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Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides

Author

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  • Jiawen Wang

    (ShanghaiTech University)

  • Faqian He

    (ShanghaiTech University)

  • Xiaoyu Yang

    (ShanghaiTech University)

Abstract

Acyclic quaternary stereocenters are widely present in a series of biologically active natural products and pharmaceuticals. However, development of highly efficient asymmetric catalytic methods for the construction of these privileged motifs represents a longstanding challenge in organic synthesis. Herein, an efficient chiral phosphoric acid catalyzed direct asymmetric addition of α-alkynyl acyclic ketones with allenamides has been developed, furnishing the acyclic all-carbon quaternary stereocenters with excellent regioselectivities and high enantioselectivities. Extensive and detailed experimental mechanistic studies were performed to investigate the mechanism of this reaction. Despite a novel covalent allyl phosphate intermediate was found in these reactions, further studies indicated that a SN2-type mechanism with the ketone nucleophiles is not very possible. Instead, a more plausible mechanism involving the elimination of the allyl phosphate to give the α,β-unsaturated iminium intermediate, which underwent the asymmetric conjugate addition with the enol form of ketone nucleophiles under chiral anion catalysis, was proposed. In virtue of the fruitful functional groups bearing in the chiral products, the diverse derivatizations of the chiral products provided access to a wide array of chiral scaffolds with quaternary stereocenters.

Suggested Citation

  • Jiawen Wang & Faqian He & Xiaoyu Yang, 2021. "Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27028-7
    DOI: 10.1038/s41467-021-27028-7
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    References listed on IDEAS

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    1. Jiawen Wang & Sujuan Zheng & Subramani Rajkumar & Jinglei Xie & Na Yu & Qian Peng & Xiaoyu Yang, 2020. "Chiral phosphoric acid-catalyzed stereodivergent synthesis of trisubstituted allenes and computational mechanistic studies," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Kyle W. Quasdorf & Larry E. Overman, 2014. "Catalytic enantioselective synthesis of quaternary carbon stereocentres," Nature, Nature, vol. 516(7530), pages 181-191, December.
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    Cited by:

    1. Po-Kai Peng & Andrew Isho & Jeremy A. May, 2024. "Regio- and enantioselective synthesis of acyclic quaternary carbons via organocatalytic addition of organoborates to (Z)-Enediketones," Nature Communications, Nature, vol. 15(1), pages 1-9, December.

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