Recently, the team of Prof. Shouguo Wang at Shenzhen University published a review article entitled “Enantioselective C(sp³)–H bond functionalization enabled by Cp^xM(III) catalysis (M = Co, Rh, Ir)” in Chemical Science, providing a comprehensive overview of recent advances in asymmetric C(sp³)–H functionalization enabled by chiral Cp^xM(III) catalytic systems. This paper was co-corresponded by Distinguished Professor Shou-Guo Wang and Assistant Professor Shi Cao of Shenzhen University, together with Professor Dong Wu from the Zhuhai Institute of Advanced Technology. Postdoctoral researcher Shubin Mou, associate researcher Mupeng Luo, and associate researcher Feifei Fang contributed as co-first authors.

The direct utilization of inert C(sp³)–H bonds for the construction of chiral molecules is widely regarded as one of the most challenging frontiers in organic synthesis. Compared with the more reactive C(sp²)–H bonds, C(sp³)–H bonds possess higher bond dissociation energies, lower polarity, and greater conformational flexibility, making precise control of regio- and stereoselectivity particularly difficult. As a result, this field has long been constrained by the challenge that, while transformations are feasible, achieving high selectivity remains difficult. In recent years, trivalent transition metal Cp^xM(III) catalytic systems, particularly those based on cobalt, rhodium, and iridium, have emerged as a powerful platform to address these challenges. Through fine-tuning of cyclopentadienyl (Cp^x) ligands, a well-defined chiral environment can be constructed around the metal center, enabling precise control over both regioselectivity and enantioselectivity. These catalytic systems combine high reactivity with excellent stereocontrol, allowing for the direct construction of structurally complex chiral molecules from simple hydrocarbon substrates. This review systematically summarizes the major strategies for enantioinduction in C(sp³)–H functionalization, including the use of chiral Cp^x ligands for direct stereocontrol, cooperative catalysis with chiral carboxylic acids to transfer chiral information, and the utilization of non-covalent interactions such as hydrogen bonding and π–π interactions to establish outer-sphere chiral environments. The continued development of these strategies has enabled asymmetric C(sp³)–H functionalization to evolve from proof-of-concept transformations into broadly applicable synthetic methodologies.

This work was supported by Guangdong Basic and Applied Basic Research Foundation (2024A1515011368 and 2024QN11C213); the Scientific Foundation for Youth Scholars of Shenzhen University (868-000001033009); and the National Natural Science Foundation of China (22333006). S.-G. is indebted to Shenzhen University for providing a start-up grant.

Link to paper:

https://pubs.rsc.org/en/content/articlelanding/2026/sc/d5sc08394j