Dynamic Kinetic Resolution of Alkenyl Cyanohydrins Derived from alpha,beta-Unsaturated Aldehydes: Stereoselective Synthesis of E-Tetrasubstituted Olefins

Abstract

A novel dynamic kinetic resolution (DKR) of tetrasubstituted alkenyl cyanohydrins prepared from the corresponding alpha,beta-unsaturated aldehydes is described. The deprotonation of a geometrical mixture of tetrasubstituted alkenyl cyanohydrins with sodium diisopropylamide (NaDA) affords the allylic anions, which enables the equilibration of the E- and Z-olefins to permit the selective functionalization of the E-adduct. Theoretical studies indicate that the nature of the alkali metal cation is a critical component to lowering the barrier for inter conversion between the two geometrical isomers, which provides the mechanistic basis for the DKR reaction. In addition, we demonstrate that the DKR reaction can be combined with a transition metal-catalyzed allylic substitution to generate a stereodefined E-tetrasubstituted olefin and quaternary center in a single cross-coupling reaction.