This thesis reports findings in two projects utilising sulfur as a chiral auxiliary in asymmetric synthesis. The first section describes the enantioselective synthesis of isomeric harmonine in 8 steps with a 21% overall yield highlighting sulfinimine chemistry to selectively install the necessary chirality at the amine in the C-17 position. Ring closing metathesis was used to install the internal olefin which led to an inseparable mixture of geometric isomers. Further efforts were made towards the selective installation of the desired Z alkene. Two approaches are discussed, the first using alkyne metathesis as a key step with the second using alkenyl silanes in metathesis. The second section provides a discussion on the novel rearrangement of 2-vinylaziridine-2-carboxylates, derived from enantiopure sulfinimines, to unprecedented chiral cyclic sulfoximines. The synthesis of substituted cyclic sulfoximines has been achieved in one pot with high yields and complete stereocontrol. The mild conditions utilised allows access to a plethora of novel sulfoximine containing heterocycles in only three steps from commercially available aldehydes. A mechanistic hypothesis for the key rearrangement step is also proposed. Further functionalisation of these novel compounds provided access to a group of interesting cyclic sulfinamides in one pot using a catalytic amount of Zn(OTf)2. The formal synthesis of trachelanthamidine via the direct transformation a cyclic sulfoximine into a pyrroline is also disclosed, highlighting the use of these novel species in targeted synthesis.

Amphiphilic polymeric materials have been used in pharmaceutical and biotechnology products for decades. These polymeric materials have grown considerably from their earlier use as surfactants, sequestering agents, drug delivery systems such as microparticles used as controlled release depots, to multifunctional polymeric micelles capable of targeting and controlling release of drugs. These generations of targeted polymeric micelles can be engineered to navigate complex biological environment, incorporate biological functionalities to achieve target specificity and control of drug concentration at tissue and cellular levels. Toward the goal to improve therapy efficacy and safety, a plethora of multivalent targeted polymeric nanocarriers fabricated from amphiphilic diblock and triblock copolymers have been investigated. Flower micelles is a type of advanced micellar architecture resulted from ABA amphiphilic triblock copolymers self-assembly. Present project focused on design, synthesis of a library of biocompatible, amphiphilic ABA triblock copolymers, based on a polyacrylate and poylacrylamide backbone, and selfassembly of these materials into flower micelles. Similar design drives the synthesis process toward precise engineering of block copolymers, therefore a combination of recently developed controlled polymerisation techniques which allowed production of uniform polymer chain and control of chain length in a reproducible quick manner have been used. A library of novel well-defined copolymers, poly(n-butyl acrylate) block-poly(Nhydroxyethylacrylamide)-block-poly(n-butyl acrylate), (n-BA)m-b-(N-HEA)nb-(n-BA)m, have been synthesised successfully using single electron transfer living radical polymerisation (SET-LRP), a 30 minutes step to yield >99% monomer conversion, and photo-induced living radical polymerisation (photoinduced LRP). Hydrophobicity can substantially influence supramolecular assembly of copolymers in aqueous environment. In this work, effect of copolymers hydrophobicity has been studied in a sub-library of copolymers in which poly(n-BA)m hydrophobic blocks length increased as follow: (n-BA)57-b-(NHEA)40-b-(n-BA)57 > (n-BA)9-b-(N-HEA)40-b-(n-BA)9 >(n-BA)3-b-(NHEA)40-b-(n-BA)3. Decreasing of polymeric micellar size was observable with increasing hydrophobic block lengths. Moreover, we found out that there is a clear relationship between copolymers cytotoxicity on Calu-3 cell line model and hydrophobicity of copolymers. Our data suggested that copolymers induce cytotoxicity by apoptotic means rather than interrupting cell membrane integrity. Covalent conjugation of active target ligands to the compositional ABA copolymers enable the formation of targeted-flower micelles. Exploiting the fact that numerous cancerous tissues are known to overexpress folate receptors, relative to normal tissues, folic acid used as active targeting ligand model. In this work, we attempted to create a folic acid-targeted flower micelle, however, conjugation data were not conclusive and therefore, no folic acid-targeted flower micelles were fabricated.

Thermoelectric devices provide an excellent method for the generation of electrical power from low grade waste heat from energy production, but the current best inorganic materials used for such devices are expensive and require dwindling resources. Organic semiconductors derived from tetracenes may therefore provide an excellent alternative. However existing synthetic methods are step and atom inefficient and as such would provide poor yield and cost efficiency in mass production, and there is a paucity of n-type organic materials compared to p-type, which limits device design. This report details attempts to develop rapid, general and scalable syntheses of tetracenes. A two-step process for the synthesis of substituted tetracenes via [3,3]-sigmatropic rearrangement cascade reaction from a series of bis-propargyl diols is disclosed. This method furnished a variety of tetracenes in up to quantitative yield from commercially available materials. Mechanistic insights into the novel anionic Chugaev cascade derived from DFT calculations are disclosed along with computed and experimentally derived HOMO-LUMO gaps. A brief analysis of the predicted electronic properties of some of the materials synthesised is then presented. In investigating bis-allenic cascades, an 8-membered ring was isolated in low yield. Mechanism of formation and the scope of the cascade which formed the carbocycle are briefly discussed. A second method toward the synthesis of tetracenes via an attempted nitrile cyclisation reaction is disclosed. The method suffered from the rapid oxidation of the derived peri-diaminotetracene, and attempts to temper the reactivity of the resultant tetracene were stymied by a difficulty in forcing a second ring closure, which proved resistant to further attempts to force cyclisation. A final method derived from an (E)-selective carbomagnesiation of 2-butyne-1,4-diol with various benzylmagnesium chlorides and trapping with iodine is disclosed. This allowed for a facile and high yielding Negishi-cross coupling with various benzylzinc halides to allow for various substitution patterns on the outermost aryl rings. A high yielding Stahl oxidation gave access to various dialdehydes in excellent to quantitative yields, allowing for a Lewis acid-mediated double closure with TiCl4. This step proved to be limited by the necessity of electron-donating groups to facilitate the double Bradsher closure, but allowed access to multiple substituted tetracenes.

The work in this thesis principally describes the synthesis and formation of a series of tiara- like complexes, a class of cyclic transition metal complexes of varying sizes. Despite the numerous examples of this class of complex within the scientific literature, little to no control over the size of the reported molecules is reported. This work aims to attain some degree of selectivity over the nuclearity of the synthesised complexes by two methods; firstly, the modification of reaction conditions with a focus on the choice of solvent used for the synthesis and the second method involving a modification of the structure of the ligand used. Five tiara-like complexes have been synthesised and characterised. The first of these, Pd NAC (1), gives only a single, six-membered product when the reaction is performed using THF as the solvent. When protic alcohols are used instead of THF, additional complexes of different sizes are seen within the MALDI mass spectrum. Replacement of the amide group of the ligand with an ester to remove the possibility of hydrogen-bonding shows the synthesis of six- membered and eight-membered rings when the complex is synthesised in THF. Electrolysis of a DMF solution of 1 results in accumulation of charge accompanied by a change of colour from yellow to red-brown; TEM imaging of the solution shows the presence of Pd nanoparticles. The second tiara synthesised, Pd ETG (2), gives a larger eight-membered ring which results from the relocation of the carbonyl moiety relative to 1. This complex was shown to be able to host two molecules of methyl iodide, as evidenced by the single crystal structure; this is the first and only example of a tiara-like complex able to encapsulate two molecules of solvent simultaneously. The same ligand, methyl 3-mercaptopropionate (MMP) was used to synthesise both nickel- and palladium-containing tiara-like complexes. The two isomers are compared in detail by NMR and crystallography; the palladium complex crystallises into a higher symmetry R-3 space group when compared to P-1 for the nickel complex. Mixed Pd/Pt tiara-like complexes were examined; it was observed that modification of the starting ratio of the metal precursors gave a corresponding shift in the ratio of the mixed products observed in the mass spectra.

Chapter 1 gives an introduction to benzisothiazole and benzothiazole natural products. It explores the scope of natural products that are known within these families and discusses what they are used for, how they have been made and how they may have been biosynthesised. Chapter 1 provides a review of each family of natural products in turn. Chapter 2 describes the total synthesis of the benzisothiazole natural products aulosirazole and pronqodine A, and a series of unnatural analogues. The Chapter begins with a short discussion on the use of the Diels-Alder reaction for the formation of naphthoquinones, then illustrates this strategy for the first synthesis of aulosirazole. The chapter continues with the synthesis of pronqodine A, a structurally similar natural product. The Chapter ends with an evaluation of these compounds as inhibitors of indoleamine-2,3-dioxygenase. Chapter 3 contains work towards the synthesis of the benzothiazole containing natural product erythrazole A. The first half of the Chapter focuses on the formation of the heterocyclic core, originally attempting to use a biomimetic strategy but switching to an approach utilising the oxidative cyclisation of thioamides. The second half of the Chapter discusses many routes to synthesise and introduce the terpene derived side chain. Chapter 4 contains experimental detail for the work carried out.

Chapter 1 starts by showing why anti-fouling natural products became an area of wide interest over the past few decades, giving some background about the main anti-fouling technologies. It is followed by the presentation of various anti-fouling natural products and the key features those compounds have in common with the target molecule of this project, synoxazolidinone C. The oxazolidinone and 4-oxazolidinone cores are shown in a few examples of natural products described in the literature, including the synoxazolidinones. The synthesis of synoxazolidinones A and B achieved by Pierceis presented, before to introduce the target molecule synoxazolidinone C. The isolation, structure, biological activity as well as a proposed biosynthesis of this compound will be shown. The Chapter ends with different methods used to build the fused bicyclic ring skeleton and an initial strategy towards the total synthesis of synoxazolidinone C. Chapter 2 focuses on the synthesis of the conjugated bicyclic ring skeleton with the substituents on the aromatic ring as present in the natural product. The Chapter begins with the study of a double ring closure mechanism towards the fused bicyclic ring skeleton with an aromatic substituent and its oxidation to install the conjugated double bond in between. The synthesis was modified to build the fused bicyclic ring and the double bond in one step. A suitable aromatic building block was then prepared to access the desired analogue of the natural product without substituents on the pyrrolidine ring. Chapter 3 explains the work towards the synthesis of deschloro-synoxazolidinone C, desguanidino-synoxazolidinone C, and the natural product synoxazolidinone C itself. With the revised strategy detailed in Chapter 2, the suitable amines were prepared to access the conjugated bicyclic ring with additional substituents on the pyrrolidine ring. Those substituents are used in an effort to install the chlorine and the guanidine. A brand new condensation double ring closure methodology was also developed as a rapid access to a late stage material towards deschloro-synoxazolidinone C. Chapter 4 describes a structure-activity relationship; it presents the biological evaluation of 18 synthetic analogues of the natural product. Several assays were performed such as the viability, anti-inflammatory, minimuminhibition concentration (MIC), inhibition of biofilm and antioxidant.

Herein is described the catalytic in situ generation of nucleophilic allylmetal species through the activation of allylic C-H bonds. Reactivity is achieved through initial carbometalation of an enyne, followed by the key 1,4-alkenyl-to-allyl metal migration which generates the allylmetal intermediate. This new mode of reactivity was firstly employed in the rhodium-catalysed diastereoselective reaction of arylboron reagents with enynones, to give products containing three contiguous stereocentres. Initial discovery and optimisation of this reaction was performed by Benjamin Partridge. Through use of a chiral sulfur olefin ligand, products could be obtained in high enantioselectivites. Secondly, a three-component coupling between 1,3-enynes, arylboronic acids and imines is described. The use of a chiral rhodium catalyst allowed the synthesis of a range of homoallylic amines with excellent control of stereoselectivity (>95:5 dr, up to 99% ee).

The intention for this thesis was to observe whether the application of microwave heating, or using CO2 as a reaction medium, could induce an acceleration for producing both homopolymers and block copolymers containing Poly(vinyl acetate) using RAFT polymerisation while maintaining the desired control. Chapter 1 examines the various polymer synthesis techniques utilised throughout this thesis. This includes an introduction to controlled radical polymerisations such as RAFT, microwave heating and the use of supercritical carbon dioxide as an alternative reaction medium. Chapter 2 details the various experimental reactors and characterisation methods used. The high pressure autoclaves used for solubility studies and producing polymers are examined, as well as the microwave reactor. Characterisation techniques used such as Gel Permeation Chromatography (GPC) and Nuclear Magnetic Resonance (NMR) are also detailed Chapter 3 examined the influence of applying conventional and microwave heating during the RAFT polymerisation of vinyl acetate. A series of experiments were designed to observe the effect of varying different reactant concentrations, as well as introducing a solvent into the reaction mixture. Each of these were examined to determine which induced an acceleration when using microwaves, while maintaining the desired control. Chapter 4 investigated the RAFT polymerisation of vinyl acetate while using CO2 as a viscosity modifier. Various reaction parameters such as monomer loading and RAFT : AIBN ratio were altered to examine the effect on the final polymer produced. Kinetic studies allowed the application of CO2 to be compared with RAFT polymerisation with conventional and microwave heating from Chapter 3. Chapter 5 studied the synthesis of block copolymers of PVAc and poly (vinyl pivalate) (PVPi). This involved the application of conventional and microwave heating for both the PVAc macro-RAFT agent and the 2nd PVPi block, to see the influence on the final block polymer properties, including the level of homopolymer impurity and final conversion. Additional reactions also looked at the use of CO2 when producing the PVPi block. Chapter 6 summarises the overall conclusions from the research presented in this thesis, and discusses possible future work.

The work described in this thesis was undertaken at the University of Nottingham between October 1981 and November 1984, under the supervision of Dr. R. Rudham. Except where indicated by reference, it is the original work of the author and has not been submitted for any other degree. The photocatalytic dehydrogenation of liquid alcohols (methanol, ethanol, propan-1-ol and propan-2-ol) by suspensions of platinum and other metals supported on anatase have been investigated by following carbonyl compound formation under a nitrogen atmosphere. Measurements were made over the temperature range 278-303 K using filtered 366 nm U.V. radiation. Reaction on photodeposited catalysts was consistently associated with an activation energy of 20 + 1 kJ mol-1 , although the activity fell in the sequence: PT/TiO2 > Pd/TiO2 > Rh/TiO2 > Au/TiO2 – O for catalysts with a metal content of 0.5 wt%. The activation energy is identical to that for photoreaction on the anatase support in the presence of oxygen and is believed to be associated with the transport of photoelectrons through the anatase to either metal particles or adsorbed oxygen. Activities and activation energies for carbonyl compound formation from the photocatalytic dehydrogenation of the individual alcohols were effectively identical on the same catalyst, indicating that the photocatalytic dehydrogenation reaction is not governed by the physical or chemical properties of the reactant alcohol. With platinized anatase prepared by hydrogen reduction there was an appreciable dark reaction, which was absent with catalysts prepared by photodeposition. It is believed that reduction in hydrogen at elevated temperature renders the anatase support non-stoichiometric, a process favoured by spillover of hydrogen atoms from the platinum particles. The low activation energy for photocatalysis on hydrogen reduced catalyst is considered to be associated with the non-stoichiometric nature of the anatase, which presumably provides an energetically favourable mechanism for photoelectron transport to the metal particles and negates the photoelectron traps responsible for an activation energy of 20 ± 1 kJ mol-1 on the non-reduced catalysts. A radical mechanism for photocatalytic dehydrogenation is proposed. This mechanism predicts a l1m1 ting quantum yield of one half, which is in good agreement with the value obtained from experiments at different light intensities.

This thesis begins in Chapter One with a discussion of the role of electrophilic cyclisation in the synthesis of tetrahydrofurans. Chapter Two begins with a discussion of the synthesis of iodo-olactones, by the iodolactonisation of β-silyloxy-δ-alkenoic acids (Scheme A). It will show how the potential of this chemistry has been expanded by proving the absolute stereochemistry at the iodine centre. Chapter Two goes on to consider the stereospecific synthesis of 2,3,5-trisubstituted iodo-tetrahydrofurans by the related iodo-etherification of homoallylic alcohols (Scheme B). This is facilitated by the use of anhydrous conditions. The synthesis of 2,3,5-trisubstituted iodo-tetrahydrofuranacetic acid esters and 2,3,5-trisubstituted hydroxy-tetrahydrofuranacetic acid esters by the iodocyclisation of geometrically pure (E)- and (Z)-β-hydroxy-δ-alkenoates was then developed and the stereochemical outcome of the reactions was proven (Scheme C). Targets were chosen which illustrated the utility of the key cyclisations of β-hydroxy-δ-alkenoates. Chapter Three discusses the synthesis of muscarine 93. It was chosen to synthesise muscarine from the cyclisation of the (Z)-β-hydroxy-δ-alkenoate 146. This synthesis is particularly versatile as it not only allows the preparation of muscarine itself, but also of various potentially highly biologically active analogues 146a. The second target selected was Goniofufurone 170. Approaches to this molecule will be discussed in Chapter Four. Model work in the synthesis of goniofufurone began with the cyclisation of the (E)-β-hydroxy-δ-alkenoate 53b, which indeed, led to the facile synthesis of the iodolactone 204. However, early attempts to incorporate the natural side chain met with limited success. Chapter Five discusses an approach to the 2-oxabicyclo-2.2.11-heptane ring system, which has been synthesised by the radical cyclisation of various β,y-unsaturated tetrahydrofurans of the general form shown in Scheme D.