Development of Electron-Deficient Alkene Asymmetric Hydroboration Methodologies

Abstract

In this thesis, the investigation of reaction optimisations and enantioselectivity explorations for the novel total synthesis route of cholesterol-lowering drug atorvastatin was demonstrated.
Firstly, an updated literature review selected the key achievements in copper-catalysed electron deficient alkene enantioselective hydroboration methodologies, mechanism investigations and synthetic applications over recent years. Based on the previous investigations, a copper-catalysed enantioselective borylation method was employed in the synthesis route to atorvastatin utilising the hydroboration of electron-deficient alkenes to successfully constructed chiral cis-1,3-diol as the key functional moiety of atorvastatin. A streamlined, one-pot synthetic process generating an intermediate homoallylic boronate carboxylate ester was successfully demonstrated for the total synthesis of atorvastatin. Moreover, the enantioselective excess determination of an intermediate homoallylic boronate carboxylate ester was explored. The separation conditions of the enantiomers were also optimised using HPLC analysis.