Light Driven Pd-catalyzed Regioselective C─H Halogenation of Benzo[b][1,4]oxazin-2-ones Using DXDMH.

A mild, visible-light-driven protocol has been developed for the regioselective ortho-C(sp2)-H mono-halogenation (Cl, Br, and I) of 3-aryl-2H-benzo[b][1,4]oxazin-2-ones via a synergistic metallaphotoredox strategy. The transformation employs Pd(OAc)2 (20 mol %) in combination with the organic photocatalyst eosin Y (WS, 10 mol %) under irradiation with a 24 W blue LED, using bench-stable N-halo-5,5-dimethylhydantoins (DCDMH, DBDMH, and DIDMH) as sustainable halogen sources. Conducted in 1,2-dichloroethane (DCE) with p-toluenesulfonic acid (1.0 equiv.) as an essential additive, the reaction proceeds under oxidant-free and thermally mild conditions to afford ortho-halogenated products in high isolated yields (75%-97%) with excellent regioselectivity. A broad range of substituents on the 3-aryl ring, including electron-donating, electron-withdrawing, and extended aromatic groups, are well tolerated. Mechanistic investigations-including radical trapping experiments (TEMPO, BHT), light on/off studies, and control reactions-support a cooperative pathway involving Pd(II)-directed C─H activation and photoredox-mediated generation of halogen radicals, followed by radical capture and reductive elimination from high-valent palladium intermediates. This operationally simple dual catalytic approach provides an efficient platform for late-stage diversification of pharmaceutically relevant 2H-benzo[b][1,4]oxazin-2-one scaffolds and advances sustainable strategies in photocatalytic C─H halogenation.