Copper-Catalyzed Asymmetric Synthesis

This book reflects the increasing interest among the chemical synthetic community in the area of asymmetric copper-catalyzed reactions, and introduces readers to the latest, most significant developments in the field. The contents are organized according to reaction type and cover mechanistic and spectroscopic aspects as well as applications in the synthesis of natural products. A whole chapter is devoted to understanding how primary organometallics interact with copper to provide selective catalysts for allylic substitution and conjugate addition, both of which are treated in separate chapters. Another is devoted to the variety of substrates and experimental protocols, while an entire chapter covers the use on non-carbon nucleophiles. Other chapters deal with less-known reactions, such as carbometallation or the additions to imines and related systems, while the more established reactions cyclopropanation and aziridination as well as the use of copper (II) Lewis acids are warranted their own special chapters. Two further chapters concern the processes involved, as determined by mechanistic studies. Finally, a whole chapter is devoted to the synthetic applications. This is essential reading for researchers at academic institutions and professionals at pharmaceutical or agrochemical companies.

Table of Contents:
Introduction THE PRIMARY ORGANOMETALLIC IN COPPER-CATALYZED REACTIONS Scope and Introduction Terminal Organometallics Sources Available Coordination Motifs in Asymmetric Copper Chemistry Asymmetric Organolithium-Copper Reagents Asymmetric Grignard-Copper Reagents Asymmetric Organozinc-Copper Reagents Asymmetric Organoboron-Copper Reactions Asymmetric Organoaluminium-Copper Reactions Asymmetric Silane and Stannane Copper-Promoted Reagents Conclusions COPPER-CATALYZED ASYMMETRIC CONJUGATE ADDITION Introduction Conjugate Addition Trapping of Enolates COPPER-CATALYZED ASYMMETRIC CONJUGATE ADDITION AND ALLYLIC SUBSTITUTION OF ORGANOMETALLIC REAGENTS TO EXTENDED MULTIPLE-BOND SYSTEMS Introduction Copper-Catalyzed Asymmetric Conjugate Addition (ACA) to Polyconjugated Michael Acceptors Copper-Catalyzed Asymmetric Allylic Substitution on Extended Multiple-Bond Systems Conclusion ASYMMETRIC ALLYLIC ALKYLATION Introduction Nucleophiles in Enantioselective Process Development Functionalized Substrates Desymmetrization of meso-Allylic Substrates Kinetic Resolution Processes Direct Enantioconvergent Transformation Conclusion and Perspectives RING OPENING OF EPOXIDES AND RELATED SYSTEMS Introduction Copper-Catalyzed Asymmetric Ring Opening of Epoxides with Amines Copper-Catalyzed Asymmetric Ring Opening of Epoxides and Aziridines with Organometallic Reagents Copper-Catalyzed Asymmetric Ring Opening of Heterobicyclic Systems with Organometallic Reagents Conclusions CARBON-BORON AND CARBON-SILICON BOND FORMATION Introduction C-B Bond Formation Reactions C-Si Bond Formation Reactions Summary CuH IN ASYMMETRIC REDUCTIONS Introduction Asymmetric Conjugate Reductions Asymmetric 1,2-Additions Heterogeneous Catalysis Conclusions and Perspectives ASYMMETRIC CYCLOPROPANATION AND AZIRIDINATION REACTIONS Introduction Asymmetric Cyclopropanation Asymmetric Aziridination Conclusion COPPER-CATALYZED ASYMMETRIC ADDITION REACTIONS OF IMINES Introduction Copper-Catalyzed Asymmetric Addition Reaction of Dialkylzinc to Imines Copper-Catalyzed Asymmetric Allylation, Arylation, and Alkynylation Reactions of Imines Copper as a Lewis Acid Catalyst for Asymmetric Reaction of Imines Conclusions CARBOMETALLATION REACTIONS Introduction Carbometallation of Cyclopropenes Carbometallation of Alkynes Summary CHIRAL COPPER LEWIS ACIDS IN ASYMMETRIC TRANSFORMATIONS Introduction Cycloadditions Claisen Rearrangements Ene Reactions Nucleophilic Addition to C=O and C=N Double Bonds Conjugate Additions Alpha-Functionalization of Carbonyl Compounds Kinetic Resolution Asymmetric Desymmetrization Free-Radical Reactions Conclusions MECHANISTIC ASPECTS OF COPPER-CATALYZED REACTIONS Introduction Conjugate Addition Allylic Alkylation and Substitution Copper as Lewis Acid 1,2-Addition to Imines and Carbonyls Copper Hydride Cyclopropanation, Aziridination, and Allylic Oxidation NMR SPECTROSCOPIC ASPECTS Introduction Copper Complexes with Phosphoramidite Ligands Copper Complexes with TADDOL-Based Thiolate Ligands Copper Complexes with Ferrocenyl-Based Ligands Conclusion APPLICATIONS TO THE SYNTHESIS OF NATURAL PRODUCTS Introduction Copper-Catalyzed Conjugate Additions in Natural Product Synthesis Natural Product Synthesis Employing Asymmetric Allylic Alkylation Asymmetric Copper-Catalyzed Diels-Alder Reactions Asymmetric Copper-Catalyzed Mukaiyama Aldol Reactions Other Asymmetric Copper-Catalyzed Aldol-Type Reactions Asymmetric 1,3-Dipolar Cycloaddition and Claisen Rearrangement Catalytic Asymmetric Cyclopropanation Asymmetric Copper-Catalyzed Conjugate Reductions Copper-Catalyzed Asymmetric 1,2-Type Addition Reactions Miscellaneous Asymmetric Copper-Catalyzed Reactions Conclusion Index