Chemoselective Thioacylation of Amines Enabled by Synergistic Defluorinative Coupling.

Abstract

A mild and chemoselective method for the thioacylation of amines, including amino acids and peptides, using gem-difluoroalkenes and sulfide, is reported. The distinguishing of the different nucleophilic sites (S-site and diverse N-sites) by the chemoselective C-F bond functionalization of gem-difluoroalkenes enables the unique synergistic defluorinative coupling reaction. This reaction features mild conditions, is operationally simple, efficient, and gram-scalable, tolerates various functional groups, and is activator-free and without racemization. Thioamide moieties were incorporated site-specifically into bioactive compounds. The proposed mechanism is illustrated by a DFT calculation.