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Multi-site programmable functionalization of alkenes via controllable alkene isomerization

Nature Chemistry volume 15, pages 988–997 (2023)Cite this article

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Abstract

Direct and selective functionalization of hydrocarbon chains is a fundamental problem in synthetic chemistry. Conventional functionalization of C=C double bonds and C(sp3)–H bonds provides some solutions, but site diversity remains an issue. The merging of alkene isomerization with (oxidative) functionalization provides an ideal method for remote functionalization, which would provide more opportunities for site diversity. However, the reported functionalized sites are still limited and focus on a specific terminal position and internal site; new site-selective functionalization, including multi-functionalization, remains a largely unmet challenge. Here we describe a palladium-catalysed aerobic oxidative method for the multi-site programmable functionalization, involving the C=C double bond and multiple C(sp3)–H bonds, of terminal olefins via a strategy that controls the reaction sequence between alkene isomerization and oxidative functionalization. Specifically, 1-acetoxylation (anti-Markovnikov), 2-acetoxylation, 1,2-diacetoxylation and 1,2,3-triacetoxylation have been realized, accompanied by controllable remote alkenylation. This method enables available terminal olefins from petrochemical feedstocks to be readily converted into unsaturated alcohols and polyalcohols and particularly into different monosaccharides and C-glycosides.

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Fig. 1: Remote functionalization of alkenes.
Fig. 2: Regioconvergent aerobic 2-hydroxylation and transformations of products.
Fig. 3: Mechanistic studies and proposed catalytic cycles.

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Data availability

The data supporting the findings of this study are available within the Article and its Supplementary Information.

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Acknowledgements

We are grateful for financial support provided by the National Natural Science Foundation of China (Nos 21620102003, 21831005 and 21991112 to W.Z.), the National Key R&D Program of China (No. 2018YFE0126800 to W.Z.) and the Shanghai Municipal Education Commission (No. 201701070002E00030 to W.Z.). We thank the Instrumental Analysis Center of SJTU for characterization experiments. We are grateful to Q. Ge and C. Xu for their contribution concerning the purification of compounds.

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Authors and Affiliations

  1. Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Zhengxing Wu, Jingjie Meng, Huikang Liu, Yunyi Li, Xiao Zhang & Wanbin Zhang

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  1. Zhengxing Wu
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Contributions

W.Z. and Z.W. conceived the work and designed the experiments. Z.W. performed the experiments and analysed the data. J.M., Y.L., H.L. and X.Z. performed the experiments. W.Z. and Z.W. wrote the paper. W.Z. guided the project. All the authors checked the paper.

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Correspondence to Wanbin Zhang.

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Supplementary Information

Supplementary Figs. 1–28, Tables 1–6, synthesis and characterization data, supplementary discussion, computational and procedural details, NMR spectra and references.

Supplementary Data 1

Cartesian coordinates (x,y,z) and coupling constants.

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Wu, Z., Meng, J., Liu, H. et al. Multi-site programmable functionalization of alkenes via controllable alkene isomerization. Nat. Chem. 15, 988–997 (2023). https://doi.org/10.1038/s41557-023-01209-x

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