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.
Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Scheme 3. Scaled-up synthesis of building blocks that are highly valuable for medicinal chemistry.Scheme 4. Mechanistic considerations. Yields were determined by 19 FNMR spectroscopy using trifluorotoluene as internalstandard. Yields of isolated products are shown in parentheses. dr = diastereomeric ratio, nd = not detected.
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