Enantioselective synthesis of α-alkenyl α-amino acids via N–H insertion reactions

Abstract

A new highly enantioselective route to α-alkenyl α-amino acid derivatives, which are important naturally occurring compounds with attractive bioactivity and synthetic utility, was developed using a N–H insertion reaction of vinyldiazoacetates and tert-butyl carbamate cooperatively catalyzed by achiral dirhodium(II) carboxylates and chiral spiro phosphoric acids under mild, neutral conditions. This reaction has a broad substrate scope, a fast reaction rate (turnover frequency > 6000 h⁻¹), a high yield (61–99%), and excellent enantioselectivity (83–98% ee). The chiral spiro phosphoric acid, which is proposed to realize the enantioselectivity of the insertion reaction by promoting the proton transfer of a ylide intermediate by acting as a chiral proton shuttle catalyst, can suppress several usual side reactions of vinyldiazoacetates and broaden the applications of these versatile carbene precursors in organic synthesis. To our knowledge, it is the first highly enantioselective carbene insertion reaction of vinyldiazoacetates with heteroatom–hydrogen bonds in which the heteroatom has lone-pair electrons.