Copper-Mediated Amination of Aryl C–H Bonds with the Direct Use of Aqueous Ammonia via a Disproportionation Pathway

The direct amination of C–H bonds with ammonia is a challenge in synthetic chemistry. Herein, we present a copper-mediated approach that enables a chelation-assisted aromatic C–H bond amination using aqueous ammonia. A key strategy was to use soft low-valent Cu(I) species to avoid the strong coordination of ammonia. Mechanistic investigations suggest that the catalysis is initiated by a facile deprotonation of bound ammonia, and the C–N coupling is achieved by subsequent reductive elimination of the resultant copper–amido intermediate from a Cu(III) intermediate that is readily generated by disproportionation of low-valent copper analogues. This mechanistic postulate was supported by a preliminary kinetic isotope effect study and computations. This new chelation-assisted, copper-mediated C–H bond amination with aqueous ammonia was successfully applied to a broad range of substrates to deliver primary anilines. Moreover, the mild conditions required for this transformation allowed the reaction to operate e...