Stereocontrolled synthesis of fluorine-containing piperidine γ-amino acid derivatives

Abstract

An efficient synthetic approach for the construction of fluorine‐containing piperidine γ‐amino acid derivatives has been developed. The synthetic concept was based on oxidative ring opening of an unsaturated bicyclic γ‐lactam (Vince‐lactam) through its ring C=C bond, followed by double reductive amination of the diformyl intermediate performed with various fluoroalkylamines. The method has been extended towards the access of alkylated and perfluoroalkylated substances and for γ‐lactam derivatives. The transformations proceeded with stereocontrol: the configuration of the stereocenters in the products were predetermined by the configuration of the chiral centers of the starting γ‐lactam. The method could be extended for the access to enantiopure piperidine γ‐amino esters.