Abstract
Selective functionalization and high-value conversion of polyfluoroalkyl compounds is of paramount importance due to their widespread use in pharmaceuticals, agrochemicals, and advanced materials. However, the formidable stability of C(sp3)–F bonds, exacerbated by strong electron-withdrawing effects, steric hindrance, and the inherent challenge of achieving precise selectivity, has significantly hampered efforts toward their controlled activation and modification. Herein, we present a dual photoredox/cobalt catalytic strategy that enables redox-driven defluoroallylation of perfluoroalkylarenes and polyfluorinated aliphatic amides. Our approach leverages single-electron reduction to cleave robust C(sp3)–F bonds, generating reactive perfluoroalkyl radicals that couple efficiently with simple alkenes. Cobalt-mediated hydrogen atom transfer, with Lewis acidic fluorine scavengers serving primarily to trap the fluoride and suppress back-electron transfer, ensures precise regioselective allylation under mild conditions. Mechanistic investigations reveal that controlled radical generation and selective activation underpin the unique site selectivity observed. This dual catalytic platform offers an efficient strategy for the construction of complex fluorinated scaffolds and expands the toolkit for the selective transformation of polyfluorinated frameworks.
Data availability
All data supporting the findings of this study are included in the article, its Supplementary Information, and the accompanying Source data file. The Supplementary Information contains experimental details, characterization data, copies of NMR spectra for all new compounds, and additional density functional theory (DFT) calculation data. The Source data file provides the Cartesian coordinates of all DFT-optimized structures. All data are available from the corresponding author upon request. Source data are provided with this paper.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China, No. 22522112 (H.Y.) and No. 22201222(X.Q.); the National Key R&D Program of China, No. 2021YFA1500104 (A.L.), and No. 2022YFA1505100 (H.Y.); Hubei Technological Innovation Program Funding 2025BAB025 (H.Y.); and the supercomputing system in the Supercomputing Center of Wuhan University (X.Q.). The authors thank Dr. Xue Zhou from the Core Research Facilities of CCMS (WHU) for her assistance with NMR analysis. The authors thank the support of the Opening Foundation of Xi’an Modern Chemistry Research Institute (grant number 204-J-2023-2325).
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H.Y. and D.R. conceived the work. D.R., H.Y., J.Y., B.W. and A.L. designed the experiments and analyzed the data. D.R., Y.W. and W.D. performed the synthetic experiments. S.W., J.Y. and P.W. contributed to the EPR data. S.D. and X.Q. contributed to the DFT calculation. D.R. wrote the original manuscript, which was revised by all authors.
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Ren, D., Deng, S., Wang, Y. et al. Radical defluoroallylation of polyfluoroalkyl compounds with alkenes via synergistic photoredox/cobalt catalysis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68840-3
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DOI: https://doi.org/10.1038/s41467-026-68840-3
