Selective reduction of amides is of great importance for generating versatile building blocks in both academia and industry. However, in contrast to ketones and carboxylic esters, amides are generally considered highly unreactive members of the carbonyl family owing to their low electrophilicity and thermodynamic stability. Herein, we describe an efficient electroreduction of amides to amines using protons as the hydrogen source. A combination of readily available zirconium catalyst (Cp2ZrCl2) with a stoichiometric halosilane enables the selective deoxygenative electroreduction process. Preliminary mechanistic investigations support the involvement of an unconventional α-aminocarbene species as the key intermediate, which is generated from the electroreductive C═O bond scission of an amide. Without the necessity of flammable H2 gas or sensitive hydrides, this electrochemical protocol is showcased by highly selective and straightforward synthesis of various functionalized and structurally diverse amines under mild conditions. Furthermore, the application of this protocol is demonstrated through valuable and practical access to N-α-deuterated amines using cost-effective and abundant deuterium sources.
Hua et al. (Mon,) studied this question.