Electricity-driven redox-neutral C(sp3)–H amidation with N-alkoxyamide as an amidating reagent

Abstract

An electrochemical redox-neutral C(sp³)–H amidation was developed with N-alkoxyamide as an amidating reagent. Under sequential paired electrolysis, N-alkoxyamides showed higher reactivity compared to the direct reaction of primary amides. With this novel approach, a broad range of bioactive amides (Bcl-xL inhibitor, AH-7614) were readily accessed and direct derivatization of pharmaceuticals was readily achieved under oxidant- and transition metal-free conditions. Moreover, solar energy could be directly used in this electrochemical transformation allowing a clean and practical approach for amide synthesis. Additionally, a plausible reaction mechanism was proposed to rationalize the experimental observations and CV experiment.