(18)F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach

The (18)F syntheses of tracers for positron emission tomography (PET) typically require several steps, including extraction of [(18)F]fluoride from H(2)[(18)O]O, elution, and drying, prior to nucleophilic substitution reaction, being a laborious and time-consuming process. The elution of [(18)F]fluoride is commonly achieved by phase transfer catalysts (PTC) in aqueous solution, which makes azeotropic drying indispensable. The ideal PTC is characterized by a slightly basic nature, its capacity to elute [(18)F]fluoride with anhydrous solvents, and its efficient complex formation with [(18)F]fluoride during subsequent labeling. Herein, we developed tri-(tert-butanol)-methylammonium iodide (TBMA-I), a quaternary ammonium salt serving as the PTC for (18)F-fluorination reactions. The favorable elution efficiency of [(18)F]fluoride using TBMA-I was demonstrated with aprotic and protic solvents, maintaining high (18)F-recoveries of 96–99%. (18)F-labeling reactions using TBMA-I as PTC were studied with aliphatic 1,3-ditosylpropane and aryl pinacol boronate esters as precursors, providing (18)F-labeled products in moderate-to-high radiochemical yields. TBMA-I revealed adequate properties for application to (18)F-fluorination reactions and could be used for elution of [(18)F]fluoride with MeOH, omitting an additional base and azeotropic drying prior to (18)F-labeling. We speculate that the tert-alcohol functionality of TBMA-I promotes intermolecular hydrogen bonding, which enhances the elution efficiency and stability of [(18)F]fluoride during nucleophilic (18)F-fluorination.