Copper-Mediated Radiofluorination of Aryl Pinacolboronate Esters: A Straightforward Protocol by Using Pyridinium Sulfonates

Dmitrii Antuganov, Michail Zykov, Vasilii Timofeev, Ksenija Timofeeva, Yulija Antuganova, Victoriya Orlovskaya, Raisa Krasikova

Research output

6 Citations (Scopus)

Abstract

Radiofluorination of arylboronic acids pinacol esters (arylBPin) mediated by copper triflate pyridine complex is one of the more promising synthetic approaches for the direct introduction of nucleophilic [18F]fluoride into non-activated arenes and heteroarenes. However, the application of this method to the production of positron emission tomography (PET) radiotracers in automated synthesizers remains a challenging task. The choice of phase-transfer catalyst (PTC) and corresponding base used for the generation of reactive [18F]fluoride species has a profound impact on the efficiency of the 18F-fluorination process. Herein we report the development of a simple procedure involving trapping of the aqueous [18F]fluoride on a weak anion-exchange resin (WAX) and its release by elution with pyridinium sulfonate in dimethyl acetamide. Obtained reactive [18F]fluoride was used as-is in a copper-catalyzed fluorination reaction employing pyridinium salt as both PTC and base. High radiochemical conversion rates (RCCs) achieved for a series of simple arylBPin substrates and 4-[18F]fluoro-D,L-phenylalanine demonstrate the efficiency of this novel 18F-processing approach. Notably, the proposed method obviates conventional azeotropic drying steps, solvents evaporation and/or changeover and can be implemented on commercial automated synthesizers.

Original languageEnglish
Pages (from-to)918-922
Number of pages5
JournalEuropean Journal of Organic Chemistry
Volume2019
Issue number5
DOIs
Publication statusPublished - 7 Feb 2019

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sulfonates
Fluorides
fluorides
Copper
esters
Esters
copper
Fluorination
synthesizers
fluorination
Anion Exchange Resins
catalysts
acids
Catalysts
Positron emission tomography
elution
Acids
phenylalanine
Phenylalanine
resins

Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Antuganov, Dmitrii ; Zykov, Michail ; Timofeev, Vasilii ; Timofeeva, Ksenija ; Antuganova, Yulija ; Orlovskaya, Victoriya ; Krasikova, Raisa. / Copper-Mediated Radiofluorination of Aryl Pinacolboronate Esters : A Straightforward Protocol by Using Pyridinium Sulfonates. In: European Journal of Organic Chemistry. 2019 ; Vol. 2019, No. 5. pp. 918-922.
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abstract = "Radiofluorination of arylboronic acids pinacol esters (arylBPin) mediated by copper triflate pyridine complex is one of the more promising synthetic approaches for the direct introduction of nucleophilic [18F]fluoride into non-activated arenes and heteroarenes. However, the application of this method to the production of positron emission tomography (PET) radiotracers in automated synthesizers remains a challenging task. The choice of phase-transfer catalyst (PTC) and corresponding base used for the generation of reactive [18F]fluoride species has a profound impact on the efficiency of the 18F-fluorination process. Herein we report the development of a simple procedure involving trapping of the aqueous [18F]fluoride on a weak anion-exchange resin (WAX) and its release by elution with pyridinium sulfonate in dimethyl acetamide. Obtained reactive [18F]fluoride was used as-is in a copper-catalyzed fluorination reaction employing pyridinium salt as both PTC and base. High radiochemical conversion rates (RCCs) achieved for a series of simple arylBPin substrates and 4-[18F]fluoro-D,L-phenylalanine demonstrate the efficiency of this novel 18F-processing approach. Notably, the proposed method obviates conventional azeotropic drying steps, solvents evaporation and/or changeover and can be implemented on commercial automated synthesizers.",
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Copper-Mediated Radiofluorination of Aryl Pinacolboronate Esters : A Straightforward Protocol by Using Pyridinium Sulfonates. / Antuganov, Dmitrii; Zykov, Michail; Timofeev, Vasilii; Timofeeva, Ksenija; Antuganova, Yulija; Orlovskaya, Victoriya; Krasikova, Raisa.

In: European Journal of Organic Chemistry, Vol. 2019, No. 5, 07.02.2019, p. 918-922.

Research output

TY - JOUR

T1 - Copper-Mediated Radiofluorination of Aryl Pinacolboronate Esters

T2 - A Straightforward Protocol by Using Pyridinium Sulfonates

AU - Antuganov, Dmitrii

AU - Zykov, Michail

AU - Timofeev, Vasilii

AU - Timofeeva, Ksenija

AU - Antuganova, Yulija

AU - Orlovskaya, Victoriya

AU - Krasikova, Raisa

PY - 2019/2/7

Y1 - 2019/2/7

N2 - Radiofluorination of arylboronic acids pinacol esters (arylBPin) mediated by copper triflate pyridine complex is one of the more promising synthetic approaches for the direct introduction of nucleophilic [18F]fluoride into non-activated arenes and heteroarenes. However, the application of this method to the production of positron emission tomography (PET) radiotracers in automated synthesizers remains a challenging task. The choice of phase-transfer catalyst (PTC) and corresponding base used for the generation of reactive [18F]fluoride species has a profound impact on the efficiency of the 18F-fluorination process. Herein we report the development of a simple procedure involving trapping of the aqueous [18F]fluoride on a weak anion-exchange resin (WAX) and its release by elution with pyridinium sulfonate in dimethyl acetamide. Obtained reactive [18F]fluoride was used as-is in a copper-catalyzed fluorination reaction employing pyridinium salt as both PTC and base. High radiochemical conversion rates (RCCs) achieved for a series of simple arylBPin substrates and 4-[18F]fluoro-D,L-phenylalanine demonstrate the efficiency of this novel 18F-processing approach. Notably, the proposed method obviates conventional azeotropic drying steps, solvents evaporation and/or changeover and can be implemented on commercial automated synthesizers.

AB - Radiofluorination of arylboronic acids pinacol esters (arylBPin) mediated by copper triflate pyridine complex is one of the more promising synthetic approaches for the direct introduction of nucleophilic [18F]fluoride into non-activated arenes and heteroarenes. However, the application of this method to the production of positron emission tomography (PET) radiotracers in automated synthesizers remains a challenging task. The choice of phase-transfer catalyst (PTC) and corresponding base used for the generation of reactive [18F]fluoride species has a profound impact on the efficiency of the 18F-fluorination process. Herein we report the development of a simple procedure involving trapping of the aqueous [18F]fluoride on a weak anion-exchange resin (WAX) and its release by elution with pyridinium sulfonate in dimethyl acetamide. Obtained reactive [18F]fluoride was used as-is in a copper-catalyzed fluorination reaction employing pyridinium salt as both PTC and base. High radiochemical conversion rates (RCCs) achieved for a series of simple arylBPin substrates and 4-[18F]fluoro-D,L-phenylalanine demonstrate the efficiency of this novel 18F-processing approach. Notably, the proposed method obviates conventional azeotropic drying steps, solvents evaporation and/or changeover and can be implemented on commercial automated synthesizers.

KW - radiopharmaceuticals • arenes • phase-transfer catalysis • copper mediated radiofluorination • [18F]fluoride • pinacol esters of arylboronic acids • positron emission tomography • pyridinium sulfonates

KW - Arenes

KW - Copper mediated radiofluorination

KW - Phase-transfer catalysis

KW - Pinacol esters

KW - Radiopharmaceuticals

KW - TRYPTOPHAN

KW - ONE-STEP SYNTHESIS

KW - F-18-FLUORINATION

KW - FLUORINATION

KW - PET

KW - F-18

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DO - 10.1002/ejoc.201801514

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JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

SN - 1434-193X

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