Sustainable synthesis of pharmaceuticals via heterogeneous photocatalytic [3+2] cycloaddition

The Huisgen [3+2] cycloaddition reaction has long served as a cornerstone for synthesizing heterocyclic scaffolds in pharmaceutical chemistry. However, its reliance on halogenating oxidants, stoichiometric bases, and multistep protocols limits synthetic efficiency. Herein, we report a heterogeneous photocatalytic strategy that directly converts oximes and alkenes into isoxazolines and isoxazoles under mild, additive-free conditions. This one-step process leverages mesoporous graphitic carbon nitride (mpg-CN) as a recyclable photocatalyst and molecular oxygen as a benign terminal oxidant. The system demonstrates exceptional functional group tolerance, accommodating heterocycles, carbohydrates, and other sensitive motifs, while operating efficiently at mild condition. Scalability is achieved through continuous-flow implementation, enabling gram-scale synthesis of pharmacologically relevant heterocyclic cores. Combined mechanistic investigations and density functional theory (DFT) calculations demonstrate that the cascade reaction is primarily mediated through energy transfer processes. Its operational simplicity, environmental compatibility, and broad substrate scope position it as a transformative platform for academic and industrial applications.