Rozprawy doktorskie na temat „Novel Catalysis”

This thesis describes work carried out on catalytic selenium reagents in a range of organic transformations. Four different areas have been investigated and are reported herein. Chapter 2 reports the unsuccessful development into prochiral ligands, where three different chalcogen atoms are incorporated into either a trisubstituted structure or into a crown ether ring. Then reports how these structures could attach to a metal atom and become chiral. A SSe I SeR Chapter 3 describes a range of selenium-based ligands, which has been used in the palladium allylic substitution reaction to see if there is good co-ordination between selenium and palladium and if good enantioselectivities can be achieved. Chapter 4 describes the use of seleninic acids as catalysts in a range of reactions where the most successful is used in asymmetric Baeyer-Villiger oxidations using a range of ketones with enantiotopic migrating groups. The enantioselectivities were investigated. Chiral Catalyst I I ,0 O H202 O ASe A X R O R R CH2CI2 R ' Chiral Catalyst Chapter 5 describes the successful work on catalytic selenium reagents used to convert /,y-alkenoic acids into their corresponding butenolides. The work describes the optimum conditions investigated, asymmetric version of the reaction and also investigates mechanistic aspects of the catalytic cycle. Cat - (PhSe)2 Oxidant R 0 R C00H " _J Solvent.

Catalysis allows for the controlled formation of new bonds, whilst reducing both time and energy expenditure in the process. Catalysis has traditionally been the realm of precious metals, which have been used to carry out a bewildering array of reactions. However, there is an ever-increasing drive for the development of catalytic methodology employing sustainable and environmentally benign catalysts. Two such candidates are organocatalysis, omitting the need for metals where possible, or the use of iron catalysis. Two key areas to the advancement of the of field catalysis are the identification and development of new catalysts as well as an understanding of the mechanisms of established catalytic processes. Novel catalysts can provide many benefits such as enhanced or even novel reactivity, access to new classes of substrates or simply be more readily accessible compared with previously developed catalysts. To this end, the first example of Lewis-base-catalysis using the recently developed cyclopropenimine motif is reported. This was exploited in the trifluoromethylation of aldehydes and ketones using the Rupert-Prakash reagent (Scheme A-1). Scheme A-1 Cyclopropenimine-catalysed trifluoromethylation of aldehydes and ketones Developing an understanding of catalytic methodologies in the terms of their mechanism and active species is also a key area in catalysis. Insight into these can direct the expansion of these systems in terms of both more effective catalysts and tailoring reaction conditions as examples. The iron-catalysed hydromagnesiation of styrene derivatives was studied in detail. This culminated in a proposed mechanism, involving a novel hydride transfer process (Scheme A-2). Studies were carried out using a combination of kinetic analysis and in situ Mössbauer spectroscopy, as well as successfully isolating and studying the reactivity of a catalytically-relevant, formal iron(0)-species.

The iron-catalysed hydromagnesiation of styrene derivatives has been developed further from previous publications, expanding the electrophile scope to enable the regioselective formation of new carbon-carbon and carbon-heteroatom bonds (Scheme A1). A commercially available pre-catalyst and ligand were used to give an operationally simple procedure that did not require prior synthesis of a catalyst. This work also investigated the hydromagnesiation of dienes, using a screen of ligands commonly used in transition metal catalysis. An investigation into the magnesium-catalysed hydroboration of olefins was also carried out. Although mostly unsuccessful, it was demonstrated that in the presence of a magnesium catalyst, a small amount of vinyl boronic ester could be formed from an alkyne (Scheme A2). Simple magnesium salts were also investigated for the reduction of carbonyls. Lastly, this work explored the titanium-catalysed hydrosilylation of olefins, using a novel activation method developed within the group (Scheme A3). The results were compared to those published previously using traditional organometallic activation methods and attempts at identifying conditions to improve chemoselectivity were carried out.

The RNA World hypothesis describes a period of time during the origins of life in which RNA molecules performed all catalysis and were the only form of information storage. A great deal of evidence has been obtained in support of this hypothesis, however a few key demonstrations are lacking. The first demonstration is of a molecule capable of self-replication that could have plausibly arisen from the prebiotic soup. Previously in the Lehman Laboratory, a 198-nucleotide RNA was discovered that could be fragmented into as many as four pieces ranging from 39 - 63 nucleotides in length. When these pieces were incubated together in a test tube, they re-formed the necessary covalent bonds to regenerate the full-length 198-nucleotide RNA. Furthermore, the full-length RNAs were catalytically active and made copies of themselves from the remaining pieces in solution, providing a model system of self-replication. I was able to remove >10% of the total length of the RNA, which substantially reduced the catalytic activity of the full-length molecule. I discovered several mutations that restored catalytic activity by improved folding and increased catalytic rates using in vitro selection. A subset of these mutations was found to aid in the assembly of the shortened full-length RNA from smaller fragments than were possible in the original system, enhancing the prebiotic relevance of this system. A second demonstration to bolster the RNA World hypothesis would be showing that RNA is capable of harvesting energy from its environment by performing oxidation and reduction reactions. Again using in vitro selection, I have completed five rounds of selection geared towards identifying a ribozyme that reduces benzoic acid to benzaldehyde using Zn2+ and NADH. Results to date suggest the selection is working and it should be continued for another five to ten generations. Finally, I have discovered an RNA sequence that forms knots during transcription, a phenomenon heretofore undocumented in RNA. This new topology has implications for RNA stability by rendering RNA more resistant to hydrolysis, and could impact catalysis through formation of more complex, knotted active sites. Taken together, these findings have improved our understanding of RNA folding and catalysis, and the plausibility of the RNA World.

The scope of the palladium catalysed allylic substitution reaction is reviewed with particular reference to stereocontrol. The use of enantiopure oxazolines and acetals in asymmetric synthesis is briefly outlined. The work presented is concerned with the design and construction of enantiopure ligands which are able to impart very high levels of enantioselectivity in the aforementioned palladium-catalysed allylic substitution reaction. The ligands exploit the stereochemistry-controlling properties of the oxazoline moiety, whilst incorporating a secondary donor atom. The ligands rely upon an electronic disparity between these two atoms to direct nucleophilic addition.

This thesis focuses on the understanding the effect of various factors, such as physical structures of metal particles, chemical composition of supports and metal-support interactions, on the catalytic performance of Pd or Pt nanocatalysts for hydrodeoxygenation (HDO) of bio-oil model compounds. The first part of the thesis addressed the alternative catalyst synthesis strategy based on emerging double-flame spray pyrolysis method (FSP), which was able to tune the catalytic properties of nanocatalysts without changing their precursors and chemical compositions during the synthesis. A series of Pd catalysts on the silica-alumina supports, SiO2- , and Al2O3 supports have been synthesized with the tunable surface properties within micro-seconds. The characterization results showed that various flow rates of precursors and gases used for the synthesis of catalysts influenced the formation of the catalyst structures and further change the surface acidity of catalysts due to the correlation between acidity and structure, but, the flow rates did not influence the electronic properties of Pd particles. Therefore, the higher conversion but the similar chemoselectivity have been reached in the hydrogenation of the bio-oil model ketone compound-acetophenone The second part is to identify the dominant effects from size of metal catalysts (under uniform shape and face) or the support acidity in the hydrodeoxygenation of the bio-oil model compounds of acetophenone, benzaldehyde, and butyrophenone. The uniform cubic Pd particles with different size (8, 13, and 21 nm) have been synthesized and loaded on the most popular supports (SiO2-, Al2O3-, and silica-alumina) with various functional groups and acidity. The results showed different acidities on the supports (Brønsted acidic site for Silica-alumina, Lewis acidic site for Al2O3-, and non/weak silanol OH group for SiO2- support) could not influence the chemoselectivity of the reaction but effected the conversion obviously. The particle size has more significant influence than the acidity. The smallest (8nm) Pd particle catalysts regardless of kinds of supports revealed the highest conversion for the hydrogenation the bio-oil model compounds. The third part focused on the influence of various types of catalysts with different acidities, chemical composition, and metal-support interaction on enantioselective hydrogenation of several model compounds in two reaction systems: 1). Pt-cinchrona modified system, and 2). Pd-(S) proline modified system. The result indicated acidic supports promoted the both conversion and enantioselectivity. Specially, Pd/SA made by double-FSP method, which has the highest Brønsted acid sites, showed 100 % conversion of isopherone on 60 min with 99% ee values.

Enzymes facilitate specific chemical reactions by lowering the Gibbs free energy of activation (AG++), thus increasing the rate of catalysis. It would be advantageous to understand exactly what within the enzyme leads to this lowering ofthe activation energy. This work describes the development ofa protocol for calculating the free energy barrier between two states of an enzyme, or other condensed phase system using computer simulation. The natute of the calculation enables it to be decomposed to reveal which vibrational modes observed in a molecular dynamics simulation are contributing to the catalytic effects. The energy gap fluctuations between the two states can be used to calculate a free energy function for the reaction coordinate between two states. A probability distribution function can be generated using , these values and, given sufficient equilibrium sampling, the Central Limit Theorem may be invoked so that the distribution can be represented by a Gaussian function. Using this distribution to represent the equilibrium constant within Transition State Theory, the free energy difference is quadratic with respect to the energy gap value. Assuming a linear response ofthe solvent bath (Marcus theory), the free energy difference function is extrapolated to a zero energy gap value, thus giving the, experimentally comparable, free energy of activation between those two states. The thesis presents the progress made in developing this novel approach for obtaining the energy gap between two states, and its initial application to the rate limiting hydride transfer step catalysed by the extensively studied horse liver alcohol dehydrogenase (LADH) enzyme. Two, independent, equilibrium trajectories ofthe states either side ofthis rate limiting step are propagated classically using the AMBER force field. Time ordered snapshots ofthe simulation's coordinates are postprocessed using a QMlMM method to obtain the ground state energy ofthe system; the active site is treated quantum mechanically, with the polarising effects ofthe surrounding protein and water bath incorporated as point charges in its one electron Hamiltonian. Development ofthe approach was facilitated using the smaller test system ofMalachite Green. This protocol offers a computationally cheaper alternative to the normal Empirical Valence Bond (EVB) I Free Energy Perturbation (PEP) approach, since only two equilibrium trajectories of both states are required instead of an ovedapping set of trajectories in the range between the states. The additional complexity of a switching Hamiltonian is also avoided. The subtracted spectrum of oscillators gives insight into which vibrational modes within the system are contributing to the catalytic effect. ' 1, I

A series of novel monodentate and bidentate phosphine ligands substituted with bulky tert-butyl and fluorinated aryl groups have been synthesised. Borane protection has proved to be an excellent method for easy synthesis and purification of bidentate ligands in some cases. However, several of the bulky fluorinated ligands do not form stable borane complexes leading to complications in the synthesis and purification of these compounds. By reaction with transition metal platinum and palladium precursors, it was possible to form dichloride complexes from the synthesised ligands, which were characterised by X-ray crystallography. The complexes were found to be effective catalysts for the hydroxycarbonylation of vinyl arenes (yields of up to 95 % with 3 mol% catalyst). An unsymmetrical bidentate complex (3.18) in combination with paratoluenesulfonic acid and LiCl promoters has given exceptional (for a diphosphine ligand) regioselectivity for the branched acid (98.7 % branched) in the hydroxycarbonylation of styrene. The role of the promoters has been found to be crucial in deciding the activity and selectivity in this reaction.

This thesis presents an investigation on synthesis of carbon nanoribbons by edged engineering and the roles of the carbon edges in several catalytic reactions, oxygen reduction reaction, aqueous organic remediation and ethanol selective oxidation. Using edge engineered nanocarbons as the model catalysts, the carbon edges are exclusively proven to be catalytically active. Further, edges significantly benefit the heteroatom incorporation into the carbon lattice, and exhibit superior catalytic activity to basal plane doped sites.

The first part of this thesis describes an improved synthetic route to hybrid (hydroquinone-Schiff base)cobalt catalysts. Preparation of the 5-(2,5-hydroxyphenyl)salicylaldehyde building block was improved by altering the protective groups of the hydroquinone (HQ) starting material. Both protection and deprotection could be carried out under mild conditions, resulting in high yields. By optimizing the reaction conditions of the Suzuki cross-coupling, an efficient and inexpensive synthetic route with a good overall yield was developed. The second part describes the use of the hybrid catalyst as an electron transfer mediator (ETM) in the palladium-catalyzed aerobic carbocyclization of enallenes. By covalently linking the HQ to the cobalt Schiff-base complex the reaction proceeded at lower temperatures with a five-fold increase of the reaction rate compared to the previously reported system. The third part describes the application of the hybrid catalyst in the biomimetic aerobic oxidation of secondary alcohols. Due to the effi­ciency of the intramolecular electron transfer, the hybrid catalyst allowed for a lower catalytic loading and milder reaction conditions compared to the previous separate-component system. Benzylic alcohols as well as aliphatic alcohols were oxidized to the corresponding ketones in excellent yield and selectivity using this methodology. The fourth part describes the synthesis and characterization of highly dispersed palladium nanoparticles supported on aminopropyl-modified siliceous mesocellular foam. The Pd nanocatalyst showed excellent activity for the aerobic oxidation of a wide variety of alcohols under air atmosphere. Moreover, the catalyst can be recycled several times without any decrease in activity or leaching of the metal into solution. Finally, the fifth part describes the application of the Pd nanocatalyst in transfer hydrogenations and Suzuki coupling reactions. The catalyst was found to be highly efficient for both transformations, resulting in chemoselective reduction of various alkenes as well as coupling of a variety of aryl halides with various boronic acids in excellent yields. Performing the latter reaction under microwave irradiation significantly increased the reaction rate, compared to conventional heating. However, no significant increase in reaction rate was observed for the transfer hydrogenations, under microwave heating.

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Manuscript.

Thesis (M. S.)--Chemical Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Jones, Christopher; Committee Member: Agrawal, Pradeep; Committee Member: Teja, Amyn; Committee Member: Weck, Marcus; Committee Member: Zhang, John.

This PhD thesis is focused on the development of novel carbon(II) and carbon(0) catalysis for organic synthesis. More specifically, the major objective has been to explore and design non-toxic and effective catalysts based on: an unusual Bertrand carbene type, a so-called bis(dialkylamino)cyclopropenylidene (BAC), and the carbodicarbene (CDC) framework; the central carbon atom in these molecules is in the formal low-oxidation state ‘+II’ and ‘0’, respectively. These species may be used in base catalysis or as ligands in metal catalysis, and in the context of frustrated Lewis pair (FLP) or dual catalysis. Prior to catalysis studies, the Lewis basicity of such carbon-based compounds has been assessed with 11B NMR analysis using various boron-based Lewis acids. Boron binding has been detected in all cases with a BAC, thereby confirming its strongly nucleophilic character and decreased steric demand. In contrast, only few ate complexes have been identified with CDCs (or precursors thereof), which means that CDCs may be more suitable for FLP catalysis. A preliminary electrophile binding study with a BAC has provided interesting data, based on which unprecedented aldimine Umpolung may be developed in the future. In the context of organocatalysis, BAC-mediated C–C bond formations between various Michael acceptors and N-tosyl imines have been developed (aza-Morita–Baylis–Hillman chemistry). In addition, C–N or C–Hal bond formations between various Michael acceptors and azodicarboxylates or electrophilic halogen reagents have been developed. The characteristic features of these unprecedented BAC catalyses include low catalyst loading, mild reaction conditions, and broad substrate scopes. Importantly, several novel chiral BACs have been synthesized and characterized, and excellent results have been achieved in BAC-catalysed asymmetric aza-MBH reactions (ee up to 97%). To the best of our knowledge, these data represent the first highly enantioselective BAC catalysis; chiral N-heterocyclic carbenes (NHCs) have proved to be substantially less effective in this context (ee up to 38%). In the same line, BAC-catalysed asymmetric borylations and silylations of Michael acceptors have been developed (preliminary ee up to 69%). These results demonstrate the high potential of the newly developed chiral BACs in asymmetric organocatalysis. Meanwhile, several BAC–gallium and BAC–iron complexes have been synthesized and characterized. These novel complexes may be used in Lewis acid catalysis after appropriate activation of the corresponding metal sites. Finally, the exploration of the catalysis potential of various C(0) compounds, namely CDCs, is still under investigation.

This thesis is focused on the development of new pincer complex-catalyzed transformations. Optimization of the catalytic properties (fine-tuning) was directed to increase the catalytic activity as well as the chemo-, stereo- and enantioselectivity of the complexes. This was achieved by varying the heteroatoms in the terdentate pincer ligand, by changing the electronic properties of the coordinated aryl moiety and by implementing chiral functionalities in the pincer complexes. In the cross-coupling reaction of vinyl epoxides and aziridines with organoboronic acids the chemoselectivity of the reaction could be increased by employment of pincer complexes instead of commonly used Pd(0) catalysts. Furthermore, the introduction of a methoxy substituent in the aromatic subunit of the complex considerably increased the activity of the pincer complex catalyst. Fine-tuning of the enantioselectivity in electrophilic allylation reactions was achieved by using a wide variety of new BINOL- and biphenanthrol-based pincer complexes. The highest enantioselectivity (85% ee) was obtained by applying biphenanthrol-based pincer complexes. Stereoselective pincer complex-catalyzed condensation of sulfonylimines with isocyanoacetate could be achieved under mild reaction conditions. By application of chiral PCP catalysts, 2-imidazolines could be obtained with up to 86% ee. A new pincer complex-catalyzed C-H bond functionalization based reaction between organonitriles and sulfonylimines affords homoallylic amines and beta-aminonitriles in high yields. The asymmetric version of this process affords beta-aminonitriles with up to 71% ee. In the last chapter, a pincer complex-catalyzed redox coupling reaction is described. In this highly regio- and stereoselective process the integrity of the pincer catalysts is fully retained. This catalytic reaction proceeds with a high level of functional group tolerance, as allylic acetate and aryl halide functionalities are retained.

This thesis discusses the synthesis, characterisation, and reactivity studies of a range of new chiral calcium complexes supported by various polydentate N-donor ligands and their suitability as catalysts for intramolecular hydroamination. Chapter One outlines the case for developing organocalcium complexes, including a general overview of their current application to a variety of heterofunctionalisation reactions. Chapter Two introduces the chiral ethylene diamines which are extensively used as calcium supporting ligands and later as precursors for the synthesis of bisimidazoline and potential imoxazoline ligands. Chapter Two provides details of the diamine synthesis and includes studies related to racemisation concerns of the chiral centre. Chapter Three discusses novel calcium complexes supported by the chiral ethylene diamine analogues presented in Chapter Two. Complex synthesis, characterisation, and catalytic performance in intramolecular hydroamination is probed and discussed. Chapter Four details a range of new bisimidazoline ligands and their employment as supporting ligands on calcium. The catalytic performance of the resulting complexes in intramolecular hydroamination is subsequently analysed and discussed. Chapter Five investigates the attempted development of a total synthetic pathway to a new class of imoxazoline ligand and related issues. Chapter Six contains all experimental procedures, characterising data pertaining to all new compounds and complexes presented in this Thesis. Appendices A-K contain additional catalytic figures and tables of crystallographic data for all new crystallographically characterised compounds. Summary sheets of every literature and new compound presented mentioned in this Thesis are also included, along with copies of both printed publications resulting from this Thesis at the time of submission.

2014 - 2015
In the great realm of organic synthesis, phase-transfer catalysis (PTC) is a well recognized methodology which plays a key role both in industry and academia research. This process involves reactions that take place between reagents which are located in different phases, for example an inorganic water-soluble reagent and a substrate soluble in the organic phase. Considering the well-defined advantages of asymmetric phase-transfer catalysis as a powerful method for organic synthesis, the aim of this research project is to introduce novel macrocycle systems as new and efficient catalysts in this field. First of all, considering the advantages of the easy synthetic process for the preparation of cyclopeptoids, their well-explored complexation properties and the preliminary study on the application as phase-transfer catalysts, the idea is to deeply investigate their use in PTC. The advantages of the solid phase synthesis, such as the easy purification of the intermediates and the modular nature of the products, make cyclopeptoids ideal candidates for the discovery of new catalytic systems, as it is possible to incorporate a wide variety of functionalities inside the backbone of the macrocycle in an expeditious way. As a consequence, a library of peptoid-based chiral macrocycles of different size, decorated with alternating residues of L-Proline and different aromatic side chains, will be prepared and used for enantioselective alkylation reactions. The scope of this project extends also to the investigation of novel chiral calixarenes. However, in this case, the idea is to exploit the ability of calixarenes to form host-guest complexes with alkali cations. The study is also devoted to further explore the potential of crown ethers in new catalytic processes. The second chapter focus first on the synthesis of novel chiral cyclopeptoids and then on their application in asymmetric phase-transfer alkylations, in particular for the enantioselective synthesis of α-amino acids. Afterwards the application of new designed calixarenes for the same alkylation reaction is described. Finally the application of cyclopeptoidic systems in the enantioselective alkylation of 2-aryl-oxazoline-4 carboxylic acid esters is discussed. The third chapter describes the application of crown ethers in phase-transfer processes. For this purpose a diasteroselective methodology for the synthesis of γ-substituted butenolides by a direct vinylogous Mukayama-Michael reaction has been developed. [edited by author]
L’attività di ricerca svolta dalla Dr.ssa Schettini Rosaria ha riguardato la sintesi e l’applicazione di nuovi sistemi macrociclici nella catalisi asimmetrica a trasferimento di fase. In particolare, il progetto di dottorato è stato incentrato sulla sintesi di nuovi sistemi chirali di natura ciclopeptoidica impiegati come catalizzatori nel campo asimmetrico. Nel corso del dottorato nuovi sistemi calixarenici chirali sono stati impiegati nel medesimo campo. L’ultima parte del progetto ha riguardato l’impiego di catalizzatori facilmente reperibili in commercio, gli eteri corna. Essi sono stati impiegati con successo in una reazione altamente diastereoselettiva. Durante il corso di dottorato, la dott.ssa Schettini Rosara ha seguito costantemente le attività didattiche previste nel progetto. [a cura dell'autore]
XIV n.s.

The key aim of this thesis was to develop suitable catalysts for sustainable processes and investigate the potential reaction mechanism. Characterizations were conducted to investigate the morphology and properties of the synthesized catalysts. The first part of this thesis is employing synthesized Au, Pt and AuPt loaded N-doped mesoporous carbon nanosphere catalysts for the photocatalytic oxidation of alcohols. Several characterizations and finite-difference time-domain (FDTD) simulation were conducted to study the intrinsic properties of the catalysts. AuPt bimetallic catalysts performed overwhelming higher catalytic activity and > 99 % selectivity to the corresponding aldehyde was detected. The Pt electronic sink effect and the co-catalyst effect were considered to enhance the catalytic activity. Moreover, reactant polarity and support conductivity influence on the catalytic performance had also been studied and a charge transfer reaction mechanism was proposed. The second part of this thesis focused on the application of Ni loaded three-dimensionally ordered macroporous (3DOM) CeO2 with different metal loading amount on CO2 conversion. The catalysts were synthesized by loading Ni nanoparticles by the wet impregnation method on 3DOM CeO2, which was pre-synthesized by sol-gel method with poly(methyl methacrylate) PMMA sphere substrate. All four catalysts with Ni loading amount from 2.5 % to 10 % showed great catalytic activity to CH4 and CO. The concentration of metallic Ni, oxygen vacancy and the macroporous structure of the catalysts played an important role during the catalytic reaction. The relatively smaller Ni nanoparticles in 2.5 % Ni loaded catalysts is proposed to result in the selectivity shift to CO. The reaction mechanism was studied and a reaction pathway demonstration diagram is depicted.

Achiral wide bite angle ligands have been shown to be highly active and to induce excellent chemo- and regioselectivities in many homogeneously catalyzed reactions. However, only a few examples of chiral wide bite angle ligands are known so far. A diphenyl ether backbone was selected to allow maximum synthetic versatility and potential for a modular approach to design and synthesize such chiral diphosphorus ligands. Three synthetic strategies have been explored in this thesis: i) introduction of chiral substituents in the ligand backbone, ii) the use of P-stereogenic donor atoms and iii) the synthesis of chiral mixed-donor ligands bearing chiral auxiliary groups on the phosphorus atoms. Functionalization of the 3,3'-positions of 2,2'-bis(diphenylphosphino)diphenyl ether by carboxylic acid or ether auxiliaries was achieved via straightforward four-step routes to generate a library of ligands that were tested in various catalytic reactions. In the Pd-catalyzed asymmetric allylic alkylation of l,3-diphenyl-2-propenyl acetate and cyclohexyl-2-enyl acetate with dimethyl malonate the enantioselectivity was found to depend on the size of the chiral auxiliary introduced within the diphenyl ether backbone and its proximity to the phosphorus donor groups and hence to the active metal centre. Two types of mixed donor bidentate diphosphorus ligands based on the diphenylether backbone have been established, i.e. phosphine-phosphite and phosphine-phosphonite derivatives. A small ligand library bearing different chiral auxiliaries was accomplished via straightforward syntheses that enable derivatization of the respective phosphite and phosphonite moieties in the final step. In the Rh-catalysed hydrogenation of several benchmark substrates high conversion and moderate to high enantioselectivities (up to 97% for dimethyl itaconate) were obtained. The enantioselectivity was influenced by the size of the ortho-substituent on the chiral auxiliary group of the phosphite or phosphonite fragment. Two modular synthetic approaches for the preparation of novel wide bite angle diphosphine ligands containing stereogenic P-atoms have been developed. Both protocols involved diphenylether as backbone and the chiral ephedrine based precursor (2R[subscript(P)],4S[subscript(C)],5R[subscript(C)])-oxazaphospholidine borane as initial auxiliary to induce chirality at phosphorus. Various novel diphosphines were isolated as highly enantioenriched compounds with dr-ratios up to 95:5.

Tese arquivada ao abrigo da portaria nº 227/2017 de 25 julho.
This research study expatiate upon the synthesis and characterisation of new nonclassical ruthenium hydride complexes bearing pincer ligands and their application in catalysis for CHactivation (H/D-exchange), hydrogen transfer processes and fixation of small molecules like N2 and CO2.

This thesis examines fundamental studies of catalysts for more sustainable processes, addressing three particular challenges: (1) Developing sulfur resistant catalysts that have potential applications in the processing of biomass for the production of liquid transportation fuels. (2) Reducing energy requirements and increasing the catalyst ease-of-use (especially water tolerance) for the hydrogenation of aromatics, particularly for the safe and feasible storage of hydrogen using the reversible toluene/methylcyclohexane couple. (3) Catalytically converting models of lignin building blocks as a source for renewable aromatic chemicals.

This thesis examines fundamental studies of catalysts for more sustainable processes, addressing three particular challenges: (1) Developing sulfur resistant catalysts that have potential applications in the processing of biomass for the production of liquid transportation fuels. (2) Reducing energy requirements and increasing the catalyst ease-of-use (especially water tolerance) for the hydrogenation of aromatics, particularly for the safe and feasible storage of hydrogen using the reversible toluene/methylcyclohexane couple. (3) Catalytically converting models of lignin building blocks as a source for renewable aromatic chemicals.

The scope of the PhD project is the investigation of acid and Palladium catalysts based on commercially available styrenic resins (both macroreticular and gel type) and a mesoporous poly-divinylbenzene (pDVB) and their application to target technologically relevant reactions, such as the esterification of stearic acid with methanol in sunflower oil and the direct synthesis of H2O2. In particular, the acid catalysts where produced by sulfonation with concentrated sulfuric acid, while the metal catalysts were prepared by TCS (Template Controlled Synthesis) approach, using the sulfonic groups to bind a suitable palladium precursor to the polymer matrix and a subsequent reduction step to form the corresponding metal nanoparticles. Being the sulfonation the main approach for the functionalization of styrenic cross-linked polymers, one of the goals of this project is the in-depth investigation of the effect of this process on the swollen state morphology of the materials. In particular, sulfonic resins prepared with different experimental protocols (i. e. by using concentrated sulfuric acid, chlorosulfonic acid and oleum), were characterized with Inverse Size Exclusion Chromatography (ISEC) to highlight the modification, if any, of pore size and total pore volume, due to the possible additional cross-linking produced by sulfone bridges. The morphological investigation is supported by the chemical analysis of the materials with solid state NMR, elemental analysis and determination of the ion-exchange capacity. As to the synthetic part of the PhD project, particular attention has been paid to the lipophilization of the cross-linked polymer matrix, in order to obtain promising materials for both the selected target reactions. In particular, an experimental procedure for the Friedel-Crafts acylation with perfluorobutyryl chloride of the aromatic rings of the resin was developed, achieving an appreciable degree of functionalization (12% and 15% of aromatic rings in pDVB and gel-type resins, respectively). The presence of hydrophobic moieties is expected to facilitate the adsorption of stearic acid inside the catalyst and, at the same time, an efficient expulsion of water, shifting the equilibrium towards the desired product. In the direct synthesis of hydrogen peroxide, the well established affinity of gases like hydrogen and oxygen to fluorinated phases could be the basis forthe enrichment in the reagents around the active Palladium nanoparticles supported by a fluorinated material, with beneficial effects on the catalytic activity. In addition, the highly lipophilic character of the catalyst should ensure an effective expulsion of the polar product H2O2, limiting its further reduction to water. As an example of acid catalysis, the esterification of stearic acid with methanol in sunflower oil has been chosen as the target reaction. It is a model for the esterification of the free fatty acids (FFA) which can be present in low-grade, cheap raw materials for the biodiesel production and must be abated before the base-catalysed transesterification process. The esterification step not only limits the consumption of the base catalyst , but also prevents the formation of soaps (from the neutralization of FFAs), which make impossible separation and purification processes. In the esterification reaction, the acid catalyst based on mesoporous pDVB showed catalytic performance comparable with those of the catalyst based on gel-type resin: thanks to the presence of an high excess of methanol, the catalysts are completely swollen and the high specific content of acidic groups in the sulfonated gel-type resin ensures conversions similar to those showed by the highly accessible pDVB. The fluorination of pDVB did not improve the catalytic behaviour, differently from related gel-type resins, suggesting that functionalization of this mesoporous material does not affect too much the lipophilic character of the catalyst, at least at the level achieved in this work. As an example of metal catalysis, the direct synthesis of hydrogen peroxide was investigated under room pressure and at a temperature of 25 °C in a semi-batch reactor, with methanol as the solvent and nano-structured Palladium catalysts based on functional macroreticular resins and macroporous pDVB. Hydrogen peroxide is currently produced by the Riedl-Pfleiderer process that exploits the auto-oxidation of an alkyl–anthrahydroquinone, giving high reaction yields without the direct contact between hydrogen and oxygen. However, this process is profitable only on a large scale, hence H2O2 is mainly used only in the bleaching agent of the cellulose pulp and in the preparation of detergents. To expand its rage of application to the production of fine chemicals (hydrogen peroxide is a strong oxidizing agent without polluting reduction by-products) a small scale production process would be highly beneficial. Under this respect, the direct synthesis is currently considered the most promising approach. In direct synthesis of hydrogen peroxide, the 1 %wt Palladium catalyst supported on poly-divinylbenzene shows a higher activity and selectivity towards H2O2 with respect to the the catalyst based on a macroreticular resin, as expected on the basis of the mesoporous morphology of the support. Finally, Palladium catalysts based on fluorinated pDVB exhibited higher activity, but smaller selectivity than the pristine material: the enrichment of the catalyst with gases efficiently promotes the hydrogenation of both oxygen hydrogen peroxide.
Lo scopo di questo progetto di dottorato ha riguardato la sintesi e la caratterizzazione di catalizzatori acidi e di Palladio, basati su resine stireniche commercialmente disponibili (sia macroreticolari che di tipo gel) e su un poli-divinilbenzene mesoporoso (pDVB), e la loro applicazione in reazioni industrialmente interessanti, come l’esterificazione dell’acido stearico in olio di girasole con metanolo e la sintesi diretta dell’acqua ossigenata. In particolare, i catalizzatori acidi sono stati prodotti per solfonazione dei supporti polimerici con acido solforico concentrato, mentre quelli metallici sono stati preparati attraverso approccio TCS (Template Controlled Synthesis), sfruttando i gruppi solfonici per legare alla matrice polimerica un opportuno precursore metallico che, attraverso un processo riducente, permette di ottenere le corrispondenti nanoparticelle metalliche. Essendo la solfonazione il principale approccio per la funzionalizzazione di resine stireniche, uno degli obbiettivi di questo progetto è stato lo studio approfondito dell’effetto di tale processo sulla morfologia allo stato rigonfiato di tali materiali. Resine solfonate con diversi protocolli sperimentali (acido solforico concentrato, acido clorosolfonico ed oleum come agenti solfonanti) sono state perciò caratterizzate con la tecnica ISEC (Inverse Size Exclusion Chromatography) per mettere in evidenza un’eventuale correlazione tra il diverso processo di solfonazione e variazioni delle dimensioni dei pori e del volume totale del sistema poroso. Lo studio morfologico è stato anche affiancato dall’analisi chimica dei materiali mediante NMR allo stato solido, analisi elementare e determinazione della capacità di scambio ionico. Per quanto riguarda la parte sintetica del progetto, particolare attenzione è stata rivolta all’ottenimento di matrici polimeriche lipofiliche per ottenere materiali potenzialmente promettenti per entrambe le reazioni studiate. E’ stata dunque messa a punto una procedura sperimentale per l’acilazione di Friedel-Crafts con perfluorobutirril cloruro degli anelli aromatici della resina, ottenendo un significativo grado di funzionalizzazione (12% e 15% degli anelli aromatici acilati, rispettivamente, nel pDVB e nella resina di tipo gel). Nella reazione di esterificazione dell’acido stearico la presenza di gruppi idrofobici dovrebbe favorire l’assorbimento e/o adsorbimento dell’acido stearico all’interno del catalizzatore e, nello stesso tempo, garantire un’efficace espulsione dell’acqua, spostando l’equilibrio di reazione verso il prodotto desiderato. Per quanto riguarda invece la sintesi diretta dell’acqua ossigenata, un supporto fluorurato dovrebbe promuovere, grazie alla nota affinità dell'idrogeno e dell'ossigeno verso le fasi fluorurate, l'arricchimento del catalizzatore nei reagenti gassosi ed aumentarne dunque l’attività catalitica. Inoltre il carattere lipofilico del catalizzatore dovrebbe assicurare un’efficace espulsione dal catalizzatore dell’H2O2 prodotta, limitandone l’ulteriore riduzione ad acqua ed incrementando in questo modo la selettività della reazione. L’esterificazione dell’acido stearico con metanolo è stata studiata come reazione modello per lo stadio di esterificazione degli acidi grassi liberi, che precede quello base-catalizzato di trans-esterificazione, nell’ambito della produzione di biodiesel da oli e grassi di scarto. La pre-esterificazione acido catalizzata non solo evita il consumo di catalizzatore basico, ma previene anche la formazione di saponi (dalla neutralizzazione dei FFAs) che rendono impossibili i successivi processi di separazione e di purificazione del biodiesel. Nella reazione di esterificazione, il catalizzatore acido basato sul pDVB mesoporoso ha mostrato prestazioni catalitiche confrontabili con quelle del catalizzatore basato sulla resina di tipo gel: grazie alla presenza di un alto eccesso di metanolo nella miscela di reazione, infatti, i catalizzatori sono completamente rigonfiati e l’alto contenuto specifico di gruppi acidi nella resina di tipo gel assicura conversioni simili a quelle osservate con il pDVB. Inoltre, la fluorurazione del pDVB non ne ha migliorato il comportamento catalitico, suggerendo che la funzionalizzazione di un sistema mesoporoso come quello del pDVB non è in grado di influenzare efficacemente il carattere lipofilico del catalizzatore, almeno ai livelli di funzionalizzazione sin qui ottenuti. Come reazione target per la catalisi metallica, è stata invece studiata la sintesi diretta dell’acqua ossigenata. Il processo è stato condotto a pressione e temperatura ambiente, usando un reattore di tipo semi-batch, metanolo come solvente e catalizzatori nano-strutturati di palladio basati su resine macroreticolari e su pDVB mesoporoso. Attualmente la quasi totalità dell’acqua ossigenata è ottenuta con il processo Riedl-Pfleiderer che sfrutta l’auto-ossidazione di un alchil-antraidrochinone, dando alte rese di reazioni ed evitando il contatto diretto tra idrogeno ed ossigeno. Tuttavia questo processo è economicamente vantaggioso solo su larga scala, il che limita l’utilizzo dell’H2O2 principalmente alla preparazione di detergenti e come agente sbiancante per la polpa di cellulosa. Dato che l’ H2O2 è un forte agente ossidante che dà acqua come unico sottoprodotto, il suo utilizzo per la produzione di fine-chemicals sarebbe potenzialmente molto interessante dal punto di vista ambientale. Pertanto sarebbe auspicabile lo sviluppo di un processo su piccola scala e la sintesi diretta è attualmente considerata l’approccio più promettente. Nella sintesi diretta dell’acqua ossigenata, un catalizzatore all’1 % in peso di palladio supportato sul pDVB mostra un più alto consumo di idrogeno ed una più alta selettività rispetto al catalizzatore basato sulla resina macroreticolare, come era prevedibile sulla base della morfologia mesoporosa del supporto. Infine, il catalizzatore di Palladio basato sul pDVB fluorurato mostra una più alta attività, ma una più piccola selettività del corrispondente catalizzatore non funzionalizzato: l’arricchimento del catalizzatore con i gas sembra quindi promuovere efficacemente sia la produzione che l’idrogenazione dell’H2O2.

Gold has emerged as valuable tool for chemists. The physico-chemical properties of the metal centre make it exceptionally prone to activate multiple bonds, such as alkynes and alkenes. Thus, its utility in catalysis has been exploited together with the synthesis of suitable catalysts to allow new, efficient transformations, and the understanding of their intrinsic mechanisms. Reported in this thesis are efforts to this goal, such as the design and study of new Au(I) and Au(III) complexes towards functionalisation of alkynes. The development of new catalytic systems is tackled in Chapter 2. An efficient method for the intermolecular hydrocarboxylation of alkynes catalysed by dinuclear Au-NHC species to access diverse vinyl esters in excellent yield and stereoselectivity is described. The successful methodology is followed by the straightforward intramolecular hydrocarboxylation of alkynoic acids to allow the stereoselective and regioselective synthesis of γ-, δ- and ε-lactones in high yield. Initial mechanistic studies into the hydrocarboxylation of alkynes are shown in Chapter 3. The discovery and characterisation of novel dinuclear gold carboxylates species is described, and their role in the catalytic inter- and intramolecular process is investigated. Chapter 4 highlights the synthesis of novel Au complexes bearing chiral isothiourea ligands. Neutral and heteroleptic Au(I) and Au(III) species are obtained in excellent yield, and their solution and solid-state behaviour studied, together with their electronic and steric properties. Further testing towards activation and functionalisation of alkynes and propargylic derivatives are shown. Dual catalytic processes involving Au and isothiourea catalysts are presented in Chapter 5. Attempts towards Lewis acid/Lewis base activation of multiple bond derivatives and activated esters towards the formation of new C-C bonds is described. The synthesis of organogold compounds, bearing NHC ligands, is described in Chapter 6. Through deprotonation of C(sp3 )-H bonds, a series of stable gold(I) complexes was synthesised and found to be suitable synthons to different gold species. Finally, the redox chemistry of organogold species is explored.

Bio-derived polymers offer a sustainable alternative to petroleum-derived polymers. One such polymer, polylactide (PLA) is synthesised from the ring-opening polymerisation (ROP) of rac-lactide (rac-LA). The monomer contains two stereocentres which gives a range of tacticities. The isotactic ROP of rac-LA yields the most desirable polymer properties (physical and mechanical properties) and is quantified using a P_i (probability of isotactic enchainment) value. This thesis investigates tri- and tetradentate ligands coordinated to zinc(II), aluminium(III) and indium(III) to understand the ligand effects on both rate and isoselectivity. The first results chapter, Chapter 3, outlines the synthesis of a tetradentate salen ligand, its analogous phosphasalen ligand, where the imine bonds are replaced with iminophosphorane bonds and a hybrid ligand containing a mixture of both imine and iminophosphorane bonds. The salen, phosphasalen and hybrid ligands are coordinated to both aluminium and indium and used as initiators for the ROP. The indium hybrid initiator yields the highest isoselectivity (P_i = 0.71) which is significantly higher than its salen and phosphasalen analogues (P_i = 0.51 - 0.52) Chapter 4 investigates structure-activity relationships of the indium hybrid initiator, by modification of the ligand scaffold. Bulkier ortho-phenolate substituents do not affect rate or isoselectivity. Electron-withdrawing chloride substituents increase rate but decrease isoselectivity (P_i = 0.61). Modification of the phosphorus substituents yields the highest isoselectivity value (P_i = 0.75). It may be hypothesised that isoselectivity depends upon steric hindrance at both ortho-substituents and at phosphorus. Furthermore, the synthesis of a ferrocene containing indium hybrid complex is developed for future use in redox-switch catalysis. Chapter 5 describes the synthesis of two tridentate half-phosphasalen ligands and their coordination chemistry with zinc(II) and indium(III). Zinc initiators are active but display poor polymerisation control and low isoselectivity values (P_i = 0.67). Zinc complexes, with a less sterically encumbered ligand, preferentially form a homoleptic complex, which cannot be used in ROP. Indium initiators are slower than analogous half Schiff base initiators reported in the literature but show an improved isoselectivity value (P_i = 0.72).

This thesis is comprised of three projects that serve to address current topics in the field of bioorganic chemistry. Chapter 1 describes the emulation of enzyme catalysis through the kinetic analysis of the DNAzyme 9₂₅-11t, a combinatorially selected RNase A mimic utilizing imiclazole and amine groups hybridized to DNA. The rate constants measured for this system are the largest to date for M²⁺ -independent self cleavage (0.020 min⁻¹), trans cleavage (0.28 ± 0.02 min⁻¹), and multiple turnover (0.030 ± 0.002 min⁻¹) by a biomimetic system at physiological ionic strength and pH. These constants rival most combinatorially selected metal dependent DNAzymes and naturally occurring ribozymes even at physiological concentrations of M²⁺. Chapters 2 and 3 discuss a novel photochemical motif, its application to biologically relevant molecules, characterization of the photochemical mechanism, and its utility in the generation of alkenes. Light is considered superior to other chemical reagents as its spatial and temporal properties can be precisely controlled and its penetrative ability makes it a perfect reagent for the non- invasive perturbation of cellular processes. Chapter 2 details the discovery of a novel photochemical reaction and its use in photochemically regulating gene function and nucleic acid chemistry. The chemistry described in Chapter 2 holds potential for the photocaging of all adenine substrates, cofactors, and products in biological systems. Chapter 3 identifies the photolytic mechanism and highlights its application to photolytic alkene synthesis. It is predicted that the photolytic thioether mechanism identified in this chapter can be extrapolated to the photolysis of a wide range of other aromatic thioethers. Chapter 4 discusses the application of the ¹⁸F acceptor, boron, to most sensitive of in vivo molecular imaging techniques: positron emission tomography. This aqueous approach simplifies the state of the art by multiple chemical steps and multiplies the final specific radioactivity of the final radiotracer by a factor of 3. This tool is expected to widen the currently limited scope of biomarkers available for in vivo imaging and will enhance our ability to image biochemical targets and pathways such that insight may be gained in the progression, diagnosis, and treatment of disease.

Ligands involving CNC structures have been of intense interest in research. With an aim to investigating this area, a modular synthesis was developed using condensation reactions between a base unit of 2,6-dichloroisonicotinic acid and N-alkyl imidazoles toprovide a range of 2,6-bis(imidazolium) salts. From this point several methods wereavailable to incorporate an active metal centre, however, state of the art microwaveaccelerated synthesis was found to be the most successful technique in forming the tridentate palladium complexes. Several strategies were investigated to attach these complexes to polymer resins, exploring a range of linking groups, coupling procedures and resins. The most effective strategy involved forming an acid functionalised palladium complex to allow loading onto an amino-functionalised resin. Although several reagents were investigated it was found that the commercially available reagent PyBop® was the most effective in forming the stable amide bond from the palladium complex to the polymer resin. By using an excess of coupling reagent and an excess of the acid functionalised palladium complex complete loading onto an amino functionalised resin could be achieved.The supported complexes were found to be highly stable catalysts in Heck, SuzukiMiyauraand Stille reactions, and capable of cross-coupling a range of aryl iodides in very high yields. The active catalysts showed very little leaching of palladium (ICPMS) and could be recycled up to fourteen times with no loss of activity. Long reaction times were overcome using tetra-n-butylammonium bromide as an additive or by using microwave irradiation. Following these catalytic studies and with an aim to using less active electrophiles, several strategies were investigated to develop enhanced activity catalysts. These strategies involved replacing one of the N-Heterocyclic carbene ligands with either an "inert" bulky group or with another alternative ligand. Full details of this research are presented in chapters 2 to 5.

This thesis describes the synthesis and catalytic testing of new bis(diphenylphosphino)amine 'PNP' ligands for use in chromium catalysed trimerisation, rhodium catalysed asymmetric hydrogenation and palladium catalysed telomerisation. Chapter 1 presents an overview of catalysis with particular emphasis on the importance of ligand design, homogeneous and heterogeneous asymmetric catalysis, oligomerisation, concluding with future prospects . Chapter 2 investigates the application of bis(diarylphosphino)amine ligands in telomerisation catalysis, comparison of PNP ligands with the benchmark ligand triphenylphosphine, optimization of the telomerisation of carbon dioxide with l,3-butadiene to give a highly active and selective novel catalyst system. Chapter 3 describes the synthesis of soft donor PNP ligands, their complexation with chromium precursors and their application in oligomerisation and co-oligomerisation catalysis with ethene, carbon dioxide, heterodienes and alkynes. Chapter 4 introduces bis(diarylphosphino) amino acid ester based ligands, their synthesis, and complexation to transition metals. The application of these ligands in asymmetric hydrogenation catalysis of methylamino cinnamic methyl ester (MAC) and methylamino methyl ester (MAA). Chapter 5 extends the synthesis of amino acid ester ligand to tripeptide backbone bis(diarylphosphino)amine ligands, development of synthetic methodology, complexation to platinum, palladium and rhodium precursors, characterisation and application in asymmetric catalysis. Chapter 6 contains the experimental details for the preceeding chapters.

This PhD thesis is focused on the development of novel catalysis with low-oxidation main group species, mainly based on the group 13 element gallium, a relatively abundant, inexpensive, and low-toxic metal. Gallium in its stable high-oxidation state ‘+III’ is a commonly used Lewis acid catalyst in organic synthesis. In contrast, gallium in its less stable low-oxidation state ‘+I’ is under-explored, but may display both acceptor and donor properties at a single site (ambiphilicity). Based on the hypothesis that potentially ambiphilic gallium(I) –oxidatively generated in situ from gallium(0) using a silver salt– may activate both basic and acidic reagents, various gallium(I)-catalyzed carbon–carbon bond formations have been developed. These include catalytic C–O and C–B bond activations of electrophiles (acetals and aminals) and pro-nucleophiles (allyl and allenyl boronates), respectively. Gallium(III) and other metal Lewis acids have proved to be ineffective. These results represent the first catalytic use of gallium(0) in organic synthesis and a rare example of gallium(I) catalysis. The identity of the gallium(I) catalyst and its regeneration have been confirmed by 71Ga NMR analysis, and a reactive allyl–Ga(I) intermediate has been detected for the first time. In combination with 11B NMR and HRMS analyses, an SN1 reaction mechanism has been proposed. Importantly, the potential for asymmetric gallium(I) catalysis has been demonstrated using a chiral silver co-catalyst (40% ee). This gallium(I) chemistry has proved to be applicable to the catalytic activation of other electrophiles, including ethers or aldehydes, and pro-nucleophiles such as boranes, silanes, or tin-based reagents. Finally, the potential of a related low-oxidation aluminium catalyst has been explored for C–C bond formation.

Biomass gasification offers the chance to produce carbon neutral, renewable fuels. One of the main problems facing the commercialization of biomass gasification technology is the presence of large quantities of methane and carbon dioxide in the biogas. Catalytic reforming of these wastes allows for effective utilization of biomass derived syngas. In most reforming studies, impregnation methods are the primary synthesis technique. Impregnation methods often lead to poor dispersion and are un-reproducible from batch to batch. In the development of a novel catalyst for reforming applications, another preparation method is implemented, controlled adsorption (CA). Ni/Al2O3 and Co/Al2O3 prepared by CA are compared against catalysts that were prepared by a more traditional method, dry impregnation (DI). It is found that controlling the metal deposition provides catalysts with higher dispersion and consequently higher activity for methane dry reforming. NiAl2O4 catalysts prepared by Pechini synthesis were also studied for catalytic conditioning of biomass derived syngas. Physicochemical characterization revealed unique structural properties, indicated a high degree of mobility of nickel in the aluminate structure, and demonstrated the regeneration properties of nickel aluminates under harsh reaction conditions, which will be important at extended reaction times when catalyst regeneration becomes necessary. Fourfold coordinated nickel species are believed to be responsible for high, stable methane dry reforming activity and metallic nickel is believed to be the active site that allows for high, stable conversion during methane dry reforming.

There is an increasing necessity for the pharmaceutical industry to develop enantiomerically pure drugs. Up till now, production of enantiomerically pure molecules has been provided by harvesting them from plants or utilising homogeneous catalysis and biocatalysis. None of these methods are efficient means of production, and attention is now being directed towards heterogeneous enantioselective catalysis as the preferred technique. This is on account of the high product yield and ease of separation of catalyst from the reaction mixture. Over the past few decades, a great deal of research has been conducted into investigating the Ni catalysed hydrogenation of β-ketoesters and Pt catalysed hydrogenation of α-ketoesters. These are the most successful systems for enantioselective heterogeneous catalysis. However, they are unsuitable for industrial purposes due to the low thermal and mechanical stability of the modified surfaces. The main goal throughout this project has been the investigation of surface-confined covalent reactions. The motivation of this research is to develop enantioselective heterogeneous catalysis; covalent networks are believed to infer the necessary thermal and chemical stability required to chirally modify catalytic surfaces for docking interactions with reactant species. Covalent organic frameworks (COFs) on surfaces hold potential for a number of chemical applications, and not just in the field of heterogeneous catalysis; for example in areas such as molecular electronics and templating.

The aim of my training period has been the synthesis of new chiral N-heterocyclic carbene precursors starting from camphoric diacid and the employment of imidazolium salts derived NHC as linker to dendrimers supports for organometallic catalysis. New chiral ligands are needed to develop new catalytic systems for enantioselective transformations. The new type of ligand described was developed starting from camphoric diacid, a cheap chiral molecule, following different synthetic strategies. Asymmetric functionalized chiral NHCs are readily available by methods developed and two of the precursors obtained were employed in preliminary tests with Aluminium and Palladium. An NHC derived from imidazolium salt has been investigated as linker to dendrimeric supports for tetraarylciclopentadienone-Ruthenium complexes with the aim to combine advantages of homogeneous catalysis to advantages of heterogeneous one, in particular easy recover of catalyst. The functionalized dendrimers obtained have been used in transfer hydrogenation and dehydrogenation reactions. Moreover a new class of functionalized dendrimer was obtained employing a new tetraarylciclopentadienone-Ruthenium complex with trimethyl silyl groups on cyclopentadienone ligand with the aim to change solubility of the system.

This thesis is comprised of six chapters describing imidazolinium and imidazolium salts and their conversion into nitrogen heterocyclic carbenes (NHCs) for use in asymmetric catalysis. It is structured thus: Chapter one provides an introduction to imidazolium and imidazolinium salts, their discovery and uses; an introduction to carbenes and NHCs, discovery and utilisation with an emphasis on those NHCs derived from imidazolinium salts. Additionally, retro synthetic approaches to NHCs, imidazolium and imidazolinium salts are overviewed. Chapter two describes the synthesis of imidazolinium salts bearing pendant sulfonate groups starting with N-Boc protected chiral aminoalcohols. Oxazolines are formed in situ from the aminoalcohols by action of 2-sulfobenzoic anhydride in a Dean-Stark apparatus. Various amines are then used to open the oxazolines resulting in amidosulfonic acids. These amidosulfonic acids are formed as a result of acid› triggered SN2 attack of the amines at the electrophilic OCH2 site in the oxazoline. The amido group can be reduced with borane-dimethylsulfide, resulting in diamino sulfonic acids which were cyclised with a suitable orthoester, such as triethyl orthoformate, to provide the imidazolinium sulfonate zwitterions. Chapter three details the synthesis of various imidazolinium salts by N-alkylation of imidazolines. Amidosulfonic acids (see Chapter two) are converted into imidazolines by a serendipitous cyclisation that has advantages over other current literature routes. Alkylation of imidazolines with different benzylic halides and bromo alcohols allows a large library of imidazolinium salt to be achieved. Chapter four gives a brief outline of current literature uses of imidazolinium salts in asymmetric catalysis before detailing the synthesis of NHCs complexes and screening of the imidazolinium sulfonate zwitterions (see Chapter two) in catalysis. Specifically additions of alkyl magnesium halides to cinnamyl halide derivates were found to give mostly y-addition products that were enantiomerically emiched (up to 80% ee). The synthesis of copper-carbene-ligands complexes for catalysis of this and other reactions was also investigated. Chapter five provides overall conclusions from this thesis and future work to be carried out. Chapter six contains full experimental details and analytical data for novel compounds prepared. An index of the novel compounds and selected spectra can be found in the appendix.