Please note that the structures do not display correctly in the pdf document. Therefore the original manuscript in MSWord has also been uploaded. Please contact us email if you cannot view these files. / Sonogashira cross-coupling of 2-aryl-4-chloro-3-iodoquinoline derivatives with stoichiometric amount of terminal alkynes in the presence of bis(triphenylphosphine)palladium(II)chloride and copper iodide in triethylamine afforded the 3-(alkynyl)-2-aryl-4-chloroquinoline, exclusively. On the other hand, the 2-aryl-4-chloro-3-iodoquinolines with excess (2.5 equiv.) of terminal alkynes in the presence of PdCl2(PPh3)2-CuI catalyst mixture and NEt3 in dioxane-water (3:1 v/v) afforded the 2-aryl-3,4-bis(alkynyl)quinoline derivatives in a one-step operation. Further transformation of the 2-aryl-3-(alkynyl)-4-chloroquinoline via Suzuki cross-coupling reaction with boronic acid derivatives in the presence of tetrakis(triphenylphosphine)palladium and tricyclohexylphosphine as a ligand in dioxane-water (3:1 v/v) afforded the 2,4-diaryl-3-(alkynyl)quinolines in moderate to high yields. The 2-aryl-3-(alkynyl)-4-chloroquinolines were also transformed to the corresponding 2-aryl-4-(methylamino)-3-(alkynyl)quinoline derivatives using methylamine in ethanol under reflux. / Chemistry / M.Sc.

The 2-aryl-2,3-dihydroquinolin-4(1H)-ones were prepared via acid-catalyzed cyclization of the corresponding 2-aminochalcones, which were in turn, prepared by base-promoted Claisen-Schmidt aldol condensation of 2-aminoacetophenone and benzaldehyde derivatives. The 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones were prepared by reacting 2-aryl-2,3-dihydroquinolin-4(1H)-ones with N-bromosuccinimide (NBS) in carbon tetrachloride-chloroform mixture at room temperature. The 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones were subjected to palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with arylboronic acid using dichlorobis(triphenylphosphine)palladium(II)-tricycohexylphosphine as catalyst mixture and potassium carbonate as a base in dioxane-water under reflux to afford the corresponding novel 2,6,8-triaryl-2,3-dihydroquinolin-4(1H)-ones in a single-pot operation. The latter were subjected to thallium(III) p-tolylsulfonate in dimethoxyethane under reflux to yield the 2,6,8-triarylquinolin-4(1H)-ones. The 2,6,8-triaryl-2,3-dihydroquinolin-4(1H)-ones were treated with molecular iodine in refluxing methanol to afford the corresponding 2,6,8-triaryl-4-methoxyquinolines. All the new compounds were characterized using a combination of 1H NMR & 13C NMR spectroscopy, IR and mass spectroscopic techniques. / Chemistry / M.Sc. (Chemistry)

Les hétérocycles aromatiques sont des motifs structuraux rencontrés dans un grand nombre de substances d'intérêts biologiques ou pharmacologiques. Plus particulièrement, les pyridazines substituées font l'objet d'un intérêt grandissant pour leurs propriétés pharmaceutiques (antibactériens, anti-inflammatoires, médicaments cardiovasculaires…). De plus, les structures comportant des pyridazines peuvent également être utilisées en tant qu'agents chélatants de cations métalliques et s'ordonner en édifices utilisés en chimie supramoléculaire.Nous nous sommes donc intéressés à l'élaboration d'éléments de base comportant des cycles pyridaziniques de type aryl ou hétéroarylpyridazines. La mise au point de méthodes impliquant des espèces organométalliques a été l'un de nos objectifs primordial. L'élaboration de ces composés a été réalisée par formation de liaisons C-C. Une approche électrochimique d'hétérocouplage associé à une catalyse au nickel a été utilisée. Quelques limites à cette méthode ont cependant été observées dans le cas des couplages mettant en jeu des 3,6-dihalogénopyridazines. Une étude par électrochimie analytique a permis d'en comprendre les raisons. La seconde partie de notre travail a consisté en l'étude de la réactivité d'arylzinciques ou de triarylbismuths vis-à-vis de 3,6-dihalogénopyridazines / Heteroaromatic rings are present in various biological and pharmacological active molecules. Substituted aryl-pyridazines have given rise to considerable interest because of their diverse pharmacological properties (antibacterial, anti-inflammatory, cardiovascular drugs…). Moreover, structures which contain pyridazines are used in supramolecular chemistry for their applications through self-assembly processes in the presence of metal ions.In order to elaborate building blocks containing pyridazine rings such as aryl or heteroaryl-pyridazines, we turned our intention on the development of complementary methods involving organometallic reagents. Transition metal-catalyzed cross-coupling reaction of organometallic compounds with organic halides is one of the most powerful methods for the generation of C-C bonds.We chose to develop the most straightforward method involves heterocoupling reaction of aryl/heteroaryl compounds under electrochemical conditions (sacrificial anode process) associated to a nickel catalysis. However some limitations have been pointed out when 3,6-dihalogenopyridazines are involved in the cross-coupling reaction. An electrochemical study was investigated in order to propose some mechanistic considerations. A second part of this work consisted in the study of arylzinc and triarylbismuths reagents toward 3,6-dihalogenopyridazines

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.

This thesis is the use of commercially available methyl 2-iodobenzoate as the starting material and was prepared into iodine - oxazoline compound 118. Then, we undergo copper-catalyzed cross-coupling reactions of compound 118with thiols, and were readily facilitated to afford the corresponding desired products 127¡B136 in good to excellent yields. This method not only modified short- comings of that adding strong base to synthesis of sulfur-oxazoline ligands in past years but also has a good yield performances, the yield is 70 -87%. And we will use this strategy to undergo one pot reaction of carbon-sulfur coupling in future. In the end, we used new sulfur-oxazoline ligands127¡B128 in the Pd-catalyzed asymmetric alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate. and reaction ee% were high, with the best result of 99% and 93% conversion.

A one-pot synthesis of ortho-arylated 9-(pyridin-2-yl)-9H-carbazoles via C-H bond activation, in which palladium(II)-catalyzed cross-coupling of 9-(pyridin-2-yl)-9H-carbazoles with potassium aryltrifluoroborates is presented. Silver nitrate and tert-butanol were proved to be the best oxidant and solvent for the process, respectively. The product yields fluctuated from modest to excellent, and the reaction showed sufficient functional group tolerance. p-Benzoquinone served as an important ligand for the transmetalation and reductive elimination steps in the catalytic process. The key intermediate of the reaction, 9-(pyridin-2-yl)-9H-carbazole palladacycle was isolated and confirmed by X-ray crystallography. The kinetic isotope effect (kH/kD) for the C-H bond activation step was measured as 0.87. In addition, Hammett experiment gave a negative rho value, -2.14 with a reasonable correlation (R2 = 0.90). The directing group, pyridyl was demonstrated as a removable functional group. Finally, a rational catalytic mechanism is presented based on all experimental evidence.

The 2-aryl-2,3-dihydroquinolin-4(1H)-ones were prepared via acid-catalyzed cyclization of the corresponding 2-aminochalcones, which were in turn, prepared by base-promoted Claisen-Schmidt aldol condensation of 2-aminoacetophenone and benzaldehyde derivatives. The 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones were prepared by reacting 2-aryl-2,3-dihydroquinolin-4(1H)-ones with N-bromosuccinimide (NBS) in carbon tetrachloride-chloroform mixture at room temperature. The 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones were subjected to palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with arylboronic acid using dichlorobis(triphenylphosphine)palladium(II)-tricycohexylphosphine as catalyst mixture and potassium carbonate as a base in dioxane-water under reflux to afford the corresponding novel 2,6,8-triaryl-2,3-dihydroquinolin-4(1H)-ones in a single-pot operation. The latter were subjected to thallium(III) p-tolylsulfonate in dimethoxyethane under reflux to yield the 2,6,8-triarylquinolin-4(1H)-ones. The 2,6,8-triaryl-2,3-dihydroquinolin-4(1H)-ones were treated with molecular iodine in refluxing methanol to afford the corresponding 2,6,8-triaryl-4-methoxyquinolines. All the new compounds were characterized using a combination of 1H NMR & 13C NMR spectroscopy, IR and mass spectroscopic techniques. / Chemistry / M.Sc. (Chemistry)

A presente dissertação de mestrado descreve estudos sobre as reações multicomponentes A3 na versão assimétrica. Diversas metodologias foram empregadas visando a obtenção de propargilaminas opticamente ativas, que são blocos sintéticos versáteis na preparação de compostos bioativos. O trabalho foi dividido em duas partes. Na primeira parte, estudou-se a utilização de aminas opticamente puras como materiais de partida para a reação tricomponente A3. Neste caso, foi utilizada a 2-metilpropan-2-sulfinamida como amina principal, no entanto, o produto de acoplamento não foi obtido, mesmo em diversas condições testadas. Outras aminas opticamente puras, como a (S)- metilbenzilamina e aminas derivadas de amino ácidos, também foram testadas. Os resultados, quanto às razões diastereoisoméricas e rendimento, foram satisfatórios quando aminas derivadas de amino ácidos foram utilizadas, principalmente quando o éster metílico da L-polina foi empregado como fonte de amina, que levou a formação do produto em bom rendimento e uma razão enantiomérica de 15:85. Na segunda parte do trabalho estudou-se a utilização de auxiliares quirais, na reação de A3, como indutores de assimetria. Para tanto, diversos compostos foram testados como oxazolinas opticamente puras e derivados de L-prolina. / This masters thesis describes studies for the asymmetric version of A3 multicomponent reactions. Several methodologies were employed in order to obtain optically active propargylamines, which are versatile synthetic building blocks on the preparation of bioactive compounds. The work was divided into two parts. In the first part, we investigated the use of optically pure amines as starting materials for the A3-coupling reaction. In this case, we used the 2-methylpropan-2-sulfinamide as the main amine, however, the coupling product was not obtained, even under several reaction conditions. Other optically pure amines such as (S)-methylbenzylamine and amines derived from amino acids, were also tested. The yields and diastereomeric excess were satisfactory when amines derived from amino acids were employed, especially when the methyl ester of L-poline was used as amine source, which led to the formation of the product in good yield and diastereoisomeric ratio. In the second part we studied the use of chiral auxiliaries in the A3-coupling reaction to induce the asymmetry. Therefore, several compounds were tested as optically pure oxazolines and L-proline derivatives.

Le développement d'une nouvelle voie de synthèse de poly(éther cétone cétone),polymères thermostables, a été étudiée pour des matériaux composites à matrice thermoplastique obtenus par le procédé de moulage par injection de résine RTM. Pour cela,nous nous sommes orientés vers une polymérisation par couplage réactif entre des monomères difonctionnels et des agents de couplage. Neuf monomères X-EKKE-X avec différentes extrémités réactives ont été synthétisés par acylation de Friedel-Crafts ou substitution nucléophile aromatique puis caractérisés structurellement et thermiquement.Des essais de couplage à partir de monomères à extrémités COOH sur des bisoxazoline sont permis la synthèse en masse de quatre polymères, semi-cristallins ou amorphes, de faibles masses molaires. A travers l'étude du comportement thermique de molécules modèles, une fragilité thermique à partir de 250°C a été mise en évidence pour ces polymères et attribuée au pont ester-amide entre deux unités EKKE. / A new synthetic route to poly(ether ketone ketone), thermostable and semi-crystalline polymers, has been studied towards composite materials with a thermoplastic matrix obtained by a resin transfer molding process (RTM). This original synthesis was conducted by coupling reactions between difunctionals monomers and coupling agents. Nine X-EKKE-X monomers with different reactive extremities have been synthesized by Friedel-Crafts acylation or nucleophilic aromatic substitution. Thermal and structural properties were thoroughly investigated. Four polymers with semi-crystalline or amorphous morphologies and low molecular weights were obtained by coupling reactions between monomers with COOH functional extremities and bisoxazolines. Through the study of the thermal behavior of models molecules, a thermal fragility was highlighted for these polymers from 250°C and assigned to the amide-ester bridge between two EKKE units.

A presente dissertação de mestrado descreve estudos sobre as reações multicomponentes A3 na versão assimétrica. Diversas metodologias foram empregadas visando a obtenção de propargilaminas opticamente ativas, que são blocos sintéticos versáteis na preparação de compostos bioativos. O trabalho foi dividido em duas partes. Na primeira parte, estudou-se a utilização de aminas opticamente puras como materiais de partida para a reação tricomponente A3. Neste caso, foi utilizada a 2-metilpropan-2-sulfinamida como amina principal, no entanto, o produto de acoplamento não foi obtido, mesmo em diversas condições testadas. Outras aminas opticamente puras, como a (S)- metilbenzilamina e aminas derivadas de amino ácidos, também foram testadas. Os resultados, quanto às razões diastereoisoméricas e rendimento, foram satisfatórios quando aminas derivadas de amino ácidos foram utilizadas, principalmente quando o éster metílico da L-polina foi empregado como fonte de amina, que levou a formação do produto em bom rendimento e uma razão enantiomérica de 15:85. Na segunda parte do trabalho estudou-se a utilização de auxiliares quirais, na reação de A3, como indutores de assimetria. Para tanto, diversos compostos foram testados como oxazolinas opticamente puras e derivados de L-prolina. / This masters thesis describes studies for the asymmetric version of A3 multicomponent reactions. Several methodologies were employed in order to obtain optically active propargylamines, which are versatile synthetic building blocks on the preparation of bioactive compounds. The work was divided into two parts. In the first part, we investigated the use of optically pure amines as starting materials for the A3-coupling reaction. In this case, we used the 2-methylpropan-2-sulfinamide as the main amine, however, the coupling product was not obtained, even under several reaction conditions. Other optically pure amines such as (S)-methylbenzylamine and amines derived from amino acids, were also tested. The yields and diastereomeric excess were satisfactory when amines derived from amino acids were employed, especially when the methyl ester of L-poline was used as amine source, which led to the formation of the product in good yield and diastereoisomeric ratio. In the second part we studied the use of chiral auxiliaries in the A3-coupling reaction to induce the asymmetry. Therefore, several compounds were tested as optically pure oxazolines and L-proline derivatives.