Synthesis of α-substituted indolylacetamide using acetonitriles as acetamide enolate equivalents through O-transfer reactions.

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 α-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.