Thesis advisor: Masayuki Wasa / When a catalytic reaction is carried out between two reactants, usually only onereactant is activated by a single catalyst while the other component is pre-activated so that the sluggish reactivity was compensated. In order to broaden the substrate scope, the development of cooperative catalysts that can generate both electrophilic and nucleophilic species in situ represents a compelling research objective. This thesis is focused on the development of cooperative catalyst systems and their applications to α- and β-amino C−H bond functionalization. In the first chapter of this thesis, a brief summary of the present cooperative catalysts will be discussed. In the second chapter, the development of cooperative acid/acid catalysts for the α-alkynylation of N-alkylamines will be discussed. Typically, catalytic α-amino C−H alkynylation process is carried out under oxidative conditions, and enantioselective reactions are confined to tetrahydroisoquinoline derivatives. We disclose a strategy for the union of N-alkylamines and trimethylsilyl alkynes through cooperative actions of two Lewis acids, B(C 6 F 5 ) 3 and a Cu-based complex without the use of oxidants. We proposed that various propargylamines can be synthesized through the reaction between a L n Cu−alkynyl complex and an iminium ion that are generated in situ. Furthermore, the utility of this protocol was demonstrated by applications in late stage α-alkynylation of bioactive amines and stereoselective synthesis of propargylamines. In the third chapter of this thesis, catalytic and regioselective deuteration of β-amino C−H bonds in an array of N-alkylamine-based pharmaceutical compounds will be described. Isotopic labeling of β-amino C−H bond is promoted by the cooperative action of Lewis acidic B(C 6 F 5 ) 3 and Brønsted basic N-alkylamine, converting a bioactive amine first into an iminium ion and then the corresponding enamine. Meanwhile, the acid/base catalysts can also promote the dedeuteration of acetone-d 6 to afford a deuterated ammonium ion and a boron enolate. Ensuing deuteration of the enamine by deuterated ammonium ion followed by borohydride reduction leads to the formation of β-deuterated bioactive amines with up to 99% deuterium incorporation. / Thesis (MS) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Les nanoparticules de métaux de transition ont suscité une attention considérable au cours des dernières années en raison de leur activité catalytique et sélectivité. Elles sont à la frontière entre la catalyse homogène et hétérogène et combinent les avantages des deux. Pour cette raison, les nanoparticules ont émergé en tant que catalyseurs pour différentes réactions telles que l'hydrogénation d'arènes. L'objectif final de cette thèse est la synthèse et la caractérisation de nanoparticules de ruthénium et l’exploration de leur performance catalytique en réactions d'hydrogénation d’arènes et polyarènes.Le Chapitre 1 contient une introduction générale à la synthèse, la caractérisation et l'application des nanoparticules en catalyse. Le Chapitre 2 définit les objectifs généraux de cette thèse.Le Chapitre 3 décrit la synthèse et la caractérisation de nanoparticules de ruthénium et de rhodium stabilisées par des ligands de type phosphine et leur application dans une étude comparative concernant la réduction d'une large gamme de phényles substitués, benzyle et de phénéthyle cétones. Dans le cas des cétones d'aryle, des nanoparticules de ruthénium ont démontré être plus sélectives pour l'hydrogénation du groupe aryle que celles de rhodium. Par contre, les nanoparticules de rhodium fournissent des produits d'hydrogénolyse. En ce qui concerne les arylcétones non conjuguées, les deux métaux sont très sélectifs envers l'hydrogénation du groupe aryle.Le Chapitre 4 décrit l'utilisation de nanoparticules de ruthénium stabilisées par la triphénylphosphine pour l'hydrogénation de substrats polycycliques aromatiques dans des conditions réactionnelles douces. Les systèmes contenant deux, trois ou plusieurs cycles aromatiques condensés sont réduites et montrent une haute sélectivité pour l’hydrogénation partielle. Le produit d'hydrogénation totale est uniquement obtenu pour les substrats moins encombrés, tels que le naphtalène et l'anthracène. L'influence d’un substituant (réductible ou non) sur l'hydrogénation du naphtalène est également étudiée.La recherche dans le Chapitre 5 explore la synthèse d'un nouveau ligand de type phosphine chirale, qui est obtenue avec un bon rendement et avec une pureté optique de 97%. Ensuite, cette phosphine et la cinchonidine commerciale (Figure 2) sont utilisées comme agents de stabilisation pour la synthèse de nanoparticules chirales.Ces nanoparticules ont été testées dans l'hydrogénation asymétrique de différents arènes disubstitués mais en terme d’énantiosélectivité, les résultats n’ont pas été bons. Une étude de deutération a été effectuée pour élucider la coordination des différents substrats à la surface de nanoparticules. Le Chapitre 6 présente les observations finales et les conclusions de cette thèse. / Transition metal nanoparticles have generated considerable attention in recent years as a result of their potential catalytic activity and selectivity. They are at the frontier between homogeneous and heterogeneous catalysis and combine the advantages of both. For this reason, nanoparticles emerged as promising catalyst for different reactions such as for the hydrogenation of arenes. The final goal of this thesis is the synthesis and characterization of ruthenium nanoparticles to explore their performance in arene and polyarene hydrogenation reactions. Chapter 1 contains a general introduction to the synthesis, characterization and application of nanoparticles in catalysis. Chapter 2 sets out the general objectives of this thesis. The research in Chapter 3 describes the synthesis and characterization of ruthenium and rhodium nanoparticles stabilized by phosphine donor ligands and their application in a comparative study in the reduction of a wide range of substituted phenyl, benzyl and phenethyl ketones. In the case of arylketones, ruthenium nanoparticles were found to be more selective than the rhodium ones towards the hydrogenation of the aryl group. Interestingly, only rhodium nanoparticles provided hydrogenolysis products. Concerning the non-conjugated aryl ketones, both metals were found to be really selective towards arene hydrogenation.The research in Chapter 4 describes the use of ruthenium nanoparticles stabilised by triphenylphosphine in the hydrogenation of polyaromatic substrates under mild reaction conditions. Systems containing 2, 3 or more fused benzene rings are reduced obtaining high selectivities towards the partial hydrogenation. The recovering of the total hydrogenated product is only achieved for the less hindered substrates like naphthalene and anthracene. Moreover, the influence on the hydrogenation of naphthalenes containing a substituent (reducible or not) is also studied. The research in Chapter 5 explores the synthesis of a new chiral phosphine ligand, which is obtained in good yield and with 97% optical purity. Then, this phosphine and commercial cinchonidine (Figure 1) are used as stabilizing agents for the synthesis of chiral nanoparticles. These nanoparticles are tested in the asymmetric hydrogenation of different substituted arenes but unsuccessful results in terms of enantioselectivity are obtained. Moreover, deuteration studies to elucidate the coordination of the different substrates to the nanoparticles surface are performed.Chapter 6 presents the final remarks and conclusions extracted from the results obtained in this thesis.

Les composés marqués aux isotopes de l’hydrogène possèdent des nombreuses applications lors des phases précliniques de développement des médicaments. Par exemple, les composés deutérés sont utilisés comme étalons internes dans la quantification par LC-MS de métabolites alors que les molécules tritiées sont souvent des radiotraceurs de choix dans les études d’absorption, distribution, métabolisme et excrétion (ADME) moléculaire des candidats médicaments. Après une brève introduction, un premier chapitre discutera du développement d’une méthode douce et sélective, catalysée par des nanoparticules de ruthénium, qui permet d’effectuer le marquage en une étape de bases azotées et de médicaments dérivés. En changeant le ligand qui stabilise le nanocatalyseur, on a réalisé des échanges isotopiques compliqués tels que des tritiations en utilisant une pression sous-atmosphérique de tritium gaz et des deutérations d’oligonucleotides sensibles. Le chapitre suivant décrira la modification des catalyseurs commerciaux à base de ruthénium grâce à la coordination de carbènes N-hétérocycliques (NHCs). La modification assure une régio- et une chimiosélectivité améliorées lors de la deutération d’alcools aliphatiques. Certains des catalyseurs modifiés ont permis l’échange hydrogène/deutérium sur des molécules, particulièrement sensibles à la réduction, qui n’ont pas pu être isolées en utilisant le catalyseur commercial. Dans le dernier chapitre, la synthèse et l’évaluation de l’activité catalytique des nanoparticules à base d’iridium seront discutées. Ces nanocatalyseurs ont démontré une réactivité intéressante dans le marquage des composés complexes. Dans certains cas, les nanoparticules d’iridium ont permis l’incorporation de deutérium sur des positions inhabituelles en comparaison avec d’autres réactions d’échange isotopique déjà décrites. / Hydrogen isotopes labelled compounds possess a broad range of application in the early pre-clinical phases of drug development process. For instance, deuterated compounds are applied as internal standard in quantitative LC-MS techniques while tritiated molecules are often the preferred radioactive tracers for the study of molecular absorption, distribution, metabolism and excretion (ADME). After a brief introduction, a first chapter will discuss the development of a mild and selective method to perform late stage labelling of variously functionalized nucleobases and drug analogues catalyzed by ruthenium nanoparticles. By changing the ligand which stabilizes the nanocatalyst, we achieved challenging isotopic exchanges such as tritiations of pharmaceuticals using subatmospheric pressure of tritium gas and deuteration of sensible oligonucleotides. The next chapter will describe the modification of commercially available ruthenium nanocatalysts via the coordination of N-Heterocyclic carbenes (NHCs). The modification granted enhanced regio and chemoselectivity for the deuteration of aliphatic alcohols. Some of the modified ruthenium catalysts allowed the hydrogen/deuterium exchange on easily reducible compounds which were not obtainable using the unmodified commercial catalyst. The final chapter will discuss the synthesis and the evaluation of the catalytic activity of iridium nanoparticles. The latter, showed an interesting reactivity for the labelling of challenging substrates. In some of the investigated compounds, IrNps were able to introduce deuterium with unusual regioselectivities compared to already described hydrogen isotope exchange reactions.

This dissertation describes the benzylation of adenine under basic conditions, the unequivocal determination of the identity of the products of this reaction, an exploration of the effect of solvent on the reaction, a thorough computational study of the reaction mechanism and an investigation into the hydrogen-deuterium exchange reaction of the N-benzyladenine products and related compounds. The preferential sites of alkylation of adenine under basic conditions in DMSO were proven to be the N9 and N3 positions. X-ray crystal structures were obtained for both compounds. Formation of the N9-benzyladenine product is the most favoured in polar aprotic solvents, such as DMSO, and as the proportion of polar protic solvents, such as water, increases, so does the formation of the N3-benzyladenine product. Characteristic 1H NMR  chemical shifts of the purine ring protons and HMBC 1H-13C correlation NMR spectroscopy were useful tools to assign the 1H and 13C NMR spectra chemical shifts and confirm that the solution structures were the same as the isolated crystals. Simulating the SN2 mechanism for the N1-, N3-, N7- and N9-pathways computationally, employing DMSO as the simulated solvent, resulted in ambiguous results when considering the electronic energies of initial, TS and final products alone. However, a novel approach was developed (employing IQA-defined energy terms) to study fragment interactions along the reaction paths. It provided a full explanation of the reaction mechanism and yielded results which supported the N3/N9 positions of alkylation over the N1/N7 sites. The preference for the sites of alkylation occurs after the transition state, in which the N1/N7 reaction paths fail to proceed favourably to the end product, N1- and N7-benzyladenine, respectively. The N9-pathway dominates the N3-pathway at the product formation step, which corresponds to the N9- benzyladenine being the major product, as shown in Figure 1, and the N3-benzyladenine being the minor product from the benzylation of adenine. The faster rate of deuteration at the C8 position of N9-benzyladenine as compared to the deuteration rates at the C2 and the C8 of N3-benzyladenine, have shown support for a sp3 mediated mechanism and a carbene mediated mechanism of deuteration based on the “push” and “pull” mechanisms proposed for the C8 proton transfer of ATP in kinase enzymes. The deuteration of the C8 proton of 2,6-dichloropurine derivatives supports the existence of the carbene mediated mechanism since these compounds lack the amine moiety necessary for the sp3 mediated mechanism. These results demonstrate how experimentation and computation have led to greater insights into the reactivity of adenine and its derivatives. This strategy provides a useful platform for future research into adenine reaction mechanisms and the role adenine plays in kinase catalysis. / Dissertation (MSc)--University of Pretoria, 2015. / National Research Foundation (NRF) / Chemistry / MSc / Unrestricted

Le milieu interstellaire (MIS) où se forment les étoiles est constitué de gaz très dilué dominé par l'hydrogène moléculaire, et de grains de poussière de taille submicrométrique. Ces poussières jouent un rôle crucial en atténuant la lumière des étoiles lointaines, protégeant ainsi les molécules du gaz des rayonnements ultra-violets, et en servant de catalyseurs à une chimie hétérogène à très basse température. Outre la synthèse de l'hydrogène moléculaire, la surface des grains permet de former des molécules organiques dites complexes comme le méthanol (CH3OH) à partir de l'hydrogénation (et la deutération) du monoxyde de carbone (CO). Les glaces ainsi formées participent à la complexification moléculaire du MIS et seront à terme intégrées au sein de disques de poussières, berceaux des astéroïdes, comètes et exo-planètes. L'objectif de cette thèse est l'étude des mécanismes d'échanges hydrogène-deuterium sur certains groupements fonctionnels de molécules organiques simples, méthanol par exemple, présentes à la surface ou dans les manteaux des grains interstellaires. La thèse est centrée sur une exploration expérimentale de ces processus en phase condensée, à l'aide d'une expérience de cryogénie synthétisant des glaces à très basse température (15K) couplée à un spectromètre infrarouge. Nous montrons que ces échanges se produisent avant la sublimation du manteau de glace sur des groupes fonctionnels capables d'établir des liaisons hydrogènes avec les molécules d'eau voisines. Le processus catalysant est vraisemblablement la cristallisation de la glace d'eau. Des études cinétiques nous permettent d'évaluer les énergies d'activation du transfert H/D (6745K) et de la transition amorphe-cristalline (8100K), et de déterminer la constante de vitesse d'échange dans le domaine de température 120-140~K. Cette constante de vitesse est, de plus, comparée à des calculs semi-classiques basés sur un traitement ab initio. En marge de ces expériences, des observations millimétriques de la molécule de méthanol en direction de proto-étoiles confirment une variabilité des abondances relatives des isotopologues simplement deutérés de cette molécule en fonction de la masse de la protoétoile. / The interstellar medium where stars are formed consists of a dilute gas which is dominated by molecular hydrogen and dust grains less than a few microm in size. The dust plays a crucial role in the attenuation of light from the stars. They also protect molecules within the gas from UV photons. Furthermore, they serve as heterogeneous catalysts for chemistry at low temperature. The surface of the grains also permit the formation of complex organic molecules such as methanol via the hydrogenation and/or deuteration of carbon monoxide. The ices are formed and subsequently participate in increasing the molecular complexity of the clouds. Finally, they are incorporated into debris disks, asteroids, comets, and exoplanets. The objective of this thesis is to study the mechanism of hydrogen/deuterium exchange within certain functionnal groups of simple organic molecules such as methanol, which are present on the surface of these grain mantles. The thesis is focused on the experimental determination of these processes in the condensed phase. This will be achieved with the aid of a cryogenic synthesis of the ices at very low temperatures coupled with infrared spectrometry. We observe that it is possible for the exchange to proceed before the sublimation of the ice mantles. However, this is only the case when the functional groups within the molecule may form hydrogen bonds with water. From our results we see that this process seems to be catalysed by the crystalization of the water ice. The kinetics study permits us to evalute the activation energy for the H/D exchange (6745 K) and for the transition from amorphous to crystaline ice (8100 K). In addition it also allows us to determine the rate constant for the exchange in the temperature range 120-140 K. In addition we have performed theoretical calulation in an attempt to elucidate the mechanism for the exchange. However, the experimental rate constant for the exchange is much larger in comparison to the one predicted by a semi- classical treatment based on the AB initio potential we have obtained. Further to this observations of methanol towards protostars have been conducted. These observations show that there is a variation in the relative abundance of the CH2DOH and CH3OD. This variation in relative abundance seems to have some dependence upon the mass of the protostar, with high mass stars showing (CH2DOH/CH3OD ≤ 1) and low/intermiediate mass stars showing (CH2DOH/CH3OD >> 3).

Les composés deutérés sont d’un intérêt grandissant dans des domaines variés. Par exemple, en pharmacologie, l'échange H/D peut améliorer les propriétés pharmacocinétiques de certains médicaments ou réduire leur toxicité. Les composés deuterés peuvent également être utilisés comme étalons internes en spectroscopie de masse. Il est donc important de trouver un moyen simple et sélectif d'échanger l'hydrogène avec le deutérium sur des molécules d’intérêt biologique. Les nanoparticules, de ruthénium en particulier, se sont révélées être des systèmes efficaces pour catalyser cet échange. Cependant, étant très actives, elles conduisent souvent à la réduction de substrats aromatiques. L'objectif principal du doctorat est l’élaboration de nouvelles nanoparticules permettant de contrôler la réactivité en échange isotopique H/D. Nous avons d’abord synthétisé des alliages Ru-Pt afin d’introduire du platine, moins actif en échange H/D, et donc empoisonner la surface du Ru. Nous avons montré qu’en changeant le précurseur de platine, on pouvait changer la distribution atomique de surface, et ainsi moduler la réactivité des nanoparticules. Nous avons finalement synthétisé des nanoparticules de nickel et d'iridium. Ces nanoparticules se sont avérées être des catalyseurs efficaces pour l'échange H/D, sans réduction de fonctions aromatiques. De plus, des sélectivités différentes ont été obtenues en fonction du métal utilisé. / Deuterated compounds are molecules of great interest in various fields. In pharmacology, the H/D exchange can improve the pharmacokinetic properties of some drugs or reduce their toxicity. In addition, deuterium-labelled compounds can be used as internal standards for mass spectroscopy, or as tracers for the understanding of different reaction mechanisms. Therefore, it is important to find a way to exchange hydrogen with deuterium in a simple, selective and efficient way. The main goal of the PhD project is the synthesis of novel nanoparticles for isotopic exchange (H/D). Metal nanoparticles and more particularly ruthenium nanoparticles, has shown their efficiency to catalyze this exchange. However, ruthenium nanoparticles are very active in arene hydrogenation, and often lead to the reduction of aromatic substrates. In a second part of the work, we synthesized Ru-Pt alloys in an attempt to passivate the Ru surface with platinum, which is less-active in H/D exchange. We have shown that by changing the platinum precursor, we can change the atomic distribution of the surface, and thus we were able to modulate the reactivity of nanoparticles. We finally synthesized Ni and Ir nanoparticles. These nanoparticles have proven to be efficient catalysts for H/D exchange, without reducing aromatic functions. In addition, different selectivity was obtained depending on the metal used.

Superheated water has been used successfully as an eluent in liquid chromatography and has been coupled to various modes of detection, ultraviolet (UV), fluorescence, and nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). A number of compounds were examined on poly(styrene-divinylbenzene) (PS-OVB), polybutadiene (PBO), and octadecylsilyl bonded silica (OOS) column with isothermal and temperature programmes.

GONÇALVES, Ricardo Oliveira. Espalhamento Raman em Policristais de L-alanina deuterados sob pressão. 2008. 78 f. Dissertação (Mestrado em Física) - Programa de Pós-Graduação em Física, Departamento de Física, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2008. / Submitted by Edvander Pires (edvanderpires@gmail.com) on 2015-06-08T19:38:31Z No. of bitstreams: 1 2008_dis_rogoncalves.pdf: 6962166 bytes, checksum: 5422b2af7936494743aae69cbce2e2e3 (MD5) / Approved for entry into archive by Edvander Pires(edvanderpires@gmail.com) on 2015-06-08T19:52:47Z (GMT) No. of bitstreams: 1 2008_dis_rogoncalves.pdf: 6962166 bytes, checksum: 5422b2af7936494743aae69cbce2e2e3 (MD5) / Made available in DSpace on 2015-06-08T19:52:47Z (GMT). No. of bitstreams: 1 2008_dis_rogoncalves.pdf: 6962166 bytes, checksum: 5422b2af7936494743aae69cbce2e2e3 (MD5) Previous issue date: 2008 / In this dissertation we present of Raman spectroscopy on deuterated L-alanine crystals under hydrostatic pressure. L-alanine is one of twenty proteic amino acids, and among them it is the simplest chiral one. L-alanine crystallizes in an orthorhombic (D24) structure with four molecules per unit cell, forming a complex network of seven hydrogen bonds. When one applies pressure on an amino acid crystal the distances between molecules are changed and, eventually, the crystal goes to a new structure with different symmetry. In this work we present the Raman spectra of deuterated L-alanine in the 50 - 2500 cm-1 spectral region with pressures changing from 0 to 6 GPa. Beyond the conventional frequency blue shift of almost all modes, we observed frequency discontinuities of both internal and external modes at 1,5 and 4,5 GPa. These discontinuities were interpreted as structural phase transitions undergone by deuterated L-alanine crystal from the orthorhombic to the tetragonal, and from the tetragonal to a monoclinic symmetry, respectively. This suggestion is based on previous results on non - deuterated L-alanine. The behavion of torcional vibration of ND3 was also studied and a comparison with studies on L-alanine, L-threonine and taurine crystals (related with dimensions of hydrogen bonds) is also given. / Nesta Dissertação são apresentados os resultados oriundos do estudo do efeito da aplicação de pressão hidrostática sobre cristais de L-alanina deuterada. A L-alanina é um dos vinte aminoácidos formadores das proteínas, sendo entre os quirais o mais simples deles. A L-alanina cristaliza-se numa estrutura ortorrômbica (D24) com quatro moléculas por célula unitária formando uma complexa rede de sete diferentes ligações de hidrogênio. Quando pressão é aplicada a um cristal de aminoácidos ocorre a aproximação das moléculas com a consequente variação nas distâncias e ângulos das ligações de hidrogênio, eventualmente obrigando a estrutura a ir para uma nova simetria. Investigou-se nesta Dissertação o comportamento dos espectros Raman da L-alanina deuterada na região espectral entre 50 e 2500 cm-1 para pressões variando entre 0 e 6 GPa. Além do usual comportamento do desvio da freqüência de quase todos os modos para altos valores, observou-se também descontinuidades nas freqüências de modos internos e modos externos para valores de pressão em 1,5 e 4,5 GPa. Estas descontinuidades foram interpretadas como sendo consequências de transições de fase estruturais de uma estrutura ortorrômbica para uma estrutura tetragonal e, a seguir, para uma estrutura monoclínica em analogia ao que ocorre com a L-alanina não deuterada. O comportamento do modo de torção da estrutura ND3 também foi estudado e uma analogia do seu comportamento com aqueles observados na L-alanina, na L-treonina e na taurina em termos das dimensões das ligações de hidrogênio também é fornecida.

In this thesis I present work done on the subject of star formation through the study of infrared dark clouds. We studied the velocity fields in several IRDCs using spectral line mapping. We also performed observations of a high density tracer and its deuterated counterpart. These observations allow me to assess the kinematics of these clouds and the evolutionary state of the observed targets. The sample observed is an important starting point for the search of early and quiescent high-mass regions. We mapped several IRDCs using the 22m ATNF Mopra Telescope in high-density molecular tracers at 3 mm, HNC (1-0) and N2H+ (1-0). We present integrated intensity emission and velocity field maps of these IRDCs. The molecular emission in the maps matches well with the extinction seen in the mid-IR. For an IRDC-complex we see connecting emission in the whole filament. We calculate kinematic distances and masses of the IRDCs. The IRDCs typically display an ordered velocity field within the clouds. The mean velocity gradient of the sample was 0.4 km/s/pc. We show how this velocity gradient can mean gas flows within the cloud into the central regions in order to feed the central cores. We observed 54 cores in IRDCs using N2H+ (1-0) and (3-2) to determine the kinematics of the densest material, where stars will form. We also observed N2D+ (3-2) towards 29 of the brightest peaks to analyze the level of deuteration which is an excellent probe of the quiescent of the early stages of star formation. There were 13 detections of N2D+ (3-2). This is one of the largest samples of IRDCs yet observed in these species. The deuteration ratio in the sources with detected N2D+ (3-2) has a mean of 0.024 and reaches a maximum value of 0.14. For most of the sources the material traced by N2D+ and N2H+ (3-2) still has significant turbulent motions, however three objects show subthermal N2D+ velocity dispersion. Surprisingly the presence or absence of an embedded 70 micron source shows no correlation with the detection of N2D+ (3-2), nor does it correlate with any change in velocity dispersion or excitation temperature. Comparison with recent models of deuteration suggest evolutionary timescales of these regions of several freefall times or less.

Les molécules marquées par des isotopes de l’hydrogène possèdent de nombreuses applications dans divers domaines tels que la chimie, la biologie ou en science des matériaux. Dans le domaine de la recherche de nouveaux médicaments, les études liées à la pharmacocinétique nécessitent un accès rapide à des molécules marquées afin de ne pas impacter les coûts et les délais de développement. Le développement de la métabolomique a aussi entrainé une augmentation du besoin en molécules marquées isotopiquement. En effet, les molécules deuterées peuvent être utilisées en tant qu’étalons internes pour la quantification rapide des métabolites présents dans des tissus ou des fluides biologiques. La première partie de cette thèse concerne le développement d’une méthode générale de marquage de motifs de type thioéther dans des molécules complexes à l’aide d’une nouvelle réaction d’échange isotopique (catalysée par des nanoparticules de Ruthénium). D’un point de vue fondamental cette transformation représente le premier exemple de (Csp³)-H activation dirigée par un atome de soufre. En termes d’application, cette nouvelle réaction permet la synthèse rapide d’étalons internes pour la quantification LC-MS/MS et le marquage tritium de molécules complexes. La seconde partie de cette thèse relate le développement d’une nouvelle méthode d’homocouplage de phénylpyridines catalysée par Ru/C. Différents substrats comportant des substituants riches et pauvres en électron ont été couplés avec de bons rendements. Ces dimères ont ensuite été utilisés pour synthétiser de nouveaux complexes de bore dont les propriétés photophysiques ont été étudiées. Dans une troisième partie, la mise au point d’une réaction palladocatalysée permettant d’obtenir des molécules polycycliques contenant un motif de type pyridine est développée. / Deuterated and tritiated compounds are widely used in numerous applications in chemistry, biology and material science. In the drug discovery and development process, ADME studies require quick access to labelled molecules, otherwise the drug development costs and timeline are significantly impacted. The rapid development of metabolomics has also increased the need for isotopically labelled compounds. In particular, deuterated molecules are used as internal standards for quantitative LC-MS/MS analysis of metabolites in biological fluids and tissues. In this context, a general method allowing the deuterium and tritium labelling of bioactive thioethers using a HIE reaction is described in the first chapter. From a fundamental point of view, this transformation is the first example of (Csp³)-H activation directed by a sulfur atom. In terms of application, this new reaction has been proved to be useful for the preparation of deuterated LC-MS/MS reference materials and tritiated pharmaceuticals owning high specific activity.In the second chapter of this manuscript, the development of a method allowing the cross-dehydrogenative homocoupling of 2-arylpyridines catalyzed by Ru/C is developed. Various substrates with different substituents were efficiently coupled to give the desired dimers in good yield. In terms of application, a series of pyridine-boron complexes derived from the phenyl pyridine dimers were also synthesized and their photophysical properties were studied.In the third chapter, a regioselective palladium catalyzed intramolecular arylation reaction allowing the synthesis of pyridine containing polycyclic compounds is described.