Brandt Jochen R, Lee Eunsung, Boursalian Gregory B, Ritter Tobias
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Chem Sci. 2014 Jan 1;5(1). doi: 10.1039/C3SC52367E.
Electrophilic fluorinating reagents derived from fluoride are desirable for the synthesis of F-labeled molecules for positron emission tomography (PET). Here, we study the mechanism by which a Pd(IV)-complex captures fluoride and subsequently transfers it to nucleophiles. The intermediate Pd(IV)-F is formed with high rates even at the nano- to micromolar fluoride concentrations typical for radiosyntheses with F due to fast formation of an outer-sphere complex between fluoride and Pd(IV). The subsequent fluorine transfer from the Pd(IV)-F complex is proposed to proceed through an unusual SET/fluoride transfer/SET mechanism. The findings detailed in this manuscript provide a theoretical foundation suitable for addressing a more general approach for electrophilic fluorination with high specific activity F PET imaging.
源自氟化物的亲电氟化试剂对于正电子发射断层扫描（PET）中F标记分子的合成而言是理想的。在此，我们研究了一种Pd(IV)配合物捕获氟化物并随后将其转移至亲核试剂的机制。即使在使用F进行放射性合成时典型的纳摩尔至微摩尔氟化物浓度下，由于氟化物与Pd(IV)之间快速形成外层配合物，中间体Pd(IV)-F也能以高速率形成。随后从Pd(IV)-F配合物进行的氟转移被认为是通过一种不寻常的单电子转移/氟化物转移/单电子转移机制进行的。本手稿中详细阐述的研究结果为采用具有高比活度的F进行PET成像的亲电氟化更通用方法提供了理论基础。
