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.