% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Kaur:304477,
      author       = {S. Kaur and B. Wenzel and R. Oehme and C. Wiesner and K.
                      Kopka$^*$ and R.-P. Moldovan},
      title        = {{T}he hydrogenation side-reaction in copper-mediated
                      radiofluorination.},
      journal      = {EJNMMI radiopharmacy and chemistry},
      volume       = {10},
      number       = {1},
      issn         = {2365-421X},
      address      = {[Cham, Switzerland]},
      publisher    = {Springer International Publishing},
      reportid     = {DKFZ-2025-01869},
      pages        = {60},
      year         = {2025},
      abstract     = {Copper-mediated radiofluorination (CMRF) is a breakthrough
                      in 18F-radiochemistry, enabling 18F incorporation into
                      molecules even at electron-rich aromatic positions. In
                      recent years, several improved protocols have been reported
                      to advance the application of CMRF. These advancements
                      primarily focus on improving radiochemical conversion,
                      expanding substrate scope, and enabling scalability for
                      remote-controlled radiotracer production. Despite these
                      improvements, one major challenge remains: the
                      protodemetallation. Protodemetallation is a common side
                      reaction in transition metal-mediated cross-couplings that
                      takes place by a mechanism that is not yet fully elucidated.
                      In 18F-chemistry, the formation of the hydrogenated side
                      product (HSP) can interfere with the chromatographic
                      purification of the desired radiotracer, resulting in
                      complex radiotracer production.The present work investigates
                      the factors influencing the rate of the hydrogenation
                      reaction as well as the source of hydrogen in the CMRF by
                      use of model precursors bearing -B(OH)2, -Bpin, -BEpin and
                      -SnBu3 as leaving groups. While the CMRF reactions are
                      usually carried out under anhydrous conditions, the
                      formation rate of the HSP was evaluated by controlling the
                      chemical constituents (type and molarity of reagents) as
                      well as the physical parameters (time and temperature).
                      Moreover, experiments with deuterated reagents complemented
                      by high-resolution mass spectrometry (HRMS) analysis were
                      carried out to identify the source of hydrogen for the
                      reductive elimination step.This study identifies reaction
                      parameters that influence hydrogenation side reactions in
                      CMRF, enabling high RCC with minimal HSP formation. The
                      optimal reaction conditions include low temperature, short
                      reaction time, and minimal amount of precursor, copper, and
                      ideally no base and alcohols as solvents. Among the
                      evaluated precursors, -BEpin afforded the lowest HSP
                      formation, while -B(OH)2 afforded the highest. Overall, this
                      study showed that the selection of proper reaction reagents
                      and the fine-tuning of reaction parameters can substantially
                      reduce the HSP formation while maintaining optimal
                      radiochemical conversion.},
      keywords     = {BEpin (Other) / CMRF (Other) / Copper-mediated
                      radiofluorination (Other) / Fluorine-18 (Other) /
                      Hydrogenated side product (Other) / Protodeboronation
                      (Other)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40921858},
      pmc          = {pmc:PMC12417351},
      doi          = {10.1186/s41181-025-00384-1},
      url          = {https://inrepo02.dkfz.de/record/304477},
}