H-Bond Mediated Photocatalyzed Oxidation of Oximes under visible light and Air. A General Route toward Dioxazoles, Oxadiazoles and Isoxazoles

Abstract

The development of sustainable and efficient synthetic methods for nitrogen-containing heterocycles remains a central focus in modern organic chemistry. Oxazoles and their derivatives are of significant interest in both academic and industrial research owing to their broad spectrum of biological activities and frequent occurrence in natural products. Here we present a photocatalyzed visible-light-induced oxidation of oximes as a versatile strategy for the construction of three distinct heterocyclic skeletons, i.e. dioxazoles, oxadiazoles and isoxazoles. This photochemical process features a broad substrate scope, functional group tolerance, and high regioselectivity delivering products in yields of up to 92%. By leveraging a metal-free photocatalyst (4-DPAIPN) and visible light irradiation at 456 nm under atmospheric air conditions, the method enables selective oxidative cyclization of structurally diverse oxime precursors. Mechanistic investigations using EPR, fluorescence quenching experiments and transient absorption spectroscopy suggest the formation of an iminoxyl radical as a key intermediate, generated through the oxidation of the oxime bound to the photocatalyst through hydrogen bonding. This interaction is proposed to contribute to the selective oxidation of the oxime by the oxidized photocatalyst.Subsequent oxidation of the iminoxyl radical into a nitrile oxide, followed by [3+2] cycloaddition with ketones, nitriles, or alkynes, affords streamlined access to the corresponding heterocycles. Overall, this photocatalytic strategy provides a green alternative to conventional methods, minimizing wastes, while delivering valuable nitrogen-oxygen atoms containing heterocycles with potential applications in pharmaceutical and materials chemistry