Silylative Amide to Nitrile Conversion Mediated by Simple Lanthanide–Organoamides: Scope and Mechanism

Abstract Efficient, selective, and environmentally benign catalytic nitrile synthesis is attractive for pharmaceuticals, specialty chemicals and materials, and large‐scale industrial applications. In this regard, metal‐catalyzed silylative conversion of primary amides to nitriles is emerging as a promising approach. This contribution reports the utilization of readily available lanthanide‐organic amido precatalysts, Ln[N(SiMe 3 ) 2 ] 3 , Ln = lanthanide, to selectively convert primary alkyl and aryl/heterocyclic amides having diverse functional groups to nitriles, including pharma building blocks, in high yields using the silane reagents PhSiH 3 and TMS‐O‐[Si(H)(Me)‐O‐] n ‐TMS in a solvent‐free process. Kinetic and mechanistic data reveal the role of lanthanide amidates as the catalytically‐active species, while DFT analysis indicates a catalytic pathway unlike that found in transition metal complex‐catalyzed processes. Thus, the lanthanide amidate resting state actively participates in the catalysis, where rate‐determining bound amidate silylation is activated by the metal center and influenced by the bound amidate electronic and steric characteristics. DFT analysis of the catalytic cycle reveals that the relative energies of three intermediate endergonic steps, hence the rate‐determining step, depends on the silane concentration.