Studies on C–F Activation and Radiofluorination Reactions: Interactions of Fluorine with Boron and Silicon Lewis Acids

• Author / Creator

  Dorian, Andreas

• Boron and silicon Lewis acids form strong bonds with fluorine. This ability facilitates a range of interesting reactivity. For example, small boron/silicon reagents are at the forefront of C-F activation, a field focused on cleaving one or more C-F bonds in organofluorine compounds. In addition to degradation of fluorine waste products, this field offers a compelling strategy to synthesize highly sought-after fluorinated motifs. Alternatively, boron/silicon functionalities can be introduced to a bioactive small-molecules or peptides of interest. These can facilitate inclusion of the radioisotope fluorine-18, a positron emitter that enables PET imaging - an important medical tool used in the diagnosis and monitoring of several diseases.
  The introductory chapter of this thesis provides a broad overview of C-F activation with boron/silicon Lewis acids. Special focus is given to reactions with trifluoromethyl arenes (ArCF₃), especially those that achieve selective single activation, resulting in the formation of valuable difluoromethyl (ArCF₂R) chemotypes. The second chapter describes a new method for ArCF₃ halogen- exchange, using readily available BX₃ and FeX₃ reagents. The reaction was optimized to form ArCX₃ and ArCF₂X products, and was evaluated with a variety of substrates.
  The third chapter begins with a general overview of PET imaging and the synthesis of 18F-labeled compounds, with a special emphasis on [18F] ArCF₃ formation. The direct and efficient synthesis of [18F] ArCF₃ from the corresponding non-radioactive ArCF₃ precursor remains an outstanding goal in radiochemistry. The efforts made towards the development of such a synthetic method are discussed, wherein BX₃/FeX₃ reagents were used to mediate the desired reactivity. The fourth chapter provides an overview of a radiofluorination approach termed non-canonical labeling. Some of the clinical applications of this strategy are discussed, in particular radiotracers targeting PSMA, a significant biomarker used for imaging prostate cancer. The efforts made towards the synthesis of a novel PSMA radiotracer are also described.

• Subjects / Keywords

  • Organic Chemistry
  • C–F Activation
  • Radiochemistry
  • PET Imaging
  • PSMA
  • Halogen Exchange
  • Iron Catalysis
  • Boron Lewis Acids
  • Silicon Lewis Acids

• Graduation date

  Fall 2022

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-q8zv-7x28

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.