Les travaux rapportés dans ce mémoire concernent le développement de nouvelles réactions métallo-catalysées pour la création de liaison carbone-hétéroatome et carbone-carbone ainsi que leurs applications à la synthèse de produits biologiquement actifs. La première partie de ce manuscrit est consacrée à l'étude de la réactivité des sucres dans les couplages organométalliques. Des conditions ont été développées pour la création de la liaison C-S entre glycosyl thiols et partenaires arylés. De plus, la création de la liaison carbone azote de glycosyl amines avec des acides boroniques a été étudiée. Les produits synthétisés dans cette première partie ont été évalués pour leur potentiel d'inhibition de la Lectine A chez Pseudomonas aeruginosa, impliquée dans de sévères infections pulmonaires.La seconde partie de ce travail est dédiée à la création d'une série inédite d'analogues du 6BrCaQ, inhibiteurs de la Hsp90 ainsi que leur évaluation biologique. Cette nouvelle série est obtenue grâce à une nouvelle méthodologie de synthèse basée sur l'activation C-H entre un hétérocycle halogéné et son partenaire C-H activable. L'activité antiproliférative et l'inhibition de la Hsp90 ont été évaluées et seront présentées dans ce manuscrit. / The work reported in this dissertation concerns the development of new metal-catalyzed reactions for the creation of carbon-heteroatom and carbon-carbon bonds as well as their applications to the synthesis of biologically active products.The first part of this manuscript is devoted to the study of the reactivity of sugars as nucleophiles in organometallic couplings. Conditions were developed for the creation of the C-S bond between glycosyl thiols and aryl partners. Moreover, the creation of the nitrogen carbon bond of glycosyl amine with boronic acids was studied. The products synthesized in this first part have been evaluated for their potential to inhibit the lectin A, in Pseudomonas aeruginosa related lung infections.The second part of this work is dedicated to the creation of a new series of 6BrCaQ analogues as Hsp90 inhibitors and their biological evaluation. This new series was synthetized through a new CH activation methodology. The antitumoral potential was evaluated and will be presented in this manuscript.

In the aviation industry, the use of software development tools is not as easily adopted as in other industries. Due to the catastrophic consequences of software errors in airborne systems, software development processes has rigorous requirements. One of these requirements is that a code standard must be followed. Code standards are used to exclude code constructions which could result in unwanted behaviours. The process of manually ensuring a specific code standard can be costly. This process could be automated by a tool for static code analysis, however, this requires a formal qualification. This thesis evaluates the process of qualifying a tool for static code analysis in accordance with the requirements of the major aviation authorities EASA and FAA. To describe the qualification process, a literature study was conducted. To further explain how an existing tool could be put through the qualification process, a case study of the existing tool Parasoft C/C++ test was conducted. The results of the literature study show what processes must be completed in order to qualify a static code analysis tool. Importantly, the study shows that no requirements are put on the development process of the tool. This was an important takeaway as it meant that an existing tool could be qualified without any additional data from the developer of the tool. The case study of Parasoft C/C++ test showed how the tool could be configured and verified to analyze code in accordance with a small set of code rules. Furthermore, three documents including qualification data were produced showing how the qualification process should be documented in order to communicate the process to an authority. The results of the thesis do not provide the full picture of how a tool could be qualified as the software, in which the tool is used, is considerations the are specific to the software the tool is used to develop still need to be taken into consideration. The thesis does, however, provide guidance on the majority of the applicable requirements. Future research could be done to provide the complete picture of the qualification process, as well as how the process would look like for other types of tools. / Inom flygindustrin är användandet av olika programmeringsverktyg inte lika självklart som inom andra industrier. På grund av de katastrofala konsekvenser som fel i mjukvaran i ett flygplan kan resultera i finns det rigorösa krav på mjukvaruutvecklingsprocessen. Ett av dessa krav är att en viss kodstandard måste upprätthållas. Kodstandarder används för att exkludera vissa strukturer i kod som kan leda till oönskat beteende. Upprätthållandet av en viss kodstandard är en långdragen process att genomföra manuellt, och kan därför automatiseras med hjälp av ett statiskt kodanalysverktyg. För att kunna använda ett sådant verktyg behövs däremot en formell verktygskvalificering. I denna uppsats kommer kvalificeringsprocessen av ett verktyg för statisk kodanalys att evalueras enligt de krav som de två stora flygmyndigheterna EASA och FAA ställer. För att förklara processen av att kvalificera ett sådant verktyg gjordes en litteraturstudie följt av en fallstudie av det existerande verktyget Parasoft C/C++ test. Resultaten av litteraturstudien beskriver de olika processerna som måste genomföras för att kvalificera ett statiskt kodanalysverktyg. Noterbart är att resultaten visar att inga krav ställs på utvecklingsprocessen av verktyget själv. Detta betyder att ett existerande kommersiellt verktyg kan kvalificeras utan att verktygsutvecklarna själva behöver bidra med extra information. Fallstudien visade hur verktyget Parasoft C/C++ test kan konfigureras och verifieras att följa en viss kodstandard. Vidare resulterade fallstudien i utkast av de nödvändiga dokumenten som behöver produceras för att kommunicera kvalificeringsprocessen till en myndighet. De resultat som presenteras i denna uppsats är i sig inte tillräckliga för beskriva hela kvalificeringsprocessen. Ytterligare överväganden som är specifika till den mjukvaran som verktyget ska användas till att utveckla måste göras för att en komplett kvalificering ska kunna genomföras. Uppsatsen bidrar däremot med riktlinjer och vägledning av majoriteten av de processerna som behöver genomföras. Ytterligare forskning kan göras för att bidra med den kompletta bilden av verktygskvalificering av ett statiskt kodanalysverktyg, samt hur kvalificering kan göras av andra typer av verktyg.

With the rapid development of cellular communication techniques, many recent studies have focused on improving the quality of service (QoS) in cellular networks. One characteristic of the systems in cellular networks, which can have direct impact on the system QoS, is the fluctuation of the system capacity. In this thesis, the QoS of systems with capacity fluctuations is studied from two perspectives: (1) priority queueing systems with preemption, and (2) the M/M/~C/~C system. In the first part, we propose two models with controlled preemption and analyze their performance in the context of a single reference cell that supports two kinds of traffic (new calls and handoff calls). The formulae for calculating the performance measures of interest (i.e., handoff call blocking probability, new call blocking and dropping probabilities) are developed, and the procedures for solving optimization problems for the optimal number of channels required for each proposed model are established. The proposed controlled preemption models are then compared to existing non-preemption and full preemption models from the following three perspectives: (i) channel utilization, (ii) low priority call (i.e., new calls) performance, and (iii) flexibility to meet various constraints. The results showed that the proposed controlled preemption models are the best models overall. In the second part, the loss system with stochastic capacity, denoted by M/M/~C/~C, is analyzed using the Markov regenerative process (MRGP) method. Three different distributions of capacity interchange times (exponential, gamma, and Pareto) and three different capacity variation patterns (skip-free, distance-based, and uniform-based) are considered. Analytic expressions are derived to calculate call blocking and dropping probabilities and are verified by call level simulations. Finally, numerical examples are provided to determine the impact of different distributions of capacity interchange times and different capacity variation patterns on system performance.

The 2,2'-disubstituated 1,1'-binaphthyls (BINOLs) are important ligands in enantioselective synthesis . The major approach for their preparation is based on transition-metal-mediated oxidative C-C coupling of 2-substituted naphtalenes. This diploma thesis examined the mechanism of the coupling reaction in the gas phase using mass spectrometry with electrospray ionization. The aim of this thesis was to compare the selectivity of the copper(II)- catalyzed coupling reaction of 2-naphthol and its derivative with an electron-withdrawing group, to detect possible reaction intermediates, and to determine the origin of the preference of the cross-coupling. The electron-withdrawing group of naphthol slows down the coupling reaction which enabled us to detect the reaction intermediates. The intermediates in the reaction of 2-naphthol were not observed, because the coupling reaction proceeds too quickly. Hence, we have observed only complexes of the coupling products. The preferential cross coupling was explaned on the basis of an interplay between the probability of the formation of binuclear copper complexes and the reactivity of such complexes.

William C. C. Claiborne found himself a stranger in a strange land. Almost more a colonial governor of a European power rather than an American statesman, Claiborne grappled with maintaining a militia force for the Territory of Orleans, now the present day state of Louisiana. He built upon the volunteer companies he found within the city of New Orleans, but had little success molding the entire militia into an effective, efficient military force. Claiborne, hoping to use the fear generated by the January 1811 slave revolt to spur militia reform, maintained an active correspondence with the state's legislators, the area's military commanders, the members of the Louisiana congressional delegation, and even the President of the United States for assistance with militia matters. Ultimately, Claiborne failed and the British attack on New Orleans in 1814/1815 made the matter of reform academic.

The non-sustainable nature of fossil fuels as feedstocks for valuable chemicals, combined with the environmental damage caused by their extraction and combustion, increases the need for the development of a bio-based economy. While industry and public opinion are slowly shifting towards acceptance of this change, efficient technologies for the depolymerization and subsequent separation of lignocellulosic biomass fall short of the ever-increasing demand. In particular, there are currently no efficient, sustainable mass scale methods to convert lignin, the most abundant source of aromatic molecules on Earth. The use of oxovanadium(V) catalyst complexes to aerobically cleave C‒C bonds has been demonstrated previously and remains an attractive option for incorporation into a sustainable bio-based economy. Two new triphenoxyamine oxovanadium(V) catalysts with reduced steric bulk and electron density at the metal center (vs. previously reported complexes) have been synthesized for aerobic oxidative diol C‒C bond cleavage. These complexes were found to cleave less activated and more complex substrates than previous generations, including cyclic diols and polyalcohols. Several insights into the reaction pathways of this class of complex were elucidated through a series of kinetic studies. Experimentally, the rate of C‒C bond cleavage of both pinacol and hydrobenzoin was determined to be unaffected by substitution of the O‒H bonds with deuterium, suggesting that currently proposed mechanisms need to be revised. Multiple catalytic regimes were observed during anaerobic reaction, which were not altered significantly by the brief addition of O2. A series of density functional theory calculations revealed a plausible mechanism for the trialkoxy complex that did not involve a proton transfer in the rate determining step, instead suggesting that ligand-arm dissociation-reassociation play a significant role in the reaction. In a second project, new bisphenoxyamine-N-appended base ligand with less steric hindrance and electron density at the metal center, has been synthesized utilizing similar design principles gained from work with triphenoxyamine catalysts. When reacting with lignin model compound 1,2-diphenyl-2-methoxyethanol, this new complex displays a higher selectivity towards aldehydes and esters (relative to previous bisphenoxyamine-N-appended ligands), leading to a higher rate of C‒C bond cleavage. Investigations into the mechanism of bisphenoxy complexes, as well as the role of the N-appended base in reactivity, were performed using substrate pre-complexed bisphenoxy compounds. Thermolysis at 60 and 100 °C produced almost exclusively oxidative C‒H bond cleavage product benzyl methyl ether, with evidence for overoxidation product benzoic acid observed. Thermolysis of labelled substrate pre-complexed revealed that N-appended base may impede C‒C cleavage of 1,2-diphenyl-2-methoxyethanol by forcing the methyl ether away from the oxovanadium(V) center. Through the use of these multidentate phenoxyamine ligands, advances have been made towards sustainable oxovanadium catalysis in the pursuit of efficient and selective lignocellulosic disassembly for a sustainable bio-based economy.

No description available.

Depuis ces vingt dernières années, les nanotechnologies représentent une aire de recherche en plein développement. En particulier, les nanoparticules métalliques ont suscité un intérêt croissant en catalyse de part leurs propriétés intermédiaires entre les catalyseurs homogènes et hétérogènes classiques. Ainsi, leur réactivité de surface peut entrainer de nouvelles sélectivités lors des synthèses de molécules d'intérêt médical, pharmaceutique ou agrochimique. Au cours de cette thèse, une nouvelle famille de ligands chiraux polyfonctionnels dérivés du 9,10-dihydroanthracène, pour la stabilisation de nanoparticules de palladium, a été synthétisée. Les colloïdes ont été obtenus par décomposition de précurseurs organométalliques en présence de ces nouveaux ligands. Les particules de taille, de forme et de composition chimique contrôlées ont été utilisées en réaction de couplage C-C de Suzuki. Ces réactions ont été réalisées en milieux organique et liquide ionique. Aussi, la réactivité de surface a été étudiée dans l'hydrogénation et la dismutation du 1,4-cyclohexadiène. Dans l'objectif d'étudier la chimie de coordination des ligands, des complexes de palladium ont été synthétisés et complètement caractérisés. L'induction asymétrique apportée par ces ligands optiquement purs a été estimée dans des réactions asymétriques d'alkylation allylique et de couplage C-C de Suzuki.

This thesis describes the development and mechanistic studies of carbocyclization reactions of allene-substituted olefins and 1,3-dienes, catalyzed by palladium(0) and palladium(II). These reactions results in the formation of [n,3,0] bicyclic systems (n = 3-5) with high stereoselectivity and in good to excellent yields. The first carbocyclization presented is a novel palladium(0)-catalyzed cyclo- isomerization of allene-substituted olefins. Secondly an efficient aerobic biomimetic system has been developed for a Pd(II)-catalyzed allylic oxidative carbocyclization of allene-substituted olefins. Additionally, during the studies of palladium-catalyzed carbocyclizations of allene-substituted olefins, it was found that in the absence of palladium a mild thermal ene-reaction occurs. In this manner stereodefined, functionalized bicyclic compounds are obtained with good regioselectivity and in high yields. The third and fourth carbocyclization developed are a palladium(II)-catalyzed oxidation and a palladium(0)-catalyzed intramolecular telomerization of allene-substituted 1,3-dienes. A mechanistic study of the palladium(II)-catalyzed oxidation of allene-substituted 1,3-dienes was made, and reaction intermediates could be isolated. The stereochemistry of the reaction intermediates was assigned, and this made it possible to suggest a mechanism for the reaction. The presented mechanism is a trans carbopalladation of the 1,3-diene, where the allene act as the carbon nucleophile. Due to different stereochemical outcomes of the stoichiometric and catalytic reactions, this mechanism could only explain the stoichiometric reaction. Another mechanism for the catalytic reaction was suggested, which rationalizes both the regio- and stereochemistry of the products.

Tridentate "pincer" ligands provide a unique balance of stability and reactivity in organometallic chemistry. The development of diarylamido-based PNP pincer ligands has led to many applications in catalysis, including the potential to facilitate unique chemical transformations at transition metal centers. The main objective of this thesis was to explore transition metal chemistry supported by the PNP pincer framework for both early and late transition metals. In Chapter I, the history behind the design and synthesis of pincer complexes is described. The advantages and disadvantages of various pincer ligands are reviewed to show the reasoning behind the synthesis of the PNP pincer framework. Chapter II discusses the synthesis of novel Hf and Ta complexes involving the PNP ligand. Reactions of (PNP)HfCl3 with large alkyl Grignards led to double alkylation and triple alkylation was achieved with methyl Grignard. (PNP)HfMe3 and (PNP)Hf(CH2SiMe3)2Cl displayed remarkably irregular coordination environments about hafnium, in contrast to the approximately octahedral structure of (PNP)HfCl3. (PNP)HfMe3 was found to be thermally stable at 75 degrees C, whereas thermolysis of (PNP)Hf(CH2SiMe3)2Cl under similar conditions led to a mixture of products. The major decomposition product is believed to be a Hf alkylidene complex on the basis of in situ NMR spectroscopic observations (e.g., delta 248.2 ppm in the 13C{1H} NMR spectrum). The reaction of (PNP)TaF4 with an excess of ethyl Grignard led primarily to the double alkylation product, (PNP)Ta(CH2CH3)2F2. Repeating this reaction in the presence of excess ethyl Grignard and dioxane resulted in the formation of an ethylene complex, (PNP)Ta(=CHCH3)(C2H4). In Chapter III, a C-C reductive elimination study is described comparing two pincer ligand scaffolds: Me(PNP) ligand and TH(PNP) ligand. The tied ligand has previously been found to be more sterically demanding than the untied ligand, which has allowed for faster N-C cleavage, faster oxidative addition and a more selective alkyne dimerization catalyst. This study reveals that the tied ligand complex, TH(PNP)Rh(C6H4CF3)(Ph), undergoes slower reductive elimination of p-Ph-C6H4CF3 (< 4% after 7 h at 38 degrees C; t1/2 = 7.7 h at 64 degrees C; t1/2 = 2.13 h at 75 degrees C) than Me(PNP)Rh(C6H4CF3)(Ph) (t1/2 = 15.6 min at 38 degrees C).