Comprehensive Chirality - 1st Edition - ISBN: 9780080951676, 9780080951683

Comprehensive Chirality

1st Edition

Editor-in-Chiefs: Hisashi Yamamoto Erick Carreira
eBook ISBN: 9780080951683
Hardcover ISBN: 9780080951676
Imprint: Elsevier Science
Published Date: 5th September 2012
Page Count: 5648
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Description

Although many books exist on the subject of chiral chemistry, they only briefly cover chiral synthesis and analysis as a minor part of a larger work, to date there are none that pull together the background information and latest advances in one comprehensive reference work. Comprehensive Chirality provides a complete overview of the field, and includes chiral research relevant to synthesis, analytic chemistry, catalysis, and pharmaceuticals. The individual chapters in each of the 9 volumes provide an in depth review and collection of references on definition, technology, applications and a guide/links to the related literature. Whether in an Academic or Corporate setting, these chapters will form an invaluable resource for advanced students/researchers new to an area and those who need further background or answers to a particular problem, particularly in the development of drugs.

Key Features

  • Chirality research today is a central theme in chemistry and biology and is growing in importance across a number of disciplinary boundaries. These studies do not always share a unique identifying factor or subject themselves to clear and concise definitions. This work unites the different areas of research and allows anyone working or researching in chiral chemistry to navigate through the most essential concepts with ease, saving them time and vastly improving their understanding.
  •  The field of chirality counts several journals that are directly and indirectly concerned with the field. There is no reference work that encompasses the entire field and unites the different areas of research through deep foundational reviews. Comprehensive Chirality fills this vacuum, and can be considered the definitive work. It will help users apply context to the diverse journal literature offering and aid them in identifying areas for further research and/or for solving problems.
  • Chief Editors, Hisashi Yamamoto (University of Chicago) and Erick Carreira (ETH Zürich) have assembled an impressive, world-class team of Volume Editors and Contributing Authors. Each chapter has been painstakingly reviewed and checked for consistent high quality. The result is an authoritative overview which ties the literature together and provides the user with a reliable background information and citation resource.

Readership

Graduate students and researchers working in organic, medicinal, and biological chemistry, as well as pharmacologists and toxicologists.

Table of Contents

Editors in Chief

Volume Editors

Preface

Permission Acknowledgments

Volume 1: Biological Significance: Pharmacology, Phamaceutical Agrochemical

1.1 Introduction: The Importance of Chirality in Drugs and Agrochemicals

Glossary

1.1.1 Drugs

1.1.2 Agrochemicals

References

1.2 Importance of Chirality in the Field of Anti-infective Agents

Glossary

1.2.1 Introduction

1.2.2 Antiinfectives from Natural Origin

1.2.3 Antiinfectives from Nonnatural Origin

1.2.4 Conclusion

Acknowledgments

References

1.3 Chirality in Antibacterial Agents

Glossary

1.3.1 Introduction

1.3.2 Membrane Synthesis Inhibitors

1.3.3 Antibacterial Agents Acting on DNA

1.3.4 Protein Synthesis Inhibitors

1.3.5 Molecules Acting on New Targets

1.3.6 Antibacterial Agents as Chiral Selectors

References

1.4 Diastereomers, Enantiomers and Bioactivity. TMC207: A New Candidate for the Treatment of Tuberculosis

Glossary

1.4.1 Introduction

1.4.2 Inhibition of ATP Synthase by TMC207

1.4.3 Chemistry

1.4.4 In Vitro Antimycobacterial Activity of TMC207

1.4.5 Conformational Analysis of TMC207

1.4.6 Molecular Basis and Stereospecificity

1.4.7 Conclusion

Acknowledgments

References

1.5 Fluorine in Medicinal Chemistry: Importance of Chirality

1.5.1 Introduction

1.5.2 Pharmaceuticals and Molecules of Biological Interest Bearing Fluorine and Trifluoromethyl Groups at an sp3-Hybridized Carbon

References

1.6 Peptides and Chirality Effects on the Conformation and the Synthesis of Medicinally Relevant Peptides

Glossary

1.6.1 Introduction

1.6.2 Chirality in Peptides from Amino Acids to Secondary Structures

1.6.3 Chirality in Peptide Turn Geometry and Nucleation of β-Sheets

1.6.4 Alternating Chirality in Peptide Helical Geometry and Cyclic Peptide Nanotubes

1.6.5 Enantiomeric and Retro-enantio Peptide Analogs of Biologically Active Peptides

1.6.6 Systematic Study of the Effects of Amino Acid Configuration on Conformation and Activity by D-Amino Acid Scanning of Peptide Hormones

1.6.7 Maintaining Configurational Integrity in Peptide Synthesis by Overcoming the Pitfall of Racemization during Amide Bond Formation

1.6.8 Industrial Synthesis of Chiral Peptides

1.6.9 Conclusion

References

1.7 Stereochemical Lability in Drug Molecules: Cases Where Chirality May Not Be Critical for Drug Development

Glossary

1.7.1 Introduction

1.7.2 Chiral Drug Candidates that are Stereochemically Labile

1.7.3 Methods for Assessing Stereomutation

1.7.4 Conclusion

Acknowledgment

References

1.8 Chirality in Agrochemicals

1.8.1 Introduction

1.8.2 Chiral Fungicides

1.8.3 Chiral Insecticides

1.8.4 Chiral Herbicides

References

1.9 The use of New Phosphines as Powerful Tools in Asymmetric Synthesis of Biologically Active Compounds

Glossary

1.9.1 General Comments on the Importance of Chirality in Biologically Active Compounds

1.9.2 New Phosphines in the Synthesis of Drug Candidates

1.9.3 Phosphines in the Synthesis of Pharmacophores

1.9.4 New Phosphines in Selected Total Syntheses

1.9.5 Summary

References

1.10 Chirality and Combinatorial Libraries for Drug Discovery, an Overview

Volume 2: Synthetic Methods I: Chiral Pool and Diastereoselective Methods

2.1 Introductory Remarks: Chiral Pool Syntheses and Diastereoselective Reactions

Glossary

References

2.2 General Principles of Diastereoselective Reactions: Rigid Templates

Glossary

2.2.1 Introduction

2.2.2 Rigid Templates

References

2.3 General Principles of Diastereoselective Reactions: Diastereoselectivity via Substrate-Directable Reactions (Internal Delivery) and Heterocyclizations

Glossary

2.3.1 Introduction

2.3.2 Internal Delivery

2.3.3 Heterocyclization

References

2.4 General Principles of Diastereoselective Reactions: Acyclic Control of Diastereoselectivity

2.4.1 Introduction

2.4.2 Simple Diastereoselectivity

2.4.3 Induced Diastereoselectivity

2.4.4 Differentiation of Diastereotopic Groups in Diastereoselective Synthesis

2.4.5 Thermodynamic Control of Diastereoselectivity

References

2.5 General Principles of Diastereoselective Reactions: Diastereoselective Domino Reactions

2.5.1 Introduction

2.5.2 Domino Reactions Involving Pericyclic Processes

2.5.3 Transition Metal-Catalyzed Domino Reactions

2.5.4 Domino Reactions Involving 1,4-Addition

2.5.5 Miscellaneous Domino Reactions

2.5.6 Conclusion

References

2.6 Chiral Pool Synthesis: From α-Amino Acids and Derivatives

Glossary

2.6.1 Introduction

2.6.2 Alanine

2.6.3 Valine: Malyngamide X (Scheme 5)

2.6.4 Cysteine Ecteinascidin Et 583(6.8) (Scheme 6)

2.6.5 Proline

2.6.6 Trans-4-Hydroxy-L-Proline

2.6.7 (+)-(R)-Pipecolinic Acid

2.6.8 Serine

2.6.9 Aspartate: Cyclomarin A (Scheme 25)

2.6.10 L-Glutamic Acid

2.6.11 Pyroglutamate (Scheme 28)

2.6.12 Allysine

2.6.13 D-Homotyrosine

2.6.14 Tryptophan

References

2.7 Chiral Pool Synthesis: Starting from Terpenes

Glossary

2.7.1 Introduction

2.7.2 Acyclic Monoterpenes: Citronellol, Citronellal, and Citronellene

2.7.3 Cyclic Monoterpenes

2.7.4 Bi- and Tricyclic Terpenes: Nepetalactone and Santonin

References

2.8 Chiral Pool Synthesis: Chiral Pool Syntheses Starting from Carbohydrates

2.8.1 Introduction

2.8.2 Background

2.8.3 Synthesis of Macrocyclic and Polycyclic Compounds

2.8.4 Synthesis of Heterocyclic Compounds

2.8.5 Synthesis of Carbocyclic Compounds

References

2.9 Chiral Pool Synthesis: Chiral Pool Syntheses from cis-Cyclohexadiene Diols

Glossary

2.9.1 Introduction

2.9.2 Discovery of the Degradation Pathway of Aromatics by Soil Bacteria

2.9.3 Isolation and Accessibility of Metabolites

2.9.4 Advantages of cis-Cyclohexadiene Diols in Synthesis

2.9.5 Microbiology Meets Chemistry – First Contact of Cyclohexadiene Diols with Chemists

2.9.6 Chiral Pool Syntheses from cis-Cyclohexadiene Diols

2.9.7 Conclusion

Acknowledgment

References

2.10 Chiral Pool Synthesis: Chiral Pool Synthesis from Hydroxy Acids: Lactic Acid, Tartaric Acid, Malic Acid, and 2-Methyl-3-hydroxypropionic Acid

Abbreviations

Glossary

2.10.1 Background

2.10.2 3-Hydroxybutyric Acid in Total Synthesis

2.10.3 Lactic Acid in Total Synthesis

2.10.4 Roche Ester in Total Synthesis

2.10.5 Mandelic Acid in Total Synthesis

2.10.6 Malic Acid in Total Synthesis

2.10.7 Tartaric Acid in Total Synthesis

References

2.11 Chiral Pool Synthesis: Chiral Pool Synthesis from Quinic Acid

2.11.1 Introduction

2.11.2 Transformations of Quinic Acid

2.11.3 Conversion of Quinic Acid to Shikimic Acid and Its Derivatives

2.11.4 Applications of Quinic Acid in Natural Product Synthesis

2.11.5 Concluding Remarks

References

2.12 Selected Diastereoselective Reactions: Additions of Achiral Carbanions to Chiral Aldehydes and Ketones

Glossary

2.12.1 Introduction and Theoretical Models

2.12.2 Addition of Polar Organometallic Reagents to Chiral Aldehydes and Ketones

References

2.13 Selected Diastereoselective Reactions: Aldoltype Additions

Abbreviations

2.13.1 Introduction

2.13.2 Aldol Reactions with Preformed Enolates

2.13.3 Catalytic Aldol Additions

References

2.14 Selected Diastereoselective Reactions: Enolate Alkylation

Abbreviations

2.14.1 Introduction

2.14.2 Alkylation of Ketone and Aldehyde Enolates

2.14.3 Alkylation of Ester and Lactone Enolates

2.14.4 Alkylation of Amide and Lactam Enolates

References

2.15 Selected Diastereoselective Reactions: Substrate Controlled Stereoselective Conjugate Addition Reactions with Organocopper Reagents

Glossary

2.15.1 Introduction

2.15.2 Organocopper Reagents in Total Synthesis

2.15.3 Conclusion

References

2.16 Selected Diastereoselective Reactions: Free Radical Additions and Cyclizations

Glossary

2.16.1 Introduction

2.16.2 General Comments on Radicals and Their Reactivity

2.16.3 Substrate-Controlled Intermolecular Reactions

2.16.4 Substrate-Controlled Intramolecular Reactions

2.16.5 Conclusion

References

2.17 Selected Diastereoselective Reactions: Intramolecular Diels–Alder Reactions

Glossary

2.17.1 Introduction

2.17.2 Synthetic Studies of Zoanthamine Alkaloids

2.17.3 Synthetic Studies of Symbioimine and Neosymbioimine

2.17.4 Synthetic Studies of Platensimycin and Platencin

2.17.5 Synthetic Studies of Vinigrol

2.17.6 Synthetic Studies of Other Natural Products Featured by Intramolecular Diels–Alder Reactions

References

2.18 Selected Diastereoselective Reactions: Diastereoselective Intra- and Intermolecular 1,3-Dipolar Cycloadditions in Natural Product Synthesis

Glossary

2.18.1 Introduction

2.18.2 General Rules (Charts 1 and 2)

References

2.19 Selected Diastereoselective Reactions: Electrocyclizations

Glossary

2.19.1 Introduction

2.19.2 2π Electrocyclizations

2.19.3 4π Electrocyclizations

2.19.4 6π Electrocyclizations

2.19.5 8π Electrocyclizations

References

2.20 Selected Diastereoselective Reactions: Ionic and Zwitterionic Cyclizations

2.20.1 Introduction

2.20.2 Nazarov-Initiated Diastereoselective Cyclization

2.20.3 Construction of Polycyclic Compounds Through the Interrupted Nazarov Reaction

2.20.4 Prins Reaction and Related Cationic Rearrangements

2.20.5 Polyaromatic Natural Products

2.20.6 Polyene/Epoxide Cyclization

2.20.7 Donor–Acceptor (D–A) Cyclopropanes

2.20.8 Internal Redox

2.20.9 Pot-Pourri

2.20.10 Conclusion

References

2.21 Selected Diastereoselective Reactions: Diastereoface-Differentiating Claisen, Cope, and [2,3]-Wittig Rearrangements in Contemporary Natural Product Synthesis

2.21.1 Introduction

2.21.2 Claisen Rearrangements

2.21.3 Cope Rearrangements

2.21.4 [2,3]-Wittig Rearrangements

2.21.5 Conclusion

References

2.22 Selected Diastereoselective Reactions: Heck Type Cyclizations

Glossary

2.22.1 Introduction

2.22.2 Cyclizations Onto Cyclic Alkenes

2.22.3 Cyclizations onto Acyclic and Exocyclic Alkenes

2.22.4 Conclusion

References

2.23 Selected Diastereoselective Reactions: Gold Catalyzed Cyclizations

2.23.1 Introduction

2.23.2 Asymmetric Aldol Reaction

2.23.3 Intrinsic Diastereoselectivity Based on Geometrical Restraints

2.23.4 Diastereoselective Formation of E/Z Isomers

2.23.5 sp3-Stereocenters from Enyne Substrates

2.23.6 sp3-Stereocenters from Enallene Substrates

2.23.7 sp3-Stereocenters from Alkyne Substrates

2.23.8 sp3-Stereocenters from Allenes

2.23.9 sp3-Stereocenters from Nucleophilic Additions to Alkenes

2.23.10 sp3-Stereocenters from Reactions with 1,3-Dipoles

2.23.11 sp3-Stereocenters from Nazarov-Like Cyclizations

2.23.12 sp3-Stereocenters from Wagner–Meerwein Shifts

2.23.13 sp3-Stereocenters from Indoles

2.23.14 Conclusion

References

2.24 Selected Diastereoselective Reactions: C–H Insertions

Volume 3: Synthetic Methods II: Chiral Auxiliaries

3.1 Amino Acid Derived Auxiliaries: Amino Acids as Chiral Auxiliaries

Glossary

3.1.1 Introduction

3.1.2 Reductions

3.1.3 C-C Bond-Forming Reactions

3.1.4 Resolutions

3.1.5 Concluding Remarks

References

3.2 Amino Acid Derived Heterocyclic Chiral Auxiliaries: The use of Oxazolidinones, Oxazolidinethiones, Thiazolidinethiones, and Imidazolidinones

3.2.1 Introduction

3.2.2 Asymmetric Addition to C–O Bonds

3.2.3 Asymmetric Alkylation and Related Reactions

3.2.4 Asymmetric Addition to C–C Bonds

3.2.5 Miscellaneous Reactions

3.2.6 Cleavage of Chiral Auxiliaries

3.2.7 Conclusion

References

3.3 Terpene Derived Auxiliaries: Camphor and Pinene Derived Auxiliaries

3.3.1 Introduction

3.3.2 Camphor

3.3.3 C-2 Functionalization

3.3.4 C1-C2 Functionalized Camphor-Derived Auxiliaries

3.3.5 C2–C3 Functionalized Camphor-Derived Auxiliaries

3.3.6 Auxiliaries Derived from Camphor-10-Sulfonic Acid

3.3.7 Aza-Camphor Class of Auxiliaries

3.3.8 Auxiliaries Derived from Pinene

3.3.9 Concluding Remarks

References

3.4 Terpene Derived Auxiliaries: Menthol and Pulegone Derived Auxiliaries

3.4.1 Menthol

3.4.2 Menthone

3.4.3 Pulegone

3.4.4 Phenylmenthol

3.4.5 Miscellaneous 8-(substituted)-menthol Derivatives

References

3.5 Terpene Derived Auxiliaries: Miscellaneous Terpene Derived Auxiliaries

Abbreviations

3.5.1 Miscellaneous Terpene Derived Chiral Auxiliaries

3.5.2 Fenchone Derivatives

3.5.3 Limonene Derivatives

3.5.4 Verbenone Derivatives

3.5.5 Longifolene Derivatives

3.5.6 Cedrene Derivatives

3.5.7 Carvone Derivatives

References

3.6 Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

3.6.1 Introduction

3.6.2 Use of Tartaric Acid and its Acid Derivatives for Asymmetric Reactions

3.6.3 Tartaric Acid Esters

3.6.4 Asymmetric Reactions Promoted by Tartramide–Metal Complexes

3.6.5 Miscellaneous

3.6.6 Conclusion

References

3.7 Acetogenin (Polypriopionate) Derived Auxillaries: Hydroxyacids

Glossary

3.7.1 Introduction

3.7.2 Background

3.7.3 Nucleophilic 1,2-Additions

3.7.4 Control of Chiral Centers in α- or β-Position of Carbonyl and Carboxylic Compounds

3.7.5 Cyclopropanations

3.7.6 Aziridinations

3.7.7 Cycloadditions

3.7.8 Miscellaneous Reactions

References

3.8 Acetogenin (Polypriopionate) Derived Auxillaries: Hydroxyacid Derivatives

Glossary

3.8.1 Introduction

3.8.2 Background

3.8.3 Access to Pantolactams

3.8.4 Enantioselective Reactions

3.8.5 Diastereoselective Reactions

References

3.9 Alkaloid Derived Auxiliaries: Cinchona Alkaloids and Derivatives

Glossary

3.9.1 Introduction

3.9.2 Chiral Auxiliaries

3.9.3 Metal-Mediated Reactions

3.9.4 Organocatalysis and Phase-Transfer Catalysis

3.9.5 Summary

References

3.10 Alkaloid-Derived Auxiliaries: Ephedra Alkaloids

3.10.1 History

3.10.2 Biosynthesis

References

3.11 Alkaloid Derived Auxiliaries: Miscellaneous Alkaloids

3.11.1 Asymmetric Aldol Addition Reaction

3.11.2 Asymmetric Aldol Addition Reaction: Application with (−)-Brucine

3.11.3 Nitroaldol (Henry) Reaction: (−)-Brucine

3.11.4 Enantioselective Reduction

3.11.5 Friedel–Crafts Alkylation of Indole

3.11.6 Cycloaddition Reactions

3.11.7 Cycloaddition Reactions

3.11.8 CarboLithiation: Conjugate Addition

3.11.9 Intramolecular Conjugate Addition

3.11.10 Synthesis and Application of Nicotine Derivatives via ortho-Lithiation

3.11.11 Kinetic Resolution

References

3.12 Carbohydrate Derived Auxiliaries: Mono (and Disaccharide) Derivatives

3.12.1 Introduction

3.12.2 Asymmetric Cycloaddition Reactions

3.12.3 Stereocontrolled Addition and Substitution Reactions

3.12.4 Rearrangement Reactions

3.12.5 Radical Reactions

3.12.6 Oxidation Reactions

3.12.7 Reduction Reactions

3.12.8 Miscellaneous Application of Carbohydrate Auxiliaries

3.12.9 Conclusions

Acknowledgments

References

3.13 Carbohydrate Derived Auxiliaries: Amino Sugar and Glycosylamine Auxiliaries

3.13.1 Introduction

3.13.2 Aminosugar-Derived Oxazolidinones

3.13.3 Glycosylamines as Auxiliaries

3.13.4 Glycosylamine-Derived Organocatalysts

3.13.5 Conclusion and Outlook

References

3.14 Synthetically Derived Chiral Auxiliaries: Uses of Derivatives of Non-Carbohydrate Aldehydes and Ketones in Asymmetric Synthesis

Glossary

3.14.1 Introduction

3.14.2 Background

3.14.3 Diastereomer Resolutions

3.14.4 Desymmetrizations of meso Compounds

3.14.5 Stereocontrolled Enolate Alkylations Involving Acetals

3.14.6 Stereocontrolled Enolate Alkylations Involving Ketals

3.14.7 Stereocontrolled 1,2-Additions to Carbonyl

3.14.8 Alkylations of Imines Derived from Chiral Aldehydes or Ketones

3.14.9 Stereocontrol of Radical Reactions Using Chiral Aldehydes or Ketones

3.14.10 Cycloaddition Reactions Involving Ketals, Hemiaminals, and Aminals Derived from Chiral Ketones

3.14.11 Miscellaneous Uses of Aldehydes and Ketones as Chiral Auxiliaries

3.14.12 Conclusion

References

3.15 Non-Chiral Pool Derived Synthetic Auxiliaries: Use of C2-Symmetric Chiral Diols

3.15.1 Introduction

3.15.2 C2-Symmetric Chiral 1,2- and 1,3-Diols

3.15.3 BINOL and BINOL-Derivatives

3.15.4 Conclusion

References

3.16 Synthetically Derived Auxiliaries: Amines (including Diamines), Hydrazines and Hydroxylamines, and Amino Alcohols

3.16.1 Introduction

3.16.2 Amines (Including Diamines)

3.16.3 Hydrazines and Hydroxylamines

3.16.4 Aminoalcohols

References

3.17 Synthetically Derived Auxiliaries: Phosphorus Derivatives

Glossary

3.17.1 Introduction

3.17.2 Preparation by Resolving Racemates

3.17.3 Stereoselective Synthesis Based on Alcohols as Chiral Auxiliaries

3.17.4 Stereoselective Synthesis Based on Diols as Chiral Auxiliaries

3.17.5 Stereoselective Synthesis Based on Aminoalcohols as Chiral Auxiliaries

3.17.6 Stereoselective Synthesis Based on Thiols as Chiral Auxiliaries

3.17.7 Stereoselective Synthesis Based on Amines as Chiral Auxiliaries

3.17.8 Stereoselective Synthesis Based on Diamines as Chiral Auxiliaries

3.17.9 Stereoselective Synthesis Based on Terpenoids as Chiral Auxiliaries

3.17.10 Conclusion

References

3.18 Synthetically Derived Auxiliaries: Sulfur Derivatives (including Sulfilamines and Sulfoximines)

3.18.1 Introduction

3.18.2 Synthesis of Chiral Sulfur Derivatives

3.18.3 Chiral Sulfur Derivatives as Auxiliaries in Asymmetric Synthesis

3.18.4 Applications of Chiral Sulfur Derivatives to the Synthesis of Biologically Active Substrates

3.18.5 Conclusions

References

3.19 Synthetically Derived Auxiliaries: Organometallic Derivatives (Main Group and Transition Metals)

3.19.1 Introduction

3.19.2 Main Group Organometallic Derivatives as Chiral Auxiliaries

3.19.3 Transition Metal Organometallic Derivatives as Chiral Auxiliaries

Acknowledgment

References

3.20 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Lithium

Glossary

3.20.1 Introduction

3.20.2 Background: Structure of Organolithiums in Solution

3.20.3 Ligands Connected to a Reactant by a Covalent Bond

3.20.4 Ligands without a Covalent Bond with a Reactant

3.20.5 Conclusions

References

3.21 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Magnesium and Calcium

3.21.1 Introduction

3.21.2 General Properties of Magnesium and Calcium Metal Salts

3.21.3 Enantioselective Diels–Alder Reactions

3.21.4 Enantioselective 1.3-Dipolar Cycloadditions

3.21.5 Lewis Acid-Mediated Radical Reactions

3.21.6 Enantioselective Nucleophilic Addition to CO and CN Double Bonds

3.21.7 Enantioselective Conjugate Additions

3.21.8 Miscellaneous

3.21.9 Conclusions

References

3.22 Chiral Ligation for Boron and Aluminum in Stoichiometric Asymmetric Synthesis

3.22.1 Introduction

3.22.2 Asymmetric Hydroboration

3.22.3 Asymmetric Reduction

3.22.4 Asymmetric Allylboration

3.22.5 Asymmetric Allenylboration

3.22.6 Asymmetric Propargylboration

3.22.7 Michael Additions to Unsaturated Substrates

3.22.8 Matteson Chain Extensions and Related Chemistry

3.22.9 Asymmetric Enolboration

3.22.10 Asymmetric Diels–Alder Cycloadditions

3.22.11 Chapter Summary and Concluding Remarks

References

3.23 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Silicon

Abbreviations

3.23.1 Introduction

3.23.2 Chiral Ligand-Modified Enolsilanes and Allylsilanes

3.23.3 Chiral Ligand-Modified Silanes as Stoichiometric Lewis Acids

3.23.4 Chiral Ligand-Modified Silanes as Lewis Acid Catalysts

3.23.5 Conclusion

References

3.24 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Tin and Stannanes

Abbreviations

3.24.1 Introduction

3.24.2 Chiral Organotin Reagents with Sn-Centered Chirality

3.24.3 Chiral Organotin Reagents with Sn-C-Linked Chiral Ligands

3.24.4 Chiral Organotin Reagents with Sn-Heteroatom-Linked Chiral Ligands

3.24.5 Conclusion

References

3.25 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Zinc

Abbreviations

3.25.1 Introduction

3.25.2 Addition to Carbonyl Compounds

3.25.3 Addition to Imine Derivatives

3.25.4 Conjugate Addition

3.25.5 Cyclopropanation

3.25.6 Miscellaneous Reactions

References

3.26 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Chromium

3.26.1 Introduction

3.26.2 Preparation of Planar Chiral Arene Chromium Complexes

3.26.3 Reactions of Arene Chromium Complexes

3.26.4 Fisher-Type Chromium Carbene Complexes

References

3.27 Stoichiometric Auxiliary Ligands for Metals and Main Group Elements: Ligands for Titanium and Zirconium Complexes

Volume 4: Synthetic Methods III: Catalytic Methods: C–C Bond Formation

4.1 Introduction: General Concepts

4.2 C–C Bond-Forming Reactions via the Heck Reaction

4.2.1 General Introduction

4.2.2 Heck Reactions

References

4.3 C–C Bond-Forming Reactions via Cross-Coupling

4.3.1 General Introduction

4.3.2 Cross-Coupling Reactions,

References

4.4 C-C Bond Formation (Metathesis)

4.4.1 Introduction

4.4.2 Diastereoselective Metathesis Reactions

4.4.3 Enantioselective Metathesis Reactions

4.4.4 Conclusions

Acknowledgment

References

4.5 C-C Bond Formation by Metal-Catalyzed Asymmetric Allylic Alkylation

4.5.1 Introduction

4.5.2 Palladium-Catalyzed Asymmetric Allylic Alkylation

4.5.3 Other Metal-Catalyzed Asymmetric Allylic Alkylations

References

4.6 C-C Bond Formation (Metal-Catalyzed Reductive Aldol Coupling)

4.6.1 Introduction

4.6.2 Rhodium

4.6.3 Cobalt

4.6.4 Iridium

4.6.5 Ruthenium

4.6.6 Palladium

4.6.7 Nickel

4.6.8 Platinum

4.6.9 Copper

4.6.10 Indium

4.6.11 Conclusion

Acknowledgments

References

4.7 C–C Bond Formation (Transition Metal-Catalyzed Michael)

4.7.1 Introduction

4.7.2 Conclusion

References

4.8 C-C Bond Formation (Metal-Carbene Catalyzed)

4.8.1 Introduction

4.8.2 Cyclopropanation

4.8.3 C–H Insertion Reactions

4.8.4 Reactions Involving Ylide Formation

4.8.5 Aromatic Addition and Substitution Reactions

4.8.6 Concluding Remarks

References

4.9 C-C Bond Formation using Lewis Acids and Silicon Enolates

4.9.1 Introduction

4.9.2 Asymmetric Lewis Acid-Catalyzed Mukaiyama Aldol Reactions

4.9.3 Asymmetric Lewis Acid-Catalyzed Mannich-Type Reactions using Silicon Enolates and Related Compounds

4.9.4 Asymmetric Lewis Acid-Catalyzed Michael Reactions with Silicon Enolates

4.9.5 Asymmetric Hetero-Diels–Alder Cycloadditions of Carbonyl Compounds and Imines with Silicon Enolates

4.9.6 Aza-Diels–Alder Cycloadditions

4.9.7 Summary

References

4.10 Enantioselective Aldol Reactions Catalyzed by Chiral Lewis Bases

Glossary

4.10.1 Introduction: Activation of Silyl Enol Ethers by Lewis Bases

4.10.2 Enantioselective Aldol Reactions of Trichlorosilyl Enol Ethers Catalyzed by Lewis Bases

4.10.3 Enantioselective Aldol Reactions Promoted by Lewis Base-activated Lewis Acids

4.10.4 Enantioselective Reductive Aldol Reactions

4.10.5 Enantioselective Direct Aldol-Type Reactions Via In Situ Generation of Silyl Enol Ethers

4.10.6 Enantioselective Aldol Reaction of Trimethoxysilyl Enol Ethers Catalyzed by Chiral Phenoxides

4.10.7 Aldol Reactions of Trimethylsilyl Enol Ethers Catalyzed by Phenoxides

4.10.8 Conclusion

References

4.11 C-C Bond-Forming Reactions via Transmetallation using Silyl Enol Ethers

Glossary

4.11.1 General Reaction Mechanism

4.11.2 Representative Examples

References

4.12 Direct C–C Bond Formation (Henry, aza-Henry)

Glossary

4.12.1 Introduction

4.12.2 Asymmetric Metal Catalysis for Henry Reaction and aza-Henry Reaction

4.12.3 Organocatalytic Henry Reaction and aza-Henry Reaction

4.12.4 Stereocontrol in Asymmetric Henry Reaction and aza-Henry Reaction

4.12.5 Outlook

References

4.13 Direct C-C Bond Formation (Michael, Aldol, and Mannich)

Glossary

Introduction

4.13.1 Metal-Catalyzed Direct Asymmetric Michael Reaction

4.13.2 Metal-catalyzed Direct Asymmetric Aldol Reaction

4.13.3 Metal-catalyzed Direct Asymmetric Mannich-type Reaction

Table Summary of Transformations

References

4.14 Reactions using Thioamide and Allylic Cyanide

4.14.1 Introduction

4.14.2 C-C Bond-Forming Reactions Using Thioamides

4.14.3 Direct Catalytic Asymmetric Mannich-Type Reaction of Thioamides

4.14.4 Direct Catalytic Asymmetric Aldol Reaction of Thioamides

4.14.5 Direct Catalytic Asymmetric Conjugate Addition of Terminal Alkynes to α,β-Unsaturated Thioamides

References

4.15 C-C Bond Formation

4.15.1 Reactions Using Chiral Lewis Acids

4.15.2 Reaction Using Chiral Metal Catalyst

4.15.3 Reaction Using Chiral Organocatalysts

References

4.16 Enantioselective Cyanation of Carbonyls and Imines

Glossary

4.16.1 Introduction

4.16.2 Background

4.16.3 Asymmetric Addition of Cyanide to Aldehydes and Ketones

4.16.4 Asymmetric Addition of Cyanide to Imines and Related Species

References

4.17 Asymmetric 1,2-Addition of Organometallics to Carbonyl and Imine Groups

4.17.1 Introduction

4.17.2 Zinc

4.17.3 Magnesium

4.17.4 Lithium

4.17.5 Other Metals

4.17.6 Outlook

References

4.18 C-C Bond Formation (1,2-Alkenylation)

4.18.1 Introduction

4.18.2 Catalytic Asymmetric Alkenylation using Alkenylzinc Reagents

4.18.3 Catalytic Asymmetric Alkenylation using Alkenylsilicon and Alkenylboron Reagents

4.18.4 Catalytic Asymmetric Nozaki–Hiyama–Kishi Reactions

4.18.5 Catalytic Asymmetric Morita–Baylis–Hillman Reactions and Their Aza Variants

4.18.6 Catalytic Asymmetric Reductive and Alkylative Coupling Reactions

4.18.7 Other Conditions

References

4.19 To Catalytic Asymmetric 1,2-Alkynylation

Glossary

4.19.1 Introduction

4.19.2 Alkynylation of Aldehydes

4.19.3 Alkynylation of Ketones

4.19.4 Alkynylation of Imines

4.19.5 Concluding Remarks

References

4.20 Other C-C Bond Formations including Au

Volume 5: Synthetic Methods IV – Asymmetric Oxidation Reduction, C–N

5.1 Asymmetric Baeyer–Villiger Oxidation

Glossary

5.1.1 Introduction

5.1.2 Mechanism of Baeyer–Villiger Oxidation

5.1.3 Asymmetric Reactions

5.1.4 Conclusions

References

5.2 Oxidation: C-O Bond Formation by C-H Activation

Glossary

5.2.1 Introduction

5.2.2 Enantioselective Benzylic Oxidation

5.2.3 Asymmetric Desymmetrization by C-H Oxidation

5.2.4 Enantioselective Allylic C-H Oxidation

5.2.5 Enantioselective Propargylic Oxidation

5.2.6 Other Stereoselective Oxidation Systems for Activated C-H Bonds

5.2.7 Selective Oxidation of Nonactivated C-H Bonds

References

5.3 Oxidation: Epoxidation (Allylic Alcohol, Homoallylic Alcohol, Simple C–C, Electron Deficient C–C)

Glossary

5.3.1 General

5.3.2 Epoxidation of Allylic Alcohols

5.3.3 Epoxidation of Homoallylic Alcohol

5.3.4 Epoxidation of Simple Carbon--Carbon Double Bonds

5.3.5 Epoxidation of Electron-Deficient Carbon–Carbon Double Bonds

References

5.4 Oxidation: α-hydroxylation of Carbonyls

Glossary

5.4.1 Introduction

5.4.2 Stoichiometric Enantioselective α-Hydroxylation of Carbonyls and their Equivalents

5.4.3 Catalytic Enantioselective α-Hydroxylation of Carbonyls and their Equivalents

5.4.4 Summary and Conclusion

References

5.5 Oxidation: C–N Bond Formation by Oxidation: C–H Bond Activation

Glossary

5.5.1 Introduction

5.5.2 Metal–Nitrene-Mediated Enantioselective C–H Amination

5.5.3 Stereoselective Allylic Amination Actuated by C–H Abstraction

5.5.4 Catalytic C–H Amination with Azides as Nitrene Precursors

References

5.6 Oxidation: C-N Bond Formation by Oxidation (Aziridines)

Glossary

5.6.1 Introduction

5.6.2 Hypervalent Iodine Reagents as Nitrene Sources for Aziridination

5.6.3 Haloamine and Other Amine Compounds as Nitrene Sources for Aziridination

5.6.4 Azides as Nitrene Sources for Aziridination

5.6.5 Conclusions

Table Summary of Transformations

References

5.7 Oxidation: C-N Bond Formation by Oxidation: Dinitrogen Addition to Double Bond (Diamino)

5.7.1 Introduction

5.7.2 1,2-Diamination of Alkenes by Stoichiometric Reactions

5.7.3 1,2-Diamination of Alkenes by Catalytic Reactions

5.7.4 Diamination of Butadienes by Catalytic Reactions

5.7.5 Conclusion

References

5.8 Asymmetric S–O Bond Formation by Oxidation

Abbreviations

5.8.1 Introduction

5.8.2 Homogeneous Catalysts for Enantioselective S–O Bond Formation

5.8.3 Enantioselective Sulfoxidation with Heterogeneous Catalysts

5.8.4 Contribution of the Kinetic Resolution of Sulfoxide to Enantioselectivity

5.8.5 Conclusions

References

5.9 Oxidation: C-X Bond Formation (X–Halogen, S, Se)

Glossary

5.9.1 Introduction

5.9.2 Enantioselective Electrophilic Fluorination

5.9.3 Enantioselective Electrophilic Chlorination

5.9.4 Enantioselective Electrophilic Bromination

5.9.5 Enantioselective Electrophilic Iodination

5.9.6 Enantioselective Electrophilic Sulfenylation

5.9.7 Enantioselective Electrophilic Selenenylation

5.9.8 Conclusion and Outlook

References

5.10 Reduction – Hydrogenation: C–C; Chemoselective

Glossary

5.10.1 Introduction

5.10.2 Homogenous Catalytic Hydrogenation of Olefins

5.10.3 Conclusion

References

5.11 Reduction – Hydrogenation: C–O; Chemoselective

Glossary

5.11.1 Introduction

5.11.2 Background

5.11.3 Asymmetric Hydrogenation of Functionalized Ketones

5.11.4 Asymmetric Hydrogenation of Nonfunctionalized Ketones

5.11.5 Asymmetric Hydrogenation of Ketones with Dynamic Kinetic Resolution

References

5.12 Asymmetric Hydrogenation of Prochiral C–N Bonds

5.12.1 Introduction

5.12.2 Survey of Imine Substrates in Asymmetric Hydrogenation

5.12.3 Concluding Remarks

References

5.13 Reduction: Hydrosilylation

5.13.1 Introduction

5.13.2 Asymmetric Hydrosilylation of Ketones

5.13.3 Asymmetric Hydrosilylation of Imines and Related C–N Bonds

References

5.14 Reduction: Hydroformylation C–H and C–C

5.14.1 Introduction

5.14.2 Mechanism

5.14.3 Asymmetric Hydroformylation of Vinylarenes

5.14.4 Asymmetric Hydroformylation of Vinyl Acetate and Allyl Cyanide

5.14.5 Asymmetric Hydroformylation of Other Substrates

5.14.6 Synthetic Application to Larger Molecules

5.14.7 Catalysts that can be Recovered

References

5.15 Reduction: Hydrocyanation of C–C

5.15.1 Introduction

5.15.2 Scope of Asymmetric C–C-double Bond Hydrocyanation

5.15.3 Mechanistic Considerations

5.15.4 Practical Aspects on Laboratory Scale

References

5.16 Reduction: Enantioselective Hydrovinylation of Alkenes

5.16.1 Introduction

5.16.2 Hydrovinylation Reactions

5.16.3 Enantioselective Hydrovinylation Reactions

5.16.4 Hemilabile Ligands, Highly Dissociated Counter Ions, and Design of New Ligands for Asymmetric Hydrovinylation of Vinylarenes

5.16.5 Generation of All-Carbon Quaternary Centers

5.16.6 Hydrovinylation of 1,3-Dienes

5.16.7 Asymmetric Hydrovinylation of Norbornene and Other Strained Alkenes

5.16.8 Applications of Asymmetric Hydrovinylation Reactions

5.16.9 Conclusions and Future Prospects

References

5.17 Reduction: Pinacol Coupling

Glossary

5.17.1 Introduction

5.17.2 Pinacol Coupling

5.17.3 Imino-Pinacol Coupling

5.17.4 Carbonyl–Imine Reductive Coupling

References

5.18 Addition Reaction: Kinetic Resolution

Abbreviations

Glossary

5.18.1 Introduction

5.18.2 Background

5.18.3 Hydrolytic Kinetic Resolution (HKR) of Epoxides

5.18.4 Kinetic Resolution of Alcohols by Acylation

5.18.5 Kinetic Resolution of Alcohols by Silylation

5.18.6 Alcoholysis of Chiral Cyclic Acid Unhydrides and Related Compounds

5.18.7 Alcoholysis of Azlactones

5.18.8 Alcoholysis of Vinyl Ethers

5.18.9 Conclusion

References

5.19 Addition Reaction: 1,4 Addition Heteroatom

5.19.1 Introduction

5.19.2 Asymmetric Aza-Michael Reactions

5.19.3 Asymmetric Thio-Michael Reactions

5.19.4 Asymmetric Conjugate Phosphination and Silylation

5.19.5 Conclusion

References

5.20 Addition Reaction: Cycloaddition Involving Oxidation (N–N, N–O; No C–C Bond Formed)

5.20.1 Introduction

5.20.2 [4+2] Cycloaddition of Nitroso Compounds and Acyl Diazenes

5.20.3 [2+2] Cycloaddition of Nitroso Compounds and Diazenes

5.20.4 Stepwise Formation of Pyrazolidine Using a Azodicarboxylate

References

5.21 Desymmetrization of meso Diols

Abbreviations

Glossary

5.21.1 Introduction

5.21.2 Acylation and Related Reactions of meso Diols and Hydrolysis of meso-Diesters

5.21.3 Oxidations of meso Diols

5.21.4 Desymmetrization of Diol Derivatives

References

5.22 Desymmetrization of meso Epoxide

Glossary

5.22.1 Introduction

5.22.2 Background

5.22.3 Desymmetrization via Ring-Opening with Nitrogen Based Nucleophile

5.22.4 Desymmetrization via Ring-Opening with Oxygen Based Nucleophiles

5.22.5 Desymmetrization via Ring-Opening with Thiols and Selenols

5.22.6 Desymmetrization via Ring-Opening with Halogens

5.22.7 Desymmetrization via Ring-Opening with Carbon Nucleophiles

5.22.8 Desymmetrization via Deprotonation and Rearrangement

5.22.9 Desymmetrization of meso Aziridines

References

5.23 Desymmetrization of meso Anhydride

Volume 6: Synthetic Methods V – Organocatalysis

6.1 C–C Bond Formation: Alkylation

6.1.1 Introduction

6.1.2 Under Biphasic Phase-Transfer Conditions

6.1.3 Enamine Catalysis

6.1.4 Utilization of Radical Intermediate

6.1.5 Electrophilic Trifluoromethylation

6.1.6 Other Alkylation

References

6.2 C-C Bond Formation: Michael Reaction

6.2.1 Introduction

6.2.2 α,β-Unsaturated Aldehydes and Ketones as Michael Acceptors

6.2.3 Nitroolefins as Michael Acceptors

6.2.4 α,β-Unsaturated Acid Derivatives as Michael Acceptors

6.2.5 Other Michael Acceptors

6.2.6 Conclusion and Outlook

References

6.3 C-C Bond Formation: Mannich Reaction

6.3.1 Introduction

6.3.2 Proline and Proline Derivatives Catalyzed Reactions

6.3.3 Brønsted Base Catalyzed Reactions

6.3.4 Brønsted Acid Catalyzed Reactions

6.3.5 Conclusion

References

6.4 C–C Bond Formation: Aldol Reaction with Proline Derivatives

Glossary

6.4.1 Introduction

6.4.2 Proline Organocatalysts

6.4.3 Supported Organocatalysts

6.4.4 Mechanistic Studies

6.4.5 Application to Natural Product Syntheses

6.4.6 Conclusions

References

6.5 C–C Bond Formation: Aldol Reaction with Non-Proline Derivatives

Glossary

6.5.1 Introduction

6.5.2 Enamine Mechanism

6.5.3 Nonenamine Mechanism

6.5.4 Conclusions

References

6.6 Henry and aza-Henry Reactions

6.6.1 Introduction

6.6.2 Organocatalytic Henry (Nitroaldol) Reaction

6.6.3 Organocatalytic aza-Henry (Nitro-Mannich-type) Reaction

References

6.7 C–C Bond Formation: Cyanation

6.7.1 Cyanohydrin Synthesis

6.7.2 Strecker Reaction

References

6.8 Allylations of C–O and C–N Double Bonds and Related Reactions

Glossary

6.8.1 Introduction

6.8.2 Allylation and Related Reactions Catalyzed by Chiral Lewis Bases

6.8.3 Allylation with Allylboronates Catalyzed by Chiral Diols or Chiral Brønsted Acids

6.8.4 Allylation with Allylmetals Catalyzed by Chiral Organic Molecules

6.8.5 Aminoallylation of Aldehydes via a 2-Aza-Cope Rearrangement

6.8.6 Outlook and Perspective

References

6.9 C-C Bond Formation: (aza) Morita–Baylis–Hillman Reaction

Glossary

6.9.1 Introduction

6.9.2 Mechanism

6.9.3 Chiral Lewis Base Catalysts

6.9.4 Chiral Acid Catalysts

6.9.5 Chiral Acid–Base Catalysts

6.9.6 Enantioselective Domino Process Based on MBH Reactions

6.9.7 Conclusion

References

6.10 C–C Bond Formation: Diels–Alder Reaction

Glossary

6.10.1 Catalysis Using a Chiral Secondary Ammonium Salt

6.10.2 Catalysis Using a Chiral Primary Ammonium Salt

6.10.3 Catalysis Using Hydrogen Bonding

6.10.4 Hetero-Diels–Alder Reaction Using Organocatalysts

References

6.11 Cyclopropanation Reactions

6.11.1 Introduction to Chiral Cyclopropanes

6.11.2 Background to Cyclopropane Synthesis

6.11.3 Asymmetric Cyclopropanation Reactions through Organocatalytic Iminium Ion Activation of α,β-Unsaturated Aldehydes and Ketones

6.11.4 Asymmetric Cyclopropanation Reactions through Organocatalytic Hydrogen Bond Activation of Electron-deficient Olefin Derivatives

6.11.5 Asymmetric Cyclopropanation Reactions through Organocatalytic Activation of Ylides

6.11.6 Organocatalytic Asymmetric Cyclopropanation through Chiral Phase-transfer Catalysis

6.11.7 Conclusion and Outlook

Table Summary of Transformations

References

6.12 Benzoin and Stetter Reactions

Glossary

6.12.1 Introduction

6.12.2 Asymmetric Benzoin Reaction

6.12.3 Asymmetric Stetter Reaction

6.12.4 Conclusion

References

6.13 C-C Bond Formation: Cascade or Domino Reaction

6.13.1 Introduction

6.13.2 Double Cascade Reactions

6.13.3 Triple Cascade Reactions

6.13.4 Quadruple Cascade Reactions

6.13.5 Conclusions

References

6.14 C–N Bond Formation: α-Amination and α-Hydrazination of Carbonyl Compounds with DEAD and Related Compounds

Glossary

6.14.1 Introduction

6.14.2 Background

6.14.3 α-Amination of Carbonyl Compounds

References

6.15 C–N Bond Formation: Aziridine Formation

6.15.1 Introduction

6.15.2 Asymmetric Synthesis of Aziridines from Chiral Sulfonylimines

6.15.3 Iodine Catalyst

6.15.4 Aza-Darzens Reaction

6.15.5 Aziridination of Unsaturated Carbonyl Compounds

6.15.6 Aziridination by Organocatalytic Reduction of α-Haloimines

6.15.7 By Quaternary Salts of Cinchona Alkaloids

6.15.8 Conclusions

References

6.16 C–O Bond Formation: α-Oxygenation

6.16.1 α-Oxygenation of Carbonyl Compounds Introduction

6.16.2 α-Oxygenation from 1,2-Diol Introduction

6.16.3 α-Oxygenation via Oxidative Dearomatization of Phenols Introduction

6.16.4 α-Oxygenation via Oxidative Cyclyzation Introduction

References

6.17 C–O Bond Formation: Acylation of meso Diols

Glossary

6.17.1 Introduction

6.17.2 Background

6.17.3 Phosphine Catalysts

6.17.4 DMAP-Related Catalysts

6.17.5 Imidazole Catalysts

6.17.6 NHC Catalysts

6.17.7 Tertiary Amine Catalysts

6.17.8 Amidine Catalysts

6.17.9 Enzymatic Asymmetric Acylation

Table Summary of Transformations

References

6.18 C-O Bond Formation: Desymmetrization of Acid Anhydride

Glossary

6.18.1 Introduction

6.18.2 Enantioselective Desymmetrization of Acid Anhydride Using Cinchona Alkaloids

6.18.3 Enantioselective Desymmetrization of Acid Anhydride Using Nonalkaloid Catalysts

6.18.4 Mechanistic Studies

6.18.5 Conclusions

References

6.19 C–O Bond Formation: Epoxide Formation

6.19.1 Introduction

6.19.2 Catalytic Cycle via Sulfide Alkylation and Deprotonation

6.19.3 Ylide Formation from a Carbene Source

6.19.4 Diastereoselectivity

6.19.5 Enantioselectivity

6.19.6 Application in Synthesis

6.19.7 Other Ylide-Catalyzed Epoxidation

6.19.8 Summary

References

6.20 C–X Bond Formation: α-Halogenation of Carbonyl Compounds

Glossary

6.20.1 Introduction

6.20.2 Asymmetric Halogenation via Enamine Catalysis

6.20.3 Asymmetric Halogenation by Chiral tert-Amine Catalysts

6.20.4 Asymmetric Halogenation by Chiral Phase-transfer Catalysts

6.20.5 Asymmetric Halogenation by Chiral N-oxide

6.20.6 Conclusions

References

6.21 C–X Bond Formation: Organocatalytic Enantioselective Halogenation of meso Epoxides

Glossary

6.21.1 Introduction: Classical Halogenation of meso Epoxides

6.21.2 Chlorination of meso Epoxides by Silicon Tetrachloride and Chiral Lewis Bases as Organocatalysts

6.21.3 Mechanistic Scope of the Chlorination Reaction by Silicon Tetrachloride and Chiral Lewis Bases

6.21.4 Fluorination of the meso Epoxides by Chiral Amines as Co-Organocatalysts

6.21.5 Conclusion

References

6.22 C–X Bond Formation: Organocatalytic α-Sulfenylation and α-Selenenylation

6.22.1 Introduction

6.22.2 Organocatalytic α-Sulfenylation

6.22.3 Organocatalytic α-Selenenylation

6.22.4 Conclusions

References

6.23 Oxidation: Organocatalyzed Asymmetric Epoxidation of Alkenes

6.23.1 Introduction

6.23.2 Chiral Ketone-Catalyzed Epoxidation

6.23.3 Iminium Salt-Catalyzed Epoxidation

6.23.4 Other Asymmetric Epoxidation Reagents

6.23.5 Conclusion

References

6.24 Oxidation: Epoxidation of Enones

Glossary

6.24.1 General Introduction

6.24.2 Epoxidation of Enones

6.24.3 Epoxidation of Enals

6.24.4 Epoxidation of Enoates and Enamides

6.24.5 Epoxidation of Miscellaneous Electron-Deficient Alkenes: Vinyl Sulfones

6.24.6 Summary and Conclusions

Table Summary of Transformations

References

6.25 Reduction: Asymmetric Transfer Hydrogenation with Hantzsch Esters

Volume 7: Synthetic Methods VI – Enzymatic and Semi-Enzymatic

7.1 Introduction and General Concepts

Glossary

7.1.1 Biocatalysis in Organic Synthesis

7.1.2 The Current Biocatalysis Toolbox

7.1.3 New Synthetic Transformations using Biocatalysts

7.1.4 Future Trends

References

7.2 Screening Methods for Enzymes

7.2.1 Introduction

7.2.2 Screening Enzymes in Living Cells

7.2.3 Screening in Microtiter Plates

7.2.4 Screening with Multiple Substrates

7.2.5 Screening with Analytical Instrumentation

7.2.6 Conclusion

Acknowledgment

References

7.3 Directed Evolution and (Semi-) Rational Design Strategies for the Creation of Synthetically useful, Stereoselective Biocatalysts

Glossary

7.3.1 Introduction

7.3.2 Library Design and Construction

7.3.3 Screening and Selection

References

7.4 Cofactor Recycling for Enzyme Catalyzed Processes

Glossary

7.4.1 Introduction

7.4.2 Nicotinamide Cofactor Regeneration

7.4.3 Flavin Regeneration

7.4.4 PLP Regeneration

7.4.5 ATP/NTP Regeneration

7.4.6 Sugar Nucleotide Regeneration

7.4.7 PAPS Regeneration

7.4.8 Acetyl-Coenzyme a Regeneration

7.4.9 Conclusions

References

7.5 Reaction Engineering of Biotransformations

Glossary

7.5.1 Introduction

7.5.2 Important Process Properties of Enzymes

7.5.3 Enzyme Stabilization

7.5.4 Typical Reactors

7.5.5 Current and Future Developments in Enzyme Technology

7.5.6 Summary

References

7.6 Hydrolysis and Reverse Hydrolysis: Hydrolysis and Formation of Amides

Glossary

7.6.1 Introduction

7.6.2 Background

7.6.3 Production of Nonchiral Amides and Amines

7.6.4 Asymmetric Synthesis of Optically Active Amides

References

7.7 Hydrolysis and Reverse Hydrolysis: Selective Nitrile Hydrolysis using Nitrilase and its Related Enzymes

Glossary

7.7.1 Background

7.7.2 Distribution of Nitrilases

7.7.3 Nitrilase Mechanism, Structure, and Properties

7.7.4 Strategies for Screening Nitrilase-Producing Microorganisms

7.7.5 Strategies to Access Biodiversity for Synthetic Applications

7.7.6 Approaches to Improve the Catalytic Potential of Nitrilases

7.7.7 Opportunities and Future Outlook

References

7.8 Hydrolysis and Reverse Hydrolysis: Halohydrin Dehalogenases

7.8.1 Introduction

7.8.2 Biochemical Properties of Halohydrin Dehalogenases

7.8.3 Biocatalytic and Environmental Applications

7.8.4 Engineering Studies

7.8.5 Conclusions and Outlook

References

7.9 Hydrolysis and Reverse Hydrolysis: Dynamic Kinetic Resolution

7.9.1 Introduction

7.9.2 Fundamentals for Dynamic Kinetic Resolution

7.9.3 Dynamic Kinetic Resolution of Alcohols

7.9.4 Dynamic Kinetic Resolution of Amines and Amino Acids

7.9.5 Synthetic Applications of Metalloenzymatic DKR

7.9.6 Summary

References

7.10 Reduction: Asymmetric Biocatalytic Reduction of Ketones

7.10.1 Introduction

7.10.2 Types of ADHs

7.10.3 Sources of ADHs Useful for Biocatalysis

7.10.4 Selected ADHs Useful for Preparative Applications

7.10.5 Biocatalytic Ketone Reduction Process Concepts

7.10.6 Enantioselective Biocatalytic Ketone Reductions with a Focus on the Synthesis of Alcohols Used as Drug Intermediates

7.10.7 Integration of Biocatalytic Ketone Reduction in Multistep One-Pot Processes

7.10.8 Summary and Outlook

References

7.11 Reduction: Enantioselective Bioreduction of C–C Double Bonds

Glossary

7.11.1 Introduction

7.11.2 Microorganisms as Biocatalysts

7.11.3 Isolated Enzymes as Biocatalysts

7.11.4 Biocatalytic Reduction of Asymmetric Alkenes

7.11.5 Conclusions and Outlook

References

7.12 Oxidation: Oxidases

Glossary

7.12.1 Introduction

7.12.2 Oxidation of C-N Bonds

7.12.3 Oxidation of C-O Bonds

7.12.4 Summary and Outlook

References

7.13 Oxidation: Stereoselective Oxidations with Cytochrome P450 Monooxygenases

Glossary

7.13.1 Introduction to Cytochrome P450 Enzymes

7.13.2 Stereoselective Oxidations Catalyzed by Mammalian P450 Enzymes

7.13.3 Stereoselective Hydroxylations and Epoxidations

7.13.4 Conclusions and Outlook

Acknowledgments

References

7.14 Oxidation: Asymmetric Enzymatic Sulfoxidation

Glossary

7.14.1 Introduction

7.14.2 Occurrence and Uses of Optically Active Sulfoxides

7.14.3 Early Studies on Biological Oxidation of Sulfur

7.14.4 Asymmetric Sulfoxidation by Microbes

7.14.5 Asymmetric Sulfoxidation by Isolated Enzymes

7.14.6 Miscellaneous Biological and Biomimetic Asymmetric Oxidations of Sulfur

7.14.7 Asymmetric Reductions of Racemic Sulfoxides

7.14.8 Conclusions

References

7.15 Oxidation: Haloperoxidases

7.15.1 Introduction

7.15.2 Halogenating Enzymes

7.15.3 Enzyme Mechanisms

7.15.4 Natural Halogenated Compounds

7.15.5 Applications in Biotransformations

References

7.16 C–X Bond Formation: Hydroxynitrile Lyases: From Nature to Application

7.16.1 Introduction

7.16.2 Biology of Hydroxynitrile Lyases

7.16.3 Stereoselective Transformations

7.16.4 Multistep and Cascade Reactions

7.16.5 Process engineering

7.16.6 Conclusions

Acknowledgments

References

7.17 C–X Bond Formation: C–C Bond Formation using TDP-Dependent Enzymes

Glossary

7.17.1 TDP Enzymes Overview

7.17.2 Transferases

7.17.3 Lyases

7.17.4 Outlook

7.17.5 Conclusions

References

7.18 C–X Bond Formation: Transaminases as Chiral Catalysts: Mechanism, Engineering, and Applications

7.18.1 PLP-Dependent Enzymes

7.18.2 Transaminase Nomenclature

7.18.3 Reaction Mechanism

7.18.4 Asymmetric Synthesis

7.18.5 Kinetic Resolution

7.18.6 Production of Amino Acids

7.18.7 Production of Chiral Amines

7.18.8 Enzyme Engineering

7.18.9 Yield Improvement

7.18.10 Other Solutions

7.18.11 Conclusion

Acknowledgment

References

7.19 C-X Bond Formation: Enzymatic Enantioselective Decarboxylative Protonation and C-C Bond Formation

Glossary

7.19.1 Introduction

7.19.2 L-Aspartate-β-Decarboxylase

7.19.3 Acetolactate Decarboxylase

7.19.4 Malonic Semialdehyde Decarboxylase from Rhodococcus sp. KU1314

7.19.5 The Arylmalonate Decarboxylases

7.19.6 Serine Hydroxymethyltransferase (SHMT)

7.19.7 Pyruvate, Phenylpyruvate, and Benzoylformate Decarboxylase

7.19.8 Conclusion

Summary of Transformations

References

7.20 Multi-Enzyme Reactions

Glossary

7.20.1 Introduction

7.20.2 Synthesis of Enantiomerically Pure Amino Acids

7.20.3 Synthesis of Enantiomerically Pure Amines

7.20.4 Preparation of Chiral Alcohols

7.20.5 Stereoselective Formation of C–C Bonds

7.20.6 From Multi-Enzyme Processes to Artificial Biosynthetic Pathways

7.20.7 Multifunctional Enzymes

Acknowledgments

References

7.21 Enzymatic Carbohydrate Synthesis

7.21.1 Introduction

7.21.2 Synthesis of Monosaccharides and Derivatives

7.21.3 Formation of the Glycosidic Bond

7.21.4 Enzymatic Modification of Oligo- and Polysaccharides

7.21.5 Summary and Outlook

References

7.22 Enzyme Catalytic Promiscuity: Expanding the Catalytic Action of Enzymes to New Reactions

Glossary

7.22.1 Introduction

7.22.2 Discovery and Application of Existing Catalytically Promiscuous Enzymes

7.22.3 New Reaction Design

7.22.4 Future Prospects

Acknowledgements

References

7.23 New Emerging Reactions

Glossary

7.23.1 Introduction

7.23.2 C-X Bond Formation

7.23.3 Asymmetric Hydrogenation

7.23.4 C–C Cleavage

7.23.5 N- and O-Demethylations

7.23.6 Chiral Amines

7.23.7 Hydroxylations

7.23.8 Halogenation

7.23.9 Peptide Synthesis

7.23.10 Sugar Biochemistry

7.23.11 Biocatalytic and Chemical Multicomponent Reactions

7.23.12 Wish List

7.23.13 Conclusion

References

7.24 Enantioselective Hybrid Catalysts

Volume 8: Separations and Analysis

8.1 Perspective and Concepts: Chirality in Nineteenth Century Science

8.1.1 Chirality Pre-1848

8.1.2 Louis Pasteur

8.1.3 Lord Kelvin

8.1.4 Chirality Post-1848

References

8.2 Perspective and Concepts: Biomolecular Significance of Homochirality: The Origin of the Homochiral Signature of Life

8.2.1 Introduction

8.2.2 Is Chirality an Essential Feature of Life?

8.2.3 Is Homochirality an Essential Feature of Life?

8.2.4 Diastereomeric Interactions

8.2.5 Is Macroscopic Biological Handedness Fixed by Biomolecular Handedness?

8.2.6 Origin of Biomolecular Chirality: Biotic or Abiotic?

8.2.7 Mechanisms for Amplification of Enantiomeric Bias

8.2.8 Is Prebiotic Homochirality of the Monomers Really a Precondition for Life?

8.2.9 Crucial Issues in the Origin of Life

8.2.10 At What Stage in the Origin of Life did Homochirality Arise?

8.2.11 Is a Chiral Influence Really Needed?

8.2.12 Possible Chiral Influences

8.2.13 Circularly Polarized Light

8.2.14 Parity-Violation by the Weak Force

8.2.15 Calculation of the PVED

8.2.16 Is the PVED too Small to be Amplified?

8.2.17 Proposals to Measure the PVED

8.2.18 Exochirality

References

8.3 Perspective and Concepts: Overview of Techniques for Assigning Stereochemistry

Glossary

8.3.1 Practical Considerations

8.3.2 Deciding on the Best Strategy

8.3.3 Case Studies

8.3.4 Summary

References

8.4 Physical Separations: Solid-State Forms and Habits of Chiral Substances

Glossary

8.4.1 Introduction

8.4.2 Background

8.4.3 Practical Examples

8.4.4 Morphology Prediction

8.4.5 Habit Prediction

References

8.5 Physical Separations: Chiral Discrimination of Enantiomers by Diastereomeric Complexation with Chiral Host Compounds

8.5.1 Introduction

8.5.2 General Methods for Resolution Experiments

8.5.3 Enantiomer Resolution by Inclusion Complexation with Homochiral Host Compounds

8.5.4 Conclusions

References

8.6 Physical Separations: Behavior of Structurally Similar Molecules in the Resolution Processes

8.6.1 Introduction

8.6.2 Self-disproportionation

8.6.3 Conclusions

Acknowledgments

References

8.7 Chromatographic Separations and Analysis: Chromatographic Separations and Analysis of Enantiomers

Abbreviations

8.7.1 Overview of the Historical Development of Chromatography

8.7.2 Chiral Separations: Chromatographic

8.7.3 Derivatization in Chiral Chromatography

8.7.4 Chiral Stationary Phases (CSPs) for High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), and Supercritical Fluid Chromatography (SFC)

References

8.8 Chromatographic Separations and Analysis: Chiral Ion and Ligand Exchange Stationary Phases

Glossary

8.8.1 Introduction

8.8.2 Chiral Stationary Phases in LE Chromatography

8.8.3 Chiral Stationary Phases in IE Chromatography

References

8.9 Chromatographic Separations and Analysis: Protein and Glycoprotein Stationary Phases

Glossary

8.9.1 Introduction

8.9.2 Preparation of Protein and Glycoprotein Stationary Phases

8.9.3 Type of Protein and Glycoprotein Stationary Phases

8.9.4 Chiral Recognition Mechanism on Protein and Glycoprotein Stationary Phases

8.9.5 Conclusions

References

8.10 Chromatographic Separations and Analysis: Cyclodextrin Mediated HPLC, GC and CE Enantiomeric Separations

8.10.1 Introduction

8.10.2 CD and CD Derivatives for Enantioselective HPLC

8.10.3 Cyclodextrin-Based Chiral Stationary Phases for Gas Chromatography

8.10.4 Cyclodextrins as Chiral Selectors in Capillary Electrophoresis

References

8.11 Chromatographic Separations and Analysis: Cellulose and Polysaccharide Derivatives as Stationary Phases

8.11.1 Introduction

8.11.2 Characteristics of Polysaccharide-Based Chiral Stationary Phases and Packing Materials

8.11.3 Chromatographic Separations Using Polysaccharide-Based Chiral Stationary Phases

8.11.4 Preparative Separation

8.11.5 Structure of Phenylcarbamate Derivatives of Cellulose and Amylose

8.11.6 Chiral Recognition Mechanism

8.11.7 Conclusions

References

8.12 Chromatographic Separations and Analysis: Macrocyclic Glycopeptide Chiral Stationary Phases

Glossary

8.12.1 Introduction

8.12.2 The Macrocyclic Glycopeptide Family

8.12.3 Macrocyclic Glycopeptide Chiral Stationary Phases

8.12.4 Chromatographic Enantioseparations on Macrocyclic Glycopeptide Selectors

8.12.5 Conclusions

Acknowledgments

References

8.13 Chromatographic Separations and Analysis: Chiral Crown Ether-Based Chiral Stationary Phases

Glossary

8.13.1 Introduction

8.13.2 CSPs Based on (3,3′-Diphenyl-1,1′-Binaphthyl)-20-Crown-6 Ethers

8.13.3 CSPs Based on (+)-(18-Crown-6)-2,3,11,12-Tetracarboxylic Acid

8.13.4 CSPs Based on Phenolic Chiral Pseudo-18-Crown-6 Ethers

8.13.5 Conclusion

Acknowledgment

References

8.14 Chromatographic Separations and Analysis: New Stationary Phases

8.14.1 Introduction

8.14.2 Cyclodextrin

8.14.3 Chemically Bonded CD-CSPs Based on Urethane Linkage

8.14.4 Chemically Bonded CD-CSPs Based on Urea Linkage

8.14.5 Chemically Bonded CD-CSPs Based on Amino Linkages

8.14.6 Chemically Bonded CD-CSPs Based on Ether Linkages

8.14.7 Chemically Bonded CD-CSPs Based on Triazolyl Linkages

8.14.8 Conclusion

References

8.15 Chromatographic Separations and Analysis: Diastereomeric Derivatization for Chromatography

8.15.1 Introduction. The Role of Enantiomeric Separations Based on Diastereomeric Derivatization in the Era of Direct Methods

8.15.2 Conditions of the Applicability of Diastereomeric Derivatization in Enantiomeric Analysis

8.15.3 Separation and Determination of Enantiomers Based on Diastereomeric Derivatization

8.15.4 Achiral Derivatization Before the Separation on Chiral Stationary Phases

References

8.16 Chromatographic Separations and Analysis: Chiral Separations by Thin Layer Chromatography

Glossary

8.16.1 Introduction

8.16.2 Chiral Stationary Phases

8.16.3 Stationary Phases Impregnated with a Chiral Selector

8.16.4 Chiral Additives to Mobile Phase

8.16.5 Indirect Separation of Enantiomers

References

8.17 Chromatographic Separations and Analysis: Chiral Gas Chromatography

Glossary

8.17.1 Introduction and History

8.17.2 Stationary Phases

8.17.3 Techniques

8.17.4 Applications

8.17.5 Conclusion

Acknowledgement

References

8.18 Chromatographic Separations and Analysis: Supercritical Fluid Chromatography for Chiral Analysis and Semi-Preparative Purification

8.18.1 Introduction

8.18.2 Chiral Stationary Phases (CSP)

8.18.3 Effect of Physical Parameters on Retention, Resolution, and Efficiency

8.18.4 Chiral Analytical SFC

8.18.5 Validating a Method

8.18.6 Analytical-Scale Instrumentation

8.18.7 Introduction to Semi-Preparative SFC

8.18.8 Issues Against Recycling-Phase Behavior

8.18.9 CO2 Supply Issues-Issues Against not Recycling

8.18.10 GDS

8.18.11 The Chromatographic Hardware

8.18.12 Summary

References

8.19 Chromatographic Separations and Analysis: Chiral Detectors for Chromatography

Glossary

8.19.1 Introduction

8.19.2 OR Detectors

8.19.3 CD Detectors

8.19.4 OR versus CD

8.19.5 Application of Chiral Detectors

8.19.6 Limitations

8.19.7 Perspectives

References

8.20 Spectroscopic Analysis: Polarized Light and Optics

8.20.1 Linearly, Elliptically, and Circularly Polarized Light

References

8.21 Spectroscopic Analysis: Polarimetry and Optical Rotatory Dispersion

8.21.1 Introduction

8.21.2 Historical Perspective

8.21.3 Linearly and Circularly Polarized Light

8.21.4 Molecular Aspects of Optical Rotations

8.21.5 Instrumental Design

8.21.6 Instrumental Operation

8.21.7 Applications and Examples

References

8.22 Spectroscopic Analysis: Electronic Circular Dichroism

8.22.1 Historical Perspective

8.22.2 Circularly and Elliptically Polarized Light

8.22.3 Differential Absorption and Light Intensities

8.22.4 Molecular Aspects of CD

8.22.5 Instrumental Design

8.22.6 Single Beam Design

8.22.7 Dual Beam Design

8.22.8 Instrumental Operation

8.22.9 Applications and Examples

8.22.10 Conformational Analysis

8.22.11 Complex Mixtures and Hyphenated CD

References

8.23 Spectroscopic Analysis: Synchrotron Radiation Circular Dichroism

8.23.1 Introduction

8.23.2 Results and Discussion

8.23.3 Summary

Acknowledgments

References

8.24 Spectroscopic Analysis: Exciton Circular Dichroism for Chiral Analysis

Glossary

8.24.1 Introduction and Outline of the CD Exciton Chirality Method

8.24.2 CD and UV Spectra and their Rotational and Dipole Strengths

8.24.3 Principles of the CD Exciton Chirality Method

8.24.4 Consistency between X-ray Bijvoet and CD Exciton Chirality Methods

8.24.5 Suitable Chromophores for the CD Exciton Chirality Method

8.24.6 Application of the CD Exciton Chirality Method to Chiral Compounds

8.24.7 Conclusion

Acknowledgments

References

8.25 Spectroscopic Analysis: Vibrational Circular Dichroism

Glossary

8.25.1 Introduction

8.25.2 Definitions

8.25.3 VCD Instrumentation

8.25.4 VCD Theory

8.25.5 VCD Calculations

8.25.6 Comparison of Measured and Calculated Spectra

8.25.7 Applications of VCD

8.25.8 Conclusions

References

8.26 Spectroscopic Analysis: Raman Optical Activity

8.26.1 Introduction

8.26.2 Instrumentation

8.26.3 ROA of Small Molecules

8.26.4 Macromolecules and Biological Molecules

8.26.5 Other Molecules

8.26.6 Other Applications

8.26.7 Calculation of ROA Spectra

8.26.8 Outlook

References

8.27 Spectroscopic Analysis: Ab initio Calculation of Chiroptical Spectra

Glossary

8.27.1 Introduction: Chiral Techniques and Interpretations of the Spectra

8.27.2 Overview of Ab Initio and DFT Methods

8.27.3 Optical Rotatory Dispersion

8.27.4 Electronic Circular Dichroism

8.27.5 Magnetic Circular Dichroism as a Chiral Method for Achiral Molecules

8.27.6 Vibrational Circular Dichroism

8.27.7 Raman Optical Activity

8.27.8 Common Aspects of the Computational Approaches

8.27.9 Conclusions

References

8.28 Spectroscopic Analysis: NMR and Shift Reagents

Glossary

8.28.1 Introduction

8.28.2 Chiral Solvating Agents

8.28.3 Metal Complexes

8.28.4 Liquid Crystals

8.28.5 Chiral Derivatizing Agents

8.28.6 Database Methods for Compounds with Multiple Stereocenters

References

8.29 Spectroscopic Analysis: Diastereomeric Derivatization for Spectroscopy

8.29.1 Introduction

8.29.2 Amines

8.29.3 Alcohols

8.29.4 Diols and Polyols

8.29.5 Amino Alcohols

8.29.6 Carboxylic Acids

8.29.7 Amino Acids

8.29.8 Aldehydes and Ketones

8.29.9 Natural Products

8.29.10 Conclusions

References

8.30 Spectroscopic Analysis: Chiroptical Sensors

Glossary

8.30.1 Introduction

8.30.2 Structure and Enantiopurity Determinations for Chiral Analytes

8.30.3 Chiroptical Sensors for Achiral Analytes

8.30.4 Conclusion

Acknowledgements

References

8.31 Physical and Spectrometric Analysis: An Overview of Chiral Physical Analysis

8.31.1 Introduction

8.31.2 Anomalous Scattering in Single-Crystal X-ray Diffraction

8.31.3 Powder X-ray Diffraction

8.31.4 Chiral Analysis using Synthetic Receptors

8.31.5 Chiral Analysis using Electrochemical Phenomena

8.31.6 Mass Spectrometry and Chiral Reporter Molecule

8.31.7 Nano-Detection of Chirality

8.31.8 Chirality Analysis using Fluorescence

8.31.9 Conclusion

References

8.32 Physical and Spectrometric Analysis: Anomalous Scattering Single Crystal X-ray Diffraction

8.32.1 Introduction

8.32.2 X-ray Diffraction – Theory Principles

8.32.3 Anomalous Scattering

8.32.4 Use of Anomalous Scattering in Absolute-Configuration Determination

8.32.5 Examples

8.32.6 Conclusion

References

8.33 Physical and Spectrometric Analysis: Absolute Configuration Determination by X-ray Crystallography

Glossary

8.33.1 Introduction

8.33.2 Single-Crystal X-ray Diffraction Techniques Using an Internal Chiral Reference

8.33.3 Single-Crystal X-ray Diffraction Techniques Exploiting Resonant Scattering

8.33.4 Powder X-ray Diffraction

8.33.5 Characterization of Compounds and Crystals

8.33.6 Technicalities

8.33.7 Advanced Examples

References

8.34 Physical and Spectrometric Analysis: Nano-Detection of Chirality

Volume 9: Industrial Applications of Asymmetric Synthesis

Industrial Applications of Asymmetric Synthesis: An Overview

9.1 Introduction to Industrial Applications of Asymmetric Synthesis

Glossary

9.1.1 Introduction

9.1.2 Scope

9.1.3 Asymmetric Chemistry in the Pharmaceutical and Fine Chemical Industry

9.1.4 Trends and Future Directions for Organic Chemistry in the Pharmaceutical and Fine Chemical Industry

9.1.5 Summary

References

9.2 Asymmetry in the Plant: Concepts and Principles for the Scale-Up of Asymmetric Organic Reactions

Glossary

9.2.1 Introduction

9.2.2 Major Development Streams in the Twentieth Century

9.2.3 In Search of the Best Methodology

9.2.4 Green Chemistry as a Driver for Asymmetric Methodologies

9.2.5 Outlook for the Future

9.2.6 Summing-up and Conclusions

References

9.3 Industrial Applications of Asymmetric Synthesis: Asymmetric Synthesis as an Enabler of Green Chemistry

Industrial Applications of Metal-Catalyzed Asymmetric Synthesis

9.4 Industrial Applications of Asymmetric Reduction of C–C Bonds

Glossary

9.4.1 Introduction

9.4.2 Citronellol by Asymmetric Hydrogenation of Nerol or Geraniol

9.4.3 (+)-cis-Methyl Dihydrojasmonate

9.4.4 Menthol Via Asymmetric Hydrogenation

9.4.5 Aliskiren

9.4.6 Laropiprant

9.4.7 Candoxatril

9.4.8 Tipranavir

9.4.9 Rozerem

9.4.10 Conclusion

References

9.5 Industrial Application of the Asymmetric Reduction of C–O and C–N Bonds, including Enamides and Enamines

Glossary

9.5.1 Introduction

9.5.2 Reactions for Asymmetric Reduction

9.5.3 Hurdles (Requirements) and Solutions in Industrialization

9.5.4 Examples of Industrial Applications

9.5.5 Concluding Remarks

References

9.6 Industrial Applications of Asymmetric Oxidations

9.6.1 Introduction

9.6.2 Epoxidations

9.6.3 Asymmetric Dihydroxylation

9.6.4 Aminohydroxylation

9.6.5 Halohydroxylations

9.6.6 Heteroatom Oxidations

9.6.7 Biological Methods

9.6.8 Summary

References

9.7 Industrial Applications of the Jacobsen Hydrolytic Kinetic Resolution Technology

Glossary

9.7.1 The Jacobsen Hydrolytic Kinetic Resolution Technology (HKR)

9.7.2 Industrial Applications of the HKR and Related Technologies

9.7.3 Future Directions and Conclusions

Acknowledgment

References

9.8 Industrial Applications of Metal–Promoted C-C, C-N, and C-O Asymmetric Bond Formations

Abbreviations

Glossary

9.8.1 Introduction

9.8.2 Asymmetric C-C Bond Formation

9.8.3 Asymmetric C-N Bond Formation

9.8.4 Asymmetric C-O Bond Formation

9.8.5 Conclusions

Acknowledgments

References

9.9 Catalyst Recovery and Recycle: Metal Removal Techniques

Industrial Applications of Organocatalyzed Asymmetric Synthesis

9.10 Industrial Applications of Organocatalysis

Industrial Applications of Biocatalysis in Asymmetric Synthesis

9.11 Industrial Applications of Biocatalysis: An Overview

Glossary

9.11.1 Introduction

9.11.2 Background – Why Biocatalysis?

9.11.3 Examples from Different Enzyme Classes

9.11.4 Some Practical Aspects

9.11.5 Further Assistance and Information

9.11.6 Conclusions

References

9.12 Industrial Applications of Biocatalytic Hydrolysis (Esters, Amides, Epoxides, Nitriles) and Biocatalytic Dynamic Kinetic Resolution

Glossary

9.12.1 Introduction

9.12.2 Enzymatic Asymmetric Hydrolysis

9.12.3 Enzymatic Asymmetric Hydrolysis of Nitriles and Amides

9.12.4 Enzymatic Acylation Reactions

9.12.5 Enzymatic Transesterification/Esterification and Ammonolysis

9.12.6 Enzymatic Hydrolysis for Preparation of Chiral Epoxides

9.12.7 Enzymatic Dynamic Kinetic Resolution (DKR) and Deracemization

9.12.8 Enzymatic Cleavage of Cbz Groups

9.12.9 Conclusion

References

9.13 Industrially Relevant Enzymatic Reductions

Glossary

9.13.1 Introduction: Industrial Enzyme Reactions

9.13.2 Reduction Classes

9.13.3 Sitagliptin Case Study: Development of a Transaminase Route to Sitagliptin

9.13.4 Conclusion

References

9.14 Industrial Applications of Asymmetric Biocatalytic C-C Bond Forming Reactions

9.14.1 Introduction

9.14.2 Thiamin Diphosphate Dependent Lyases

9.14.3 Aldolases

9.14.4 Hydroxynitrile Lyases

9.14.5 Summary and Future Outlook

References

9.15 Industrial Applications of Asymmetric Synthesis using Cross-Linked Enzyme Aggregates

Industrial Applications: Enabling Technologies

9.16 Crystallization as a Tool in Industrial Applications of Asymmetric Synthesis

Glossary

9.16.1 Introduction

9.16.2 Classical Diastereomeric Resolutions

9.16.3 Discovery of Resolution Methods

9.16.4 Phase Diagrams of Racemates

9.16.5 Phase Diagrams

9.16.6 Dynamic Thermodynamic Asymmetric Transformations by Crystallization

9.16.7 Resolutions without Resolving Agents

9.16.8 Resolution of Racemizable Conglomerates by Attrition-Induced Grinding

9.16.9 Conclusion

Acknowledgment

References

9.17 Industrial Applications of Chiral Chromatography

Glossary

9.17.1 Introduction

9.17.2 Principles of Preparative Chiral Chromatography

9.17.3 Chiral Stationary Phases for Large-Scale Separations of Enantiomers by Chromatography

9.17.4 Preparative and Process-Scale Chromatographic Technologies

9.17.5 Chromatography Process Design Methodology

9.17.6 Large-Scale Synthesis Using Chiral Chromatography: Benefits and Industrial Examples

9.17.7 Conclusion

References

9.18 Industrial Applications of Process Analytical Technology to Asymmetric Synthesis

Industrial Applications of Asymmetric Synthesis: Case Studies

9.19 Synthesis of the Leading HCV Protease Inhibitors

9.19.1 Introduction

9.19.2 Ciluprevir (BILN-2061)

9.19.3 Boceprevir

9.19.4 Telaprevir

9.19.5 BI 201335

9.19.6 Danoprevir

9.19.7 Conclusions

References

Index

Author Index

Details

No. of pages:
5648
Language:
English
Copyright:
© Elsevier Science 2012
Published:
Imprint:
Elsevier Science
eBook ISBN:
9780080951683
Hardcover ISBN:
9780080951676

About the Editor-in-Chief

Hisashi Yamamoto

Chemists' ability to perform syntheses on a routine basis is due in large part to the development of new methods for synthesizing organic molecules which would have been impossible just a few decades ago. The availability of such new methods of synthesis has increased not only the range of structures which can be assembled but also the ease and economy of synthesis. During the past 30 years of his research, Professor Hisashi Yamamoto has had a tremendous impact on the field of organic chemistry through his reports of dramatic new advances in organic synthesis. Yamamoto's publications are numerous (over 450), and almost every one of them has provided an innovative new development or idea. Applications of this original and versatile chemistry have allowed him and other scientists to realize truly efficient syntheses of organic molecules of both theoretical and practical importance.

Hisashi Yamamoto has uncovered novel aspects of Lewis and Brønsted acid catalysts in selective organic synthesis. During his career he has discovered a wide variety of powerful new synthetic reactions, reagents, and catalysts based on acid catalysis chemistry. Through his dedicated efforts, Lewis and Brønsted acid are now recognized as major tools in the synthesis of both simple and complex organic molecules. Among Yamamoto's many superb contributions the following are especially worthy of mention.

His research in the area of organoaluminum chemistry has had a great impact on synthetic organic chemistry. The strong Lewis acidity of organoaluminum compounds appears to account for their strong tendency to form a stable 1:1 complex. Thus, the coordination of molecules invariably causes a change of reactivity, and the coordinated group may be activated or deactivated depending upon the type of reaction. Furthermore, with coordination of organic molecules an auxiliary bond can become coupled to the reagent and promote the desired reaction. In short, the reagents make a combined Lewis acid - Lewis base attack on a substrate with less activation energy, a field opened by Yamamoto's early and highly original studies. His aluminum amide reagents for epoxide rearrangement, biogenetic-type terpene synthesis, and the Beckmann rearrangement-alkylation reaction sequence are notable examples.

He was intrigued by the chemistry of the carbonyl compound-Lewis acid complex and introduced the unusually bulky organoaluminum reagents, methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD) and aluminum tris(2,6-diphenylphenoxide) (ATPH). These reagents were successfully utilized for the selective alkylation of cyclic ketones and aldehydes to generate equatorial alcohol and an anti-Cram type product, respectively, for trans- and cis-selective Claisen rearrangement, for regioselective Diels-Alder reaction, and for epoxide-aldehyde rearrangement. The ATPH - aromatic carbonyl complex reacts with nucleophiles selectively at the para-position of the aromatic ring to generate cyclohexadiene derivatives.

After these pioneering researches in Lewis acid chemistry, Yamamoto has become aware of the vast importance of chiral Lewis acids in modern asymmetric synthesis. In 1985, he first introduced binaphthol as a key ligand for chiral Lewis acid catalysts. This work was the forerunner of a vast quantity of present-day research on the binaththol based chiral Lewis acid catalyst. Based on his knowledge of organoaluminum chemistry, he designed a new and powerful organoaluminum catalyst for asymmetric hetero-Diels-Alder reaction. It was his Brønsted acid-Lewis acid combined system, however, which gave him a unique opportunity for the most efficient asymmetric Lewis acid catalyst for Diels-Alder reaction. A similar concept was employed for his catalytic asymmetric protonation under acidic conditions, which now creates a long sought proton induced asymmetric polyene cyclization.

His discovery of tartaric acid based catalyst (CAB catalyst) and amino acid based catalyst led to the first enantioselective Diels-Alder reaction of a broad range of dienes and dienophiles. The same catalyst was shown to be the first highly efficient catalyst for asymmetric aldol and ene type reactions. The reaction is simple, exceedingly stereoselective, and environmentally friendly.

Direct condensation of carboxylic acids by alcohols or amines is the most important transformation of organic synthesis. Yamamoto found Lewis acid catalyst could play an important role for such esterification and amidation processes. For example, his new hafnium catalyzed esterification and boron catalyzed amidation are now becoming increasingly important to the chemical industry.

More recently, he has developed new asymmetric oxidation processes based on an acid catalysis concept. His nitroso chemistry offers an entirely new access to selective organic synthesis and provides catalytic enantioselective reaction to introduce oxygen and/or nitrogen into the molecule. His pyridine based nitroso- and azo-hetero-Diels-Alder provides powerful tool for asymmetric synthesis. He also recently reported asymmetric epoxidation of homoallylic alcohols based on new vanadium catalyst, one of the most difficult asymmetric oxidations to date.

After moving to Chicago, he proposed the use of 8-hydroxyquinole based chiral Lewis acid catalysis. The catalyst is designed as a rigid metal complex of cis-b-configuation. The reagent turned out to be a brand-new "privileged ligand" for asymmetric synthesis. Catalytic asymmetric pinacol coupling, NH reaction, Mukaiyama-Michael addition, and Pudovik reactions are now able to proceed with complete enantioselectivities.

His laboratory is also noted for its introduction of metal reagents that allow highly selective SN2 cross coupling with carbonyl and allylic electrophiles. Allylic organobarium reagent, so-called "Yamamoto's reagent", reacts with a variety of electrophiles selectively at less substituted termini with complete stereospecificity, resolving a long-standing problem in terpene synthesis.

Affiliations and Expertise

The University of Chicago, Illinois, USA, Chubu University, Aichi, Japan

Erick Carreira

Erick M. Carreira was born in Havana, Cuba in 1963. He obtained a B.S. degree in 1984 from the University of Illinois at Urbana­Champaign under the supervision of Scott E. Denmark and a Ph.D. degree in 1990 from Harvard University under the supervision of David A. Evans. After carrying out postdoctoral work with Peter Dervan at the California Institute of Technology through late 1992, he joined the faculty at the same institution as an assistant professor of chemistry and subsequently was promoted to the rank of associate professor of chemistry in the Spring of 1996, and full professor in Spring 1997. Since September 1998, he has been full professor of Organic Chemistry at the ETH Zürich. He is the recipient of the American Chemical Society Award in Pure Chemistry, Nobel Laureate Signature Award, Fresenius Award, a David and Lucile Packard Foundation Fellowship in Science, Alfred P. Sloan Fellowship, Camille and Henry Dreyfus Teacher Scholar Award, Merck Young Investigator Award, Eli Lilly Young Investigator Award, Pfizer Research Award, National Science Foundation CAREER Award, Arnold and Mabel Beckman Young Investigator Award, and a Camille and Henry Dreyfus New Faculty Award. He is also the recipient of the Associated Students of the California Institute of Technology Annual Award in Teaching and a Richard M. Badger Award in Teaching.

His research program focuses on the asymmetric synthesis of biologically active, stereochemically complex, natural products. Target molecules are selected which pose unique challenges in asymmetric bond construction. A complex multistep synthesis endeavor provides a goal-oriented setting within which to engage in reaction innovation and design. Drawing from the areas of organometallic chemistry, coordination chemistry, and molecular recognition, Carreira's group is developing catalytic and stoichiometric reagents for asymmetric stereocontrol.

Affiliations and Expertise

ETH Zürich, Switzerland