Amide Bond Formation Assisted by Vicinal Alkylthio Migration in Enaminones: Metal- and CO-Free Synthesis of α,β-Unsaturated Amides

Amide bond formation is one of the most important transformations in organic synthesis, drug development, and materials science. Efficient construction of amides has been among the most challenging tasks for organic chemists. Herein, we report a concise methodology for amide bond (−CONH−) formation assisted by vicinal group migration in alkylthio-functionalized enaminones (α-oxo ketene N,S-acetals) under mild conditions. Simple treatment of such enaminones with PhI­(OAc)2 at ambient temperature in air afforded diverse multiply functionalized α,β-unsaturated amides including β-cyclopropylated acrylamides, in which a wide array of functional groups such as aryl, (hetero)­aryl, alkenyl, and alkyl can be conveniently introduced to a ketene moiety. The reaction mechanism was investigated by exploring the origins of the amide oxygen and carbon atoms as well as isolation and structural characterization of the reaction intermediates. The amide bond formation reactions could also be efficiently performed under solventless mechanical milling conditions.