Amide Bond Formation via Reversible, Carboxylic Acid-Promoted Lactone Aminolysis

Abstract

A rapid carboxylic acid-promoted lactone aminolysis is reported. A number of carboxylic acids were found to promote this amide bond-forming transformation, with aliphatic acids being the most efficient. This reaction is an equilibrium process (Keq ≈ 1.8), and mechanistic investigations are consistent with mediation of a kinetically important proton-transfer step by the carboxylate, i.e., the conjugate base of the acid employed.