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.