Transition metal catalysis in the presence of fluorinating reagents

Thesis

In this thesis, the effect of fluorinating reagents on a selection of transition metal-mediated organic transformations was investigated. The first four chapters are focused on gold-catalysed nucleophilic addition processes performed in the presence of “F⁺” sources.

Chapter 1 provides a general introduction to homogeneous gold catalysis and summarises the aims and objectives of the project.

The effect of the electrophilic fluorinating reagent Selectfluor (82) on the gold-catalysed rearrangement of propargyl acetates 85 is discussed in Chapter 2. α-Fluoroenones 92 resulting from fluorodeacetylation of an allenyl acetate intermediate were delivered as the major products of these reactions (Scheme i).

[Scheme i Gold-Catalysed Rearrangement-Fluorodeacetylation of Propargyl Acetates 85.]

By contrast, performing the gold(I)-catalysed cyclisation of allenoates 102 in the presence of Selectfluor (82) led to products of oxidative coupling. The “F⁺” source in these processes most likely acts as an external oxidant in an Au^I

III redox cycle. In Chapter 3, the cascade cyclisation-intramolecular arylation of benzyl-substituted substrates is discussed whilst the extension of the methodology towards intermolecular homocoupling and intermolecular alkynylation is presented in Chapter 4 (Scheme ii).

[Scheme ii Gold-Catalysed Cyclisation-Oxidative Coupling of tert-Butyl Allenoates 102.]

In Chapter 5, the feasibility of palladium-catalysed allylic [¹⁸F]radiofluorination was investigated using high-specific-activity [¹⁸F]fluoride. This study led to the development of the first transition metal-mediated C-¹⁸F bond-forming process of relevance for the preparation of radiotracers for PET imaging (Scheme iii).

[Scheme iii Palladium-Catalysed Allylic [18F]Radiofluorination of Allylic Methyl Carbonate 227b.]

Chapter 6 gives full experimental procedures and characterisation data for all compounds.

Authors: Hopkinson, M

• Publication date: 2011
• DOI: 10.5287/ora-6ryp29kex
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: gold; radiochemistry; homogeneous catalysis; fluorine; oxidative coupling
• Subjects: Organic chemistry; Organometallic Chemistry; Organic synthesis