New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

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dc.contributor.advisor Mcglacken, Gerard P. en
dc.contributor.author McSweeney, Christina M.
dc.date.accessioned 2016-09-13T09:09:18Z
dc.date.available 2016-09-13T09:09:18Z
dc.date.issued 2015
dc.date.submitted 2015
dc.identifier.citation McSweeney, C. M. 2015. New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols. PhD Thesis, University College Cork. en
dc.identifier.endpage 246 en
dc.identifier.uri http://hdl.handle.net/10468/3078
dc.description.abstract A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules. en
dc.description.sponsorship Science Foundation Ireland (SFI Grant 09/RFP/CHS2353) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2015, Christina M. McSweeney. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Asymmetric synthesis en
dc.subject Chiral ligand en
dc.subject Chiral auxiliary en
dc.subject Sparteine en
dc.subject Azaenolate en
dc.subject Dimethylhydrazones en
dc.subject α-Alkylated ketones en
dc.subject 1,3-Amino alcohols en
dc.title New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en
dc.check.info No embargo required en
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en
dc.internal.school Chemistry en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
ucc.workflow.supervisor g.mcglacken@ucc.ie
dc.internal.conferring Autumn 2015 en


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© 2015, Christina M. McSweeney. Except where otherwise noted, this item's license is described as © 2015, Christina M. McSweeney.
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