Nickel‐Catalyzed Cyanoalkylation of Ketone Derivatives

Abstract

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, NiII‐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.

Advances in the Application of Acetonitrile in Organic Synthesis since 2018

“…The enantioselective cyanomethylation catalyzed by Ni(II) was developed by Shibasaki and Kumagai [31,32]. Very recently, Oudeyer and co-workers established a Ni-catalyzed cyanoalkylation of ketone derivatives 14 and acetonitrile derivatives (Scheme 4) [33]. Acetonitrile was added to various isatins or activated ketones with the Ni catalyst C1, affording products 15 in up to a 99% yield.…”