Ligand-Promoted Copper-Catalyzed Radical Relay for Alkyl-Alkynylation of Alkenes

The alkynylation of alkenes provides an efficient platform for synthesizing compounds containing C≡C bonds. However, the intermolecular alkynylation of alkenes has been largely restricted to precious metal palladium-catalyzed systems, limiting reaction versatility. Herein, we report a copper-catalyzed radical relay strategy for intermolecular alkyl-alkynylation of alkenes and construction of challenging C(sp³)-C(sp³) bonds and C(sp³)-C(sp) bonds in one pot. This method utilizes alkene-tethered α-carbonyl bromides as the alkyl source, which undergo single-electron transfer to generate alkyl radicals and then add across the C═C bonds to form cyclic alkyl radical intermediates. This intermediate inserts into copper-acetylide complexes, achieving intermolecular alkyl-alkynylation of alkene-tethered substrates. Notably, the introduction of an electron-rich tridentate nitrogen ligand (^<i>t</i>Bu₃-TERPY) boosts the copper catalyst's reducing power and stabilizes the copper-acetylide intermediate. This dual effect reduces byproduct formation during atom transfer radical addition (ATRA) while circumventing β-hydrogen elimination and direct radical addition of the cyclic alkyl radical intermediate to the alkyne. Moreover, density functional theory (DFT) calculations indicate that C(sp³)-C(sp) bond formation between the cyclic alkyl radical intermediate and copper-acetylide complex proceeds predominantly through an inner-sphere pathway.