Cette thèse apporte une contribution au développement de complexes carbènes N-hétérocycliques-palladium basés sur des calix[4]arènes: leur synthèse, leur caractérisation ainsi que l'évaluation de leur activité catalytique est presenté. Pour cela, un calix[4]arène mono-substitué a été préparé conformément aux procédures classiques, puis les précurseurs de nouveaux ligands NHC ont été obtenus. Subissant l'alkylation avec du n-butylbromide et puis une métallation subséquente avec du palladium et de la pyridine, quatorze nouveaux complexes ont été obtenus. Après les caractérisations complètes en solution et à l'état solide, l'évaluation de l'activité catalytique a été réalisée dans réactions couplage de Suzuki-Miyaura. De bonnes performances ont pu être observées permettant d'obtenir des taux de transformation de 99% avec des quantités de catalyseur descandant jusqu'à 0.08 mol%. L'étude de conformation ainsi que les résultats catalytiques en catalyse n'ont pas permis de mettre en évidence un effet supramoléculaire de la cavité macrocyclique envers le processus de couplage. Dans le but d'orienter le centre catalytique à l'intérieur de la cavité, des contraintes stériques ont été appliquées sur des nouveaux Pd-NHC-complexes. Ainsi des complexes dimeriques de palladium ont été synthétisés et entièrement caractérisés. Plusieurs approches pour construire des linkers intramoléculaires permettant de fixer la conformation ont été énvisagées mais n'ont pas permis à ce jour un gel conformationnel / This thesis will focus on development of N-heterocyclic carbene palladium complexes based on calix[4]arenes: from synthesis, characterization and structural study to evaluation of catalytic activity. A new series of calix[4]arene supported N-heterocyclic carbene palladium complexes was developed and fully characterized. A mono-substituted calix[4]arene was prepared through conventional procedures, following with the attachment of imidazolyl derivative groups to compose the precursors of novel NHCs ligands. Undergoing the alkylation with n-butylbromide and corresponding metallation with palladium and pyridine, original complexes were obtained. After a full characterization in solution and solid state, the evaluation of catalytic activity was undertaken through Suzuki-Miyaura cross-coupling reactions which revealed good performances. The conformational study as well as the catalytic results in catalysis did not allow putting in evidence a supramolecular effect of the macrocycle cavity towards the coupling process. With the aim of localize catalytic center inside of the cavity, steric constrain was involved in the form of new Pd-NHC-complexes. Dimeric Pd complexes were synthesized and fully characterized as well. Several approaches to construct intramolecular linkers for fixing the conformation were elaborated. The conception of ‘flexible steric bulky’ inspired the research on confined structure of calix[4]arene, such as encapsulation and capped configuration. Relative progresses were carried out and discussed

A wide variety of computational methods are available for exploring molecular structures and reactivity in chemistry. These range from molecular mechanics calculations allowing determination of the geometry of a molecule to ab initio calculations for the electronic structure of compounds. Electronic structure calculations can be carried out with sufficient rigor so that the results are now comparable with experimental results in many cases. Density Functional Theory (DFT) with hybrid functional like B3LYP, for example, is very popular especially for studies on organometallic molecules and their reactions. Traditional ab initio approaches including Hartree-Fock (HF) and post-HF methods that include configuration interaction, such as MP2 and MP4 continue to be used, often for comparison with DFT based methods. Semi-empirical methods now appear to have only limited use except in large systems, in combination with molecular mechanics (MM) calculations. A relatively new use of MM for large systems is in hybrid calculations where the reactive center of the system is treated at a higher level leaving the remainder to be treated at the MM level. These hybrid QM/MM (quantum mechanics/molecular mechanics) calculations, such as ONIOM (our own n-layered integrated molecular orbital and molecular mechanics developed by Morokuma and co-workers) enable one to treat the steric bulk of the big system effectively and computationally efficiently. They appear to be very standard methods particularly in studies relating to reactions of organometallic systems and structures of large biomolecules. A short description of these methods is given below. • ab initio: a wide variety of programs that calculate the electronic structure of molecules using the Schrödinger equation, the values of the fundamental constants and the atomic numbers of the atoms present (Atkins, 1991). Molecular structures, optimized as a function of the electronic structure, are valuable starting points for many studies. • Density Functional Theory (DFT): a theoretical model in which the energy of an N-electron system is described as a functional of the density. • Semi-empirical techniques use approximations to evaluate the overlap, repulsion and exchange integrals in solving the Schrodinger equation. Often, these integrals are not evaluated but estimated to reproduce experimental data. • Molecular mechanics uses classical physics to explain and interpret the behavior of atoms and molecules. • Molecular dynamics (MD): Newton’s laws of motion are used to examine the time-dependent behavior of systems, including vibrations and Brownian motion, using a classical mechanical description. When combined with DFT, it leads to the Car-Parrinello method. • QM/MM method: It is a molecular simulation method that combines the strength of both QM (accuracy) and MM (speed) calculations, thus resulting in an extremely powerful tool for the study of bigger systems like chemical process in solution, interaction of drugs with biomolecules etc. Several commercial and educational packages in computational chemistry include a suite of programs that enable study of organic and organometallic molecules in an integrated fashion. While no list can be comprehensive, those that are more popular and useful are listed in several websites URL (http://www.ccl.net/chemistry/links/software/index.shtml). In the early days of computational chemistry up to 1980's, detailed studies were only carried out on small organic compounds or empirical studies were carried out on transition metal containing organometallics. However, in recent times, significant advancements in theoretical methods and computer capability (hardware and software), have led to the acceleration of theoretical and computational studies of complex systems including compounds containing transition metal elements. Computational and theoretical studies of organometallic complexes and their reactions have gained immense popularity and the numbers of papers including theoretical studies are dramatically increasing. One reason for this popularity is that organometallic complexes exhibit unusual geometries, bonding, and reactivity which often do not fall into the domain of inorganic or organic chemistry making them difficult to understand. Catalysis is one of the most extensively studied areas in organometallic chemistry where computational studies already make a real and valuable contribution to the analysis and interpretation of experimental data. However, what might be called ‘in silico’ catalyst screening and design, has rarely been achieved. One might say that successful prediction of catalyst performance is still a dream. A recent review summarizes the current state of the art in computational chemistry as applied to organometallic catalysis, covering both calculated ligand property descriptors and mechanistic studies of catalytic cycles.1 Some of the widely studied catalytic reactions of current interest, that provide huge scope for computational and theoretical analysis, are allylic alkylation (Pd),2 hydrogenation (Rh),3 hydroformylation (Rh),4 alkene metathesis (Ru),5 cross-coupling (Pd),6 C–H activation (Pd)7 and amination (Pd).8 There are many more examples where computational studies appear to be very useful for analysis of crystal structures and NMR structures or prediction of structures where no experimental data are available for complicated organometallic systems. There are a number of studies on drug-DNA/nucleobases interactions using QM/MM-MD simulations where people have investigated the interactions of metal complexes with double stranded (ds) DNA/nucleobases and the effects of their binding on the local and the global structure of DNA. QM/MM methods are also very helpful for studying catalytic reactions, interpretation of structure of large systems (proteins) and understanding reactions in biological systems. Scope of the Thesis In this thesis an attempt is made to use computational chemistry to understand organometallic reactions that are of significance from biological and synthetic view points, such as the action of organometallic complexes on DNA and the mechanism of some catalytic reactions. In many of these cases, the key step involved a nucleophillic attack. Specifically four such problems have been addressed where experimental results are not sufficient to provide a complete mechanistic picture of the reaction. Hence, the thesis contains four chapters with each having an independent brief introduction. The first chapter deals with the substitution reaction where water replaces chloride ion in the piano stool type ruthenium (II)-arene complexes and subsequently coordination of Ru to guanine/adenine occurs in these complexes. These steps have been studied using density functional theory at the B3LYP level. The complexes have promising anticancer activity. These nucleophilic substitution reactions are very important for activating these complexes so that they can interact with DNA, because DNA is thought to be primary target for their anticancer activity. In this chapter, both associative and dissociative pathways have been explored in the gas phase, as well as in the presence of other solvents for substitution reactions. Among the associative paths, a variety of possibilities can exist for the hydrolysis based on the direction of the nucleophilic attack by a water molecule. The proposed theoretical model for hydrolysis provides new insight into the hydrolysis process in half sandwich ruthenium complexes. The second chapter deals with the QM/MM calculations to investigate the structural and electronic properties of drug-DNA interactions, where DNA acts as nucleophile towards the metal complex. A series of piano-stool type ruthenium (II)-arene complexes were selected for the present study. These interactions were analyzed using the two layer ONIOM method. The importance of this study lies in the detailed understanding of factors that govern DNA binding and reactivity which is clearly of great pharmacological interest, as it may provide the basis for designing better anticancer agents. Experimental results that explore the structural feature of DNA-metal complexes at a molecular level are very limited. Thus theoretical calculations of molecular and electronic structure represent a valuable complement to experiments. They provide an alternative way to explore structure-activity relationships, and the drug binding mechanism, in detail. The third chapter reports the use of QM/MM methods in understanding the reaction mechanism and enantioselectivity in an organic transformation. In this section, a computational investigation of the enantioselectivity observed in the allylation of cinnamaldehyde, catalyzed by chiral platinum phosphinite complexes, have been carried out. The catalysts are ascorbic acid based phosphinite complexes where enantioselectivity depends on the substitution of benzyl groups on the chiral phosphinite ligands. From the experiment, it is not clear how the effect of an ancillary ligand can make such a big impact on enantioselectivity. To find out the origin of stereoselectivity, a computational study was taken up. A reaction mechanism was established where the nucleophilic attack determines the rate of the reaction and the corresponding enantioselectivity. A screening process has been utilized to select relevant reactant adducts and corresponding transition states from approximately 200 theoretically possible conformers using MM calculations. Finally with the help of QM/MM calculations, the numbers of contributions of these conformers were estimated. This approach correctly predicts the enantioselectivity in these reactions catalyzed by these complexes especially when the experimental enantioselectivity is very high. The fourth chapter of the thesis discusses the use of computational techniques to study the nucleophilic attack of an imine on a Ti-olefin complex. The reaction of Grignard reagents with imines mediated by stoichiometric amounts of titanium isopropoxide has been reported recently. On the basis of deuterium labeling experiments, nucleophilic attack of an imine on a Ti-olefin complex was believed to be a key step. Effect of deuterium labeling on the ratio of products formed is not easy to understand from experiments. Hence a computational study was performed using the DFT method to establish the mechanism of substitution and to understand the role of deuterium labeling. The thesis also includes a study of Cu-Cu interactions using Atoms in Molecules (AIM) theory in copper complexes with reasonably short Cu-Cu distances. The concept of bond critical points (BCP) from AIM analysis is employed to investigate the CuI-CuI bonding interactions in ligand unsupported copper complexes where the CuI-CuI contacts are shorter than the sum of their van der Waals radii. There is extensive debate about the nature of interactions between d10 "closed shell" systems in copper (CuI) complexes, which is known as cuprophilicity. In this study, an attempt has been made to compute the electron density between the two CuI centers and examine the nature of this “interaction”. As this falls outside the main theme of nucleophilic interactions in metal complexes, it has been relegated to an appendix.

There is a continuing interest in the subject of arene carbonylation, especially in strong acids and environmentally-benign alternatives are sought to HF/BF3 and to AlCl3 as conversion agents. Ionic liquids offer a powerful solvent for useful conversion agents such as aluminum chloride. The ILs permit AlCl3 to be used at lower HCl partial pressures than with other solvents. The superior reactivity demonstrated by acidic, chloroaluminate ILs is probably due to their enhanced solvation power for HCl and CO. Addition of HCl gas increased reactivity of the system by forming Brnsted acids, and toluene carbonylation is a Brnsted demanding reaction. It was found that reaction is stoichiometric in Al species and only intrinsically acidic ILs are active for toluene carbonylation, therefore it was possible to correlate observed conversion with predicted amounts of Lewis + Brnsted acids. Molecular modeling provided information about the different species present in these ILs and predicted 1H NMR, and 27Al NMR spectrum. Predictions suggested that three types of HCl species are present; and these predictions were confirmed using data of 13C-labeled acetone and its 13C-NMR spectra. These data showed that only one of the three types of HCl in the IL were super acidic. Reactivity towards arene formylation can be tuned by adjusting the ligands R and R in the organic cation and by changing the anion. This reactivity tuning can be exploited in a process where high acidity is required for the conversion of substrate but where separation of product from IL is facilitated by low acidity.

Durant les darreres dècades, el disseny de processos en el marc de la química sostenible ha anat creixent de forma exponencial. La recerca constant de processos mes benignes amb el medi ambient ha implicat un gran esforç per obtenir millors rendiments mitjançant l'activació de llocs específics, i possant especial èmfasi amb el control de la quimio-, la regio- i la enantioselectivitat, punts crucials per a l'economia atómica. En aquest sentit, els dissolvents juguen un paper crític, i com podrà veure's al llarg d'aquesta memòria..Aquesta Tesi s'enfoca en l'ús de mitjans de reacció alternatius i sostenibles, com són els líquids iònics (ILs), el diòxid de carboni supercrític (scCO2) i la barreja de ambdós dissolvents, amb l'objectiu de disminuir l'ús de dissolvents orgànics convencionals i la seva aplicació en els següents processos catalítics: hidrogenació asimètrica, reacció de Suzuki d'acoblament creuat C-C, reacció d'alquilació al·lílica asimètrica i la hidrogenació de arens. / In the last decades, the design of processes in the framework of the sustainable chemistry has been exponentially growing. The constant searching of cleaner processes has led to a lot of effort to obtain higher yields by activation of specific sites, and improving chemo-, regio- and enantio-selectivities, which are crucial from a point of view of an atom economy strategy. In this sense, solvents play a critical role. This PhD thesis focuses on the use of alternative sustainable reaction media such as ionic liquids (ILs), supercritical carbon dioxide (scCO2) and mixtures of both solvents in different catalytic processes, with the aim of decreasing the use of conventional organic solvents applied in the following catalytic reactions: homogeneous and supported rhodium catalysed asymmetric hydrogenation, biphasic palladium catalysed Suzuki C-C cross-coupling, homogeneous palladium catalysed asymmetric allylic alkylation, and ruthenium and rhodium nanoparticles catalysed arene hydrogenation were tested.

This thesis covers combination of two independent works accomplished throughout the study. One part research is about the unexpected cyclization of Dipyridyl-glycoluril, and the other part is about synthesis of precursor calix[4]arene derivatives. In an attempted synthesis of peripherally pyridine substituted cucurbituril, an unexpected cyclized product was obtained. A careful NMR analysis followed by mass spectrometry and preliminary crystallographic analyses, helped us in resolving the structure. The structure has two quaternized pyridine functionalities and a groove suitable as a potential receptor site. In addition, just like the parent glycoluril structure, two remaining urea-derived nitrogens can be alkylated by alkyl halides. Thus, we believe this high yielding reaction may become an entry point to a new class of anion receptors. In the second work, certain important calix[4]arene derivatives were synthesized. They are the building blocks of important potential molecular, anion and cation sensing, and enzyme mimics. For these precursor molecules, functionalizations both on lower and upper rim have been studied. A careful study on NMR data has been performed and detailed investigation on the NMR data was discussed herein. Applying further one or two step procedures produces important target molecules having potential as sensors or artificial enzymes.

O fígado desempenha um papel central na disposição metabólica de vários agentes químicos endógenos e exógenos, incluindo quase todos os fármacos. Neste processo de biotransformação pode ocorrer a formação de metabólitos intermediários altamente reativos que se não forem convenientemente eliminados podem interagir com macromoléculas celulares lesando o órgão. A hepatotoxicidade idiossincrática associada ao uso de antiepilépticos aromáticos (AEA) é bem conhecida e tem sido atribuída ao acúmulo de intermediários tóxicos (areno-óxidos) formados durante a bioativação hepática. Embora a participação de processos imunológicos no mecanismo de ação tóxica dos AEA tenha sido demonstrada, existe a possibilidade de mecanismos adjuvantes envolvendo a toxicidade mitocondrial, evento ainda não explorado na literatura científica. Neste estudo avaliou-se, in vitro, o efeito dos AEA: carbamazepina, fenitoína e fenobarbital, bem como dos seus respectivos metabólitos na função mitocondrial e na indução do estresse oxidativo em mitocôndrias de fígado de rato, como possível mecanismo de ação hepatotóxica desses fármacos. Sistema microssomal hepático de rato foi utilizado para bioativação dos fármacos e produção dos respectivos metabólitos in vitro. Sem a bioativação, somente o fenobarbital (em concentrações elevadas) apresentou efeitos inibidores sobre o estado 3 da respiração, síntese de ATP e potencial de membrana, sem, contudo induzir o estresse oxidativo. Quando bioativados, todos os fármacos apresentaram efeitos sobre a função mitocondrial através de processo mediado por estresse oxidativo. Todos os fármacos bioativados afetaram a respiração mitocondrial, causando diminuição do consumo de oxigênio no estado 3, diminuição do RCR e aumento do consumo de oxigênio no estado 4. Foram também evidenciadas alterações na captação/liberação de cálcio, inibição da síntese de ATP, diminuição do potencial de membrana e inibição do intumescimento mitocondrial induzido pelo cálcio. A oxidação de proteínas e lipídeos mitocondriais foi demonstrada pela formação de proteínas carboniladas, diminuição de proteínas com grupamentos sulfidrila, aumento de malondialdeído (MDA) e pela oxidação da cardiolipina. O sistema de defesa antioxidante mitocondrial também foi afetado, como evidenciado pela diminuição da relação GSH/GSSG (glutationa reduzida/glutationa oxidada). Os resultados sugerem fortemente a participação do dano mitocondrial, mediado pelo estresse oxidativo causado pelos metabólitos dos AEA, no desenvolvimento da hepatotoxicidade idiossincrática induzida por esses fármacos. / The liver plays a central role in the metabolic disposition of various endogenous and exogenous chemicals, including almost all drugs. During the biotransformation process, highly reactive metabolites can be produced, and if they are not detoxified, they can interact with cellular macromolecules and cause organ injury. Idiosyncratic hepatotoxicity is a well-known complication associated with aromatic antiepileptic drugs (AAED), and it has been suggested to occur due to the accumulation of toxic arene oxide metabolites. Although the participation of an immune process in the toxic action mechanism of AAED has been demonstrated, adjuvant mechanisms involving mitochondrial toxicity is also possible and such event has not been studied yet. Therefore, we investigated, in vitro, the effects of carbamazepine (CB), phenytoin (PT), phenobarbital (PB) and their respective metabolites on the hepatic mitochondrial function as well as their ability to induce oxidative stress in rat liver mitochondria, as a possible hepatotoxic action mechanism. The murine hepatic microsomal system was used to bioactivate the drugs and to produce the anticonvulsant metabolites in vitro. As an unaltered drug, only phenobarbital (in high concentrations) presented inhibitory effects on state 3 respiration, ATP synthesis, and membrane potential; however, it did not induce oxidative stress. All the bioactivated drugs affected mitochondrial function through an oxidative stress-mediated process. All the bioactivated drugs affected mitochondrial function causing decrease in state 3 respiration, decrease in RCR and increase in state 4 respiration. They also caused impairment of Ca+2 uptake /release, decrease in ATP synthesis, decrease in membrane potential and inhibition of calcium-induced swelling. Oxidation of proteins and lipids was evidenced by carbonil proteins formation, decrease in thiol proteins, increase in malonaldehyde (MDA) and cardiolipin oxidation. The mitochondrial antioxidant defense system was also affected, as evidenced by the decreased GSH/GSSG ratio (reduced glutathione/oxidized glutathione). Results strongly suggest the involvement of mitochondrial damage, which is mediated by the oxidative stress caused by the AAED metabolites, in the development of AAED-induced idiosyncratic hepatotoxicity.

Analogues aux cyclotrivératrilènes et aux calix[n]arènes, les pillar[n]arènes sont composés de n unités hydroquinoliques et reliés entre elles par un pont méthylénique en position para. Ces macrocycles ont été utilisés en tant que supports fonctionnalisables afin de préparer divers nanomatériaux. Dans ce contexte, la modification chimique du pont méthylénique a été réalisée sur le pillar[5]arène afin d’obtenir un nouveau site de fonctionnalisation, à ce jour jamais exploité. L’oxydation de cette position a permis dans un premier temps de réaliser une extension de cycle par une réaction de Colvin, afin d’obtenir un macrocycle portant une triple liaison tendue. Cette particularité a permis la réalisation de cycloaddition 1,3-dipolaire de Huisgen ou chimie click sans utilisation de cuivre(I), mais également l’obtention de produits de cycloadditions [2+2] par voie thermique normalement interdites. L’introduction d’un fullerène C60 sur ce pont méthylénique a également été réalisée sans déformation de la cavité. C’est pourquoi dans un deuxième temps des [2]rotaxanes photoactifs ont pu être élaborés à partir de ce fulléropillar[5]arène. Dans un dernier temps, une nouvelle méthode de préparation des [2]rotaxanes a été développée. Par échange de bouchons activés, divers [2]rotaxanes ont pu être synthétisés, sans être limités par la nature des bouchons souhaités. A partir de cette méthode de préparation, des cristaux liquides ont pu être obtenus en substituant ces bouchons activés par des bouchons portants des groupements post-fonctionnalisables, puis en greffant des groupements cyanobiphényles. / Analogues of cyclotriveratrylenes and calix[n]arenes, pillar[n]arenes are composed of 1,4-disubstituted hydroquinone subunits linked by methylene bridges in their para positions. This macrocyclic core has been used as a compact scaffold for the preparation of nanomaterials. In this context, the chemical modification of the methylene bridge has been achieved to further functionalize the core in a way never explored so far. Firstly, oxidation of this position followed by Colvin reaction generated a strained triple bond in the macrocyclic scaffold. This particularity allowed the introduction of functional groups under copper free Huisgen 1,3-dipolar cycloadditions as well as by thermal [2+2] cycloadditions normally prohibited. Insertion of [60]fullerene on the methylene bridge has been also carried out. In a second time, photoactive [2]rotaxanes have been obtained from this fulleropillar[5]arene. Finally, a new methodology for the preparation of [2]rotaxanes has been developed. By exchange of activated stoppers, various [2]rotaxanes were thus obtained and this method is not limited by the nature of the stopper. This methodology has been used to prepare new liquid crystalline rotaxane derivatives by introduction of clickable stoppers followed by the grafting of dendritic mesogenic subunits.

Le retraitement des déchets radioactifs est un problème crucial de nos jours. Ce travail est dédié au développement de nouveaux systèmes d'extraction des radionucléides sur la base de solvants "verts", les liquides ioniques (LI). Dans ce but, des LI ont été fonctionnalisés avec des motifs variés : oxyde de phosphine, carbamoyl oxyde de phosphine et fragments malonamides. De même, les plateformes calix[4]arènes ont été utilisées pour la synthèse de LI fonctionnalisés (LIF) et de leurs précurseurs. Des LIF de deux types (cationiques et anioniques) ont été obtenus.Les LIF synthétisés ont été testés pour l'extraction liquide/liquide de radionucléides. Il a été montré que l'extraction est bien due aux motifs extractants. Toutefois, la charge de l'ion modifié influence l'extraction.Différentes expériences d'extraction et une modélisation mathématique ont été effectuées pour déterminer les mécanismes d'extraction. Ces études ont montré que chacun des systèmes d'extraction est caractérisé par un ensemble d'équilibres d'extraction différent, basés essentiellement sur l'échange cationique. / Radioactive waste treatment is a crucial problem nowedays. This work was dedicated to the development of the new extracting systems for radionuclides on the basis of "green" solvents Ionic Liquids {Ils). For this purpose Ils were functionalized with various extracting patterns: phosphine oxide, carbamoyl phosphine oxide groups and malonamide fragment. Also the calix[4]arene platforms were used for the synthesis of functionalized ionic liquids (Fils) and their precursors. The Fils of both types cationic and anionic have been obtained. The synthesized Fils were tested for the liquid-liquid extraction of radionuclides. lt was found that extraction well occurs due to the extracting patterns, however a charge of a modified ion influences extraction.The various extracting experiments and mathematical modelling have been performed to determine the mechanisms of extraction. These studies showed that each extracting system is characterized by a different set of extracting equilibria, based mostly on cationic exchange.

Cette thèse porte sur la synthèse de ligands P-stéréogéniques dérivés du calix[4]arène et leur utilisation en catalyse asymétrique dans des complexes de métaux de transition. Des mono et diphosphines ont été préparées sur la cavité supérieure du macrocycle par réaction du mono ou dianion du calix[4]arène avec des chlorophosphines borane ou le complexe d’oxazaphospholidine borane préparés à partir d’éphédrine. La meilleure sélectivité est observée par réaction du dianion avec le complexe d’oxazaphospholidine borane qui conduit à une bisaminophosphine borane. Après acidolyse par HCl pour donner la bischlorophosphine correspondante puis réaction avec organolithien, les diphosphines diborane sont obtenus avec 40 à 60 % de rendement. Les structures cristallographiques des ligands préparés confirment la stéréospécificité de la méthode éphédrine. La préparation de diphosphines P-stéréogéniques surélevées au dessus de la cavité supérieure du calix[4]arène a été effectuée par réaction de phosphures borane avec le dérivé bisiodométhyl correspondant. Des ligands de type aminophosphinephosphinite (AMP*P) ont également été préparés à partir du produit d’ouverture du complexe d’oxazaphospholidine borane par l’anion du calixarène. Les différents ligands ont été synthétisés en série complexée au borane. La décomplexation est ensuite réalisée par réaction avec le DABCO et les phosphanes libres obtenus quantitativement ont été utilisés pour la préparation de catalyseurs chiraux de métaux de transition. Les AMP*P porteurs d’un substituant calix[4]arène sur le fragment aminophosphine ont permis d’obtenir de très bonnes inductions asymétriques en catalyse d’hydrogénation de l’α-acétamidocinnamate de méthyle par des complexes de rhodium (98% e.e.). L’étude comparée avec des ligands homologues d’un point de vue stérique et/ou électronique montre clairement l’influence bénéfique du substituant calix[4]arène. Les mono et diphosphines P-stéréogéniques fonctionnalisées sur la partie supérieure du calix[4]arène ont été utilisés en substitution allylique catalysée par des complexes de palladium. La réaction donne d’excellents rendements et stéréosélectivités avec des nucléophiles carbonés et azotés. Les meilleures inductions ont été obtenues avec une diphosphine porteuse de substituants méthyl et phényl au niveau des atomes de phosphore, qui entraîne des excès énantiomériques de 82% et 79 % en alkylation et en amination, respectivement. / We were interested in synthesis of P-stereogenic ligands derived from calix[4]arene and in their application in asymmetric catalysis. Mono et diphosphines were prepared on the upper rim of the macrocyle starting from the mono or dianion of the calix[4]arene and chlorophosphines borane or the oxazaphospholidine borane complex. The best selectivity was obtained by reaction of the dianion with the oxazaphospholidine borane complex leading to a bisaminophosphine borane. After acidolysis with HCl giving the corresponding bischlorophosphine and reaction with organolithium reagents, diphosphines diborane were obtained with good yields (40 à 60 %). X-ray structures of the prepared ligands confirmed the stereospecificity of the ephedrine method. Preparation of P-stereogeniques diphosphines elevated above the upper rim of the calix[4]arène was carried out by reaction of phosphides borane with the corresponding bisiodomethyl derivative. Ligands aminophosphinephosphinite (AMP*P) were also prepared from the opened product of the oxazaphospholidine borane complex by the calixarene anion. Ligands were synthetised in borane complex serie. Decomplexation with DABCO affords quantitatively the free phosphanes which were used in the preparation of transition metal catalysts. AMP*P bearing calix[4]arene on the aminophosphine moeity gave very high asymetric induction in hydrogenation catalysis of methyl α-acetamidocinnamate with rhodium complexes (98% e.e.). Compared study with isoelectronic or sterically similar ligands obviously prove the positive influence of the calix[4]arene substituent. P-stereogenic mono and diphosphines on the upper rim of the macrocycle were used in asymetric allylic subtitution catalyzed with palladium complexes. High yields and enantioselectivities were obtained with carboned and nitrogened nucleophiles. The best inductions were carried out with a diphosphine bearing methyl and phenyl on the phosphorous centers, affording enantiomeric excesses of 82 % and 79 % in alkylation and in amination, respectively.

This diploma thesis is focused on the design and synthesis of new half-sandwich titanium complexes for anchoring to selected supports (SiO2, SBA-15) and the study of their catalytic activity and selectivity in ethylene trimerization to 1-hexene. The synthetic strategy of half-sandwich titanium complexes with a suitable leaving group for direct anchoring through Ti−O bond was carried out (Cl, Oi-Pr). In addition, the titanium complexes with pendant alkenyl group were prepared and utilised for anchoring to a SiMe2H modified support by Pt-catalysed hydrosilylation reaction. Prepared compounds were characterised by standard spectroscopic methods (IR, NMR, MS). The heterogeneous systems were characterised by MAS NMR and IR spectroscopy, powder XRD, ICP-OES, TGA and the textural parameters were determined from nitrogen adsorption/desorption isotherms. For all prepared materials was studied the catalytic activity for ethylene trimerization and the selectivity to 1-hexene.