Thesis advisor: Kian L. Tan / Thesis advisor: James P. Morken / Described herein are four different research projects spanning over two different research groups. The first two projects describe the development and application of scaffolding catalysts for the (1) site-selective silylation of ribonucleosides and (2) the distal and diastereoselective hydroformylation of homoallylic alcohols. These projects emphasize the effectiveness of scaffolding catalysts to bind a hydroxyl-containing substrate and control the site- or regioselectivity of a reaction using said substrate. The third project describes a hydroxyl-directed diboration of homoallylic and bis-homoallylic alcohols. The hydroxyl-containing 1,2-bis(boronates) are valuable intermediates for further synthetic manipulations. One such manipulation, a hydroxyl-directed Suzuki cross-coupling reaction, is the focus of the final project. This directed cross-coupling reaction forges carbon-carbon bonds in a stereoselective manner, highlighted in the total synthesis of the naturally occurring compound, debromohamigeran E. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / This dissertation describes the development of four metal-catalyzed carbon-carbon bond forming methods. The first project presented is a palladium-catalyzed proparyl-allyl cross-coupling which proceeds via a kinetic resolution to give enantioenriched 1,5-enynes. Next the asymmetric rhodium-catalyzed hydroformylation of 1-alkenes is described. This reaction delivers synthetically useful a-chiral aldehydes in up to 98:2 er and up to 15:1 branched to linear ratio. The development of a unique nickelcatalyzed asymmetric Kumada coupling of cyclic sulfates is presented. Mechanistic studies reveal the reaction proceeds via an SN2 oxidative addition of a chiral nickelcomplex. Finally, a-Substituted allyl bis(boronic) esters, which are derived from 1,2-diboration of 1,3-dienes are shown to undergo allylation and subsequent Suzuki coupling with aldehydes tethered to sp2 electrophiles. The carbocycle products obtained bear three contiguous stereocenters and were used as intermediates in the synthesis of complex molecules. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / This dissertation will discuss in depth four main projects pertaining to the synthesis and utility of organoboronates for the construction of enantioenriched small molecules. First, reaction optimization and substrate scope expansion of the platinum-catalyzed enantioselective diboration of alkenes are reported. Based on extensive experimental and computational mechanistic analysis, a preliminary stereochemical model is also proposed. A practical boron-Wittig reaction is presented in which synthetically challenging di- and trisubstituted vinyl boronates can be accessed in a highly stereoselective fashion from readily available starting materials. The enantioselective diboration of cis- and trans-vinyl boronates furnished novel 1,1,2-tris(boronate) esters in up to 95:5 er. The intermediate tris(boronate) esters were employed successfully in deborylative alkylations to furnish enantioenriched internal vicinal bis(boronates) in excellent diasteoselectivity. In the final chapter, an enantioselective palladium-catalyzed intramolecular Suzuki-Miyaura coupling between allyl boronates and aryl electrophiles is disclosed. The newly developed transformation provides enantioenriched 5, 6, and 7-membered carbocycles in up to 93:7 er. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / This dissertation will describe the development of three transition metal-catalyzed syntheses of nonracemic organoboronates. The first chapter explains the development of a palladium-catalyzed enantiotopic-group-selective cross-coupling of geminal bis(boronates) with alkenyl electrophiles. This process enables the synthesis of highly valuable nonracemic disubstituted allylic boronates. Chapter two describes a palladium-induced 1,2-metallate rearrangement of vinylboron “ate” complexes. The newly developed process incorporates an alternative route for the transmetallation step of Suzuki-Miyaura cross-couplings. Lastly, an enantioselective platinum-catalyzed hydrosilylation of alkenyl boronates is disclosed. This reaction enables the synthesis of nonracemic geminal silylboronates for the divergent synthesis of functionalized / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Evan R. Kantrowitz / Thesis advisor: Mary F. Roberts / Living organisms depend on enzymes for the synthesis using small molecule precursors of cellular building blocks. For example, the amino acid aspartate is synthesized in one step by the amination of oxaloacetate, an intermediate compound produced in the citric acid cycle, exclusively by means of an aminotransferase enzyme. Therefore, function of this aminotransferase is critical to produce the amino acid. In the Kantrowitz Lab, we seek to understand the molecular rational for the function of enzymes that control rates for the biosynthesis of cellular building blocks. If one imagines the above aspartate-synthesis example as a single running conveyer belt, any oxaloacetate that finds its way onto that belt will be chemically transformed to give aspartate. We can extend this notion of a conveyer belt to any enzyme. Therefore, the rate at which the belt moves dictates the rate of synthesis. Now imagine many, many conveyer belts lined in a row to give analogy to a biosynthesis pathway requiring more than one enzyme for complete chemical synthesis. This is such the case for the biosynthesis of nucleotides and glucose. Nature has developed clever tricks to exquisitely control the rate of product output but means of altering the rate of one or some of the belts in the line of many, without affecting the rate of others. This type of biosynthetic rate regulation is termed allostery. Studies described in this dissertation will address questions of allosteric processes and the chemistry performed by two entirely different enzymes and biosynthetic pathways. The first enzyme of interest is fructose-1,6-bisphosphatase (FBPase) and its role in the biosynthesis of glucose. Following FBPase introduction in Chapter One, Chapter Two describes the minimal atomic scaffold necessary in a new class of allosteric type 2 diabetes drug molecules to effect catalytic inhibition of <italic>Homo sapiens</italic> FBPase. Following, is the second enzyme of interest, aspartate transcarbamoylase (ATCase) and its role in the biosynthesis of pyrimidine nucleotides. Succeeding ATCase introduction in Chapter Three, Chapter Four describes a body of work exclusively about the catalysis by ATCase. This work was inspired by the human form of the enzyme following the human genome project completion providing data that show likely <italic>Homo sapiens</italic> ATCase is not allosterically regulated. Chapter Five describes work on a allosterically-regulated, mutant ATCase and provides a biochemical model for the molecular rational for the catalytic inhibition upon cytidine triphosphate (CTP) binding to the allosteric site. The experimental techniques used for answering research questions were enzyme X-ray crystallography, <italic>in silico</italic> docking, kinetic assay experiments, genetic sub-cloning and genetic mutation. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / Described herein are methods for asymmetric allylation. Chapter 1 describes the scope of the Pd-catalyzed asymmetric diboration of prochiral allenes. The products of this process possess both a chiral allylboronate functional group and a vinylboronate moiety. The allylboronate functionality can subsequently be used for imine allylation, without isolation of the diboron intermediate, resulting in the formation of atypical allylation products through a tandem, one-pot sequence. Furthermore, enantioselection in the catalytic diboration and chirality transfer in the subsequent imine allylation are high; thus, non-racemic, protected homoallylic amines, and other derivatives, are produced in high enantiomeric excess. Chapter 2 describes the discovery and development of a transition-metal-catalyzed asymmetric conjugate allylation of allylboronate ester nucleophiles to activated enones. The scope, utility, and mechanistic aspects of this new reaction are discussed. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Kian L. Tan / Chapter 1. We reported the first synthesis of all-carbon quaternary centers via hydroformylations using a catalytic directing group. With the ability of reversibly and covalently binding to a substrate, and coordinating to a metal center, scaffolding catalyst 1.1 is able to direct the branch-selective hydroformylation of 1,1-disubstituted olefins under mild temperature. Chapter 2. We have designed and synthesized a chiral organocatalyst 2.11. This catalyst is able to covalently bind to one hydroxyl, and utilize the induced intramolecularity to stereoselectively functionalize the other hydroxyl within a cis-1,2-diol via electrophile transfer. Catalyst 2.11 was used in the desymmetrization of meso-1,2-diols under mild conditions (4 C to room temperature), leading to high yields and selectivities for a broad substrate scope. Chapter 3. Catalyst 3.1 and 3.6 were demonstrated to selectively bind to primary hydroxyls over secondary hydroxyls. By combining the binding selectivity with asymmetric catalysis, these scaffolding catalysts were shown to promote the selective silylation of secondary hydroxyls within terminal (S)-1,2-diols. The reversal of substrate bias was further applied to a regiodivergent kinetic resolution of racemic terminal 1,2-diols, producing secondary protected products in synthetically practical levels of enantioselectivity (>95:5 er) and yields (≥40%). Time course studies of this reaction further revealed the optimal condition to form the primary silylated product in high s-factor. Chapter 4. Based on the previous understanding of catalyst 4.5 and 4.6, the exclusive catalyst recognition of cis-1,2-diols within polyhydroxylated molecules was further discovered. This unique functional group display recognition was further allied with the catalyst's ability to stereoselectively differentiate hydroxyls within cis-1,2-diols, enabling the site-selective protection, functionalization, and activation of the inherently less reactive axial hydroxyl groups within carbohydrates. This methodology also enables the selective functionalization of multiple complex molecules, including digoxin, mupirocin, and ribonucleosides, demonstrating the potential power of scaffolding catalysis in the rapid access to valuable synthetic derivatives of polyhydroxylated compounds. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Dehydroaromatization of methane (MDA) reaction was investigated over platinum modified Mo/H-ZSM-5 catalysts which were pre-carbided at 750 oC. The influence of platinum on the catalytic performance and product selectivity of Mo/H-ZSM-5 catalysts for the MDA reaction at 700 oC was studied. The presence of platinum led to a slight decrease in methane conversion. As the platinum loading increased, the methane conversion decreased further and the catalytic stability increased with time-on-stream (TOS) during the MDA reaction. Aromatic selectivities above 90% were obtained with catalysts containing low platinum loadings (0.5 and 1.0 wt.%), with benzene being the most prominent product. A decrease in coke selectivity and coke deposits was noted with the platinum modified Mo/H-ZSM-5 zeolite catalysts. A comparative study was performed to compare platinum, palladium and ruthenium promoted Mo/H-ZSM-5 zeolite catalysts with un-promoted Mo/H-ZSM-5. The ruthenium promoted catalyst proved to be superior in catalytic performance, with a higher methane conversion obtained than found for platinum promoted and palladium promoted Mo/H-ZSM-5 catalysts. Benzene selectivity of about 60% was obtained for ruthenium and palladium promoted Mo/HZSM- 5 catalysts and the total aromatic selectivity was maintained at 90%. TGA results showed a total reduction of 50% by weight of carbon deposited on the promoted Mo/H-ZSM-5 catalyst. Dehydroaromatization of methane was studied over tin modified Pt/Mo/HZSM-5 catalysts and compared to Pt/Mo/H-ZSM-5 catalyst at 700 oC. Addition of tin decreased the activity towards methane aromatization. However, the formation of aromatic compounds was favoured. The CO FT-IR adsorption and CO chemisorption techniques showed that the catalyst preparation method had an effect on the catalytic performance of tin modified Pt/Mo/H-ZSM-5 catalysts. High aromatic selectivity and low coke selectivity were obtained with co-impregnated and sequentially impregnated Pt/Sn catalysts. While a decrease in the formation rate of carbonaceous deposits is mainly dependent on the availability of platinum sites for the hydrogenation of carbon. The order of sequentially loading platinum and tin has an effect on the electronic and structural properties of platinum as shown by XPS and FT-IR studies. CO chemisorption and the FT-IR adsorption studies showed that addition of tin decreased the adsorption capacity of the platinum surface atoms. Catalyst preparation methods and successive calcination treatments affected the location of both tin and platinum atoms in the catalyst. Catalysts prepared by the coimpregnation method showed a good platinum dispersion, better than found for the sequentially impregnated catalysts. The MDA reaction was carried out at 800 oC over manganese modified H-ZSM-5 zeolite catalysts prepared by the incipient wetness impregnation method. The effect of a number of parameters on the catalytic performance and product selectivity was investigated, such as reaction temperature, manganese precursor-type, tungsten as promoter, manganese loading and use of noble metals. The study of the effect of reaction temperature showed that the methane conversion increased linearly with increase in reaction temperature from 700 to 850 oC. The selectivity towards aromatic compounds (of about 65%) was attained for the reactions performed at 750 and 800 oC. Formation rate of carbonaceous deposits increased linearly with increase in reaction temperature. The use of different manganese precursors to prepare Mn/H-ZSM-5 catalysts had an effect on both the catalytic behaviour and the product distribution. High catalytic activities were obtained for the catalysts prepared from Mn(NO3)2 and MnCl2 salts. However, the product distribution was significantly different, with the Mn(NO3)2 catalyst being more selective towards aromatic compounds while the MnCl2 catalyst was more selective toward coke. The effect of manganese loading was studied at 800 oC and an optimum catalyst activity was obtained at 2 and 4 wt.% manganese loadings. The aromatic selectivity above 70% and coke selectivity of 20% were obtained for a 2 wt.% loaded catalyst. Addition of tungsten as a promoter onto the 2 wt.% loaded catalyst (2Mn/H-ZSM-5) lowered the catalytic activity but the catalyst remained fairly stable with increase in TOS. Tungsten modified catalysts favoured the formation of carbonaceous deposits over aromatic compounds. TGA results showed a coke deposit of 164 mg/g.cat, an 88% increase in coke deposit when tungsten was used a promoter. Noble metals were added to reduce the total amount of coke on the tungsten modified Mn/H-ZSM-5 catalysts. The presence of a noble metal favoured the formation of aromatic compounds and suppressed the formation of coke. Platinum and ruthenium promoted catalysts were the active catalysts and aromatic selectivity increased from 12% to 55% and 46% respectively. A reduction in the total amount of coke deposit on the platinum promoted catalyst (42%) and the ruthenium promoted catalyst (31%) was noted.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment for the degree of Master of Science in Chemistry, 2017 / The aim of this study was to synthesize helical carbon nanofibers with controlled diameter by using copper nanoparticles contained inside hollow carbon sphere. In this work, different methods have been explored to synthesize copper nanoparticles contained inside mesoporous hollow carbon spheres in order to minimize the sintering effect of the copper nanoparticles. Mesoporous hollow carbon spheres were used not only as a support for the copper nanoparticles but to stabilize and disperse these nanoparticles to prevent the formation of aggregates. Mesoporous hollow carbon spheres were synthesized using a hard templating method, in which mesoporous silica spheres or polystyrene spheres were used as a sacrificial template. Carbon nanofibers with different morphologies, including straight and helical fibers were obtained by a chemical vapor deposition method where acetylene was decomposed over copper nanoparticles contained inside mesoporous hollow carbon spheres catalyst at 350 °C. The synthesized carbon nanofibers were grown on the surface of the mesoporous hollow carbon spheres as the methods used to synthesize the catalyst failed to incorporate copper nanoparticles inside the spheres. Differences in the diameter of the straight and helical carbon nanofibers were observed from both catalysts. This supports the important effect of particle size on influencing the shape of the synthesized carbon nanofibers. / XL2018

MSc (Chemistry), Faculty of Science, University of the Witwatersrand, 2002