The copper-catalyzed oxidative radical process of site selective C–N bond cleavage in twisted amides: batch and continuous-flow chemistry

Abstract

Due to the significance of amide bonds, it is crucial to develop a new catalytic strategy to produce amides by selective C–N bond cleavage, one of the most potent and rapid processes in chemical synthesis. This work represents the first example of copper-superoxo radical activation in twisted amides which mediates the aerobic oxidative process. Herein, we describe a mild, simple, chemoselective and copper-catalyzed method to synthesize primary amides from readily available and bench stable crystalline solid N-acyl glutarimide. Pertinently, this copper catalytic transformation permits formation of a wide range of amides in batch and continuous-flow conditions effectively. Moreover, the reaction shows excellent functional group tolerance in high yields and is applicable for wide substrate scope including late-stage functionalization of complicated APIs. While using this copper-catalytic C–N bond cleavage in applications, gram-scale primary amide and various important scaffolds were successfully synthesized. We further present mechanistic and UV-visible spectral studies that outline the copper reactive oxygen species involved in the reaction mechanism for selective C–N bond cleavage.