Late-stage fluorination and perfluoroalkylation

Thesis

In this thesis new synthetic routes towards perfluorinated compounds are described, as well as their radiolabelling with fluorine-18, with the aim of application in pharmaceutically interesting targets.

Part A investigates late-stage fluorination, i.e. retrosynthetic C–F bond disconnections. A silver catalysed electrophilic fluorodecarboxylation of fluorinated carboxylic acids for the formation of difluoromethyl-, trifluoromethyl-, and pentafluoroethylarenes is developed and transferred to a radiochemistry setting using [¹⁸F]Selectfluor bis(triflate).

Part B explores late-stage perfluoroalkylation via cross-coupling strategies. The use of visible light-mediated ruthenium catalysis is investigated for the radical trifluoromethylation and pentafluoroethylation of vinyl- and alkynylsilanes and alkynes. Finally, the first generally applicable copper-mediated cross-coupling of Ruppert-Prakash-like aryl(tetrafluoroethyl)trimethylsilanes (ArCF2CF2SiMe3) is presented.

Authors: O'Duill, M

• DOI: 10.5287/ora-jvxvw229p
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: 18F Radiochemistry; Perfluoroalkylation; Photocatalysis; Trifluoromethylation; Fluorination; Transition Metal Catalysis; Fluorine
• Subjects: Chemistry, Organic