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Rapid Trifluoromethylation and Perfluoroalkylation of Five-Membered Heterocycles by Photoredox Catalysis in Continuous Flow

Authors

  • Natan J. W. Straathof,

    1. Department of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven (The Netherlands)
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  • Hannes P. L. Gemoets,

    1. Department of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven (The Netherlands)
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  • Dr. Xiao Wang,

    1. Harvard NeuroDiscovery Center, Harvard Medical School and Brigham & Women's Hospital, 65 Landsdowne Street, Cambridge, MA 02139 (USA)
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  • Prof. Dr. Jaap C. Schouten,

    1. Department of Chemical Engineering and Chemistry, Chemical Reactor Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven (The Netherlands)
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  • Prof. Dr. Volker Hessel,

    1. Department of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven (The Netherlands)
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  • Dr. Timothy Noël

    Corresponding author
    1. Department of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven (The Netherlands)
    2. Ghent University, Department of Organic Chemistry, Krijgslaan 281 (S4), 9000 Ghent (Belgium)
    • Department of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven (The Netherlands)===

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Abstract

Trifluoromethylated and perfluoroalkylated heterocycles are important building blocks for the synthesis of numerous pharmaceutical products, agrochemicals and are widely applied in material sciences. To date, trifluoromethylated and perfluoroalkylated hetero-aromatic systems can be prepared utilizing visible light photoredox catalysis methodologies in batch. While several limitations are associated with these batch protocols, the application of microflow technology could greatly enhance and intensify these reactions. A simple and straightforward photocatalytic trifluoromethylation and perfluoroalkylation method has been developed in continuous microflow, using commercially available photocatalysts and microflow components. A selection of five-membered hetero-aromatics were successfully trifluoromethylated (12 examples) and perfluoroalkylated (5 examples) within several minutes (8–20 min).

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