Growth Mechanism of Cadmium Sulfide Nanocrystals

We investigate the growth kinetics of CdS nanocrystals in the quantum confinement regime using time-resolved small-angle X-ray scattering. In contrast to earlier reports for similar systems, we establish that the growth kinetics in this case follows the Lifshitz-Slyozov-Wagner theory, for not only growth of the average diameter of the nanocrystals but also the time dependence of the size distribution and the temperature dependence of the rate constant. This is the first rigorous example of the coarsening process in the quantum confinement (< 5 nm)regime. Ab initio studies for the reaction pathways provide a microscopic understanding of this finding.

Novel kinetic scheme for the ammonium perchlorate gas phase

A novel gas-phase kinetic scheme for ammonium perchlorate (AP) deflagration involving 22 reactions among 18 species is developed. The kinetic scheme is based on a study of the effect of initial conditions on the solution of the differential equations of adiabatic constant-pressure combustion kinetics. The existence of condensed-phase reaction products providesalternate pathways for the consumption of NH3 and HCIOl produced by gas-phase dissociation of AP. Theoretically obtained temperature-time profiles of the novel scheme do not change when the conventional reaction pathways are included, indicatingthat the novel scheme is a substantially faster rate process. The new scheme does not involve the species CIO, which has long been considered a critical component of the AP gas phase and which is included in the conventional reaction pathways.The new scheme develops faster overall reaction rates, steeper temperature-time profiles, and in a deflagration model will result in higher heat-transfer rates from gas phase to the condensed phase.

Charge Density Analysis of a Pentaborate Ion in an Ammonium Borate: Toward the Understanding of Topological Features in Borate Minerals

Structural and charge density distribution studies have been carried out on a single crystal data of an ammonium borate, [C(10)H(26)N(4)][B(5)O(6)(OH)(4)](2), synthesized by solvothermal method. Further, the experimentally observed geometry is used for the theoretical charge density calculations using the B3LYP/6-31G** level of theory, and the results are compared with the experimental values. Topological analysis of charge density based on the Atoms in Molecules approach for B-O bonds exhibit mixed covalent/ionic character. Detailed analysis of the hydrogen bonds in the crystal structure in the ammonium borate provides insights into the understanding of the reaction pathways that net atomic charges and electrostatic potential isosurfaces also give additional such systems. could result in the formation of borate minerals. The input to evaluate chemical and physical properties in such systems.

Bromenium-Catalysed Tandem Ring Opening/Cyclisation of Vinylcyclopropanes and Vinylcyclobutanes: A Metal-Free 3+2+1]/4+2+1] Cascade for the Synthesis of Chiral Amidines and Computational Investigation

We present a detailed study of a 3+2+1] cascade cyclisation of vinylcyclopropanes (VCP) catalysed by a bromenium species (Brd+?Xd-) generated in situ, which results in the synthesis of chiral bicyclic amidines in a tandem one-pot operation. The formation of amidines involves the ring-opening of VCPs with Br?X, followed by a Ritter-type reaction with chloramine-T and a tandem cyclisation. The reaction has been further extended to vinylcyclobutane systems and involves a 4+2+1] cascade cyclisation with the same reagents. The versatility of the methodology has been demonstrated by careful choice of VCPs and VCBs to yield bicyclo4.3.0]-, -4.3.1]- and -4.4.0]amidines in enantiomerically pure form. On the basis of the experimental observations and DFT calculations, a reasonable mechanism has been put forth to account for the formation of the products and the observed stereoselectivity. We propose the existence of a p-stabilised homoallylic carbocation at the cyclopropane carbon as the reason for high stereoselectivity. DFT studies at B3LYP/6-311+G** and M06-2X/6-31+G* levels of theory in gas-phase calculations suggest the ring-opening of VCP is initiated at the p-complex stage (between the double bond and Br?X). This can be clearly perceived from the solution-phase (acetonitrile) calculations using the polarisable continuum model (PCM) solvation model, from which the extent of the ring opening of VCP was found to be noticeably high. Studies also show that the formation of zero-bridge bicyclic amidines is favoured over other bridged bicyclic amidines. The energetics of competing reaction pathways is compared to explain the product selectivity.

Metallacyclocumulenes: A Theoretical Perspective on the Structure, Bonding, and Reactivity

CONSPECTUS: Transition metals help to stabilize highly strained organic fragments. Metallacycles, especially unsaturated ones, provide much variety in this area. We had a sustained interest in understanding new C-C bond formation reactions affected by binuclear transition metal fragments Cp2M. One such study led to the exploration of the bimetallic C-C cleavage and coupled complexes, where the acetylide ligands bridge two metal atoms. The underlying M-C interaction in these complexes inspired the synthesis of a five-membered cyclocumulene complex, which opened a new phase in organometallic chemistry. The metallacyclocumulene produces a variety of C-C cleavage and coupled products including a radialene complex. Group 4 metallocenes have thus unlocked a fascinating chemistry by stabilizing strained unsaturated C4 organic fragments in the form of five-membered metallacyclocumulenes, metallacyclopentynes, and metallacycloallenes. Over the years, we have carried out a comprehensive theoretical study to understand the unusual stability and reactivity of these metallacycles. The unique (M-C-beta) interaction of the internal carbon atoms with the metal atom is the reason for unusual stability of the metallacycles. We have also shown that there is a definite dependence of the C-C coupling and cleavage reactions on the metal of metallacyclocumulenes. It demonstrates unexpected reaction pathways for these reactions. Based on this understanding, we have predicted and unraveled the stabilization factors of an unusual four-membered metallacycloallene complex. Indeed, our prediction about a four-membered heterometallacycle has led to an interesting bonding situation, which is experimentally realized. This type of M-C bonding is intriguing from a fundamental perspective and has great relevance in synthesizing unusual structures with interesting properties. In this Account, we first give a short prologue of what led to the present study and describe the salient features of the structure and bonding of the metallacyclocumulenes. The unusual reaction pathway of this metallacycle is explored next. Similar features of the metallacyclopentynes and metallacycloallenes are briefly mentioned. Then, we discuss the exploitation of the unique M-C bonding to design some exotic molecules such as a four-membered metallacycloallene complex. Our efforts to build a conceptual framework to understand these metallacycles and to exploit their chemistry continue.

Wastewater Electrolysis Cell for Environmental Pollutants Degradation and Molecular Hydrogen Generation

This study proposes a wastewater electrolysis cell (WEC) for on-site treatment of human waste coupled with decentralized molecular H₂ production. The core of the WEC includes mixed metal oxides anodes functionalized with bismuth doped TiO₂ (BiO_x/TiO₂). The BiO_x/TiO₂ anode shows reliable electro-catalytic activity to oxidize Cl- to reactive chlorine species (RCS), which degrades environmental pollutants including chemical oxygen demand (COD), protein, NH4⁺, urea, and total coliforms. The WEC experiments for treatment of various kinds of synthetic and real wastewater demonstrate sufficient water quality of effluent for reuse for toilet flushing and environmental purposes. Cathodic reduction of water and proton on stainless steel cathodes produced molecular H2 with moderate levels of current and energy efficiency. This thesis presents a comprehensive environmental analysis together with kinetic models to provide an in-depth understanding of reaction pathways mediated by the RCS and the effects of key operating parameters. The latter part of this thesis is dedicated to bilayer hetero-junction anodes which show enhanced generation efficiency of RCS and long-term stability.

Chapter 2 describes the reaction pathway and kinetics of urea degradation mediated by electrochemically generated RCS. The urea oxidation involves chloramines and chlorinated urea as reaction intermediates, for which the mass/charge balance analysis reveals that N₂ and CO₂ are the primary products. Chapter 3 investigates direct-current and photovoltaic powered WEC for domestic wastewater treatment, while Chapter 4 demonstrates the feasibility of the WEC to treat model septic tank effluents. The results in Chapter 2 and 3 corroborate the active roles of chlorine radicals (Cl•/Cl₂^-•) based on iR-compensated anodic potential (thermodynamic basis) and enhanced pseudo-first-order rate constants (kinetic basis). The effects of operating parameters (anodic potential and [Cl^-] in Chapter 3; influent dilution and anaerobic pretreatment in Chapter 4) on the rate and current/energy efficiency of pollutants degradation and H₂ production are thoroughly discussed based on robust kinetic models. Chapter 5 reports the generation of RCS on Ir_0.7Ta_0.3O_y/Bi_xTi_1-xO_z hetero-junction anodes with enhanced rate, current efficiency, and long-term stability compared to the Ir_0.7Ta_0.3O_y anode. The effects of surficial Bi concentration are interrogated, focusing on relative distributions between surface-bound hydroxyl radical and higher oxide.

Manganese: Minerals, Microbes, and the Evolution of Oxygenic Photosynthesis

Oxygenic photosynthesis fundamentally transformed our planet by releasing molecular oxygen and altering major biogeochemical cycles, and this exceptional metabolism relies on a redox-active cubane cluster of four manganese atoms. Not only is manganese essential for producing oxygen, but manganese is also only oxidized by oxygen and oxygen-derived species. Thus the history of manganese oxidation provides a valuable perspective on our planet’s environmental past, the ancient availability of oxygen, and the evolution of oxygenic photosynthesis. Broadly, the general trends of the geologic record of manganese deposition is a chronicle of ancient manganese oxidation: manganese is introduced into the fluid Earth as Mn(II) and it will remain only a trace component in sedimentary rocks until it is oxidized, forming Mn(III,IV) insoluble precipitates that are concentrated in the rock record. Because these manganese oxides are highly favorable electron acceptors, they often undergo reduction in sediments through anaerobic respiration and abiotic reaction pathways.

The following dissertation presents five chapters investigating manganese cycling both by examining ancient examples of manganese enrichments in the geologic record and exploring the mineralogical products of various pathways of manganese oxide reduction that may occur in sediments. The first chapter explores the mineralogical record of manganese and reports abundant manganese reduction recorded in six representative manganese-enriched sedimentary sequences. This is followed by a second chapter that further analyzes the earliest significant manganese deposit 2.4 billon years ago, and determines that it predated the origin of oxygenic photosynthesis and thus is supporting evidence for manganese-oxidizing photosynthesis as an evolutionary precursor prior to oxygenic photosynthesis. The lack of oxygen during this early manganese deposition was partially established using oxygen-sensitive detrital grains, and so a third chapter delves into what these grains mean for oxygen constraints using a mathematical model. The fourth chapter returns to processes affecting manganese post-deposition, and explores the relationships between manganese mineral products and (bio)geochemical reduction processes to understand how various manganese minerals can reveal ancient environmental conditions and biological metabolisms. Finally, a fifth chapter considers whether manganese can be mobilized and enriched in sedimentary rocks and determines that manganese was concentrated secondarily in a 2.5 billion-year-old example from South Africa. Overall, this thesis demonstrates how microbial processes, namely photosynthesis and metal oxide-reducing metabolisms, are linked to and recorded in the rich complexity of the manganese mineralogical record.

Quantum Mechanics Studies of Fuel Cell Catalysts and Proton Conducting Ceramics with Validation by Experiment

We carried out quantum mechanics (QM) studies aimed at improving the performance of hydrogen fuel cells. This led to predictions of improved materials, some of which were subsequently validated with experiments by our collaborators.

In part I, the challenge was to find a replacement for the Pt cathode that would lead to improved performance for the Oxygen Reduction Reaction (ORR) while remaining stable under operational conditions and decreasing cost. Our design strategy was to find an alloy with composition Pt3M that would lead to surface segregation such that the top layer would be pure Pt, with the second and subsequent layers richer in M. Under operating conditions we expect the surface to have significant O and/or OH chemisorbed on the surface, and hence we searched for M that would remain segregated under these conditions. Using QM we examined surface segregation for 28 Pt₃M alloys, where M is a transition metal. We found that only Pt₃Os and Pt₃Ir showed significant surface segregation when O and OH are chemisorbed on the catalyst surfaces. This result indicates that Pt₃Os and Pt3Ir favor formation of a Pt-skin surface layer structure that would resist the acidic electrolyte corrosion during fuel cell operation environments. We chose to focus on Os because the phase diagram for Pt-Ir indicated that Pt-Ir could not form a homogeneous alloy at lower temperature. To determine the performance for ORR, we used QM to examine all intermediates, reaction pathways, and reaction barriers involved in the processes for which protons from the anode reactions react with O₂ to form H₂O. These QM calculations used our Poisson-Boltzmann implicit solvation model include the effects of the solvent (water with dielectric constant 78 with pH 7 at 298K). We found that the rate determination step (RDS) was the O_ad hydration reaction (O_ad + H₂O_ad -> OH_ad + OH_ad) in both cases, but that the barrier for pure Pt of 0.50 eV is reduced to 0.48 eV for Pt₃Os, which at 80 degrees C would increase the rate by 218%. We collaborated with the Pu-Wei Wu’s group to carry out experiments, where we found that the dealloying process-treated Pt2Os catalyst showed two-fold higher activity at 25 degrees C than pure Pt and that the alloy had 272% improved stability, validating our theoretical predictions.

We also carried out similar QM studies followed by experimental validation for the Os/Pt core-shell catalyst fabricated by the underpotential deposition (UPD) method. The QM results indicated that the RDS for ORR is a compromise between the OOH formation step (0.37 eV for Pt, 0.23 eV for Pt_2ML/Os core-shell) and H₂O formation steps (0.32 eV for Pt, 0.22 eV for Pt_2ML/Os core-shell). We found that Pt_2ML/Os has the highest activity (compared to pure Pt and to the Pt₃Os alloy) because the 0.37 eV barrier decreases to 0.23 eV. To understand what aspects of the core shell structure lead to this improved performance, we considered the effect on ORR of compressing the alloy slab to the dimensions of pure Pt. However this had little effect, with the same RDS barrier 0.37 eV. This shows that the ligand effect (the electronic structure modification resulting from the Os substrate) plays a more important role than the strain effect, and is responsible for the improved activity of the core- shell catalyst. Experimental materials characterization proves the core-shell feature of our catalyst. The electrochemical experiment for Pt_2ML/Os/C showed 3.5 to 5 times better ORR activity at 0.9V (vs. NHE) in 0.1M HClO₄ solution at 25 degrees C as compared to those of commercially available Pt/C. The excellent correlation between experimental half potential and the OH binding energies and RDS barriers validate the feasibility of predicting catalyst activity using QM calculation and a simple Langmuir–Hinshelwood model.

In part II, we used QM calculations to study methane stream reforming on a Ni-alloy catalyst surfaces for solid oxide fuel cell (SOFC) application. SOFC has wide fuel adaptability but the coking and sulfur poisoning will reduce its stability. Experimental results suggested that the Ni4Fe alloy improves both its activity and stability compared to pure Ni. To understand the atomistic origin of this, we carried out QM calculations on surface segregation and found that the most stable configuration for Ni₄Fe has a Fe atom distribution of (0%, 50%, 25%, 25%, 0%) starting at the bottom layer. We calculated that the binding of C atoms on the Ni4Fe surface is 142.9 Kcal/mol, which is about 10 Kcal/mol weaker compared to the pure Ni surface. This weaker C binding energy is expected to make coke formation less favorable, explaining why Ni₄Fe has better coking resistance. This result confirms the experimental observation. The reaction energy barriers for CHx decomposition and C binding on various alloy surface, Ni₄X (X=Fe, Co, Mn, and Mo), showed Ni₄Fe, Ni₄Co, and Fe₄Mn all have better coking resistance than pure Ni, but that only Ni₄Fe and Fe₄Mn have (slightly) improved activity compared to pure Ni.

In part III, we used QM to examine the proton transport in doped perovskite-ceramics. Here we used a 2x2x2 supercell of perovskite with composition Ba₈X₇M₁(OH)₁O₂₃ where X=Ce or Zr and M=Y, Gd, or Dy. Thus in each case a 4⁺ X is replace by a 3⁺ M plus a proton on one O. Here we predicted the barriers for proton diffusion allowing both includes intra-octahedron and inter-octahedra proton transfer. Without any restriction, we only observed the inter-octahedra proton transfer with similar energy barrier as previous computational work but 0.2 eV higher than experimental result for Y doped zirconate. For one restriction in our calculations is that the O_donor-O_acceptor atoms were kept at fixed distances, we found that the barrier difference between cerates/zirconates with various dopants are only 0.02~0.03 eV. To fully address performance one would need to examine proton transfer at grain boundaries, which will require larger scale ReaxFF reactive dynamics for systems with millions of atoms. The QM calculations used here will be used to train the ReaxFF force field.

One-step synthesis of 2-pentanone from ethanol over K-Pd/MnOx-ZrO2-ZnO catalyst

A highly active and selective K-Pd/MnOx-ZrO2-ZnO catalyst for the one-step synthesis of 2-pentanone from ethanol is described. The possible reaction pathways for ethanol reaction over K-Pd/MnOx-ZrO2-ZnO catalyst were investigated by means of TPSR, CO2- and NH3-TPD techniques. The reactions were performed in a fixed bed continuous flow reactor. Complete conversion with high selectivity for 2-pentanone, was observed under 370 similar to 390degreesC, 2 similar to 4 MPa, GHSV = 8000 similar to 10,000 h(-1) and LHSV < 1.25 h(-1) conditions. Ethanol reactions over K-Pd/MnOx-ZrO2-ZnO catalyst showed that the catalyst could catalyze dehydrogenation. aldol. dehydration and hydrogenation reactions. Both acidic and basic properties are found on the surface of K-Pd/MnOx-ZrO2-ZnO catalyst, whose multifunctionality with the combination of basic, acid and metal sites may be responsible for the efficiency of the K-PdMnOx-ZrO2-ZnO catalyst. (C) 2004 Elsevier B.V. All rights reserved.

Investigation of catalyst effects in enantioselective copper- and rhodium-mediated transformations of α-diazocarbonyl compounds

This thesis describes the synthesis and reactivity of a series of α-diazocarbonyl compounds with particular emphasis on the use of copper-bis(oxazoline)-mediated enantioselective C–H insertion reactions leading to enantioenriched cyclopentanone derivatives. Through the use of additives, the enantioselectivity achieved with the copper catalysts for the first time reaches synthetically useful levels (up to 91% ee). Chapter one provides a comprehensive overview of enantioselective C–H insertions with α-diazocarbonyl compounds from the literature. The majority of reports in this section involve rhodium-catalysed systems with limited reports to date of asymmetric C–H insertion reactions in the presence of copper catalysts. Chapter two focuses on the synthesis and C–H insertion reactions of α-diazo-β-keto sulfones leading to α-sulfonyl cyclopentanones as the major product. Detailed investigation of the impact of substrate structure (both the sulfonyl substitutent and the substituent at the site of insertion), the copper source, ligand, counterion, additive and solvent was undertaken to provide an insight into the mechanistic basis for enantiocontrol in the synthetically powerful C–H insertion process and to enable optimisation of enantiocontrol and ligand design. Perhaps the most significant outcome of this work is the enhanced enantioselection achieved through use of additives, substantially improving the synthetic utility of the asymmetric C–H insertion process. In addition to the C–H insertion reaction, mechanistically interesting competing reaction pathways involving hydride transfer are observed. Chapter three reports the extension of the catalyst-additive systems, developed for C–H insertions with α-diazo-β-keto sulfones in chapter two, to C–H insertion in analogous α-diazo-β-keto phosphonate and α-diazo-β-keto ester systems. While similar patterns were seen in terms of ligand effects, the enantiopurities achieved for these reactions were lower than those in the cyclisations with analogous α-diazo-β-keto sulfones. Extension of this methodology to cyclopropanation and oxium ylide formation/[2,3]-sigmatropic rearrangement was also explored. Chapter four contains the full experimental details and spectral characterisation of all novel compounds synthesised in this project, while details of chiral stationary phase HPLC analysis and X-ray crystallography are included in the appendix.

Synthetic and mechanistic aspects of the reactions of α-diazosulfoxides

The research described in this thesis focuses, principally, on synthesis of stable α-diazosulfoxides and investigation of their reactivity under various reaction conditions (transition-metal catalysed, photochemical, thermal and microwave) with a particular emphasis on the reactive intermediates and mechanistic aspects of the reaction pathways involved. In agreement with previous studies carried out on these compounds, the key reaction pathway of α-diazosulfoxides was found to be hetero-Wolff rearrangement to give α-oxosulfine intermediates. However, a competing reaction pathway involving oxygen migration from sulfur to oxygen was also observed. Critically, isomerisation of α-oxosulfine stereoisomers was observed directly by 1H NMR spectroscopy in this work and this observation accounts for the stereochemical outcomes of the various cycloaddition reactions, whether carried out with in situ trapping or with preformed solutions of sulfines. Furthermore, matrix isolation experiments have shown that electrocyclisation of α-oxosulfines to oxathiiranes takes place and this verifies the proposed mechanisms for enol and disulfide formation. The introductory chapter includes a brief literature review of the synthesis and reactivity of α-diazosulfoxides prior to the commencement of research in this field by the Maguire group. The Wolff rearrangement is also discussed and the characteristic reactions of a number of reactive intermediates (sulfines, sulfenes and oxathiiranes) are outlined. The use of microwave-assisted organic synthesis is also examined, specifically, in the context of α-diazocarbonyl compounds as substrates. The second chapter describes the synthesis of stable monocyclic and bicyclic lactone derivatives of α-diazosulfoxides from sulfide precursors according to established experimental procedures. Approaches to precursors of ketone and sulfimide derivatives of α-diazosulfoxides are also described. The third chapter examines the reactivity of α-diazosulfoxides under thermal, microwave, rhodium(II)-catalysed and photochemical conditions. Comparison of the results obtained under thermal and microwave conditions indicates that there was no evidence for any effect, other than thermal, induced by microwave irradiation. The results of catalyst studies involving several rhodium(II) carboxylate and rhodium(II) carboxamidate catalysts are outlined. Under photochemical conditions, sulfur extrusion is a significant reaction pathway while under thermal or transition metal catalysed conditions, oxygen extrusion is observed. One of the most important observations in this work was the direct spectroscopic observation (by 1H NMR) of interconversion of the E and Z-oxosulfines. Trapping of the α-oxosulfine intermediates as cycloadducts by reaction with 2,3-dimethyl-1,3-butadiene proved useful both synthetically and mechanistically. As the stereochemistry of the α-oxosulfine is retained in the cycloadducts, this provided an ideal method for characterisation of this key feature. In the case of one α-oxosulfine, a novel [2+2] cycloaddition was observed. Preliminary experiments to investigate the reactivity of an α-diazosulfone under rhodium(II) catalysis and microwave irradiation are also described. The fourth chapter describes matrix isolation experiments which were carried out in Rühr Universität, Bochum in collaboration with Prof. Wolfram Sander. These experiments provide direct spectroscopic evidence of an α-oxosulfine intermediate formed by hetero-Wolff rearrangement of an α-diazosulfoxide and subsequent cyclisation of the sulfine to an oxathiirane was also observed. Furthermore, it was possible to identify which stereoisomer of the α-oxosulfine was present in the matrix. A preliminary laser flash photolysis experiment is also discussed. The experimental details, including all spectral and analytical data, are reported at the end of each chapter. The structural interpretation of 1H NMR spectra of the cycloadducts, described in Chapter 3, is discussed in Appendix I.

Synthesis and reactivity of α-diazo-β-keto sulfoxides: scope and synthetic potential

The research described in this thesis focuses on the design and synthesis of stable α-diazosulfoxides and investigation of their reactivity under a variety of conditions (transition-metal catalysis, thermal, photochemical and microwave) with a particular emphasis on the synthesis of novel heterocyclic compounds with potential biological activity. The exclusive reaction pathway for these α-diazosulfoxides was found to be hetero-Wolff rearrangement to give α-oxosulfine intermediates. In the first chapter, a literature review of sulfines is presented, including a discussion of naturally occurring sulfines, and an overview of the synthesis and reactivity of sulfines. The potential of sulfines in organic synthesis and recent developments in particular are highlighted. The second chapter discusses the synthesis and reactivity of α-diazosulfoxides, building on earlier results in this research group. The synthesis of lactone-based α-diazosulfoxides and, for the first time, ketone-based benzofused and monocyclic α-diazosulfoxides is described. The reactivity of these α-diazosulfoxides is then explored under a variety of conditions, such as transition-metal catalysis, photochemical and microwave, generating labile α-oxosulfine intermediates, which are trapped using amines and dienes, in addition to the spontaneous reaction pathways which occur with α-oxosulfines in the absence of a trap. A new reaction pathway was explored with the lactone based α-oxosulfines, involving reaction with amines to generate novel 3-aminofuran-2(5H)-ones via carbophilic attack, in very good yields. The reactivity of ketone-based α-diazosulfoxides was explored for the first time, and once again, pseudo-Wolff rearrangement to the α-oxosulfines was the exclusive reaction pathway observed. The intermediacy of the α-oxosulfines was confirmed by trapping as cycloadducts, with the stereochemical features dependant on the reaction conditions. In the absence of a diene trap, a number of reaction fates from the α-oxosulfines were observed, including complete sulfinyl extrusion to give indanones, sulfur extrusion to give indanediones, and, to a lesser extent, dimerisation. The indanediones were characterised by trapping as quinoxalines, to enable full characterisation. One of the overriding outcomes of this thesis was the provision of new insights into the behaviour of α-oxosulfines with different transition metal catalysts, and under thermal, microwave and photolysis conditions. A series of 3-aminofuran-2(5H)-ones and benzofused dihydro-2H-thiopyran S-oxides were submitted for anticancer screening at the U.S. National Cancer Institute. A number of these derivatives were identified as hit compounds, with excellent cell growth inhibition. One 3-aminofuran-2(5H)-one derivative has been chosen for further screening. The third chapter details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research. The data for the crystal structures are contained in the attached CD.

Catalyst, additive and substrate effects in intramolecular aromatic additions of alpha-diazoketones

This thesis is focused on transition metal catalysed reaction of α-diazoketones leading to aromatic addition to form azulenones, with particular emphasis on enantiocontrol through use of chiral copper catalysts. The first chapter provides an overview of the influence of variation of the substituent at the diazo carbon on the outcome of subsequent reaction pathways, focusing in particular on C-H insertion, cyclopropanation, aromatic addition and ylide formation drawing together for the first time input from a range of primary reports. Chapter two describes the synthesis of a range of novel α-diazoketones. Rhodium and copper catalysed cyclisation of these to form a range of azulenones is described. Variation of the transition metal catalyst was undertaken using both copper and rhodium based systems and ligand variation, including the design and synthesis of a novel bisoxazoline ligand. The influence of additives, especially NaBARF, on the enantiocontrol was explored in detail and displayed an interesting impact which was sensitive to substituent effects. Further exploration demonstrated that it is the sodium cation which is critical in the additive effects. For the first time, enantiocontrol in the aromatic addition of terminal diazoketones was demonstrated indicating enantiofacial control in the aromatic addition is feasible in the absence of a bridgehead substituent. Determination of the enantiopurity in these compounds was particularly challenging due to the lability of the products. A substantial portion of the work was focused on determining the stereochemical outcome of the aromatic addition processes, both the absolute stereochemistry and extent of enantiopurity. Formation of PTAD adducts was beneficial in this regard. The third chapter contains the full experimental details and spectral characterisation of all novel compounds synthesised in this project, while details of chiral stationary phase HPLC and 1H NMR analysis are included in the appendix.

The synthesis and biological evaluation of lanostane and cholestane-type natural products

The main objective of this thesis is to outline the synthetic chemistry involved in the preparation of a range of novel lanostane and cholestane derivatives, and subsequent investigation into their biological activity in cancer cells. The biological results obtained throughout the project have driven the strategic synthesis of new compounds, in an effort to optimise the anti cancer potential of lanostane and cholestane derivatives. The first chapter begins with an overview of steroidal compounds and details a literature review of the natural sources of these moieties, as well as their biosynthesis and reported synthetic derivatives. The biological activity of interesting natural and synthetic analogues is also discussed. In addition, an insight into some currently prescribed pharmaceutical compounds, with functional groups relevant to this project, is presented. The second chapter discusses the methods employed for the synthesis of these novel lanostane and cholestane derivatives, and comprises three main sections. Firstly, various oxidation products of lanosterol are synthesised, mainly via epoxidations of the C-8,9 and C- 24,25 alkenes, and also allylic oxidations at these positions. Secondly, amine derivatives of lanosterol are formed by cleaving the lanostane side chain, thereby yielding a new cholestane nucleus, and performing several reductive aminations on the resulting key aldehyde intermediates. Various amines such as piperidine, morpholine, diethylamine and aniline are employed in the reductive amination reactions to yield novel cholestane steroids with amine side chains. Finally, starting from stigmasterol and proceeding with the same methodology of cleaving the steroidal side chain and subsequently performing reductive aminations, novel cholestane derivatives of the biologically active amines are synthesised. The cytotoxicity of these compounds against CaCo-2 and U937 cell lines is presented in terms of percentage viability of cells, IC50 value and apoptosis. The MTT assay is used to determine the percentage viability of cells, and the IC50 data is generated from the MTT results. Apoptosis is measured in terms of fold increase relative to a carrier control. In summary, the compounds formed are discussed in terms of chemical synthesis, spectroscopic interpretation and biological activity. The main reaction pathways involved in the chemistry within this project are various oxidations and reductive amination. The final chapter is a detailed account of the full experimental procedures for the compounds synthesised during this work, including characterisation using spectroscopic and analytical data.