Exploring New Asymmetric Reactions Catalysed by Dicationic Pd(II) Complexes

Dicationic palladium(II) complexes have been shown to catalyse a number of important asymmetric transformations including Michael, Mannich and aldol reactions. This PhD thesis describes work undertaken to discover and develop novel applications of dicationic palladium(II) complexes in asymmetric catalysis. The introductory chapter outlines the advances in catalytic asymmetric α-functionlisation of β-ketoesters. This includes both metal-catalysed and organocatalytic processes with reference to C-C, C-X (X = F, Cl, Br), C-N, C-O and C-S bond forming reactions. Chapter 2 discusses the work towards the synthesis of β-amino acids via Michael reactions catalysed by Pd(II) complexes. These reactions failed to proceed with good enantioselectivities, leading to the investigation of a number of related transformations. In the following Chapter the reaction of β-ketoesters with oxaziridines to generate α- hydroxy-β-ketoesters was discovered. Extensive screening of reaction parameters led to the identification of dimethyldioxirane (DMD) as a superior oxidant for this reaction, providing ee’s of up to 98%. Examining a range of substrates revealed several key structural elements required for both reactivity and enantioselectivity. Determination of the absolute stereochemistry of the products revealed opposite facial selectivity to that reported in a number of related reactions. Chapter 4 discusses the results of DFT calculations undertaken by a colleague (Prof H. S. Rzepa), to identify the origins of stereoselectivity in the Pd(II) mediated α-hydroxylation of β-ketoesters with DMD. Chapter 5 discusses the investigation of carboxylated pyrrolidinones and succinimides as substrates in the hydroxylation reaction. Successful α-hydroxylation provided access to 3 classes of synthetically useful hydroxylated N-heterocyclic products with high optical purity, and brief synthetic studies directed towards the natural product Pramanicin were undertaken. The last Chapter contains experimental procedures and characterisation data of all the compounds synthesised during the course of this project