Separation of enantiomers : sysnthetic methods / edited by Matthew Todd.

Format:

Book

Contributor:

Todd, Matthew H., editor.

Language:

English

Subjects (All):

Enantiomers--Separation.

Enantiomers.

Physical Description:

x, 298 pages : illustrations ; 25 cm

Place of Publication:

Weinheim : Wiley-VCH, [2014]

Summary:

In one volume this book summarizes the most common synthetic methods for the separation of enantiomers, allowing an easy comparison of the different strategies described in the literature. Alongside classical and reagent-based methods, the authors consider kinetic resolutions, dynamic kinetic resolutions, divergent reactions of racemic mixtures, and enzymatic examples of such processes, a well as a number of "neglected" cases not previously brought together. The result is a thorough introduction to the field plus a long-needed overview of the relevant chemical, biological, and physical methods and their applications. Newcomers to the field, students as well as experienced synthetic chemists will benefit from the highly didactic presentation: Every method is presented in detail, from relatively simple separation problems to advanced synthetic resolution methods. Book jacket.

Contents:

1 Introduction: A Survey of How and Why to Separate Enantiomers / Matthew Todd Todd, Matthew 1

1.1 Classical Methods 2

1.2 Kinetic Resolution ('KR') 3

1.3 Dynamic Kinetic Resolution ('DKR') 5

1.4 Divergent Reactions of a Racemic Mixture ('DRRM') 7

1.5 Other Methods 8

Acknowledgments 9

References 9

2 Stoichiometric Kinetic Resolution Reactions / Mahagundappa R. Maddani Maddani, Mahagundappa R., Jean-Claude Fiaud Fiaud, Jean-Claude, Henri B. Kagan Kagan, Henri B. 13

2.1 Introduction 13

2.2 Kinetic Treatment 14

2.2.1 Reactions First-Order in Substrate 14

2.2.1.1 Scope and Validity of Equation 2.6 18

2.2.1.2 Equivalent Formulations of the Basic Equation 2.6 19

2.2.2 Reactions Zero- or Second-Order in. Substrate 19

2.2.3 Improvement of Kinetic Resolution Processes 20

2.2.4 Use of Enantio-Impure Auxiliaries 21

2.3 Chiral Reagents and Racemic Substrates 22

2.3.1 Esterification 22

2.3.2 Amide and Peptide Formation 30

2.3.3 Cycloaddibon Reactions 35

2.3.4 Conjugate Additions 39

2.3.5 Borane-Involving Reactions 41

2.3.6 Kinetic Resolution of Allenes 43

2.3.7 Olefination Reactions 45

2.3.8 Deprotonation Reactions 48

2.3.9 Miscellaneous 49

2.4 Enantiodivergent Formation of Chiral Product 51

2.4.1 Introduction 51

2.4.2 Creation of a Stereogenic Unit 52

2.4.3 Formation of Regioisomers 54

2.5 Enantiocouvergent Reactions 55

2.6 Diastereomer Kinetic Resolution 56

2.7 Some Applications of Kinetic Resolution 58

2.7.1 Organometallics and Analogues 58

2.7.2 Racemic Catalysts 61

2.7.3 Enantiomeric excess's and Stereoselectivity Factor Measurements by Mass Spectrometry 63

2.7.4 Mechanistic Studies. The Hoffmann Test 66

2.7.5 Miscellaneous 69

2.8 Conclusion 70

2.A Table of s Factors Higher than 10 for Some Reactions 70

References 72

3 Catalytic Kinetic Resolution / Helaie Pellissier Pellissier, Helaie 75

3.1 Introduction 75

3.2 Kinetic Resolution of Alcohols 76

3.2.1 KR of Alcohols Using Chiral Acylation Catalysts 76

3.2.2 Oxidative KR of Alcohols 81

3.2.3 Miscellaneous Kinetic Resolutions 87

3.3 Kinetic Resolution of Epoxides 88

3.3.1 Hydrolytic Kinetic Resolution 88

3.3.2 Ring Opening of Epoxides by Nucleophiles Other than Water 92

3.4 Kinetic Resolution of Amines 93

3.5 Kinetic Resolution of Alkenes 97

3.6 Kinetic Resolution of Carbonyl Derivatives 101

3.7 Kinetic Resolution of Sulfur Compounds 202

3.8 Kinetic Resolution of Ferrocenes 103

3.9 Conclusions 105

Abbreviations 105

References 107

4 Application of Enzymes in Kinetic Resolutions, Dynamic Kinetic Resolutions and Deracemization Reactions / Cara E. Humphrey Humphrey, Cara E., Marwa Ahmed Ahmed, Marwa, Ashraf Ghanem Ghanem, Ashraf, Nicholas J. Turner Turner, Nicholas J. 123

4.1 Introduction 123

4.2 Kinetic Resolutions Using Hydrolytic Enzymes 123

4.2.1 Lipases in Organic Synthesis 123

4.2.2 Structural Features of Lipases 124

4.2.3 Typical Substrates for Lipases and Esterases 125

4.2.4 Monitoring the Progress of Lipase-Catalysed Resolutions 126

4.2.5 Kazlauskas' Rule 127

4.2.6 Activated Acyl Donors 128

4.2.7 Examples of Lipase-, Lipolase- and Hydrolase-Catalysed Reactions in Synthesis 129

4.2.7.1 Resolution of Secondary Alcohols 129

4.2.7.2 Resolution of Amines 131

4.2.7.3 Hydrolysis of Lactams and Nitriles 132

4.2.7.4 Epoxide Hydrolases 133

4.2.8 Strategies for Controlling and Enhancing the Enantioselectivity of Enzyme-Catalysed Reactions 134

4.2.8.1 Substrate Engineering 134

4.2.8.2 Solvent Engineering 135

4.2.8.3 Immobilization and Chemical Modification 136

4.2.8.4 Directed Evolution and Enzyme Libraries 137

4.3 Dynamic Kinetic Resolution 138

4.3.1 Non-Enzyme-Catalysed Racemization 139

4.3.1.1 In Situ Racemization via Protonation/Deprotonation 139

4.3.1.2 In Situ Racemization via Addition/Elimination 140

4.3.1.3 In Situ Racemization via Oxidation/Reduction 140

4.3.1.4 In Situ Racemization via Nucleophilic Substitution 141

4.3.1.5 In Situ Racemization via Free Radical Mechanism 141

4.3.2 Metal-Catalysed Racemization 141

4.3.2.1 Ruthenium-Based Catalysts 142

4.3.2.2 Non-Ruthenium Catalysts 145

4.3.3 Enzyme-Catalysed Racemization 147

4.4 Deracemization 148

4.4.1 Deracemization of Secondary Alcohols 148

4.4.2 Deracemization of Carboxylic Acids 150

4.4.3 Deracemization of Amino Acids and Amines 151

4.4.4 Deracemization of Enol Actates 152

4.5 Enantioconvergent Reactions 153

4.6 Conclusions 153

References 154

5 Dynamic Kinetic Resolution (DKR) / Keiji Nakano Nakano, Keiji, Masato Ritamura Ritamura, Masato 161

5.1 Introduction 161

5.2 Definition and Classification 162

5.3 Dynamic Kinetic Resolution (DKR) 164

5.3.1 Tautomerization 164

5.3.2 Pyramidal Inversion, Deformation and Rotation 181

5.3.3 Elimination-Addition and Addition-Elimination 184

5.3.4 Nucleophilic Substitution 193

5.3.5 Others 198

5.4 Mathematical Expression 201

5.5 DKR-Related Methods 204

5.5.1 DYKAT through a Single Enantiomeric Intermediate 205

5.5.2 DTR of Two Diastereomeric Intermediates 206

5.5.3 Stereoinversion 206

5.5.4 Cyclic Deracemization 207

5.5.5 Enantio-Convergent Transformation 207

5.6 Concluding Remarks 208

References 209

6 Enantiodivergent Reactions: Divergent Reactions on a Racemic Mixture and Parallel Kinetic Resolution / Trisha A. Russell Russell, Trisha A., Edwin Vedejs Vedejs, Edwin 217

6.1 Introduction: The Conceptual Basis for Kinetic Resolution and Enantiodivergent Reactions 217

6.2 Divergent RRM Using a Single Chiral Reagent: Ketone Reduction 222

6.2.1 Racemic Ketones and Chiral Non-Enzymatic Hydride Donors 227

6.3 Divergent RRM under Oxidative Conditions 229

6.4 Organometallic Reagents and Regiodivergent RRM 237

6.5 Regiodivergent RRM in Selective Reactions of Difunctional Substrates 248

6.6 Divergent RRM Using Two Chiral Reagents: Parallel Kinetic Resolution (PKR) 252

6.7 Conclusion 262

Acknowledgement 262

References 262

7 Rare, Neglected and Potential Synthetic Methods for the Separation of Enantiomers / Matthew Todd Todd, Matthew 267

7.1 Resolution through the Selfish Growth of Polymers: Stereoselective Polymerization 267

7.2 Resolution through Photochemical Methods 271

7.3 Combinations of Crystallization and Racemization 274

7.3.1 Crystallization-Induced Dynamic Resolution (CIDR) 275

7.3.2 Ripening 277

7.4 Destruction Then Recreation of Stereocentres: Enantioselective Protonations 278

7.5 Dynamic Combinatorial Chemistry 280

7.6 Asymmetric Autocatalysis 282

7.7 Miscellaneous 283

7.8 Concluding Remarks 283

Acknowledgements 284

References 284.

ISBN:

9783527330454

3527330453

OCLC:

881845802