Difluorocarbene-Enabled Dehydration of Primary Amides To Access Nitriles

A cost-effective and environmentally friendly method for the direct conversion of primary amides to nitriles was developed using commercially available non-toxic ethyl bromodifluoroacetate as a difluorocarbene precursor under metal-free and ligand-free conditions. The reaction features high yields and tolerates various sensitive moieties, including alkyl, alkenyl, ether, sulfone, sulfoxide, heteroaryl, chloro, bromo, iodo, hydroxyl, nitro, and cyano groups, and late-stage modification of complex molecules is also feasible. Moreover, the present method is effective on large scales, showing potential for industrial application.