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Allylic C(sp3)–H arylation of olefins via ternary catalysis

Nature Synthesis volume 1, pages 59–68 (2022)Cite this article

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Abstract

Transforming C(sp3)–H bonds efficiently and selectively into C(sp3)–C(sp3) or C(sp3)–X bonds is a highly relevant task. The direct arylation of allylic C(sp3)–H bonds provides an elegant method for the formation of unconjugated aryl-substituted olefins. Although both ionic- and radical-based transition metal catalysis has been applied to achieve this transformation, numerous challenges remain. The requirement for persistent radical coupling partners, moderate selectivity and the need for tri- or tetrasubstituted olefins have limited the generality of existing methods. Now we report a ternary catalytic method that combines organic photoredox, hydrogen atom transfer and nickel catalysis, and can directly arylate allylic C(sp3)–H bonds of readily available olefins. This process operates under mild conditions and exhibits a remarkable reaction scope in both aryl halide and olefin coupling partners. Mechanistic experiments, coupled with density functional theory calculations of Ni-oxidation states and reaction energetics allowed the elucidation of a ternary catalytic cycle and the origin of regioselectivity.

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Fig. 1: Direct allylic C(sp3)–H arylation, state-of-the-art and design of this work.
Fig. 2: Reaction components and optimization.
Fig. 3: Reaction scope.
Fig. 4: Reaction scope with regard to allylic substrates.
Fig. 5: Mechanistic experiments.
Fig. 6: DFT analysis of the allylic arylation reaction.
Fig. 7: DFT analysis of the regio-determining transition state and thermodynamics of products.

Data availability

Materials and methods, detailed optimization studies, experimental procedures, mechanistic studies and copies of the NMR spectra are available in the Supplementary Information. NMR data in a mnova file format and gas chromatography–mass spectroscopy data for KIE analysis are available at Zenodo at https://zenodo.org/record/5614753#.Yaq8DN8kGUk, under the Creative Commons Attribution 4.0 International license.

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Acknowledgements

This work was generously supported by the Alexander von Humboldt Foundation (H.-M.H.) and the Deutsche Forschungsgemeinschaft (Leibniz Award, SBF 858), the National Science Foundation (CHE-1764328 to K.N.H.) and Zhejiang University for support of P.-P.C. Calculations were performed on the IDRE Hoffman2 cluster at the University of California, Los Angeles, and the Vienna Scientific Cluster. We thank J. Cornella (Max-Planck-Institut für Kohlenforschung) for the generous donation of a sample of Ni(Fstb)3 and X. Zhang, T. Dalton, J. Li, J. Ma, H. Wang and T. Hu (all University of Münster) for helpful discussions and experimental support.

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  1. These authors contributed equally: Huan-Ming Huang, Peter Bellotti, Pan-Pan Chen.

Authors and Affiliations

  1. Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Münster, Germany

    Huan-Ming Huang, Peter Bellotti & Frank Glorius

  2. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA

    Pan-Pan Chen & Kendall N. Houk

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Contributions

H.-M.H and F.G. conceived the project. H.-M.H and P.B. performed all of the experiments and analysed all the data. P.-P.C. performed the DFT calculations. H.-M.H, P.B., P.-P.C., K.N.H. and F.G. supervised the research and co-wrote the manuscript.

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Correspondence to Kendall N. Houk or Frank Glorius.

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Nature Synthesis thanks Gabriel dos Passos Gomes and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Thomas West was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Huang, HM., Bellotti, P., Chen, PP. et al. Allylic C(sp3)–H arylation of olefins via ternary catalysis. Nat Synth 1, 59–68 (2022). https://doi.org/10.1038/s44160-021-00006-z

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