Nickel-Catalyzed Cyanoalkylation of Ketone Derivatives

Although the metal-based catalyzed cyanomethylation of aldehydes is well-developed, a similar approach to ketones with acetonitrile derivatives remains a challenge. Thanks to Tolman type complexes, Ni-II-complexes with a pyridine(dicarboxamide) pincer ligand, an alternative metal-catalyzed (1-5 mol% catalyst) cyanomethylation of an array of isatins and activated ketones is reported at room temperature. High isolated yields (up to 99%) were obtained not only with the poorly acidic acetonitrile but also with more challenging substituted alkyl cyanide nucleophiles. The in situ generated putative ion paired catalysts [NiCR2CN](-)Cat(+) likely benefit from the cation part (Cs+ or n-Bu4N+) to facilitate their formation and catalytic activity.