Amide Synthesis via Transaminative Amidation of Aromatic Aldehydes/Ketones: An Entry to 15 N Isotopologs

Abstract Herein, we develop the first one‐pot amide synthesis from aldehyde/ketone and amino acids via transaminative amidation reaction and the method requires no catalyst or promoters, by allowing a concise access to structurally diverse amides and lactams with good efficiency. This transformation could also proceed smoothly by direct use of ether solvent as the formylated reagent in stead of formylic acid, thus furnishing an unique synthesis of formamides. The underlying principles of this unique amide synthesis was rationalized by a series of mechanistic studies, which involved a concerted decarboxylatively structural isomerization/acylation process as the key for amidation and a transamination/imine formation/aerobic oxidation cascade for formamidation. The potential utility of this strategy has been demonstrated by the readily accessible late‐stage transformation of biologically active molecules by 15 N incorporating. This protocol was also applied to the total synthesis of a kind of drug Butenafine with 15 N‐enrichment.