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Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch

Author

Listed:
  • Jiangtao Ren

    (Yunnan University
    Southwest United Graduate School)

  • Zheng Sun

    (Yunnan University)

  • Shuang Zhao

    (Yunnan University
    Yunnan University)

  • Jinyuan Huang

    (Yunnan University
    Yunnan University)

  • Yukun Wang

    (Yunnan University)

  • Cheng Zhang

    (Yunnan University
    Yunnan University)

  • Jinhai Huang

    (Yunnan University)

  • Chenhao Zhang

    (Yunnan University)

  • Ruipu Zhang

    (Yunnan University
    Yunnan University)

  • Zhihan Zhang

    (Central China Normal University)

  • Xu Ji

    (Yunnan University
    Yunnan University)

  • Zhihui Shao

    (Yunnan University
    Southwest United Graduate School)

Abstract

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)−C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Suggested Citation

  • Jiangtao Ren & Zheng Sun & Shuang Zhao & Jinyuan Huang & Yukun Wang & Cheng Zhang & Jinhai Huang & Chenhao Zhang & Ruipu Zhang & Zhihan Zhang & Xu Ji & Zhihui Shao, 2024. "Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48175-7
    DOI: 10.1038/s41467-024-48175-7
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    References listed on IDEAS

    as
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