Trifluoromethylation of Aromatic Isoxazoles: Regio- and Diastereoselective Route to 5-Trifluoromethyl-2-isoxazolines

Authors

  • Hiroyuki Kawai,

    1. Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555 (Japan)
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  • Kentaro Tachi,

    1. Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555 (Japan)
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  • Etsuko Tokunaga,

    1. Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555 (Japan)
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  • Dr. Motoo Shiro,

    1. Rigaku Corporation, 3-9-12 Mastubara-cho, Akishima, Tokyo 196-8666 (Japan)
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  • Prof. Norio Shibata

    Corresponding author
    1. Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555 (Japan)
    • Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555 (Japan)
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  • This study was financially supported in part by Kakenhi (21390030, 22106515). We also thank TOSOH F-TECH INC. for a gift of Me3SiCF3.

Abstract

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It all adds up: The activation of aromatic isoxazoles with a nitro group at the 4-position has enabled the first regio- and diastereoselective trifluoromethylation at the 5-position of isoxazoles by nucleophilic addition using Me3SiCF3 (see scheme; DMF=N,N′-dimethylformamide). The process was demonstrated with a broad range of 3,5-aromatic, heteroaromatic and aliphatic substrates.

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