Selective syntheses of no-carrier-added 2- and 3-[18F]fluorohalopyridines through the radiofluorination of halopyridinyl(4′-methoxyphenyl)iodonium tosylates

Chun, Jongsuk; Pike, Victor W.

doi:10.1039/c2cc35005j

Cited by 30 publications

(22 citation statements)

References 25 publications

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“…The preparation of [ 18 F]fluoroarenes from the reactions of [ 18 F]fluoride ion with diaryliodonium salts (Scheme 1) [9,10] is finding increasing application for preparing labeling synthons [11–13] and PET radiotracers [14–17]. This radiofluorination method, unlike aromatic nucleophilic substitution ( S N Ar) in non-hypervalent substrates, allows NCA [ 18 F]fluoride ion to be introduced readily into electron-deficient or electron-rich rings, irrespective of ring substituent positions [9,10,18,19].…”

Section: Introductionmentioning

confidence: 99%

Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

Chun

Telu

et al. 2013

Org. Biomol. Chem.

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Positron emission tomography (PET) has growing importance as a molecular imaging technique for clinical research and drug development. Methods for producing PET radiotracers utilizing cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min) without the need for complete removal of irradiated target [18O]water and addition of cryptand are keenly sought for practical convenience and efficiency. Several structurally diverse diaryliodonium tosylates, XArI+Ar′Y TsO− (X = H or p-MeO), were investigated in a microfluidic apparatus for their reactivity towards radiofluorination with high specific activity (no-carrier-added) [18F]fluoride ion in mixtures of DMF and irradiated target [18O]water in the absence of cryptand. Salts bearing a para or ortho electron-withdrawing group Y (e.g., Y = p-CN) reacted rapidly (~ 3 min) to give the expected major [18F]fluoroarene product, [18F]ArY, in useful moderate radiochemical yields even when the solvent had [18O]water content up to 28%. Salts bearing electron-withdrawing groups in meta position (e.g., Y = m-NO2), or an electron-donating substituent (Y = p-OMe), gave low radiochemical yields under the same conditions.

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Section: Introductionmentioning

confidence: 99%

Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

Chun

Telu

et al. 2013

Org. Biomol. Chem.

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“…We have also previously observed resistance to aryl halogen displacement by S N Ar when in well-activated positions in (halopyridinyl)aryliodonium salts during their radio-fluorinations to produce [ 18 F]fluorohalopyridines. 15 We tested if this resistance might also occur in the homoaryl diaryliodonium salt ( 15 ), which bears a bromo substituent in a position that is well-activated for S N Ar by a p -keto group. Remarkably, [ 18 F]4-bromo-4′-fluorobenzophenone ([ 18 F] 30 ) was obtained in excellent yield (98%) from 15 (Table 3, entry 6; see ESI † for radio-HPLC chromatogram).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we have reported the use of diaryliodonium salts for the radiosyntheses of aryl and heteroaryl labeling synthons, such as [ 18 F]fluorohalopyridines 15 and [ 18 F]azidomethyl-fluoro-arenes. 16 Herein, we extend the use of diaryliodonium salts for single-step radiosyntheses of various other functionalized 18 F-labeling synthons.…”

Section: Introductionmentioning

confidence: 99%

Single-step syntheses of no-carrier-added functionalized [18F]fluoroarenes as labeling synthons from diaryliodonium salts

Chun

Pike

2013

Org. Biomol. Chem.

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Radiotracers labelled with short-lived fluorine-18 (t1/2 = 109.7 min) are keenly sought for biomedical imaging with positron emission tomography (PET). The radiotracers are mostly required at high specific radioactivities, necessitating their radiosyntheses from cyclotron-produced no-carrier-added [18F]fluoride ion. PET radiotracers encompass wide structural diversity and molecular weight. Hence, diverse 18F-labeling methodology is needed to accomplish the required radiosyntheses in a simple and rapid manner. A useful strategy is to introduce nucleophilic [18F]fluoride ion first into a labeling synthon that may then be applied to label the target radiotracer. Here, we show that various functionalized [18F]fluoroarenes may be rapidly synthesized as labeling synthons through single-step reactions of appropriate diaryliodonium salts with [18F]fluoride ion. Decay-corrected radiochemical yields (RCYs) varied with position of functional group, choice of electron-rich aryl ring in the diaryliodonium salt, and choice of anion. Under best conditions, 18F-labeled fluorobenzaldehydes, fluorobenzyl halides, fluorobenzoic acid esters and fluoro-phenyl ketones were obtained selectively in 40–73%, 20–55%, 46–89% and 81–98% RCYs, respectively. This versatile straightforward methodology will enhance the scope for producing structurally complex, yet useful, PET radiotracers.

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“…[2–5] These compounds arylate a multitude of organic and inorganic nucleophiles to provide functionalized arenes in excellent yields. In particular, the use of diaryliodonium salts as precursors to radiopharmaceuticals is an area of increasingly active research; [6] Sanford and Scott, [7] Pike, [8] Coenen, [9] DiMagno, [10] and other groups [11] have all demonstrated successful conversion of diaryliodonium salt precursors into 18 F-labeled compounds for PET imaging.…”

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A Mild and General One‐Pot Synthesis of Densely Functionalized Diaryliodonium Salts

Qin

Neumann

et al. 2015

Eur J Org Chem

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Diaryliodonium salts are powerful and widely used arylating agents in organic chemistry. Here we report a scalable, synthesis of densely functionalized diaryliodonium salts from aryl iodides under mild conditions. This two-step, one-pot process has remarkable functional group tolerance, is compatible with commonly employed acid-labile protective group strategies, avoids heavy metal and transition metal reagents, and provides a direct route to stable precursors to PET imaging agents.

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Selective syntheses of no-carrier-added 2- and 3-[18F]fluorohalopyridines through the radiofluorination of halopyridinyl(4′-methoxyphenyl)iodonium tosylates

Cited by 30 publications

References 25 publications

Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

Single-step syntheses of no-carrier-added functionalized [18F]fluoroarenes as labeling synthons from diaryliodonium salts

A Mild and General One‐Pot Synthesis of Densely Functionalized Diaryliodonium Salts

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