Chemoselective Transamidation of Thioamides by Transition?Metal?Free N?C(S) Transacylation

Thioamides represent highly valuable isosteric in the strictest sense “single-atom substitution” analogues of amides that have found broad applications chemistry and biology. A long-standing challenge is direct transamidation thioamides, a process which would convert one thioamide bond (R?C(S)?NR1R2) into another (R?C(S)?NR3N4). Herein, we report first general method for thioamides by chemoselective N?C(S) transacylation. The relies on site-selective N-tert-butoxycarbonyl activation 2° 1° resulting ground-state-destabilization thus enabling to rationally manipulate nucleophilic addition bond. This showcases remarkably scope including late-stage functionalization (>100 examples). We further present extensive DFT studies provide insight chemoselectivity guidelines development methods