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1 article(s) from Liu, Feng

Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

Wenyan Yao,
Huanhuan Zhang,
Xiaolong Yang and
Feng Liu

Beilstein J. Org. Chem. 2026, 22, 1122–1150, doi:10.3762/bjoc.22.91

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Graphical Abstract

Figure 1: FDA-approved drugs containing CF₂ groups (2016–2025). a) For tezacaftor (4), the 2018 approval year...

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Figure 2: Synthesis of the alkyl–CF₂ side chain in glecaprevir (1) and voxilaprevir (2).

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Figure 3: Synthesis of the difluorinated intermediate 38 for ivosidenib (3).

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Figure 4: Synthesis of the difluorinated intermediate for cedazuridine (5).

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Figure 5: Synthesis of the difluorinated intermediate for omaveloxolone (10).

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Figure 6: Synthesis of the difluorinated intermediate for 1-(perfluorohexyl)octane (11).

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Figure 7: Synthetic routes towards difluorinated intermediates for the synthesis of inavolisib.

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Figure 8: Synthesis of the difluorinated intermediate for glecaprevir.

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Figure 9: Synthesis of the difluorinated intermediate for voxilaprevir.

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Figure 10: Synthesis of the difluorinated intermediate for lenacapavir.

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Figure 11: Synthesis of the difluorinated intermediate for oteseconazole.

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Figure 12: Synthesis of the difluorinated intermediate for tezacaftor.

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Figure 13: Synthesis of the difluorinated intermediate for difamilas (6).

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Figure 14: Synthesis of the difluorinated intermediate for asciminib.

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Figure 15: Mechanism of the deoxyfluorination of carbonyl groups using DAST.

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Figure 16: Mechanism of the deoxyfluorination of carbonyl groups using SF₄.

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Figure 17: Mechanism of the fluorination of dithioketals using Olah’s reagent.

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Figure 18: Mechanism of the fluorination of xanthates using AgF.

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Figure 19: Mechanism of electrophilic fluorination using NFSI.

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Figure 20: Mechanism of the Ni-catalyzed conversion of Ar–X to Ar–CF₂H using Hu’s reagent.

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Figure 21: Mechanism of the (Me₃Si)₃SiH-mediated intermolecular perfluoroalkylation of alkenes in water.

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Figure 22: Mechanism of the formation of ArO–CF₂H from ClF₂COONa and ArOH.

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Figure 23: Mechanism of the formation of ArO–CF₂X from TMSCF₂X and ArOH.

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Review

Published 04 Aug 2026

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Construction of CF2 moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations