Copper/O₂-Mediated Oxidative C–C Activation of Nitriles for Selective Acylation-Bromination of Anilines

This study reports selective dual amino acylation and C–H bromination of aniline compounds enabled by Cu/O2 catalyst systems. This method involves crucial oxidation-induced C–CN bond cleavage of α-methylene nitriles to generate an acylcyanide intermediate that is facilely intercepted by anilines. After amino acylation, the Cu(II) precatalyst in combination with NBS generates Cu(III)–Br in situ that engages in selective electrophilic para- or ortho–C–H bromination. The substrate scope, mechanistic aspects, and late-stage functionalization of biologically active anilines are studied. This study shows the synthetic potential of oxidative C–CN bond activation of nitriles for the development of valuable reactions.