I. Development of the In Situ Reductive Ozonolysis of Alkenes with Tertiary Amine N-Oxides. II. Progress toward the Asymmetric Synthesis of Peroxyplakoric Acid A3.

Ozone, first discovered in the mid 1800’s, is a triatomic allotrope of oxygen that is a powerful oxidant. For over a century, research has been conducted into the synthetic application and mechanism of reactions of ozone with organic compounds. One of the major areas of interest has been the ozonolysis of alkenes. The production of carbonyl compounds is the most common synthetic application of ozonolysis. The generally accepted mechanism developed by Rudolf Criegee for this reaction involves the 1,3-electrocyclic addition of ozone to the π bond of the alkene to form a 1,2,3-trioxolane or primary ozonide. The primary ozonide is unstable at temperatures above -100 °C and undergoes cycloreversion to produce the carbonyl oxide and carbonyl intermediates. These intermediates then recombine in another 1,3-electrocyclic addition step to form the 1,2,4-trioxolane or final ozonide. While the final ozonide is often isolable, most synthetic applications of ozonolysis require a subsequent reductive or oxidative step to form the desired carbonyl compound. During investigations into the nucleophilic trapping of the reactive carbonyl oxide, it was discovered that when amines were used as additives, an increased amount of reaction time was required in order to consume all of the starting material. Surprisingly, significant amounts of aldehydes and a suppression of ozonide formation also occurred which led to the discovery that amine N-oxides formed by the ozonation of the amine additives in the reaction were intercepting the carbonyl oxide. From the observed production of aldehydes, our proposed mechanism for the in situ reductive ozonolysis reaction with amine N-oxides involves the nucleophilic trapping of the carbonyl oxide intermediate to produce a zwitterionic adduct that fragments into 1O2, amine and the carbonyl thereby avoiding the formation of peroxidic intermediates. With the successful total syntheses of peroxyacarnoates A and D by Dr. Chunping Xu, the asymmetric total synthesis of peroxyplakorate A3 was investigated. The peroxyplakoric acids are cyclic peroxide natural products isolated from the Plakortis species of marine sponge that have been found to exhibit activity against malaria, cancer and fungi. Even though the peroxyplakorates differ from the peroxyacarnoates in the polyunsaturated tail and the head group, the lessons learned from the syntheses of the peroxyacarnoates have proven to be valuable in the asymmetric synthesis of peroxyplakorate A3. The challenges for the asymmetric synthesis of peroxyplakorate A3 include the stereospecific formation of the 3-methoxy-1,2-dioxane core with a propionate head group and the introduction of oxidation sensitive dienyl tail in the presence of a reduction sensitive 1,2-dioxane core. It was found that the stereochemistry of two of the chiral centers could be controlled by an anti-aldol reaction of a chiral propionate followed by the stereospecific intramolecular cyclization of a hydroperoxyacetal. The regioselective ozonolysis of a 1,2-disubstituted alkene in the presence of a terminal alkyne forms the required hydroperoxyacetal as a mixture of diastereomers. Finally, the dienyl tail is introduced by a hydrometallation/iodination of the alkyne to produce a vinyl iodide followed by a palladium catalyzed coupling reaction. While the coupling reaction was unsuccessful in these attempts, it is still believed that the intramolecular cyclization to introduce the 1,2-dioxane core could prove to be a general solution to many other cyclic peroxides natural products.

Rhodium-Catalyzed Hydroboration: Directed Asymmetric Desymmetrization

Rhodium-catalyzed asymmetric hydroboration in conjunction with directing groups can be used control relative and absolute stereochemistry. Hydroboration has the potential to create new C–C, C–O, and C–N bonds from an intermediate C–B bond with retention of stereochemistry. Desymmetrization resulting in the loss of one or more symmetry elements can give rise to molecular chirality, i.e., the conversion of a prochiral molecule to one that is chiral. Unsaturated amides and esters hold the potential for two-point binding to the rhodium catalyst and have been shown to direct the regiochemistry and impact stereochemistry in asymmetric hydroborations of acyclic β,γ-unsaturated substrates. In the present study, the pendant amide functionality directs the hydroboration cis in the cyclic substrates studied; the corresponding ester substrates do so to a lesser extent. The enantioselectivity is determined by regioselective addition to the re or si site of the rhodium-complexed alkene. The effect of catalyst, ligand and borane on the observed diastereoselectivity and enantioselectivity for a variety of cyclopentenyl ester and amide substrates is discussed.

MOLECULAR DYNAMICS STUDIES OF SIMPLE MODEL FLUIDS AND WATER CONFINED IN CARBON NANOTUBE

Molecular Dynamics (MD) simulation is one of the most important computational techniques with broad applications in physics, chemistry, chemical engineering, materials design and biological science. Traditional computational chemistry refers to quantum calculations based on solving Schrodinger equations. Later developed Density Functional Theory (DFT) based on solving Kohn-Sham equations became the more popular ab initio calculation technique which could deal with ~1000 atoms by explicitly considering electron interactions. In contrast, MD simulation based on solving classical mechanics equations of motion is a totally different technique in the field of computational chemistry. Electron interactions were implicitly included in the empirical atom-based potential functions and the system size to be investigated can be extended to ~106 atoms. The thermodynamic properties of model fluids are mainly determined by macroscopic quantities, like temperature, pressure, density. The quantum effects on thermodynamic properties like melting point, surface tension are not dominant. In this work, we mainly investigated the melting point, surface tension (liquid-vapor and liquid-solid) of model fluids including Lennard-Jones model, Stockmayer model and a couple of water models (TIP4P/Ew, TIP5P/Ew) by means of MD simulation. In addition, some new structures of water confined in carbon nanotube were discovered and transport behaviors of water and ions through nano-channels were also revealed.

HIGH TEMPERATURE RARE EARTH COMPOUNDS: SYNTHESIS, CHARACTERIZATION AND APPLICATIONS IN DEVICE FABRICATION

As the area of nanotechnology continues to grow, the development of new nanomaterials with interesting physical and electronic properties and improved characterization techniques are several areas of research that will be remain vital for continued improvement of devices and the understanding in nanoscale phenomenon. In this dissertation, the chemical vapor deposition synthesis of rare earth (RE) compounds is described in detail. In general, the procedure involves the vaporization of a REClx (RE = Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho) in the presence of hydride phase precursors such as decaborane and ammonia at high temperatures and low pressures. The vapor-liquid-solid mechanism was used in combination with the chemical vapor deposition process to synthesize single crystalline rare earth hexaboride nanostructures. The crystallographic orientation of as-synthesized rare earth hexaboride nanostructures and gadolinium nitride thin films was controlled by judicious choice of specific growth substrates and modeled by analyzing x-ray diffraction powder patterns and crystallographic models. The rare earth hexaboride nanostructures were then implemented into two existing technologies to enhance their characterization capabilities. First, the rare earth hexaboride nanowires were used as a test material for the development of a TEM based local electrode atom probe tomography (LEAP) technique. This technique provided some of the first quantitative compositional information of the rare earth hexaboride systems. Second, due to the rigidity and excellent conductivity of the rare earth hexaborides, nanostructures were grown onto tungsten wires for the development of robust, oxidation resistant nanomanipulator electronic probes for semiconductor device failure analysis.