ph

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PCy2

Ph

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O

BPh4

PCy2

+

Ph

Fc CH2Cl2, 25 ºC

Fe

Ph 4

O

BPh4 PCy2

Ti

Ph

Ph 5

Scheme 9.1 Titanium-based frustrated Lewis pairs reported by the group of Erker (a)

R

Ph

R

P

HCCPh

Ti N

Toluene 25 ºC

R R 6 R=Ph,iPr

Ti

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7

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Cl or F

R' C9H19

X Ti O

N R R

Toluene, 25 ºC (R' = Cl, Ph) 10, R = Et, CH2Ph

X = Cl, R' = CH2Cl 11 X = Cl, R' = CH2Ph X = F, R' = C10H21

Scheme 9.2 C–H and C–halogen bond activation of electrophilic titanium complexes stabilized by Cp-based tridentate ligands with pendant basic functionalities. The [BCH3 (C6 F5 )3 ]− counteranion has been omitted for clarity

9 Frustrated Lewis Pairs Based on Transition Metals

325

evinced the phosphorus center playing a key role that remains under investigation. The same group reported a year later a similar d 0 titanium complex stabilized by a Cp,O,N ligand (10, Scheme 9.2b) [49]. The pendant amine enabled the activation of C–halogen bonds, including C(sp3 )–F bonds, of different substrates under mild conditions, while compounds of type 6 were inactive. The introduction of zirconium as the acidic component in FLP systems precedes and inspired the titanium pairs just described. Zirconium has been the most extensively investigated transition metal in the field of FLPs and set the basis for subsequent progress after the pioneering work of Wass [9–11] and Erker [12, 13]. As stated in the introduction, this Chapter mainly focuses on the developments of the last five years, since early examples have already been thoroughly discussed elsewhere [14, 15]. Some comments on the earliest systems are, however, required. The cationic zirconocene 12 (Fig. 9.2) bearing a phosphinoaryloxide is likely the first TMFLP that was designed as such and whose reactivity was exhaustively investigated [9–11] Shortly after the group of Erker reported a geminal Zr+ /P pair (13) by the simple insertion of diphenylacetylene into the Zr–C σ-bond of cation [Cp*2 Zn(CH3 )]+ [12, 13]. Interestingly, a related vicinal Zr-based TMFLP (14), as well as its hafnium version, were also prepared. Those derived from the reaction of the same cationic zirconocene with diphenylphosphino(trimethylsilyl)acetylene (Me3 SiCCPPh2 ) followed an alternative and unusual 1,1-carbozirconation reaction [50]. These earliest systems exhibit FLP-like reactivity toward common small molecules such as dihydrogen, carbon dioxide, or a range of heterocumulenes. To compare the behavior of the electrophilic Zr center with respect to the widely used borane moiety, an elegant competition study was carried out [51]. t

Cp*

Bu2 P

H 3C

Ph

Zr Cp*

Cp*2Zr

O 12

PPh2

H3 C Cp*2Zr

O

Cp

Zr

O Zr

Cp*

NiPr2

Cp 16

15

P Ph2

Cp2Zr

17

Cp Cp

PR2 Zr

Cp

O 18

R

Cp* R

PPh2 14

13

Cp*

SiMe3

Zr OAr

Cp*

+ PR3 or + NR3

Me Zr

Cp

PPh2

O N

19 20

Fig. 9.2 Representative examples of zirconocene-based FLPs. Counteranions have been omitted for clarity

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N. Hidalgo et al.

The potential for catalysis is likely the most appealing benefit of extending the concept of frustration to transition metals. This became obvious since the publication of the aforementioned original works. For instance, while compound 14 promotes the catalytic dimerization of alkynes, zirconocene 12 mediates the dehydrogenation of amine boranes, the latter being the first example of such transformation in the FLP arena [52–55]. This has been lately explored in deeper detail by testing several intramolecular Zr+ /P complexes constructed around a variety of cyclopentadienyl and phosphinoaryloxide ligands [56]. These compounds are active in dimethylamineborane (Me2 NH·BH3 ) dehydrogenation toward cyclic diborazane [Me2 N–BH2 ]2 . Moreover, compound 12-Ind, containing two indenyl ligands instead of the (substituted) cyclopentadienyl fragments common to all other attempted catalysts, revealed the highest activity (TOF > 600 h−1 ; Scheme 9.3). Although the more donating character of indenyl compared to cyclopentadienyl ligands [57] seems to indicate that the superior activity could be rationalized in terms of electronics, the authors highlight that steric factors and the more facile η3 ring slippage of indenyl ligands [58] may also play a role. Mechanistic investigations using intermolecular Zr+ /P models evinced the existence of two concurrent pathways, the first involving the previously proposed FLP-like dehydrogenation, while the complementary route implies a phosphine-independent process that facilitates formation of the cyclic diborazane. Introducing a pendant amine as the basic partner in this type of Zr-based FLPs allowed Erker to disclose a highly reactive frustrated system that was active not only in the activation of small molecules (H2 , CH2 Cl2 , terminal alkynes), but also in the catalytic hydrogenation of alkenes and internal alkynes under mild conditions (25 ºC, 1.5 bar H2 , 1–4 mol % Zr+ /N cat.). The authors propose a mechanism (Scheme 9.4) involving the FLP-like cleavage of H2 to produce a zirconium hydride and a pendant ammonium group, followed by hydrozirconation of the olefin (or alkyne) substrate and subsequent protonolysis of the Zr–C σ-bond to release the hydrogenated product and regenerate the catalyst. Interestingly, the use of the persistent radical TEMPO permitted the isolation of compound 20 where the nitrogen center behaves as an internal base for the FLP-like activation of phenylacetylene [59]. In a more recent report, Rocchigiani and Budzelaar explored the mechanism of related zirconaziridinium compounds of formula [Cp2 Zr(η2 -CH2 NR2 ]+ , which could potentially behave as TMFLPs for H2 splitting [60]. However, a σ-bond metathesis mechanism seems to prevail in that case. Nevertheless, this reactivity generates Scheme 9.3 Catalytic dehydrocoupling of dimethylamine-borane by a Zr+ /P intramolecular frustrated Lewis pair

tBu2 P Zr

Me2NH·BH 3 5 mol% Zr+/P H2

PhCl, 25 ºC

O 12-Ind TOF > 600 h-1

Me2N H2 B

BH2 NMe2

9 Frustrated Lewis Pairs Based on Transition Metals Scheme 9.4 Catalytic hydrogenation of alkenes by Zr+ /N FLP 15

327 O

Cp*

R

Zr R

Cp* 15

NiPr2

O

Cp*

H2

Zr

i

Cp*

O

Cp*

Zr N Pr2

R

Cp*

NiPr2

H

H

H

R

R

R

cation [Cp2 ZrH]+ , whose subsequent combination with a released amine facilitates FLP-type H2 cleavage. The same group explored other related intramolecular Zr+ /P architectures, some of which are collected in Fig. 9.2. Those include a P-based version of 15 in which the pendant amine is substituted by a PPh2 terminus [61]. The corresponding zirconium cation dimerizes to yield an oxygen bridged dicationic product, despite which it undergoes the 1,4-addition of chalcone in an FLP-like manner. A richer reactivity was reported for compound 16, whose bulkier steric profile prevented dimerization [61]. The latter compound exhibits FLP reactivity with benzaldehyde, nitrosobenzene, and an ynone (Scheme 9.5). The similar Zr+ /P compound 17 was described shortly after and its FLP reactivity toward ketones, aldehydes, α,β-unsatutated carbonyl compounds, and heterocumulenes was demonstrated [62]. Scheme 9.5 FLP reactivity of Zr+ /P compound 16 toward benzaldehyde, nitrosobenzene, and an ynone. Counteranions have been omitted for clarity

O Cp

O Zr

Cp 16

Ph

H

P Ph2

Cp

O Zr PPh2

Cp O Ph

H

PhNO

O Ph Cp

Cp

O Zr

Cp O Ph

PPh2

·

O Zr

Cp O

PPh2 N Ph

328

N. Hidalgo et al.

Fine control of stereoelectronic properties in this type of systems remains a challenge from a synthetic point of view. To overcome this limitation, a more convenient route toward Zr+ /pairs was reported by means of facile insertion of nonenolisable carbonyl compounds (including CO2 ) into the Zr–E (E = P, N) bond of phosphido- and amidozirconocene complexes of type [Cp2 Zr(ER2 )Me] (E = P, N) and subsequent (or former) methyl abstraction by B(C6 F5 )3 [63, 59]. Compounds 18 were prepared by this approach and their coordinating ability as ambiphilic ligands examined [63]. Drawing on the same theme, Wass explored intermolecular Zr+ /P FLPs by combining zirconocene aryloxide compounds with a range of phosphines [64]. This approach offers even greater versatility considering the extensive amount of phosphines commercially available. The reactivity of these pairs toward H2 , CO2 , THF, and phenylacetylene was investigated providing evidence for significant differences derived from subtle modification of the stereoelectronic properties of the phosphine base. For instance, while the weakly basic P(C6 F5 )3 did not exhibit any FLP reactivity, the use of PPh3 and PMes3 led to opposite selectivity during phenylacetylene activation (Scheme 9.6). Besides, DOSY NMR spectroscopic studies were applied for the first time to a TMFLP system [65] and uncovered some degree of preorganization between the cationic zirconocene and the phosphine fragments. The same intermolecular approximation was subsequently employed by the group for the hydrogenation C 5 R5 Zr OAr C 5 R5 O PR'3 O C5R5 C5 R5 Zr OAr C5 R5 D +

R=H

CO2 (1 bar) PhCl

C5R5

C5R5 D2 (1 bar) PhCl

D-PR'3

Zr OAr

R' = Ph

Zr OAr + PR'3 C5R5 19

H

PhCCH PhCl 20 ºC

Ph PR'3

C 5 R5

R = Me

THF PhCl

+ H-PR'3 Ph

C5 R5 Zr OAr C5 R5 O

Zr OAr R' = Mes C R 5 5

PR'3

Scheme 9.6 FLP activation of small molecules by intermolecular Zr+ /P pairs based on zirconocene 19 and commercial phosphines. Counteranions have been omitted for clarity

9 Frustrated Lewis Pairs Based on Transition Metals

329

of imines using a range of zirconocenes bearing mesityl aryloxide and where the imine substrate served as the base as well [66]. Moving forward to group 6 of the periodic table, Bullock explored the reversible and heterolytic cleavage of the H–H bond in a series of molybdenum complexes containing a pendant amine (Scheme 9.7) [67]. These studies built upon their previous expertise on related manganese [68, 69] and iron [70–72] complexes with pendant amines as effective electrocatalysts for H2 oxidation. The latter systems are particularly attractive since they serve as synthetic models of the [FeFe]-hydrogenase and [NiFe]-hydrogenases [73, 74]. Back to molybdenum, it becomes clear that the strength of the interaction between the pendant amine and the acidic molybdenum center is crucial to achieve H2 splitting. Thus, while compounds 20 are unable to attain this activation [75], introducing ring strain to destabilize the Mo–N interaction in 21 permits rapid cleavage of the H–H bond. The authors propose a mechanism involving initial coordination of H2 to form a molybdenum dihydrogen or dihydride intermediate (not observed) followed by intramolecular deprotonation by the lateral amine, though a concerted FLP-like cleavage is not completely ruled out. The newly formed hydride and proton rapidly exchange even at low temperature, as evinced by NMR spectroscopy, while the rate of the process can be tuned by modifying the substituents of the phosphine and amine groups (Scheme 9.7). Introducing less basic amines and poorer P-donors increases acidity to the extent of recording a surprisingly high first-order kinetic constant of up to 107 s−1 . The relation between acidity and exchange rate was experimentally investigated and provides important insights for future developments in TMFLPs and in the broader context of bifunctional catalysis. The potential of metal-free FLP systems to activate dinitrogen, a great chemical challenge owing to the strength of the N≡N triple bond, has been recently highlighted [76]. First insights into this Holy Grail process were delivered by Stephan in 2017 [77]. During the same year, Szymczak [78] and Simonneau [79] independently reported the activation of N2 by a TMFLP approach based on iron (23) and

Me H2

N OC Mo R 2P R 2P 20

No reaction

R R' Ph Bn

R' OC Mo P P R N R'

21

N

H2 -H2

R

OC H

N R'

RP H

Rapid and tunable H-H exchange

R P

Mo

N R'

k (s-1) 3.9 x 105 4.0 x 107 6.9 x 104

Ph Ph t Bu Bn t Bu Ph 4.1 x 106 t Bu tBu 2.1 x 103

pKa 13.8 9.3 15.3 10.7 17.7

22

Scheme 9.7 Reversible activation of dihydrogen by molybdenum complexes with a pendant amine base. Counteranions have been omitted for clarity

330

N. Hidalgo et al.

N Ph2 N Ph2 P P M P P Ph2 N Ph2 N 23; M=Mo, W PEt2 Et2P Et2P

Fe PEt2

N

N

(C6F5)3B

Ph2 N P M P Ph2 H

B(C6F5)3 Toluene, 25 ºC -N2

B(C6F5)3

Et3Si

N Ph2 P P

HSiEt3 Ph

Toluene, 25 ºC, 15 min

N Ph2 N P M P Ph2 H

PEt2 Et2P

PhF, 25 ºC Et2P

Fe

Ph2 P P

Ph

PEt2 N

PEt2

N

B(C6F5)3

HBArF

Et2P

PhF, -30 ºC Et2P

Fe PEt2

N

N

B(C6F5)3

H

24

Scheme 9.8 Dinitrogen activation and functionalization by combining transition metal Lewis bases with B(C6 F5 )3

molybdenum/tungsten (24) complexes, respectively (Scheme 9.8). On the basis of the similarities of the two systems, they will be jointly presented here rather than shifting the discussion on the iron pair to the next section on late transition metals. In both metallic systems, the high barrier associated to the activation of the triple N≡N bond is overcome by a push–pull strategy in which the highly acidic B(C6 F5 )3 borane releases electron density from the coordinated dinitrogen. Computational analysis carried out on the iron system reveals that the trapped dinitrogen gets polarized, while its π * orbital is stabilized, much like what is seen in traditional FLPs during H2 activation [80–83]. Similarly, this approach mimics the mechanism by which the active site of nitrogenase enzymes initially weakens the N≡N bond [84]. Moreover, while protonation of N2 was achieved for the iron system by using HBArF ·(OEt2 )2 (BArF − = [3,5-(CF3 )2 C6 H3 ]4 B− ), the molybdenum/borane and tungsten/borane pairs permit the stoichiometric borylation and silylation of N2 under mild conditions (Scheme 9.8).

9.2.2 Late Transition Metals The Lewis acidity or basicity of a late transition metal can be rationally tuned by ligand and oxidation state modification. In most cases, the metal has been employed as the acidic component of the FLP system, which parallels traditional bifunctional catalysts with pendant bases. However, the use of late transition metals as Lewis bases has also been contemplated, with the work above by Szymczak [78] on N2 activation taking place at an Fe(0)/B(C6 F5 )3 pair being a paramount example. Also working with iron complexes, Poater and Renaud have found inspiration in the FLP concept to exploit a family of iron carbonyl compounds stabilized by noninnocent functionalized cyclopentadiene fragments (Scheme 9.9) [85–87]. These bifunctional complexes, highly reminiscent of the prominent Shvo catalyst, [88]

9 Frustrated Lewis Pairs Based on Transition Metals R

R O 1) Me3NO (-CO2) R

X X

331

Fe OC OC CO

R O

X X

R Fe H OC OC H

2) H2

OH

X X

R

Fe OC OC

H

25, X = NCH3, CH2 R N N

NHiPr 1) Me3NO R (-CO2)

Fe OC OC CO

2) H2

R N

R H

Fe

OC OC

R

NHiPr

N

H

NHiPr

N R'NH2 - R'NH2H+

N

R Fe OC H OC

26

Scheme 9.9 Dihydrogen activation by intra (25) and intermolecular (26) cooperative systems with mechanisms reminiscent of FLPs. Counteranions have been omitted for clarity

efficiently promoted reductive amine alkylation [85, 87] and ketone alkylation [86]. Carbon monoxide abstraction with Me3 NO provides a vacant site on the electrophilic iron center where H2 is coordinated. Computational studies revealed that substituting the cyclopentadienone in 25 by a cyclopentadienyl with a pendant amine group in 26 has an impact on the mechanism of H2 splitting. While in the former case dihydrogen splitting is mediated by direct action of the oxygen center, in compound 26 the lower energy pathway involves the action of an external amine. Although this may not be strictly considered a TMFLP, the authors highlighted the importance of applying the concepts derived from the field of frustrated systems to the area of cooperative catalysis with transition metals. In another cooperative example that somehow resembles the chemistry of FLPs, the group of Oestreich investigated in detail the tethered ruthenium(II) thiolate complex 27, whose Ru–S bond facilitates the cooperative activation of Si–H bonds to yield a terminal ruthenium hydride and an acidic silicon fragment (stabilized by sulfur) that behaves as a silylium cation (28, Scheme 9.10). The electrophilic nature of the latter has been exploited for a number of catalytic applications [89–96], including the enantioselective reduction of imines after introducing axial chirality at the sulfur ligand [97]. At variance with other examples of cooperative activation across metal–ligand bonds, the Ru–S bond remains virtually intact after Si–H cleavage (27, d RuS = 2.21; 28 d RuS = 2.39 Å). A detailed mechanistic investigation into this activation event by a joint experimental/computational effort was also Scheme 9.10 Cooperative Si–H bond activation at a Ru–S bond. Counteranions have been omitted for clarity

R 3P

Ru 27

HSiR'3

S

R3 P

Ru

H 28

S

SiR'3

332

N. Hidalgo et al.

undertaken [98]. A concerted σ-bond metathesis pathway across the Ru–S bond was proposed which, although conceptually differs from the mode of action of FLPs, shares some common features with the latter such as the polarized landscape between the two intervening nuclei and the heterolytic nature of the splitting. Related work by Tatsumi and Sakaki on a hydroxo-/sulfido-bridged ruthenium—germanium complex also draws the analogy with the heterolytic mode of activation of FLPs [99, 100]. In the group 9, a very recent study by Carmona and Rodríguez demonstrated that a thermally induced [101] rhodium FLP constructed around a tridentate guanidinephosphine ligand (29) was effective for FLP-like activation of dihydrogen and the O–H bond of water (Scheme 9.11). The lability of one of the Rh–N bond of 29 results from strong ring strain within the Rh–N–C–N moiety and gives access to a vacant coordination site at the acidic Rh(III) centre. This vacant is in close proximity to the basic imine and as such shows potential for FLP-like activation. Heterolytic dihydrogen splitting takes place under relatively mild conditions to yield a rhodium hydride fragment and a pendant iminium ion (29-H2 ), as corroborated by X-ray diffraction studies. Partial reversibility was accomplished (ca. 30%) by heating the hydrogenated sample at 120 °C for 30 min. More interesting is the reaction with deuterated water, which results in rapid H/D scrambling in all the methyl positions at the cyclopentadienyl fragment. Although the authors could not detect any intermediate for such a process, computational investigations support the notion of an initial FLP activation of the O–H bond by the cooperative action of the acidic Rh(III) center and the basic role played by the pendant imine, followed by methyl deprotonation by the newly formed metal-hydroxide to produce a transient fulvene. Rapid equilibration among all proposed intermediates results in full deuteration of the cyclopentadienyl ring. d15

Ph2P 29-H2

Rh H H N N NAr

H2 (3 bar) THF, 25 ºC Ar

Rh Ph2P

N Ar

N

120 ºC

NAr

29

D2O

Rh Ph2P

N Ar

N

-60 ºC

NAr

29-d15

CH2 Ph2P

Rh O D D N Ar N ArN

Ph2P

Rh O D N

H D N Ar

ArN

Scheme 9.11 Dihydrogen and D2 O heterolytic activation by an intramolecular rhodium/imine frustrated Lewis pair, including subsequent H/D scrambling at the cyclopentadienyl ring

9 Frustrated Lewis Pairs Based on Transition Metals

333

The use of ligands with pendant boranes has been successful for designing efficient cooperative catalysts, particularly those involving hydrogen transfer between the metal center and the boron atom [102]. The cooperative mechanism by which these complexes activate E–H (E = H, Si, C, O, N…) bonds is reminiscent of frustrated systems. This analogy was drawn by Peters regarding the study of a nickel metalloborane bearing a diphosphine-borane ligand which turned out to be an efficient hydrogenation catalyst [103]. The same group has made extensive use of diphosphine-borane ligands to impart cooperative reactivity to first-row transition metals [104–106]. In a recent study, the bond activation capacity of iron and cobalt metalloborane complexes was tested [107]. Compounds of type 30 permit rapid activation of a series of substrates containing E–H (E = O, S, N, C, Si) bonds (Scheme 9.12). Interestingly, the activation of a hydrosilane (Ph2 SiH2 ) was found to be reversible for the cobalt system. This result prompted the authors to investigate the role of these compounds as hydrosilylation catalysts. In fact, cobalt compound 30 is remarkably efficient in the hydrosilylation of ketones and aldehydes. The use of a bisphosphine Pt(0) complex (31) as a transition metal Lewis base in combination with a fluorinated borane as the acid allowed Wass to unveil an apparently simple TMFLP. This system perfectly emulates the behavior of main group frustrated systems and, in the case of ethylene activation, even revealed a novel and unexpected reactivity involving its coupling with carbon monoxide to yield a fivemembered metallacycle (Scheme 9.13) [108]. Mixing compound 31 with B(C6 F5 )3 provided no spectroscopic hint of adduct formation, though broadening of 31 P{1 H} NMR signal of 31 was discernible in chlorobenzene. This was attributed to the presence of weak Lewis acid–base interactions in solution (i.e., Pt → CO → B or Ph

N

B i

Pr2 P

H M

PiPr2

iPr

-N2

B 2P

M

N

PiPr2

N N 30, M = Co, Fe

M = Co PhOH or PhSH -N2, -0.5 H2 M = Fe PhOH -N2, -0.5 H2

-N2

N2 (1 bar)

M = Co

-Ph2SiH2

Ph2SiH2 -N2

XPh

M = Fe PhSH -N2 Ph B

Ph

i

B i

Pr2 P

H M

Pr2 P

Ph

PiPr2 B

NH N

PiPr2

M

X = O, S

H2N N

B

iPr 2P

i

Pr2 P

H Co

i

PiPr2

SiHPh2

H

PiPr2

Fe

S

S Fe

Pr2 P

H

Ph

P iPr2

B Ph

Scheme 9.12 Cooperative E–H bond activation using metalloborane iron and cobalt complexes

334

N. Hidalgo et al.

P P

Pt CO 31 + B(C F ) 6 5 3

H2 (1 atm)

P

25 ºC, 10 h

P

P

H

H

CO

B(C6F5)3

CO2 (1 atm) 3 days

C 2 H4 (1 atm) P

Pt

O

Pt

P O

P P

Pt

P

B(C6F5)3

=

B(C6F5)3

C O

PtBu2 PtBu2

Scheme 9.13 Small molecule FLP activation by a Pt(0)/B(C6 F5 )3 pair

Pt → B). Beyond the intriguing formation of the metallacycle derived from ethylene/CO coupling, the reactivity with CO2 is rather interesting since it involves CO displacement by a considerably poorer ligand such as CO2 . As expected, 31 does not react with CO2 by itself, but in the presence of B(C6 F5 )3 the corresponding CO2 adduct is quantitatively formed after three days as a result of push–pull stabilization. These results were later extended to other related bisphosphine ligands and the products derived from the activation of small molecules analyzed with regard to ligand modification [109]. An intramolecular Pt(0)/borane pair (32) has also been disclosed by Figueroa after hydroboration of a bis-isonitrile Pt(0) compound that enables the formation of a chelating (boryl)iminomethane ligand [110, 111]. The small bite angle of the latter framework seems to facilitate small molecule activation across the Pt→B bond in an FLP manner with a wide range of substrates (Scheme 9.14). For instance, compound 32 reacts with dihydrogen to produce the expected hydride/borohydride complex. Cleavage of polar E–H (O, N, C) bonds is also easily achieved for amines, alcohols, and a terminal alkyne. Ketones and aldehydes react in the same fashion as main group FLPs, namely with the nucleophilic platinum center coordinated to the carbon atom and the electrophilic boron to the carbonylic oxygen. Contrarily, reaction with CO2 produces a metal-free boracarbamate with concomitant release of the parent bis-isonitrile Pt(0) from which compound 32 is prepared. The reaction with tertbutylisocyanate to generate a boraurea proceeds in a similar fashion. These two metalfree species are alternatively prepared by the free ambiphilic (boryl)iminomethane ligand whose FLP behavior was also explored. Other unsaturated substrates such as azides or acetonitrile also provided the corresponding FLP-like activation products, while addition of elemental sulfur (S8 ) yielded the formal insertion of a sulfur atom into the Pt → B dative bond.

9 Frustrated Lewis Pairs Based on Transition Metals

335 O2N H

H B

B But N

N C Pt N

N N C

N

H

B

Pt

N

H

O

t

BuNCO

H2

N C

R

p-O2NC6H4NH2

B Pt N

O

MeCN

N

B

N C Pt

N

H

B N C

Pt

ROH N

S8

S N C

Pt

Ph

B

C

PhCCH 32 N

N C

RN3

C Pt

B N

H

1 2

R RC O R1, R2= Me R1= Ph, R2=H

CO2

R N

N N

N C

Pt

B O N

R2 O R1

B N

N C

Pt

B N

H

O

Scheme 9.14 Cooperative small molecule activation pinwheel for the geometrically constrained (boryl)iminomethane platinum compound 32

In the same series as platinum, gold became an obvious target to develop late transition metal FLPs due to the well-known electrophilicity of the [LAu(I)]+ fragment, where L is a two-electron donor ligand, typically a phosphine or a N-heterocyclic carbene (NHC) [112–118]. In a recent attempt to design a frustrated Au(I)/Phosphine pair, Hashmi combined a cationic Au(I) fragment stabilized by an extremely bulky NHC ligand (IPr**) [119] with the sterically hindered phosphine PMes3 (Mes = 2,4,6-Me3 -C6 H2 ). Despite the bulkiness of the two ligands, the corresponding cationic complex [(NHC)Au(PMes3 )]+ was readily formed, [120] which illustrates the hurdle of achieving metallic frustration with a linear complex. The group of Zhang explored the possibility of geometric frustration by developing a bifunctional phosphine ligand that incorporates a pendant tertiary amine unavailable to intramolecular interaction with gold due to geometric constraints [121]. As a soft Lewis acid, the Au(I) site in complex 33 (Scheme 9.15) readily coordinates C≡C bonds with simultaneous weakening of the α-C–H bond, which is profited by the lateral amine to abstract the proton despite being a rather weak base (pK a ≈ 4; c.f. R2 C(H)C≡CR’: pK a > 30). Conformational rigidity proved to be key for efficient isomerization, since substituting the adamantyl moieties bound to phosphorus considerably decreased the rate of catalysis. Based on this approach, a number of related studies were conducted to exploit the catalytic potential of gold compounds bearing this type of bifunctional PN ligands [122–124]. The key feature

336 Scheme 9.15 Catalytic isomerization of alkynes to 1,3-dienes by a bifunctional FLP-like Au(I)/NR3 complex (33) that accelerates propargylic deprotonation

N. Hidalgo et al. R2

F3C

Ad P

33

R3 Ad

R1

Au R

[Au] (2 mol%) NaBArF PhCF3, 60 ºC

N

H H

R'

Deprotonation

R2 R1

R3

in all cases is to maintain a geometry that avoids gold-amine adduct formation while forcing conformational constraints that facilitate activation of the organic substrate by the cooperative action of the two active sites.

9.2.3 Rare-Earth elements Despite being less explored than transition metals, the choice of rare-earth (RE) metal complexes as acids to build TMFLPs becomes evident considering their widespread use as Lewis acids in catalysis [125]. Piers and Eisenstein exploited the electrophilicity of the decamethylscandocinium cation [Cp*2 Sc]+ in combination with the hydrido-(perfluorophenyl)-borate anion [HB(C6 F5 )3 ]− [126, 127]. This pair acts as an ionic FLP in which small molecules such as CO or CO2 can be trapped in the polarized Sc+ /- HB pocket and subsequently activated by hydride transfer from the borate anion. This approach allowed developing an efficient cooperative method for the deoxygenative hydrosilylation of CO2 . Cationic zirconocenes are likely the most investigated fragments in the area of metallic FLPs (see Sect. 2.1 and Fig. 9.2). Neutral complexes based on rare-earth elements are isolelectronic with them. On this basis, Xu reported an easily accessible bisaryloxide scandium complex (34) bearing a bifunctional alkoxyde with a pendant phosphine [128, 129]. Indeed, the ligand is identical to that present in the related zirconium FLP 16 (see Fig. 9.2). The scandium compound 34 exhibits a rich reactivity (Scheme 9.16) that compares well with related zirconium systems and with other metal-free FLPs. Thus, it reacts with benzaldehyde or chalcone to produce the corresponding 1,2- and 1,4-addition products, respectively. Addition of an ynone or dimethyl acetylenedicarboxylate yielded a nine-membered metallacycle and an intriguing bimetallacyclic structure that was confirmed by X-ray diffraction studies. Other interesting cyclic structures are derived from the FLPactivation of unsaturated substrates such as an α-diketone, a cyclopropyl ketone, and an epoxide (Scheme 9.16). Carbon–halogen bond cleavage was achieved in the presence of benzyl bromide, while the addition of nitrogen containing species

9 Frustrated Lewis Pairs Based on Transition Metals

ArO ArO ArO

PPh2

O

O

Sc ArO O

ArO

O Sc

·

O

ArO

Ph

ArO

Ph

Ph

ArO

CO2Me

Ph

Ph

O

ArO

OAr Sc OAr O

THF

C O

COOMe

Ph

N2

PPh2 N

Ph

SiMe3

ArO O ArO Sc ArO Br

ArO ArO

PPh2 Ph

ArO H

Ph

O Sc N

MeO

Ph O

ArO

O Sc

PPh2 N

O

BzBr

O

Sc ArO O

O

N2

S8 N

PPh2

Ph

PPh2

PPh2 Ph

O Sc

Ph

Sc

O

ArO ArO

O

ArO

Ph

O

ArO

O

Ph2P

Ph

H

O

PPh2

OMe

MeO2C

34 O Sc

PPh2

O

O Ph

O

ArO

O Sc

MeO

O

O

Ph

PPh2

Ph

Ph

Ph

ArO

O

PPh2

O

O Sc

O Sc

Ph

Ph

ArO

ArO

337

Sc N

PPh2

ArO

S

PPh2

N

Me3Si

Scheme 9.16 Small molecule activation pinwheel of a bisaryloxide scandium complex containing a bifunctional alkoxide-phosphine ligand

and elemental sulfur further confirmed the cooperative capacity of this intramolecular FLP to activate a wide variety of small molecules. In a related approach, the same group reported the synthesis of several rare-earth metal complexes of scandium, yttrium, and lutetium anchored by β-diketiminate ligands functionalized with a weakly coordinating phosphine [130, 131]. These pairs also exhibit a rich FLP reactivity toward the activation of small molecules and in polymerization catalysis. Rare-earth elements have been employed as efficient catalysts in the polymerization of polar alkenes [132, 133]. This topic was also examined by Xu using readily available and synthetically tunable intermolecular versions of their prior rare-earthbased FLPs. Following this approach, several RE complexes of type [RE(OAr)3 ] (RE = Sc, Y, Sm, La; Ar = 2,6-t Bu2 -C6 H3 ) were combined with a range of commercial phosphines as Lewis bases, more precisely PPh3 , PCy3 , PEt3 , and PMe3 [134, 135]. Mechanistic investigations demonstrated that polymerization of polar alkenes is initiated by the FLP-like 1,4 addition of the substrate across the intermolecular Lewis pair.

338

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An addition complex of that kind could even be structurally characterized by singlecrystal X-ray diffraction studies. An example of this reactivity based on a trisalkoxide scandium compound cooperating with PEt3 is represented in Scheme 9.17. The use of carbon-based Lewis bases, more precisely two well-known Nheterocyclic carbene (NHC) ligands such as It Bu and IMes was also interrogated during the polymerization of polar alkenes by Xu [134]. In the same vein, the group demonstrated that a combination of rare-earth homoleptic aryloxides [RE(OAr)3 ] (where RE = La, Sm or Y) with common N-heterocyclic carbenes effected dihydrogen activation [136]. Moreover, the rare-earth complexes were found to be active catalysts in the hydrogenation of NHCs toward aminals under mild conditions. These studies were connected to prior work from the group of Arnold based on the lability of RE–NHC [137, 138] bonds, after which even a U–NHC bond was successfully examined [139]. In a more recent study, the same research group took advantage of a bidentate ortho-aryloxide–NHC motif to prepare a series of homoleptic lanthanide complexes (36) based on cerium, samarium, and europium. Insertion of CO2 , RNCO (R = t Bu, Mes) and t BuNCS into the labile Ce–NHC bond was readily achieved under mild conditions [140]. Quantitative insertion of CO2 into the three Ce–C bonds is instant under all attempted conditions (Scheme 9.18), while the number of isocyanate and isothiocyanate molecules inserted was controlled by solvent and steric tuning of the substrate, ranging from monoinserted to triply activated products.

(MMA) t t

t

Bu O

Bu

t

t

Sc

O

t

Bu

O

Bu O

Bu

O

Et3P

PEt3

O

O

MeOOC

nMMA

Et3P n

Sc(OAr)3

H

Bu

35

Scheme 9.17 1,4-addition of methyl methacrylate (MMA) into the intermolecular FLP Sc/P pair formed by 35 and PEt3 followed by MMA polymerization t

Bu

t

t

Bu t Bu

O

N t

Bu

R R N

Ce

O

Bu

N

N

N

N

O N

O t Bu N R

36 R = iPr, tBu, Mes

t

Bu

CO2 (1 atm) < 5 min

t

Bu t

Bu

O

O

N

O

Ce O

R R N O t

O

t

O

Bu

O t

Bu

N

N

R

Scheme 9.18 Triple insertion of CO2 across the Ce–NHC bonds in compounds 36

Bu

9 Frustrated Lewis Pairs Based on Transition Metals

339

In terms of reversibility, only the more congested aryloxide–NHC ligand, namely the mesityl substituted one, liberates one molecule of CO2 under dynamic vacuum (100 °C, 10–3 mbar). This may be directly connected to the catalytic potential of these complexes, since only the latter promotes formation of propylene carbonate from propylene oxide and CO2 , while the compounds constructed around the less sterically demanding ligands provided no activity under the same conditions. Triple activation over a related cerium-based FLP stabilized by a heptadentate N4 P3 ligand was also achieved recently. Capitalizing on the lability of Ce–P bonds, Zhu accomplished the triple activation of isocyanates, isothiocyanates, diazomethane, and azides [141].

9.3 Frustrated Lewis Pairs and Related Systems based on Two Transition Metals The previous section describes a plethora of examples in which transition metal elements behave as either Lewis acids or bases within a frustrated framework. However, systems in which the two components are based on transition metals are rather rare, despite the fact that many polarized heterobimetallic complexes exhibit cooperative reactivity that is reminiscent of FLPs [142–146]. In this section, we will first focus on the single currently available example of a genuine transition metal only FLP (TMOFLP) and its reactivity toward small molecules to later examine recent results on polarized heterobimetallic species and their connection to the field of FLPs, particularly in cases where the analogy has been explicitly drawn by the authors.

9.3.1 Transition Metal Only Frustrated Lewis Pairs (TMOFLPs) In a first attempt toward an all-transition metal FLP, the group of Wass anticipated the use of a phosphinoaryloxide zirconocene as a suitable framework to coordinate an electron rich Pt(0) center through its pendant phosphine. Contrary to the expected Zr(IV)/Pt(0) FLP, a new heterobimetallic compound is formed instead by formal insertion of the platinum center into a Zr–C bond [147]. Shortly after, Campos described the first TMOFLP by combining [(PMe2 ArDipp2 )Au(I)]NTf2 (37b; ArDipp2 = C6 H3 -2,6-(C6 H3 -2,6-i Pr2 )2 ; NTf2 − = [N(SO2 CF3 )2 ]− ) and [Pt(0)(Pt Bu3 )2 ] (38), motivated by their proven Lewis acidic and basic character, respectively [148]. In these studies, the choice of rather bulky phosphine ligands was essential to avoid the formation of a metal-only Lewis pair (MOLP) [149]. This was investigated in detail by modifying the substituents of the terphenyl phosphine ligand that binds the Au(I) fragment, more precisely by incorporating PMe2 ArXyl2 and PCyp2 ArXyl2

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N. Hidalgo et al.

(ArXyl2 = C6 H3 -2,6-(C6 H3 -2,6-Me2 )2 ) ligands [150]. The steric shielding provided by the three investigated phosphines follows the order PCyp2 ArXyl2 > PMe2 ArDipp2 > PMe2 ArXyl2 , which has a direct impact on the equilibrium between metal adduct formation and complete frustration (Scheme 9.19). This solution equilibria is deeply affected by solvent conditions as well, in analogy to traditional FLPs [151]. Thus, while the least congested system 37a yields exclusively the corresponding metal adduct under all attempted conditions, the more hindered 37c shifts to the opposite end. Interestingly, the system with the intermediate size phosphine PMe2 ArDipp2 presents an in-between situation in which the two extreme scenarios are modulated depending on experimental conditions [150, 152]. Reactivity studies toward dihydrogen [148, 150] and acetylene [148, 153] revealed a strong influence of the equilibrium depicted in Scheme 9.19 on the activity of the bimetallic pairs. In the case of dihydrogen, it is necessary to remark that neither gold nor platinum precursors react with H2 by themselves even under more forcing conditions. However, the bimetallic system involving the medium-sized phosphine (37b) was highly active, as evinced by the immediate splitting of H2 even at − 20 °C. Full conversion of the gold precursor in the bulkier system (37c) required longer reaction times, though the least active pair was clearly the one based on 37a, in which formation of the bimetallic Lewis adduct hampers H2 activation. A joint experimental/computational effort revealed that the latter system acts as a thermally induced FLP, [101] in which generation of the individual monometallic fragments is a prerequisite for dihydrogen splitting to occur, thus ruling out more traditional heterobimetallic activation mechanisms [150]. A key termolecular transition state (TS1 in Scheme 9.20) that parallels those proposed for main group FLPs [80–82] was inferred from computational investigations. In addition, a rather strong inverse kinetic isotopic effect of 0.4–0.5 was recorded, for which a non-conventional origin was outlined. R'

R' NTf2 R' P

R'

R'

R

Au + R

Solvent

Pt

R'

P( Bu)3

Au R

Pt

R

P(tBu)3

R'

38 37a: R = Me, R' = Me 37b: R = Me, R' = iPr 37c: R = Cyp, R' = Me

R' P

t

+ NTf2-

(tBu)3P

P(tBu)3

C6D 6 37a Adduct 37b Frustration 37c Frustration

CD2Cl2 Adduct Equilibrium Frustration

CD2Cl2/MeOH Adduct Adduct Frustration

Scheme 9.19. Metal adduct formation vs full frustration in solution as a function of ligand sterics and solvent conditions

9 Frustrated Lewis Pairs Based on Transition Metals

341 + NTf2-

R' 37b: H2 (0.5 bar), C6D6 -20 ºC, < 5 min

(PMe2Ar)Au(NTf2) (37)

+ [Pt(PtBu3)2] (38)

R'

H Au

R'

P(tBu)3

Au

R'

P

37c: H2 (0.5 bar), C6D6 25 ºC, 18 h

R'

R

R'

+

H

P R

R

R

+ NTf2-

Pt P(tBu)3

R' R'

37a: R = Me, R' = Me 37b: R = Me, R' = iPr 37c: R = Cyp, R' = Me 37a: H2 (0.5 bar), C6D6, 25 ºC, 48 h

37b: 12 h, 25 ºC

NTf2 R'

H Au

R'

R'

R

R'

R

Au

R'

P(tBu)3

P R'

R

R'

TS1

P(tBu)3

H

Pt

P R'

+ NTf2-

P(tBu)3

H

Pt P(tBu)3

R

H

Scheme 9.20. Heterolytic dihydrogen activation by Au(I)/Pt(0) pairs highlighting the modelled FLP-type transition state (TS1)

While the activation of dihydrogen by these Au(I)/Pt(0) pairs resulted in different product distributions, exposure of 37:38 to acetylene atmosphere evidenced strong selectivity effects derived from subtle modifications of the substituents of the phosphine ligands (Scheme 9.21) [153]. For instance, the medium size phosphine in 37b yielded a 4:1 mixture of a bridging heterobimetallic σ,π-acetylide, and a rare vinylene (-CH = CH-) structure. In turn, reducing the steric pressure around the gold center increases the ratio of σ,π-acetylide/vinylene up to 95:5, while moving toward the fully frustrated system accomplished exactly the opposite, that is, quantitative formation of the heterobimetallic vinylene. It is worth noting that the two heterobimetallic products derived from acetylene activation highly resemble those obtained in the area of main group FLPs, where a competition between deprotonation and addition mechanisms usually takes place [154].

R'

NTf2 R'

+

P R' R'

R

P(tBu)3

P(tBu)3

Au

R

C2 H2

Pt P(tBu)3

C6D6 25 ºC

Au ArR2P

P(tBu)3

Pt

H

Pt

+ NTf2-

(tBu)3P

+ NTf2-

+ Au

H

H

P(tBu)3

ArR2P

38 37a: R = Me, R' = Me 37b: R = Me, R' = iPr 37c: R = Cyp, R' = Me

37a: 37b: 37c:

95 80