Handbook of Metathesis

Robert H. Grubbs received his Ph.D. from Columbia University for work with Ron Breslow. After a postdoctoral year with Jim Collman at Stanford University, he joined the faculty at Michigan State University. In 1978, he moved to the California Institute of Technology, where he is now the Victor and Elizabeth Atkins Professor of Chemistry. Among many other awards he received the Nobel Prize in 2005 for his research on the metathesis reaction. His research interests include polymer chemistry, organometallic catalysis, and development of new synthetic organic methodology. Daniel J. O?Leary received his PhD at UCLA in the group of Prof. Frank A. L. Anet. Following an NSF postdoctoral fellowship with Prof. Yoshito Kishi at Harvard University, he became Assistant Professor at Pomona College, where he is presently the Carnegie Professor of Chemistry. His research interests are in the area of organic synthesis, isotope effects, and nuclear magnetic resonance.

Preface

GENERAL RING-CLOSING METATHESIS
Introduction
Carbocycles (Introduction)
Synthesis of Bridged Bicycloalkenes
Synthesis of Heterocycles Containing Si, P, S, or B
Synthesis of O-Heterocycles
Synthesis of N-Heterocycles
Synthesis of Cyclic Conjugated Dienes
Alkyne Metathesis
Enyne Metathesis
Tandem Processes
Synthesis of Macrocycles
RCM and Isomerization via Ru-H
Relay RCM (RRCM)
Z-Selective RCM
Enantioselective RCM
Conclusion

CROSS-METATHESIS
Early Examples Using Well-Defined Molybdenum and Ruthenium Catalysts
The General Model for Selectivity in CM Reactions
Definition of Cross-Metathesis Reaction Categories and Chapter Organization
Hydrocarbons
Boron
Nitrogen
Oxygen
Halides
Phosphorus
Sulfur
Fragment Coupling Reactions
Conclusions

VIGNETTE: EXTENDING THE APPLICATION OF METATHESIS IN CHEMICAL BIOLOGY - THE DEVELOPMENT OF SITE-SELECTIVE PEPTIDE AND PROTEIN MODIFICATIONS
Introduction
Cross-Metathesis Methodology Studies in Aqueous Media
Strategies for Allyl Chalogenide Incorporation into Proteins
Olefin Metathesis on Proteins
Outlook

RUTHENIUM-CATALYZED TANDEM METATHESIS/NON-METATHESIS PROCESSES
Introduction
Metathesis/Isomerization
Metathesis/Hydrogenation
Metathesis/Oxidation
Metathesis/Cyclization
Metathesis/Atom-Transfer Radical Addition
Metathesis/Rearrangement
Metathesis/Cyclopropanation
Metathesis/Miscellaneous
Conclusions

ENYNE METATHESIS
Introduction
Enyne Metathesis
Strategic Application of Enyne Metathesis in Organic Synthesis
Perspective

ALKYNE METATHESIS
Introduction
Background Information
Molybdenum Alkylidyne Catalysts with Silanolate Ligands
Other Catalytically Active Molybdenum Alkylidyne Complexes
Novel Tungsten Alkylidyne Catalysts
Basic Types of Applications
Selected Applications
Conclusions

CATALYST-CONTROLLED STEREOSELECTIVE OLEFIN METATHESIS
Introduction
Enantioselective Ring-Opening/Cross-Metathesis (EROCM)
Enantioselective Ring-Opening/Ring-Closing Metathesis (ERORCM)
Enantioselective Ring-Closing Metathesis (ERCM)
Z-Selective Olefin Metathesis Reactions with Mo- andW-Based Complexes
Z-Selective Olefin Metathesis Reactions with Ru Complexes
Z-Selective Ring-OpeningMetathesis Polymerization
Conclusions and Outlook

TWO VIGNETTES: RCM IN NATURAL PRODUCT TOTAL SYNTHESIS
Vignette 1: Allylsilane RCM/Electrophilic Desilylation as a Means to Access Rings with Exocyclic Alkenes
Vignette 2: Synthesis of Antimetastatic Agents Using Ring-Closing Metathesis

METATHESIS OF SILICON-CONTAINING OLEFINS
Introduction
Homo and Cross-Metathesis versus Silylative Coupling of Vinylsilicon Compounds
Homometathesis of Allylsilanes and Their Cross-Metathesis with Olefins
Silylative Coupling versus Cross-Metathesis of Vinylsilanes in Sequential Synthesis of Functionalized Alkenes
Silylative Coupling Cyclization of Silicon-Containing Dienes
Ring-Closing Metathesis of Silicon-Containing Dienes
Acyclic Diene Metathesis (ADMET) versus Silylative Coupling (SC) Polycondensation of Silicon-Containing Dienes
Ring-OpeningMetathesis Polymerization of Silyl-Substituted Cycloalkenes

RING-CLOSING METATHESIS IN THE LARGE-SCALE SYNTHESIS OF PHARMACEUTICALS
Introduction
Ciluprevir (BILN2061) and Analogs
Vaniprevir (MK-7009)
Simeprevir (TMC435)
SB-462795
Approaches to the Scale-Up of RCM Reactions

METATHESIS STRATEGIES IN DIVERSITY-ORIENTED SYNTHESIS
Introduction
Synthesis of Small- to Medium-Sized Rings via Metathesis Strategies
Synthesis of Macrocycles via Metathesis Strategies
Metathesis Cascade Strategies in Diversity-Oriented Synthesis
Synthesis of Small- to Medium-Sized Rings via Metathesis Cascade Strategies
Synthesis of Macrocycles via Metathesis Cascade Strategies
Metathesis Strategies in Solid-Phase Library Synthesis
Immobilized Scavengers and Catalysts
Conclusions

OLEFIN METATHESIS: COMMERCIAL APPLICATIONS AND FUTURE OPPORTUNITIES
Introduction
Ruthenium Olefin Metathesis Catalysts
Renewable Seed Oil Feedstocks
Production of Fatty Acids and Amino Acids from Renewables
Olefin Metathesis and Natural Materials Chemistry
Pharmaceutical Applications
ROMP-Derived Oligomers for Facilitated Synthesis
Conclusion

Index