Diastereoselective Trifluoroacetylation of Highly Substituted Pyrrolidines by a Dakin−West Process

A robust approach allowing for the efficient trifluoroacetylation of a series of highly substituted pyrrolidines in a diastereoselective manner is reported. The transformation is based on a Dakin–West reaction of advanced pyrrolidine 2-carboxylic acid derivatives that can be assembled stereoselectively in four synthetic steps. Importantly, this work demonstrates how the introduction of lateral substituents on the pyrrolidine scaffold enables the generation of the desired trifluoroacetylation products, which was not possible previously due to the exclusive formation of trifluoromethylated oxazoles (vide infra). In the course of this work we succeeded for the first time in isolating and characterizing (HRMS, IR, 1H, 13C and 19F NMR, X-ray) different intermediates of the Dakin–West reaction allowing us to probe its mechanism.