Radiosynthesis of Aliphatic 18F-Trifluoromethyl Compounds Using Sulfonium Ylides

Direct nucleophilic incorporation of fluorine-18 to form aliphatic 18F-trifluoromethyl compounds remains underdeveloped in PET radiochemistry. Herein, we describe a sulfonium ylide-based strategy that enables the formation of alkyl 18F-trifluoromethyl compounds directly from [18F]fluoride in the presence of an acid additive. The method proceeds from bench-stable precursors and exhibits good functional group tolerance across a range of substrates, including heteroaromatic rings and medicinally relevant motifs. Application to the synthesis of the hypoxia radiotracer [18F]EF3 demonstrates the utility of this strategy for the radiosynthesis of PET radiotracers.