Abstract: 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 for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.
Reference: Sap, J. B.I.; Straathof, N. J. W.; Knauber, T.; Meyer; C. F.; Médebielle, M.; Buglioni, L.; Genicot, C.; Trabanco, A. A.; Noël, T.; Ende, C. W.; Gouverneur, V. J. Am. Chem. Soc. 2020