Synthesis of [¹⁸F]Fluoroarenes by Nucleophilic Radiofluorination of N‐Arylsydnones

Abstract

Apractical method for radiofluorination of anilines with [ 18 F]fluoride via N-arylsydnone intermediates is described. These precursors are stable,e asy to handle and facilitate direct and regioselective 18 F-labeling to prepare [ 18 F]fluoroarenes.T he value of this methodology is further highlighted by successful application to prepare an 18 F-labeled neuropeptide.

18F-Fluorination: Challenge and Opportunity for Organic Chemists

“…In 2017, the Murphy group developed the first method to radiofluorinate anilines by converting them into N -arylsydnones, followed by nucleophilic attack by [ 18 F]fluoride ( Scheme 11 ). 62 The transformation is operationally simple and can be automated but can only be used for arenes bearing electron-withdrawing groups.…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…[116] It was found that the sydnone was not only inductively more electron withdrawing than the nitro group,b ut was also positioned away from the aryl plane and limited full resonance with the arene.T his makes the sydnone aw eak anion stabilizer and an excellent activating group for 18 Fincorporation. [116] It was found that the sydnone was not only inductively more electron withdrawing than the nitro group,b ut was also positioned away from the aryl plane and limited full resonance with the arene.T his makes the sydnone aw eak anion stabilizer and an excellent activating group for 18 Fincorporation.…”

Development, Optimization, and Scope of the Radiosynthesis of 3/5-[18F]Fluoropyridines from Readily Prepared Aryl(pyridinyl) Iodonium Salts: The Importance of TEMPO and K2CO3

“…A dozen 3/5-[ 18 F]fluoropyridines functionalized with electron donating or withdrawing substituents were thus obtained in 6− 78% isolated yields. The 13 C, 19 F, and 11 B NMR spectra were recorded on a Bruker Avance 400 or 500 MHz spectrometer. Samples were dissolved in an appropriate deuterated solvent (CDCl 3 , MeOD, or DMSO-d 6 ).…”

“…More recently, N-5-(2-cyanopyridinyl)sydnone was successfully converted to the corresponding 2-cyano-5-[ 18 F]fluoropyridine under harsh temperature conditions (150 °C) but no additional examples were reported. 13 The copper mediated radiofluorination of a pyridinylboronate ester precursor was attempted for the preparation of 2-chloro-5-[ 18 F]fluoropyridine, but yields did not exceed 10%. 14 The 18 F-deoxyfluorination approach via a concerted nucleophilic aromatic substitution (CS N Ar) was only reported from 3-hydroxypyridines bearing an electronwithdrawing group at an appropriate position.…”