Highly selective hydrolysis of amides via electroreduction

Abstract

Deprotection of amides is a virtually universal transformation in organic synthesis, often employing traditional active reductants such as SmI₂, hydrosilanes, hydroboranes or H₂ under high-pressure. Herein, we describe a green and sustainable electrocatalytic hydrolysis of amides utilizing water as the hydrogen source, thereby ideally avoiding the use of high-pressure and flammable hydrogen gas or other toxic and costly hydrogen donors. Our methodology utilized green electrons as reductants, facilitating highly selective and efficient electrocatalytic C–N hydrolysis of amides. This environmentally friendly electrochemical approach can also be successfully applied to the C–N hydrolysis of carbamates, formamides, and thioamides. Furthermore, this method extends to the dissociation of O–N and N–N bonds, exhibiting a wide scope and high functional group tolerance. Preliminary mechanistic studies support a proposed mechanism involving the electroreductive conversion of the carbonyl group into a hemiaminal intermediate, which subsequently collapses to yield free amines.