Iodine-Mediated Multicomponent Deaminative Cyclization for Direct Transformation of Inert Amides into Aromatic Lactones.

Amide bonds, due to their significant resonance stabilization, make the C-N bond extremely difficult to cleave, posing a major challenge for amide functionalization. Herein, we describe the first multicomponent [3+2+1] deaminative cyclization strategy that enables one-pot selective amide activation, deamination, and cyclization under I2/DMSO conditions for the direct construction of aromatic heterocyclic scaffolds. This protocol employs readily available aryl ethyl ketones, 4-hydroxy-1-methylquinolin-2(1H)-one, and amides containing an active methylene group to efficiently assemble structurally unique α-pyrone aromatic lactones. Notably, this work achieves the direct transformation of amides into aromatic lactones within a multicomponent framework, overcoming the traditional limitation of forming only linear esters, and establishes a new platform for inert amide functionalization and complex heterocycle synthesis.