Visible-Light-Catalyzed In Situ Generation of Nitrile Oxides from Aryl Trichloromethane and TBN for [3 + 2] Cycloaddition to Access Isoxazoline/Isoxazole Scaffolds

Abstract

Abstract A facile, photochemical three-component protocol for the regioselective synthesis of isoxazolines has been developed using commercially available aryl trichloromethane, alkene, and tert-butyl nitrite as starting materials. Unlike conventional methods that require presynthesized 1,3-dipolar precursors or transition-metal catalysts, this transformation proceeds smoothly under visible-light irradiation. Control experiments were performed to probe the reaction mechanism, which confirmed that PhCHCl2 is a plausible reaction intermediate, and the process is proposed to proceed via in-situ generation of a nitrile oxide 1,3-dipole followed by regioselective [3 + 2] cycloaddition. This strategy features mild reaction conditions, wide functional group compatibility, and operational simplicity, providing straightforward and efficient access to functionalized isoxazoline/isoxazole derivatives with potential biological and synthetic utility.