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Title: New late-stage strategies towards difluoromethylarenes
Author: Sap, Jeroen
ISNI:       0000 0004 9355 0772
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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This thesis consists of the development of novel methodology to access difluoromethylated compounds both in the context of photoredox catalysis and fluorine-18 radiochemistry for Positron Emission Tomography (PET). First a general introduction to late-stage difluoromethylation will be showcased in Chapter I. In Chapter II, a metal-free visible light catalysed synthesis of difluoromethylarenes via a controlled hydrodefluorination of electron-poor trifluoromethylarenes is described. The reaction works both in batch and in flow and proves to be useful in the context of late-stage functionalisation. In Chapter III, a general introduction to PET is provided. General radiochemistry concepts are also introduced. In Chapter IV, a facile and robust radiochemical methodology for PET describing the synthesis of 18F-difluoromethylarenes from aryl boronic acids, ethyl bromofluoroacetate and cyclotron produced [18F]fluoride is presented. The two key steps involve a copper catalysed cross-coupling reaction using bench-stable aryl boronic acids to yield 2-fluoro-2-arylacetic acids in a two-step one-pot reaction followed by a manganese mediated 18F-fluorodecarboxylation to afford 18F-difluoromethylarenes in a streamlined fashion. Chapter V discusses the synthesis of the first 18F-difluorocarbene reagent and its application to react as a difluoromethylating reagent with phenols, thiophenols, N-heterocycles, and boronic acids. Chapter VI provides experimental data for compounds described within this thesis.
Supervisor: Gouverneur, Veronique Sponsor: Pfizer ; Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Photoredox Catalysis ; Radio chemistry ; Organic Chemistry