A new PdII-catalysed interrupted oxidative-Mizoroki-Heck reaction has been developed. This reaction enables the synthesis of a wide range of polyheterocycles in a single step starting with simple substrates and involves the addition of a tethered diene unit across two joined heterocycles. The reaction has proven to be general for dienes tethered to indoles and pyrroles (in blue) and for 1t-allylcapturing heterocycles such as furan, thiophene and pyrrole (in red). In some cases the non-oxidized variant can be obtained through careful choice of oxidant and reaction conditions The scope and mechanism of this reaction have been explored leading to the proposed mechanism shown below. C-H activation of the first, tethered, heterocycle (in this case pyrrole), leads to migratory insertion of the pendant alkene and rapid capture of the π-allyl system by the second heterocycle (in this case furan). Initial products show complete diastereoselectivity and in some cases can be isolated, or oxidized in situ to fully aromatic systems

This thesis details ultrafast absorption spectroscopy studies of photo-induced processes in solution phase aromatic molecules. Application of this technique to the systems detailed below, using both a broadband infrared (IR) and/or ultraviolet (UV)/visible probe, has allowed the key species created directly by photo-excitation and subsequent processes to be identified as well as their transient behaviour to be followed. Kinetic and mechanistic information on the process or reaction is obtained, adding to both the understanding of the underlying photo-physics that drive the process in addition to the transient behaviour of the process itself. The systems investigated are; the UV photodissociation of phenol, the photo-Claisen and photo-Fries rearrangement of allyl phenyl ether and phenyl acetate respectively all in cyclohexane solvent, and three Paterno-Bilchi reactions between c),clohexene, furan or 2,3- dihydrofuran. The photodissociation of phenol in cyclohexane was studied by transient vibrational absorption spectroscopy. The spectra obtained supp0l1ed the results of a previous study of the photodissociation of phenol in solution using transient electronic absorption which found that the mechanism of photodissociation of phenol in a weakly interacting solvent remained the same as observed in the gas phase. Additionally, solution phase specific processes were observed following dissociation, such as recombination. Study of the photo-Claisen and photo-Fries rearrangements in solution using both transient absorption techniques allowed kinetic and mechanistic information on these processes to be obtained including rate coefficients for individual processes and quantum yields for the competing processes that determine the fate of the produced radical pair; solvent cage escape, recombination to form a cyclohexadienone of the original So product. The Paterno-Bilchi reactions between benzaldehyde and three solvents were also investigated. The first studied was the reaction with cyclohexene. This study proved that the biradical intermediates in this reaction along with other key species could be identified using these techniques. The subsequent study of the Paterno-Bilchi reaction with furan and 2,3- dihydrofuran investigated more detailed facets of this reaction.

Carbohydrate recognition in water still remains one of the most challenging tasks for supramolecular chemists. Despite the challenges, the Davis group has had good success in designing and synthesising compounds capable of carbohydrate recognition. Within this body of work 6 novel carbohydrate receptors are reported, based upon the anthracene design shown below. The majority of the reported receptors displayed good to excellent affinities to all-equatorial carbohydrates. One of the synthesised receptors, containing methoxy functionality on the anthracene units, demonstrated remarkably high affinity to maltodextrins, such as maltotriose and maltotetraose (Chapter 2). The binding affinities displayed towards maltodextrins by this receptor, ~2000 M-1, are amongst the highest affinities reported for synthetic carbohydrate receptors in water, and they also are of a similar magnitude to the binding affinities displayed by natural carbohydrate receptors, lectins. A selection of unsymmetrical receptors were also synthesised, wherein one anthracene moeity was unsubstituted and the other was substituted with either bromines, methylesters or carboxylic acids (Chapter 3). These designs were implemented in order to red-shift the receptor's fluorescence emission wavelength, something they did achieve, however only at the consequence of a reduced increase in the receptor's fluorescence intensity upon carbohydrate binding. Of the unsymmetrical receptors synthesised, one, containing a tetracarboxylic acid substituted anthracene, displayed exceptional binding to all-equatorial carbohydrates, binding D-glucose with a binding affinity of 186 M-1. This represents the highest binding affinity to glucose reported. Additionally, the receptor displayed a selectivity of 186:1 for glucose over mannose, a selectivity higher than many lectins. One receptor, wherein one anthracene unit was substituted with a naphthalene, displayed no affinity towards carbohydrates in water (Chapter 4). Such a result, highlighted the importance of hydrophobic interactions are in achieving carbohydrate recognition in water. Finally, further investigations into the reported binding of carbohydrates by a porphyrin based system were carried out (Chapter 6). The results showed tight 1:1 binding between the carbohydrate and the porphyrin was absent, and instead kinetically slow readjustments of porphyrin aggregates appeared to be responsible for the change in UV-vis and fluorescence properties of the porphyrin.

Substituted arenes are ubiquitous frameworks within the pharmaceutical, agrochemical and materials science industry. These valuable motifs have traditionally been prepared by electrophilic or radical substitution reactions, e.g. Friedel-Crafts acylation, however, their synthesis has been revolutionised through the development of transition metal catalysed C-H functionalisatipn reactions. The palladium-catalysed direct arylation of estrone has been achieved using a carbamate directing group to create a modest library of 2-aryl-3-diethylcarbamate estrones. Cleavage of the carbamate directing group with lithium aluminium hydride affords the corresponding 2- arylestradiol.

The reactivity of a new class of hindered amides has been investigated. These amides have been found to undergo facile nucleophilic substitution reactions with a range of nucleophiles. The enhanced reactivity of these compounds, described as "rotamides", is attributed to an exceptionally low barrier to C-N bond rotation, as a result of their sterically hindered structures. This thesis describes the studies undeliaken to elucidate the reaction mechanism. The case for the previously proposed proton switchlketene mechanism has been strengthened by a kinetics study into the nucleophilic substitution reaction of a highly reactive rotamide with butanol. Ketene trapping experiments have also provided strong evidence to support the existence of the ketene intermediate suggested by the proposed proton switch/ketene mechanism.

The application of lithiationiborylation of benzylic carbamates and subsequent protodeboronation methodology for the syntheses of the antidepressant drug (+ )-seltraline, the monoamine reuptake inhibitor (+ )-indatraline, the muscarine receptor anatagonist (R)-tolterodine, the antiandrogen bifluranol and the potential oestrogen receptor-based imaging agent fluorohexestrol is reported. In addition, a strategy towards the synthesis of the antituberculosis drug bedaquiline is discussed. However, some modifications of the standard conditions in the lithiationlborylation reaction were found to be necessary. In the syntheses of (+)-sertraline and (+)-indatraline involving homoallylic carbamate 1, it was necessary to add a crown ether or to carry out a solvent exchange from diethyl ether to CHCb to achieve efficient 1,2-metallate rearrangement of the intermediate boron-ate complex. For the synthesis of (R)-tolterodine the addition of MgBr2 in MeOH was needed. Thus, tertiary boronic esters 2 were obtained in high yield and with high enantioselectivity with retention of the stereo centre. After protodeboronation to provide gel11- diarylalkyls 3, the intermediates were converted to provide (+)-serh'aline, (+)-indatraline and (R)-tolterodine. Our lithiationlborylation methodology has also been applied to the syntheses of bifluranol and fluorohexestrol. By using a convergent synthetic strategy both stereo genic centres were generated by two subsequent lithiationibOlylation reactions followed by protodeboronation. Bifluranol was obtained after further elaboration of tertiary boronic ester 4. For the synthesis of fluorohexestrol employing sterically more hindered coupling partners, the use of a more of a more electrophilic borane species was necessalY to afford intermediate tertiaty borane 5.

The use of nitrogen containing heterocyclic boronic esters in the lithiation-borylation reaction was investigated; a range of pyridyl boronic esters were utilised, and it was found that not only could the α-heterocyclic tertiary alcohols be generated, but also I-pyridyl-l-arylethanes could also be accessed by protodeboronation of the intermediate tertiary boronic esters. This work focuses on the use of highly electrophilic dimethylboranes to effect iterative homologations with secondary benzylic carbamates to create tertiary alcohols or C-tertiary amides with an adjacent quaternary stereo center. The reaction has a reasonable scope, and stereocontrol at each quaternary center is extremely high, giving the double homologation products in excellent enantio- and diastereoselectivity. In addition to the homologation methodology, a method to aminate the tertiary dimethylborane products was developed. A new process was developed that allows for the synthesis oftetrasubstituted alkenes with high stereo control. Lithiation-borylation of secondary benzylic carbamates with trisubstituted vinylic boronic esters gives α,α-disubstituted allylic tertiary boronic esters, which undergo allylboration to give homoallylic alcohols with full control over two stereogenic centres and complete olefin selectivity.

One of the most exciting new areas in main group chemistry over the past 10 years has been Frustrated Lewis Pair (FLP) chemistry. Recent work within the Wass group has focussed on developing a transition-metal based analogue, which was shown to not only activate molecules in analogous fashion to the main group systems, but previously unknown substrates too. Following on from this seminal work, the work in this thesis has sought to expand the area by investigating a number of variations on the original complex.

Polymer brushes anchored to surfaces offer an effective route to modification of interfacial properties such as propensity to fouling , friction mediation and wetting. However, direct physical measurements of such systems, facilitating the refinement of polymer brush growth and comparison against polymer brush theories, remain limited despite considerable research efforts in this area. This thesis describes an investigation on normal and lateral forces between surfaces bearing a polY(2-(methacryloyloxy)ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide), P(SBMA), brush grafted from a novel two dimensional cationic macroinitiator using a surface force apparatus, SFA. Preceding such results this thesis first details the design principles, synthesis and characterisation of a two dimensional cationic macroinitiator facilitating the grafting of polymers from mica and silicon substrates. From this, several polymers were successfully grafted on both mica and silicon. Normal force measurements are then reported in an aqueous environment as well as Na(N03) and Ca(N03)2 salt solutions in addition to solutions composed of water and an ionic liquid, l-hexyl-3-methylimidazolium chloride. These results show the presence of salts altering brush swelling and solvent tenacity, manifesting as changes in measured brush thickness and the force required to deform such a brush layer. Observation of friction mediated by the polymer brush systems was also made with sliding as well as stick-slip behaviours seen for P(SBMA) systems in Ca(N03)2 salt solutions. Finally, the thermal response for ethylene glycol methyl ether methacrylate polymer brushes anchored to polystyrene particles was investigated. Results gathered for this system show that the presence of a dynamic monomer density along the length of a polymer chain gave rise to a complex interplay of forces. This complex relationship exhibited a marked difference in brush response compared to similar systems grafted from flat surfaces.

The synthesis of chiral N-heterocycles through palladium- and copper-catalysed aza-Heck cyclisations of oxime esters has been developed. Initial studies focussed on the development of a palladium-catalysed aza-Heck-π-allyl cascade with carbon, nitrogen and hydride nucleophiles. These reactions were limited to oxime esters bearing gem-α-disubstitution. Investigation into aza-Heck cyclisations involving 1,2-disubstituted alkenes was subsequently undertaken. Here, control of β-hydride elimination regioselectivity was crucial to obtaining chiral products. A series of oxygen-based, sulfur-based and aryl substituents were evaluated for their ability to promote regioselective β-hydride elimination. Both oxygen and sulfur substituents gave low selectivity, whereas aryl groups promoted β-hydride elimination in the direction of chiral products. Catalyst-controlled cyc1isation of alkyl-substituted alkenes provided chiral products and a selectivity model for this process was proposed. Highly diastereoselective manipulations of the dihydropyrrole products obtained from this chemistry allowed access to more complex N-heterocycles. A complementary copper-catalysed aza-Heck cyclisation was next developed. Mechanistic studies of both palladium- and copper-catalysed reactions revealed a mechanistic dichotomy. Reactions involving electron-deficient palladium catalysts proceed through the formation of imino-Pd(II) intermediates, whereas copper catalysts form an iminyl radical, or radical-like species. Reactions involving electron-rich palladium catalysts also resulted in the formation of an iminyl radical, and in the presence of a hydrogen-atom donor formed the product of a 'reductive' aza-Heck reaction. Finally, an enantioselective palladium-catalysed aza-Heck reaction has also been developed. Spirocyclic P,N-based SIPHOX ligands were privileged for this transformation and the synthesis of a series of SIPHOX derivatives allowed the aza-Heck reaction to proceed in high yield and enantioselectivity. A selectivity model was proposed for these reactions