18F-Labelling of (Hetero)aryl Halides via Sequential Miyaura Borylation/Copper-Mediated Radiofluorination

Abstract

This Article describes the development of a mild, general, and highly reproducible method for the radiofluorination of (hetero)aryl iodide, bromide, and chloride substrates. This transformation proceeds via sequential Pd-catalysed Miyaura borylation with B₂Pin₂ followed by in situ Cu-mediated radiofluorination of the (hetero)aryl-BPin intermediate with K¹⁸F. Successful implementation of this method required identifying and replacing/removing components of the borylation reaction that impede the radiofluorination step. This method is applied to electronically and sterically diverse (hetero)aryl halides and enables the synthesis of ¹⁸F-labelled analogues of bioactive molecules such as indomethacin, dimethomorph, and metaxalone. In addition, this sequence is effective for the radiofluorination of a variety of amino acids and peptides.