Ni-Catalyzed Cyanation of (Hetero)aryl Halides with Acetonitrile as Cyano Source

We present a highly efficient method for cyanating challenging substrates with a specific focus on aryl fluorides. This innovative methodology has been successfully expanded to encompass a diverse array of aryl halides, underscoring its versatility and broad applicability. The nickel-catalyzed protocol utilizes acetonitrile under mild temperature conditions, providing a clean and safe alternative for cyanation. Notably, it employs a nonhazardous, nongaseous, metal-free cyanide source and demonstrates a wide substrate scope, accommodating aryl chlorides, fluorides, bromides, and iodides. The reaction is particularly effective with acetonitrile. This catalytic cyanation process serves as a valuable route for synthesizing pharmaceuticals such as letrozole, citalopram, and other NNRTI drugs. Mechanistically, we propose that a catalytic cycle involving zerovalent nickel and divalent nickel is more plausible for this reaction.