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

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dc.check.embargoformatNot applicableen
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dc.contributor.advisorMcglacken, Gerard P.en
dc.contributor.authorMcSweeney, Christina M.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2016-09-13T09:09:18Z
dc.date.available2016-09-13T09:09:18Z
dc.date.issued2015
dc.date.submitted2015
dc.description.abstractA 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.sponsorshipScience Foundation Ireland (SFI Grant 09/RFP/CHS2353)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMcSweeney, 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.endpage246en
dc.identifier.urihttps://hdl.handle.net/10468/3078
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2015, Christina M. McSweeney.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectAsymmetric synthesisen
dc.subjectChiral liganden
dc.subjectChiral auxiliaryen
dc.subjectSparteineen
dc.subjectAzaenolateen
dc.subjectDimethylhydrazonesen
dc.subjectα-Alkylated ketonesen
dc.subject1,3-Amino alcoholsen
dc.thesis.opt-outfalse
dc.titleNew methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcoholsen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorg.mcglacken@ucc.ie
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