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

A novel dynamic kinetic resolution (DKR) of tetrasubstituted alkenyl cyanohydrins prepared from the corresponding α,β-unsaturated aldehydes is described. The deprotonation of a geometrical mixture of tetrasubstituted alkenyl cyanohydrins with sodium diisopropylamide (NaDA) enables the equilibration of the E- and Z-olefins and the selec-tive functionalization of former to selectively afford the E-adduct. Theoretical studies indicate that the nature of the alkali metal cation is a critical component to lowering the barrier for interconversion be-tween 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