Divergent Synthesis of Quinolones through Radical C-H Functionalization/Cyclization

Divergent synthesis is an effective, yet challenging method to selectively access different molecules from a single starting material. Herein, we demonstrate a divergent and controllable synthesis of quinolones by sulfonyl chloride-controlled, copper-catalyzed, site-selective radical C-H functionalization/cyclization of quinoline scaffolds. Our catalytic system can tolerate a wide range of functional groups and provide both 2-thioquinolone and 4-quinolone derivatives in moderate to good yields. Control experiments and density functional theory calculations indicate a single-electron transfer mechanism, and the steric hindrance of sulfonyl chlorides and their electronic effect are decisive for reaction selectivity. This transformation provides not only a novel example of divergent radical C-H functionalization controlled by small organic molecules, but also an efficient way to rapidly derivatize medicinally important scaffolds and ultimately facilitate late-stage drug modification.