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

Abstract

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.