h1

% 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”.

@PHDTHESIS{Halder:979821,
      author       = {Halder, Riya},
      othercontributors = {Ritter, Tobias and Patureau, Frédéric W.},
      title        = {{L}ate-stage aromatic {C}−{H} difluoroalkylation and
                      amination $via$ arylthianthrenium salts and
                      $^{18}${F}-labeling of peptide $via$ ruthenium-mediated
                      deoxyfluorination},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Aachen},
      publisher    = {RWTH Aachen University},
      reportid     = {RWTH-2024-01865},
      pages        = {1 Online-Ressource : Illustrationen},
      year         = {2024},
      note         = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
                      University; Dissertation, RWTH Aachen University, 2024},
      abstract     = {This thesis addresses the pressing need for methodologies
                      facilitating late-stage aromatic C–N and C–CF$_{2}$ bond
                      formations, crucial in the realm of drug discovery. The
                      significance of aromatic C–N bonds in pharmaceutical
                      compounds underscores the demand for diversification at
                      advanced stages. Aromatic C–H functionalization, a
                      strategy involving the conversion of carbon-bound hydrogen
                      atoms into functional groups, offers an avenue to enhance
                      aromatic molecule complexity. Challenges in C–H
                      functionalization include positional selectivity and
                      tolerance towards reactive functional groups. The Ritter
                      group's work on selective C–H thianthrenation paved the
                      way for constructing aryl electrophiles, utilized in
                      subsequent transformations like fluorination, amination, and
                      oxygenation. Part I of this thesis showcases the novel use
                      of arylthianthrenium salts for C(sp$^{2}$)–CF$_{2}$ bond
                      construction via palladium-catalyzed Negishi cross-coupling,
                      enabling late-stage incorporation of difluoroalkyl groups.
                      The method extends to generate even fluorolkylated arenes.
                      Part I also demonstrates Ni(I)-catalyzed amination of
                      arylthianthenium salts, broadening substrate scope and
                      offering an alternative to dual Ni/photoredox-catalyzed
                      amination, particularly for electron-rich substrates. Part
                      II of this thesis shifts the focus to positron-emission
                      tomography (PET)-tracer development. As of 2023, the U.S.
                      Food and Drug Administration (FDA) has approved just
                      seventeen PET-tracers, of which seven have been developed in
                      the last five years and only one was developed in last two
                      years. Beyond factors like regulatory requirements, high
                      costs, need for specialized expertise etc., the scarcity of
                      approved tracers results from complications in research and
                      development as identifying compounds that can effectively
                      target specific biological processes or diseases in animals
                      can be challenging. Moreover, introducing short-lived
                      radionuclides in the final or penultimate step of the
                      synthesis adds up to the challenge. Complex molecular
                      structures can hinder reactivity, necessitating innovative
                      strategies. Peptides, due to selective binding and rapid
                      clearance, are promising for PET-tracer design. The second
                      part introduces a method for radio-deoxyfluorination,
                      yielding peptide with 4-[$^{18}$F]fluoro-phenylalanine side
                      chain, preserving biological function and enabling versatile
                      labeling. This thesis tackles critical challenges in
                      late-stage bond formations and PET-tracer development,
                      contributing valuable methods to advance drug discovery and
                      molecular imaging.},
      cin          = {152310 / 150000},
      ddc          = {540},
      cid          = {$I:(DE-82)152310_20140620$ / $I:(DE-82)150000_20140620$},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2024-01865},
      url          = {https://publications.rwth-aachen.de/record/979821},
}