[18F]CuCF3: A [18F]Trifluoromethylating Agent for Arylboronic Acids and Aryl Iodides

Ivashkin, Pavel; Lemonnier, Gérald; Cousin, Jonathan; Grégoire, Vincent; Labar, Daniel; Jubault, Philippe; Pannecoucke, Xavier

doi:10.1002/chem.201403630

Cited by 67 publications

(53 citation statements)

References 34 publications

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“…A reaction mechanism has been proposed by Ivashkin et al, involving the formation of difluorocarbene and subsequent release of both [ 19 F]fluorine atoms . As a consequence, the molar activity of the [ 18 F]trifluoromethylated compounds was low (0.1–1 GBq/µmol at end of synthesis (EOS)) for almost all reported procedures , . Previous work published by our group demonstrated acceptable molar activities by (i) reducing the amount of precursor and thereby reducing the amount of fluorine‐19 in the [ 18 F]fluoroform formation reaction, (ii) reducing the amount of base and cryptand 10‐fold compared to standard elution conditions and (iii) increasing the starting amount of [ 18 F]fluoride.…”

Section: Introductionmentioning

confidence: 90%

“…Most likely, [ 19 F]fluoride from the precursor is released in the presence of trace amounts of water and excess of base originating from the drying of [ 18 F]fluoride. A reaction mechanism has been proposed by Ivashkin et al, involving the formation of difluorocarbene and subsequent release of both [ 19 F]fluorine atoms . As a consequence, the molar activity of the [ 18 F]trifluoromethylated compounds was low (0.1–1 GBq/µmol at end of synthesis (EOS)) for almost all reported procedures , .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of [¹⁸F]Fluoroform with High Molar Activity

et al. 2020

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Fluoroform is an interesting motif for the isotopologue labelling of biologically active compounds with fluorine‐18 for PET imaging. However, so far the building block [18F]fluoroform and consequently the [18F]trifluoromethylated products suffered from low molar activities ranging from 0.1 to 30 GBq/µmol due to isotopic dilution under the strongly basic standard radiofluorination conditions. In this article the synthesis of high molar activity [18F]fluoroform is described. By implementing a recently reported novel radiofluorination reagent, [18F]triflyl fluoride, the concentration of base‐cryptand complex in the reaction could be reduced 100‐fold compared to standard radiofluorination conditions and molar activities close to 100 GBq/µmol (at end of [18F]fluoroform synthesis) could be obtained, enabling the imaging of low density receptors. Furthermore, an automated procedure was developed on the commercially available NEPTIS® perform synthesizer to provide access of high molar activity [18F]fluoroform to other PET centres.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Synthesis of [¹⁸F]Fluoroform with High Molar Activity

et al. 2020

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“…The most extensive work to date on multi‐fluorinated 18 F‐labeled molecules has been directed at the synthesis of 18 F‐trifluoromethyl groups: Gouverneur and co‐workers have established a practical method based on [ 18 F]CuCF 3 species, with a large substrate scope . A year later, three other groups independently reported different methods to prepare [ 18 F]CuCF 3 , which was also explored for the [ 18 F]trifluoromethylation of aryl boronic acids –. Groves and co‐workers have reported a direct C−H to C− 18 F transformation based on Mn‐salen‐catalyzed benzylic fluorination with [ 18 F]fluoride, which was also extended to 18 F‐trifluoromethylarenes .…”

Section: Methodsmentioning

confidence: 99%

Synthesis of ¹⁸F‐Difluoromethylarenes from Aryl (Pseudo) Halides

et al. 2016

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We report a general method for syntheses of [ 18 F]CHF 2 -arenes from [ 18 F]fluoride for radiopharmaceutical discovery. The method is practical, operationally simple, tolerates a wide scope of functional groups, enables labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay corrected) from 10% to 60%. The 18 F-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides and triflates, respectively. Seven 18 F-difluoromethylarene drug analogs and radiopharmaceuticals including claritin, fluoxetine (prozac), and [ 18 F]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design. Keywords18 F-difluoromethylarene; aryl (pseudo) halides; fluorine-18; positron emission tomography; radiopharmaceuticals Fluorine-18 ( 18 F) is the most commonly used radionuclide for molecular imaging by positron emission tomography (PET). 1 Over the past five years, several modern fluorination reactions have been developed with 18 F, many of which are achieved with high specific activity (SA) [ 18 F]fluoride. 2 Development of modern 18 F-multi-fluoromethylation reactions, for example to incorporate 18 F into trifluoromethyl groups, are now also addressed, due to the prospects of having more labeled chemotypes available for imaging. 3 A challenge in the preparation of 18 F-labeled compounds that contain more than one fluorine atom, especially when located on the same carbon atom, is the probability of isotope exchange that can substantially lower the specific activity. Here we describe a general method for difluoromethyl [ 18 F]CHF 2 -arenes from [ 18 F]fluoride. The method is practical and general over a wide variety of arenes and heteroarenes. On a fundamental level, the crucial but unusual C-F bond formation occurs by nucleophilic substitution on a fully substituted carbon.The most extensive work to date on multi-fluorinated 18 F-labeled molecules has been directed at the synthesis of 18 Gouverneur's group improved the substrate scope of Ag I -mediated halogen-exchange; but the CHFCl-arene starting materials still require several synthetic steps for preparation. 3m To date, no method has been reported for the 18 F-labeling of difluoromethylarenes with high specific activity. Here, we describe progress toward the goal of high-specific-activity difluoromethylation in a practical and general reaction.To overcome the challenge of C-F bond formation to achieve 18 To demonstrate the potential utility of the 18 F-labeling procedure, we examined a variety of well-known biologically active molecule analogues, including fenofibrate (cholesterol scavenger), fluoxetine (selective serotonin reuptake inhibitor), DAA-1106 (translocator protein 18 kDa radiotracer), SC-58125 (COX 2 inhibitor) and analepticon (respiratory stimulant). The labeling method was selective on a claritin derivative, which possesses five benzylic C-H bonds and four allylic C-H bonds. To achieve 18 F-labeling of tertiary amines, a stepwise method was developed, wi...

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“…[165] Et 3 N·3 HF was added to stabilize [ 18 F]CuCF 3 , [166] and this method could increase the molar activity of 18 Flabeled products to 25 GBq mmol À1 . [168] Scheme 29. [167] By using adifluoromethyl sulfonium salt as ad ifluorocarbene regent, Jubault, Labar,a nd co-workers developed an alternative method to generate [ 18 F]HCF 3 (Scheme 30 B2), which was used for the formation of [ 18 F]CuCF 3 and the subsequent 18 F-trifluoromethylation in high RCY (78-88 %).…”

Section: F-labeled Aryl-cf 3 Groups By Transition-metal-mediated Cmentioning

confidence: 99%

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

et al. 2019

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Positron emission tomography (PET) is a molecular imaging technology that provides quantitative information about function and metabolism in biological processes in vivo for disease diagnosis and therapy assessment. The broad application and rapid advances of PET has led to an increased demand for new radiochemical methods to synthesize highly specific molecules bearing positron-emitting radionuclides. This article provides an overview of commonly-used labeling chemistry in the examples of clinically relevant PET tracers, and highlights most recent development and breakthroughs over the past decade with focus on 11C, 18F, 13N, and 15O.

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[¹⁸F]CuCF₃: A [¹⁸F]Trifluoromethylating Agent for Arylboronic Acids and Aryl Iodides

Cited by 67 publications

References 34 publications

Synthesis of [¹⁸F]Fluoroform with High Molar Activity

Synthesis of [¹⁸F]Fluoroform with High Molar Activity

Synthesis of ¹⁸F‐Difluoromethylarenes from Aryl (Pseudo) Halides

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

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[18F]CuCF3: A [18F]Trifluoromethylating Agent for Arylboronic Acids and Aryl Iodides

Cited by 67 publications

References 34 publications

Synthesis of [18F]Fluoroform with High Molar Activity

Synthesis of [18F]Fluoroform with High Molar Activity

Synthesis of 18F‐Difluoromethylarenes from Aryl (Pseudo) Halides

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

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Product

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[¹⁸F]CuCF₃: A [¹⁸F]Trifluoromethylating Agent for Arylboronic Acids and Aryl Iodides

Synthesis of [¹⁸F]Fluoroform with High Molar Activity

Synthesis of [¹⁸F]Fluoroform with High Molar Activity

Synthesis of ¹⁸F‐Difluoromethylarenes from Aryl (Pseudo) Halides

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