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Diastereoselektive Synthese von anellierten Pyrrolidinen über eine NO3.-induzierte, oxidative, selbstterminierende RadikalcyclisierungskaskadeStademann, Arne. Unknown Date (has links) (PDF)
Universiẗat, Diss., 2004--Kiel.
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Novel developments of palladium and radical mediated cyclisationsLyon, Jessica Elisabeth January 2009 (has links)
In this project cyclisation chemistry using palladium and radical methodologies has been developed. The aim was to compare palladium and radical mediated cyclisations. Initially small molecules containing amine and amide functional groups were synthesised to screen the methodology. Later the design of these molecules was changed to be based on the imidoyl functional group. A series of N-benzyl protected aliphatic amine and amides were synthesised in the hope (with the aim of cyclisation) that they could be cyclised using both palladium and radical conditions. When these examples failed, which was attributed to the strain of the cyclic molecules, alternative precursors were sought. Initially, the N-protecting group was changed to a tosyl-group. However, when this had no positive effect, the size of the precursor molecules were examined. Two alternative amine precursors were designed which would remove the strain element in the cyclised molecules. The lengthy synthesis of these two molecules was not favourable for the development of methodology. Although it appeared that the cyclisations were now occurring it did not prove favourable to carry on down this path. The final part of this research project utilises imines and imidoyl selenides as radical and palladium cyclisation precursors respectively. A series of aromatic imines and imidoyl selenides were synthesised. The irnines were synthesised from amino-biphenyl and a range of p-substituted benza1dehydes. The corresponding imidoyl selenides were synthesised from amino-biphenyl and a range of p-substituted benzoyl chlorides to give the amides which in tum were converted to the target molecules via the imidoyl chlorides. The successful cyclisations using both methodologies resulted in a series of phenanthridines. This success of these cyclisations led to further precursors being developed which included bisphenanthridine, alkyne, alkyl and heteroaromatic precursors. However, most of the cyclisations of these molecules proved problematic and require further development of methodology.
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Design, synthesis and characterization of bis-azobenzenes - their synthetic applications and incorporation into polymer / Conception, synthèse et caractérisation de bis-azobenzènes - leurs applications synthétiques et leur incorporation dans des polymèresXiao, Hui January 2018 (has links)
Abstract: Owing to the light-induced switching between their trans- and cis-isomers, azobenzenes display a wide range of applications including stimuli-responsive polymers, acid-base indicators, colorful systems, liquid crystals, and bio-medicals. In the past decades, much research on azobenzenes has been carried out and they have become a growing research topic. Particularly, the synthetic methodology of azobenzene derivatives has become mature. However, a general synthetic method of furnishing the bis- and tris-azobenzene compounds in one step is still lacking, and the study of bis-azobenzene is nearly blank including the solution properties and applications. In this thesis, we focus on the design, and preparation of bis-, tris- and small cyclic azobenzene derivatives; followed by a further investigation of their properties in solution. We also explore the preparation and applications of azobenzene-based stimuli-responsive polymeric materials. The first chapter describes an efficient strategy for the synthesis of bis- and tris-azobenzene derivatives. In this synthetic pathway, the bis- and tris-azobenzenes could be obtained in one pot, together with mono-azobenzene side products. By modifying the reaction conditions, the yields of the azobenzene compounds were mainly dependent on the substituents on the phenols and diazonium salts, and the molar ratio of starting materials. Compared with the unsubstituted aniline, the use of anilines with electron-withdrawing groups, leading to electron-deficient diazonium salts, favors the formation of mono-azobenzenes, rather than bis-azobenzenes. Whereas, anilines with electron-donating groups are not efficient during the first step leading to the formation of mono-azobenzene and thus favor the generation of bis-azobenzenes. Large amounts of anilines (over two-fold and three-fold excess), are the best choice to obtain bis- and tris-azobenzenes in good yields. In Chapter 2, we describe a novel method for the cyclization of mono- and bis-azobenzenes without ultraviolet light to form seven-membered heterocycles. The starting materials contain ortho-fluoro atom and ortho-phenol groups on the phenyl rings of the azobenzene systems. The role of the fluoro substituent is twofold. It promotes the stability of the cis-form of the azobenzene and it acts as a leaving group when its carbon atom neighbor is attacked by the phenolate. The nature of solvents was found to have a pronounced effect on the spontaneous cyclization reaction by stabilizing the intermediate complex. The cyclization rate could be accelerated under the UV irradiation and by using more polar solvents. Due to the competing keto-enol tautomerizations and cyclizations, we observed complicated changes in UV-vis absorption and color of solutions over time. It was revealed that, for ortho-hydroxyl azobenzenes with ortho-fluorine atom in polar solvents, the trans-to-cis isomerization and cyclization happened under daylight, and keto-enol tautomerization occurred in the dark. In Chapter 3, we studied a class of novel dual-responsive (photo- and thermo-) copolymers by modifying Poly(N-isopropylacrylamide) (PNIPAM) with bis-azobenzene moieties. The copolymers were prepared from a free radical copolymerization of N-isopropylacrylamide (NIPAM) and bis-azobenzenes bearing electron-donating or electron-accepting substituents. It was found that bis-azobenzene moieties could influence the cloud point of aqueous copolymer solution due to the photoisomerization of bis-azobenzenes and the conformation of polymer chain upon the photoreactions. Varying substituents on bis-azobenzene moieties, the copolymer solutions displayed an opposite cloud point shift after the photoreactions of the chromophores. When the substituents on azobenzene have push-pull feature, the polymer chains prefer aggregation after UV irradiation, which decreases the cloud point. By contrast, the cloud point shifts to higher temperature upon UV light irradiation when the bis-azobenzenes bears the donors, which is caused by cis-isomer being more hydrophilic than the trans-isomer. However, the effect of photoisomerization of azobenzene on the cloud point shift appears to be greater on PNIPAM containing mono-azobenzene pendent groups. / En raison de la commutation induite par la lumière entre leurs isomères trans et cis, les azobenzènes affichent une gamme étendue d'applications. On y retrouve des polymères sensibles aux stimuli, des indicateurs acido-basiques, des systèmes colorés, des cristaux liquides et des matériaux aux applications biomédicales. Dans les dernières décennies, de nombreuses recherches sur les azobenzènes ont été menées et ils sont devenues un sujet de plus en plus important. En particulier, la méthodologie de synthèse des dérivés d'azobenzène est devenue mature. Cependant, une méthode synthétique générale pour l’obtention des composés bis- et tris-azobenzène en une seule étape est encore manquante, et l'étude du bis-azobenzène est presque vierge, y compris les propriétés et les applications en solution. Dans cette thèse, nous nous concentrons sur la conception et la préparation de bis-, tris- et de petits dérivés cycliques de l'azobenzène. Ce premier volet est suivi d'une étude plus poussée de leurs propriétés en solution. Nous explorons également la préparation et l'application de matériaux polymères d'azobenzène, réagissant à plusieurs stimulations. Le premier chapitre décrit une stratégie efficace pour la synthèse des dérivés bis- et tris-azobenzène. Dans cette voie de synthèse, les bis- et tris-azobenzènes peuvent être obtenus dans un pot réactionnel, avec des produits secondaires mono-azobenzène. En modifiant les conditions de réaction, les rendements des composés azobenzène dépendent principalement des substituants sur les phénols et les sels de diazonium, et du rapport molaire des produits de départ. Par rapport à l'aniline non substituée, l'utilisation d'anilines avec des groupes électroattracteurs, conduisant à des sels de diazonium déficients en électrons, favorise la formation de monoazobenzènes plutôt que de bis-azobenzènes. En revanche, les anilines à groupements donneurs d'électrons ne sont pas efficaces au cours de la première étape conduisant à la formation de monoazobenzènes et favorisent ainsi la génération de bis-azobenzènes. De grandes quantités d'anilines (excès de plus de deux et trois fois) sont le meilleur choix pour obtenir des bis- et tris-azobenzènes avec de bons rendements. Dans le chapitre 2, nous décrivons une nouvelle méthode de cyclisation des mono- et bis-azobenzènes, sans lumière ultraviolette, pour former des hétérocycles à sept chaînons. Les produits de départ contiennent des groupes ortho-fluoro et orthophénol sur les cycles phényle des systèmes azobenzène. Le rôle du substituant fluoro est double. Il favorise la stabilité de la forme cis de l'azobenzène et agit comme un groupe partant lorsque son atome de carbone voisin est attaqué par le phénolate. La nature des solvants s'est avérée avoir un effet prononcé sur la réaction de cyclisation spontanée en stabilisant le complexe intermédiaire . La vitesse de cyclisation peut être accélérée sous l'irradiation UV et en utilisant des solvants plus polaires. En raison des tautomérisations céto-énol et des cyclisations en compétition, nous avons observé que l’évolution des spectres d'absorption UV-vis et de la couleur des solutions au fil du temps était compliqué. Il a été révélé que, pour les ortho-hydroxyl azobenzènes avec un atome d'ortho-fluor dans les solvants polaires, l'isomérisation et la cyclisation trans-cis se produisaient à la lumière du jour et que la tautomérisation céto-énol se produisait dans l'obscurité. Dans le chapitre 3, nous avons étudié une classe de nouveaux copolymères biosensibles (photo- et thermo-) en modifiant le poly(N-isopropylacrylamide) (PNIPAM) avec des portions bis-azobenzène. Les copolymères ont été préparés à partir d'une copolymérisation radicalaire de N-isopropylacrylamide (NIPAM) et de bis-azobenzènes portant des substituants donneurs ou accepteurs d'électrons. Il a été constaté que les fragments bis-azobenzène pouvaient influencer le point de trouble de la solution aqueuse de copolymère en raison de la photoisomérisation des bis-azobenzènes et de la conformation de la chaîne polymère lors des photoréactions. En changeant les substituants sur les fragments bis-azobenzène, les solutions de copolymères présentaient un décalage du point de trouble opposé après les photoréactions des chromophores. Lorsque les substituants sur l'azobenzène ont une influence «push-pull», les chaînes polymères préfèrent l'agrégation après l'irradiation UV, ce qui diminue le point de trouble. En revanche, le point de trouble passe à une température plus élevée lors de l'irradiation par la lumière UV lorsque les bis-azobenzènes portent des donneurs, ce qui est dû au fait que l'isomère cis est plus hydrophile que l'isomère trans. Cependant, l'effet de la photo-isomérisation de l'azobenzène sur le décalage du point de trouble semble être plus important sur les groupes pendants mono-azobenzène contenant du PNIPAM.
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Directing a SmI2 radical cyclisation using a C-Si bond : a second generation approach to pestalotiopsin A, 6-epitaedolidol and punctaporonin CHarb, Hassan Youssef January 2011 (has links)
An improved second generation approach to pestalotiopsin A and 6-epitaedolidol has been developed. A silicon group bonded directly to carbon has been used as a stereocontrol element in cyclisation substrates for a SmI2 – mediated 4-exo-trig radical cyclisation. The silicon groups acts as a steric block to set up three new stereocentres in high to complete diastereocontrol. Several approaches to the cyclisation substrates are outlined, including a silyl transfer/aldol cascade and a novel C2-symmetric N-heterocyclic carbene – copper catalyst to asymmetrically install a C-Si bond. The silicon group is a versatile handle for further manipulation and has been oxidised using Fleming oxidation conditions to install the hydroxyl functionality required in the target compounds. The silicon group also simplifies the alcohol protecting group strategy in the approach to pestalotiopsin A and 6‐epitaedolidol. The first application of N-heterocyclic carbene – copper catalysed silyl transfer in natural product synthesis and the first use of a SmI2 – mediated cyclisation directed by a C-Si stereocontrol element are described.
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Synthesis of ZSM-5 zeolite from South African fly ash and its application as solid catalystMissengue-Na-Moutoula, Roland January 2016 (has links)
Philosophiae Doctor - PhD / Zeolites are widely used as environmentally friendly solid catalysts or catalyst supports in the refining and petrochemical industries. ZSM-5 zeolite is composed of a three-dimensional medium pore structure (openings of 5-5.5 Å) with high silica content, high temperature stability and strong acidity making it a well-known and an established catalyst for several petroleum derived chemical processes such as cracking, aromatic alkylation, disproportionation, Methanol-to-Gasoline, isomerisation, etc. Nowadays, the synthesis of ZSM-5 zeolite from silica, alumina sources and structure directing agents (templates) is well known. Its synthesis is possible from fly ash, which is a low cost source of both silica and alumina. Fly ash is an inorganic residue resulting from the combustion of coal in electricity generating plants, consisting mostly of SiO₂ and Al₂O₃. ZSM-5 zeolite has not been synthesised from South African coal fly ash and the literature reports that fly ash-based ZSM-5 zeolite was synthesised only with tetrapropylammonium (TPA+) as structure directing agent and required an excessive amount of additional silica. The final ZSM-5 product was reported to still contain fly ash mineral phases after synthesis. This prevents the use of fly ash as a ZSM-5 zeolite precursor. Moreover, the synthesis of a high purity ZSM-5 zeolite from fly ash without additional silica has not been yet reported. This study aimed to synthesise high purity ZSM-5 zeolite from South African coal fly ash without additional silica, and with tetrapropylammonium bromide (TPABr), 1,6- hexanediamine (HDA) or 1-propylamine (PA) as structure directing agent.
This aim was achieved by first optimising the synthesis of ZSM-5 zeolite from South African coal fly ash based on a formulation reported in the literature with fumed silica and TPABr as additional source of silica and structure directing agent respectively. Thereafter, the obtained optimum conditions were used to synthesise other fly ash-based ZSM-5 zeolite products by substituting TPABr with HDA or PA. Two routes of treating the as-received fly ash prior to the hydrothermal synthesis were applied in order to improve the quality of the final products or reduce the amount of the fumed silica that was used. The first route consisted of treating the as-received fly ash with concentrated H₂SO₄ in order to remove a certain amount of aluminium and increase the Si/Al in the acid treated fly ash solid residue but also remove some other elements such as Fe, Ca, Mg, and Ti which might have an undesirable effect on the product quality. The acid treated fly ash solid residue was used as ZSM-5 precursor with fumed silica as additional silica source and TPABr, HDA or PA as structure directing agent. The ZSM-5 zeolite products that were synthesised from the as-received fly ash as well as from the H₂SO₄ treated fly ash were treated with oxalic acid solution in order to reduce the aluminium content in the final products. The second route consisted of fusing the as-received fly ash with NaOH and treating the powder fused fly ash extract with oxalic acid solution. The obtained fused and oxalic acid treated fly ash extracts were used as ZSM-5 precursors without additional fumed silica and with TPABr, HDA or PA as structure directing agent. ZSM-5 zeolite was synthesised from the as-received South African coal fly ash not only with the commonly used structure directing agent TPABr but also with two other, lower cost structure directing agents, HDA and PA. The synthesis process did not generate any solid waste as fly ash was used as bulk, which could be a way of valorising South African coal fly ash. However, the final products contained some fly ash mineral phases such as mullite and quartz, and had poor physical and chemical properties compared to a commercial H-ZSM-5 zeolite. The treatment of the as-received fly ash with H₂SO4 resulted in fly ash-based ZSM-5 zeolite products with better physical and chemical properties than those of ZSM-5 zeolite products that were synthesised from the as-received fly ash. Moreover, the post-synthesis treatment of the fly ash-based ZSM-5 zeolite products with oxalic acid resulted in an increase in the Si/Al ratio, offering a post-synthesis route to adjust the acidity of the catalysts. However, mullite and quartz phases were still present in the synthesised products. Alternatively, high purity ZSM-5 zeolite was synthesised from the fused and oxalic treated fly ash extracts without additional silica and with TPABr, HDA or PA as structure directing agent. Moreover, these synthesised fly ash-based ZSM-5 zeolite products had similar physical and chemical properties to the commercial H-ZSM-5 zeolite. The synthesised fly ash-based ZSM-5 zeolite products were used as solid catalysts in the Methanol-to-Olefins (MTO) and Nazarov reactions. The ZSM-5 zeolite products that were synthesised from the H₂SO4 treated fly ash as well as fused and oxalic treated fly ash were successfully used as solid catalysts in the MTO and Nazarov reactions. The ZSM-5 zeolite products that were synthesised from the H₂SO₄ treated fly ash presented a similar trend in MTO and Nazarov reactions depending on the structure directing agent that was used, and the ZSM-5 zeolite that was synthesised with HDA as structure directing agent had the highest MTO and Nazarov conversion. However these catalysts deactivated more quickly compared to the commercial H-ZSM-5 zeolite. On the other hand, the zeolites that were synthesised from the fused and oxalic acid treated fly ash had a high initial MTO conversion equivalent to the commercial H-ZSM-5 zeolite. However, they deactivated after 5 h of time on stream due to diffusional constraints, because of their large crystal sizes. This study developed novel routes in the synthesis of high value zeolites from fly ash. ZSM-5 zeolite was synthesised from fly ash with structure directing agents other that TPA+ cation and had acceptable Brønsted acidity and high initial conversion in MTO and Nazarov reactions. This has not been yet reported in the literature. Moreover, for the first time a high purity ZSM-5 zeolite was synthesised from fly ash without additional silica and had similar properties to a commercial H-ZSM-5 zeolite. This constituted a breakthrough in the fly ash-based ZSM-5 zeolite synthesis procedure, which will promote the valorisation of fly ash through ZSM-5 synthesis due to avoiding the addition of silica source in the hydrothermal gel and preventing the presence of fly ash mineral phases in the final products. This study can have a significant economic and environmental impact in South Africa if the synthesis process is scaled up as it provides a potentially cheap and innovative way of using waste for making a high value green and acid catalyst, namely ZSM-5 zeolite that has several catalytic applications; and it promotes the valorisation of South African coal fly ash that is considered by many as waste material. / National Research Foundation (NRF)
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Synthèse de CF₂-carbasucres par cyclisation radicalaire et application à la synthèse d'analogues de glycoconjugués à visée thérapeutique / Synthesis of fluorinated carbasugars by 5-exo radiacl cyclization : a general route to new glycomimeticsFourrière, Gaëlle 29 November 2010 (has links)
Les O-glycoconjugués et les dérivés glycosidiques sont des composés naturels impliqués dans de nombreux processus biologiques. Cependant, leurs propriétés sont grevées par la médiocre stabilité in vivo de la liaison osidique. Il est donc intéressant de développer des mimes non hydrolysables. Nous nous sommes intéressés au remplacement de l’oxygène intracyclique par un groupement gem-difluorométhylène.La synthèse d’analogues difluorocarbocycliques de 5-désoxypentofuranoses et de 1-amino-5-désoxypentofuranoses a été décrite. La synthèse comporte une addition dePhSeCF2TMS sur des aldéhydes dérivés de sucres ou sur les tert-butanesulfinylimines correspondantes, suivie d’une cyclisation radicalaire. La diastéréosélectivité de ces deux étapes-clés a été étudiée, puis cette stratégie de synthèse a été appliquée à la synthèse deCF2-carbasucres, notamment l’analogue CF2-carbocyclique du D-arabinose. / O-Glycoconjugates and carbohydrate-based molecules are natural compoundsimplied in many biological processes. However, their properties are burdened by the low invivo stability of the osidic bond. It is thus interesting to develop non hydrolyzable mimetics.We were interested in the replacement of the intracyclic oxygen by a gem-difluoromethylenegroup.The synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses and1-amino-5-deoxypentofuranoses is described. The sequence involves an addition ofPhSeCF2TMS to carbohydrate-derived aldehydes or their corresponding tertbutanesulfinyliminesfollowed by a radical cyclization. The stereochemical outcome of these two key steps was studied, and then this strategy was applied to CF2-carbasugars, inparticular of the CF2-carbocyclic analogue of D-arabinose.
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Réactivité des alpha-amino allénylphosphonates : des amino vinylphosphonates aux spirodiénones lactames / Reactivity of alpha-amino allenylphosphonates : from amino vinylphosphonates to spirodienones lactamsAdler, Pauline 16 September 2016 (has links)
Ces dernières années, les aminophosphonates, analogues des acides aminés, ont suscité un vif intérêt. En effet, ces composés présentent un large éventail d'activités biologiques. Récemment, une nouvelle approche pour la préparation des aminophosphonates a été développée, basée sur la réduction asymétrique des amino vinylphosphonates (AVPs). Bien que de nombreuses synthèses d’AVPs soient rapportées dans la littérature, leur application sur large échelle et la possibilité d’avoir une grande diversité de substituants restent un défi. C’est ce qui nous a conduits à préparer stéréosélectivement des alpha-AVPs. Nous avons développé une synthèse courte, efficace et stéréosélective pour accéder à ces composés. La première partie de ce travail a été le développement d'une synthèse efficace des alpha-amino allénylphosphonates (AAPs) afin d’étudier leur réduction en AVPs. Le second défi a été la réduction chimio- et stéréosélective des AAPs en AVPs. Nous avons établi des règles afin de prédire la stéréosélectivité de cette réduction qui dépend de la substitution sur l’allène, le groupement phosphonate et sur l'atome d'azote afin de préparer, au choix, l’AVP de configuration (Z) ou (E).Comme alternative à cette réduction chimique, nous avons entrepris une étude électrochimique sur nos substrats (Collaboration avec Pr. Pedro de Oliveira, Université Paris Sud). Nous avons montré que nous étions en mesure de réduire chimiosélectivement les AAPs en amino allylphosphonates. Afin d'élargir notre catalogue d’AVPs, nous avons étudié la réactivité des AVPs vis à vis des réactions de métathèse (Collaboration avec Dr. Joëlle Prunet, University of Glasgow). Nous avons développé une synthèse courte qui nous donne accès à de nouveaux AVPs cycliques. Enfin, dans le cadre de notre étude, nous nous sommes intéressés au traitement oxydant de nos AAPs protégés par un groupement para-méthoxybenzyle. Cela nous a permis de préparer trois types d’azaspirodiénones différents. Une étude approfondie du mécanisme a été entreprise. / In the past few years, aminophosphonates have attracted considerable attention due to their use as analogues of aminoacids. These compounds show a wide range of biological activities. Recently a new approach for the preparation of aminophosphonates, based on the asymmetric reduction of amino vinylphosphonates (AVPs), has been developed. Although several synthesis of AVPs are reported in the literature, their applicability to large scale and with a large diversity of substituents remains a challenge. This observation led us to stereoselectively prepare alpha-AVPs. We developed a short, efficient and stereoselective synthesis to access these AVPs. The first part of the work was the development of an efficient synthesis of alpha-amino allenylphosphonates (AAPs) to investigate their reduction as AVPs.The following challenge was the chemo- and stereoselective reduction of the AAPs into AVPs. We have established some rules to predict the stereoselectivity of this reduction, depending on the substitution on the allenyl moiety, on the phosphonate group and on the nitrogen atom in order to prepare either the (E)- or the (Z)-AVP.As an alternative to this chemical reduction, we started an electrochemical study on our substrates (Collaboration with Pr. Pedro de Oliveira, Université Paris Sud). We showed that we were able to chemoselectively reduce the AAPs into amino allylphosphonates. In order to enlarge our catalog of AVPs, we studied the reactivity of AVPs towards the metathesis reaction (Collaboration with Dr. Joëlle Prunet, University of Glasgow). We developed a short synthesis that gives us access to new cyclic AVPs. In the course of our studies on AAPs, we explored their reactivities towards oxidation. This led us to prepare three different types of azaspirodienones. A comprehensive study of the mechanism has been undertaken.
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New catalytic tools for the functionalization of alcohols and unactivated alkenes / Nouveaux outils catalytiques pour la fonctionnalisation d'alcools et d'alcènes non-activésQi, Chenxiao 04 July 2019 (has links)
A l’heure actuelle, il y a une forte demande de l’industrie de la chimie fine pour développer des procédures basées sur des réactions n’impliquant pas l’utilisation de métaux de transition et mettant en jeu des produits de départ facilement accessibles. Les principales raisons sont la disponibilité, le coût et la toxicité des métaux de transition ou des électrophiles. Dans ce contexte, utiliser d’alcools et alcènes pour la formation de liaisons carbone-carbone et carbone-hétéroatome est particulièrement attractif, cependant cela reste encore un challenge, surtout quand les substrats sont extrêmement désactivés ou susceptibles de piéger le catalyseur. Récemment, nous avons démontré que l’acidité de l’hexafluoroisopropanol (HFIP) pouvait être augmentée de façon significative par des sels de calcium(II) afin d’activer des liaisons C-O et C-C, surpassant les acides de Lewis et de Brønsted habituels que ce soit en termes d’activité ou de sélectivité grâce à la coordination de HFIP au calcium et la formation d’assemblages par liaison hydrogène. De plus, grâce à sa capacité à former des liaisons hydrogène fortes, HFIP peut faciliter la libération d’acides de Lewis piégés par une coordination non désirée avec le substrat (ou le produit), permettant, le turn-over du procédé catalytique. En particulier, l’association Ca²⁺/HFIP peut être un outil puissant pour promouvoir des électrocyclisations, hydroamidations, hydroarylations, hydroacyloxylations et des halofonctionnalisations. Ces réactions sont à la fois générales et compatibles avec un plus large éventail de substrats que les systèmes catalytiques classiques. / Today, there is a strong demand from the fine chemicals industry to develop procedures based on transition metal-free reactions using readily available starting materials. The main reasons behind this are the availability, cost and toxicity of transition-metals or electrophiles. In that respect, employing simple alcohols and alkenes for C-C and C-heteroatom bond forming reactions is truly appealing, but it can remain challenging, notably when the substrates are highly deactivated or prone to sequester the catalyst. Recently, we have demonstrated that the acidity of hexafluoroisopropanol (HFIP) could be significantly harnessed by calcium(II) salts in order to activate C-O and C-C bonds, outperforming common Lewis and Brønsted acids in terms of activity or efficiency in several reactions through the coordination of HFIP to calcium and the formation of hydrogen-bond clusters. Moreover, due to its strong hydrogen-bond donor ability, HFIP has the capacity to facilitate the release of Lewis acids trapped by unwanted coordination to the substrate (or the product), allowing the catalytic process to turn over. In particular, the combination Ca²⁺/HFIP can be a powerful tool to promote electrocyclizations, hydroamidations, hydroarylations, hydroacyloxylations and halofunctionalizations. These reactions proved to be general and compatible with a wider range of substrates than the traditional catalytic systems.
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Synthetic Methodology and Application of Enamine [2+2] Cyclisations for Cyclobutane Synthesis. Development of Integrin Antagonists as Anticancer Therapeutics Towards a Total Synthesis of ProvidencinThroup, Adam E. January 2015 (has links)
Cyclobutanes represent an underutilised structural feature in medicinal chemistry, partially due to difficulties in forming them in an easy and controlled manner. Herein is described their application to a drug discovery project and development of the enamine [2+2] cyclisation; a straightforward synthesis of functionalised cyclobutanes.
A library of 30 cyclobutane based integrin antagonists have been designed and synthesised to explore the SAR around the hit dual β3 integrin antagonist ICT9055. Several of which were shown to be highly potent antagonists inhibiting cancer cell adhesion, migration and invasion while remaining non-toxic. ICT9072 had comparable β3 activity to hit compound ICT9055 but also had activity against αvβ5 and therefore showed greater inhibition of migration of DLD-1 cells. This showed the ability to modify this scaffold for multi integrin antagonism and potential benefit of this.
Synthetic studies towards the marine natural product providencin has led to the development of a previously unknown intramolecular enamine [2+2] cyclisation which has been shown to proceed in a diastereoselective manner. This reaction has been applied to the synthesis of a highly functionalised enatiopure cyclobutene suitable for inclusion into the total synthesis. A model furyl cyclobutane has also been synthesised to exemplify the route from the enantiopure cyclobutene through to the furyl cyclobutane fragment of providencin. / Yorkshire Cancer Research
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Étude de la cycloalcoylation de phénanthrylpentènes et de phénanthrylbutènesGangloff-Delepoulle, Marie-France 01 February 2019 (has links)
Montréal Trigonix inc. 2018
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