Alcohol-Enhanced Cu-Mediated Radiofluorination

Abstract

The potential of many ¹⁸ F-labeled (hetero)aromatics for applications in positron emission tomography remains underexplored because convenient procedures for their radiosynthesis are lacking. Consequently, simple methods to prepare radiofluorinated (hetero)arenes are highly sought after. Herein, we report the beneficial effect of primary and secondary alcohols on Cu-mediated ¹⁸ F-labeling. This observation contradicts the assumption that such alcohols are inappropriate solvents for aromatic fluorination. Therefore, we developed a protocol for rapid radiolabeling of an extraordinarily broad scope of boronic and stannyl substrates under general reaction conditions. Notably, radiofluorinated indoles, phenols, and anilines were synthesized directly from the corresponding unprotected precursors. Furthermore, the novel method enabled the preparation of radiofluorinated tryptophans, [¹⁸ F]F-DPA, [¹⁸ F]DAA1106, 6-[¹⁸ F]FDA, and 6-[¹⁸ F]FDOPA.

Keywords: copper; fluorination; imaging agents; positron emission tomography; radiopharmaceuticals.