The stereochemical complexity evident in agrochemicals, pharmaceuticals, and natural products continues to provide motivation for the development of novel synthetic methods. In the last decade, research in the field of asymmetric organocatalysis has provided new tools for the functionalisation of the carbon atoms adjacent to a carbonyl. This thesis describes the use of asymmetric organocatalysis for the ɑ-chlorination of aldehydes and the subsequent use of these compounds as building-blocks for the preparation of a variety of oxygen-containing heterocycles. With the successful preparation of optically enriched ɑ-chloroaldehydes, these linchpin compounds were elaborated into trans-epoxides, substituted-tetrahydrofuranols, and carbohydrate analogues. In particular, this thesis describes the addition of organolithium reagents and lithium enolates to optically pure ɑ-chloroaldehydes to afford 1,2-anti-chlorohydrins in a highly diastereoselective manner. Further elaboration of these compounds allowed access to a variety of trans-epoxides, in an approach that is flexible and concise. Following the discovery of a novel silver-mediated cyclisation process substituted-tetrahydrofuranols were afforded from the 1,2-anti-chlorohydrins and the trans-epoxides. It was also realised that chloropolyols undergo regio- and stereoselective cyclisation by simply heating them in water to provide highly functionalised tetrahydrofuranols, including carbohydrate analogues. Together, these methods allowed access to a wide-range of stereochemically diverse oxygen-containing scaffolds. The methodologies described within this thesis were further applied to the synthesis of an array of biologically active natural products. To demonstrate the utility of
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Thesis advisor: Britton, Robert A.
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