Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery.
Sap JBI., Straathof NJW., Knauber T., Meyer CF., Médebielle M., Buglioni L., Genicot C., Trabanco AA., Noël T., Am Ende CW., Gouverneur V.
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.