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

Abstract

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.