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

Bachera, Dominika (2016) 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. Doctoral thesis, University of East Anglia.

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Abstract

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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Chemistry
Depositing User: Mia Reeves
Date Deposited: 04 May 2016 12:05
Last Modified: 04 May 2016 12:05
URI: https://ueaeprints.uea.ac.uk/id/eprint/58573
DOI:

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