Principles of Asymmetric Synthesis

The world is chiral. Most of the molecules in it are chiral, and asymmetric synthesis is an important means by which enantiopure chiral molecules may be obtained for study and sale. Using examples from the literature of asymmetric synthesis, this book presents a detailed analysis of the factors that govern stereoselectivity in organic reactions.

After an explanation of the basic physical-organic principles governing stereoselective reactions, the authors provide a detailed, annotated glossary of stereochemical terms. A chapter on "Practical Aspects of Asymmetric Synthesis" provides a critical overview of the most common methods for the preparation of enantiomerically pure compounds, techniques for analysis of stereoisomers using chromatographic, spectroscopic, and chiroptical methods.

The authors then present an overview of the most important methods in contemporary asymmetric synthesis organized by reaction type. Thus, there are four chapters on carbon-carbon bond forming reactions, one chapter on reductions, and one on oxidations (carbon-oxygen and carbon-nitrogen bond forming reactions). This organization allows the reader to compare the leading methods for asymmetric synthesis in an appropriate context.

A highlight of the book is the presentation and discussion of transition states at the current level of understanding, for important reaction types. In addition, extensive tables of examples are used to give the reader an appreciation for the scope of each reaction. Finally, leading references are provided to natural product synthesis that has been accomplished using a given reaction as a key step.

• Authoritative glossary to aid understanding of stereochemical terminology
• Explanations of the key factors influencing stereoselectivity with numerous examples, organized by reaction type
• A handy reference guide to the literature of asymmetric synthesis for practitioners in the field

This book is intended for advanced undergraduate or graduate students needing a guide to the principles of asymmetric synthesis and stereoselective reactions, and for practicing chemists seeking a similar level of understanding or who want leading references to the primary literature. The book could be used for a course in organic mechanisms, stereochemistry, reactions, or synthesis. It will also be a valuable reference source for the expert.

Dedication

Foreword

Preface

Chapter 1. Introduction, General Principles, and Glossary of Stereochemical Terms

1.1 Why We Do Asymmetric Syntheses

1.2 What is an Asymmetric Synthesis?

1.3 Stereoselectivity, and What It Takes to Achieve It

1.4 Selectivity: Kinetic and Thermodynamic Control

1.5 Entropy, the Isoinversion Principle, and the Effect of Temperature on Selectivity

1.6 Single and Double Asymmetric Induction

1.7 Kinetic Resolution

1.8 The Curtin–Hammett Principle

1.9 Asymmetric Transformations and Dynamic Resolutions

1.10 Asymmetric Catalysis and Nonlinear Effects

1.11 Glossary of Stereochemical Terms22

References

Chapter 2. Practical Aspects of Asymmetric Synthesis

2.1 Choosing a Method for Asymmetric Synthesis

2.2 How to Get Started

2.3 General Considerations for Analysis of Stereoisomers

2.4 Chromatography

2.5 Nuclear Magnetic Resonance

2.6 Chiroptical Methods

2.7 Summary

References

Chapter 3. Enolate, Azaenolate, and Organolithium Alkylations

3.1 Enolates and Azaenolates1

3.2 Chiral Organolithiums

References

Chapter 4. 1,2- and 1,4-Additions to CX Bonds

4.1 Cram’s Rule: Open-Chain Model

4.2 Cram’s Rule: Rigid, Chelate, or Cyclic Model

4.3 Chiral Catalysts and Chiral Auxiliaries

4.4 Conjugate Additions

References

Chapter 5. Aldol and Michael Additions of Allyls, Enolates, and Enolate Equivalents

5.1 1,2-Allylations and Related Reactions

5.2 Aldol Additions5

5.3 Michael Additions15

References

Chapter 6. Cycloadditions and Rearrangements

6.1 Cycloadditions

6.2 Rearrangements

References

Chapter 7. Reductions and Hydroborations

7.1 Reduction of Carbon–Heteroatom Double Bonds

7.2 Reduction of Carbon–Carbon Bonds

7.3 Hydroborations

References

Chapter 8. Oxidations

8.1 Epoxidations and Related Reactions

8.2 Asymmetric Dihydroxylation (AD) Reaction

8.3 α-Functionalization of Carbonyl Groups and Their Equivalents

8.4 Miscellaneous Oxidations that Necessitate Differentiation of Enantiotopic Groups

References

Index