Chemoselective transition-metal-free acylation of thioamides by N–C(S) bond cleavage using acyclic twisted thioamides†

A new method for chemoselective transition-metal-free acylation of thioamides with ketones by N–C(S) bond cleavage is reported. The approach exploits acyclic twisted thioamides to accomplish selective thio-Claisen condensation by ground-state-destabilization of the thioamide bond. The valuable 3-hydroxy-1-thioxoketone products are obtained from bench-stable thioamide precursors under mild transition-metal-free, room temperature conditions. Various ground-state-destabilized thioamides are amenable to this selective thio-acylation protocol. The method advances the reactivity of twisted thioamides to C–C bond forming reactions under transition-metal-free conditions.