Synthesis of ¹⁸F-Labeled Aryl Fluorosulfates via Nucleophilic Radiofluorination

Abstract

Sulfuryl fluoride gas is a key reagent for SO₂F transfer. However, conventional SO₂F transfer reactions have limited ¹⁸F-radiochemistry translation, due to the inaccessibility of gaseous [¹⁸F]SO₂F₂. Herein, we report the first SO₂F₂-free synthesis of aryl [¹⁸F]fluorosulfates from both phenolic and isolated aryl imidazylate precursors with cyclotron-produced ¹⁸F^-. The radiochemical yields ranged from moderate to good with excellent functional group tolerance. The reliability of our approach was validated by the automated radiosynthesis of 4-acetamidophenyl [¹⁸F]fluorosulfate.