Regioselective Transition Metal-Free C-H Chalcogeno-Coupling of 8-Hydroxyquinolines: Experimental and DFT Exploration

Herein, we have demonstrated a novel, operationally straightforward NaH-promoted strategy for regioselective C-5 chalcogenation of 8-hydroxyquinoline using diselenides and disulfides under mild reaction conditions. This approach showcases excellent atom economy and remarkable versatility, enabling the efficient synthesis of diverse chalcogenated 8-hydroxyquinolines. Furthermore, the selective preparation of mono- and dideuterated 8-hydroxyquinoline derivatives through the developed protocol exemplified the method's applicability. Mechanistic investigations, supported by controlled experiments, LC-MS, EPR, and DFT analyses, provide compelling evidence for the involvement of radical intermediates in the catalytic cycle. Notably, the reaction tolerates diverse functional groups and demonstrates utility in the gram-scale synthesis as well as late-stage functionalization of bioactive molecules.