Phosphoric acid-catalyzed regioselective amidation of para-quinone methides with acetonitrile

An efficient and atom-economical phosphoric acid-catalyzed amidation of para-quinone methides (p-QMs) with acetonitrile has been developed under mild conditions. Water serves as the sole source of both hydrogen and oxygen atoms, enabling 100 % atom economy in amide bond formation. The reaction exhibits excellent generality across a broad spectrum of electronically and sterically diverse p-QMs, facilitating efficient and highly regioselective synthesis of synthetically valuable N-diarylmethyl-substituted acetamides in good to excellent yields. Step-by-step control experiments and competitive deuterium-labeling KIE studies elucidated the reaction pathway and led to a plausible mechanism based on cumulative experimental evidences.