Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

C–N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles, including complex examples on oligopeptides, medicinally-relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations as well as procedures for both batch and flow scale-ups (100 gram) are also described.