Palladium mediated allylic fluorination

Thesis

In this thesis, the construction of the allylic fluorides under palladium catalysis was investigated.

Chapter 1 provides a general introduction to organofluorine compounds and the use of palladium for the formation of both Csp²- and Csp³-F bonds. The aims of the thesis are presented.

In Chapter 2 the identification that a p-nitrobenzoate is the optimum leaving group under Pd-catalysis to give allyl fluorides is described. A range of allylic fluorides was synthesized in 35->95% yield using the nucleophilic fluorinating reagent, TBAF(tBuOH)₄. To further develop this transformation we have examined the effect of a variety of leaving groups and phosphine ligands. This methodology led to the development of the first transition metal mediated C-¹⁸F bond formation. The development of Ir-catalysed fluorination of allylic carbonates to give allylic fluorides is also discussed. This system provided access to branched, E- and Z-linear allylic fluorides in a regioselective manner. This methodology was also translated to ¹⁸F radiochemistry.

In Chapter 3 the synthesis of allylic fluorides via a C-H functionalisation with Pd and nucleophilic source of fluorine was investigated. Comprehensive screening of Pd sources, fluoride reagents and additives was performed. The presence of a quinone was found to be crucial for this transformation.

Chapter 4 describes the synthesis and characterization of a series of allylpalladium(II) complexes and their subsequent reactivity towards a range of electrophilic fluorination reagents.

Chapter 5 gives full experimental procedures and characterization data for all compounds.

Authors: Hollingworth, C

• Publication date: 2013
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Palladium; fluorine; allylic; catalysis
• Subjects: Physical Sciences; Organic chemistry; Organometallic Chemistry; Chemistry & allied sciences; Organic synthesis