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Discovery and synthesis of atropisomerically chiral acyl-substituted stable vinyl sulfoxonium ylides

Nature Chemistry volume 16, pages 132–139 (2024)Cite this article

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Abstract

Atropisomerism is a type of conformational chirality that plays a critical role in various fields of chemistry, including synthetic, medicinal and material chemistry, and its impact has been widely recognized. Although chiral atropisomerism in rotationally restricted aryl–aryl bonds has garnered substantial interest and led to important discoveries in chiral catalysts and drug development, the exploration of non-aryl atropisomers has fallen behind. Here we reveal a previously unexplored form of non-aryl atropisomerism by linking a sterically congested olefin to a sulfoxonium ylide. A streamlined synthetic approach to these novel molecules was developed through the hydrofunctionalization of alkynyl sulfoxonium ylides. Notably, an enantioselective organocatalytic strategy was developed to prepare these non-aryl atropisomers in high optical purity. This form of atropisomerism offers new routes for investigating the functional properties of axially chiral molecules.

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Fig. 1: Representative atropisomeric chiral molecules and the design of non-aryl atropisomeric chirality.
Fig. 2: Difunctionalization of the alkynyl sulfoxonium ylide and calculated rotational barriers for selected VSYs.
Fig. 3: Transformations of chiral VSYs.
Fig. 4: Mechanism study based on DFT calculations.

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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 2199007 (1), 2199008 (44), 2255173 (73), 2255174 (86) and 2259612 (88). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Experimental procedures, characterization of new compounds and all other data supporting the findings are available in the Supplementary Information.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (21825101), Hong Kong RGC (16302122, 16300320 and 16309021) and the Shenzhen Science and Technology Innovation Commission (SGDX2019081623241924). We thank Z. Lin for insightful discussions.

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Authors and Affiliations

  1. The Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong SAR, China

    Fengjin Wu, Yichi Zhang, Ruiqi Zhu & Yong Huang

  2. Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen, China

    Fengjin Wu

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Contributions

F.W. and Y.H. designed the project. Y.H. directed the project. F.W. conducted the experiments. R.Z. conducted the transformation experiments. Y.Z. performed computation of the rotational barriers and the mechanism study. All authors contributed to designing, performing and analysing the experiments, as well as to the writing of this manuscript.

Corresponding author

Correspondence to Yong Huang.

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The authors declare no competing interests.

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Peer review information

Nature Chemistry thanks Dao-Juan Cheng, Michele Mancinelli and Takanori Shibata for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Sections 1–9, Figs. 1–12, Tables 1–44 and refs. 1–18.

Supplementary Data 1

Crystallographic data for compound 1; CCDC reference 2199007.

Supplementary Data 2

Crystallographic data for compound 44; CCDC reference 2199008.

Supplementary Data 3

Crystallographic data for compound 73; CCDC reference 2255173.

Supplementary Data 4

Crystallographic data for compound 86; CCDC reference 2255174.

Supplementary Data 5

Crystallographic data for compound 88; CCDC reference 2259612.

Supplementary Data 6

Computational data for DFT calculations.

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Wu, F., Zhang, Y., Zhu, R. et al. Discovery and synthesis of atropisomerically chiral acyl-substituted stable vinyl sulfoxonium ylides. Nat. Chem. 16, 132–139 (2024). https://doi.org/10.1038/s41557-023-01358-z

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