Silane Reagents and Catalysts for Asymmetric Synthesis of Carbinamines

Columbia University, New York NY

Investigators

Abstract

This project will continue the development of a family of highly practical chiral silane Lewis acids for asymmetric synthesis. The silanes activate acylhydrazones and other imines towards highly enantioselective attack by a wide variety of nucleophiles. Reactions under investigation include Pictet-Spengler and Friedel-Crafts reactions, Imine-Diene [4+2] cycloaddition and related cycloaddition reactions, tandem aza-Darzens/Friedel-Crafts reactions, and Mannich reactions. Mechanistic studies will guide the development of the chemistry into new realms of efficiency and practicality, as the development of a family of enabling reagents and catalysts for the rapid synthesis of a diverse array of medicinally relevant structures is pursued. Efforts to commercialize the technology will continue as well. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor James Leighton of the Department of Chemistry at Columbia University. Professor Leighton's research programs are directed towards the design of highly practical and useful synthetic methods for the preparation of a wide variety of compounds with relevance to medicinal chemistry. The chemistry in this proposal is based upon the use of silicon, and such reactions will contribute to the development of ever more efficient and environmentally benign methods in organic synthesis. Success will continue to make a strong impact in the pharmaceutical and agricultural industries, as chemists engaged in these arenas continue to adopt the methods for use in their own research projects.