Electrochemical fluorodecarboxylation for the labelling of gem-difluoro(cyclo)alkanes/amines

正电子发射断层扫描(PET)是一种强大的分子成像手段，可用于诊断、监测疾病进展、研究体内生物过程和研究药物的疗效。在用于制备PET探针的放射性同位素中，氟-18是一种广泛使用和临床相关的放射性核素，部分原因是它具有良好的衰变特性，以及大量的临床应用。虽然放射化学家近年来致力于使18F标记的(杂环)芳烃氟化和三氟甲基化的方法，但18F标记的GEM-二氟化反应的研究要少得多，尽管GEM-二氟亚甲基(CF2)在药物发现计划的放射性配体设计中非常重要。在这里，我们提出了一种融合了电化学和18F放射化学的解决方案，并开发了一种新的电化学氟脱羧化过程，得到了18F标记的GEM-二氟(环)烷烃和(环)胺，包括结构复杂的药物。

Positron emission tomography (PET) is a powerful molecular imaging modality for diagnosis, monitoring disease progression, studying biological processes in vivo, and investigating the efficacy of drugs. Among the radioisotopes employed for the preparation of PET probes, fluorine-18 is a widely used and clinically relevant radionuclide in part due to its favourable decay properties, and the numerous clinical applications. While radiochemists have in recent years focused their efforts on methods enabling 18F-labelled fluorination and trifluoromethylation of (hetero)arenes, 18F-radiolabelled gem-difluorinated reactions have been much less studied despite the importance of the gem-difluoromethylene group (CF2) in radioligand design for drug discovery programmes. Herein, we propose a solution merging electrochemistry and 18F radiochemistry with the development of a novel electrochemical fluorodecarboxylation process affording 18F-labelled gem-difluoro(cyclo)alkanes and (cyclo)amines including structurally complex pharmaceutical drugs.