3857-04-3

Upstream product

• 768-32-1 trimethylphenylsilane 
• 791-29-7 methyltriphenylsilane 
• 934-56-5 trimethyl(phenyl)stannane 
• 90467-12-2 tert-butyldimethylphenylsilane 
• 6293-66-9 diphenyliodonium p-toluenesulfonate 
• 144930-55-2 (4-iodophenyl)(phenyl)iodonium trifluoromethanesulfonate 
• 144930-53-0 (4-bromophenyl)(phenyl)iodonium triflate 
• 115298-63-0 phenyl(4-methoxyphenyl)iodonium triflate 
• 2665-62-5 phenyl(2-thienyl)iodonium bromide 
• 103185-00-8 1-bromo-4-[¹⁸F]fluorobenzene 
• 74-88-4 methyl iodide 
• 27126-77-8 (4-methoxyphenyl)phenyliodonium p-toluenesulfonate 
• 1483-72-3 diphenyliodonium chloride 
• 59907-05-0 (2-methylphenyl)(phenyl)iodonium iodide 

Relevant academic research and scientific papers

Optimization and synthesis of an 18F-labeled dopamine D3 receptor ligand using [18F]fluorophenylazocarboxylic tert-butylester

There is still no efficient fluorine-18-labeled dopamine D3 subtype selective receptor ligand for studies with positron emission tomography. We aim at improving the D3 selectivity and hydrophilicity of a candidate ligand by changing the substitution pattern to a 2,3-dichlorophenylpiperazine and hydroxylation of the butyl chain. The compound [18F]3 exhibited D3 affinity of Ki = 3.6 nM, increased subtype selectivity (Ki(D2/D3) = 60), and low affinity to 5-HT1A and α1 receptors (Ki (5-HT1A/D3) = 34; Ki (α1/D3) = 100). The two-step radiosynthesis was optimized for analog [18F]4 by reducing the necessary concentration of the precursor amine (57 mM), which reacted with [18F]fluorophenylazocarboxylic tert-butylester under basic conditions. The optimization of the base (Cs 2CO3, 23 mM) and the adjustment of reaction temperature led to the radiochemical yield of 63% after 5 min at 35C. The optimized reaction conditions were transferred on to the synthesis of [18F]3 with an overall non-decay corrected yield of 8-12% in a specific activity of 32-102 GBq/μmol after a total synthesis time of 30-35 min. This provides a D 3 radioligand candidate with improved attributes concerning selectivity and radiosynthesis for further preclinical studies.

Exploration of alcohol-enhanced Cu-mediated radiofluorination toward practical labeling

Copper-mediated nucleophilic radiofluorination using boronic precursors is a promising, general method to label aromatic compounds with [18F]fluoride. However, in various reports, large amounts of precursor (60 μmol) were needed to achieve high

Chemoselective Radiosyntheses of Electron-Rich [18F]Fluoroarenes from Aryl(2,4,6-trimethoxyphenyl)iodonium Tosylates

Hypervalent diaryliodonium salts have been used to produce various [18F]fluoroarenes. The iodonium salt approach as a labeling precursor has been established to equally afford complex 18F-fluorinated molecules. Because of the inheren

Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic 18F-Fluorination

Herein, we report a novel intramolecular ring-closing reaction of biaryl thioethers that give access to highly functionalized dibenzothiophene sulfonium salts under mild conditions. The resulting precursors react regioselectively with [18F]fluo

Crystal Structures of Diaryliodonium Fluorides and Their Implications for Fluorination Mechanisms

The radiofluorination of diaryliodonium salts is of value for producing radiotracers for positron emission tomography. We report crystal structures for two diaryliodonium fluorides. Whereas diphenyliodonium fluoride (1 a) exists as a tetramer bridged by four fluoride ions, 2-methylphenyl(phenyl)iodonium fluoride (2 a) forms a fluoride-bridged dimer that is further halogen bonded to two other monomers. We discuss the topological relationships between the two and their implications for fluorination in solution. Both radiofluorination and NMR spectroscopy show that thermolysis of 2 a gives 2-fluorotoluene and fluorobenzene in a 2 to 1 ratio that is in good agreement with the ratio observed from the radiofluorination of 2-methylphenyl(phenyl)iodonium chloride (2 b). The constancy of the product ratio affirms that the fluorinations occur via the same two rapidly interconverting transition states whose energy difference dictates chemoselectivity. From quantum chemical studies with density functional theory we attribute the “ortho-effect” to the favorable electrostatic interaction between the incoming fluoride and the o-methyl in the transition state. By utilizing the crystal structures of 1 a and 2 a, the mechanisms of fluoroarene formation from diaryliodonium fluorides in their monomeric, homodimeric, heterodimeric, and tetrameric states were also investigated. We propose that oligomerization energy dictates whether the fluorination occurs through a monomeric or an oligomeric pathway.

Alcohol-Enhanced Cu-Mediated Radiofluorination

The potential of many 18F-labeled (hetero)aromatics for applications in positron emission tomography remains underexplored because convenient procedures for their radiosynthesis are lacking. Consequently, simple methods to prepare radiofluorinated (hetero)arenes are highly sought after. Herein, we report the beneficial effect of primary and secondary alcohols on Cu-mediated 18F-labeling. This observation contradicts the assumption that such alcohols are inappropriate solvents for aromatic fluorination. Therefore, we developed a protocol for rapid radiolabeling of an extraordinarily broad scope of boronic and stannyl substrates under general reaction conditions. Notably, radiofluorinated indoles, phenols, and anilines were synthesized directly from the corresponding unprotected precursors. Furthermore, the novel method enabled the preparation of radiofluorinated tryptophans, [18F]F-DPA, [18F]DAA1106, 6-[18F]FDA, and 6-[18F]FDOPA.

A practical method for the preparation of 18F-labeled aromatic amino acids from nucleophilic [18F]fluoride and stannyl precursors for electrophilic radiohalogenation

In a recent contribution of Scott et al., the substrate scope of Cu-mediated nucleophilic radiofluorination with [18F]KF for the preparation of 18F-labeled arenes was extended to aryland vinylstannanes. Based on these findings, the potential of this reaction for the production of clinically relevant positron emission tomography (PET) tracers was investigated. To this end, Cu-mediated radiofluorodestannylation using trimethyl(phenyl)tin as a model substrate was re-evaluated with respect to different reaction parameters. The resulting labeling protocol was applied for 18F-fluorination of different electron-rich, -neutral and -poor arylstannyl substrates in RCCs of 16-88%. Furthermore, this method was utilized for the synthesis of 18F-labeled aromatic amino acids from additionally N-Boc protected commercially available stannyl precursors routinely applied for electrophilic radiohalogenation. Finally, an automated synthesis of 6-[18F]fluoro-L-m-tyrosine (6-[18F]FMT), 2-[18F]fluoro-L-tyrosine (2-[18F]F-Tyr), 6-[18F]fluoro-L-3, 4-dihydroxyphenylalanine (6-[18F]FDOPA) and 3-O-methyl-6-[18F]FDOPA ([18F]OMFD) was established furnishing these PET probes in isolated radiochemical yields (RCYs) of 32-54% on a preparative scale. Remarkably, the automated radiosynthesis of 6-[18F]FDOPA afforded an exceptionally high RCY of 54 5% (n = 5).

An Investigation of (Diacetoxyiodo)arenes as Precursors for Preparing No-Carrier-Added [18F]Fluoroarenes from Cyclotron-Produced [18F]Fluoride Ion

Treatment of (diacetoxyiodo)arenes (1a-1u) with cyclotron-produced [18F]fluoride ion rapidly affords no-carrier-added [18F]fluoroarenes (2a-2u) in useful yields and constitutes a new method for converting substituted iodoarenes into substituted [18F]fluoroarenes in just two steps.

METAL OXIDE CATALYZED RADIOFLUORINATION

Inter alia, the first titania-catalyzed [18F]-radiofluorination in highly aqueous medium is provided. In embodiments, the method utilizes titanium dioxide, 1 : 1 acetonitrile- thexyl alcohol solvent mixture and tetrabutylammonium bicarbonate as a base. Radiolabeling may be directly performed with aqueous [18F]fluoride without the need for drying/azeotroping step, which reduces radiosynthesis time while keeping high fluoride conversion. The general applicability of the synthetic strategy to the synthesis of the wide range of PET probes from tosylated precursors is demonstrated.

Solid-Supported Iodonium Salts for Fluorinations

Solid-supported iodonium salt precursors have been prepared and used for the production of fluoroarenes. The importance of the resin functionality for the attachment of the iodonium salt moieties has been demonstrated. Furthermore, the production of new i