Visible Light-Mediated Decarboxylative Annulations of Oxamic Acids and Alkynes via Hydrogen Atom Transfer

Abstract

β- and γ-lactams are critically important heterocycles in organic and medicinal chemistry, primarily due to their potent biological activities and distinctive three-dimensional architectures. Herein, a facile photochemical synthesis of a range of functionalized β- and γ-lactams derivatives from decarboxylative annulations of easily accessible oxamic acids and alkynes, enabled by a hydrogen atom transfer (HAT) strategy, is described. Notably, this efficient protocol proceeds under mild conditions with a straightforward work-up, accommodates a broad spectrum of functional groups, and can be readily applied to the derivatization of pharmaceutically relevant scaffolds. Based on mechanistic evidences and computational studies, it is suggested that the electronic nature of the alkyne modulates the reactivity of the readily formed alkenyl radical intermediate to unlock a carbon-to-carbon 1,5-HAT and consequently selective four- or five-membered ring cyclization. This strategy provides a streamlined access to a variety of β- and γ-lactams, offering a conceptually different approach to HAT-mediated C(sp3)–H functionalization.