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Asymmetric 1,2-oxidative alkylation of conjugated dienes via aliphatic C–H bond activation

Nature Synthesis volume 1, pages 946–955 (2022)Cite this article

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A Publisher Correction to this article was published on 06 January 2023

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Abstract

The merging of transition-metal catalysis with radical chemistry offers a versatile platform for three-component difunctionalization of alkenes, allowing the construction of molecular complexity from readily available feedstocks. However, the direct use of hydrocarbon feedstocks as sp3-hybridized carbon radical precursors to participate in catalytic enantioselective functionalization of alkenes remains elusive. Here we describe an asymmetric 1,2-oxidative alkylation of conjugated dienes based on direct functionalization of strong and neutral C(sp3)–H bonds enabled by the combination of hydrogen atom transfer and copper catalysis. This approach allows carbon-centred radicals to be generated by selective activation of aliphatic C–H bonds, which are ubiquitous in hydrocarbons and other radical precursors. These radicals then react with 1,3-dienes to give allylic radicals which participate in copper-mediated asymmetric C–O coupling. This protocol provides a single-step access to various synthetically useful allylic esters directly from widely available chemical feedstocks.

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Fig. 1: Radical difunctionalization of alkenes.
Fig. 2: Synthetic applications of chiral allylic esters.
Fig. 3: Mechanistic investigation.

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Data availability

All data generated or analysed during this study are included in this published article (and its Supplementary Information). Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition number CCDC 2167286 (compound 73). 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 from the National Key R&D Program of China (2021YFA1500100) and NSFC (22188101) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, University of Science and Technology of China, Hefei, China

    Lian-Feng Fan, Rui Liu, Xiao-Yun Ruan, Pu-Sheng Wang & Liu-Zhu Gong

  2. Center for Excellence in Molecular Synthesis of Chinese Academy of Sciences, Hefei, China

    Liu-Zhu Gong

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Contributions

L.-Z.G. and L.-F.F. conceived the project. L.-F.F., R.L. and X.-Y.R. performed the experiments and analysed the data. L.-Z.G. and P-S.W. supervised the research. L.-F.F. and L.-Z.G. co-wrote the manuscript.

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Correspondence to Liu-Zhu Gong.

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Nature Synthesis thanks Wangqing Kong and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary handling editor: Peter Seavill, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary Information

Supplementary Discussion, Figs. 1–4, NMR spectra, HPLC data and Tables 1–8.

Supplementary Data 1

Crystallographic data for compound 73, CCDC 2167286.

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Fan, LF., Liu, R., Ruan, XY. et al. Asymmetric 1,2-oxidative alkylation of conjugated dienes via aliphatic C–H bond activation. Nat. Synth 1, 946–955 (2022). https://doi.org/10.1038/s44160-022-00172-8

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