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. 2026 Feb 20;28(7):2421-2426.
doi: 10.1021/acs.orglett.6c00078. Epub 2026 Feb 9.

Friedel-Crafts-Type Electrophilic Radiocyanation of (Hetero)arenes

Casey J McCarthy  1   2 , Marius Müller  2   3   4 , Richard Ma  1 , Umberto Maria Battisti  3 , Jay S Wright  2 , E William Webb  2 , Melanie S Sanford  5 , Matthias M Herth  3   4 , Peter J H Scott  1   2   6
Affiliations

Friedel-Crafts-Type Electrophilic Radiocyanation of (Hetero)arenes

Casey J McCarthy et al. Org Lett. .

Abstract

Radiocyanation is an attractive approach to introduce carbon-11 into radiopharmaceuticals, as nitriles and other acyl moieties. This report describes a Friedel-Crafts-type electrophilic radiocyanation of (hetero)aryltrimethylgermanes and trimethylstannanes as well as a direct C-H radiocyanation of (hetero)arenes. This approach leverages the in situ oxidation of [11C]CN- to [11C]CNCl to enable electrophilic aromatic substitution pathways for accessing relevant 11C-aryl nitrile scaffolds. This method proceeds in short reaction times with readily available, shelf-stable reagents and enables radiocyanation of diverse substrates in good radiochemical yields.

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Conflict of interest statement

The authors claim no competing financial interest.

Figures

Scheme 1:
Scheme 1:. 11C-Cyanation Methods
A. Prior work, nucleophilic aryl 11C-cyanation. B. This work, in-situ [11C]CN− oxidation for electrophilic radiocyanations.
Scheme 2:
Scheme 2:. Cu-Mediated 11C-Cyanation of Organogermaniums
Attempted Cu-mediated 11C-cyanation of aryl germanes and germatranes; details in Supplementary Information. aradiochemical conversion by radio-HPLC.
Scheme 3:
Scheme 3:. Comparison of Aryl Nucleophiles
Conditions: 1-2 mCi [11C]KCN, 25 μmol precursor, 63 μmol AlCl3, 0.3 μmol NCS, 120 °C, 5 min. RCCs (n = 3) were determined by radio-HPLC.
Scheme 4:
Scheme 4:. Mechanistic Experiments
A. General Friedel-Crafts mechanism for cyanation of arenes from [11C]CNCl. B. Alternative pathway for electrophilic cyanation from [11C]N-cyanosuccinimide. C. Reaction probing: 1-2 mCi [11C]KCN was oxidized with 0.3 μmol oxidant and radiochemical species were profiled by rHPLC and rTLC.
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References

    1. Rong J; Haider A; Jeppesen TE; Josephson L; Liang SH Radiochemistry for Positron Emission Tomography. Nat. Commun 2023, 14 (1), 3257. 10.1038/s41467-023-36377-4. - DOI - PMC - PubMed
    1. Schwenck J; Sonanini D; Cotton JM; Rammensee H-G; la Fougère C; Zender L; Pichler BJ Advances in PET Imaging of Cancer. Nat. Rev. Cancer 2023, 23 (7), 474–490. 10.1038/s41568-023-00576-4. - DOI - PubMed
    1. Kristensen JL; Herth MM Textbook of Drug Design and Discovery: In Vivo Imaging in Drug Discovery. In Textbook of Drug Design and Discovery; CRC Press, 2017.
    1. Antoni G The Radiopharmaceutical Chemistry of Carbon-11: Basic Principles. In Radiopharmaceutical Chemistry; Lewis JS, Windhorst AD, Zeglis BM, Eds.; Springer International Publishing: Cham, 2019; pp 207–220. 10.1007/978-3-319-98947-1_11. - DOI
    1. Pees A; Chassé M; Lindberg A; Vasdev N Recent Developments in Carbon-11 Chemistry and Applications for First-In-Human PET Studies. Molecules 2023, 28 (3), 931. 10.3390/molecules28030931. - DOI - PMC - PubMed

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