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Palladium-catalysed construction of butafulvenes

Nature Chemistry volume 14, pages 1185–1192 (2022)Cite this article

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Abstract

Butafulvene is a constitutional isomer of benzene, comprising a cyclobutene skeleton bearing two exocyclic conjugated methylene units. As a result of the intrinsic high strain energy and anti-aromaticity, the preparation of butafulvene compounds has been a fundamental issue for the development of butafulvene chemistry. Here an efficient palladium-catalysed coupling protocol involving propargylic compounds has been developed, providing a solid and versatile strategy for the rapid assembly of symmetric butafulvene derivatives. Based on mechanistic studies, two complementary mechanisms, both involving palladium catalysis, have been confirmed. With the mechanism unveiled, the synthesis of non-symmetric butafulvenes has also been achieved. Advantages of this strategy include tolerance to a wide range of propargylic molecules, mild reaction conditions, simple catalytic systems and easy scalability. The synthetic potential of the products as platform molecules for cyclobutene derivatives has also been demonstrated.

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Fig. 1: Triple-conjugated carbocycles and approaches to strained butafulvenes.
Fig. 2: Mechanistic studies on reaction intermediates and proposed mechanism for the two developed strategies.
Fig. 3: Scope of non-symmetric butafulvenes via three different strategies.
Fig. 4: Synthetic transformations of butafulvenes.

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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC1875931 (2a), 2035320 (5h), 2045841 (18a), 2049400 (19a) and 2131557 (22). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

We acknowledge financial support from the National Key R&D Program of China (2021YFF0701600 for J.Z.), the National Natural Science Foundation of China (22071239 for Q.-A.C. and 21988101 for S.M.), the Dalian Institute of Chemical Physics (DICPI201902 for Q.-A.C.). S.M. is a Qiu Shi Adjunct Professor at Zhejiang University. We thank F. Jiang in our group for reproducing the results of 2o and 12b.

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  1. These authors contributed equally: Xin Huang, Bing-Zhi Chen.

Authors and Affiliations

  1. Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, China

    Xin Huang, Pengbin Li, Jinxian Liu, Chunling Fu, Yankai Huang, Jian Zheng & Shengming Ma

  2. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

    Bing-Zhi Chen, Ding-Wei Ji, Hao Zheng, Sa-Na Yang, Yan-Cheng Hu, Boshun Wan, Xiang-Ping Hu & Qing-An Chen

  3. University of Chinese Academy of Sciences, Beijing, China

    Bing-Zhi Chen

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Contributions

S.M. and Q.-A.C. conceived and supervised the project. S.M., Q.-A.C., J.Z., X.H. and B.-Z.C. designed the experiments. X.H., B.-Z.C., P.L., D.-W.J., J.L., H.Z., S.-N.Y., Y.-C.H., B.W., X.-P.H., C.F., Y.H. and J.Z. performed the experiments and analysed the data. All authors discussed the results and commented on the article.

Corresponding authors

Correspondence to Jian Zheng, Qing-An Chen or Shengming Ma.

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The authors declare no competing interests.

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Nature Chemistry thanks Dorian Didier and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

General information; synthesis of starting materials; synthesis of symmetric butafulvenes; mechanistic studies; synthesis of non-symmetric butafulvenes; DFT computations; synthetic applications; X-ray crystal structures for 2a, 5h, 18a, 19a and 22; references; copies of the 1H NMR and 13C NMR spectra.

Supplementary Data 1

Crystallographic data for compound 2a; CCDC reference 1875931.

Supplementary Data 2

Crystallographic data for compound 5h; CCDC reference 2035320.

Supplementary Data 3

Crystallographic data for compound 18a; CCDC reference 2045841.

Supplementary Data 4

Crystallographic data for compound 19a; CCDC reference 2049400.

Supplementary Data 5

Crystallographic data for compound 22; CCDC reference 2131557.

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Huang, X., Chen, BZ., Li, P. et al. Palladium-catalysed construction of butafulvenes. Nat. Chem. 14, 1185–1192 (2022). https://doi.org/10.1038/s41557-022-01017-9

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