Separation of Enantiomers E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 483

Veröffentlichungsjahr: 2014

Beschreibung

Seit den Anfängen durch Louis Pasteur hat die Racematspaltung eine rasante Entwicklung durchlaufen. Nicht zuletzt wegen des hohen Bedarfs an enantiomerenreinen Wirkstoffe in der Medizin sind die Methoden für die Darstellung enantiomerer Verbindungen durch die Racematspaltung immer eleganter und ausgereifter geworden. Dynamisch kinetische Racematspaltung oder enzymatische Methoden - die Möglichkeiten werden immer vielfältiger und ausgereifter. Dieses Buch mit den Beiträgen zahlreicher renommierter Autoren stellt nun erstmals alle wichtigen Aspekte dieser faszinierenden Methode zusammen. Die zahlreichen Querverweise innerhalb des Buches und Referenzen für weiterführende Literatur ermöglichen eine rasche Recherche auf diesem Gebiet. Von einfachen Trennungsproblemen bis hin zu komplizierten Fragestellungen wird der Einsteiger mit didaktischem Geschick an die Thematik herangeführt und der Experte erhält wertvolle Informationen zu diesem Fachgebiet.

Leseprobe

Table of Contents

Cover

Title Page

Related Titles

Copyright

List of Contributors

Chapter 1: Introduction: A Survey of How and Why to Separate Enantiomers

1.1 Classical Methods

1.2 Kinetic Resolution (‘KR’)

1.3 Dynamic Kinetic Resolution (‘DKR’)

1.4 Divergent Reactions of a Racemic Mixture (‘DRRM’)

1.5 Other Methods

Acknowledgments

References

Chapter 2: Stoichiometric Kinetic Resolution Reactions

2.1 Introduction

2.2 Kinetic Treatment

2.3 Chiral Reagents and Racemic Substrates

2.4 Enantiodivergent Formation of Chiral Product

2.5 Enantioconvergent Reactions

2.6 Diastereomer Kinetic Resolution

2.7 Some Applications of Kinetic Resolution

2.8 Conclusion

References

Chapter 3: Catalytic Kinetic Resolution

3.1 Introduction

3.2 Kinetic Resolution of Alcohols

3.3 Kinetic Resolution of Epoxides

3.4 Kinetic Resolution of Amines

3.5 Kinetic Resolution of Alkenes

3.6 Kinetic Resolution of Carbonyl Derivatives

3.7 Kinetic Resolution of Sulfur Compounds

3.8 Kinetic Resolution of Ferrocenes

3.9 Conclusions

Abbreviations

References

Chapter 4: Application of Enzymes in Kinetic Resolutions, Dynamic Kinetic Resolutions and Deracemization Reactions

4.1 Introduction

4.2 Kinetic Resolutions Using Hydrolytic Enzymes

4.3 Dynamic Kinetic Resolution

4.4 Deracemization

4.5 Enantioconvergent Reactions

4.6 Conclusions

References

Chapter 5: Dynamic Kinetic Resolution (DKR)

5.1 Introduction

5.2 Definition and Classification

5.3 Dynamic Kinetic Resolution (DKR)

5.4 Mathematical Expression

5.5 DKR-Related Methods

5.6 Concluding Remarks

References

Chapter 6: Enantiodivergent Reactions: Divergent Reactions on a Racemic Mixture and Parallel Kinetic Resolution

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

6.2 Divergent RRM Using a Single Chiral Reagent: Ketone Reduction

6.3 Divergent RRM under Oxidative Conditions

6.4 Organometallic Reagents and Regiodivergent RRM

6.5 Regiodivergent RRM in Selective Reactions of Difunctional Substrates

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

6.7 Conclusion

Acknowledgement

References

Chapter 7: Rare, Neglected and Potential Synthetic Methods for the Separation of Enantiomers

7.1 Resolution through the Selfish Growth of Polymers: Stereoselective Polymerization

7.2 Resolution through Photochemical Methods

7.3 Combinations of Crystallization and Racemization

7.4 Destruction Then Recreation of Stereocentres: Enantioselective Protonations

7.5 Dynamic Combinatorial Chemistry

7.6 Asymmetric Autocatalysis

7.7 Miscellaneous

7.8 Concluding Remarks

Acknowledgements

References

Index

End User License Agreement

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Guide

Table of Contents

List of Illustrations

Scheme 1.1

Scheme 1.2

Scheme 1.3

Scheme 1.4

Scheme 1.5

Scheme 1.6

Scheme 1.7

Scheme 1.8

Scheme 1.9

Scheme 1.10

Scheme 2.1

Figure 2.1

Figure 2.2

Figure 2.3

Scheme 2.2

Scheme 2.3

Scheme 2.4

Scheme 2.5

Scheme 2.6

Scheme 2.7

Scheme 2.8

Scheme 3.1

Scheme 3.2

Scheme 3.3

Scheme 3.4

Scheme 3.5

Scheme 3.6

Scheme 3.7

Scheme 3.8

Scheme 3.9

Scheme 3.10

Scheme 3.11

Scheme 3.12

Scheme 3.13

Scheme 3.14

Scheme 3.15

Scheme 3.16

Scheme 3.17

Scheme 3.18

Scheme 3.19

Scheme 4.1

Scheme 4.2

Scheme 4.3

Scheme 4.4

Scheme 4.5

Scheme 4.6

Scheme 4.7

Scheme 4.8

Scheme 4.9

Scheme 4.10

Scheme 4.11

Scheme 4.12

Scheme 4.13

Scheme 4.14

Scheme 4.15

Scheme 4.16

Scheme 4.17

Scheme 4.18

Scheme 4.19

Schemes 4.20

Figure 4.21

Scheme 4.22

Scheme 4.23

Scheme 4.24

Scheme 4.25

Scheme 4.26

Scheme 4.27

Scheme 4.28

Schemes 4.29

Figure 4.30

Scheme 4.31

Scheme 4.32

Scheme 4.33

Scheme 4.34

Figure 4.35

Scheme 4.36

Scheme 4.37

Scheme 4.38

Scheme 4.39

Scheme 4.40

Scheme 4.41

Scheme 4.42

Scheme 4.43

Scheme 4.44

Scheme 4.45

Scheme 4.46

Scheme 4.47

Scheme 4.48

Scheme 4.49

Figure 5.1

Figure 5.2

Scheme 5.32

Scheme 5.1

Scheme 5.2

Scheme 5.3

Scheme 5.4

Scheme 5.5

Scheme 5.6

Scheme 5.7

Scheme 5.8

Scheme 5.9

Scheme 5.10

Scheme 5.11

Scheme 5.12

Scheme 5.13

Scheme 5.14

Scheme 5.15

Scheme 5.16

Scheme 5.17

Scheme 5.18

Scheme 5.19

Scheme 5.20

Scheme 5.28

Scheme 5.21

Scheme 5.22

Scheme 5.23

Scheme 5.24

Scheme 5.25

Scheme 5.26

Scheme 5.27

Scheme 5.29

Scheme 5.30

Scheme 5.31

Scheme 5.33

Scheme 5.34

Scheme 5.35

Scheme 5.36

Scheme 5.37

Scheme 5.38

Scheme 5.39

Scheme 5.40

Scheme 5.41

Scheme 5.42

Scheme 5.43

Scheme 5.44

Scheme 5.45

Scheme 5.46

Scheme 5.47

Scheme 5.48

Scheme 5.49

Schemes 5.50

Figure 5.52

Scheme 5.51

Scheme 5.53

Figure 5.3

Figure 5.4

Scheme 5.54

Scheme 5.55

Scheme 5.56

Scheme 5.57

Scheme 5.58

Figure 6.1

Figure 6.2

Figure 6.3

Scheme 6.1

Scheme 6.2

Scheme 6.3

Scheme 6.4

Scheme 6.5

Scheme 6.6

Scheme 6.7

Scheme 6.8

Scheme 6.9

Scheme 6.10

Scheme 6.11

Scheme 6.12

Schemes 6.13

Figure 6.15

Scheme 6.14

Scheme 6.16

Scheme 6.17

Scheme 6.18

Scheme 6.19

Scheme 6.20

Scheme 6.21

Scheme 6.22

Scheme 6.23

Scheme 6.24

Scheme 6.25

Scheme 6.26

Schemes 6.27

Figure 6.28

Scheme 6.29

Scheme 6.30

Scheme 6.31

Scheme 6.32

Scheme 6.33

Scheme 6.34

Scheme 6.35

Scheme 6.36

Scheme 6.37

Scheme 6.38

Scheme 6.39

Scheme 6.40

Scheme 6.41

Schemes 6.42

Figure 6.43

Scheme 7.1

Scheme 7.2

Scheme 7.3

Scheme 7.4

Scheme 7.5

Scheme 7.6

Scheme 7.7

Scheme 7.8

List of Tables

Table 2.1

Table 2.2

Table 3.1

Table 3.2

Table 6.1

Table 6.2

Separation of Enantiomers

Synthetic Methods

Edited by

Matthew Todd

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The Editor

Dr. Matthew Todd

The University of Sydney

Faculty of Science

School of Chemistry

Sydney, NSW 2006

Australia

Cover

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List of Contributors

Marwa Ahmed

University of Canberra

Faculty of Education, Science, Technology & Mathematics (ESTeM)

Biomedical Science Discipline

Kirinari Street, Bruce

Canberra, ACT 2601

Australia

Jean-Claude Fiaud

Université Paris-Sud

Laboratoire de Catalyse Moléculaire (UMR 8182)

Institut de Chimie Moléculaire et des Matériaux d'Orsay

rue Georges Clemenceau

Orsay

France

Ashraf Ghanem

University of Canberra

Faculty of Education, Science, Technology & Mathematics (ESTeM)

Biomedical Science Discipline

Kirinari Street, Bruce

Canberra, ACT 2601

Australia

Cara E. Humphrey

Investigator III

NIBR/GDC/PSB Prep Labs

class="item1">Klybeckstrasse 141

Basel

Switzerland

Henri B. Kagan

Université Paris-Sud

Laboratoire de Catalyse Moléculaire (UMR 8182)

Institut de Chimie Moléculaire et des Matériaux d'Orsay

rue Georges Clemenceau

Orsay

France

Masato Kitamura

Nagoya University

Department of Basic Medicinal Science

Graduate School of Pharmaceutical Science

Furo-cho, Chikusa-ku

Nagoya 464-8601

Japan

Mahagundappa R. Maddani

Mangalore University

Department of Chemistry

Mangalagangotri-574199

Karnataka

India

Keiji Nakano

Kochi University

Department of Applied Science

2-5-1 Akebono-cho

Kochi 780-8520

Japan

Hélène Pellissier

Aix Marseille Université

Centrale Marseille

CNRS

iSm2 UMR 7313

Marseille 13397

France

Trisha A. Russell

Whitworth University

Department of Chemistry

W. Hawthorne Rd.

Spokane, WA 99218

USA

Matthew Todd

The University of Sydney

Faculty of Science

School of Chemistry

Sydney, NSW 2006

Australia

Nicholas J. Turner

The University of Manchester

Manchester Institute of Biotechnology-3.019

School of Chemistry

Princess Street

Manchester M13 9PL

UK

Edwin Vedejs

University of Michigan

Department of Chemistry

N. University Ave.

Ann Arbor, MI 48109

USA

1Introduction: A Survey of How and Why to Separate Enantiomers

Matthew Todd

This book is about the separation of enantiomers by synthetic methods, which is to say methods involving some chemical transformation as part of the separation process. We do not in this book cover chromatographic methods for the separation of enantiomers [1]. Nor do we focus on methods based on crystallizations as these have been amply reviewed elsewhere (see below). We are concerned mainly therefore with resolutions that involve a synthetic component, so mostly with the various flavours of kinetic resolutions through to more modern methods such as divergent reactions of a racemic mixture (DRRM). This introduction briefly clarifies the scope of the book.

The reasons such methods are of continued importance are threefold:

Society: the need for enantiopure compounds

. New molecules as single enantiomers are important to our continued well-being because they are the feedstocks of new medicines, agrochemicals, fragrances and other features of modern society in a chiral world. Of the 205 new molecular entities approved as drugs between 2001 and 2010, 63% were single enantiomers [2]. Nature provides an abundance of enantiopure compounds, but we seek, and need, to exceed this by obtaining useful unnatural molecules as single enantiomers, and we may reasonably want to access both enantiomers of some compounds.

Academia: the basic science involved in the behaviour of chiral compounds

. If we seek the state of the art in our discipline, we cannot help but think that rapid and selective chemical distinction between enantiomers, which results in their facile separation, is something beautiful in itself. There have been many successful methods developed for the synthetic separation of enantiomers, as we shall see, and these are both interesting and instructive to consider for the design of future examples of such processes. The relationship between kinetic resolution and asymmetric catalysis is strong, and one can inform the design of the other. It is hoped that the diverse examples described in this book stimulate thoughts in the reader of what is possible next.