Dual Lewis Acid−Lewis Base Activation in Enantioselective Cyanation of Aldehydes Using Acetyl Cyanide and Cyanoformate as Cyanide Sources

Abstract
Dual activation by a chiral Lewis acid and an achiral or chiral Lewis base enabled cyanation of both aromatic and aliphatic aldehydes with acetyl cyanide and ethyl cyanoformate to provide direct access to O-acetylated and O-alkoxycarbonylated cyanohydrins, respectively, under mild conditions. With a combination of a Ti−salen catalyst and Et3N, benzaldehyde was converted to the O-acetylated cyanohydrin with 94% ee within 10 h at −40 °C in 89% isolated yield.