L’essor de la chimie supramoléculaire et plus particulièrement de la tectonique moléculaire a rendu la formation de matériaux poreux hautement organisés possible. La fonctionnalisation de tels composés favorise leur utilisation pour de nombreuses applications. Les travaux présentés dans cette thèse ont été consacrés aux réseaux moléculaires poreux homochiraux ainsi que leur utilisation pour le stockage de gaz, la reconnaissance et la séparation d’énantiomères.Le premier chapitre décrit la synthèse de divers ligands organiques optiquement purs et leur assemblage avec des sels de cuivre pour l’obtention de monocristaux. Les isothermes d’adsorption de chacun de ces composés cristallins ont été mesurés via des analyses BET et le stockage de N2,CO2 et CH4 ont été évalué.Le second chapitre s’intéresse à l’utilisation de ces mêmes composés chiraux pour la reconnaissance des énantiomères (L)- et (D)-tryptophane. Des tests de séparation énantiosélective de molécules aminées ou dérivées d’amides sont également exposés.Le dernier chapitre décrit la formation de réseaux moléculaire mono- et tridimensionnels par l’association de ligands organiques avec des sels métalliques variés. Leurs structures cristallines ont pu être déterminées par diffraction des rayons X sur monocristal. / The development in supramolecular chemistry and more particularly in molecular tectonics has madepossible the formation of porous and highly organized materials. The functionalization of suchcompounds favored their use for various applications. This PhD work is about the application ofporous homochiral coordination networks for storage, enantioselective recognition or separation.The first chapter deals with the synthesis of chiral ligands and their combinations with copper salts toenable the formation of single crystals. Their adsorption isotherms were evaluated by BETmeasurements. Storage of N2, CO2 and CH4 by these crystalline architectures was also evaluated.The second part describes the use of these chiral compounds for enantioselective recognition of (L)-and (D)-tryptophan. Tests of enantioselective separation of amines or amides were also carried out.The last part of this work deals with the formation of mono- or tridimensional coordination polymersby combinations of organic ligands and a variety of metallic salts. Their structures were determinedby X-ray diffraction on single crystal.

Enantiopure α-alkyl-substituted aldehydes are widely recognised as important building blocks in synthesis. Despite this, methods to prepare such substrates are limited. Strategically, asymmetric intermolecular S_N2 α-alkylation represents a highly straightforward transformation, but still remains an elusive feat. This thesis describes efforts to address this challenge, with attempted access to enantioenriched α-alkyl aldehydes by way of C-alkylation of chiral, non-racemic, hindered aldenamines using simple alkyl halides. Enamines derived from four types of auxiliary (a tropane, an oxazolidine, a pyrrolidine and a homotropane) have been prepared, and their alkylation profile examined. While the desired levels of asymmetric induction were not attained, use of the tropane and homotropane auxiliaries, which differ only by a single methylene group, interestingly, gave complimentary diastereocontrol during alkylation with EtI. The observed stereoselectivity is supported by density functional studies performed for ethylation of both enamines. Additionally, in the course of preparing the homotropane a highly efficient asymmetric synthesis of a homotropinone bearing gem-α-substitution has been developed.

Benzylic fluorides are attractive target molecules for medicinal chemistry, agrochemicals and materials chemistry. The enantioselective synthesis of benzylic fluorides is challenging and few general methods exist. This thesis describes several approaches to the synthesis of benzylic fluoride targets, including enantioselective processes. Chapter 1: Reviews the properties, uses and synthetic approaches to fluorinated molecules, with a particular focus on benzylic fluorides and enantioselective syntheses. Chapter 2: Describes the fluorination cyclisation of prochiral indole precursors. The use of catalytic amounts of a bis-cinchona alkaloid gave good enantioselectivities for the cyclisation. Alcohol, tosylamine, amide and carbamate pendant nucleophiles all cyclised successfully to give quaternary benzylic fluorides in moderate yields and with enantioselectivities up to 92%. The substrate scope of the reaction is described, as well as methodology for deprotection of cyclised nitrogen nucleophiles. Chapter 3: Details an investigation of the Pd catalysed substitution of polycyclic benzylic fluorides by a range of nucleophiles and their relative reactivity in comparison to oxygen leaving groups. Modification of the methodology to enable reaction of monocyclic substrate substitution was enabled by the use of a protic solvent. Chemoselective reaction conditions were identified for selective reaction of Bn-F or Ar-Cl bonds and comparative reactivity studies were undertaken. The feasibility of Pd(0)/(II) catalysed nucleophilic C-F bond formation was examined. Chapter 4: The development of the defluorination methodology from Chapter 3 for secondary substrates is described. The stereochemical course of defluorination was probed, showing that displacement of fluoride is mechanistically similar to that of oxygen leaving groups. A kinetic resolution with a low selectivity was developed for access to enantioenriched benzylic fluorides.

Ce mémoire décrit le développement d’une nouvelle méthodologie d’expansion de cycle irréversible à partir de N-alkyl-3,4-déhydroprolinols pour former des N-alkyl tétrahydropyridines 3-substituées en passant par un intermédiaire aziridinium bicyclique. Cette méthode permet l’introduction d’un vaste éventail de substituants à la position 3 et tolère bien la présence de groupements aux positions 2 et 6, donnant accès à des pipéridines mono-, di- ou trisubstituées avec un excellent diastéréocontrôle. De plus, il est démontré que l’information stéréogénique du 3,4-déhydroprolinol de départ est totalement transférée vers le produit tétrahydropyridine. Additionnellement, une méthodologie fut dévelopée pour la préparation des produits de départ 3,4-déhydroprolinols en forme énantiopure, avec ou sans substituants aux positions 2 et 5, avec un très bon stéréocontrôle. Le premier chapitre présente un résumé de la littérature sur le sujet, incluant un bref survol des méthodes existantes pour la synthèse de pipéridines 3-substituées, ainsi qu’une vue d’ensemble de la chimie des aziridiniums. L’hypothèse originale ainsi que le raisonnement pour l’entreprise de ce projet y sont également inclus. Le second chapitre traite de la synthèse des N-alkyl-3,4-déhydroprolinols utilisés comme produits de départ pour l’expansion de cycle vers les tétrahydropyridines 3-substituées, incluant deux routes synthétiques différentes pour leur formation. Le premier chemin synthétique utilise la L-trans-4-hydroxyproline comme produit de départ, tandis que le deuxième est basé sur une modification de la réaction de Petasis-Mannich suivie par une métathèse de fermeture de cycle, facilitant l’accès aux précurseurs pour l’expansion de cycle. Le troisième chapitre présente une preuve de concept de la viabilité du projet ainsi que l’optimisation des conditions réactionnelles pour l’expansion de cycle. De plus, il y est démontré que l’information stéréogénique des produits de départs est transférée vers les produits. iv Au quatrième chapitre, l’étendue des composés pouvant être synthétisés par cette méthodologie est présentée, ainsi qu’une hypothèse mécanistique expliquant les stéréochimies relatives observées. Une synthèse énantiosélective efficace et divergente de tétrahydropyridines 2,3-disubstituées est également documentée, où les deux substituants furent introduits à partir d’un intermédiaire commun en 3 étapes. / This thesis describes the development of a novel methodology of irreversible ring expansion from N-alkyl-3,4-dehydroprolinols to N-alkyl-3-substituted tetrahydropyridines through a bicyclic aziridinium ion intermediate. This method allows a wide variety of substituents at the 3-position, and also permits substitution at the 2- and 6-positions of the tetrahydropyridine giving mono-, di- or tri-substituted piperidines with excellent diasterocontrol. Complete transfer of the stereogenic information of the 3,4- dehydroprolinol to the tetrahydropyridine product is demonstrated. Also, a methodology was developed to prepare the 3,4-dehydroprolinol starting materials in enantiopure form, with the possibility of substitution at the 2- and 5-positions with excellent diasterocontrol. The first chapter presents the literature background, including a brief summary of methodologies for the synthesis of 3-substituted piperidines, and an overview of aziridinium ion chemistry. Also presented is the original hypothesis of the project, and our reasoning for undertaking this project. The second chapter describes the synthesis of N-alkyl-3,4-dehydroprolinols used as precursors for the ring expansion to 3-substituted tetrahydropyridines, including two different synthetic routes. The first route route converts L-trans-4-hydroxyproline to enantioenriched N-benzyl-3,4-dehydroprolinol in 6 steps. The second synthetic route was developed using a variant of the Petasis-Mannich reaction and a ring closing metathesis,making the precursors more readily available and simple to synthesize. The third chapter presents the proof of concept of the viability of the project and optimization studies. Moreover, the transfer of stereogenic information to the resulting product is demonstrated. The fourth chapter demonstrates the broad scope of the ring expansion and mechanistic insight is given based on the relative configuration of the products. An expedient divergent enantioselective synthesis of a 2,3-disubstituted tetrahydropyridine is also shown, with both substituents being chosen from a common intermediate in 3 steps.

This thesis concerns the development of the first BINOL phosphoric acid (BPA) catalysed enantioselective N-acyliminium cyclisation reactions and their incorporation into domino sequences that allow for the construction of architecturally complex enantioenriched polycycles in a single step from easily accessible starting materials. More specifically, this thesis deals with the discovery of a BPA-catalysed enantioselective N-acyliminium cyclisation cascade of enol lactones and tryptamines. Its extension to a doubly catalysed process involving gold(I) to cycloisomerise alkynoic acids and a BPA to effect the enantioselective N-acyliminium cyclisation is presented. In addition, the exploitation of this method in highly diastereo- and enantioselective N-acyliminium cyclisations of oxoacids and tryptamines and in a site isolated base-catalysed Michael addition / acid-catalysed N-acyliminium cyclisation cascade is described. A study on the proposed mechanism and model for the origin of enantioselectivity is discussed, based on experimental data and a computational study. As a separate part of our programme, the development of a new class of stronger Brønsted acids, chiral benzenesulphonic acids, is described. The optimisation of the synthetic routes as well as the synthesis of a library of acids is presented and their assessment in precedented reactions is discussed.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Dans ce mémoire, deux principaux sujets seront présentés. Nos efforts se sont d’abord tournés vers la synthèse du cylindrocyclophane F, un [7,7]-paracyclophane naturel, puis vers l’élaboration d’une nouvelle classe d’hétérocycles fluorescents. Premièrement, la cyclopropanation, une des étapes clés de la synthèse du cylindrocyclophane F, ainsi qu’une nouvelle voie de synthèse passant par une réaction de cyclopropénation ont été revisitées. La possibilité d’employer une méthode de macrocyclisation, incluant une réaction de couplage de Suzuki sur deux centres sp3, a ensuite été étudiée sur un substrat modèle. Deuxièmement, la synthèse de benzo[a]imidazo[2,1,5-c,d]indolizines à partir de N-[(6-bromo-2-pyridinyl)méthyl]benzamides a été développée. Dans un premier temps, le tandem cyclodéshydratation/aromatisation effectué en présence de 2-méthoxypyridine a été optimisé afin d’obtenir la 5-bromo-3-phénylimidazo[1,5-a]pyridine. Puis, une arylation intramoléculaire en présence d’une quantité catalytique d’un complexe de palladium a permis d’obtenir l’hétérocycle fusionné désiré. Les propriétés photochimiques de cette nouvelle classe d’hétérocycles seront aussi présentées. / In this thesis, two main points will be introduced. First, we focused our efforts on a synthetic approach towards cylindrocyclophane F, a natural [7,7]-paracyclophane. Then, the synthesis of a new fluorescent class of molecule will be disclosed. First, an asymmetric cyclopropanation, one of the key steps of the synthesis of cylindrocyclophane F, will be revisited. Furthermore, a new route, including a cyclopropenation reaction, was explored. Then, the possibility of using a Suzuki coupling reaction on two sp3 centres for macrocyclisation has been studied on a model substrate. In a separate study, the synthesis of benzo[a]imidazo[2,1,5-c,d]indolizines from N-[(6-bromo-2-pyridinyl)methyl]benzamides will be disclosed. A mild cyclodehydratation-aromatisation was performed in the presence of 2-methoxypyridne in order to obtain 5-bromo-3-phenylimidazo[1,5-a]pyridine. This sequence was followed by an intramolecular direct arylation to form the desired compound. The photophysical properties of this new heterocycle class were measured.

No description available.

Thesis advisor: Amir H. Hoveyda / Chapter 1. Through the use of quantum theory of atoms in molecules (QTAIM) the similarities and differences between transition metal complexes ligated by phosphines and N-heterocyclic carbenes (NHC) were elucidated. Among the key findings, the phosphines were identified as stronger charge donors than NHCs; however, the latter class of ligands exhibits a weaker p-accepting character than the former. Furthermore, Tolman electronic parameter (TEP) was determined to be an inadequate gauge for the total electron donating ability of phosphines and NHCs; rather TEP can serve as a measurement of population of dp set of orbitals of a metal center in question. Computational and experimental studies of the mechanism of NHC-catalyzed boron and silicon addition to a,ß-unsaturated carbonyls reactions were carried out. Through the use of radical traps the mechanisms involving homolytic cleavage of B-B or B-Si bonds were ruled out. Computational (DFT) studies of the mechanism identified two pathways: (1) direct activation of diboron or borosilyl reagents through coordination of NHC to the B atom, (2) net oxidative addition of the diboron or borosilyl reagents to the carbon (II) of the NHC. The insights gained from the aforementioned studies were employed to rationalize the observed lack of reactivity of NHC-activated diboron complexes in the presence of aldehydes. Chapter 2. New C(1)-symmetric chiral monodentate N-heterocyclic carbenes were prepared, and corresponding chiral Ru-carbene complexes were synthesized. These complexes were employed to gain empirical understanding of factors that govern stereoselectivity in Ru-catalyzed enantioselective olefin ring-closing metathesis. The data thus obtained was employed to infer that syn-to-NHC reaction pathways are competitive and non-selective. One plausible mechanism, through which syn-to-NHC pathways can be accessed, involves Berry pseudorotations. Through the use of stereogenic-at-Ru complexes diastereomeric Ru-carbenes were isolated (silica gel chromatography) and spectroscopically characterized in solution phase. The diastereomeric Ru-carbenes were found to undergo non-metathesis stereomutations at Ru center, thereby providing additional support for the above hypothesis regarding accessibility of syn-to-NHC olefin metathesis pathways. Non-metathesis stereomutation at Ru was found to be accelerated in the presence of protic additives, suggesting the plausibility of hydrogen bonding between the acidic proton and the X-type ligands on Ru. Occurrence of hydrogen bonding was corroborated through the use of chiral allylic alcohols in Ru-catalyzed diastereoselective ring-opening/cross metathesis, which was developed into a versatile method for highly diastereoselective functionalization of terminal olefins. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Des oligomères de taille définie de chitosane ont été préparés et testés en tant qu'organocatalyseurs dans des réactions d'aldolisation énantiosélectives. Les précurseurs de ces catalyseurs sont obtenus en une seule étape par une réaction d'acétolyse contrôlée de la chitine, second polysaccharide le plus abondant. Une méthodologie reposant sur des réactions de glycosylation sous activation micro-ondes a été développée afin de fonctionnaliser la position anomérique de ces oligomères. Ainsi, le triflate de cuivre(II), utilisé en quantité catalytique, s’est révélé être le promoteur le plus efficace pour l’activation de la glucosamine ou du chitobiose peracétylés de configuration α. La sélectivité α des produits glycosylés résultent d’une isomérisation in situ des produits cinétiques β. Des organocatalyseurs se différenciant par leur partie aglycone et par leur degré de substitution ont été synthétisés en peu d’étapes. Les résultats les plus intéressants ont été obtenus avec un dérivé du chitobiose soluble en milieu aqueux. Nous avons montré, qu’en présence d’un co-catalyseur acide, l’acide 4-nitrobenzoïque, la réaction entre la cyclohexanone et le 4-nitrobenzaldéhyde, conduit à l’adduit anti avec un bon excès énantiomérique (89% ee). De plus, nous avons également montré que ce catalyseur pouvait être réutilisé dans plusieurs cycles catalytiques sans perte de sélectivité. / The catalytic behaviour of size-defined chitosan oligomers has been evaluated for asymmetric aldol reactions. These oligomers were obtained from chitin, which is one of the most abundant naturally occurring polymers, as a renewable starting biomolecule. Thus, controlled depolymerization of chitin was carried out by acetolysis providing per-O-acetylated N-acetyl-α-D-glucosamine oligomers with a polymerization degree from 2 to 4. To investigate the influence of the aglycon moiety, we developed a Lewis acid-promoted glycosylation reactions under microwave irradiation. Thus, a catalytic amount of copper(II) triflate proved to be the most effective promoter for the activation of α-per-O-acetylated glucosamine oligomers, which are considered as poorly reactive substrates, to selectively obtain α-glycosylated compounds. This selectivity results from in situ isomerization of kinetic β products. Chitosan-based catalysts, which differ in the distribution pattern, were synthesized in a few steps. The most promising results were obtained with a chitobiose derivative, which efficiently catalyzed the aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, in the presence of 4-nitrobenzoic acid as a co-catalyst, in water, providing the anti-adduct in high yield with good enantioselectivity (89% ee). In addition, this homogeneous organocatalyst can be reused in several cycles without loss of catalytic activity.