Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

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 includi...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-05, Vol.142 (20), p.9181-9187
Main Authors: Sap, Jeroen B. I, Straathof, Natan J. W, Knauber, Thomas, Meyer, Claudio F, Médebielle, Maurice, Buglioni, Laura, Genicot, Christophe, Trabanco, Andrés A, Noël, Timothy, am Ende, Christopher W, Gouverneur, Véronique
Format: Article
Language:English
Subjects:
Chemical Sciences
Communication
Drug Discovery
Halogenation
Hydrocarbons, Fluorinated - chemical synthesis
Hydrocarbons, Fluorinated - chemistry
Molecular Structure
Oxidation-Reduction
Photochemical Processes
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.0c03881