Radical alpha-Trifluoromethoxylation of Ketones by Means of Organic Photoredox Catalysis

    Thibaut Duhail[a]†, Tommaso Bortolato[b]†, Javier Mateos[b], Elsa Anselmi[a,c], Benson Jelier[d], Antonio Togni[d], Emmanuel Magnier[a], Guillaume Dagousset[a], Luca Dell’Amico[b]

    • [a] Université Paris-Saclay, UVSQ, CNRS, UMR 8180, Institut Lavoisier de Versailles, 78035 Versailles Cedex (France)
    • [b]Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131, Padova (Italy)
    • [c] Université de Tours, Faculté des Sciences et Techniques, 37200 Tours (France)
    • [d]Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir-Prelog-Weg 2, 8093 Zurich (Switzerland)

    The first light-driven method for the alpha-trifluoromethoxylation of ketones is reported. Enol carbonates, in particular Boc derivatives, react with N-trifluoromethoxy-4-cyano-pyridinium triflimide (2a) using the photoredox-catalyst 4-CzIPN (5 mol-%) under irradiation at 456 nm affording the corresponding α-trifluoromethoxy ketones in up to 50% isolated yield and virtually complete chemoselectivity. As shown by 35 examples, representing a great variety of substrates, the reaction is general and proceeds rapidly under batch (1h) and flow conditions (2 min). Mechanistic investigations reveal that a radical-chain propagation is operative, as efficiently orchestrated by the activity of the organic photoredox catalyst. Diverse products manipulations, including ketone reduction and reductive amination, demonstrate the synthetic potential of the disclosed method to accessing elusive trifluoromethoxylated potentially bioactive ingredients.

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