Abstract:

The unnatural isotope fluorine–18 (18F) is used as a positron emitter in molecular imaging. Currently, many potentially useful 18F-labeled probe molecules are inaccessible for imaging, because no fluorination chemistry is available to make them. Syntheses must be rapid on account of the 110-minute half-life of 18F and benefit from using [18F]fluoride due to practical access and suitable isotope enrichment. But [18F]fluoride chemistry has been limited to nucleophilic fluorination reactions. I will describe the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic 18F-labeled molecules via late-stage fluorination. In addition, I will discuss new reaction chemistry for introduction of fluorine into functionalized molecules. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as pre-clinical and clinical PET imaging.