Activated cyclopropanes have been extensively used in synthetic chemistry as precursors for cycloaddition reactions. The rationale behind this is their ability to undergo ring-opening when activated by a Lewis acid, this can be enhanced further by the presence of a carbocation stabilising group like electron-rich aromatics. The stabilised dipole formed after ring opening can be trapped with suitable electrophiles such as imines and aldehydes via a [3+2] cycloaddition reaction. This results in the synthesis of pyrrolidines and tetrahydrofurans in excellent yields but moderate diastereoselectivity. Similarly, 6-membered heterocycles can be formed via a [3+3] cycloaddition reaction of activated cyclopropanes with nitrones. Now to extend the scope of the methodology, a [3+3] dipolar cycloaddition has been developed using activated 2,3 disubstituted cyclopropane diesters to access a range of highly functionalised oxazines in moderate to good yields (50-75%) and with reasonable diastereoselectivity. The use of activated symmetrical disubstituted cyclopropanes afforded the desired oxazines in a regio- and diastereocontrolled manner, while the use of unsymmetrical cyclopropanes significantly reduced the diastereoselectivity of the reaction. The stereochemistry outcome of the reaction developed was determined by nOe analyses and X-ray diffraction structures could be recorded in some examples. A new methodology has also been developed to gain access to novel N-heterocyclic- and phenol- substituted cyclopropanes in one step from the corresponding cyclopropene via a conjugated addition.

The main focus of this research was to examine the molecular complexes formed by the proton sponge material DMAN [1,8-bis(dimethylamino)naphthalene]. It is well known that DMAN will readily protonate – forming the DMANH+ – leaving the second molecule in a DMAN complex negatively charged. In addition to the preparation of materials by crystallisation techniques, full characterisation was carried out using X-ray diffraction of the single crystal samples obtained. Neutron diffraction was also carried out on some of the samples for which the hydrogen atom information was most important to obtain, though this was restricted by the amount of beamtime available on the central facilities used. Several families of DMAN complexes were studied, including DMAN : benzoic acid (chapter 4), DMAN with a wide series of halo-substituted benzoic acids (Chapter 4), DMAN with hydroxyl-, nitro- and methyl- substituted benzoic acids (Chapter 5), and its complexes with a selection of other organic acids (Chapter 6). Several general patterns are found in this work, including the following: • The DMAN is usually protonated (DMANH+), with the hydrogen atom held in a short N−H···N intramolecular hydrogen bond, as observed previously; • The carboxylic acids tend to form dimers, but with a carboxyl and a deprotonated carboxylate group involved, these DIMER− units are formed through a single, very short, strong, charge-assisted O−H···O hydrogen bond; • a wide range of C−H···O and C−H···π weaker hydrogen bonds are present, together with consistent stacking of the DMAN rings, including π···π interactions, but with additional stacking at a range of interplanar distances; • the overall packing in several complexes includes chains or sheets of DIMER− units with DMANH+ included in pockets in the structure. There are some exceptions to these patterns, for example: • varying stoichiometry, resulting in the first example of the occurrence of both protonated (DMANH+) and unprotonated DMAN in a single complex • the inclusion of solvent water in some hydrated complex, which interrupts some of the patterns of intermolecular interactions In addition to the studies of DMAN, a ternary hydrogen bonded complex was studied using X-ray and neutron diffraction and the new molecular porous material 4-phenoxyphenol, containing a range of solvents, was fully characterised using these diffraction techniques as well as the thermal methods TGA and DSC.

The cobalt-catalysed alkylative aldol cyclisations of α,β-unsaturated amides with an appendant ketone were studied using a range of trialkylaluminium reagents. Investigations revealed that Co(acac)2·2H2O acts as an effective precatalyst for this transformation and the reaction provides β-hydroxylactam products containing three contiguous stereocentres with high levels of diastereoselection. The substrate scope of the reaction was explored and attempts were made to develop an asymmetric variant of this process. Two plausible reaction mechanisms have been proposed; the first invokes a π-allylcobalt species as a key intermediate in the reaction mechanism and the second involves a radical-mediated pathway. A stereochemical rationale for the observed relative stereochemistry of the β-hydroxylactam products has been discussed. II. Rhodium-Catalysed Carbometallations of Ynamides in the Preparation of Multisubstituted Enamides A highly stereo- and regioselective rhodium-catalysed carbozincation of ynamides using organozinc reagents has been disclosed. A careful examination of ligand effects on the rhodium catalyst yielded a complementary set of hydrozincation conditions. The alkenylzinc intermediates produced during the course of these reactions have been harnessed in further transformations with electrophilic species and in cross-couplings, thus providing access to multisubstituted enamides in a stereo- and regioselective fashion. Additionally, a rhodium-catalysed tandem carbometallation−conjugate addition with ortho-boronate substituted cinnamic acid derivatives has been described. The enamide−indene products were obtained in good yields and regioselectivities. Preliminary work has been undertaken on an asymmetric variant of this transformation and the initial results have been reported.

Information processors that harness quantum mechanics may be able to outperform their classical counterparts at certain tasks. Quantum information processing (QIP) can utilize the quantum mechanical phenomenon of entanglement to implement quantum algorithms. Endohedral fullerenes, where atoms, ions or clusters are trapped in a carbon cage, are a class of nanomaterials that show great promise as the basis for a solid-state QIP architecture. Some endohedral fullerenes are spin–active, and offer the potential to encode information in their spin-states. This thesis addresses the challenges of how to engineer the components of a scalable QIP architecture based on endohedral fullerenes. It focuses on the synthesis and characterization of molecules which may, in the future, permit the demonstration of entanglement; the optical read-out of quantum states; and the creation of quasi-one-dimensional molecular arrays. Due to its long spin decoherence time, N@C₆₀ is the selected as the basic molecular unit for ‘coupled’ fullerene pairs, molecular systems for which it may be possible to demonstrate entanglement. To this end, isolated fullerene pairs, in the form of spin-bearing fullerene dimers, are created. This begins with the processing of N@C₆₀ at the macroscale and leads towards the synthesis of ¹⁵N@C₆₀-¹⁵N@C₆₀ dimers at the microscale. High throughput processing is introduced as the most efficient technique to obtain high purity N@C₆₀ on a reasonable timescale. A scheme to produce symmetric and asymmetric fullerene dimers is also demonstrated. EPR spectroscopy of the dimers in the solid-state confirms derivatization, whilst permitting the modelling of spin–spin interactions for 'coupled' fullerene pairs. This suggests that the optimum inter–spin separation for which to observe spin–spin coupling in powders is circa 3 nm. Motivated by the properties of the trivalent erbium ion for the optical detection of quantum states, optically–active erbium–doped fullerenes are also investigated. These erbium metallofullerenes are synthesized and isolated as individual isomers. They are characterized by low temperature photoluminescence spectroscopy, emitting in the infra- red at a wavelength of 1.5 μm. The luminescence is markedly different where a C₂ cluster is trapped alongside the erbium ions in the fullerene cage. Er₂C₂@C₈₂ (isomer I) exhibits emission linewidths that are comparable to those observed for Er³⁺ in crystals. Finally, the discovery of a novel praseodymium-doped fullerene is reported. The balance of evidence favours the structure being assigned as Pr₂@C₇₂. This novel endohedral fullerene forms quasi-one-dimensional arrays in carbon nanotubes, which is a useful proof-of-principle of how a scaled fullerene-based architecture may be achieved.

In this thesis, firstly, a Pd-catalysed diastereoselective carbocyclisation of allenes with aryl halides or vinyl iodides was designed and developed to form arylative or vinylative spirolactam compounds. High yields and diastereoselectivities were obtained in the presence of Pd₂(dba)₃/dppe and K₂CO₃ in DMSO at 70 &deg;C, particularly when spiropiperidin-2-ones were formed. The method is simple to perform and broad in scope. Having established the diastereoselective methodology for the arylative or vinylative allene carbocyclisation, a Pd-catalysed enantioselective version was developed by using bisoxazolines as chiral ligands. Aryl halides and vinyl iodides were investigated in this carbocyclisation. High yields and enantioselectivities were obtained in the presence of Pd(OAc)₂, a bisoxazoline ligand <strong>L7d</strong> derived from L-isoleucine and Ag₃PO₄ in 1,2-dichloroethane at 70 &deg;C. No olefin isomerisation was observed when cis-vinyl iodides were used. The method is mild, efficient and broad in scope. A palladium catalysed diastereoselective allene carbocyclisation reaction was developed via enamine catalysis and palladium catalysis, which allows for the efficient carbocyclisation of formyl or ketone allenes. Good yields and high diastereoselectivities were obtained in the presence of Pd(OAc)₂ and pyrrolidine in toluene at 60 °C when formyl allenes were investigated. The cyclisation is diastereoselective and can also performed as a catalytic asymmetric reaction by using prolinol derivatives as chiral catalysts. Good yields and high diastereo- and enantioselectivities were obtained in the presence of catalyst <strong>(S)-L19</strong>. Additionally, a boronic acid catalysed ene carbocyclisation of acetylenic dicarbonyl compounds was developed. An attempted transesterification of a &beta;-ketoester substrate bearing a pendent terminal alkyne substituent at the &beta;-position led to the discovery of an efficient 3-nitrobenzeneboronic acid catalysed ene carbocyclisation of acetylenic dicarbonyl compounds. The reaction is easy to perform, efficient, broad in scope and provides a convenient transition metal-free alternative to existing catalytic protocols.

The aims of this project were to develop a cascade approach towards decahydroquinoline frameworks (Scheme I) and apply this to the synthesis of decahydroquinoline-containing natural products such as lycopodine, cermizine B and lepadin D (Scheme I). Scheme I. Several linear precursors were synthesized via a modular strategy. For example, lycopodine linear precursor i was synthesized in a total of 12 steps (Scheme II). Scheme II. Conditions for cyclization and hydrogenation were tested, with the diastereoselectivity examined in each system. For example, the lepadin linear precursor ii produced two decahydroquinolines iii and iv upon cyclization (Scheme III). Scheme III. It was found that the diastereoselectivity was dependent on the ring substituents and variation of the hydrogenation conditions could change the facial selectivity of enamine reduction.

It is over 100 years since scientists first postulated the existence of arynes as reactive intermediates. Their use in organic synthesis is now well-established and investigations into novel methods for their generation and utility in carbon-carbon bond forming reactions continue to this day. In 1983 Kobayashi and co-workers introduced a novel method of generating benzyne under mild conditions, using a fluoride induced decomposition of 2-(trimethylsilyl)phenyl triflate 1. This development has opened the door to employing arynes in a variety of transitionmetal mediated carbon-carbon bond forming processes. Intermolecular carbopalladation, in particular, stands out as a powerful methodology for the construction of diverse 1,2-functionalised arenes through multi-component coupling processes. Initial benzyne carbopalladation with an organopalladium species produces the arylpalladium intermediate 3, which can then undergo a second coupling to any one of the vast numbers of nucleophiles that have been demonstrated to work in palladium cross coupling. Presented herein are investigations towards the realisation of such methodology. Initial efforts focussed on its application to the Heck reaction, using acryates as the nucleophilic component. The chemistry has been developed to incorporate a variety of organo-halides in order to generate a variety of molecular architectures; the resultant 1,2-substituted diaryls being useful in the synthesis of both natural products and medicinal chemistry targets. Following successful development of the Heck reaction, investigations of other palladium catalysed couplings were also undertaken, in particular the Buchwald reaction. Initial mechanistic studies are also discussed.

In the multi-step synthesis of Lilestralis, a synthetic muguet fragrance, the kinetics and mechanism of the formation of 3-(3-t-butylphenyl)-2-methylpropan-1-ol (m-LOL) and 4-(3-t-butylphenyl)-2-methylpropan-1-ol (p-LOL) from 2-methyl-3-phenylpropan-1-ol (MPP) and isobutylene using concentrated liquid phosphoric acid as a catalyst was investigated. By-products that include phosphate esters of MPP, m-LOL and p-LOL and oligomers of isobutylene were produced during this reaction and their role within the kinetics and mechanism was also investigated. When crystalline phosphoric acid is dissolved in water, it can form equilibrium polyphosphate mixtures at high acid concentrations. The phosphate species have the general formula Hn+2PnO3n+1 and consist of species such as orthophosphoric acid (H3PO4), pyrophosphoric acid (H4P2O7) and triphosphoric acid (H5P3010). The presence of polyphosphate within liquid phosphoric acid solutions used in this study was investigated using 31P NMR. To investigate the influence of water on the reaction, a number of experiments were performed using 1,4-dioxane as a solvent. This was chosen as the boiling points and density are similar to water, although it is classified as an aprotic solvent. Phosphate esters of MPP, m-LOL and p-LOL are produced as by-products and can potentially undergo hydrolysis when water is present, therefore reactions using aqueous phosphoric acid solutions may not give a true reflection of the concentration of phosphate esters produced. The use of heterogeneous catalysts was also investigated in order to improve yield and selectivity for p-LOL and m-LOL. These include acid catalysts such as solid phosphoric acid supported on Kieselguhr (SPA), sulphated zirconia and ultra stable zeolite-Y (H-USY).

In this project cyclisation chemistry using palladium and radical methodologies has been developed. The aim was to compare palladium and radical mediated cyclisations. Initially small molecules containing amine and amide functional groups were synthesised to screen the methodology. Later the design of these molecules was changed to be based on the imidoyl functional group. A series of N-benzyl protected aliphatic amine and amides were synthesised in the hope (with the aim of cyclisation) that they could be cyclised using both palladium and radical conditions. When these examples failed, which was attributed to the strain of the cyclic molecules, alternative precursors were sought. Initially, the N-protecting group was changed to a tosyl-group. However, when this had no positive effect, the size of the precursor molecules were examined. Two alternative amine precursors were designed which would remove the strain element in the cyclised molecules. The lengthy synthesis of these two molecules was not favourable for the development of methodology. Although it appeared that the cyclisations were now occurring it did not prove favourable to carry on down this path. The final part of this research project utilises imines and imidoyl selenides as radical and palladium cyclisation precursors respectively. A series of aromatic imines and imidoyl selenides were synthesised. The irnines were synthesised from amino-biphenyl and a range of p-substituted benza1dehydes. The corresponding imidoyl selenides were synthesised from amino-biphenyl and a range of p-substituted benzoyl chlorides to give the amides which in tum were converted to the target molecules via the imidoyl chlorides. The successful cyclisations using both methodologies resulted in a series of phenanthridines. This success of these cyclisations led to further precursors being developed which included bisphenanthridine, alkyne, alkyl and heteroaromatic precursors. However, most of the cyclisations of these molecules proved problematic and require further development of methodology.

The construction of tertiary alkylamines is a synthetic challenge exacerbated by the poor electrophilicity of imines. Due to the presence of this kind of building block in a large number of bioactive molecules, the development of new strategies to synthesise the quaternary carbon centre is essential. This thesis describes the work carried out on the rearrangement of lithiated vinyl ureas in order to form α-tertiary amines. The first part presents how vinyl ureas were synthesised, using the reaction between an imine and an aryl isocyanate. The development of one-pot process allows the synthesis of a range of ureas in large scale. These vinyl ureas present unusual reactivity: the electron-rich double bond can undergo syn umpolung carbolithiation followed by retentive aryl migration in order to generate highly substituted amines after cleavage of the urea. The complete mechanism is investigated to understand fully the diastereoselective pathway of the reaction. In the next part, the rearrangement of lithiated ureas is extended to the N to C vinyl transfer. Different vinyl migrating group are investigated and α-tertiary amines have been synthesised in high yields and enantiomerically pure form using this new rearrangement. The mechanistic insights of the reaction are also studied and a retentive mechanism will be identified. Finally, N to C vinyl transfer is applied toward the synthesis of Erythrina alkaloids.