Visible light-driven construction of isoxazoline/isoxazole scaffolds via [2+2+1] cyclization of alkenes with tert-butyl nitrite

Abstract

A visible light-driven [2+2+1] cyclization of alkenes with tert-butyl nitrite (TBN) has been developed for the efficient construction of isoxazoline and isoxazole scaffolds. This protocol operates under mild conditions—utilizing ambient air as an oxygen source, room temperature, and visible-light irradiation—enabling both cross- and self-coupling of a wide range of alkenes with high functional group tolerance (including unprotected alcohols and terminal alkynes). The method has been successfully applied to the late-stage modification of bioactive drug molecules. Mechanistic studies reveal that O₂ serves as the key oxygen atom source for the carbonyl group in the products. This work represents a sustainable and practical strategy for heterocycle synthesis, aligning with the principles of green chemistry by minimizing energy input, avoiding transition metals, and employing benign reaction media.