Catalytic Asymmetric Baylis–Hillman Reaction of Imines

Abstract

We have shown for the first time that the β-ICD-catalyzed Baylis–Hillman reaction of aromatic imines with HFIPA proceeds with S-selectivity, in contrast to the reaction of aldehydes, which afford R-selectivity. We propose a reaction mechanism where the phenolic OH of β-ICD plays a crucial role on enantioselectivity. This work provides an effective method for the preparation of aryl substituted α-methylene β-amino acid derivatives in >93% ee by the reaction of diphenylphosphinoyl imines followed by recrystallization. The synthetic utility of the β-ICD-catalyzed Baylis–Hillman reaction of imines was successfully demonstrated by the conversion of the Baylis–Hillman adduct to the β-lactam.