Visible-light promoted late-stage chlorination and bromination of quinones and (hetero)arenes utilizing aqueous HCl or HBr as halogen donors

Abstract Late-stage C–H chlorination and bromination of bioactive scaffolds is significant for drug discovery, as carbon–halogen bonds can effectively modulate biological activity, metabolic stability, and physicochemical profiles. Here, we develop an atom-economical, radical-mediated protocol that synthesizes high-value chlorinated or brominated quinones and (hetero)arenes. The system employs inexpensive, low-molecular-weight HCl or HBr as the halogen source, commercially available NaNO₂, and blue light irradiation, without any photocatalyst or metal catalyst. The mild reaction conditions, ready availability of reagents, excellent functional-group tolerance, high regioselectivity, and facile scalability under continuous-flow operation collectively render this approach a practical and efficient protocol for the late-stage aromatic C(sp²)–H chlorination and bromination of complex drugs and natural products. Mechanistic investigations reveal that nitrosyl halides, generated in situ by reaction of NaNO 2 and aqueous HCl or HBr, undergo photo-promoted homolysis to produce the corresponding halogen radicals that selectively initiate the radical halogenation of quinones and (hetero)arenes.