18F-Labeled Aryl-Tracers through Direct Introduction of [18F]fluoride into Electron-Rich Arenes

Rapid and efficient methods using no-carried-added [¹⁸F]fluoride as the source of fluorine-18 for nucleophilic aromatic fluorination play an important role in the development of new radiopharmaceuticals for positron emission tomography (PET). Molecules that bear electron-rich aromatic moieties are especially difficult to label by direct single-step nucleophilic no-carrier-added radiofluorination. Classical Balz-Schiemann reaction with its modifications, Wallach reaction and diaryliodonium salts methodology are a few methods to enable this. The present review provides a critical overview of these chemical methods with the emphasis on diaryliodonium salt as precursors for the direct introduction of [¹⁸F]fluoride into electron-rich arenes in synthesis of ¹⁸F-labeled molecules for PET scanning.