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dc.contributor.authorMack, Kyle
dc.date.accessioned2018-10-23T13:23:24Z
dc.date.available2018-10-23T13:23:24Z
dc.date.issued2018-05-30
dc.identifier.otherMack_cornellgrad_0058F_10720
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:10720
dc.identifier.otherbibid: 10489555
dc.identifier.urihttps://hdl.handle.net/1813/59470
dc.description.abstractEnolizations of highly substituted acyclic ketones used in the syntheses of tetrasubstituted olefin-based anticancer agents are described. Lithium hexamethyldisilazide (LiHMDS)-mediated enolizations are moderately Z-selective in neat tetrahydrofuran (THF) and E-selective in 2.0 M THF/hexane. The results of NMR spectroscopy show the resulting enolates to be statistically distributed ensembles of E,E-, E,Z-, and Z,Z-enolate dimers with subunits that reflect the selectivities. The results of rate studies trace the preference for E and Z isomers to tetrasolvated- and pentasolvated-monomer-based transition structures, respectively. Enolization using LiHMDS in N,N-dimethylethylamine or triethylamine in toluene affords a 65:1 mixture of LiHMDS−lithium enolate mixed dimers containing E and Z isomers, respectively. Spectroscopic studies show that condition-dependent complexation of ketone to LiHMDS occurs in trialkylamine/toluene. Rate data attribute the high selectivity exclusively to monosolvated-dimer-based transition structures. Rate and mechanistic studies of ortholithiations by lithium 2,2,6,6-tetramethylpiperidine focus on four arenes: 1,4-bis(trifluoromethyl)benzene, 1,3-bis(trifluoromethyl)benzene, 1,3-dimethoxybenzene, and 4,4-dimethyl-2-phenyl-2-oxazoline. Metalations occur via substrate-dependent combinations of monosolvated monomer, disolvated monomer, and tetrasolvated dimer (triple ions). Density functional theory computational studies augment the experimental data. We discuss the challenges presented by shifting dimer–monomer proportions in determining the observable reaction orders and our mathematical treatment of such shifting in reactant structure.
dc.language.isoen_US
dc.subjectOrganic chemistry
dc.titleStructure-Reactivity Relationships of Lithium Amides: LiHMDS-Mediated Enolizations of Hindered Aryl Ketones and LiTMP-Mediated Ortholithiations
dc.typedissertation or thesis
thesis.degree.disciplineChemistry and Chemical Biology
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Chemistry and Chemical Biology
dc.contributor.chairCollum, David B.
dc.contributor.committeeMemberCoates, Geoffrey
dc.contributor.committeeMemberFors, Brett P.
dcterms.licensehttps://hdl.handle.net/1813/59810
dc.identifier.doihttps://doi.org/10.7298/X4J101FT


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