Development of late-stage difluoromethylation strategies

Thesis

In the last decades, the introduction of the difluoromethyl group has attracted many interests in drug discovery. This thesis discusses the development of novel strategies for the late-stage introduction of the difluoromethyl group in the context of photochemistry and F-18 radiochemistry. The relevance of the difluoromethyl group and an introduction to the field of late-stage difluoromethylation is described in Chapter 1. In Chapter 2, a novel methodology for the photochemical late-stage hydrodifluoromethylation of alkenes with difluoroacetic acid is discussed. Chapter 3 describes the expansion of this methodology to the hydrochlorofluoromethylation and hydrobromofluoromethylation of alkenes. Radiochemistry and its applications to positron emission tomography are introduced in Chapter 4. Chapter 5 describes our recent efforts for the synthesis of an [¹⁸F]difluorocarbene reagent for the ¹⁸F-difluoromethylation of phenols, thiophenols and N-heterocycles. Experimental data for the work described in this thesis is given in Chapter 6.

Authors: Meyer, CF

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Difluoromethylation; Radical; Radiochemistry; Carbene
• Subjects: Radiochemistry; Chemistry, Organic