fluorotransfer

Fluorotransfer is a term used in organofluorine chemistry to describe reactions in which a fluorine atom or a fluorinated fragment is transferred from a donor reagent to a substrate. This encompasses both electrophilic fluorotransfer, in which a fluorine electrophile is delivered to a nucleophilic site, and nucleophilic fluorotransfer, in which a fluoride source provides F− to an electrophilic center or leaving group.

Electrophilic fluorotransfer often employs reagents such as Selectfluor (F-TEDA-BF4) and N-fluorobenzenesulfonimide derivatives (NFSI) to install C–F bonds on alkenes, arenes, or heteroatoms. Mechanisms may involve formation of cationic or radical intermediates that couple with the substrate.

Nucleophilic fluorotransfer uses fluoride donors including cesium fluoride (CsF) or tetrabutylammonium fluoride (TBAF) in combination with activators or catalysts, enabling substitution of leaving groups (such as sulfonates or halides) or direct SN2 fluorination to form alkyl or aryl fluorides.

Specialized difluoromethylation and difluoromethyl transfer reagents also contribute to the fluorotransfer repertoire, delivering CHF2 groups to substrates, though these are often categorized separately as difluoromethylation.

Fluorotransfer is valuable for pharmaceutical development, agrochemistry, and radiolabeling with fluorine-18 for positron emission tomography (PET). Challenges include achieving selectivity among multiple reactive sites, controlling over-fluorination, handling reactive reagents, and ensuring compatibility with sensitive functional groups.

See also: fluorination, organofluorine chemistry, radiolabeling with fluorine-18.