Aromatic addition reactions of α-diazo-β-ketonitriles

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dc.check.date2035-05-31
dc.contributor.advisorMaguire, Anita
dc.contributor.advisorCollins, Stuart
dc.contributor.authorTyner, Ciaraen
dc.contributor.funderIrish Research Council
dc.contributor.funderHigher Education Authority
dc.date.accessioned2025-02-06T15:10:19Z
dc.date.available2025-02-06T15:10:19Z
dc.date.issued2024en
dc.date.submitted2024
dc.description.abstractThe central focus of this thesis is the intramolecular aromatic addition reaction of α-diazo-β-ketonitriles using rhodium and copper catalysts, and examination of the structural properties and reactivity of the resulting azulenones. In depth comparison of the reactivity and properties of the α-diazo-β-ketonitriles and the resulting azulenones to the analogous α-diazoketones and azulenones bearing a bridgehead methyl group in place of the nitrile is a key element of the work. The power of benchtop NMR spectroscopy to monitor labile intermediates is demonstrated in this work. Chapter One provides an overview of the literature related to this work with a particular focus on recent developments in aromatic addition reactions of α-diazocarbonyl compounds. Chapter Two describes the successful synthesis and characterisation of a series of α-diazo-β-ketonitriles (13 novel compounds) and their precursors. A number of synthetic routes were explored to lead to these compounds, each of which involved multiple reaction steps and required considerable optimisation. Conjugation with the nitrile unit contributed to the increased stability of the α-diazo-β-ketonitriles which could be readily stored for long periods without deterioration, while the precursor β-ketonitriles were labile and had to be used shortly after preparation. Chapter Three describes the investigation of the aromatic addition reactions of the novel α-diazo-β-ketonitriles using a range of rhodium and copper catalysts and, on one occasion, a ruthenium catalyst. The impact of the nitrile substituent on the reactivity of the α-diazocarbonyl is explored in detail resulting in cleaner reactions than with the corresponding α-diazoketones due to fewer side reactions, presumably due to the more stable carbenoid. Enantioselection in the aromatic addition process was successful using a copper bis(oxazoline) catalyst providing the corresponding azulenone with up to 75% ee. Interestingly, the presence of the nitrile on the carbene had little impact on the enantiofacial discrimination. The impact of the nitrile substituent on the stability and reactivity of the azulenones is very significant, increasing their lability towards rearrangement to form tetralones and, indeed in many cases, the azulenones could not be isolated or recovered from the reaction mixtures. The tetralones exist predominantly as the enol tautomers due to conjugation with the nitrile. One of the key advances in this study was successful trapping of the novel labile azulenones as cycloadducts through addition of PTAD to the aromatic addition reactions. Interestingly, the presence of PTAD did not impact negatively on the transition metal catalysed process. The impact of the nitrile substituent on the position of the norcaradiene-cycloheptatriene equilibrium is also explored in detail, principally through 1H and 13C NMR spectroscopy and IR spectroscopy at room temperature and in variable temperature NMR studies. The presence of the nitrile substituent has a very significant impact in shifting the equilibrium towards the norcaradiene relative to the position of the equilibrium in the corresponding azulenones with a bridgehead methyl substituent. Chapter Four describes the use of a benchtop NMR spectrometer to monitor the aromatic addition reactions of the α-diazo-β-ketonitriles to form labile azulenones followed by rearrangement to the tetralones, demonstrating the power of this technique for monitoring and detecting labile intermediates at relatively low field (80 MHz). The reactivity profiles of α-cyano-α-diazoacetamides were also monitored by benchtop NMR spectroscopy in both static and flow mode. Chapter Five contains the full experimental details and spectroscopic characterisation of the compounds synthesised in this work.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationTyner, C. 2024. Aromatic addition reactions of α-diazo-β-ketonitriles. PhD Thesis, University College Cork.
dc.identifier.endpage424
dc.identifier.urihttps://hdl.handle.net/10468/17001
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2024, Ciara Tyner.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectIntramolecular aromatic addition
dc.subjectBuchner
dc.subjectα-Diazo-β-ketonitrile
dc.subjectNitrile
dc.subjectα-Cyano-α-diazoacetamide
dc.subjectEnantioselective catalysis
dc.titleAromatic addition reactions of α-diazo-β-ketonitrilesen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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