Enantioselection in Asymmetric Catalysis

Enantioselection in Asymmetric Catalysis


Author:
Ilya D. Gridnev & Pavel A. Dub
Published in: CRC Press
Release Year: 2017
ISBN: 978-1-4987-2654-2
Pages: 247
Edition: First Edition
File Size: 4 MB
File Type: pdf
Language: English



Description of Enantioselection in Asymmetric Catalysis


The idea of writing Enantioselection in Asymmetric Catalysis book came when the authors were finalizing their long-term studies of the mechanisms of asymmetric Rh-catalyzed hydrogenation of activated olefins (IDG) and Ru-catalyzed hydrogenation and transfer hydrogenation of aromatic ketones (PAD). Both fields have attracted considerable interest from researchers due to the utmost effectiveness and extremely high levels of enantioselectivity that were achieved in certain reactions of this type. This supports the attempts to uncover the real mechanism of the generation of chirality because the observation of optical yields of over 99% ee suggests it would be easier to locate a real catalytic pathway among the numerous possibilities.
Nevertheless, during their experimental and computational studies, the authors became convinced that, even in the case of extremely high optical yields, it is not easy to establish reliably the actual pathways taken in the multistep catalytic cycles and elucidate the factors important for the effective generation of chirality.
There are several reasons for these complications, but all of them come from the same origin: the multistep character of the catalytic cycles. It means, for example, that several stages of a chiral catalytic cycle can be enantioselective. Therefore, we can compute or even observe experimentally high enantioselectivity for a certain step of the catalytic cycle but still cannot be completely confident if it is actually this step that is responsible for the overall chirality of the product.
Practically it means that the whole network of possible catalytic pathways that may be converging and/or may contain bifurcation points must be computed before a reliable decision on the nature of the enantioselective step can be made. This, in turn, requires accurate knowledge of all possible experimental data on the relative stabilities of the intermediates, structure of the resting state, kinetics, etc., to calibrate and control the computational results.
In other words, the elucidation of the mechanism of enantioselection in an asymmetric catalytic reaction is not an easy and straightforward task; it requires extensive experimental and computational studies. The first two reactions discussed in Enantioselection in Asymmetric Catalysis book are evidently exceptional with respect to the amount of research that has been used to elucidate the mechanism of these reactions. One can confidently claim no other catalytic asymmetric reaction can be compared in this respect to Rh-catalyzed asymmetric hydrogenation of activated olefins and Ru-catalyzed hydrogenation and transfer hydrogenation of ketones. However, despite the research carried out in this field over several decades, some problems still
remain unresolved.
Unfortunately, this means the research of the mechanism of enantio selection of many other reactions presented in Enantioselection in Asymmetric Catalysis book can hardly be considered complete, and this problem has recently been discussed using the Morita–Baylis–Hillman reaction as an example.1 Taking into account all these complications, Enantioselection in Asymmetric Catalysis book does not attempt to give a comprehensive compilation of the current research in this field. Rather, representative asymmetric catalytic reactions catalyzed by chiral complexes of transition metals or organocatalytic reactions not highlighted in the recent reviews2,3 are discussed.
Although the authors tried to make the illustrations of the important transition states as clear as possible, this is not always possible for complex 3D structures. Hence, for the convenience of the readers, Enantioselection in Asymmetric Catalysis book is accompanied by a CD containing the key structures in the “.mol” format that is readily readable by most commercial and freeware visualization software.

Content of Enantioselection in Asymmetric Catalysis


Chapter 1 Transition metal-catalyzed hydrogenation 1
1.1 Rh-catalyzed asymmetric hydrogenation of activated olefins 1
1.1.1 Overview 
1.1.2 Asymmetric hydrogenation catalyzed
by Rh–diphosphine ligands 1
1.1.2.1 Resting state of the catalytic cycle:
Formation of the catalyst–substrate complexes 1
1.1.2.2 Activation of H2 8
1.1.2.3 Formation of solvate dihydrides 12
1.1.2.4 Oxidative addition to chelate
catalyst–substrate complexes 15
1.1.2.5 Reactions of solvate dihydrides with
prochiral substrates  22
1.1.2.6 Catalytic cycle and enantioselective step 33
1.1.2.7 Process of enantioselection 37
1.1.2.8 Sense of enantioselection and the relative
size of substituents 54
1.1.3 Catalysis with rhodium complexes of monophosphates 62
1.1.4 Conclusions 65
1.2 Ru-catalyzed asymmetric hydrogenation and transfer
hydrogenation of ketones 68
1.2.1 Overview 68
1.2.2 A brief critical overview of experimental and
computational techniques used in the early
mechanistic studies of 1 and 2 71
1.2.2.1 The characteristic time and sensitivity of
NMR spectroscopy 71
1.2.2.2 Kinetics 71
1.2.2.3 Computations in the gas-phase 73
1.2.3 Progress of the reaction mechanism with 1 and 2 74
1.2.4 The origin of the enantioselectivity 85
1.2.5 Unresolved problems 89
1.2.5.1 Reaction mechanism 89
1.2.5.2 Enantioselectivity 92
1.3 Ir-catalyzed asymmetric hydrogenation of
C=C and C=N bonds 94
1.3.1 Overview
1.3.2 Catalytic cycle and intermediates 94
1.3.3 Mechanism of enantioselection 97
1.3.3.1 Simple olefins 98
1.3.3.2 Imines 100
1.3.3.3 Heterocycles 101
1.3.4 Conclusion
1.4 Pd-catalyzed asymmetric hydrogenation of indoles 104
1.4.1 Overview 104
1.4.2 Catalytic cycle 105
1.4.3 Enantioselectivity 106
References 108

Chapter 2 Other enantioselective reactions catalyzed by

transition metals 133
2.1 Enantioselective reactions catalyzed by bifunctional Ru and
Ir complexes 133
2.1.1 Mechanism of the Michael addition catalyzed by
bifunctional Ru catalysts 133
2.1.2 Mechanism of C–C, and C–N bond-forming reactions
catalyzed by bifunctional Ir catalysts 135

2.2 Rh-catalyzed stereoselective isomerization of

Test-cyclobutanols into chiral indoles 143
2.2.1 Overview 143
2.2.2 Catalytic cycle 144
2.3 Os-catalyzed asymmetric dihydroxylation
(Sharpless reaction) 147
2.3.1 Overview 147
2.3.2 Catalytic cycle 149
2.3.3 Enantioselectivity 149
2.4 Pd- and Rh-catalyzed conjugate additions of arylboronic acids
to enones and nitrostyrene (Hayashi−Miyaura reaction) 152
2.4.1 Overview 152
2.4.2 Catalytic cycle 152
2.4.3 Catalytic cycle (M = Rh, Scheme 2.12) 154
2.4.4 Origin of enantioselectivity (M = Pd) 155
2.4.5 Origin of enantioselectivity (M = Rh) 157
2.5 Rh-catalyzed asymmetric hydroboration of vinyl arenes 158
2.5.1 Overview 158
2.5.2 Catalytic cycle 160
2.5.3 Enantioselectivity 161
2.6 Mechanism of auto amplifying Soai reaction 164
2.6.1 Introduction 164
2.6.2 Studies of the reaction pool of Soai reaction 166
2.6.3 Structure of the catalyst and computations of the
catalytic cycle of Soai reaction 168
References 172

Chapter 3 Mechanism of enantioselection in organocatalytic

reactions 183
3.1 Phosphoric acids 183
3.1.1 Asymmetric allylboration 183
3.1.2 Kinetic resolution in Robinson-type cyclization 184
3.1.3 Friedel–Crafts alkylation of indoles with nitroalkenes 185
3.1.4 Petasis–Ferrier-type rearrangement 188
3.1.5 Enantioselective indole aza-Claisen rearrangement 190
3.1.6 Asymmetric Thiocarboxylysis of Meso-epoxide 190
3.1.7 Asymmetric sulfoxidation reaction 192
3.2 Cinchona alkaloids 192
3.2.1 Asymmetric olefin isomerization 194
3.2.2 Friedel–Crafts alkylation of indoles with
α,β-unsaturated ketones 195
3.2.3 Conjugate addition of dimethyl malonate to
β-nitrostyrene 198
3.2.4 Fluorination of cyclic ketones 199
3.2.5 Phase-transfer-catalyzed alkylation reaction 200
3.3 Urea and thiourea-based catalysts 201
3.3.1 Catalytic Strecker reaction 202
3.3.2 Michael addition reactions 203
3.3.3 Enantioselective decarboxylative protonation 205
3.3.4 Henry reaction 207
3.3.5 α-Hydroxylation of β-ketoesters 209
3.4 N-Protonated chiral oxazaborolidine 212
3.4.1 C−C insertion reaction 212
3.5 FLP-catalyzed asymmetric hydrogenation of imines and
enamines 214
3.5.1 Overview  214
3.5.2 Catalytic cycle 216
3.5.3 Enantioselectivity 216
References 218
Conclusions 225
Index 229
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