title: Alcohol-Enhanced Cu-Mediated Radiofluorination.
abstract: The potential of many18F-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-mediated18F-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, [18F]F-DPA, [18F]DAA1106, 6-[18F]FDA, and 6-[18F]FDOPA.
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany.|Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, Kerpener Str. 62, 50937, Cologne, Germany.|Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Johannes
authors.identifier: http://orcid.org/0000-0003-3996-7473
authors.initials: J
authors.lastname: Zischler
authors.affiliation: Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Kolks
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Modemann
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany.|Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, Kerpener Str. 62, 50937, Cologne, Germany.|Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Bernd
authors.identifier: http://orcid.org/0000-0001-5425-3116
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, Kerpener Str. 62, 50937, Cologne, Germany.|Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931, Cologne, Germany.
authors.forename: Boris D
authors.initials: BD
authors.lastname: Zlatopolskiy
keywords: copper; fluorination; imaging agents; positron emission tomography; radiopharmaceuticals