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Photoinduced gold-catalyzed divergent dechloroalkylation of gem-dichloroalkanes

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Abstract

The use of alkyl chlorides as C(sp3)-hybridized electrophiles for the construction of C(sp3)–C(sp3) bonds represents one of the most challenging issues in organic synthesis, associated with their low reduction potential and strong bond dissociation energy. Here we report a divergent radical transformation of a rich library of structurally diverse gem-dichloroalkanes by the controllable dechloroalkylation of alkenes by excited-state dinuclear gold catalysis. The gem-dichloroalkanes can be used to assemble C(sp3)–C(sp3) bonds as a chloroalkyl radical, an alkyl radical cation and a carbene equivalent precursor for carbon-chain propagation, or formal [4+1] and [2+1] cyclization of alkenes. The use of commercially available deuterium-labelled polychloromethanes provides a practical method to incorporate CD2Cl, CDCl2, CDCl and CD2 moieties into organic scaffolds. Studies of the mechanism have revealed an inner-sphere single electron transfer pathway for the homolytic cleavage of a strong C–Cl bond.

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Fig. 1: The challenges of photoredox activation of unactivated C–Cl bonds.
Fig. 2: Scope of hydrochloroalkylation of alkenes.
Fig. 3: Substrate scope of tandem chloroalkylarylation of alkenes.
Fig. 4: Substrate scope of the formal [4+1] cyclization reaction.
Fig. 5: Scope of the cyclopropanation reaction.
Fig. 6: Synthetic applications.
Fig. 7: Mechanism studies.

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Data availability

Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2157587 (1a) and CCDC 2157457 (1b). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Data related to materials and methods, optimization of conditions, experimental procedures, mechanistic experiments, density functional theory calculations and spectra are provided in the Supplementary Information. All data are available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank the National Natural Science Foundation of China (22122103 and 21971108 to J.X., 22101130 to J.H., 21971111 and 21732003 to C.Z.), the National Key Research and Development Program of China (2022YFA1503202 and 2021YFC2101901 to J.X.), Natural Science Foundation of Jiangsu Province (grant no. BK20190006 to J.X.), Fundamental Research Funds for the Central Universities (020514380252 and 020514380272 to J.X.) for financial support. S. Wang, Y. He, Y. Li and N. Li are acknowledged for their reproduction of the experimental procedures for products 4aa, 6a, 7i and 8g. All theoretical calculations were performed at the High-Performance Computing Center (HPCC) of Nanjing University.

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Author notes

  1. These authors contributed equally: Cheng-Long Ji, Jie Han.

Authors and Affiliations

  1. State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China

    Cheng-Long Ji, Jie Han, Tingrui Li, Chuan-Gang Zhao, Chengjian Zhu & Jin Xie

  2. Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou, China

    Chengjian Zhu

  3. State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi, China

    Jin Xie

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Contributions

C.-L.J., J.H. and J.X. conceived the work and designed the experiments. C.-L.J., T.L. and C.-G.Z. performed the experiments and analyzed the experimental data. T.L. and C.-L.J. performed the EPR measurements. J.H. performed the density functional theory calculations and discussed the results with C.-L.J. and C.Z., and J.X. co-wrote the manuscript with input from all the other authors.

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Correspondence to Jin Xie.

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Nature Catalysis thanks Rongxiu Zhu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Tables 1–7, Figs. 1–285 and Discussion.

Supplementary Data 1

Crystallographic data for compound 1a.

Supplementary Data 2

Crystallographic data for compound 1b.

Supplementary Data

Atomic coordinates of the optimized structures.

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Ji, CL., Han, J., Li, T. et al. Photoinduced gold-catalyzed divergent dechloroalkylation of gem-dichloroalkanes. Nat Catal 5, 1098–1109 (2022). https://doi.org/10.1038/s41929-022-00881-5

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