Ortalli Sebastiano, Ford Joseph, Szpera Robert, Stoessel Barbara, Trabanco Andrés A, Tredwell Matthew, Gouverneur Véronique
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Global Discovery Chemistry, Therapeutics Discovery, Johnson & Johnson Innovative Medicine, Janssen-Cilag, S.A., E-45007 Toledo, Spain.
Org Lett. 2024 Nov 1;26(43):9368-9372. doi: 10.1021/acs.orglett.4c03611. Epub 2024 Oct 23.
Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative F-fluorodecarboxylation with [F]fluoride affording biologically relevant 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 [F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including -heteroarylation and amide as well as sulfonamide bond formation.
在此，我们报告α-氟代羧酸在锰介导下与[F]氟化物发生氧化F-氟脱羧反应，生成具有生物学相关性的含F-二氟甲基（烯）分子。这种无载体添加过程为放射化学中一个已知的挑战提供了解决方案，并扩展了可用于正电子发射断层扫描（PET）配体发现的放射化学空间。在全自动化放射合成平台上的可扩展性通过[F]4,4-二氟哌啶的生产得到例证，我们证明，它适合进行后标记官能化，包括-杂芳基化、酰胺以及磺酰胺键的形成。
