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Enantioselective acyl-trifluoromethylation of olefins by bulky thiazolium carbene catalysis

Author

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  • Sripati Jana

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Matthew D. Wodrich

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Nicolai Cramer

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

Abstract

Enantioenriched α-chiral β-fluorinated ketones are valuable structural motifs with application in several fields. The recently emerged concept of NHC-catalyzed radical acyl-trifluoromethylation of olefins offers a rapid route to construct racemic β-fluorinated ketones in a single step. Due to the lack of competent chiral NHC catalysts constructing these molecules in an enantioselective manner remains an unmet challenge. Herein, we report a family of chiral thiazolium carbenes having bulky chiral flanking groups and offering three distinct positions with broad steric and electronic tunability. The catalysts display so far unmatched enantioselectivities for acyl-trifluoromethylations of simple unactivated olefins with a wide variety of aldehydes and Togni’s reagent. The method provides a variety of enantioenriched β-trifluoromethylated α-chiral ketones in high yields and excellent enantioselectivities up to 98:2 er. A potential applicability of this methodology is demonstrated through enantio- and diastereoselective late-stage functionalizations of pharmaceutical compounds.

Suggested Citation

  • Sripati Jana & Matthew D. Wodrich & Nicolai Cramer, 2025. "Enantioselective acyl-trifluoromethylation of olefins by bulky thiazolium carbene catalysis," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58423-z
    DOI: 10.1038/s41467-025-58423-z
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    References listed on IDEAS

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    1. Yuki Matsuki & Nagisa Ohnishi & Yuki Kakeno & Shunsuke Takemoto & Takuya Ishii & Kazunori Nagao & Hirohisa Ohmiya, 2021. "Aryl radical-mediated N-heterocyclic carbene catalysis," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    2. Yi-Xuan Cao & Matthew D. Wodrich & Nicolai Cramer, 2023. "Nickel-catalyzed direct stereoselective α-allylation of ketones with non-conjugated dienes," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    3. Yuanyuan Xu & Hongwei Chen & Lu Yu & Xichao Peng & Jiawei Zhang & Zhongqiu Xing & Yuyan Bao & Aokun Liu & Yue Zhao & Changlin Tian & Yong Liang & Xiaoqiang Huang, 2024. "A light-driven enzymatic enantioselective radical acylation," Nature, Nature, vol. 625(7993), pages 74-78, January.
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