Electrochemical radiofluorination. 3. Direct labeling of phenylalanine derivatives with [18F]fluoride after anodic oxidation

Abstract

SummaryAs an example of applying the electrochemical method in radiofluorination a new procedure was developed for preparing [ Best results were obtained for N-trifluoroacetylphenylalanine methyl ester (1) (10.5 AE 2.5%) with a relative isomeric distribution of 50.5 AE 1.5% ortho isomer, 11.5 AE 1.5% meta isomer and 38.8 AE 2.1% para isomer. Optimized reaction conditions were with Et 3 N Á 3HF as supporting electrolyte and temperatures between 0 and -108C. By variation of working potential (1.5-2.0 V) and chloride concentration (added as supporting electrolyte, 0.0-0.36 M) it was demonstrated that an indirect electrolysis as reaction mechanism or a halogen exchange (halex) reaction with primary formation of a chlorinated product followed by halogen exchange are highly improbable.

Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate

“…Table 1 shows that the radiofluorination efficiency was nearly doubled by lowering the T from 25 °C to 0 °C. The above results are consistent with those reported in the literature (Kienzle et al, 2005). Additionally, we investigated the effect of the supporting electrolyte by adding NBu 4 PF 6 instead of NBu 4 ClO 4 .…”

“…Among the methods to generate an electron-poor carbon in arenes (Ermert et al, 2004; Gao et al, 2012; Nozaki and Tanaka, 1967; Shiue et al, 1984), electrochemical anodic oxidation is technically elegant because the reactions can be carried out under mild conditions and there is no hazardous chemical oxidant required (Fuchigami and Inagi, 2011). Radiofluorination of complex molecules by electrochemistry has been done under galvanostatic conditions by Reischl et al in their series publications (Kienzle et al, 2005; Reischl et al, 2002, 2003). Different from the umpolung strategy (Gao et al, 2012), the oxidation effect can be precisely controlled by the applied potential on the working electrode.…”

An automated synthesizer for electrochemical 18F-fluorination of organic compounds

“…Recently we and others have reported on the electrochemical 18 F-fluorination of aromatic compounds (Reischl et al, 2002; Reischl et al, 2003; Kienzle et al, 2005). The concept was exemplified by the synthesis of di- tert -butyl-(4-[ 18 F]fluoro-1,2-phenylene)-dicarbonate ( 1 ) – a model compound for synthesis of [ 18 F]F-DOPA (Fig.…”

Metal‐Free Oxidative Fluorination of Phenols with [18F]Fluoride

“…[11,12] Based on these principles, [ 18 F]fluorophenol could be accessed directly from phenol in the presence of a [ 18 F]fluoride source upon oxidative fluorination/dearomatization, followed by rearomatization (Scheme 2). [17] Herein, we report the successful validation of the proposed aryl umpolung radiolabelling strategy with a new method to access no-carrier-added (NCA) [ 18 F]4fluorophenol from [ 18 F]fluoride and 4-tert-butylphenol, a commercially available precursor. [13] Mechanistically, a hypovalent phenyloxenium ion is more often proposed as the key intermediate captured with fluoride.…”

“…[16] Based on these precedents, we were poised to examine the potential of metal-free oxidative fluorination in the context of 18 F radiochemistry. [17] Herein, we report the successful validation of the proposed aryl umpolung radiolabelling strategy with a new method to access no-carrier-added (NCA) [ 18 F]4fluorophenol from [ 18 F]fluoride and 4-tert-butylphenol, a commercially available precursor. The strategy, which is easy to implement, is extended to variously substituted phenol derivatives.…”