This thesis outlines the work carried out in the last three and half years concerning the development of environmentally benign acylation reactions and determination of the range of these reactions through substrate screening and investigations into the mechanisms by which they are operating.

The focus of this thesis is the development of conjugated homo- and heterometallic polyyne complexes for which the opto-electronic properties may be tuned to provide potential applications in molecular electronic devices.

This thesis investigates the use of aluminium trichloride and acetyl chloride to functionalise saturated hydrocarbons and probe the mechanism by which this functionalisation occurs. It also looks at the use of iridium catalysis to form carbon-boron bonds from carbon-hydrogen bonds in naphthalenediimides or NDIs. Chapter one reviews work published in the field of carbon-hydrogen bond functionalisation; from the traditional reactions of hydrocarbons as simple as combustion to cutting-edge selective C-H activation in natural product synthesis. Chapter two investigates experimentally the mechanism of the “Baddeley reaction”; the low-temperature interaction of decalin with aluminium trichloride and acetyl chloride, identifying key intermediates on the mechanistic pathway and the order of reaction in acylating reagent and substrate. Chapter three applies the Baddeley methodology to other saturated hydrocarbons, selected for certain commonalities with decalin based on the mechanism established. The results of these reactions include unusual sketetal rearrangements and the synthesis of novel compounds. Chapter four focuses on C-H borylation of NDIs at the naphthalene core; optimisation of the reaction uses microwave heating and both mono-borylated and di-borylated isomers can be synthesised. These boronic esters formed are suitable starting materials for further reactions; examples of possible Suzuki reactions are detailed. Chapter five details experimental procedures associated with the work of the previous three chapters.

The activation of styrene towards nucleophilic addition and a Diels‒Alder reaction through η6-binding to ruthenium in [RuCp(η6-stryene)]PF6 has been achieved. Nucleophilic addition solely took place at the terminal carbon of the alkene, to give the anti-Markovnikov product. Good to excellent conversions were gained for a variety of cyclic secondary and primary amines, as well as dimethyl malonate. A Diels‒Alder reaction with 1,2,3,4,5-pentamethylcyclopentadiene was achieved with moderate to good conversions. An SNAr reaction with amines and dimethyl malonate has also been shown to occur with activated 4-chlorotoluene, through [RuCp(η6-4-chlorotoluene)]PF6. Arene exchange has been achieved for [RuCp(η6-benzene)]PF6 with 4-chlorotoluene in up to a 69% conversion using a combination of heat and irradiation using a 400 W medium pressure mercury lamp. Unfortunately attempts to achieve a catalytic reaction proved unsuccessful. The N,N’-dimethylurea promoted activation of 1-chloro-4-nitrobenzene towards SNAr reactions was achieved. Under optimised conditions, good to excellent yields were obtained for a series of cyclic secondary amines. Primary and acyclic secondary amines were less successful under optimised condition, with the exception of 5-amino-1-pentanol. The imidazole catalysed conversion of unactivated carboxylic acids to primary amides was achieved using urea as the nitrogen source. Good to excellent yield were obtained for variety of carboxylic acids under optimised conditions. It was demonstrated secondary amides could also be synthesised, when substituted ureas were used such as N,N’-dimethylurea and 1,3-diphenylurea, to give N-methyl and N-phenyl amides. Although possible mechanisms were explored, results so far are inconclusive.

This investigation addresses the understudied area of the research and development of hydrogen bonded metal-organic complexes featuring the alkaline earth metals magnesium and calcium. This work presents the crystal structures and thermal behaviour of a series of metal-organic and organic crystalline complexes synthesised from metal salts and pyridine carboxylic, dicarboxylic acid and chloranilic acid ligands, characterised primarily by X-ray diffraction. Chapter 1 introduces crystal engineering, intermolecular interactions, and functional crystalline materials, followed by a literature review addressing metal-organic frameworks (MOFs), hydrogen bonded metal-organic complexes, magnesium MOFs and alkaline earth metal complexes synthesised from pyridine carboxylic, dicarboxylic and tricarboxylic acid and chloranilic acid. Chapter 2 outlines the theory of the techniques used to analyse the synthesised materials, focusing on single crystal X-ray diffraction, followed by Chapter 3 which documents the sample preparation and the experimental details. Chapter 4 describes the crystal structures of fourteen coordination complexes synthesised from magnesium and calcium salts and the three isomers of pyridine carboxylic acid. This work was carried out in order to identify structural trends such as the most common coordination geometries of the metal centres, the ways in which the ligands coordinate and any recurring hydrogen bonding motifs. Chapter 5 discusses attempts to synthesise an alkaline earth metal analogue of a metal-containing ‘metalloligand’ of the formula M(C7H4NO4)2(H2O)2, in which the metal (M) is N,O-chelated by pyridine-2-carboxylate-4-carboxylic acid, and the subsequent combination of these materials with the diamines o-tolidine and m-xylylenediamine. This chapter also reports the structure of a magnesium coordination complex resulting from a hydrothermal reaction, and the subsequent transformation of this complex to a new crystal structure which contains the doubly deprotonated magnesium analogue of the originally targeted ‘metalloligand’. Chapter 6 describes the crystal structures of three complexes synthesised from pyridine carboxylic acids and chloranilic acid, and the complex resulting from the combination of one of these organic ‘supramolecular ligands’ with a copper salt. Finally, two new calcium-chloranilate coordination polymers are reported, one of which has an interesting anionic 3D structure.

This thesis presents research into the development of sustainable methodology for the synthesis of amides, esters and polypropionate fragments. As well as a literature review of efficient natural product synthesis. Acylals are a known class of reagent that have been utilized within literature for a wide range of synthetic methodologies. Herein we present acylals as new highly active reagents for the N-/O-acylation of amines and alcohol nucleophiles for the synthesis of a range of formamides, acetamides, formate esters and acetate esters. It has been demonstrated that a range of acyl groups can be transferred including short and long chain alkyls, acryloyl, benzoyl, phenyl acetyl and biologically important trifluoroacetyl group, thus enabling the synthesis of a range of benzylamides and esters. These acylation reagents have also been shown to demonstrate inherent N-/O- selectivity towards the amine and alcohol groups of serine methyl ester. The scope and limitations of these reagents of the use of acylals has been investigated through the N-formylation of a range of unprotected amino acids, and for the synthesis of the biologically important tripeptide f-MLP. As well as the acylation/formylation of the ω-amino residue of a lysine residue within a decapeptide. Finally, it has also been demonstrated that a simple switch in pH from basic to acidic conditions for diols can change from O-acylation to acetal formation. The synthesis of enantiomerically enriched dihydropyrans from the heteo-Diels-Alder reaction of 1-alkoxy dienes and ethyl glyoxalate has been presented. A series of stereoselective derivatisation reactions were developed including, hydroboration, hydrogenation, epoxidation, dihydroxylation and epimerization which procced with stereoselectivity to afford a range of complex enantiomerically enriched polypropionate based building blocks, which are ideally suited for the synthesis of polyketide natural products through a “plug and play” approach. Chemistry has also been presented which makes use of the orthogonally addressable synthetic handles of the pyran building blocks. Utilization of either the masked aldehyde character or the ester functionality present allows for further elaboration of the pyran building blocks by selectively introducing new functionality.

Rats were chronically treated with methamphetamine over a seven week period during which time their weights, food consumption and drinking rates were recorded. The effects of chronic treatment with, and withdrawal from, methamphetamine on amine metabolism in selected brain regions was investigated. Three groups of experimental animals were studied: chronically treated rats, rats which had been withdrawn from the drug for 36 h and controls. The parameters chosen to reflect changes in catecholamine metabolism in the brain were: tyrosine hydroxylase activity and the levels of noradrenaline, dopamine and their non-O-methylated metabolites and of phenylalanine and tyrosine. The metabolism of serotonin was studied by measuring the levels of "free" tryptophan in the plasma,and the levels of tryptophan and serotonin in the brain. Initially the methamphetamine was administered in the drinking water at doses of 5, 10, 20 and 40 mg/kg/24 h increasing in a stepwise manner over a period of 20 days. This dose was found to produce toxic reactions in the rats and it was found that it was not possible to control the intake of the drug. In subsequent experiments the rats were given 5, 10 and 15 mg/kg/24 h i.p. increasing in a stepwise manner over a period of 15 days. The first set of injected animals did not develop tolerance to the anorexic effects of methamphetamine and the chronically treated and withdrawn animals showed changes in tyrosine hydroxylase activity and in the levels of noradrenaline and dopamine. The three other sets of injected animals did develop tolerance to the anorexic effects of methamphetamine. Tyrosine hydroxylase and the levels of noradrenaline, dopamine, their non-O-methylated metabolites and of tryptophan and serotonin did not change in these chronically-treated or withdrawn animals, but changes were seen in the levels of "free" tryptophan in the plasma and the levels of most amino acids in the brain.

Both unsupported and supported cuprous compounds have been shown to be totally as catalysts for the hydrogenation of propylene at temperatures up to 185°C and one atmosphere total pressure. Various other supported copper catalysts are, however, active for this reaction and a model for the catalytic hydrogenation is proposed. The most active copper catalyst was used to study the hydrogenation of alpha-methyl styrene in a 250 ml. slurry reactor and the conditions necessary for kinetic control of the reaction rate were determined. The reaction was found to be first order in hydrogen and zero order in alpha-methyl styrene. Application of these results requires a knowledge of the solubility of hydrogen in alpha-methyl styrene and cumene and was acquired by experiment. The solubility in both liquids increased in the range from room temperature to 150°C and obeyed Henry's law at pressures up to 7 bar. The diffusivity of hydrogen in alpha-methyl styrene was determined at temperatures between 110 and 150°C and was found to increase with temperature and to be independent of pressure. A 2.5 litre slurry reactor was also utilized to study the hydrogenation of alpha-methyl styrene under conditions leading to mass transfer control of the reaction rate. Mass transfer coefficients were evaluated and compared with those calculated from correlations in the literature.

A brief summary of the anti-cancer activity of the ellipticines is made together with an indication of the geographical distribution of plants containing ellipticine and related alkaloids. A comprehensive review of the reported synthetic routes to ellipticine and its derivatives is included. During the course of investigations of one route to the tetracyclic system several new dihydropyridines have been isolated and identified. Modification of this route has led to the preparation of several, previously unreported, ellipticine derivatives while the examination of a new synthetic route has led to the preparation of 5-ethylellipticine. Attempts have been made to adapt this procedure to the preparation of other derivatives.

This thesis concerns itself with developing methodology for the synthesis of vinyl-isocyanide natural products and evaluating the biological properties of their common aglycone’s vinyl-isocyanide warhead.