Radical α,β-Dehydrogenation of Saturated Amides via α-Oxidation with TEMPO under Transition Metal-Free Conditions.

A transition metal-free radical process for the selective alpha,beta-dehydrogenation of saturated amides under mild conditions is developed. Utilizing radical activation strategy, the challenging issue associated with the low alpha-acidity of amides is resolved. For the first time, alpha,beta-unsaturated Weinreb amides and acrylamides could be efficiently prepared directly from corresponding saturated amides. Mechanistic studies confirm the radical nature of this transformation. Two gram scale alpha,beta-dehydrogenation have also been performed to demonstrate the utility of this method.