In the first part of this thesis, the de novo syntheses of novel fluorinated carbohydrate analogues and the syntheses of fluorosugars from carbohydrate precursors were investigated. The second part was focused on a IH and 19F NMR study of fluorine hydrogen bonding (O-H··F-C) in suitably substituted sugars. Chapter 1 provides a general introduction to fluorine chemistry and summarises the aims and goals of the project. The asymmetric de novo synthesis of fluorinated L-mannitols 73 and L-glucitols 74 is discussed in Chapter 2. The fluoropolyol structures were constructed in nine steps from three two carbon building blocks 75, 76 and 77 with overall yields of up to 26%. The key carbon- fluorine bond was formed using a fluorodesilylation reaction (Scheme i, a). A diversity oriented de novo synthesis of 4-deoxy-4,4-difluoro sugars is presented in Chapter 3. Five di- and trifluorinated hexopyranosides (±)-156 have been synthesised in 8-9 steps with overall yields of up to 29%. A 6-endo-dig gold cyc1isation was of the ynone (±)-159 was used as the key step to prepare the common late stage intermediate glycal (±)-136 (Scheme i, b). Chapter 4 describes the synthesis of methyl 4-fluoro talo- and idopyranosides 218 and 219 from the mannopyranoside 223 and the 2,4-difluoro talopyranoside 220 from the glucopyranoside 222 (Scheme i, c). In Chapter 5, a O-H··F-C hydrogen bonding study of ten of mono-, di- and trifluoro sugars prepared in Chapters 3 and 4 is presented. The selected probes were analysed by lH and 19F NMR spectroscopy and provide new insights into substitution effects on O-H··F-C hydrogen bonding.

This thesis describes investigations into the utility of boron fluorides and tetrafluoroborates as sources of nucleophilic fluorine. Chapter 1 discusses the history and importance of the field of organofluorine chemistry and outlines some of the principle motivations for the site-selective fluorination of organic molecules. Some of the most commonly useed methods of nucleophilic fluorination are briefly surveyed, with an emphasis on the formation of fluorinated stereogenic centres. Literature precedent for the use of tetrafluoroborates and boron trifluoride as nucleophilic fluorinating agents is also presented. Chapter 2 describes the development of a highly regio- and stereoselective S_Ni-type ring-opening fluorination of trans-β-substituted aryl epoxides using BF₃●OEt₂ as a nucleophilic fluorinating agent. This robust and scalable protocol grants efficient access to a variety of functionalised benzylic fluoride building blocks, and provides a solution to the problem of stereocontrol in the synthesis of this class of compounds. To highlight the utility of the resultant syn-fluorohydrins in the synthesis of stereodefined β-fluoro β-aryl amines, their elaboration to a range of aryl-substituted β-fluoroamphetamines is demonstrated. Chapter 3 introduces the concept of tuning the reactivity of BF₃ by replacing one or two of the fluoro ligands on boron for electron-donating alkoxy group(s). On this basis, pinacolatoboron fluoride (pinBF) [which may be prepared in situ by pre-mixing BF₃●OEt₂ and bis(O-trimethylsilyl)pinacol] is identified as a superior reagent to BF₃●OEt₂ for the ring-opening fluorination of trans-β-substituted aryl epoxides bearing electron-rich aryl groups. Chapter 4 details a highly regioselective and stereospecific S_N2-type ring-opening fluorination of 2,3- and 3,4-epoxy amines using HBF₄●OEt₂ as a nucleophilic flurine source. The reactions are both operationally simple to perform and readily scalable, and proceed to completion within 5 min at ambient temperature, providing a highly practical and economical route to stereodefined amino fluorohydrins. To highlight the synthetic utility of this reaction in the preparation of pharmaceutically-important β-fluoro amines, a concise de novo asymmetric synthesis of (S,S)-3-deoxy-3-fluorosafingol is performed. Chapter 5 chronicles the successful development of a protocol for the direct hydroxyfluorination of allylic amines to the corresponding amino fluorohydrins, using m--CPBA as the oxidant and HBF₄●OEt₂ in a dual role as both the Brønstead acid N-protecting agent and nucleophilic fluorine source. With chiral allylic amines which are conformationally biased or constrained, the diastereofacial selectivity of the reaction can be controlled by altering the concentration of HBF₄●OEt₂ employed in the reaction, allowing for a diastereodivergent hydroxyfluorination process. The synthetic utility of this methodology is demonstrated via its application to the diastereodivergent synthesis of 4-deoxy-4-fluoro-L-xylo-phytosphingosine and 4-deoxy-4-fluoro-L-lyxo-phytosphingosine, each in 5 steps from Garner's aldehyde. Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in chapters 2, 3, 4 and 5.