Synthesis of geminal difluorides by oxidative desulfurization- difluorination of alkyl aryl thioethers with halonium electrophiles in the presence of fluorinating reagents and its application for ~(18)F- radiolabeling

摘要

Figure presented. Various ω-substituted 1,1-difluoroalkanes are synthesized in good yields from alkyl aryl thioethers by a new oxidative desulfurization-difluorination protocol with the reagents combination of 1,3-dibromo-5,5-dimethylhydantoin (DBH) as an oxidizer and pyridine·9HF (Py·9HF) as a fluoride source. The reaction proceeds via a fluoro-Pummerer-type rearrangement followed by an oxidative desulfurization- fluorination step. Starting from α-fluorinated thioethers, this reaction is promising for ~(18)F-labeling (τ_(1/2) = 110 min) of ligands applicable for positron emission tomography (PET). Using the combination of DBH and carrier-added Py·9H[~(18)F]F, an ~(18)F- labeled difluoride was synthesized from the corresponding α-fluoro thioether with a radiochemical yield of 9%.