RT Journal Article
SR Electronic
T1 Radiofluorination of Electron-Rich Arenes via LED-Promoted Photoredox Reactions
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1458
OP 1458
VO 62
IS supplement 1
A1 Li Wang
A1 Wei Chen
A1 Zhanhong Wu
A1 David Nicewicz
A1 Zibo Li
YR 2021
UL http://jnm.snmjournals.org/content/62/supplement_1/1458.abstract
AB 1458Background: Fluorine-18 (18F) is one of the most widely used positron emission tomography (PET) isotopes. Significant effort has been devoted to developing robust methods to introduce 18F into organic pharmaceuticals to generate corresponding PET agents.Traditionally, fluorinations of electron-deficient aromatic arenes were generally performed via nucleophilic aromatic substitution, but the rates of nucleofuge extrusion diminish on the introduction of electron-rich groups. In this study, we explore the use of LED light to initiate radiofluorination of electron-rich arenes. Methods: Previously, we have established a program studying radiofluorination catalyzed by organic photooxidation catalysts under mild reaction conditions using an expensive laser setup. Inspired by flow chemistry and microfluidic design, we constructed a microtubing reactor that greatly increased the surface area exposed to the light source. Both light wavelength and terminal oxidants were evaluated. The optimized conditions were used to radiofluorinate electron-rich and neutral arenes through direct C-H fluorination and SNAr reactions. Results: Radiofluorination of electron-rich arenes were found to be efficiently carried out using 425 nm LED lights in the presence of 5% photocatalyst (with respect to substrate). Compared with the laser promoted reaction, the use of this LED microtubing reactor resulted in improved labeling yields on 11 of the substrates and comparable or decreased yields on 10 of the substrates for C-H radiofluorination. To better control the position of radiofluorination, SnAr reactions were also tested and 18F-labeled amino acids were isolated in 50% yield. Conclusion: An efficient and user-friendly photoredox system have been developed for arene radiofluorination, which may enable the general use of this methodology for the synthesis of 18F-labeled PET agents.