Silane Reagents and Catalysts for Asymmetric Synthesis of Carbinamines

Columbia University, New York NY

Investigators

Abstract

With this grant, the Chemical Synthesis Program is funding Professor James L. Leighton of Columbia University to explore the use of silanes as Lewis acids in the design of asymmetric nucleophilic imine addition reactions. Silicon is in many ways the ideal element on which to base such a program - it is abundant and inexpensive, and its derivatives are generally non-toxic and easily prepared shelf-stable compounds. Its derivatives are also, however, chemically inert in many instances, and the conceptual underpinning of the program is the identification of ways to modify the silanes so that they display the desired reactivity. The Leighton group will continue its efforts both to devise new and better ways of inducing the desired reactivity in silanes and to elucidate the mechanistic origin of the induced Lewis acidity. Other major focuses of the project are the reactions themselves and the products to which they allow access. Chiral carbinamines are of importance in drug design, and the reagents and methods that have thus far emerged from this program have found a commercial market and have been adopted by pharmaceutical chemists, in the design, discovery, and scale-up phases of the drug candidate evaluation process. Additionally, this project will provide sound practical and mechanistic training for graduate and undergraduate students, including those from groups historically underrepresented in the sciences.