Abstract
Molecules labelled with the unnatural isotope fluorine-18 are used for positron emission tomography. Currently, this molecular imaging technology is not exploited at its full potential because many 18F-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with 18F radiochemistry are the short half-life of 18F (<2 h), the use of sub-stoichiometric amounts of 18F, relative to the precursor and other reagents, as well as the limited availability of parent 18F sources of suitable reactivity ([18F]F– and [18F]F2). There is a high-priority demand for general methods allowing access to [18F]CF3-substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [18F]trifluoromethylation of (hetero)arenes from [18F]fluoride using commercially available reagents and (hetero)aryl iodides. This [18F]CuCF3–based protocol benefits from a large substrate scope and is characterized by its operational simplicity.
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Acknowledgements
Financial support was provided by Imanova, GlaxoSmithKline, the European Union (grant PIIF-GA-20100274903 to S.M.), the Engineering and Physical Sciences Research Council (M.T.) and the Cancer Research UK (M.T.). The authors thank P. Holdship (Department of Earth Sciences, University of Oxford) for the ICP-MS measurements. V.G. is a recipient of a Royal Society Wolfson Research Merit Award.
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M.H., M.T. and S.M. performed and analysed experiments. All authors contributed to the design of experiments to develop this reaction and probe its utility. V.G. and J.P. prepared the manuscript.
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Huiban, M., Tredwell, M., Mizuta, S. et al. A broadly applicable [18F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging. Nature Chem 5, 941–944 (2013). https://doi.org/10.1038/nchem.1756
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DOI: https://doi.org/10.1038/nchem.1756
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