Dissertations / Theses on the topic 'Binaphtyle'

Ces travaux de recherches s'articulent autour de la synthèse et de l'étude des propriétés de nouvelles architectures moléculaires hélicoïdales. La première partie concerne la synthèse d'une nouvelle plateforme moléculaire à motif diarylnaphtalene et son utilisation pour la synthèse de plusieurs molécules hélicoïdales polysubstituées. Ainsi a partir de ces briques moléculaires, des 6,11-diamino-[6]-hélicènes et des cyclooctahélicènes ont été prépares, selon une séquence réactionnelle simple et courte. Une seconde partie est dédiée à l’évolution de cette sequence réactionnelle dont l’étape clé est une substitution électrophile aromatique. En effet, a partir d’un motif binaphtyle ou ortho-terphényles, il a été possible d’orienter sélectivement l’accès a des molécules planes ou hélicoïdales. Ce chapitre est conclu par leur utilisation dans la construction de nouveaux clusters de bores dérives de l’ortho-carborane. En plus de la synthèse et de la caractérisation, les propriétés de ces nouvelles molécules ont été étudiées (arrangement a l'état solide, conformation en solution) et de nombreux calculs théoriques ont été entrepris afin d'expliquer certaines sélectivités observes ou de déterminer les barrières de racémisation des édifices synthétises
This work is dealing with the synthesis and properties of new helical molecular architectures. The first part is dedicated to the synthesis of a new molecular platform based on diarylnaphthalene compounds and their use as key starting material new polysubstituted molecules such as 6,11-diamino-[6]-helicenes and cyclooctahelicenes have been elaborated using a short and facile reaction sequence;. In the second part the study aims to control the aromatic electrohpilic subtitution key step. In this context, starting from binaphthyl or terphenyl patterns, we were able to selectively control the outcome of the reaction and obtain planar or helical architectures. Finally, novel architectures have been obtain by mixing some of these molecules with valuable boron cluster derivatives. In addition to the synthesis, physical properties of these new architectures have been studied (crystal packing, conformation in solution…) and theorical calculations investigated in order to explain some of the observed selectivities and to determine racemization barriers

Nous avons étudié en détail la photodynamique VUV et le PECD (un effet chiroptique intense) de l'acide aminé Proline (Pro) en phase gaz, seul acide aminé naturel contenant un cycle pyrrolidine. Plusieurs températures ont été utilisées pour faire varier la population de conformères de Pro native, afin d'effectuer une analyse complète des conformères à l'aide des calculs PECD CMS Xα, et ce faisant de raffiner le paysage conformationnel. Le signe des asymétries, similaire au cas de l’alanine, renforce le scenario astrophysique en lien avec l’homochiralité, sans contraintes de température. De plus, nous avons étudié, le PECD sur des acides aminés aromatiques (tryptophane & tyrosine), des chromophores importants des protéines. Nous avons également étendu la portée de nos études de PECD vers de grands édifices moléculaires tels que des dipeptides à base d’acides aminés (c-Pro-Pro, Gly-Pro et Pro-Gly), jusqu’à des systèmes beaucoup plus complexes comme des nanoparticules homochirales (Pro, Trp et Tyr), pour tester, phénoménologiquement, les limites de sensibilité du PECD par rapport à la complexité moléculaire. Enfin, nous présentons pour la première fois l'étude d'une famille de 3 molécules à chiralité axiale (dérivées de binaphtyles), dont nous avons notamment étudié l'influence de l'angle diédral sur le PECD
We studied in great details, the VUV photodynamics and PECD (an intense chiroptical effect) of the gas phase amino acid Proline (Pro), the only naturally occurring amino acid containing a pyrrolidine ring. Several temperatures were used to vary the conformer population of the nascent Pro in order to perform a comprehensive conformer analysis of the PECD with the help of CMS-Xα PECD calculations allowing to refine the conformational landscape. The sign of the chiral asymmetry, similar to the one of alanine, strengthen the astrophysical scenario in link to the origin of homochirality, without any temperature constraints. We studied also, the PECD of two aromatic amino-acids (tryptophan & tyrosine), which are important chromophores of proteins. We extended the scope of our PECD studies to larger amino-acids-based systems, such as dipeptides (c-Pro-Pro, Gly-Pro and Pro-Gly), up to much more complex systems like homochiral nanoparticles (Pro, Trp and Tyr), to test, phenomenologically, the limits of sensitivity of PECD with respect to molecular complexity. Finally, we present for the first time the study of a family of 3 molecules with axial chirality (binaphthyls derivatives), of which we studied in particular the influence of the dihedral angle on the PECD

Thesis presented to the CAPE PENINSULA UNIVERSITY OF TECHNOLOGY for the degree of MASTER OF TECHNOLOGY Department of Chemistry, Cape Peninsula University of Technology, Cape Town Campus, Zonnebloem, October 2013
In this thesis, the complexation behaviour of the host compounds, 1,1’-binaphthyl- 2,2’-dicarboxylic acid (BNDA) and 1,1’-binaphthyl-2,2’-diol (BINOL) were investigated. These hosts are large, bulky and scissor shaped; they contain functionalities to selectively interact with other molecules. A series of small organic compounds, particularly amines, were used in the preparation of the complexes. BNDA formed three complexes with acyclic amines, two complexes with the cyclic amines and two complexes with a racemic amine in different solvents. All the complexes formed were salts. The amines used were diethylamine, di-nbutylamine, cyclohexylamine, dicyclohexylamine, and sec-butylamine. For the studies with the acyclic amines and cyclic amines, crystals were grown in methanol as a co-solvent. Similar experiments were conducted with BINOL. Successful complexation only occurred with cyclohexylamine and dicyclohexylamine respectively. An amine host, 1,1’-binaphthyl-2,2’- diamine (BINDIA) was also considered with acidic and amide guests to extend the study of the binaphthyl derivatives, but from the array of guests used, the host only formed an inclusion compound with dimethylacetamide (DMA). The structures of all the complexes were elucidated using single crystal X-ray diffraction. Thermal analysis was performed in order to determine the thermal stability of the complexes, including techniques such as thermogravimetry, differential scanning calorimetry and hot stage microscopy. The kinetics of desolvation was investigated for some of the complexes.

Although the chemical and physical properties of enantiomers are identical, they exhibit different biological activities. Therefore, one enantiomer often shows maximum therapeutic activity, but the other enantiomer may have no effect, inhibit the ability of the therapeutic form, or can even be harmful. Since enantiomers can be found in different area, such as drugs, pesticides, waste compounds, etc, it is important and necessary to develop simple, fast, low cost, and accurate methods for determination of enantiomeric composition. Xu and McCarroll have developed a method to determine enantiomeric composition by steady-state fluorescence anisotropy based on guest and host theory, where the guest is the chiral analyte, and the host is the chiral selector. The first part of this thesis is an extension of this study investigating different chiral analytes. The chiral selectors that were chosen for this study are different sizes of cyclodextrins, and the chiral analytes that were selected to examine are binaphthyl derivatives, which are 1, 1'-bi-2-napththol (BOH), 1, 1'-binaphthyl-2, 2'-diyl hydrogen phosphate (BNP), and propanol hydrochloride. β-cyclodextrin (CD) was found to be a better chiral selector for determination of BNP enantiomeric composition in this system. Moreover, the chiral selector that was better for determination of BOH and propanol hydrochloride enantiomeric composition in the study was found to be α-CD and γ-CD, respectively. A temperature study was carried out to investigate the best temperature for the determination of BNP enantiomeric composition with β-CD as the chiral selector, and 10 °C was found to be the best temperature in the system. Following an unexpected observation of new species found to be produced after light exposure, a detailed study was applied in order to determine the possible mechanism of the reactions and the identity of the various chemical structures. This investigation is of relevance since BNA is used in various applications and was mentioned in the second part of this thesis. Beside fluorescence spectroscopy, other techniques were applied in this study, such as laser desorption/ionization mass spectrometry (LSI-MS), ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance spectroscopy (NMR), and thin layer chromatography (TLC). There were 5 possible species that were determined when BNA in chloroform was exposed to 377 nm light, which are hypothesized as 7H-Dibenzo[c,g]carbazole (DBC), 7, 8-Diaza[5]helicene N.N'-Dioxide produced through oxidation and three additional compounds formed through excited state proton transfer (ESPT). Evidence supporting these hypotheses is discussed, as well as the need for further study to confirm the structures of the various species produced during light exposure.

La synthèse de plusieurs dérivés de l'acide cholique, mettant à profit les diverses possibilités de transformations régio-sélectives de ce composé, a permis de préparer différentes phases stationnaires chirales, afin d'évaluer, par chromatographie liquide haute performance, le potentiel énantiosélectif de ce stéroïde greffé sur silice. Le choix des différentes structures tient compte de l'introduction d'une oléfine terminale, nécessaire au greffage sur silice. Trois phases stationnaires, préparées à partir de sélecteurs représentatifs de l'ensemble des précurseurs retenus, se sont montré énantiosélectives, à des degrés divers. La phase stationnaire la plus apte à la discrimination chirale a permis l'optimisation des conditions de phase mobile et le choix de différentes séries de solutés appartenant à plusieurs classes de composés (aminoalcools, amines, hydantoïnes, composés à motif 1,1'-binaphthyle), utilisés pour l'étude des mécanismes de séparation chirale. Le sélecteur le plus énantiosélectif est également employé pour une étude comparative de trois modes de greffage. La méthode de greffage la mieux adaptée est appliquée à la préparation de l'ensemble des phases stationnaires, dont l'énantiosélectivité est évaluée par chromatographie en phase liquide, dans les conditions de phase mobile définies, avec les séries de solutés sélectionnés. L'étude des mécanismes de reconnaissance met en évidence le rôle prépondérant des interactions par liaisons hydrogène. Des études complémentaires, centrées sur un couple soluté/phase stationnaire choisi, ont permis la détermination de la stoechiométrie 1 : 1 du complexe, et des grandeurs thermodynamiques liées à sa formation au sein de la colonne chromatographique. Une approche des mécanismes de reconnaissance chirale par modélisation moléculaire confirme le rôle prépondérant des liaisons hydrogène dans le processus de discrimination énantiomérique.

Après une revue bibliographique des phases stationnaires chirales (PSC) en chromatographie en phase gazeuse (CPG) et en phase liquide haute performance (CLHP), la synthèse et l'étude de nouvelles PSC dérivées de molécules d'oxazolines sont présentées parallèlement dans ces deux techniques chromatographiques. La synthèse de polyhydrogénométhylsiloxanes (PHMS) de rapports d'unités siloxanes différents et le greffage d'oxazolines insaturées par réaction d'hydrosilylation ont permis d'accéder à différents polysiloxanes chiraux. La caractérisation des PHMS et des polysiloxanes chiraux est réalisée en IR, RMN 1H, GPC, analyse élémentaire et pyrolyse couplée à la spectrométrie de masse. Le dépôt de ces polymères chiraux sur paroi capillaire de silice a permis d'obtenir la séparation de quelques énantiomères d'aminoacides dérivés en CPG. D'autre part, les résolutions d'énantiomères de dérivés d'aminoacides, d'amines et du binaphtol sont obtenues par chromatographie liquide en phase normale sur des PSC derivées d'oxazolines greffées sur silice par des liaisons siloxane Si-O-Si-C ou par des liaisons silane Si-C. L'importance relative des interactions PSC oxazolines-solutés est étudiée grâce à l'association des deux techniques chromatographiques. De plus, un modèle de reconnaissance chirale est proposé sur l'une des phases stationnaires oxazolines en CLH

Les recherches présentées dans ce mémoire s’inscrivent dans l’application de la « Chimie Verte » en Sciences Séparatives. En effet, les Liquides Ioniques représentent une nouvelle génération dans la famille des «solvants verts» avec leurs propriétés physico-chimiques uniques et ils apparaissant particulièrement bien adaptés aux techniques électrocinétiques. Ainsi, nous nous sommes proposés de tester les potentialités de Liquides Ioniques originaux à base respectivement de phénylcholine et d’éthylcholine comme des nouveaux milieux dans ce contexte par l’Electrophorèse Capillaire. Deux thématiques ont été suivies : la première étant consacrée à l’analyse de cations alcalins et alcalino-terreux par Electrophorèse Capillaire en détection UV indirecte, le Liquide Ionique jouant conjointement le rôle d’électrolyte de séparation et de chromophore, générant le signal de fond ; la seconde se rapportant quant à elle l’étude de la enantioséparations d’atropoisomères originaux de la série du binaphtol, par Electrophorèse Capillaire au moyen de cyclodextrines (CD-CZE), en présence ou non de Liquides Ioniques chiraux. C3a and C5a receptors in the remodeling and development of tissues
This work takes its place in the application of «Green Chemistry» in Separation Sciences. Indeed, the Ionic liquids represent a new generation in the family of green solvents with their unique physicochemical properties and they appear particularly well adapted to the electrokinetic techniques. Thus, we intended to test the potentialities of original Ionic Liquids based on phenylcholine and ethylcholine respectively, as new mediums in this context by Capillary Electrophoresis. Two sets of themes were envisaged: the first was related to the analysis of alkaline and alkaline-earth cations by Capillary Electrophoresis, with indirect UV detection, the Ionic Liquid played simultaneously the role of the running electrolyte and the chromophore, generating the background signal. While the second was referred to the study of the enantioseparations of original binaphthols atropisomers, in Capillary Electrophoresis by means of cyclodextrins (CD-CZE), in presence or not of chiral ionic liquids

Ce travail de thèse est dédié au développement des deux familles de complexes chiraux binaphtolates de terres rares et leur application en catalyse asymétrique dans les réactions d’addition de Michael, de Henry, de Strecker et d’hydroalkoxylation. La préparation d’une nouvelle famille de complexes chiraux bisbinaphtolates de terres rares a été optimisée. Ces nouveaux complexes ont été entièrement caractérisés grâce à des analyses RMN, IR, de spectroscopie de masse et des études de DRX de monocristaux isolés. Après une étude de stabilité, nous avons pu montrer que ces nouveaux complexes de terres rares peuvent être pesés à l’air libre et utilisés dans des réactions asymétriques sans dégazage des réactifs ni des solvants. Les comportements catalytiques de ces nouveaux complexes hétérobimétalliques ont été étudiés en détail dans des réactions énantiosélectives de Henry, de Strecker et d’addition de Michael. Une température d’isoinversion et un effet non linéaire ont notamment été mis en évidence dans la réaction d’addition de Michael de malonates sur des énones conduisant à des produits énantioenrichis avec des excès énantiomériques allant jusqu’à 83%. Une seconde famille de complexes monobinaphtolate monoalkyl de terres rares a été synthétisée et complètement caractérisée. Une structure DRX de ce type de complexe a pu être obtenue pour la première fois. Ces complexes ont été évalués dans des réactions de Strecker et d’hydroalkoxylation. Concernant cette dernière, la sélectivité a tout d’abord été étudiée avec ces complexes dans le cas des allènes et un mécanisme a pu être proposé. D’autre part, les premiers exemples d’hydroalkoxylation asymétrique d’alcènes, catalysés par ces complexes monobinaphtolate monoalkyl de terres rares, ont pu être décrits
This thesis is mainly devoted to the development of two families of rare earths chiral binaphtolate complex and their application in asymmetric catalysis such as Michael addition, Henry reaction, Strecker reaction and hydroalkoxylation reaction. At first, the preparation of a new family of rare earth bisbinaphtolate complexes has been optimized with complete characterizations including NMR, IR, mass spectroscopy and XRD studies on isolated single crystals. These new rare earths complexes are relative stable which can be used under air condition. The catalytic behavior of these new heterobimetallic complexes have been studied in detail: an isoinversion temperature was determined and the nonlinear effect was observed for asymmetric Michael additions of malonates on enones wich lead products with enantiomeric excess up to 83%. Secondly, a family of rare earth monobinaphtolate monoalkyl complexs has been synthesized and characterized. The first XRD structure of this family of complex was obtained. Steric substitutions of binaphtolate ligands on position 3,3’ have been proven to be essential for the formation of these complex. The selectivity of reaction of hydroalkoxylation of allene was studied with a proposed mechanism. First examples of asymmetric hydroalkoxylation of alkene catalyzed by rare earth complexes have been achieved by our rare earth monoalkyl monobinaphtolate complex

La complexation du fer est un probleme biologique fondamental, resolu chez les microorganismes par les siderophores, ligands de bas poids moleculaire aptes a solubiliser selectivement les ions ferriques, puis a livrer le metal a la cellule via des processus de reconnaissance complexes. Les siderophores synthetiques presentent a la fois un interet pour l'etude du metabolisme du fer et peuvent avoir des applications therapeutiques dans le cas des surcharges en fer. Un nouveau siderophore synthetique tripodal, base sur trois sous-unites chelatantes de type o,o'-dihydroxybiphenyle, a ete prepare et ses proprietes complexantes vis-a-vis des ions ferriques ont ete decrites. Les memes sous-unites chelatantes ont ete integrees a un systeme macrobicyclique dont la synthese est detaillee. D'autre part, la premiere cavite moleculaire chirale a six hydroxyles convergents est preparee a partir de sous-unites de type o,o'dihydroxybinaphtyle. Lors de la complexation de fe#3#+, ga#3#+ et cr#3#+, ce ligand permet un controle stereospecifique de la chiralite ( ou ) du centre metallique octaedrique cree. Ceci est mis en evidence par rmn et dichroisme circulaire et etaye par des calculs de mecanique moleculaire

New liquid crystals have been synthesized and their transition phases have been studied. It was found that a family of (-)-2-methyl 2R,3S-epithio-4'-alkoxybiphenyl pentanoates are liquid crystals but a similar system of ( + )-2-methyl 2S,3R-epoxy-4'-alkoxybiphenyl pentanoates are not. Of the liquid crystals, MEAOBP-S-7 exhibits smectic A and B phases; MEAOBP-S-8 and MEAOBP-S-9 show only the smectic B phases; MEAOBP-S-10 shows a monotropic chiral smectic C phase. This distinction is in agreement with the argument that the internal dipolar interaction of the molecule plays an important role in determining liquid crystalline behaviour of this ester system. The reaction rate of the racemization of optically active binaphthyl can be moderately increased in the presence of finely divided titanium dioxide (anatase) powder. This first order catalyzed reaction has a proportional relationship with the concentrations of both the catalyst and the binaphthyl. The catalyzed reaction can be poisoned permanently by the addition of polynuclear aromatic compounds and the poisoning efficiency is dependent of the number of the aromatic rings the poison posesses. By comparison with the catalyzed racemizations of binaphthyl by platinum, nickel and carbon and from the kinetic and mechanistic studies on the titanium dioxide catalyzed racemization, we conclude that (1) this catalytic phenomenon is common among heterogeneous inorganic solids and can be extended to other simple reactions, and that (2) the mechanism of the catalysis probably involves a radical anion intermediate.
Science, Faculty of
Chemistry, Department of
Graduate

碩士
國立交通大學
應用化學系碩博士班
100
Binaphthylcrown-6 derivative of calix[4]arene at the 1,2-position of the lower rim was synthesized, which followed by attaching two carboxylate groups at the remaining phenols gave compound (R)-(+)-32. The synthetic route needed 5 steps and overall yield was about 15%. Structures of all products were confirmed by 1H-, 13C NMR and FAB-mass. We then investigated the complexation process of the title compound (R)-(+)-32 with (R/S)-1-phenylpropan-1-amine (R/S)-38 and (R/S)-2-amino-2 -phenylethanol (R/S)-39 via 1H NMR titration. From these data, we applied the nonlinear least-squares regression to calculate the association constants, and they are 83.7 M-1 ((R)-38), 8.5 M-1 ((S)-38), 23.8 M-1 ((R)-39), and 12.0 M-1 ((S)-39), respectively. The complexation ratio was determined to be H:G = 1:2 by Job plot using 1H NMR. Furthermore, theoretical calculation using the Gussain View was carried out which provided possible binding modes for the host (R)-(+)-32 and guests. Due to the large error for Ka determined by 1H NMR titration, we conducted the chiral recognition experiment by Narumi—Hattori method for (R/S)-38、(R/S)-44、(R/S)-45 and (R/S)-46. Comparing (R)-(+)-32 with 23 in ??飣(S-R), we found the ??飣(S-R) of (R)-(+)-32 were smaller than the ??飣(S-R) of 23. It showed (R)-(+)-32 had little chiral recognition ability toward chiral amines.

Tese de doutoramento em Química, na área de Química Macromolecular, apresentada ao Departamento de Química da Faculdade de Ciências e Tecnologia da Universidade de Coimbra
The work presented in this dissertation was guided toward the synthesis of BINOL-based monophosphite ligands with helical structures and C3 symmetry, containing different OR groups, for development of new homogeneous catalysts. Chapter 1 presents a critical review of the literature, essentially focused on the main themes developed in the course of the experimental work. In Chapter 2 the synthesis of a family of enantiomerically pure monophosphite ligands containing three units of (S)- or (R)-BINOL derivatives is described. Their syntheses involved BINOL monoetherification, via Mitsunobu reaction, with different alcohols, as methanol, benzyl alcohol, diphenylmethanol and adamantan-1-ol. For the synthesis of a monoester analogue, the reaction of BINOL with adamantanoyl chloride was performed. From phosphorylation of the resulting monoprotected BINOL derivatives with PCl3, the synthesis of chiral tris-binaphthyl monophosphites was achieved, with yields ranging from 74-83%. In this section, the preparation of 2'-(benzyloxy)-3-methyl-1,1'-binaphthyl-2-ol and 2'-(benzyloxy)-3'-methyl-1,1'-binaphthyl-2-ol, is also described. In Chapter 3, studies regarding the application of chiral tris-binaphthyl monophosphite ligands, previously developed, are presented in asymmetric catalytic reactions, including hydroformylation and hydrovinylation. Concerning the hydroformylation of aryl olefins, the studies indicated that, only in the case of disubstituted double bonds, the activity and selectivity of Rh(I)/monophosphite complexes strongly depend on the structure of the OR group at the ligand, with Rh/tris[(R)-2'-(1-adamantyloxy)-1,1'-binaphthyl-2-yl]phosphite being the most active (TOF=260 h-1, 84% regioselectivity), and Rh/tris[(R)-2'-(benzyloxy)-1,1'-binaphthyl-2-yl]phosphite being the most regioselective catalytic system (TOF=197 h-1, 89% regioselectivity). These works were further supplemented with kinetic studies involving the catalytic system Rh/tris[(R)-2'-(benzyloxy)-1,1'-binaphthyl-2-yl]phosphite in the hydroformylation of trans-β-methylstyrene. Despite the high activities and selectivities, none of the catalytic systems has achieved enantiomeric excesses above 20%. Furthermore, Rh/monophosphite catalysts were able to promote the diastereoselective hydroformylation of compounds with potential biological activity, namely the steroid 17β-acetoxyandrost-4-ene, achieving as major product 4β-formyl-17β-acetoxy-5β-androstane (86% chemoselectivity, 100% regioselectivity and 72% diastereoselectivity). The synthesis and characterization of allyl-palladium/monophosphite complexes (in 50-71% isolated yields) was performed, as well as their evaluation in the asymmetric hydrovinylation of styrene. All catalytic systems led to high chemoselectivities for 3-phenylbut-1-ene (>85%) without occurrence of homodimerization reactions and with only slight isomerization. In general, the palladium complexes containing BINOL-based monophosphite derivatives with ether groups gave moderate to high enantioselectivities (40-71% ee). However, the most remarkable result was achieved with the complex containing the ligand tris[(S)-2’-(1-adamantanoate)-1,1'-binaphthyl-2-yl]phosphite, which resulted in one of the most enantioselective palladium-based catalytic systems reported so far, in hydrovinylation of styrene, with 92% ee. In Chapter 4, optimization studies of palladium-catalyzed aminocarbonylation reactions were carried out, aiming the synthesis of carboxamides, keto-carboxamides and bis-carboxamide dimers with potential biological activity. The aminocarbonylation of iodobenzene and 1-iodo-cyclohexene as model substrates was performed using palladium complexes formed in situ with the tris-binaphthyl monophosphite ligands, leading to active catalytic systems. After optimization of reaction conditions towards the selective formation of keto-carboxamides, the synthesis and isolation of cyclohexenylglyoxylamides with unprecedented structures, N-tert-butyl-2-(cyclohex-1-enyl)-2-oxoacetamide, 1-cyclohexenyl-2-morpholinoethane-1,2-dione and 1-cyclohexenyl-2-(piperidin-1-yl)ethane-1,2-dione was performed, with isolated yields varying from 60 to 66%. Next, using Pd/triphenylphosphine catalysts, the synthesis of a family of monocarboxamide-carbasugars was developed from the aminocarbonylation of bromo- or iodo-conduritol derivatives, with isolated yield varying from 50 to 85%. Furthermore, it should be highlighted the pioneering application of this catalytic reaction for the synthesis of a series of dicarboxamides, by using, for the first time, different diamines, as nucleophiles. This atom economic methodology allowed synthesize, in a single step, relevant molecules such as steroid dimers containing dicarboxamide bridges with diverse structures, in isolated yields up to 95%. In Chapter 5, the techniques and instrumentation used are described, as well as the characterization of all products synthesized during the experimental work.
O trabalho apresentado nesta dissertação orientou-se no sentido de desenvolver métodos de síntese de monofosfitos derivados do BINOL contendo diferentes grupos OR, com estrutura helicoidal e simetria C3, para preparar novos catalisadores para reações homogéneas. No Capítulo 1 apresenta-se uma revisão crítica da literatura focalizada essencialmente nas principais temáticas desenvolvidas no decurso do trabalho experimental. No Capítulo 2 encontram-se descritos os métodos de síntese de uma família de monofosfitos enantiomericamente puros contendo três unidades de derivados de (S)- ou (R)-BINOL. A sua síntese iniciou-se com a monoeterificação do BINOL com diferentes álcoois, via reação de Mitsunobu, nomeadamente com metanol, álcool benzílico, difenilmetanol e adamantan-1-ol. Para a síntese de um derivado monoesterificado, recorreu-se à reação do BINOL com cloreto de adamantanoilo. Da reação dos resultantes derivados do BINOL monoprotegidos com PCl3, deu-se uma importante contribuição para a síntese de monofosfitos quirais com estrutura helicoidal, com rendimentos compreendidos entre 74-83%. Neste capítulo descreve-se ainda a preparação de 2'-(benziloxi)-3-metil-1,1'-binaftil-2-ol e 2'-(benziloxi)-3’-metil-1,1'-binaftil-2-ol. No Capítulo 3, apresentam-se os estudos da aplicação dos monofosfitos quirais desenvolvidos neste trabalho em reações de catálise assimétrica, nomeadamente de hidroformilação e hidrovinilação. No que diz respeito à hidroformilação do estireno e derivados, os estudos indicaram que apenas no caso de olefinas dissubstituídas, a atividade e seletividade dos complexos de ródio/monofosfito depende fortemente na estrutura do grupo OR do ligando, sendo o sistema catalítico Rh/tris[(R)-2'-(1-adamantiloxi)-1,1'-binaftil-2-il]fosfito o mais activo (TOF=260 h-1, 84% de regiosseletividade) e o Rh/tris[(R)-2'-(benziloxi)-1,1'-binaftil-2-il]fosfito o mais regiosseletivo (TOF 197 h-1, 89% de regiosseletividade). Estes trabalhos foram ainda complementados com estudos cinético envolvendo o sistema catalítico Rh/tris[(R)-2'-(benziloxi)-1,1'-binaftil-2-il]fosfito na hidroformilação de trans-β-metilestireno. Apesar das elevadas atividades e seletividades, nenhum dos sistemas catalíticos conduziu à obtenção de excessos enantioméricos superiores a 20%. Estes estudos permitiram ainda promover a hidroformilação diastereoseletiva de compostos com potencial atividade biológica, nomeadamente, do esteróide 17β-acetoxiandrost-4-eno, tendo-se obtido como produto maioritário 4β-formil-17β-acetoxi-5β-androstano (86% quimiosseletividade, 100% de regiosseletividade e 72% de diastereoseletividade). Os estudos prosseguiram com a síntese e caracterização de complexos de paládio-alilo/monofosfito (com rendimentos 50-71%) e sua avaliação na reação de hidrovinilação do estireno. Todos os sistemas catalíticos conduziram a uma elevada quimioseletividade para a formação de 3-fenibut-1-eno (> 85%), sem ocorrência de reações homodimerização e baixa isomerização. Salienta-se que, de uma forma geral os complexos de paládio contendo fosfitos derivados do BINOL com grupos éter deram origem a enantioseletividades moderadas a altas (40-71% ee), enquanto o complexo contendo o ligando tris[(S)-2'-(1-adamantanoato)-1,1'-binaftil-2-il]fosfito deu origem a um dos sistemas de paládio mais enantiosseletivos descritos na literatura para a hidrovinilação do estireno (92% ee). No Capítulo 4, efetuaram-se estudos de otimização de reações de aminocarbonilação catalisadas por complexos de paládio/ligando de fósforo, tendo em vista a síntese de produtos com potencial atividade biológica, nomeadamente carboxamidas, ceto-carboxamidas e dímeros de bis-carboxamidas. Após otimização da reação, usando como substratos modelo iodobenzeno e 1-iodo-ciclo-hexeno, e com catalisadores de paládio modificados com os monofosfitos sintetizados neste trabalho, foi possível isolar e caracterizar os compostos do tipo ceto-carboxamida, N-tert-butil-2-(ciclohex-1-enil)-2-oxoacetamide, 1-ciclohexenil-2-morpholinoetano-1,2-dione, e 1-ciclohexenil-2-(piperidin-1-il)etano-1,2-dione com rendimentos isolados entre 60-66%. Utilizando catalisadores de Pd/trifenilfosfina, desenvolveu-se também a síntese de uma família de monocarboxamidas derivadas de açúcares, através de reações de aminocarbonilação de derivados de bromo- ou iodo-conduritol, com rendimentos de produtos isolados entre 50-85%. É de salientar, o uso desta reação catalítica para a preparação de uma série de dicarboxamidas, utilizando, pela primeira vez, diaminas como nucleófilos. Esta metodologia, de elevada economia atómica, permitiu sintetizar, num só passo, moléculas tão relevantes quanto dímeros de esteróides contendo pontes de dicarboxamida com estruturas diversificadas com rendimentos de produtos isolados até 95%. No Capítulo 5, são descritas as técnicas utilizadas bem como as caracterizações de todos os produtos sintetizados no decorrer do trabalho experimental que conduziu à escrita desta dissertação.
FCT - SFRH/BD/60499/2009

Research directed toward the design, synthesis, and screening of binaphthyl ketones for catalytic asymmetric epoxidation of alkenes is reported. To date, an easily accessible and recyclable catalyst that tolerates a wide structural variety of unfunctionalized alkenes has not been developed. It has been discovered that fluorinated chiral binaphthyl ketones catalyze the asymmetric epoxidation of alkenes with a high degree of enantiocontrol. A series of five binaphthyl ketone catalysts with variable distribution of fluorine atoms alpha to the carbonyl were synthesized. These catalysts were screened in the asymmetric epoxidation of trans-beta-methyl styrene. A trend of epoxidation efficiency as a function of alpha fluorination was revealed. Although, several of these catalysts performed well in the screening process, the most accessible was an alpha-fluorinated binaphthyl ketone. This ketone epoxidized trans-beta-methylstyrene to trans-beta-methylstyrene oxide with 57% conversion in 80% enantioselectivity. In order to improve conversion and enantioselectivity with this catalyst, a study of the various reaction parameters such as pH, organic cosolvent, and the amount of primary oxidant used was undertaken. During this study a significant dependence on these parameters was revealed, particularly, that of the organic cosolvent. Optimization of these conditions has led to dramatic improvements in the epoxidation efficiency of alpha-fluorinated binaphthyl ketone. This efficiency is highlighted in the epoxidation of trans -beta-methylstyrene to trans-beta-methylstyrene oxide with 100% conversion and 94% ee (from 57% conversion and 80% ee). Moreover, a substrate study suggests the optimized solvent allows for a pi-stack interaction which contributes to high enantioselectivity and conversions for both 1,1-disubstituted and terminal alkenes.

碩士
國立交通大學
應用化學研究所
98
In this thesis, a series of binaphthyl-derived chiral calix[4]crowns were synthesized and their recognition abilities toward chiral amino alcohols and metal ions were studied. We have synthesized a series of (S)-(-)-binaphthyl-appended calix[4]crown-n ether (n = 6, 8) 41-49, which were substituted with mono- or proximal bis-carboxyl groups. The complexation properties of binaphthyl hosts (S)-(-)-44a-b and (S)-(-)-49a toward chiral amines, amino alcohols, alcohols and diols 50-57 were investigated by the UV-visible, fluorescence and CD spectroscopies. Possible binding modes of these chiral hosts toward amino alcohols 50 and 52-55 were discussed. The association constants (Kass)63 of 44a, 44b or 49a with chiral guest molecules were calculated by the nonlinear fitting method of the fluorescence spectra. Furthermore, the binding ratio of 44a-b and 49a with chiral guests were determined by Job plots. The results showed that the binding abilities of 44a toward guests decrease in the order of (S)-53 (S)-55 ? (S)-54 ? (S)-52 ? (S)-50 (S)-51 (S)-56 ? (S)-57. Furthermore, 44a exhibited a great performance for 53 in enantiomeric discrimination (Kass(R) = 3.41*104 M-1, Kass(S) = 3.21*105 M-1, Kass(R)/Kass(S) = 1/9.41). The comparisons of these complexes would gives an insight into the chiral recognition.

碩士
國立交通大學
應用化學系碩博士班
101
How can we understand crystal structure besides employing X-ray diffraction analysis? Low-frequency (LF) Raman spectra provide a wealth of precious information on crystal structure and orientation and can potentially be a complementary approach to the conventional X-ray diffraction method. However, observation of LF Raman spectra is very challenging due to severe interference of gigantic Rayleigh scattering. In this study, the author uses a laboratory-built LF Raman spectrometer that has the ability to observe Raman signals down to 9.8 cm-1. Because this apparatus is combined with a confocal microscope, it has become feasible to perform space-resolved measurements of crystals under the microscope for in-situ crystal structure analysis. Here, the author demonstrates this novel approach by studying crystal polymorphs of 1,1′-binaphthyl. This biaryl compound occurs as two crystal polymorphs with different dihedral angles between the two naphthyl groups: namely, the cisoid (C) and transoid (T) forms. As the C form is heated up, it gradually transforms to the T form via sublimation and subsequent recrystallization. In this thesis, the author presents tracing of this transformation dynamics and LF Raman imaging that visualizes the spatial distribution of the C and T forms after the transformation takes place. The only effective way to distinguish between the C and T forms by high-frequency Raman bands would be to calculate the intensity ratio for a pair of marker bands (510/532 cm-1). However, the two forms show much more distinct spectral patterns in the LF region. For example, the C form shows the strongest band at 100 cm-1, whereas the T form shows the most intense band at 26 cm-1. Thus, these two LF bands were chosen as markers to selectively probe different crystal polymorphs that coexist in proximity. In sharp contrast with the intensity-ratio image, the LF Raman images at 100 and 26 cm-1 show markedly high contrast and clearly discriminate one crystal form from the other. Moreover, we observed inhomogeneous distribution patterns in the LF Raman images, suggesting different crystal orientations within an apparent single crystal. Our results show that LF Raman spectroscopy and imaging should be a facile yet powerful addition to the toolbox for crystal structure analysis.

Les ligands de carbènes N-hétérocycliques (NHC) qui possèdent une symétrie C1 attirent beaucoup l’attention dans la littérature. Le présent projet de recherche propose de synthétiser une nouvelle série de ligands NHC C1-symétriques avec deux groupements N-alkyles qui exploitent un relais chiral. Un protocole modulaire et efficace pour la synthèse des sels d’imidazolium chiraux qui servent comme préligands pour les NHC a été développé. Quelques-uns de ces nouveaux ligands ont été installés sur le cuivre et de l’or, créant de nouveaux complexes chiraux. Les nouveaux complexes à base de cuivre ont été évalués comme catalyseurs pour le couplage oxydatif de 2-naphthols. Les ligands C1-symmétriques ont fourni des meilleurs rendements que les ligands C2-symmétriques. Au cours de l’optimisation, des additifs ont été évalués; les additifs à base de pyridine ont fourni des énantiosélectivités modérées tandis que les additifs à base de malonate ont donné des meilleurs rendements de la réaction de couplage oxydatif. Ultérieurement, les additifs à base de malonate ont été appliqués envers l’hétérocouplage de 2-naphthols. Le partenaire de couplage qui est riche en électrons est normalement en grand excès à cause de sa tendance à dégrader. Avec le bénéfice de l’additif, les deux partenaires de couplage peuvent être utilisés dans des quantités équivalentes. La découverte de l’effet des additifs a permis le développement d’un protocole général pour l’hétérocouplage de 2-naphthols.
A new class of C1-symmetric N-heterocyclic carbene (NHC) ligands has been developed. The new ligands exploit a biaryl methyne as a chiral relay, and an N-methyl group as a reactivity controlling element. The precursors for the new ligands were synthesized via a modular scheme that allows for facile diversification. Several of the new ligands were installed onto both copper and gold, generating mono N-heterocyclic carbene transition metal complexes. The new C1-symmetric copper complexes were tested as catalysts for the synthesis of binaphthols via the oxidative coupling of electron poor 2-naphthols. The new C1-symmetric ligands afforded higher yields than their C2-symmetric counterparts. During the course of the optimization, small molecule additives were found to modulate the reactivity of the copper catalyst. Pyridine additives, such as 2-picoline, were found to induce low to moderate enantioselectivity in the oxidative coupling reaction, while diethylmalonate was found to improve the reaction yield without affecting the selectivity. The malonate additive was employed in the catalytic oxidative heterocoupling of electronically dissimilar 2-naphthols. The electron-rich coupling partner is normally added in a large excess due to its tendency to degrade. When the malonate additive is used, the coupling partners can be used in equimolar quantities. The discovery resulted in the development of a general protocol for the additive assisted aerobic oxidative heterocoupling of electronically dissimilar 2-naphthols.

碩士
國立交通大學
應用化學系碩博士班
99
Low-frequency (<200 cm−1) Raman spectroscopy enables us to investigate intermolecular vibrations and lattice vibrations in condensed phase materials. However, low-frequency Raman signals can be almost completely buried under vast Rayleigh scattering. Typical commercial notch filters are not effective enough to eliminate Rayleigh scattering and do not allow us to reach the frequency region below 200 cm−1. Moreover, in order to keep track of dynamic processes such as phase transitions, multichannel detection rather than single-channel detection with a double/triple monochromator is required. In this work, by combining an I2 vapor-containing cell as a Rayleigh rejection filter with a multichannel Raman spectrometer, we have successfully recorded Raman spectra down to ~10 cm−1 in both Stokes and anti-Stokes sides simultaneously. The constructed Raman spectrometer has then been applied to crystalline 1,1'-binaphthyl, which has two different crystal polymorphs, that is, the cisoid and transoid forms. They show quite distinct spectral features in the low-frequency region (−200–+200 cm−1). Real-time tracing of the melting process of two crystalline forms have also been conducted with rapid heating. A series of Raman spectra have been recorded every 0.2 sec, in which spectral changes of low-frequency bands are clearly observed. In addition, the sample temperature has been accurately estimated from the Stokes/anti-Stokes intensity ratio of the Raman bands. Base on the temperature-dependent Raman spectra and theoretical calculations, the 26 cm−1 band of the transoid form and the 100 cm−1 band of the cisoid form are assigned to the torsional vibration and out-of-plane deformation of the C–C single bond, respectively. Moreover, the peak position of each low-frequency band has been determined from the fitting. We found that peak shifts due to thermal expansion for the transoid form are smaller than those for the cisoid form. Thus, intermolecular interactions in the transoid form are stronger compared with those in the cisoid form. This finding is consistent with their X-ray crystal structures.

L’intérêt pour les hélicènes s’est accru au fur et à mesure que de nouvelles applications pour ce genre de molécules ont été découvertes. Par contre, la recherche dans ce domaine a été limitée par le petit nombre de voies de synthèse de ces molécules, la plupart nécessitant une étape de résolution ou de séparation des énantiomères par HPLC à la fin de la synthèse. Le présent projet de recherche propose d’utiliser la réaction de fermeture de cycle asymétrique par métathèse d’oléfines (asymmetric ring closing metathesis, ARCM) pour effectuer une synthèse d’hélicène à la fois catalytique et énantiosélective. La synthèse énantiosélective du [7]hélicène a été effectuée à l’aide d’une résolution cinétique du précurseur racémique. Au cours de cette synthèse, nous avons été en mesure de démontrer l’efficacité de différents catalyseurs de métathèse chiraux en plus de démontrer l’effet de l’ajout de simples oléfines comme additifs à la réaction. De plus, nous avons formulé une hypothèse expliquant cet effet à l’aide du mécanisme de la réaction. Finalement, nous avons aussi montré l’effet du changement de solvant sur la sélectivité de la réaction. Au cours de ces travaux, nous avons également développé une nouvelle méthode de synthèse de binaphtols à l’aide d’une réaction de couplage oxydatif impliquant un catalyseur de cuivre. À l’aide d’études de réactivité, nous avons été en mesure de démontrer que le métal portait deux ligands N-hétérocycliques (NHC). Nous avons aussi observé que le catalyseur favorisait la formation de binaphtol non symétrique avec un groupement naphtol avec une densité électronique élevée et un autre groupement naphtol avec une faible densité électronique.
The interest in helicenes has increased as new potential applications have been proposed for these twisted conjugated aromatics. However, further research is limited by the lack of methods for the enantioselective synthesis of helicenes. The current traditional syntheses often conclude with a resolution, most often via separation on a chiral stationary phase. This thesis describes the development of new catalytic method for the synthesis of helicenes using ring closing metathesis (RCM) employing highly reactive Ru-based catalysts or commercially available catalysts and microwave heating. Furthermore, an enantioselective variant of the asymmetric ring closing metathesis (ARCM) reactions was developed for the synthesis of enantioenriched [7]helicene via a kinetic resolution protocol. The development of the kinetic resolution involved the preparation and screening of a number of novel chiral Ru-based olefin metathesis catalysts. During these studies, the beneficial effect of simple olefins additives on the selectivity of the reaction was observed and a hypothesis to explain these effects has been proposed. In addition, intriguing solvent effects were also observed. Lastly, this thesis describes the investigation of a new method for the preparation of binaphthol via an oxidative coupling with a novel copper catalyst bearing two N-heterocyclic carbene (NHC) ligands. It was demonstrated that the cationic catalyst allowed for the formation of mixed oxidative couplings between electron rich and electron poor 2-naphthols to form C1-symmetric binaphthol derivatives.

Le présent mémoire décrit la synthèse et l’utilité de complexes Cu-NHC. En premier lieu, la synthèse de complexes de cuivre porteurs de ligand(s) de type carbène-N-hétérocyclique (NHC) via une génération décarboxylative de carbènes sera présentée. En effet, de précédents rapports font état de l’utilisation de carboxylates d’imidazol(in)ium en tant que précurseurs carbéniques sous conditions thermolytiques. Ainsi, la présente étude montre l’utilisation de ces espèces zwitterioniques pour la synthèse de complexes de cuivre(I) mono- et bis-NHC comportant divers substituants et contre-ions. Une seconde partie du projet se concentrera sur l’évaluation de complexes Cu-NHC en tant que catalyseurs pour la synthèse de 2,2’-binaphtols via une réaction de couplage oxydatif de naphtols. L’objectif de ce projet de recherche est d’étudier les effets de variations structurales de différents complexes Cu-NHC afin de construire un processus catalytique plus efficace. Les effets de la structure du catalyseur sur la réaction de couplage ont été évalués en variant son contre-ion, le nombre de ligands NHC se coordonnant au cuivre, ainsi que la nature des substituants du ligand.
The present thesis describes the synthesis and utility of NHC-Cu complexes. First, the synthesis of N-heterocyclic carbene (NHC) copper complexes via the decarboxylative generation of carbenes is presented. Indeed, literature precedents reported that imidazol(in)ium-2-carboxylates may be used as carbene precursors under thermolytic conditions. As such, the present study demonstrates how zwitterionic carboxylates may be utilized in the formation of both mono- and bis-NHC Cu complexes with various substitution patterns and counterions. Secondly, the NHC-Cu complexes were evaluated for the synthesis of 2,2’-binaphthols via the oxidative coupling of naphthol derivatives. The objective of the study was to investigate how structural variations to various NHC-Cu catalysts may generate a more efficient catalytic process. Effects of the structure of the catalyst on the coupling reaction have been studied by varying the number of NHC ligands coordinating to Cu, as well as the nature of the NHC ligand substituents and the counterions.