The biosynthesis of the steroid precursor molecule lanosterol is a remarkable process in which the enzyme-bound substrate 2,3-S-oxidosqualene forms four new carbocyclic rings by a cascade of cation-alkene addition reactions, followed by a series of 1,2-methyl and hydride shifts. The work presented in this thesis is a computational study of the reactions of compounds designed to model the oxidosqualene-lanosterol cyclisation in order to establish details of the mechanism of this amazing cyclisation. The initiation of oxidosqualene cyclisation has been modelled by the intermolecular reaction of protonated oxirane and methylpropene. The SN2-like ring opening of the protonated epoxide is strongly exothermic with a low barrier to reaction; the geometry of the gas phase reaction has been found to be significantly affected by hyperconjugative stabilisations and low energy steric interactions. The energy profile and geometry of this reaction can now be compared to analogous intramolecular reactions such as the formation of the lanosterol A-ring. The competing five- and six-membered cyclisations of a series of substituted A-ring model compounds was investigated. It has been found that the facile cleavage of the protonated epoxide causes the reaction to behave more as an electrophilic addition than as a nucleophilic ring-opening substitution. This behaviour accounts for the general preference of protonated epoxides to react at the more substituted carbon atom, while epoxides in neutral or basic media react at the least sterically hindered carbon. With consideration for Baldwin's rules for ring closure, it is seen that the series of model compounds generally favours six-membered ring formation endo at the epoxide. The formation of the lanosterol B-ring was studied using a bicyclic model system. Previous computational studies had predicted the B-ring to close with readily with an activation energy of less than 1 kcal mol-1, however the present study has found a significant barrier to cyclisation of ca. 5-7 kcal mol-1 in this gas-phase model at the HF/6-31G(d) level of theory. This barrier is thought to arise from the closure of the B-ring in a sterically hindered twist-boat conformation.

The biosynthesis of the steroid precursor molecule lanosterol is a remarkable process in which the enzyme-bound substrate 2,3-S-oxidosqualene forms four new carbocyclic rings by a cascade of cation-alkene addition reactions, followed by a series of 1,2-methyl and hydride shifts. The work presented in this thesis is a computational study of the reactions of compounds designed to model the oxidosqualene-lanosterol cyclisation in order to establish details of the mechanism of this amazing cyclisation. The initiation of oxidosqualene cyclisation has been modelled by the intermolecular reaction of protonated oxirane and methylpropene. The SN2-like ring opening of the protonated epoxide is strongly exothermic with a low barrier to reaction; the geometry of the gas phase reaction has been found to be significantly affected by hyperconjugative stabilisations and low energy steric interactions. The energy profile and geometry of this reaction can now be compared to analogous intramolecular reactions such as the formation of the lanosterol A-ring. The competing five- and six-membered cyclisations of a series of substituted A-ring model compounds was investigated. It has been found that the facile cleavage of the protonated epoxide causes the reaction to behave more as an electrophilic addition than as a nucleophilic ring-opening substitution. This behaviour accounts for the general preference of protonated epoxides to react at the more substituted carbon atom, while epoxides in neutral or basic media react at the least sterically hindered carbon. With consideration for Baldwin's rules for ring closure, it is seen that the series of model compounds generally favours six-membered ring formation endo at the epoxide. The formation of the lanosterol B-ring was studied using a bicyclic model system. Previous computational studies had predicted the B-ring to close with readily with an activation energy of less than 1 kcal mol-1, however the present study has found a significant barrier to cyclisation of ca. 5-7 kcal mol-1 in this gas-phase model at the HF/6-31G(d) level of theory. This barrier is thought to arise from the closure of the B-ring in a sterically hindered twist-boat conformation.

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Chemical catalysts are divided into two traditional categories: homogeneous and heterogeneous catalysts. Although homogeneous (molecular) catalysts tend to have high activity and selectivity, their wide application is hampered by the difficulties in catalyst separation. In contrast, the vast majority of industrial scale catalysts are heterogeneous catalysts based on solid materials. Immobilized catalysts, combining the advantages of homogeneous and heterogeneous catalysts, have developed into an important field in catalysis research. This dissertation presents synthesis, characterization and evaluation of several novel immobilized catalysts. In the first part, MNP supported aluminum isoproxide was developed for ROP of Є-caprolactone to achieve facile magnetic separation of catalysts from polymerization system and reduce toxic metal residues in the poly(caprolactone) product. Chapter 3 presents a silica coated MNP supported DMAP catalyst that was synthesized and displayed good activity and regio-selectivity in epoxide ring opening reactions. In Chapter 4, hybrid sulfonic acid catalysts based on polymer brush materials have been developed. The unique polymer brush architecture permits high catalyst loadings as well as easy accessibility of the active sites to be achieved in this catalytic system. In Chapter 5, aminopolymer-silica composite supported Pd catalysts with good activity and selectivity were developed for the selective hydrogenation of alkynes. In this case, the aminopolymer composite works as a stabilizer for palladium nanoparticles, as well as a modifier to tune the catalyst selectivity. All in all, the general theme of the thesis is developing new immobilized catalysts with improved activity/selectivity as well as easy separation via rational catalyst design.

Dans le cadre de cette thèse, les dérivés d’huiles végétales sont utilisés pour la synthèse de bioplastifiants bio-résistants pour le PVC d’une part et la plastification et la réticulation d’un élastomère d’autre part (EPDM). Les huiles ont été choisies comme matières premières renouvelables car elles ont des fonctions esters qui permettent la solubilisation du PVC et des chaines grasses compatibles avec l’EPDM. Les réactions d’ouvertures d’époxydes d’esters gras en di-esters (symétriques et dissymétriques) ont été étudiées et principalement appliquées à la plastification du PVC. L’ouverture des époxydes d’esters gras en éther-esters a aussi été étudiée, principalement pour la plastification de l’EPDM. Les conditions réactionnelles ont été optimisées par l’étude de catalyseurs, homogène (TBACl) et hétérogène (TiO2) pour l’ouverture en hydroxy-ester, et par des résines sulfoniques pour l’ouverture en éther et pour l’estérification des hydroxyles résiduels. Une large variété de réactifs choisis suivant l’application désirée a été utilisée. Le dérivé cyclohexanoate/acétate d’esters méthyliques de colza présente les meilleures propriétés plastifiantes pour le PVC mais il n’est malheureusement pas biorésistant. Les dérivés éther-ester ne sont pas stables thermiquement et ne permettent pas la plastification de l’EPDM. Un dérivé di-insaturé et peu polaire (oléate d’oléyle) a été synthétisé en vue de la plastification et la réticulation de l’EPDM. Plusieurs réactions ont été examinées pour lier l’huile et le polymère (hydrosilylation, ène-réaction et métathèse) mais la réactivité est trop faible pour permettre la réticulation / During this thesis, derivatives of vegetable oils are used to synthesize bio-resistant bio plasticizers for PVC and plasticizer / cross linker for an elastomer (EPDM). The oils possess ester functional groups which allow the solubilization of PVC and fatty chains compatible with EPDM. The reactions of epoxide ring-opening of fatty esters to di esters (symmetrical and asymmetrical) have been studied and applied mainly to the plasticization of PVC. The ring-opening of epoxides of fatty esters to ether-esters has also been studied, primarily for plasticization of EPDM. Optimization of the reaction conditions was carried: homogeneous (TBACl) and heterogeneous (TiO2) catalysts were efficient for the preparation of hydroxy-ester, and sulfonic resins in ether and the esterification of residual hydroxyls. A wide variety of reagents selected according to desired application were used. The derivative cyclohexanoate / acetate rapeseed methyl esters present the best plasticizing properties for PVC but it is unfortunately not bio-resistant. Ether-ester derivatives are not stable thermally and do not allow the plasticization of EPDM. A relatively non-polar di-unsaturated derivative (oleyl oleate) was synthesized for the plasticization and cross linking of EPDM. Several reactions are considered to link the oil and the polymer (hydrosilylation, ene- reaction and metathesis), but the reactivity is too low to allow the cross linking

Es wurden Untersuchungen zur Synthese von Modellsystemen des heterobicyclischen Grundgerüsts der Saragossasäuren/Squalestatine durch Acetalisierung unterschiedlich konfigurierter acyclischer Diketohexaole durchgeführt. In diesem Zusammenhang gelang die biderektionale Darstellung eines Modellsystems in sieben Stufen mit einer Gesamtausbeute von 34 %. Als Methode zur Etablierung der korrekten Konfiguration der Hydroxygruppen diente die asymmetrische Dihydroxylierung nach Sharples. In einem weiteren Teil der Arbeit wurde die selektive mono-Debenzylierung verschiedener N,N-Dibenzylamine mit Cer(IV)ammoniumnitrat (CAN) und DDQ untersucht. In diesem Kontext konnte eine neue, sehr schonende, Methodik zur chemoselektiven mono-Debenzylierung tertiärer N,N-Dibenzylamine erarbeitet werden. Im letzten Teil der Arbeit wurden zwei neue, verbrückte Heterobimetall-Katalysatoren auf Basis von BINOL-Liganden entwickelt. Diese Katalysatoren wurden für die asymmetrische Ringöffnung verschiedener meso-Epoxide mit 4-Methoxyphenol genutzt und lieferten die Öffnungsprodukte in guten Ausbeuten und Enantiomerenüberschüssen (ee: 80 - 90 %). / The intramolecular acetalisation of several diketohexaols tko the bicyclic skelleton of saragozic acids/squalestatines were investigated. It was possible, by using a bidirectional synthesis sequence, to obtain a model for the core structure of saragozic acids in seven steps with a total yield of 34 %. To establish the correct configuration of up to six hydroxygroups the Sharpless asymmetric dihydroxylation protocoll was used. In the second part of the dissertation a new and mild method for debenzylation of N,N- Dibenzylamines was elaborated. Tertiary amines incorporating two N-benzyl substituents are readily mono-debenzylated with CAN or DDQ. In the last part of the dissertation the synthesis of two bridged heterobimetallic catalysts for the catalytic enantioselective ring opening of meso-epoxides is described. The ring opening reaction was performed using 4-methoxyphenol as a nucleophile an different meso-epoxides to give the ring opened products in good yields and enaniomeric excesses (ee: 80 - 90 %).

Es wurden Untersuchungen zur Synthese von Modellsystemen des heterobicyclischen Grundgerüsts der Saragossasäuren/Squalestatine durch Acetalisierung unterschiedlich konfigurierter acyclischer Diketohexaole durchgeführt. In diesem Zusammenhang gelang die biderektionale Darstellung eines Modellsystems in sieben Stufen mit einer Gesamtausbeute von 34 %. Als Methode zur Etablierung der korrekten Konfiguration der Hydroxygruppen diente die asymmetrische Dihydroxylierung nach Sharples. In einem weiteren Teil der Arbeit wurde die selektive mono-Debenzylierung verschiedener N,N-Dibenzylamine mit Cer(IV)ammoniumnitrat (CAN) und DDQ untersucht. In diesem Kontext konnte eine neue, sehr schonende, Methodik zur chemoselektiven mono-Debenzylierung tertiärer N,N-Dibenzylamine erarbeitet werden. Im letzten Teil der Arbeit wurden zwei neue, verbrückte Heterobimetall-Katalysatoren auf Basis von BINOL-Liganden entwickelt. Diese Katalysatoren wurden für die asymmetrische Ringöffnung verschiedener meso-Epoxide mit 4-Methoxyphenol genutzt und lieferten die Öffnungsprodukte in guten Ausbeuten und Enantiomerenüberschüssen (ee: 80 - 90 %). / The intramolecular acetalisation of several diketohexaols tko the bicyclic skelleton of saragozic acids/squalestatines were investigated. It was possible, by using a bidirectional synthesis sequence, to obtain a model for the core structure of saragozic acids in seven steps with a total yield of 34 %. To establish the correct configuration of up to six hydroxygroups the Sharpless asymmetric dihydroxylation protocoll was used. In the second part of the dissertation a new and mild method for debenzylation of N,N- Dibenzylamines was elaborated. Tertiary amines incorporating two N-benzyl substituents are readily mono-debenzylated with CAN or DDQ. In the last part of the dissertation the synthesis of two bridged heterobimetallic catalysts for the catalytic enantioselective ring opening of meso-epoxides is described. The ring opening reaction was performed using 4-methoxyphenol as a nucleophile an different meso-epoxides to give the ring opened products in good yields and enaniomeric excesses (ee: 80 - 90 %).