Enantioselective C(sp3)–H bond functionalization enabled by CpxM(iii) catalysis (M = Co, Rh, Ir)

Abstract

Trivalent group 9 transition metals (Co, Rh, and Ir) bearing pentamethylcyclopentadienyl (Cp^x) or structurally tailored Cp^x ligands have emerged as a transformative platform for asymmetric C(sp³)–H functionalization. Despite significant progress in C(sp²)–H activation, achieving site- and stereoselective transformation of C(sp³)–H bonds remains a formidable synthetic challenge due to their intrinsic inertness, increased steric congestion and conformational flexibility. This review provides a comprehensive overview of recent advances in asymmetric C(sp³)–H functionalization catalyzed by Cp^xM(III) (M = Co, Rh, Ir) complexes. Particular emphasis is placed on the evolution of chiral ligand frameworks, the strategic use of directing groups, and mechanistic insights into enantioselectivity. By integrating recent developments, this review highlights novel reactions and effective catalytic systems, clarifies remaining challenges, and outlines future research directions in this dynamic field. We anticipate that more novel Cp^xM(III)-catalyzed asymmetric C(sp³)–H functionalization reactions will be developed and will find broad applicability in the near future.