A Unified Platform for Direct Alkynylation from Alcohols via Deoxygenative Metallaphotoredox Catalysis.

Alkyne motifs are privileged functional groups in medicinal chemistry and serve as key handles in bioorthogonal click chemistry. Herein, we report a general metallaphotoredox deoxygenative C(sp3)-C(sp) coupling strategy that enables the direct conversion of alcohols into alkynes using alkynyl bromides as coupling partners. This protocol operates under redox-neutral, mild conditions via NHC-mediated alcohol activation and nickel catalysis, enabling the generation of alkyl radicals from alcohols and their subsequent cross-coupling with alkynyl electrophiles. The method exhibits broad substrate scope across structurally complex alcohols, including pharmaceuticals, peptides, nucleosides, and natural products, providing a practical platform for the synthesis of click-ready alkynes from readily available alcohol feedstocks. In addition, the alkynyl bromide manifold enables modular diversification and late-stage functionalization of amino acid side chains and other bioactive molecules, significantly expanding the accessible chemical space for alkyne-based medicinal and bioconjugation chemistry.