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@INPROCEEDINGS{Humpert:866622,
      author       = {Humpert, Swen and Holschbach, Marcus and Bier, Dirk and
                      Zlatopolskiy, Boris and Neumaier, Bernd},
      title        = {{P}reparation of [18{F}]fluoroalkenyliodonium salts and
                      their application for radiolabeling by cross‐coupling
                      reactions},
      reportid     = {FZJ-2019-05701},
      year         = {2019},
      abstract     = {Objective(Fluoroalkenyl)(aryl)iodonium salts are valuable
                      building blocks for Pd‐catalyzed cross‐coupling
                      reactions [1]. These prosthetic groups are easily available
                      via nucleophilic addition of fluoride to the respective
                      (alkynyl)(aryl)iodonium salts under exceptionally mild
                      conditions [2]. Herein we report the preparation of
                      18F‐labeled (2‐fluorohexen‐1‐yl)(aryl)iodonium salts
                      ([18F]FHexI+X–) and their application in various
                      Pd‐catalyzed cross‐coupling reactions. Finally,
                      [18F]FHexI+OTs– was used for the site selective labeling
                      of clinically relevant compounds and
                      peptides.Methods(Alkynyl)(aryl)iodonium salts were
                      radiolabeled using [18F]fluoride in aqueous media in the
                      presence of different bases and K2.2.2. The reaction
                      conditions were optimized with respect to different
                      parameters including reaction temperature, time, solvent,
                      precursor amount and counter ion. After isolation,
                      [18F]FHexI+OTs– was applied in Pd‐catalyzed
                      cross‐couplings with different model substrates.
                      Additionally, radiofluorinated amino acid derivatives as
                      well as a PSMA ligand potentially suitable for the detection
                      of prostate carcinoma lesions were prepared starting from
                      [18F]FHexI+OTs–.ResultsUnder optimized conditions (KHCO3,
                      K2.2.2, $67\%$ aq. DMSO, 75°C) [18F]FHexI+X– salts were
                      prepared in RCYs of about $60\%$ (HPLC) within 10 min.
                      Remarkably, time consuming azeotropic drying was not
                      necessary. Radiolabeling of the phenylethynyl substituted
                      precursors also furnished the respective 18F‐labeled
                      iodonium salts although in lower RCYs of $20\%$ to $30\%$
                      (HPLC). The respective counter ion (OTs–, OMs–, BF4–,
                      TFA–) did not have a significant influence on RCYs.
                      [18F]FHexI+OTs– was purified by HPLC followed by solvent
                      exchange and thereafter used for subsequent cross‐coupling
                      reactions. Sonogashira, Stille, and Suzuki reactions
                      afforded the respective radiolabeled products as pure
                      Z‐isomers in RCYs of $61\%$ to $74\%$ (HPLC) within 3 to
                      10 min at ambient temperature. In the case of the Heck
                      cross‐coupling the corresponding 18F‐fluorinated diene
                      was prepared in RCY of 27 ± $2\%$ as a mixture of E/Z
                      isomers.In particular, the one‐pot Sonogashira
                      cross‐coupling reaction turned out to be very fast and
                      robust under very mild conditions. Therefore, this reaction
                      was selected to demonstrate the applicability of [18F]FHexI+
                      for the labeling of biomolecules. Nine ethynyl‐substituted
                      amino acid derivatives were conjugated with
                      [18F]FHexI+OTs– using the Sonogashira reaction affording
                      the respective radiolabeled enynes in RCYs of $38\%$ to
                      $88\%$ (HPLC). Furthermore, a novel 18F‐labeled PSMA
                      ligand was prepared in an isolated RCY of $40\%$ in two
                      steps within 35 min. Conjugation of [18F]FHexI+OTs– to a
                      suitably modified model dipeptide (H‐Arg‐Pra‐OBn)
                      afforded the corresponding conjugate in $61\%$ RCY based on
                      isolated [18F]FHexI+OTs– using only 50 nmol peptide
                      precursor.ConclusionThe novel radiolabeled prosthetic group
                      [18F]FHexI+OTs– is easily available in aqueous media
                      obviating any evaporation steps. Thus, [18F]FHexI+OTs– can
                      be used in Pd‐catalyzed cross‐coupling reactions as a
                      fast, high yielding, site specific and versatile procedure
                      for the preparation of clinically relevant PET tracers. [1]
                      Yoshida et al., Tetrahedron 62 (2006) 8636‐8645 [2] Nguyen
                      et al., Tetrahedron 67 (2011) 3434‐34939image},
      month         = {May},
      date          = {2019-05-26},
      organization  = {The 23rd International Symposium on
                       Radiopharmaceutical Sciences, Beijing
                       (China), 26 May 2019 - 31 May 2019},
      subtyp        = {After Call},
      cin          = {INM-5},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/866622},
}