Copper-Mediated Enantioselective C–H Thiolation of Ferrocenes Enabled by the BINOL Ligand

Transition-metal-catalyzed enantioselective C–H activation has transformed the landscape of asymmetric synthesis, enabling the efficient conversion of C–H bonds into C–C and carbon–heteroatom (C–X) bonds. However, the formation of C–S bonds through enantioselective C–H thiolation remains underdeveloped due to challenges such as catalyst deactivation and competitive coordination of sulfur-containing compounds with chiral ligands. Herein, we report an unprecedented approach to constructing sulfur-substituted planar chiral ferrocenes (PCFs) through copper-mediated enantioselective C–H thiolation enabled by only a 2.5 mol % 1,1′-bi-2,2′-naphthol (BINOL) ligand. A variety of sulfur-substituted PCFs were obtained in good yields (up to 83%) with excellent enantioselectivity (up to >99% ee). Mechanistic studies reveal that the irreversible C–H activation serves as both the stereo- and rate-determining step and can be achieved with catalytic amounts of Cu species. Furthermore, the utility of this protocol is illustrated through gram-scale synthesis, removal of the directing group, and the synthesis of N,S-chiral ligands as well as chiral rotaxanes. This significant advancement not only expands the tool kit for constructing chiral organosulfur compounds but also highlights the potential of enantioselective C–H activation in asymmetric synthesis.