Metallaphotoredox-enabled enantioselective aryldifluoromethyl-alkynylation of alkenes via C(sp3)–F bond activation†

Due to the prevalence of trifluoromethylarene (ArCF₃) units in drug-related molecules, direct late-stage functionalization of C(sp³)–F bonds in ArCF₃ offers an appealing strategy for rapid derivatization of ArCF₃-containing drugs, and holds significant promise in drug discovery and modification. Following the success of two-component reactions for C(sp³)–F bond functionalization in ArCF₃, preliminary studies have also been conducted on non-asymmetric three-component reactions. However, enantioselective three-component reactions via C(sp³)–F bond activation in ArCF₃ have not yet been developed. Herein, we report the first enantioselective three-component aryldifluoromethyl-alkynylation of alkenes through C(sp³)–F bond cleavage via dual photoredox/copper catalysis. This protocol is compatible with a wide array of trifluoromethylarenes bearing diverse substituents, various terminal alkynes and alkenes, enabling straightforward access to structurally diverse ArCF₂-containing propargylic compounds in good yields with excellent enantioselectivities under mild conditions. Furthermore, the utility of this protocol was showcased through its application in the late-stage functionalization of a few drugs and bioactive molecular derivatives.