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SmI2-mediated enantioselective reductive dearomatization of non-activated arenes

Nature Synthesis volume 1, pages 401–406 (2022)Cite this article

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Abstract

Arenes are fundamental feedstocks for many chemical processes within organic synthesis. The dearomatization of arenes, especially non-activated benzene derivatives, has long been recognized as an important synthetic transformation. However, developing enantioselective variants of these dearomative reactions remains a challenge due to the inherent stability of benzene derivatives. Here we report the development of a samarium diiodide (SmI2)-mediated enantioselective reductive dearomatization of non-activated benzene derivatives. The use of chiral tridentate aminodiol ligand forms a chiral samarium complex, mediating the intramolecular addition of a ketyl radical onto one of the two enantiotopic arene rings in a stereoselective fashion. The scope of the process is displayed through the synthesis of a range of dearomatized bicycles bearing three stereogenic centres, in good yield and stereocontrol. Scale-up of the process and further reductive and olefination transformations of the bicyclic products showed the synthetic utility of the SmI2-mediated process.

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Fig. 1: Strategies for enantioselective dearomatization of non-activated arenes.
Fig. 2: Reaction scale-up and product transformations.

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Data availability

Crystallographic data are available free of charge from the Cambridge Crystallographic Database Centre under CCDC 2094419 (2a) and 2094418 (2t). All other characterization data are in the Supplementary Information. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

Financial support for this work was provided by the National Key R&D Program of China (grant number 2021YFA1500100), the National Natural Science Foundation of China (grant numbers 21821002, 22031012 and 91856201) and the Science and Technology Commission of Shanghai Municipality (grant numbers 19590750400 and 21520780100). S.-L.Y. acknowledges support from Tencent Foundation through an Xplorer Prize.

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  1. These authors contributed equally: Ye Wang, Wen-Yun Zhang.

Authors and Affiliations

  1. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Ye Wang, Wen-Yun Zhang, Zong-Lun Yu, Chao Zheng & Shu-Li You

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Contributions

S.-L.Y. conceived and supervised the project. Y.W. developed SmI2-mediated asymmetric reductive dearomatization of non-activated arenes. W.-Y.Z. and Z.-L.Y. contributed to expanding the substrate scope. C.Z. wrote the manuscript and incorporated revisions suggested by all authors.

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Correspondence to Shu-Li You.

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Nature Synthesis thanks Robert Flowers, Kjell Jorner 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 discussion and Tables 1–3.

Crystallographic Data 1

Crystallographic Data for 2a, CCDC 2094419.

Crystallographic Data 2

Crystallographic Data for 2t, CCDC 2094418.

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Wang, Y., Zhang, WY., Yu, ZL. et al. SmI2-mediated enantioselective reductive dearomatization of non-activated arenes. Nat. Synth 1, 401–406 (2022). https://doi.org/10.1038/s44160-022-00065-w

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