A malária é uma das principais causas de morte em muitos países de clima tropical, matando mais de 438 mil pessoas anualmente em todo o mundo. Desta forma, o objetivo do presente trabalho foi sintetizar compostos fluorescentes 2,5- diarilfuranos através da reação de acoplamento cruzado tipo Suzuki-Miyaura e acoplar ao fármaco Primaquina para utilizá-los laboratorialmente como biomarcadores específicos, carreadores de substâncias, parasiticidas, além do desenvolvimento de novo método diagnóstico. Através deste tipo de reação, foram sintetizados 3 compostos fluorescentes: a sonda 3-AFA, 3-AFA ala e a 4-AFAPQ. Inicialmente foram utilizadas células primárias, células da linhagem RAW 264.7 e células eritrocíticas, estas provenientes de camundongos Balb/c inoculados pela via intraperitoneal com 106 EI/mL de P. berghei ANKA GFP. Os compostos fluorescentes sintetizados 3-AFA e 3-AFA ala foram incubados com as células acima citadas e verificou-se a capacidade de as sondas penetrarem e marcarem células sadias e/ou infectadas. A aquisição dos resultados foi realizada por meio de citometria de fluxo e microscopia confocal. A partir daí, utilizou-se também sangue humano proveniente de doação que foi infectado com P. falciparum 3D7. A análise dos resultados realizada com microscopia de fluorescência e testes de EC50 com estes eritrócitos, além de células HepG2. As sondas 3-AFA e 4-AFAPQ foram incubadas com estas células para avaliar a ação parasiticida, bem como a citotoxicidade destes compostos. Nossos resultados mostraram que as sondas 3-AFA e 3-AFA ala não foram capazes de penetrar os macrófagos. Entretanto, foram capazes de atravessar a membrana dos eritrócitos infectados marcando o parasita. Quando os compostos 3- AFA e a 4-AFAPQ foram inseridos em eritrócitos humanos infectados pelo P. falciparum 3D7, foi possível observar que ambos marcaram o parasita em suas 3 fases. Mas resultados de EC50 mostraram que os compostos não possuem efeito parasiticida. E podemos concluir que estes compostos não são citotóxicos ás células possuindo então, um potencial em serem estudados mais a fundo, com algumas modificações em suas estruturas para melhorar assim, sua eficiência quanto a seletividade. Diante destes compostos potencialmente fluorescentes, foi possível também desenvolver um novo método de diagnóstico rápido simples e barato que pode possibilitar o alcance em locais aonde os métodos convencionais de microscopia não chegam. / Malaria is a major cause of death in many tropical countries, killing over 438 thousand people annually worldwide. Thus, the objective of this study was to synthesize fluorescent compounds 2,5-diarylfuranes through cross-coupling reaction like Suzuki-Miyaura and engage the drug Primaquine to use them as laboratory specific biomarkers, carriers of substances, parasiticide, and the development new diagnostic method. Through this type of reaction, three fluorescent compounds were synthesized: probe 3-AFA, 3-AFA ala and 4-AFAPQ. Initially were used primary cells, strain RAW 264.7 cells line and erythrocytic cells, those derived from Balb/c mice inoculated intraperitoneally with 106 IE/mL of P. berghei ANKA GFP. The synthesized fluorescent compounds 3-AFA and 3-AFA ala were incubated with the above said cells and found the ability of penetrating probes and mark healthy cells and/or infected. The acquisition of the results was performed by flow cytometry and confocal microscopy. From there, it was also used human blood from that donation was infected with P. falciparum 3D7. The analysis performed with fluorescence microscopy and EC50 these tests with erythrocytes, and HepG2 cells. The probes 3-AFA and 4-AFAPQ were incubated with these cells to evaluate the parasiticidal activity and cytotoxicity of these compounds. Our results showed that the probes 3-AFA and 3-AFA ala were not able to penetrate macrophages. However, they were able to pass the membrane of the parasite infected erythrocytes marking. When the fluorescents probes 3-AFA and 4- AFAPQ (coupled Primaquine) were inserted into human erythrocytes infected with P. falciparum 3D7, it was observed that both marked the parasite in her 3 phases. But EC50 results showed that the compounds do not have parasiticidal effect. And we can conclude that these compounds are not cytotoxic to the cells having then a potential be studied further, with some modifications in their structures to improve thus efficiency and selectivity. Given these potentially fluorescent compounds, it was possible to develop a new method of simple and inexpensive rapid diagnosis that can enable the range in places where conventional methods of microscopy not arrive.

Le myricanol est un [7,0]-métacyclophane naturel qui appartient à la famille des diarylheptanoïdes cycliques et qui possède des propriétés structurales et biologiques intéressantes (activité anti-Alzheimer ou anticancéreuse). L’objectif de ce travail de thèse est la préparation ambitieuse en voie racémique puis atropostéréosélective du myricanol, rendue délicate de part la tension de cycle existante. Pour se faire, deux nouvelles approches rétrosynthétiques ont été considérées. Une première route racémique a été envisagée et a permis de préparer le macrocycle par le biais d’une réaction de métathèse croisée suivie d’une réaction de Suzuki-Miyaura domino intramoléculaire avec un rendement de 2.55% en 11 étapes. Une autre voie racémique a également été explorée où la préparation du noyau biarylique du myricanol a été envisagé par une réaction de couplage intermoléculaire métallo-catalysée suivie d’une réaction de métathèse cyclisante. Des intermédiaires avancés ont également été préparés. / The myricanol, a natural [7.0]-meta-cyclophane which belongs to the family of strained and cyclic diarylheptanoids, possess an interesting structure and attractive biologically activities (anti Alzheimer and anti cancer properties). Actually only two synthesis of racemic (+/-)-myricanol have been reported in the literature. The goal of this research was to prepare this strained cyclophane in a racemic and then in an atropostereoselective route taking into account the challenging ring closure. Thus a linear diarylheptanoid was prepared using an efficient cross-metathesis reaction followed by an intramolecular Suzuki-Miyaura domino reaction giving rise to the desired cyclophane with 2.55% overall yield in 11 steps. On the other side, the biaryl core of myricanol was envisaged by an intermolecular metallo-catalysed coupling reaction between already highly functionalized fragments, followed by a ring closure metathesis. Two advanced intermediates were already attempted.

Des membranes polymères catalytiques ont été préparées via la polymérisation photo-amorcée de monomères acryliques à la surface de membranes support MicroPES(r). Des nanoparticules de palladium (PdNP) avec diamètre moyen compris entre 4 et 10 nm sont ensuite synthétisés et immobilisées dans ces gels polymères greffés. Cette thèse se focalise sur le greffage d'un gel de polymère neutre : (2-hydroxyethyl acrylate) (PHEA), pour négliger les contributions ioniques du réseau polymère sur la synthèse in-situ des PdNP. La stabilisation de PdNP dans le gel de PHEA greffé est possible par des moyens stériques étant donné que la distance entre des chaînes de polymère réticules (entre 0.3 à 2.5 nm) est plus petite que le diamètre moyen de PdNP. Une approche à la fois théorique et expérimentale, sur la base des mecanismes de nucléation et de croissance, permet la conception de PdNP de taille spécifique. La performance catalytique des membranes a été évaluée avec une configuration en filtration traversée. Sur la réaction de couplage de Suzuki-Miyaura, des conversions et sélectivités de 100 % ont été obtenues pour des temps de séjour de 10 secondes avec des membranes planes. Les réactions d'hydrogénation de plusieurs composés aromatiques ont également été testées. Des taux de conversion élevés ont été obtenus en quelques secondes avec des membranes planes en filtration avec des solutions saturés d'H2. Des taux de conversion élevés sont obtenus en seulement quelques minutes avec des membranes fibres creuses catalytiques en mode contacteur permettant une importante intensification du procédé. / Catalytic polymeric membranes are prepared via photo-grafting polymerization of neutral acrylic monomers onto the surface of a MicroPES(r) membrane support. Palladium nanoparticles (PdNP) of mean diameter of 4-10 nm are synthetized and immobilized within the grafted polymer gels. The research is focused on grafting a neutral polymer gel: poly (2-hydroxyethyl acrylate) (PHEA), to avoid any ionic contribution of the polymer network on the in-situ synthesis of PdNP. The stabilization of PdNP within the grafted PHEA is achieved by steric means as the distance between polymeric crosslinked chains (ca. 0.3 to 2.5 nm) is smaller than the mean diameter of PdNP. Both theoretical and experimental approaches are presented on the PdNP synthesis as an approach to conceive PdNP of specific sizes using nucleation and growth theories. Catalytic performance of the membranes is evaluated in flow-through configuration. Catalytic tests are performed on Suzuki-Miyaura cross-coupling reactions. Full conversion and selectivity within 10 seconds of residence time using flat sheet membrane are obtained. Hydrogenation of several aromatic compounds are also tested and high conversions were achieved within seconds of residence time using flat sheet membranes in flow-through configuration with H2-saturated solutions and within minutes using catalytic hollow fibers in contactor mode.

In the field of electronic organic materials, conjugated polymers (CPs) have attracted much attention in recent years. It has been well-established that performances of thin-film devices based on π-conjugated polymers, such as light-emitting diodes, field-effect transistors and photovoltaic cells, are strongly dependent on the organisation of the polymer molecules and their interactions with other constituents in multicomponent devices. The use of CPs in integrated circuits, solar cells, light-emitting diodes or sensors often requires their covalent fixation and patterning on various surfaces. CPs can be grafted to functionalized surfaces by (electro)chemical cross-linking; however, it is difficult to control a structural order within the cross-linked films. The attachment of CP chains to substrates by their end-points to form polymer brushes would be an interesting alternative, and could possibly be crucial for many devices requiring charge injection and charge transport processes. The main aim of this work, which was the synthesis of covalently grafted conjugated polymer brushes on solid substrates using a "grafting from" approach, was successfully performed. During the course of this work, the process of surface-initiated polycondensation was investigated. The newly developed method to selectively graft conjugated polymers from different substrates such as Si-wafers, quartz slides or modificated nanoparticles allowed us to produce different architectures which were earlier possible to prepare only non-conductive polymers. Exposure of the substrate with an activated surface layer into the monomer solution produced polymer brushes in a very economical way. Since only monomer was consumed for grafting from the surface. The grafting process was extensively investigated by different methods, and the thickness of the obtained poly(fluorene) films was elucidated by Null-ellipsometry and confirmed by the AFM scratch-test. Preliminary characteristics of the device, based on PS(Br)-core poly(octylfluorene)-shell nanoparticles, showed satisfactory results (such as turn-on voltage and electroluminescence in a blue region). They could be improved by replacement of the insulating PS(Br)-core of nanoparticles with other substances (semiconductive, etc.). There is still plenty of room for further development and improvement of the synthesis of poly(fluorene)-based polymer brushes. The polymer structures developed in this work can be utilized as an active layer in lab-on-chip devices. Alkyl groups in the 9th position of the poly(fluorene) monomer unit can be replaced by tailored receptors to detect specific species including small molecules, metal ions and biomolecules due to enhanced sensitivity through sensory signal amplification. Post-polymerization modifications may lead to highly water-swellable conjugated polyelectrolyte brushes. Also, polymerization of initially optically active fluorene-monomers may be the crucial step to the generation of a light source devices with a large degree of circularly polarized electroluminescence. This is of great interest for utilization as backlight for liquid crystalline displays. We believe that the utilization of covalently surface-immobilized conjugated polymers may have a great impact on the development of present-day technological processes.

[pt] A reação de acoplamento C-C de Suzuki, desde a sua descoberta, sempre atraiu o interesse de diversos pesquisadores e encontrou aplicação em diversos campos tanto na academia como na indústria. Movidos pelos problemas ambientais que tanto preocupam nossa sociedade e pelos princípios da química verde, criados para guiar os químicos na direção de uma ciência sustentável, pesquisadores tem buscado criar catalisadores eficientes para essa reação, que consigam uma alta seletividade em condições reacionais brandas. O desenvolvimento de catalisadores heterogêneos é motivado pela sua fácil remoção do meio reacional e seu possível reuso para um elevado número de reações. Uma abordagem para criação desses catalisadores é a ancoragem de íons metálicos ou de nanopartículas (Nps) metálicas em suportes que facilitem seu manuseio, remoção e reuso. Neste trabalho foram sintetizadas nanopartículas de paládio (Nps Pd) estabilizadas por carboximetilcelulose (CMC), em cuja síntese foi utilizado o ácido L-ascórbico (AA) como agente redutor. Essas Nps foram caracterizadas por UV-VIS, FT-IR-ATR, DLS, potencial zeta, MEV e EDS. A reação de redução do 4-nitrofenol foi utilizada como teste preliminar para verificar a atividade catalítica dessas Nps e, em diferentes condições, a reação ocorreu com tempos que variaram de 3 a 10 minutos. Depois, foram empregadas três diferentes metodologias para a síntese de Nps Pd que utilizaram a CMC como agente redutor e estabilizador a fim de eliminar o uso do AA. As três Nps sintetizadas foram usadas para catalisar uma reação de acoplamento entre o ácido fenilborônico e o 4-iodofenol com rendimentos de 68-76 por cento em duas horas. As Nps que obtiveram maior rendimento foram escolhidas para dar prosseguimento ao projeto. Foram caracterizadas por UV-VIS, FT-IR-ATR, DLS, potencial zeta, MEV e EDS e foram utilizadas para catalisar mais três acoplamentos de Suzuki com rendimentos de 74 por cento a 86 por cento. Um suporte lignocelulósico, mecanicamente e termicamente resistente, feito a partir da biomassa de bambu foi funcionalizado com 1-oxil-2,2,6,6-tetrametilpiperidina (TEMPO) e caracterizado por FT-IR-ATR. Foi, então, impregnado para a imobilização de Na2PdCl4 (T_PdCl2) e das Nps Pd reduzidas e estabilizadas com CMC escolhidas (T_PdCMC_R). Os catalisadores desenvolvidos foram caracterizados por FT-IR-ATR, MEV e EDS. O catalisador T_PdCl2 foi utilizado em 4 reações seguidas com perdas de rendimento a cada reação (de 92,2 por cento até 18,4 por cento). Por ICP OES foi determinado que a quantidade de paládio lixiviada foi de 0,20 ppm na primeira reação e de 0,10 ppm nas reações seguintes. O catalisador T_PdCMC_R foi usado para a reação acoplamento entre ácido fenilborônico e 4-iodofenol e, em diferentes condições, obteve rendimentos de 35 por cento e 43 por cento. / [en] Suzuki C-C coupling reaction, since its discovery, has always attracted the interest of researchers and has found application in several fields both in academia and industry. Driven by environmental problems that concern our society so much and by the principles of green chemistry, created to guide chemists towards a sustainable science, researchers have sought to create efficient catalysts for this reaction, which achieve high selectivity in mild reaction conditions. The development of heterogeneous catalysts is motivated by its easy removal from the reaction medium and its possible reuse for a high number of reactions. One approach for creating these catalysts is to anchor metallic ions or metallic nanoparticles (Nps) in supports that facilitate their handling, removal and reuse. In this work, palladium nanoparticles (Nps Pd) reduced by ascorbic acid (AA) and stabilized by carboxymethylcellulose (CMC) were synthesized. These Nps were characterized by UV-VIS, FT-IR-ATR, DLS, zeta potential, SEM and EDS. The 4-nitrophenol reduction reaction was used as a preliminary test to verify the catalytic activity of these Nps and, under different conditions, the reaction occurred with times ranging from 3 to 10 minutes. Then, three different methodologies for the synthesis of Nps Pd using CMC as reducing and stabilizing agent were proposed in order to eliminate the use of AA. The three synthesized Nps were used to catalyze the coupling reaction between phenylboronic acid and 4-iodophenol with yields of 68-76 percent in two hours. The Nps that obtained the highest yield were chosen to be used in the next steps of the project. These Nps were characterized by UV-VIS, FT-IR-ATR, DLS, zeta potential, SEM and EDS and were used to catalyze three more Suzuki couplings with yields of 74-86 percent. A mechanically and thermally resistant lignocellulosic support, made of bamboo biomass, was functionalized with 1-oxyl-2,2,6,6-tetramethylpiperidine (TEMPO) and characterized by FT-IR-ATR. It was then impregnated for the immobilization of Na2PdCl4 (T_PdCl2) and the chosen Nps Pd reduced and stabilized by CMC (T_PdCMC_R). The developed catalysts were characterized by FT-IR-ATR, MEV and EDS. The catalyst T_PdCl2 was used in 4 reactions in a row with yield losses for each reaction (from 92.2 percent to 18.4 percent). By ICP OES it was determined that the amount of palladium leached was 0.20 ppm in the first reaction and 0.10 ppm in the following reactions. The catalyst T_PdCMC_R was used for the coupling reaction between phenylboronic acid and 4-iodophenol and, under different conditions, obtained yields of 35 percent and 43 percent.

L'objectif de ce travail consiste en la synthèse de nouveaux 5-nitroimidazoles fonctionnalisés à visée thérapeutique. Dans un premier temps, l'étude de la réactivité du 4-bromo-1,2-diméthyl-5-nitro-1H-imidazole vis-à-vis du couplage de Suzuki-Miyaura sous irradiation micro-ondes a permis la synthèse de nouveaux produits substitués en position 4 par différents groupements aryle ou styryle. Dans un second temps, la réactivité LD-SRN1 a été étudiée entre le 4-[4-(chlorométhyl)phényl]-1,2-diméthyl-5-nitro-1H-imidazole et différents nucléophiles centrés sur l'atome de carbone ou de soufre. Cette étude a révélé l'importance de la température dans l'activation de la réaction par transfert monoélectronique. De nouveaux dérivés substitués en position 4 par divers groupements sulfonyles ont ensuite été synthétisés, par réactions SN2 et SNAr entre des dérivés 5-nitroimidazolés et différents anions sulfinates. Cette synthèse a été suivie par la mise au point de tests biologiques sur Trichomonas vaginalis. L'activité trichomonacide a été évaluée sur certaines de ces molécules, à l'origine de relations structure-activité montrant l'influence de la position du groupement sulfonyle substituant le noyau 5-nitroimidazole. La dernière partie de ce travail décrit une réaction de O-arylation pallado-catalysée inattendue et originale, d'un dérivé fluoré en série nitro(o-nitrophényl)imidazole impliquant des acides arylboroniques dans les conditions opératoires de la réaction de Suzuki-Miyaura. / The aim of this work consists of the synthesis of new potentially bioactive functionalized 5-nitroimidazoles. Initially, the reactivity study of the 4-bromo-1,2-dimethyl-5-nitro-1H-imidazole under microwave-assisted Suzuki-Miyaura cross-coupling conditions gave new derivatives substituted by various aryl or styryl groups in 4-position. In a second step the 4-[4-(chloromethyl)phenyl]-1,2-dimethyl-5-nitro-1H-imidazole was prepared in order to study LD-SRN1 reactivity with different carbon and sulphur centered nucleophiles. This study pointed the role of the temperature for the electron transfer reactions. Then, new 4-position sulfonyl substituted derivatives were synthesized by SN2 and SNAr reactions between sulfinate anions and three substrates in 5-nitroimidazole series. This synthesis was followed by the development of biological assays on Trichomonas vaginalis. This assay was performed on some of these molecules, which revealed a relation between the structure and the position of the sulfonyl group and the antitrichomonas activity. The last part of this work describes an unexpected and original palladium-catalyzed O-arylation in fluorinated nitro(o-nitrophenyl)imidazole series involving arylboronic acids under Suzuki-Miyaura cross-coupling reaction conditions.

En aquesta tesi doctoral es va estudiar la preparació de pèptids biarílics en fase sòlida. En primer lloc, es varen borilar residus de fenilalanina o tirosina presents a la seqüència peptídica a través d’una reacció de Miyaura. A continuació, es varen arilar els boronats resultants a través d’una reacció de Suzuki-Miyaura sota irradiació de microones, utilitzant diversos halurs d’aril i haloaminoàcids. La metodologia trobada es va estendre a la preparació de pèptids biarílics cíclics. Aquesta aproximació presenta l’avantatge d’evitar la síntesi en dissolució i la purificació del boronoaminoàcid. A més, permet la preparació d’una àmplia diversitat de pèptids biarílics a partir d’un únic boronopèptid. L’avaluació de l’activitat biològica dels pèptids sintetitzats va permetre idenficar seqüències actives enfront dels bacteris Erwinia amylovora, Xanthomonas vesicatoria, i Pseudomonas syringae, que són responsables de malalties greus en plantes d’interès econòmic com pereres i pomeres, i que varen resultar ser molt poc tòxics enfront cèl•lules eucariotes. / The present PhD study was focused on the preparation of biaryl peptides on solid-phase. First, phenylalanine or tyrosine residues were borylated through a Miyaura reaction. Then, the resulting boronates were arylated via a Suzuki-Miyaura reaction under microwave irradiation, using a range of aryl halides and haloamino acids. This methodology was extended to the solid-phase synthesis of biaryl cyclic peptides. This strategy is advantageous because it avoids the synthesis and purification of amino acid boronates in solution. Moreover, it allows the preparation of a large diversity of biaryl peptides from a single boronopeptide intermediate. The evaluation of the biological activity allowed the identification of active sequences against the economically important plant pathogenic bacteria Erwinia amylovora, Xanthomonas vesicatoria, and Pseudomonas syringae, and moreover they were not toxic against eukaryotic cells.

Die Immobilisierung homogener Katalysatoren ist eine wichtige Methode zur Realisierung der Abtrennbarkeit und Wiederverwendbarkeit aktiver Spezies. Im Rahmen dieser Arbeit wurde durch die Komplexierung von Palladium mit 1,4-Bis-(4′-pyrazolyl)benzen ein neues mikroporöses Koordinationspolymer generiert und dieses als heterogener Katalysator in der Suzuki-Miyaura-Kreuzkupplungsreaktion erfolgreich eingesetzt. Dabei konnten vollständige Umsätze und hohe Selektivitäten erzielt werden, die vergleichbar zu bereits kommerziell erhältlichen homogenen Katalysatoren sind. Die Besonderheit des Katalysators ist, neben dessen außergewöhnlich hohen chemischen Stabilität, die Variation seiner Struktureigenschaften durch die Wahl der Synthesebedingungen und die damit verbundene Steuerung seiner katalytischen Aktivität.:1 EINLEITUNG 1 2 KENNTNISSTAND 5 2.1 Immobilisierung von Palladium 5 2.1.1 Organische Trägermaterialien 6 2.1.1.1 Polyanilin 6 2.1.1.2 Polymerverankerte Phosphanliganden 8 2.1.1.3 Imprägnierung komplexfunktionalisierter Polymere 10 2.1.2 Anorganische Trägermaterialien 11 2.1.2.1 Aktivkohle 11 2.1.2.2 Metalloxide 13 2.1.3 Hybridmaterialien 14 2.1.3.1 Infinite Coordination Polymers 14 2.1.3.2 Metal-Organic Frameworks 17 2.2 Die Suzuki-Miyaura-Kreuzkupplungsreaktion 24 2.2.1 Allgemeine mechanistische Vorstellungen zur Reaktion 27 2.2.2 Die PdII/PdIV-Katalyse – Ein umstrittener Mechanismus 29 3 AUFGABENSTELLUNG UND LÖSUNGSSTRATEGIE 33 4 ERGEBNISSE UND DISKUSSION 38 4.1 Charakterisierung des Koordinationspolymers [Pd(BPB)]n 38 4.1.1 Bis(triphenylphosphan)palladium(II)dichlorid als Palladiumprecursor 38 4.1.1.1 Synthese und Charakterisierung 38 4.1.1.2 Porosität 49 4.1.1.3 Oxidationsstufe des Palladium 57 4.1.1.4 Strukturdiskussion 64 4.1.2 Mechanistische Untersuchungen zur Bildung von [Pd(BPB)]n 74 4.1.2.1 Verfolgung des Reaktionsablaufes mittels Kernresonanzspektroskopie 74 4.1.2.2 Vorschläge zum Reaktionsmechanismus 81 4.1.3 Alternative Palladiumprecursoren für [Pd(BPB)]n 88 4.1.3.1 Bis(triphenylphosphan)palladium(II)dibromid 88 4.1.3.2 Natriumtetrachloropalladat 90 4.1.3.3 Weitere Palladiumprecursoren 93 4.1.4 Alternative Synthesetechniken für [Pd(BPB)]n 94 4.1.4.1 Solvothermale Synthese 94 4.1.4.2 Basendiffusionsmethode 95 4.2 Heterogen katalysierte Suzuki-Miyaura-Reaktion mit [Pd(BPB)]n 97 4.2.1 Verifizierung des Versuchsablaufes mittels Vergleichskatalysatoren 97 4.2.2 Die katalytische Aktivität von [Pd(BPB)]n in der Suzuki-Reaktion 100 4.2.3 Katalysatorstabilität und Wiederverwendbarkeit von [Pd(BPB)]n 104 4.2.4 Einfluss der Reaktionstemperatur 110 4.2.5 Einfluss des phosphanhaltigen Palladiumprecursors 114 5 ZUSAMMENFASSUNG 116 A EXPERIMENTELLER TEIL 120 A.1 Synthese und Charakterisierung von [Pd(BPB)]n 120 A.1.1 Arbeitstechniken und verwendete Chemikalien 120 A.1.2 Synthesevorschriften für [Pd(BPB)]n 122 A.1.2.1 Darstellung von 1,4-Bis-(4′-pyrazolyl)benzen (H2BPB) 122 A.1.2.2 Fällungssynthese von [Pd(BPB)]n 122 A.1.2.3 Solvothermale Synthese von [Pd(BPB)]n 123 A.1.2.4 Diffusionskontrollierte Synthese von [Pd(BPB)]n 124 A.1.2.5 Synthese aus Natriumtetrachloropalladat 124 A.1.2.6 Synthese aus Palladiumacetat 124 A.1.2.7 Synthese aus PdBr2(PPh3)2 125 A.1.3 Charakterisierung von [Pd(BPB)]n 125 A.2 Durchführung der Suzuki-Miyaura-Reaktion 127 A.2.1 Umsetzung von 4-Bromacetophenon mit Phenylboronsäure 127 A.2.2 Katalysatorstabilität und Wiederverwendbarkeit 128 A.2.3 Analyse und Identifizierung der Reaktionsprodukte 129 B ANHANG 134 B.1 Charakterisierung von [Pd(BPB)]n 134 B.2 Mechanistische Untersuchungen zur Bildung von [Pd(BPB)]n 140 B.3 Katalytische Aktivität von [Pd(BPB)]n 141 B.4 Tabellenverzeichnis 143 B.5 Abbildungsverzeichnis 145 B.6 Symbole und Abkürzungen 150 B.7 Literaturverzeichnis 154

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

L'objet de ce travail de thèse concerne la synthèse par réaction cascade pallado-catalysé d'une nouvelle famille de chromophores pentacycliques azotés dont les propriétés de fluorescence peuvent être modulées en fonction des groupements fonctionnels présents dans la molécule. Ces chromophores sont obtenus par réaction one-pot entre des acides 2-formyl boroniques et des 2,5-dihalopyridines. Le processus cascade est initié par un couplage de Suzuki suivi par deux cyclisations successives. La première se fait sur l'azote de la pyridine et la seconde se produit de façon régio-sélective sur le carbone adjacent à l'azote. Les structures cristallines et le calcul théorique DFT ont montré la régio et la stéréo-sélectivité de la réaction. De plus, des études préliminaires ont montré que ces composés polycycliques possèdent d'excellentes propriétés de fluorescence ainsi qu'une activité biologique qui devraient nous permettre d'étendre le champ d'application de ces nouveaux chromophores vers le domaine médical et l'électronique moléculaire / The aim of this work concerns the synthesis of a new family of aza-pentacyclic chromophore whose fluorescence properties can be modulated according to the functional groups present in the molecule. These chromophores were obtained through a cascade process between 2-formylbenzene boronic acid and 2,5-dihalopyridines. The cascade process is initiated by a palladium-catalyzed cross-coupling reaction and is followed by two successive nucleophilic cyclizations; the first cyclization performed on the pyridine nitrogen and the second occurred regioselectively on the adjacent carbon atom. This new cascade reaction allowed the formation of a pentacycle as a single regioisomer with four new bonds and two contiguous stereocenters with trans relationships. In addition, preliminary studies have shown that these polycyclic compounds have excellent fluorescence properties as well as biological properties that should enable us to extend the scope of these new chromophores to the medical field and molecular electronics