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Fluoroform upcycling to trifluorovinylamine as a C2 reagent to prepare difluoromethylated molecules

Nature Synthesis (2026)Cite this article

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Abstract

The valorization of fluorinated waste for the synthesis of value-added non-per- and polyfluoroalkyl substances (PFASs) presents a substantial challenge. Fluoroform (HFC-23), an extremely potent waste greenhouse gas produced in multi-tonne quantities, has traditionally been incinerated or utilized as a C1 building block. Here we report the application of fluoroform to the synthesis of trifluorovinylamine, an original C2 building block. Trifluorovinylamine exhibits unique reactivity and functions as a difluoroacylium surrogate. This distinctive reactivity facilitates the efficient formation of α,α-difluoromethyl ketones via electrophilic aromatic substitution and enables the development of a hydrodifluoroacetylation reaction. This class of reagent not only introduces alternative chemical reactivity but also offers an innovative pathway for the valorization of HFC-23, advancing the synthesis of non-PFAS compounds.

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Fig. 1: Strategy for the synthesis of TFVA from HFC-23 and its synthetic utility.
Fig. 2: Method to access TFVA molecules and evaluation of their reactivity.
Fig. 3: Reactivity of TFVA as an α,α-difluoroacylium equivalent.
Fig. 4: Scope of the process—reaction with alkenes and alkynes.

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The data that support the findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

J.D., T.P. and P.J. acknowledge Normandy Valorisation (FLUORO project) for funding. J.D., I.M. and T.P. acknowledge the RIN ZIRCO_PHOTO_COP programme (Normandy Region, ERDF/FSE 2021–2027, no. 21E05645) for funding. I.M. and T.P. acknowledge the PHOTODERACS programme (Normandy Region, no. 0015464) for funding. P.I., T.P. and P.J. acknowledge the RIN CYLIA programme (Normandy Region ERDF/FSE 2021–2027, no. 22E02979) for funding. We acknowledge the API programme and NFC (NormandyFlowChem platform) supported by the European Union through the operational programme (Normandy Region, ERDF/FSE 2014–2020, no. 20E04976) and FNADT-DRACCARE (programme 2020–2023 (N)15179) for funding. Normandie Université (NU), Région Normandie, CNRS, Université Rouen Normandie, INSA Rouen Normandie, Labex SynOrg (ANR-11-LABX0029), the graduate school for research XL–Chem (ANR-18-EURE-0020 XL CHEM) and Innovation Chimie Carnot (I2C) are acknowledged for support.

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  1. These authors contributed equally: Pavel Ivashkin, Jonathan Decaens.

Authors and Affiliations

  1. INSA Rouen Normandie, Université Rouen Normandie, CNRS, Normandie Université, Institut CARMeN, UMR 6064, INC3M FR, Rouen, France

    Pavel Ivashkin, Jonathan Decaens, Isabelle Marchand, Matthieu Hedouin, Hassan Oulyadi, Thomas Poisson & Philippe Jubault

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  1. Pavel Ivashkin
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Contributions

P.I., J.D., T.P. and P.J. conceived the project. P.I., J.D. and I.M. performed the synthetic work. M.H. performed the NMR spectroscopy studies under the supervision of H.O. Funding was secured by T.P. and P.J. who also supervised the research and wrote the paper with contributions from all authors.

Corresponding authors

Correspondence to Thomas Poisson or Philippe Jubault.

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Competing interests

P.I., J.D., T.P. and P.J. are inventors on an international patent application PCT 2024/051749, held by INSA Rouen Normandie, Université Rouen Normandie and CNRS and submitted by Normandie Valorisation, which covers the synthesis of the TFVA reagents and their reactivity. The other authors declare no competing interests.

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Ivashkin, P., Decaens, J., Marchand, I. et al. Fluoroform upcycling to trifluorovinylamine as a C2 reagent to prepare difluoromethylated molecules. Nat. Synth (2026). https://doi.org/10.1038/s44160-026-01001-y

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