Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups

Single
fluoride substitution in trifluoromethylarenes is an ongoing
synthetic challenge that often leads to “over-reaction”,
where multiple fluorides are replaced. Development of this reaction
would allow simple access to a vast range of difluoromethyl derivatives
of current interest to pharmaceutical, agrochemistry, and materials
sciences. Using a catalytic frustrated Lewis pair approach, we have
developed a generic protocol that allows a single substitution of
one fluoride in trifluoromethyl groups with neutral phosphine and
pyridine bases. The resulting phosphonium and pyridinium salts can
be further functionalized via nucleophilic substitution, photoredox
coupling, and electrophilic transfer reactions allowing the generation
of a vast array of difluoromethyl products.