Evaluation of tetraethylammonium bicarbonate as a phase-transfer agent in the formation of [18F]fluoroarenes

Reed, Christopher; Launay, Guillaume G.; Carroll, Michael A.

doi:10.1016/j.jfluchem.2012.07.015

Cited by 17 publications

(10 citation statements)

References 47 publications

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“…These reactions were typically carried out under 'open-flask' conditions (Supplementary Methods) and in all cases afforded crystalline products. Among many commonly-used radiolabelling conditions, a simple combination of dried [ 18 F]fluoride with tetraethylammonium bicarbonate (TEAB 27 ) and spirocyclic iodine precursor in DMF was deemed to be optimal (Supplementary Table 1). The use of 2,2,6,6-tetramethyl-1-piperidinyloxy and butylated hydroxytoluene, as radical scavengers, offered no improvement of radiolabelling efficiency.…”

Section: Resultsmentioning

confidence: 99%

Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics

et al. 2014

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Fluorine-18 (t ½ ¼ 109.7 min) is the most commonly used isotope to prepare radiopharmaceuticals for molecular imaging by positron emission tomography (PET). Nucleophilic aromatic substitution reactions of suitably activated (electron-deficient) aromatic substrates with no-carrier-added [ 18 F]fluoride ion are routinely carried out in the synthesis of radiotracers in high specific activities. Despite extensive efforts to develop a general 18 F-labelling technique for non-activated arenes there is an urgent and unmet need to achieve this goal. Here we describe an effective solution that relies on the chemistry of spirocyclic hypervalent iodine(III) complexes, which serve as precursors for rapid, one-step regioselective radiofluorination with [ 18 F]fluoride. This methodology proves to be efficient for radiolabelling a diverse range of non-activated functionalized arenes and heteroarenes, including arene substrates bearing electron-donating groups, bulky ortho functionalities, benzylic substituents and meta-substituted electron-withdrawing groups. Polyfunctional molecules and a range of previously elusive 18 F-labelled building blocks, compounds and radiopharmaceuticals are synthesized.

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Section: Resultsmentioning

confidence: 99%

Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics

et al. 2014

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“…The aryl ring selectivity of the process can be controlled by choosing a relatively electron-rich ring as one of the ring partners so that radiofluorination occurs preferentially at the other ring. [20–24] Often the selected electron-rich ring is 2-thienyl [19–23] or 4 methoxyphenyl [19]. Alkyl substituents in ortho position tend to direct radiofluorination onto the same ring [18], and the addition of a radical scavenger ( e.g., TEMPO) improves some radiofluorination reactions.…”

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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“…This yield well exceeds that recently reported for the synthesis of ethyl [ 18 F]fluorobenzoate through the radiofluorination of (4-(ethoxy-carbonyl)phenyl)(2-thienyl)iodonium trifluoroacetate, under various conditions, including the use of tetraethylammonium bicarbonate as a phase transfer agent. 27 The t -butyl and ethyl ester analogs of [ 18 F] 26 have themselves been prepared through S N Ar on non-hypervalent substrates and used to prepare [ 18 F]SFB, but in three-stage radiosyntheses. 28 We note that a single-step radiosynthesis of [ 18 F]SFB from a diaryliodonium salt appears feasible with a reported non-optimized yield of up to 26%.…”

Section: Resultsmentioning

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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Evaluation of tetraethylammonium bicarbonate as a phase-transfer agent in the formation of [18F]fluoroarenes

Cited by 17 publications

References 47 publications

Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics

Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics

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

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