The racemic (±)-2,4-di-tert-butyl-6-(((2-(dimethylamino)cyclohexyl)(methyl) amino)methyl)phenol ((±)-(NNMeOtBu)H), (±)-2,4-di-tert-butyl-6-((2-(dimethylamino) cyclohexylamino)methyl)phenol ((±)-(NNHOtBu)H), and (±)-2-(((2-(dimethylamino) cyclohexyl)(methyl)amino) methyl)phenol ((±)-(NNMeOH)H) are chiral ancillary NNO proligands, which synthesis was adapted from a published procedure. Reaction of (±)-(NNMeOtBu)H ((±)-2), (±)-(NNMeOH)H ((±)-3) and (±)-(NNHOtBu)H ((±)-1) with ZnEt2 successfully yielded the corresponding zinc ethyl complexes (±)-5, (±)-6 and (±)-7 respectively; the enantiomerically pure (R,R)-5 was synthesized from (R,R)-2. NMR spectroscopy experiments and X-ray crystallography allowed identification of two stereoisomers for (±)-5, which were observed in solution and in the solid state. The two stereoisomers, 5-α and 5-β, are in equilibrium in solution, with 5-β being thermodynamically favored. The zinc ethyl complexes were found to be unreactive towards weakly acidic alcohols (methanol, ethanol, isopropanol). However, the zinc chloride complex (±)-(NNMeOtBu)ZnCl ((±)-8) and the zinc phenoxide (NNMeOtBu)ZnOPh ((±)-9 and (R,R)-9) could be isolated and characterized. Comparison of the reactivity of both (±)-5 and the reported L₁ZnEt (L₁ = 2,4-di-tert-butyl-6- {[(2'-dimethylaminoethyl) methylamino]methyl}phenolate) in presence of pyridine led to the proposal of a dissociative mechanism explaining the fundamental difference between the two zinc ethyl species. Polymerization of rac-lactide catalyzed by 9 showed that the complex, in its racemic or enantiomerically pure version, has a slow activity and is not stereoselective.

Title from PDF of title page (University of Missouri--Columbia, viewed on March 1, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Michael Harmata. Vita. Includes bibliographical references.

Thesis (Ph.D.)--Baylor University, 2009. / Includes bibliographical references (p. 255-262).

This thesis concerns the catalytic asymmetric synthesis of epoxides. An introduction highlights the utility of chiral epoxides in asymmetric synthesis. The important methods that have been developed towards the construction of this influential functional group are also described.

Doctor of Philosophy / Department of Chemistry / Duy H. Hua / Small molecules are of great importance in drug discovery currently. The first three chapters discussed the design, synthesis and bio-evaluation of three different classes of small molecules and exploration of their biological targets. Triacsin C analogs were designed as long chain fatty acyl-CoA synthetase (ACSL) inhibitors for attenuating ischemia and reperfusion (I/R) injury. Oxadiazole derivatives were designed as T-type calcium channel inhibitors, which have potential application in the treatment of seizure and epilepsy. Tricyclic pyrone derivatives were reported as anti-Alzheimer lead compounds in previous research done by the Hua group. TP70 and CP2 were synthesized to explore their pharmacokinetics properties. Chapter 4 described chiral-substituted poly-N-vinylpyrrolidones (CSPVP) supported Cu/Au nanoclusters mediation of cyclization reaction of 5-substituted nona-1,8-dien-5-ols. A five-member cyclized lactone possessing a stereogenic tetrasubstituted carbon center was formed in a one-step Cu/Au nanoclusters-hydrogen peroxide oxidation reaction. This developed a novel and simple method to synthesize tetrasubstituted carbon stereogenic center. Drawbacks of the method in my initial study were low reaction yield and moderate enantioselectivity. The chemical yield and enantioselectivity have been significantly improved by introducing bulkier substitution in C3 and C4 positions of CSPVP according to the updates of ongoing research.

Synthesis of optically active dendrimers based on 1,1'-bi-2-naphthol enantiomers and their derivatives as core units is growing rapidly due to the unique behavior and properties of the new compounds and their various valuable applications in several fields such as asymmetric catalysts, enantioselective fluorescent sensors and in chiral molecular recognition. To the best of our knowledge, the synthesis of binaphthyl-based symmetrical and asymmetrical axially chiral dendrimers via 1,3-cycloaddition reactions ["Click" chemistry] using Fréchet-type dendrons and their azido-analogues has not been studied yet. The principal aim of this project was the synthesis and characterization of a novel series of binaphthyl-based symmetrical and asymmetrical axially chiral dendrimers via "Click" and etherification reactions, and then determination of the specific and molar rotation of the new dendrimers to investigate the influence of linkage nature between the dendritic wedges and the core units on the optical properties in presence of the triazole ring by comparing of the properties of the new dendrimers with the dendrimers reported in literature, in addition to study the influences of different chemical groups near the dendritic wedges on the optical properties of the novel synthesized dendrimers. In conclusion, several families of novel BINOL-based symmetrical and asymmetrical axially chiral dendrimers have been synthesized by the reaction of well-known BINOL derivatives as core units with Fréchet-type dendrons and their azido-analogues via "Click" and etherfication reactions for the first time. All new dendrimers were obtained in very good yields which confirm the effectiveness of "Click" reaction in this type of synthesis. The new dendrimers were fully characterized by 1H, 13C and HMQC NMR spectroscopy, mass spectrometry, IR spectroscopy and UV-Vis spectrometry. All new dendrimers show moderate optical activity. Changes in the specific and molar rotation are characterized by a general decrease in the specific rotation and a general increase in the molar rotation with the increase in the dendritic wedges generation in each series of the synthesized dendrimers. By our current knowledge, the increase in the specific rotation as generation increases of (S)-358, (S)-359 and (S)-360 observed in this research is the first such observation. The presence of the triazole ring in the linkage between the core unit and the dendritic wedges plays an important role in reducing of the steric repulsion between the two naphthyl units and in reducing of the effect of the dendritic wedges generation on the torsional angle by making the wedges far away from the attachment point of the two naphthyl units.

The racemic (±)-2,4-di-tert-butyl-6-(((2-(dimethylamino)cyclohexyl)(methyl) amino)methyl)phenol ((±)-(NNMeOtBu)H), (±)-2,4-di-tert-butyl-6-((2-(dimethylamino) cyclohexylamino)methyl)phenol ((±)-(NNHOtBu)H), and (±)-2-(((2-(dimethylamino) cyclohexyl)(methyl)amino) methyl)phenol ((±)-(NNMeOH)H) are chiral ancillary NNO proligands, which synthesis was adapted from a published procedure. Reaction of (±)-(NNMeOtBu)H ((±)-2), (±)-(NNMeOH)H ((±)-3) and (±)-(NNHOtBu)H ((±)-1) with ZnEt2 successfully yielded the corresponding zinc ethyl complexes (±)-5, (±)-6 and (±)-7 respectively; the enantiomerically pure (R,R)-5 was synthesized from (R,R)-2. NMR spectroscopy experiments and X-ray crystallography allowed identification of two stereoisomers for (±)-5, which were observed in solution and in the solid state. The two stereoisomers, 5-α and 5-β, are in equilibrium in solution, with 5-β being thermodynamically favored. The zinc ethyl complexes were found to be unreactive towards weakly acidic alcohols (methanol, ethanol, isopropanol). However, the zinc chloride complex (±)-(NNMeOtBu)ZnCl ((±)-8) and the zinc phenoxide (NNMeOtBu)ZnOPh ((±)-9 and (R,R)-9) could be isolated and characterized. Comparison of the reactivity of both (±)-5 and the reported L₁ZnEt (L₁ = 2,4-di-tert-butyl-6- {[(2'-dimethylaminoethyl) methylamino]methyl}phenolate) in presence of pyridine led to the proposal of a dissociative mechanism explaining the fundamental difference between the two zinc ethyl species. Polymerization of rac-lactide catalyzed by 9 showed that the complex, in its racemic or enantiomerically pure version, has a slow activity and is not stereoselective. / Science, Faculty of / Chemistry, Department of / Graduate

Enantiomerically pure amines have a variety of industrial applications. They are valuable components within the pharmaceutical and agrochemical industry, resolving agents for separation of racemic mixtures by dimeric salt formation and ligands for transition metal catalysts and chemocatalysts. Biocatalysis is increasingly seen as the method of choice for the synthesis of chiral amines. New commercial enzymes being readily available and new screening/evolution technologies allow for enzyme optimisation towards a set of required conditions for chiral amine synthesis. Transaminases are a class of pyridoxal 5’-phosphate (PLP) dependant enzymes that catalyse the reversible transfer of ammonia from an amine donor (e.g. alanine) to a keto acceptor (e.g. acetophenone), allowing the potential for asymmetric methodologies. Transaminases are already well established for the industrial production of α-amino acids and now that research scientists have dealt with some of the problems with equilibrium and substrate/product inhibition, they are being investigated for the industrial application of chiral amines. A multi-enzyme kinetic assay has been utilised for characterisation of newly identified transaminase enzymes in solution phase. Identified transaminases that showed desirable characteristics were cloned and expressed and utilised in the synthesis of amines of interest to industry. Dual enzyme cascade reactions utilising transaminases and either galactose oxidase from Fusarium sp. or monoamine oxidase from Aspergillus niger were used to produce a number of primary and secondary amines in high e.e. and conversion.

The reaction of [BrRe(CO)₄]₂ with 2-(diphenylphosphino)pyridine (PN) and 6-(diphenylphosphino)-2-formylpyridine (PON) was investigated. The reactions were regiospecific and exclusively produced the phosphorus-coordinated products, BrRe(CO)₄(κᵖ-PN) and BrRe(CO)₄(κᴾ-PON). The kinetics for the chelate ring closure (κᴾ→ κᴾᴺ) in BrRe(CO)₄(κᴾ-PN) were confirmed to occur by dissociative CO loss. The reaction of [BrRe(CO)₄]₂ with 2-(diphenylphosphino)pyridine (PN) was modeled computationally by DFT calculations. The preferred reaction pathway for the substitution reaction was determined to occur by direct attack of the pnictogen donor on the dimer and formation of the κᴺ isomer as the kinetic substitution product occurs. The κᴺ kinetic product then rapidly isomerizes to the κᴾ thermodynamic product by way of a reversible ligand dissociation. Treatment of the tetrahedral cluster H₂Ru₃(CO)₃(μ₃-S) (1) with 2-(diphenylphosphino)thioanisole (PS) furnishes the cluster H₂Ru₃(CO)₇(κ²-PS)(μ₃-S) (2). Cluster 2, which exhibits a chelated thiophosphine ligand (κ²-PS), exists as a pair of diastereomers with Keq = 1.55 at 298 K that differ in their disposition of ligands at the Ru(CO)(κ²-PS) center. The PS ligand occupies the equatorial sites (Peq, Seq) in the kinetic isomer and axial and equatorial sites (Pax, Seq) in the thermodynamically favored species. The reversible first-order kinetics to equilibrium have been measured experimentally by NMR spectroscopy and HPLC over the temperature range 293-323 K. The substitution reaction involving 1 and the isomerization of the PS ligand in 2 were investigated by DFT calculations. The computational results support a phosphine-induced expansion of the cluster polyhedron that is triggered by the associative addition of the PS donor to 1. The observed isomerization of the PS ligand in 2 is best explained by a tripodal rotation of the CO and PS groups at the Ru(CO)(κ²-PS) center that is preceded by a regiospecific migration of one of the edge-bridging hydrides to the non-hydride-bridged Ru-Ru bond in 2. The chiral clusters 1,2-Ru₃(μ-H)₂(μ₃-S)(CO)₇(μ-1p1,2p2-POP) (A) and 1,2-Ru₃(μ-H)₂(μ₃-S)(CO)₇(μ-1p2,2p1-POP) (B) were formed were formed from reaction of Ru₃(μ-H)₂(μ₃-S)(CO)₉ with 1-diphenylphosphino-2-[2-(diphenylphosphino)ethoxy]benzene (POP). Chiral clusters A and B were fully characterized by IR and NMR spectroscopy. Additionally, the molecular structure of A was solved by X-ray crystallography. Chiral cluster A was resolved into its enantiomers by preparative HPLC with a chiral column. The enantiomers were characterized by electronic circular dichroism (ECD) spectroscopy and their absolute stereochemical configuration was determined by X-ray crystallography.

No description available.