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.

Alexandre Alexakis is Professor of Organic Chemistry at the University of Geneva, Switzerland. He received his PhD from Paris VI University in 1975, and following a two-year postdoctoral at Johns Hopkins University, Baltimore, USA, joined the CNRS at Pierre et Marie Curie University, where he was appointed Head of Research in 1985. In 1996 he became a full professor at Pierre et Marie Curie University, before moving to the University of Geneva in 1998. Professor Alexakis is a recipient of the Silver Medal of the CNRS, as well as the Novartis Lectureship Award, and has authored 300 articles. His research focuses on asymmetric synthesis and methodologies, using both metal catalysts, particularly copper reagents, and non-metallic catalysts. Norbert Krause received his PhD from the Technical University of Braunschweig, Germany in 1986. After postdoctoral stays at the ETH Zurich and Yale University, he joined TU Darmstadt where he obtained his lecturing qualification in 1993. The following year he moved to the University of Bonn as an associate professor, before taking up his present position as a full professor at Dortmund University of Technology in 1998. He has been a fellow of the Japan Society for the Promotion of Science, a guest professor at the Universite Catholique de Louvain, Belgium, the University of California, Santa Barbara, USA, and at the Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris, France. Professor Krause has been on the editorial board of the European Journal of Organic Chemistry between 2006 and 2013. His research focuses on the stereoselective synthesis and transformation of functionalized allenes, taking advantage of coinage metal catalysis. Simon Woodward is a Professor in Synthetic Organic Chemistry at Nottingham University, UK, and has authored over 120 publications in the areas of organic methodology, organometallic chemistry, and selective/ asymmetric catalysis. He has been Director of both the European Ligand Bank and an International Marie Curie PhD School in Catalysis of Organic Reactions incorporating the universities of Nottingham, Geneva, Sassari, and Dortmund. Professor Woodward also chaired the European Cooperation in Science and Technology Action D40 in Innovative Catalysis and is a member of related Action CM0903 in Biomass Utilisation. His research group is greatly enhanced by extensive collaboration with over 20 other groups, involved in the selective catalysis of organic reactions, throughout Europe and beyond.

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