Synthesis of Amides and Peptides by Employing [4-(Acetylamino) phenyl]imidodisulfuryl Difluoride (AISF) as a Coupling Reagent

A new synthetic approach for the preparation of amides and peptides containing amino acids as well as aryl acids and amines by employing [4-(acetylamino)phenyl]imidodisulfuryl difluoride (AISF) as a carboxylic acid activator under mild conditions is delineated. The use of AISF as an acid activator allows the reaction to be performed efficiently. This operationally simple amidation is amenable to a wide variety of carboxylic acids and Nα-protected amino acids. Further, racemization did not occur during the coupling. In addition, a gram-scale reaction is demonstrated.