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Review of 'Direct Nucleophilic Difluoromethylation of Aromatic Isoxazoles Activated by Electron-Withdrawing Groups Using (Difluoromethyl)trimethylsilane'

An extension of previous work
Average rating:
    Rated 4 of 5.
Level of importance:
    Rated 3 of 5.
Level of validity:
    Rated 4 of 5.
Level of completeness:
    Rated 4 of 5.
Level of comprehensibility:
    Rated 4 of 5.
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Reviewed article

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Direct Nucleophilic Difluoromethylation of Aromatic Isoxazoles Activated by Electron-Withdrawing Groups Using (Difluoromethyl)trimethylsilane

The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups, such as the nitro, triflyl and the phenylsulfonyl groups, at the 4-position has enabled the first regio- and diastereoselective difluoromethylation at the 5-position of isoxazoles by nucleophilic addition using (difluoromethyl)trimethylsilane, Me3SiCF2H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles were also nicely converted into the corresponding CF2H adducts with high regio- and excellent diastereoselectivities. Since the trifluoromethylated analogues of the corresponding diaryl-isoxazolines are effective ectoparasiticides, represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained, they would be of great importance as promising drug candidates in this field.

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    Review text

    The authors reported a new method for the preparation of 5-difluoromethyl-2-isoxazoline derivatives through direct nucleophilic difluoromethylation of aromatic isoxazoles activated by electron-withdrawing groups using TMSCF2H. Although this is an extension of their previous work and the yields of difluoromethylated products are moderate, the manuscript still can be published in ScienceOpen because of the difficulty in nucleophilic difluormethylation of aromatic isoxazoles. In addition, the resulting new 5-difluoromethyl-2-isoxazoline derivatives may have potential applications in agrochemicals. If the authors could stereoselectively synthesize compounds 2 and 4, it will improve the quality of the manuscript.


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