Base-Promoted Tandem Pathway for Keto-Amides: Visible Light-Mediated Room-Temperature Amidation Using Molecular Oxygen as an Oxidant.

Abstract

Herein, we report metal- and photocatalyst-free room-temperature amidation for α-ketoamide synthesis from feedstock phenacyl bromides and amines using molecular oxygen as an oxidant as well as a source of oxygen in the amide segment. Visible light-mediated base-promoted one-pot sequential C-N/C═N/C═O bond formation takes place in a tandem manner to afford the desired product. Functional group tolerance (benzylic alcohol, keto, cyano, nitro, halo, etc.), a broad substrate scope, and gram-scale synthesis make this synthetic methodology more attractive. We have observed that electron-rich aromatic amines, aliphatic amines, and phenacyl bromide derivatives proceeded the present transformation with marginally superior reactivity in comparison to electron-deficient aromatic amines and phenacyl bromide derivatives. Moreover, several control experiments, in situ isolation of secondary amine and imine as key intermediates, and 18O-labeling experiments provide complete insight into the mechanism of the tandem pathway.