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 13:05
    Last Modified: 04 May 2016 13:05
    URI: https://ueaeprints.uea.ac.uk/id/eprint/58573
    DOI:

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