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Divergent sulfur(VI) fluoride exchange linkage of sulfonimidoyl fluorides and alkynes

Nature Synthesis volume 1, pages 455–463 (2022)Cite this article

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Abstract

Sulfur(VI) fluoride exchange reactions have been applied to the linkage of a diverse range of molecules. However, the connectivity of fluorosulfuryls with alkynes remains a formidable challenge owing to the high reactivity of π systems. Here, we report a divergent sulfur(VI) fluoride exchange reaction between sulfonimidoyl fluorides and alkynes to afford vinylic and acetylenic sulfoximines. Experimental and computational mechanistic studies elucidated key BF3-bridged six-membered transition states that enabled the synchronous activation of silicon-capped alkynes and sulfonimidoyl fluorides via the interactions of F···Si and B···F. Mechanistic studies also revealed that N-benzyl sulfonimidoyls undergo a 1,5-hydrogen migration from the benzylic position to the acetylenic position, which generates the observed vinylic sulfoximines. A range of synthetic transformations, which include azide–alkyne cycloadditions were demonstrated on the vinylic and acetylenic sulfoximine products.

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Fig. 1: Application of SuFEx reactions and design of the SuFEx linkage between sulfonimidoyl fluorides and alkynes.
Fig. 2: Further synthetic transformations of vinylic sulfoximines.
Fig. 3: Control experiments and NMR spectroscopy studies.
Fig. 4: DFT analysis of the potential reaction pathways to form vinylic sulfoximines from acetylenes and N-benzyl sulfonimidoyl fluoride.
Fig. 5: Proposed reaction pathway for the divergent SuFEx linkage between sulfonimidoyl fluoride and acetylenes pathway.

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Data availability

The X-ray crystallographic coordinates for the structures reported in this study have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition numbers CCDC 2094839 (4y) and CCDC 2094841 (5f). These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. All other data supporting the findings of this study are available within the paper and Supplementary Information.

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Acknowledgements

We are grateful for financial support provided by NSFC (22125103, 22071057 and 21871089), STCSM (20XD1421500 and 20JC1416800), and the Fundamental Research Funds for the Central Universities.

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Authors and Affiliations

  1. Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, P. R. China

    Daming Zeng, Yinhao Ma, Ming Wang & Xuefeng Jiang

  2. School of Pharmacy and Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, P. R. China

    Daming Zeng & Wei-Ping Deng

  3. State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, P. R. China

    Xuefeng Jiang

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Contributions

X.J. and M.W. conceived the idea and supervised the project. M.W. and D.Z. designed and carried out the experiments. Y.M. conducted the DFT calculations. X.J., M.W. and W.-P.D. discussed the results, contributed to the writing of the manuscript and commented on the manuscript. All the authors approved the final version of the manuscript for submission.

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Correspondence to Ming Wang or Xuefeng Jiang.

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Nature Synthesis thanks Han Zuilhof and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Thomas West, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–6 and Tables 1–7.

Supplementary Data 1

Crystallographic data of 4y CCDC 2094839.

Supplementary Data 2

Crystallographic data of 5f CCDC 2094841.

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Zeng, D., Ma, Y., Deng, WP. et al. Divergent sulfur(VI) fluoride exchange linkage of sulfonimidoyl fluorides and alkynes. Nat. Synth 1, 455–463 (2022). https://doi.org/10.1038/s44160-022-00060-1

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