One-Step Synthesis of [¹⁸F]Aromatic Electrophile Prosthetic Groups via Organic Photoredox Catalysis

To avoid the harsh conditions that are oftentimes adopted in direct radiofluorination reactions, conjugation of bioactive ligands with ¹⁸F-labeled prosthetic groups has become an important strategy to construct novel PET agents under mild conditions when the ligands are structurally sensitive. Prosthetic groups with [¹⁸F]fluoroarene motifs are especially appealing because of their stability in physiological environments. However, their preparation can be intricate, often requiring multistep radiosynthesis with functional group conversions to prevent the decomposition of unprotected reactive prosthetic groups during the harsh radiofluorination. Here, we report a general and simple method to generate a variety of highly reactive ¹⁸F-labeled electrophiles via one-step organophotoredox-mediated radiofluorination. The method benefits from high step-economy, reaction efficiency, functional group tolerance, and easily accessible precursors. The obtained prosthetic groups have been successfully applied in PET agent construction and subsequent imaging studies, thereby demonstrating the feasibility of this synthetic method in promoting imaging and biomedical research.