Royal Society of Chemistry (RSC) Acta Medica Okayama 1359-7345 57 61 2021 Synthesis of α-substituted indolylacetamide using acetonitriles as acetamide enolate equivalents through O-transfer reactions 7493 7496 EN Takumi Abe Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Noda Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Sawada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University We introduce readily available ammonium hemiaminals as O-transfer reagents and commercially available acetonitriles as a primary amide enolate precursor. The combination serves as an amide enolate equivalent, thereby providing one-pot access to alpha-substituted indolylacetamides. A broad substrate scope and good functional group tolerance as well as gram-scale synthesis make this protocol highly attractive. Mechanistic experiments suggest that the cyano group is trapped by a hydroxy group of hemiaminals en route to the desired primary amides under metal-free conditions. No potential conflict of interest relevant to this article was reported.