Copper/N-Heterocyclic Carbene Cooperatively Catalyzed Remote Asymmetric <i>ε</i> -Alkylation of Yne-Thiophene Esters with Enals

A highly enantioselective Cu/NHC cooperative catalytic system was developed for the remote <i>ε</i>-alkylation of yne-thiophene esters with enals. The dual catalysis couples a chiral Cu-PyBox complex, which generates a reactive copper-vinylallenylidene intermediate, with an N-heterocyclic carbene (NHC) catalyst that forms a nucleophilic Breslow intermediate via umpolung activation of the enal. The synergistic interaction between the two chiral catalysts enables smooth C-C bond formation at the <i>ε</i>-position, delivering a broad range of 3,3-disubstituted oxindoles in up to 99% ee, >95:5 dr, and 94% yield. Mechanistic studies─including control and nonlinear-effect experiments─reveal that only one NHC molecule participates in the stereodetermining step and that matched chiral configurations of the Cu-PyBox and NHC catalysts are essential for both efficiency and selectivity. This strategy provides a versatile platform for remote asymmetric transformations and the streamlined synthesis of complex oxindole architectures.