Expedient Access to 18 F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts.

Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [ ¹⁸ F]fluoride. The value of this new ¹⁸ F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl ¹⁸ F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.
(© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)