F-Fluorination Using Tri--Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach.

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