Design and synthesis of components for optically active metal-organic frameworks (MOFs) and synthetic routes to diverse deuterium labelled α-diazoacetates, α-diazoacetamides, α-diazoketones, and the antibiotic azaserine
Metal-organic frameworks (MOFs) are porous crystalline solids that consist of metal nodes connected to organic linkers that assemble into one-, two- or three-dimensional frameworks. Among other applications they have recently found use in heterogeneous asymmetric catalysis. Since that time the demand for new optically active MOFs has increased and novel chiral non-racemic building blocks for their assembly are required. The first part of this PhD thesis entails the synthesis of a novel linear organic linker equipped with ester functional groups for the future introduction of a chiral centre. In addition, a selection of novel axially chiral (S)-BINOL-derived building blocks bearing 1,2,3-triazole moieties is described. Secondary functional groups can undergo post-synthetic modification resulting in the introduction of a catalytically active site. Within this research project an effective method for purification of commercially available acetylene was developed and a reliable protocol for a [2+2+2] cycloaddition reaction of 1,6-diyne with acetylene was established. The 2,2'-bipyridine moiety was successfully installed in the axially chiral (S)-BINOL-based linker providing a highly effective chelating ligand. α-Diazocarbonyl compounds are useful intermediates for various chemical transformations. Although known since the mid-1800s, they still offer an area for future studies and development of preparative methods as well as applications. With the recently growing need for labelled compounds, they appear to be ideal candidates for the introduction of deuterium. This area of research is presented in the second part of this PhD thesis. The synthesis of an array of α-diazocarbonyl acetic acid esters and α-diazoketones and their utilisation in a hydrogen / deuterium exchange reaction are described. Within this research project a quick, reliable and highly efficient protocol for a base-catalysed hydrogen / deuterium exchange reaction at the α-carbon atom of α-diazocarbonyl compounds was successfully developed furnishing products with moderate to high yields (63% to 90%) and excellent levels of deuterium incorporation (≥96%). This protocol was also successfully utilised in the synthesis of α-deutero-α-diazoacetic acid ester-derived α-amino acids and α-diazoacetamide-derived α- and β-amino acids. The first chemical synthesis of a deuterium-labelled azaserine analogue was accomplished. Additionally, two protocols for the preparation of α-deuterated aromatic aldehydes have been established. The third part of this PhD thesis illustrates briefly the synthesis of (S)-N-triflyl VANOL phosphoramide and its employment as a catalyst in asymmetric aziridination reactions.
Networked Digital Library of Theses and Dissertations