Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

• DOI: 10.1021/jacs.0c03881
• Publication Date: 2020-05-07T21:14:36Z
• Authors: Jeroen B. I. Sap; Natan J. W. Straa...; Thomas Knauber; Claudio F. Meyer; Maurice Médebielle; Laura Buglioni; Christophe Genicot; Andrés A. Trabanco; Timothy Noël; Christopher W. am...; Véronique Gouverneur
• Keywords: Hydrogen atom; Fluorine; Catalytic cycle

Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol the replacement of fluorine with hydrogen electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates range functional groups heterocycles commonly found bioactive Preliminary studies allude to catalytic cycle whereby excited state organophotocatalyst reductively quenched by donor, returned its original oxidation trifluoromethylarene.