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The work described in the thesis is concerned with the development of new methodologies for the aminoalkylation of a wide range of aromatic substrates using non-aqueous conditions. The Mannich reagents derived from secondary amines, bis(N,N-dialkylamino)methanes laminalsl, and alkoxy(N,N-dialkylamino)methanes laminol ethersl, were used in "in situ" reactions activated by various Lewis acids. The objective was to devise new methods whereby a high concentration of hydrogen chloride did not accumulate in the reaction mixture. It was established that aminals activated by acetyl chloride or sulphur dioxide can be used for the aminoalkylation of n-excessive heterocycles. Good regioselective control was achieved for orthaaminoalkylation of phenols, especially 2,5-dimethylphenol, by both aminals and aminol ethers in the presence of sulphur dioxide. The use of chlorosilane derivatives in "in situ" reactions of aromatic heterocycles was investigated. Good yields of monosubstitution products were obtained using trichloromethyl-, dichlorodimethyl- and chlorotrimethyl-silane with aminol ethers in reactions with N-methylpyrrole. Aminals, however, activated by chlorotrimethylsilane afforded the 2,5-diaminoalkylated pyrroles. The catalytic effect of chlorotrimethylsilane in this system was established. The ipso addition-with-elimination reactions of aryltrialkylstannanes with aminals and aminol ethers in the presence of chlorosilane derivatives were examined. The Mannich reagents derived from primary amines bis(N-alkoxymethyl)-alkyl and -aralkyl amines lbis(aminol ethers)1 have been used in reactions with electron rich aromatic compounds. The aim was to activate an alkoxymethyl group and to protect the product by the same functional group. A versatile method for the preparation of secondary amine Mannich bases was developed. The possibility of carrying out tandem reactions with two different nucleophiles was investigated briefly. Bis(aminol ethers) derived from B -phenylethylamines, possessing a methoxy substituent at the 3-position of the ring, afforded a convenient method for the preparation of N-arylmethyltetrahydroisoquinoline derivatives.

The work contained in this thesis re-examines the mechanism of formation of aziridines from lead tetra-acetate (LTA) oxidation of N-aminoquinazolones in the presence of alkenes. Hitherto, the intermediates involved in these aziridinations were thought to be the corresponding N-nitrenes. However, evidence presented in this thesis shows that these intermediates are the corresponding N-acetoxyaminoquinazolones. This conclusion was supported, inter alia, by the low temperature (-20C) 1H n.m.r. spectra of N-acetoxyaminoquinazolones, obtained by LTA oxidation of the corresponding N-aminoquinazolones at -20C. Solutions of N-acetoxyamino-2-ethylquinazolone were found to be stable at this temperature but brought about the aziridination of alkenes when allowed to warm to room temperature in the presence of the latter. An analogy is drawn between aziridination of alkenes using N-acetoxyaminoquinazolones and epoxidation of alkenes using peracids. Using N-acetoxyamino-2-ethylquinazolone, aziridination of geraniol is more regioselective and aziridination of cyclohex-2-en-1-ol is more facially selective than epoxidation of these alkenes using peracids. Aziridination of cyclohex-3-en-1-ol is also examined and in contrast to epoxidation using peracids, aziridination of this alkene is stereo- specific and gives only the syn-aziridine. As solutions of the N-acetoxyamino-2-ethylquinazolone are stable at -20C, it is now possible to bring about aziridination of LTA-labile alkenes: the addition of silyl ketene acetals to these solutions followed by warming to room temperature afforded the corresponding N-protected alpha-amino acid esters in excellent yields. The same methodology has been used to bring about aziridination of vinylstannanes and vinylsilanes. Desilylation of the derived silyl-substituted aziridines provides a new route to 2H-azirines and the presumed intermediate aziridinyl carbanions have been intercepted with benzaldehyde or protons as electrophiles. Aziridination of alkenes by oxidative (LTA or PhI(OAc)2) addition of N-aminoquinazolones in the presence of trifluoroacetic acid is also examined; the dramatic increases in yields in some cases are rationalised by protonated N-acetoxyaminoquinazolone intermediates.

This thesis is a continuation of the work by Bonnert to produce taxanes from glucose. The application of a Stork silyl methylene radical cyclisation to the allylic alcohol (1) led to the diol (2). This has a trans ring junction and has introduced regiospecifically a hydroxy methylene group adjacent to an hydroxyl group. This provides the necessary stereochemistry for the B-C ring junction in taxanes. However the ring hydroxyl group has the wrong stereochemistry for taxinine. In an endeavour to correct this, the allylic alcohol (1) was inverted and the radical cyclisation performed again. This resulted though in the radical and the hydrogen atom adding trans, once more, despite the fact that this gave rise to the formation of two cis ring junctions. Therefore, this too produced the wrong stereochemistry at the B-C ring junction. A series of studies were undertaken to assess the generality of the Robinson annulation of a carbohydrate. This study was extended to the incorporation the C-7 hydroxyl group in taxol during this annulation. A study of the C-ring functionality was performed leading to the formation of a carbohydrate oxetane. Several attempts at the production of 2-trimethyl-3-lithiobutadiene, as a synthetic building block, resulted in failure. Following previous work at Leicester, involving the use of intramolecular Diels-Alder reactions in the synthesis of taxanes, studies were initiated to convert (2) and (3) into diene-dienophile systems. The first approach was to construct the dienophile, prior to the diene, on C-9 (C-1 carbohydrate numbering). This approach failed due to the difficulties encountered when differentially protecting several similar hydroxyl groups. Altering our initial ideas, such that the diene is built before the dienophile, on C-6, has met though with more success. However, before attempting the construction of the diene on our intermediate (4) a model study was undertaken on a simple carbohydrate aldehyde, using a selenium directed synthesis. This was successful and so this approach has the potential for providing the means for the formation of a diene-dienophile system in our intermediate (4), and hence eventually resulting in the creation of a highly substituted taxane skeleton.

Several novel nitrogen containing bicyclic systems have been synthesised and their chemistry investigated. The kinetic and thermodynamic invertomer ratios of N-chloro-1,2,3,4-tetrahydro-2-keto-l, 4-iminonaphthalene derivatives were determined. The results suggested that a repulsive interaction existed between the positive end of the carbonyl dipole and the incoming electrophilic chlorine. Despite reaction under favourable solvolytic conditions, it appeared that homolysis of the N-chloroamines was favoured over heterolysis. Under conditions of negligible inversion, N-chloro-1,4-dihydro-1-methyl-l,4-iminonaphthalenes underwent heterolytic rearrangement to form 4-inethyIquinclines. From these experiments it was deduced that the quinoline products must be derived from the anti-N-chloroamines with loss of a bridgehead carbon atom. A mechanism for the formation of these products was proposed. Nortropane was synthesised in high overall yield and the first synthesis of a simple derivative of nortrop-6-ene which has been achieved in significant yield was also accomplished. The procedure demonstrated the viability of an intramolecular cyclisation approach given an appropriately nucleophilic nitrogen. Investigation of the reactions of chlorosulphonyl isocyanate with 7-substituted cycloheptatrienes provided evidence that choice of solvent and reaction time along with careful monitoring exerts control over the addition of either the C=0 or C=N moiety across the termini of the triene unit.

Rate and equilibrium constants for chemical systems involving two- stage processes in aqueous media have been measured and analysed. The major part of this thesis discusses the effect of added organic cosolvents or salts on the reaction kinetics of transition metal complexes in solution. The thesis also includes an analysis of published rate and equilibrium data in order to derive thermodynamic activation and reaction parameters. The oxidation of iodide by the 12-tungstocobaltate(III) anion by an outer-sphere process, of iron (II) by the chloropentammine cobalt (III) cation by an inner-sphere process, and the mercury(II)-catalysed aquation of seme rhodium (III) and chramium(III) chloro-ccmplexes have been studied in binary aqueous mixtures. The aquation of the N,N,N",N" tetraethyldiethylenetriamine-chloro palladium (II) cation and the reaction of cis-bis-(4-cyanopyridine) dichloro platinum (II) with thiourea have been studied in aqueous salt solutions. For the above reactions, it has been possible to dissect the effects of solvent variation or added salt on the rate constants into their initial state and transition state contributions. This has been done by estimating the change in the chanical potential of the initial state from appropriate solubility measurements. The results obtained are discussed in terms of the solvation characteristics of the species involved. The reactions of two anionic iron(II) tris-diimine ccmplexes with hydroxide and cyanide in aqueous media have been studied. Kinetic and spectroscopic evidence for intermediates is reported. With regard to computer-based studies, the tamperature dependence of the rate constant for solvolysis of t-butyl chloride in binary aqueous mixtures has been analysed in terms of the two-stage Albery-Robinson mechanism. The derived enthalpies and heat capacities of activation are examined. The temperature dependence of acid dissociation constants has been analysed using the Gurney equation and the two-stage Eigen mechanism.