<sup>18</sup>F-Difluoromethyl(ene) Motifs via Oxidative Fluorodecarboxylation with [<sup>18</sup>F]Fluoride
Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative <sup>18</sup>F-fluorodecarboxylation with [<sup>18</sup>F]fluoride affording biologically relevant <sup>18</sup>F-difluoromethyl(ene)-containing molecules. This no-carrier added process provides a solution to a known challenge in radiochemistry and expands the radiochemical space available for positron emission tomography (PET) ligand discovery. Scalability on a fully automated radiosynthetic platform is exemplified with the production of [<sup>18</sup>F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including <i>N</i>-heteroarylation and amide as well as sulfonamide bond formation.
Authors
- Joseph Ford (ORCID: https://orcid.org/0000-0001-7959-2085)
- Sebastiano Ortalli
- Véronique Gouverneur (ORCID: https://orcid.org/0000-0001-8638-5308)
- Andrés A. Trabanco (ORCID: https://orcid.org/0000-0002-4225-758X)
- Robert Szpera (ORCID: https://orcid.org/0000-0003-1351-1750)
- Matthew Tredwell (ORCID: https://orcid.org/0000-0002-4184-5611)
- Barbara Stoessel
Institutions
- University Hospital of Wales (GB)
- Oxford Research Group (GB)
- University of Oxford (GB)
- Cardiff University (GB)
Publication Details
- Journal
- Organic Letters
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1021/acs.orglett.4c03611
- Citations
- 7
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 1.46
Funders
- National Science Foundation
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Novartis
- Diamond Light Source
- University of Oxford
- Cardiff University
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Defence Science and Technology Laboratory
- Defence Science and Technology Group
- Cilag