Fluoridation of 2‐thienyliodonium salts

Carroll, Michael A.; Jones, C.J.C.; Tang, Shu-Ling

doi:10.1002/jlcr.1189

Cited by 20 publications

(20 citation statements)

References 7 publications

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“…In all cases significant amounts of the 4-iodoanisole are generated during the thermal decomposition reactions of 4, even when 2-functionalized thiophenes are not observed. These data support Carroll's assessment [32] and the original observations by Yamada and Okawara [33] that the directing group ability of the 2-thienyl and 4-methoxyphenyl substituents are similar.Though the data in Table 1 are limited, it appears that for oxygen or sulphur nucleophiles the directing group ability of the cyclophane ligand diminishes as nucleophile basicity and the driving force for functionalizing the more electron-poor ring increase. Such a trend is consistent with Hammond's postulate and a concerted, reductive elimination mechanism in which less steric strain is developed at the cyclophane ipso carbon atom as the reaction becomes more exergonic.…”

supporting

confidence: 86%

Regiospecific Reductive Elimination from Diaryliodonium Salts

et al. 2010

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StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) is provided by the cyclophane substituent on iodine(III).Computational and experimental studies demonstrate that out of plane steric bulk strongly destabilizes the reductive elimination transition state, and leads to regiochemical control. This approach should be general for high valent main group and transition metal ions.Keywords reductive elimination; stereoelectronic effects; regiochemistry; iodanes; cyclophanes Diaryliodonium salts are useful precursors for arylation of diverse carbon and heteroatom nucleophiles. [1][2][3][4] In practice, poor regioselectivity for reductive elimination narrows the synthetic scope of diaryliodonium salts (Scheme 1). Efficient conversion is best obtained when two identical aryl substituents are on I(III), however, the preparation of symmetrical diaryliodonium salts can be problematic and uneconomical. [11] For relatively complex aromatic molecules, the tandem synthesis and protection of the oxidized (I(III)) and reduced (organometallic) coupling partners necessary to prepare the symmetrical diaryliodonium salt is often a significant challenge, and purification of the functionalized product from the reductively eliminated aryl iodide can prove difficult.In the thermal decomposition of unsymmetrical diaryliodonium salts, the identity of the aryl iodide reductively eliminated is typically dictated by electronic effects; the electron-rich aryl iodide and the functionalized electron-poor aromatic compound are formed predominantly (Scheme 1). Selectively functionalized electron-rich aromatic rings are often the desired target compounds, but extremely electron-rich diaryliodonium salts are prone to side reactions involving redox and inner-sphere electron transfer, thus there is a limit to using electronic control to achieve regioselectivity.We sought a universal "locked" aryl substituent that would result in StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) from diaryliodonium salts. Since electronic effects cannot be used exclusively to achieve this end, steric and/or stereoelectronic effects must be exploited to gain regiocontrol of reductive elimination. Here we show that the use of cyclophane-derived iodonium salts permits regiospecific reductive elimination (Scheme 2).The impact of steric effects upon reductive elimination in diaryliodonium salts has been investigated in some detail. Aryl methyl substituents ortho to the I(III) center offer a modest acceleration in elimination rates, so that there is a slight preference for the more highly substituted product to be functionalized (Scheme 1). [7,12] "ortho effect" are: 1) the more sterically demanding aromatic ring prefers an equatorial position syn to the nucleophile, and 2) the ortho-substituted aromatic is more likely to prefer a conformation in which the p-system is more likely to align with the incoming nucleophile. [13][14][15] In an exception to this rule, Ochiai and coworkers have shown that for binaphthyl aryl iod...

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confidence: 86%

Regiospecific Reductive Elimination from Diaryliodonium Salts

et al. 2010

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“…As shown in Fig. 2a, the extent of such stabilization should still enable the formation of 18 F-labelled products via the addition/reductive elimination mechanism 16,24 that has been invoked for diaryliodonium salts and other I(III) species [15][16][17]20,25,26 . Initial experiments (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, 18 F-incorporation into the relatively electron-deficient (activated) arene is accompanied by production of undesired radioactive byproducts arising from the electron-rich aryl auxiliary. 17,20 Although diaryliodonium salts represent the most investigated class of hypervalent iodine(III) compounds in PET, there is scant patent literature 21 on how one might achieve the desired regiospecific radiofluorination based on the use of aryliodonium ylides (ArI ¼ CX 2 ; X¼ electron-deficient substituent) as precursors with Meldrum's acid auxiliaries.…”

mentioning

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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“…[47][48][49][50][51][52] To this end, we searched for methods to iodinate palonosetron (1). Direct iodination of non-activated aromatic rings is far less common than the corresponding chlorination or bromination.…”

Section: Synthesis Of 5-ht3 Receptor Ligands and Precursors For Radiomentioning

confidence: 99%

Synthesis and Pharmacological Evaluation of [¹¹C]Granisetron and [¹⁸F]Fluoropalonosetron as PET Probes for 5-HT₃ Receptor Imaging

Herde

Rüefli

et al. 2016

ACS Chem. Neurosci.

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Serotonin-gated ionotropic 5-HT3 receptors are the major pharmacological targets for antiemetic compounds. Furthermore, they have become a focus for the treatment of irritable bowel syndrome (IBS) and there is some evidence that pharmacological modulation of 5-HT3 receptors might alleviate symptoms of other neurological disorders. Highly selective, high-affinity antagonists, such as granisetron (Kytril®) and palonosetron (Aloxi®), belong to a family of drugs (the 'setrons') that are well established for clinical use. To enable us to better understand the actions of these drugs in vivo, we report the synthesis of 8-fluoropalonosetron (15)

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Fluoridation of 2‐thienyliodonium salts

Cited by 20 publications

References 7 publications

Regiospecific Reductive Elimination from Diaryliodonium Salts

Regiospecific Reductive Elimination from Diaryliodonium Salts

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

Synthesis and Pharmacological Evaluation of [¹¹C]Granisetron and [¹⁸F]Fluoropalonosetron as PET Probes for 5-HT₃ Receptor Imaging

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Fluoridation of 2‐thienyliodonium salts

Cited by 20 publications

References 7 publications

Regiospecific Reductive Elimination from Diaryliodonium Salts

Regiospecific Reductive Elimination from Diaryliodonium Salts

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

Synthesis and Pharmacological Evaluation of [11C]Granisetron and [18F]Fluoropalonosetron as PET Probes for 5-HT3 Receptor Imaging

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Synthesis and Pharmacological Evaluation of [¹¹C]Granisetron and [¹⁸F]Fluoropalonosetron as PET Probes for 5-HT₃ Receptor Imaging