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Trifluoroethanol-assisted asymmetric propargylic hydrazination to α-tertiary ethynylhydrazines enabled by sterically confined pyridinebisoxazolines

Author

Listed:
  • Yi Gong

    (East China Normal University)

  • Zheng Zhang

    (East China Normal University)

  • Huijuan Liu

    (East China Normal University)

  • Tao Wang

    (East China Normal University)

  • Mengmeng Jiang

    (East China Normal University)

  • Nan Feng

    (East China Normal University)

  • Peiying Peng

    (East China Normal University)

  • Huimin Wang

    (East China Normal University)

  • Feng Zhou

    (East China Normal University)

  • Xin Wang

    (Sichuan University)

  • Jian Zhou

    (East China Normal University
    Shanghai Institute of Organic Chemistry
    Henan University)

Abstract

We report the highly enantioselective Cu-catalyzed asymmetric propargylic substitution (APS) of α-tertiary propargylic electrophiles using hydrazines and hydroxylamines as a fruitful strategy to access multifunctional α-tertiary hydrazines or hydroxylamines. Using trifluoroethanol (TFE) as the solvent play a key role to decrease the nucleophilicity of hydrazines to suppress side reactions such as elimination, thus improve the yield and the enantioselectivity. NMR analysis and theoretical calculations suggest the formation of an H-bond adduct of TFE with hydrazide, stabilized by multiple H-bonding interactions, including C–F···H–N interaction. The sterically confined pyridinebisoxzolines (PYBOX), featuring a bulky benzylthio shielding group also contribute to the excellent enantioselectivity. Aryl- and aliphatic-ketone-derived α-ethynylalcohol carbonates, α-tertiary α-ethynyl epoxides, cyclic carbonates and and α-hydroxycarboxylates all are competent substrates to afford α-tertiary α-ethynylhydrazines with high structural diversity. The obtained products can be readily converted into various α-tertiary hydrazines and azacycles featuring an aza-quaternary stereocenter.

Suggested Citation

  • Yi Gong & Zheng Zhang & Huijuan Liu & Tao Wang & Mengmeng Jiang & Nan Feng & Peiying Peng & Huimin Wang & Feng Zhou & Xin Wang & Jian Zhou, 2025. "Trifluoroethanol-assisted asymmetric propargylic hydrazination to α-tertiary ethynylhydrazines enabled by sterically confined pyridinebisoxazolines," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59845-5
    DOI: 10.1038/s41467-025-59845-5
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    References listed on IDEAS

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    1. Mingyang Wang & Shihan Liu & Hao Liu & Yujie Wang & Yu Lan & Qiang Liu, 2024. "Asymmetric hydrogenation of ketimines with minimally different alkyl groups," Nature, Nature, vol. 631(8021), pages 556-562, July.
    2. Ji-Jun Chen & Jia-Heng Fang & Xuan-Yi Du & Jia-Yong Zhang & Jun-Qian Bian & Fu-Li Wang & Cheng Luan & Wei-Long Liu & Ji-Ren Liu & Xiao-Yang Dong & Zhong-Liang Li & Qiang-Shuai Gu & Zhe Dong & Xin-Yuan, 2023. "Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines," Nature, Nature, vol. 618(7964), pages 294-300, June.
    3. Kyle W. Quasdorf & Larry E. Overman, 2014. "Catalytic enantioselective synthesis of quaternary carbon stereocentres," Nature, Nature, vol. 516(7530), pages 181-191, December.
    4. Caiyou Chen & Jonas C. Peters & Gregory C. Fu, 2021. "Photoinduced copper-catalysed asymmetric amidation via ligand cooperativity," Nature, Nature, vol. 596(7871), pages 250-256, August.
    5. Jonathan Clayden & Andrew Lund & Lluís Vallverdú & Madeleine Helliwell, 2004. "Ultra-remote stereocontrol by conformational communication of information along a carbon chain," Nature, Nature, vol. 431(7011), pages 966-971, October.
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