Organic chemistry

Combinatorial chemistry

Pyridinium

Phosphine

Fluoride

Electrophile

Nucleophilic aromatic substitution

Substitution reaction

Catalysis

Lewis acids and bases

Nucleophilic substitution

Computational chemistry

Medicinal chemistry

Inorganic chemistry

Chemistry

Trifluoromethyl

Programming language

Substitution (logic)

Pyridine

Alkyl

Computer science

Phosphonium

Journal of the American Chemical Society

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.

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