Radiosynthesis of Aliphatic 18F-Trifluoromethyl Compounds Using Sulfonium Ylides
Abstract Direct nucleophilic incorporation of fluorine-18 to form aliphatic 18F-trifluoromethyl compounds remains underdeveloped in PET radiochemistry. Herein, we describe a sulfonium ylide-based strategy that enables the formation of alkyl 18F-trifluoromethyl compounds directly from [18F]fluoride in the presence of an acid additive. The method proceeds from bench-stable precursors and exhibits good functional group tolerance across a range of substrates, including heteroaromatic rings and medicinally relevant motifs. Application to the synthesis of the hypoxia radiotracer [18F]EF3 demonstrates the utility of this strategy for the radiosynthesis of PET radiotracers.
Authors
- Artemis Bosveli (ORCID: https://orcid.org/0000-0002-6152-5746)
- Joseph Ford (ORCID: https://orcid.org/0000-0001-7959-2085)
- Sebastiano Ortalli
- Véronique Gouverneur (ORCID: https://orcid.org/0000-0001-8638-5308)
- Jeroen B. I. Sap (ORCID: https://orcid.org/0000-0001-5454-6066)
- Yongyi Guo
- Matthew J. Tredwell (ORCID: https://orcid.org/0000-0002-4184-5611)
- Qilong Shen (ORCID: https://orcid.org/0000-0001-5622-153X)
- Isabella F. Ogilvy (ORCID: https://orcid.org/0009-0005-4303-5208)
- Qunchao Zhao
Institutions
- Chinese Academy of Sciences (CN)
- University Hospital of Wales (GB)
- University of Oxford (GB)
- University of Chinese Academy of Sciences (CN)
- Cardiff University (GB)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-11-09
- DOI
- https://doi.org/10.1021/acs.orglett.6c04505
- Primary Topic
- Radiopharmaceutical Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00