<p> This thesis describes an investigation into the effects of Lewis acid complexation on the photochemistry of α,β unsaturated carbonyl compounds.</p> <p> Initial studies involved the use of Nuclear Magnetic Resonance (NMR) and Ultraviolet (UV) spectroscopy in examining Lewis acid modification of the photostationary state for E/Z isomerization of various acyclic enones. The results obtained provide a good understanding of the origin of the perturbation of the photostationary state of these systems. In the course of these investigations, the question also arose as to the possible effects of complexation upon the photochemistry of cyclic enone systems where E/Z isomerization cannot occur, particularly whether this would catalyze [2+2] cycloadditions to the enone carbon/carbon double bond. Lewis acid complexed enones are widely used as activated dienophiles in Diels Alder reactions, and have been recently reported to serve as activated 'enophiles' in a photochemical dimerization of coumarin.</p> </p> The examination here is focused upon endo-tricyclo [5.2.1.02,6] deca-4,8-dien-3-one. (See Diagram in thesis). </p> <p> Reported here is a detailed investigation of the photochemistry of the AlEtCl2 complex of this compound, and the results are interpreted mechanistically. The reaction gives rise to a single product which reaches a photostationary state with the reactant complex. The isomerization is formally a [1,3] sigmatropic shift involving the isolated double bond. It seems likely however, to proceed by the formation of an allyl cation intermediate.</p> / Thesis / Master of Science (MSc)

Yes / A highly enantioselective rhodium catalysed asymmetric arylation (RCAA) of nitroolefins with arylboronic acids is presented using a newly developed, C1-symmetric, non-covalent interacted, phellandrene derived, nordehydroabietyl amide-containing chiral diene under mild conditions. Stereoelectronic effects were studied, suggesting an activation of the bound substrate through the secondary amide as a hydrogen-bond donor.

No description available.

The aim of this work was to investigate palladium-catalysed cyclisations of bromoenynamides in the synthesis of amidodienes, which on further reaction or oxidation can lead to a diverse range of heteroaromatic systems. Building upon work within the Anderson group on the palladium-catalysed cyclisations of bromoenynes, we have been able to successfully apply a palladium-catalysed carbopalladation/Stille coupling/electrocyclisation cascade to bromoenynamides and then further develop this to incorporate a Suzuki coupling, leading to bicyclic amidodienes which can undergo selective oxidation to a range of heteroaromatics including indolines, indoles, tetrahydroquinolines and benzazepines. During the investigations into the cascade cyclisation, a reductive cyclisation was discovered which enabled access to a range of monocyclic amidodienes. These could subsequently be subjected to a series of Diels-Alder cycloadditions (thermal, Lewis acid-catalysed, arynes) and oxidations to afford a complimentary range of heteroaromatic systems. Whilst this methodology was successful with bromoenynamides, extension of its application to bromoenynhydrazides, with the hope of accessing a relatively unusual range of heteroaromatic structures including indazoles, cinnolines and diazepines, proved to be more problematic. Finally, expansion of the cascade methodology into a fully intramolecular cyclisation, enabled studies towards the synthesis of the trikentrin family of natural products to be conducted.

C-H functionalisation reactions aim for the selective cleavage of C-H bonds, and formation of a new carbon or heteroatom bond, often with the use of a transition metal catalyst. These reactions offer potential for functionalisation of hydrocarbons in fewer steps than conventional methods, and with high atom efficiency. They are therefore a subject of intense research in organic synthesis. Carbon-heteroatom bond forming reactions are particularly sought after, and useful in the efficient synthesis of many biologically significant groups such as oxazolidinone rings, 1,2 or 1,3 amino alcohols and amino acid analogues. An efficient, cheap and robust method for C-H amination would also be adaptable to varied syntheses of important large molecules. The necessity for complex and efficient transformations with a minimal number of steps means that heteroatom ring closures are also attractive and widely used reactions in such large molecule syntheses. The nitroso group is a highly reactive species which is normally generated in situ by oxidation of a hydroxylamine, for carbon-nitrogen bond forming reactions including the nitroso Heteroatomic Diels Alder reaction, nitroso ene reaction, and nitroso aldol reaction. Nitroso group reactions often show high stereo- and regioselectivity, and have formed key components of the syntheses of important biological molecules. Enantioselectivive protocols for the nitroso-ene reaction and, to a lesser extent, the nitroso HDA reaction, are poorly developed, however, and the range of available intramolecular nitroso reactions is limited. We aimed to establish efficient single-step intermolecular C-H amination reactions, to give 1,2 and 1,3 heteroatom functionalised molecules, and to develop the capacity for enantioselective induction in this reaction, if possible. Having synthesised a model set of unsaturated hydroxycarbamates, we identified a suitable system for nitroso generation, using a catalytic metal and stoichiometric oxidant. This resulted in in situ generation of cyclised product, with the olefin functionality intact. This cyclisation was then optimised and used to obtain a range of new heterocycles. The possibility of enantioselective induction via chiral catalysts was explored, as well as catalytic systems to increase the stereoselectivity of the reaction. In summary, a cheap, novel and reliable method was developed for formation of oxazolidinone rings from unsaturated hydroxycarbamates using an original intramolecular nitroso ene reaction, and a range of unsaturated heterocycles were synthesised in fairly good yields. Distereoselectivity of the nitroso ene cyclisations was optimised. However, to-date, we were unable to develop an enantioselective varient of the reaction. Several related aminations, as well as transformations of N-hydroxyoxazolidinone products, were also attempted during the project.

A highly diastereoselective nickel-catalysed reductive aldol cyclisation is described. Using Ni(acac)2 as a precatalyst and diethylzinc as a stoichiometric reductant, various α,β-unsaturated carbonyl compounds tethered through an amide or ester linkage to a ketone electrophile underwent efficient cyclisation to afford β-hydroxylactams and β-hydroxylactones respectively. The scope of this process is broad with variation in the α,β-unsaturated carbonyl component, ketone and, where applicable, the nitrogen protecting group all tolerated. A series of experiments, including deuterium-labelling studies, were carried out in an attempt to gain insight into the possible reaction mechanisms that might be operative. II. Development of Novel Methodologies for the Silylation and Stannylation of Base-Sensitive Cyclopropenes Two distinct approaches to the synthesis of silyl- and stannylcyclopropenes are described. Using substoichiometric quantities of Cu(acac)2 and 1,2-bis(diphenylphosphino)ethane in combination with (trifluoromethyl)trimethylsilane, a diverse range of 1,3,3-trisubstituted cyclopropenes underwent direct silylation to afford the corresponding 1-silylcyclopropenes in good to excellent yield. Attempts to adapt these conditions to synthesise the corresponding stannylcyclopropenes proved unsuccessful. However, by employing (pentafluoroethyl)tributylstannane and stoichiometric potassium fluoride, it was possible to access 1-stannylcyclopropenes in comparable yields. It was also demonstrated that both the stannyl- and silylcyclopropene derivatives synthesised using these methodologies were able to serve as precursors for a variety of novel molecules that might otherwise be difficult to access using alternative methods.

In contrast to the classic ‘passive template’ approach, an ‘active-metal’ template strategy involves a metal centre which acts as both a template and the catalyst for covalent bond formation in the construction of mechanically interlocked architectures. The crucial formation of a covalent bond between two ‘half-threads’ is promoted by the catalyst and directed through the cavity of the macrocycle by the catalyst’s coordination requirements. The main attractive features of such a synthetic approach are the efficiency (as one step is required instead of two), the rapid assembly of inaccessible structures, the possibility of ‘traceless’ assemblies, the versatility, the possibility to use catalytic amount of the metal template and to provide mechanistic insight. This novel concept was successfully introduced by our group and applied to a wide range of well-known transition metal-catalysed reactions. The thesis will present several examples of active-metal template reactions for the synthesis of interlocked architectures, including Cu(I)-catalysed alkyne-azide cycloaddition (CuAAC popularised as the click reaction), Pd(II)-catalysed alkyne homocouplings Pd(II)-catalysed oxidative Heck cross-couplings and Lewis acids mediated Diels-Alder reactions.

Enzymes as tools in organic synthesis have provided enormous advantages. This thesis deals with the applications of enzymes in the kinetic resolutions of racemic compounds. The stereochemistry of chiral compounds and the kinetics of α/β hydrolase lipases are presented. From a practical point of view, the handling of a large number of parameters that influences the kinetic resolutions, especially enantioselectivity (E-value) are systematically described. A variety of approaches employed for raising the yields to over 50% are additionally discussed. Methods for the preparation of synthetically useful chiral building blocks were developed in this thesis. Thus, resolution of secondary alcohols bearing two vicinal stereocentres are studied. These building blocks can serve as starting materials for the synthesis of various enantiomerically pure compounds for agrochemistry, pharmaceuticals, chemical industry, and particularly for the total synthesis of pheromones. Racemic 3-substitued 2-hydroxybutane derivatives were produced in fairly high diastereomeric purities by a variety of chemical approaches, such as epimerization, metal-catalysed asymmetric addition etc. Kinetic resolution of these racemates was achieved by enzyme-catalysed reactions. Two lipases, Candida antarctica lipase B and Pseudomonas cepacia lipase were found to be useful in acylations as well as hydrolyses. In the biotransformations studied, the presence and nature of the second vicinal stereocentre in the chiral secondary alcohols investigated seemed to be important, e.g. in terms of the efficiencies of sequential kinetic resolutions, and altering the selectivities as well. / QC 20101020

<p>Enzymes as tools in organic synthesis have provided enormous advantages. This thesis deals with the applications of enzymes in the kinetic resolutions of racemic compounds. The stereochemistry of chiral compounds and the kinetics of α/β hydrolase lipases are presented. From a practical point of view, the handling of a large number of parameters that influences the kinetic resolutions, especially enantioselectivity (E-value) are systematically described. A variety of approaches employed for raising the yields to over 50% are additionally discussed.</p><p>Methods for the preparation of synthetically useful chiral building blocks were developed in this thesis. Thus, resolution of secondary alcohols bearing two vicinal stereocentres are studied. These building blocks can serve as starting materials for the synthesis of various enantiomerically pure compounds for agrochemistry, pharmaceuticals, chemical industry, and particularly for the total synthesis of pheromones.</p><p>Racemic 3-substitued 2-hydroxybutane derivatives were produced in fairly high diastereomeric purities by a variety of chemical approaches, such as epimerization, metal-catalysed asymmetric addition etc. Kinetic resolution of these racemates was achieved by enzyme-catalysed reactions. Two lipases, Candida antarctica lipase B and Pseudomonas cepacia lipase were found to be useful in acylations as well as hydrolyses. In the biotransformations studied, the presence and nature of the second vicinal stereocentre in the chiral secondary alcohols investigated seemed to be important, e.g. in terms of the efficiencies of sequential kinetic resolutions, and altering the selectivities as well.</p>

Thesis submitted in fulfilment of the requirements for the degree Master Technologiae: Chemical Engineering In the Faculty of Engineering at Cape Peninsula University of Technology / Most biodiesel plants operate batch-wise using homogeneous alkali catalysts. Recently, several heterogeneous catalysts have been suggested in literature, as they have shown potential for overcoming most of the challenges associated with the application of homogeneous catalysts. Previous published techno-economic comparisons of the two technologies on large-scale processes located in the developed world, have revealed the economic superiority of heterogeneously catalysed processes. Hence, prospect exists for current homogeneously catalysed process plants to be converted to heterogeneously catalysed ones. The objective of this research was to investigate the actual cost benefit of converting a small-scale batch biodiesel plant from homogeneous to heterogeneous catalysed process. For this purpose, a small-scale batch biodiesel plant located in South Africa was taken as the base case homogeneous process. Aspen Batch Process Developer® software was used to perform the process simulations. The homogeneous process was converted to the heterogeneous one and results from process simulation were used to evaluate the economics of both processes, which were compared in terms of fixed capital cost, total manufacturing cost and profitability indicators. During economic evaluation, two types of cost factors were used: one prevailing in developed world and the other one relevant to South Africa. The sensitivity analysis of both processes was further performed in order to investigate the impact of some uncertain parameters on their profitability. Finally, a debottlenecking study was carried out. Results obtained from this study showed an increase in the annual throughput of biodiesel as well as significant savings in the total capital cost for the heterogeneous catalysed process relative to the homogeneous one. As regards the estimation of the total unit manufacturing cost of biodiesel, significant differences arose when using the two types of cost factors. Results of economic analyses estimated using cost factors relative to South Africa suggest an increase in the unit manufacturing cost of biodiesel while using the developed world’s cost factors suggests the opposite. This is due to the higher raw material and energy requirement for the CaO process, while knowing that the direct costs are a bigger proportion of the manufacturing costs estimated using the South African cost factors. Profitability and sensitivity analyses only provided positive results when estimated using the South African cost factors. In all cases, the heterogeneous catalysed process was found to be more promising than the homogeneous one over the prescribed project life. The study showed the importance of using cost factors relevant to a particular economic environment during techno-economic assessment of a process. It was also shown that there are economic benefits when replacing settling with centrifugation in biodiesel production processes. In summary, this thesis makes some important contributions. It presents the first process simulation for biodiesel production using Aspen Batch Process Developer® software and thereby proposes a methodology that is currently scarce in the literature. It also reports the first techno-economic analysis applied to the biodiesel field in South Africa and provides a preliminary insight to owners of biodiesel plants as regards the decision to convert or not their homogeneous catalysed plant to heterogeneous one.