Reductive Cleavage of Azoarene as a Key Step in Nickel-Catalyzed Amidation of Esters with Nitroarenes

A nickel-catalyzed reductive amidation of unactivated esters was recently reported, employing readily available and low-cost nitroarenes as nitrogen sources. Here, we describe a comprehensive experimental and computational study, which reveals an intricate mechanism of this process. The reaction profile indicated azoarene as the terminal nitrogen intermediate formed from the reduction of nitroarene. The activation of azoarene en route to amidation was probed by kinetics, Hammett plots, and density functional theory (DFT) calculations. The activation likely involves Ni-catalyzed, ZnCl2-promoted, reductive cleavage of the N═N double bond in an azoarene to form a bridging imido species, which then reacts in a rate-determining step with an ester to give an amide. Besides the nickel catalyst, ZnCl2 has an important influence on the rates and orders of the reaction. DFT computations suggest ZnCl2 stabilizes many of the intermediates in the reaction pathway of azoarene activation, including forming the key Ni–Zn heterobimetallic imido intermediate. The mechanistic insights revealed in this study lay the foundation for the development of synthetic methods employing azoarenes as stable and easily accessible nitrogen sources.