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Pavlyuk, Oksana M. "Synthesis of Nitrogen-Containing Heterocycles via Carbenoid Insertion/Ring-Closing Metathesis Sequence." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1303761092.
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Salvador, Mayra Beloti. "Estudos visando a elucidação estrutural de uma diidro-2H-piranona natural." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/249254.
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Orientador: Ronaldo Aloise PilliDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica
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Resumo: Esta dissertação de mestrado trata da síntese da Criptomoscatona D2, uma lactona isolada pelo grupo de pesquisa dos Profs. Cavalheiro e Yoshida a partir da Cryptocarya moschata, planta encontrada em território brasileiro, cujas configurações relativa e absoluta ainda não foram determinadas. Além de auxiliar em sua elucidação estrutural a síntese desta molécula nos permitiria realizar estudos sobre sua atividade citotóxica, dando prosseguimento a estudos anteriores desenvolvidos em nosso laboratório com essa classe de compostos. Partindo-se do benziloxiacetaldeído obteve-se o álcool homoalílico quiral correspondente através de uma reação de alilação assimétrica com alilestanana e (S)-binaftol. Clivagem oxidativa da dupla ligação e reação de alilação mediada por InCl3 e estanho metálico na presença de brometo de alila forneceu uma mistura de álcoois homoalílicos sin/anti 1:1 cuja separação cromatográfica permitiu o prosseguimento da síntese racêmica com cada um dos diasteroisômeros. A reação de proteção das hidroxilas com o grupo TBS, seguida de clivagem oxidativa da dupla ligação e reação de alilação com BF3.Et2O e alilestanana forneceu o terceiro álcool homoalílico com mistura diastereoisomérica de cerca de 2:1 em ambas as rotas. Por fim, uma reação de esterificação do álcool remanescente na forma de acrilato seguida de reação de metátese de olefinas para formação do anel lactônico nos possibilitou o mapeamento de grande parte da rota sintética da Criptomoscatona D2 em sua forma racêmica
Abstract: This work describes the preliminary studies on the racemic and the asymmetric synthesis of Cryptomoscatone D2 based on sequential allylation reactions for the construction of its three stereogenic centers and ring-closing methatesis reaction to construct the lactone scaffold. Besides allowing the structure elucidation of the molecule isolated from a typical brazilian plant by the research groups of Profs. Cavalheiro and Yoshida, the synthesis of such a lactone would allow us to carry new cytotoxic studies which are being lately developed with this class of compound. The synthesis started with the allylation reaction of benzyloxyacetaldehyde under the conditions described by Keck and coworkers to furnish corresponding homoallylic alcohol. After an oxidative cleavage of the double bond, an InCl3 promoted allylation reaction allowed the preparation a 1:1 mixture of syn/anti homoallylic alcohols which were as the TBS ethers and submitted separately to double bond oxidative cleavages. These aldehydes were used as substrates for another allylation reaction with BF3.Et2O and allyltri-n-butyltin and the homolallylic alcohols (2:1 diatereoisomeric mixtures) were converted to the corresponding acrylates in order to carry out the planned RCM reaction. Several allylation reactions were tested and the homoallylic alcohols were prepared in 1:1 diasteroisomeric excesses. Efforts will be carried out in order to enhance the distereoselectivity of the allylation reactions for an efficient approach to Cryptomoscatone D2 (12) backbone
Mestrado
Quimica Organica
Mestre em Química
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Kavitake, Santosh. "A synergy between well-defined homogeneous and heterogeneous catalysts : the case of Ring Opening - Ring Closing Metathesis of cyclooctene." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10211/document.
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Dans le cadre de la formation sélective d'oligomères cycliques à partir du cyclo-octène, des matériaux hybrides organiques-inorganiques mésostructurés bien-définis contenant les unités Ru-NHC dissymétriques le long des canaux poreux de leur matrice de silice ont été développés et caractérisés à un niveau moléculaire. Tous les systèmes obtenus ont montré des fortes activités et sélectivités en oligomères cycliques (dimères : 50% et trimères : 25%) en RO-RCM du cyclo-octène, contrairement aux complexes homogènes Ru-NHC analogues symétriques (G-II et GH-II), qui conduisent préférentiellement à la formation de polymères. La variation de la longueur et de la flexibilité des bras espaceurs, dans le cas des catalyseurs hétérogènes, a prouvé que les bras courts et flexibles stabilisent grandement les sites actifs Ru-NHC pendant la réaction de métathèse et ce, grâce à la présence d'interactions entre les sites Ru-NHC catalytiquement actifs et la surface silicique. La présence de telles interactions a été mise en évidence par RMN du phosphore 31 à l'état solide. Des études supplémentaires concernant les performances catalytiques de complexes organométalliques Ru-NHC dissymétriques (analogues aux sites Ru-NHC contenus dans les catalyseurs hétérogènes) et Ru-NHC symétriques (G-II et Nolan) ont clairement montré que le facteur clé influençant la sélectivité en oligomères cycliques est la dissymétrie des ligands NHC. Cette dissymétrie génère la présence de deux sites actifs de configurations différentes au sein même des espèces Ru-NHC. Un des sites favorise la réaction intramoléculaire de fermeture de cycle par métathèse alors que l'autre site permet la réaction intermoléculaire d'ouverture de cycle conduisant ainsi à la formation des oligomères cycliques de petite tailleIn the context of the selective formation of cyclic oligomers from cyclooctene, well-defined hybrid organic-inorganic mesoporous materials containing unsymmetrical Ru-NHC units along the pore channel of their silica matrix have been developed and characterized at a molecular level. All systems displayed high activity and selectivity towards the formation of lower cyclic oligomers in the RO-RCM of cyclooctene yielding mainly the dimer and the trimer with 50% and 25% selectivity, respectively, in contrast to classical symmetrical homogeneous analogues (G-II and GH-II), which yield mainly to polymers. Variation of length and flexibility of the tethers showed that flexible short tethers were critical for high stability of the catalysts during metathesis, which is consistent with the stabilization of Ru-NHC active sites by surface functionalities; this surface interaction was further corroborated by the absence of a PCy3 ligand coordinated to Ru when short flexible linkers are used. Further investigations using homogeneous symmetrical (G-II and Nolan) and unsymmetrical (analogues to heterogeneous catalysts) Ru-NHC catalysts clearly showed that the key factor influencing the selectivity towards low cyclic oligomers is the unsymmetrical nature of NHC ligands, which creates dual site configuration in the catalyst architecture thus alternatively favouring one reaction over another, Ring Opening (ROM) vs. Ring Closing (RCM) Metathesis (propagation vs. backbiting), thus leading to the selective tandem RO RCM of cyclooctene. Finally, we have also investigated Grubbs Hoveyda-II (GH-II) type catalysts immobilized on silica support through adsorption, which showed the same product selectivity as that of the well-defined Ru-NHC materials. This result implies that the adsorbed symmetrical GH-II catalyst “becomes unsymmetrical upon adsorption”. Adsorbing unsymmetrical molecular GH II catalysts did not however improve the performances of these types of catalysts. Overall, the unique property of unsymmetrical NHC Ru catalyst, whether supported or not, opens new perspectives in the selective synthesis of macrocycles from other cyclic alkenes via metathesis
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Finelli, Fernanda Gadini. "Sintese da macrolactona da migrastatina e analogo : sinteses e aplicações de novos substratos em reações de RCAM catalisadas por [Mo]." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/248483.
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Orientador: Luiz Carlos DiasTese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica
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Resumo: O capítulo 1 relata as sínteses da macrolactona da migrastatina 11 e da macrolactona análoga 62a. A macrolactona da migrastatina é o composto que apresenta a maior atividade de inibição de migração de células tumorais in vitro dentre os compostos da família da migrastatina até hoje sintetizados. A macrolactona 62a, ainda inédita na literatura, é epímero em C8 da macrolactona 62b sintetizada pelo grupo do Professor Danishefsky em 2004 e apresenta atividade de inibição semelhante à macrolactona 11. Além disso, foram realizados estudos visando à síntese da macrolactona 124, epímero da macrolactona 11. Paralelamente, em colaboração com a Farmoquímica Cristália e o grupo do Professor Adriano Andricopulo, do IF/USP de São Carlos, foram realizados testes de avaliação biológica de diversos compostos sintetizados neste trabalho com o intuito de gerar novas substâncias químicas bioativas candidatas a novos fármacos no tratamento do câncer de mama. O capítulo 2 relata a síntese e aplicação de alguns substratos contendo grupos funcionais que ainda não haviam sido testados frente à reação de metátese de alcinos utilizando um novo catalisador de molibdênio. Este projeto foi desenvolvido no laboratório do Professor Alois Fürstner, no Instituto Max-Planck, em Mülheim an der Ruhr ¿ Alemanha. Além disso, um precursor do fragmento B das Latrunculinas A e B foi sintetizado em grande escala, fornecendo material para subsequentes estudos químicos e biológicos
Abstract: Chapter 1 describes the syntheses of macrolactones 11 and 62a. Macrolactone 11 presents the best tumor cell migration inhibitory effect among the compounds of the migrastatin family synthesized so far. Macrolactone 62a, not described in the literature, is the C8-epimer of macrolactone 62b, which was synthesized by Professor Danishefsky¿s group in 2004 and shows similar antitumor activities when compared to macrolactone 11. Studies aiming at the synthesis of macrolactone 124, epimer of macrolactone 11, were also performed. Besides, in collaboration with Farmoquímica Cristália and Professor Andricopulo¿s group (IF/USP, São Carlos), biological assays of several compounds synthesized in this work were carried out, with the purpose of developing new bioactive chemical substances which may soon be employed in the manufacturing of novel drugs in the treatment of breast cancer.Chapter 2 describes the syntheses of new substrates for applications in Mo-catalyzed RCAM. This project was carried out in Professor Fürstner¿s laboratory, at Max-Planck Institute, in Mülheim an der Ruhr ¿ Germany. In this part of the work, a Latrunculin A and B fragment precursor was also synthesized in large scale to provide further material for new biological and chemical studies
Doutorado
Quimica Organica
Doutor em Ciências
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Helmboldt, Hannes. "Studien zur Synthese von Jatrophan-Diterpenen." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1149002173288-83354.
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Es wird die enantioselektive Synthese eines substituierten Cyclopentanfragmentes beschrieben, welches zur Synthese einer Vielzahl von Diterpenen aus Euphorbiaceae genutzt werden kann. Schlüsselschritt hierbei ist eine intramolekulare Carbonyl-En-Reaktion. In zwei verschiedenen Syntheseansätzen wurde versucht, dieses zu einem Jatrophan-Diterpen umzusetzen. Versuche hinsichtlich einer Nozaki-Hiyama-Kishi-Kupplung werden beschrieben. Im zweiten Ansatz, wurde über eine Ringschlussmetathese bzw. eine Relay-Ringschlussmetathese versucht entsprechende Jatrophane herzustellen. Dies gelang bei einem Substrat, welches eine zweifach substituierte Doppelbindung beinhaltet. Somit konnte ein nichtnatürliches 17-Norjatrophan enantioselektiv synthetisiert werdenThe enantioselective synthesis of a highly substituted cyclopentan, useful for the synthesis of diterpenes from Euphorbiaceae is described. Key step is a intramolecular carbonyl-en reaction. Two different approaches towards Jatrophanes were examined. The first one envisioning a Nozaki-Hiyama-Kishi coupling didn´t work. The second one employed a ring-closing-metathesis which was successful in the case of a disubstituted double bond formed. The use of an relay-ring-closing-metathesis was also examined. The enantioselective synthesis of a nonnatural 17-Norjatrophane is described in all details
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Aitken, Steven Geoffrey. "Design, synthesis and testing of β-strand mimics as protease inhibitors." Thesis, University of Canterbury. Chemistry, 2006. http://hdl.handle.net/10092/1984.
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Chapter 1 gives background information on proteases and discusses the concept of protease inhibition as a therapeutic strategy for humans. It introduces the key concept that conformation defines biological activity. It also outlines how proteases almost universally bind their substrate/inhibitors in an extended β-strand conformation. The use of calpain as a prototype protease for the testing of β-strand mimics synthesised later in the thesis is also discussed. Chapter 2 describes how molecular modeling was used to rationalise the structure based activity relationships (SAR) of known calpain inhibitors. Molecular modeling was then used to successfully design a number of acyclic β-strand mimics. The synthesis and testing of eight such inhibitors is described. The most potent β-strand mimic prepared was 2.13. This was determined to have an IC₅₀ of 30 nM against calpain II. Chapter 3 outlines the history and application of ring closing metathesis (RCM) to the synthesis of cyclic compounds. The attempted synthesis of an eight membered cyclic nitrogen to nitrogen conformationally constrained dipeptide is described. The synthesis of a conformationally constrained β-amino acid calpain inhibitor (3.73) is also described. A novel calpain inhibitor motif was designed in Chapter 4. On the basis of this an in-silico combinatorial library of two hundred and eighty eight possible β-strand templates was prepared. Conformational analysis of this library was performed and from this a number of excellent β-strand templates were identified and selected for synthesis. The preparation of ten β-strand templates is described. New microwave irradiation methodology was developed to achieve this. vii The formation of a six-membered catalyst deactivating chelate is also proposed to explain why some dienes fail to undergo RCM. Two methods to circumvent the formation of such a chelate are outlined. The addition of Lewis acid chloro-dicyclohexyl borane to the RCM reaction mixture and chain length alteration are investigated. Chapter 5 describes the design of macrocyclic β-strand mimics using induced fit molecular modelling. The physicochemical properties of these were calculated in-silico. From this analysis a number of Tyr-XX-Gly based and Tyr-XX-Cys based macrocyclic calpain inhibitors were selected for synthesis. The preparation and testing of these are described. In the Tyr-XX-Gly macrocyclic system a number of variables were investigated and numerous SAR implications concluded. Aldehyde 5.14 was identified as the best electrophilic warhead macrocyclic calpain inhibitor with an IC₅₀ against calpain II of 27 nM. The best non-electrophilic warhead macrocycle (5.13) had an IC₅₀ against calpain II of 704 nM. Chapter 6 describes synthetic optimisation for the preparation of calpain inhibitors 2.13, 5.14 and 5.17. Multi-gram quantities of each were prepared. Aldehydes 2.13 and 5.14 were evaluated as anti-cataract agents using in-vivo cataract sheep model. Both of these β-strand mimics were demonstrated to retard cataract development. Macrocycle 5.14 was found to be the most effective, decreasing the rate of cataract development between forty four and forty nine per cent relative to control. Chapter 7 outlines the attempted development of RCM methodology for the chiral synthesis of α-α disubstituted amino acid lactams. In addition, methodology for the stereoselective incorporation of a C-N constrained β-amino acid carbocycle into a peptide or peptidomimetic is described.
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Coe, Samuel. "Phyllostictine A ring assembly via ring closing metathesis." Thesis, University of Warwick, 2014. http://wrap.warwick.ac.uk/67101/.
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This thesis describes work focused on the chemical synthesis and herbicidal activity of the natural product phyllostictine A, a molecule of unique structure and unknown mode of action. Chapter 1 serves to introduce the natural product and describe the known activity of the natural product. Furthermore, it discusses literature methods for the construction of a-methylene-b-lactams, a key component of phyllostictine A. Chapter 2 describes work towards the construction of the macrocyclic rings found in phyllostictine A. As a result a-methylene-b-lactams have been shown, for the first time, to participate in RCM reactions. Formation of 11- and 12-membered trisubstituted membered rings was possible, however, the nature of the nitrogen substituent has a large impact. For example, 12-membered rings 124, 130 were formed in 37% yield when a para-methoxyphenyl group was utilised, while simple ethyl substitution could only achieve yields of 20%. Boc protected lactam 169 produced only linear dimer 170. The synthesis of tetrasubstituted alkenes via RCM was attempted with lactam 145, however, resulted in an unexpected rearrangement product. Not only was the RCM sensitive to the nitrogen substituent but also the size of ring being formed. For example, 11-membered rings produced significant amounts of the 22-membered dimers 89 and 87. Throughout the RCM reactions performed in this thesis held a preference for the Z-alkene. The trend was confirmed both by NMR shift analysis and X-ray crystallography. Chapter 3 describes work towards the synthesis of 4,4-disubstituted a-methylene-b-lactam subunit of phyllostictine A. Three methods: epoxide rearrangement, carbonylation of methyleneaziridines and carbonylation of 2-bromo-allyl-propenes were explored. Chapter 4 describes the herbicidal activity of phyllostictine A against the single celled algae C. reinhardtii. ED50 data was obtained for phyllostictine A against C. reinhardtii for the first time. Furthermore, it was shown to be comparable to the commercial herbicide glyphosate. Six novel a-methylene-b-lactams synthesised in Chapter 2 were tested for herbicidal activity against C. reinhardtii which has enabled us to develop preliminary structure-activity relationships.
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Salim, Sofia Saima. "Synthesis of sulfamides using ring closing diene metathesis and enyne metathesis." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417402.
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Miles, Steven Malcolm. "Bio-active molecule synthesis incorporating ring-closing metathesis." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406173.
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Barker, William D. "Photoannulation and ring closing metathesis of carbohydrate derivatives." Thesis, University of Leicester, 2000. http://hdl.handle.net/2381/30040.
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The 'chiron approach' is a well-recognised technique for converting carbohydrates and other naturally occurring compounds into new chiral target molecules. The success of this area of chemistry can be attributed to the vast array of novel methods for transforming carbohydrates that have been developed over the last 50 years. Chapter 1 describes some of the key discoveries and pioneers within the field of carbohydrate annulation. As part of the Jenkins groups' on-going studies into the development of new methods for carbohydrate annulation, we have demonstrated the ease in which simple carbohydrate derivatives can be cyclised by Ring Closing Metathesis (RCM). Using Grubbs ruthenium catalyst 176b, we have cyclised a range of substrates derived from D-glucose to give annulated products such as 307. Some of the adducts have been reduced by well known methodology to give chiral fragments such as 348 which may be used as 'chiron' in further synthesis (Chapter 2). (Fig. 10916A). We have also utilised the copper (I) triflate catalysed intramolecular [2+2] photocycloaddition reaction to cyclise a range of carbohydrate derivatives such as 306 to afford enantiomerically pure products 400 and this represents a novel method to add to the increasingly wide range of techniques for annulating carbohydrates. (Fig. 10916B). To further extend the scope of the catalysed [2+2] photochemical ring closure reaction, we have investigated a variety of reagents in an attempt to make it an asymmetric catalytic process. The chiral diene 535 can be cyclised in the presence of a number of chiral catalysts such as 554 to give two enantiomeric tricyclic products 536a and 536b, which can be quantitatively analysed by chiral hplc. The chiral catalyst should favour on enantiomer over the other. We have considered a variety of substrates, reagents and reaction conditions, and the results are reported in chapter 4. (Fig. 10916C).
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Jamieson, Jennifer Yvonne 1975. "Ligand variation in molybdenum asymmetric ring-closing metathesis catalysts." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/8053.
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Vernall, Andrea J. "Cross Metathesis and Ring-Closing Metathesis Reactions of Modified Amino Acids and Peptides." Thesis, University of Canterbury. Chemistry, 2005. http://hdl.handle.net/10092/5798.
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This thesis investigates the application of cross metathesis and ring-closing metathesis to amino acid and peptide-based substrates that are suitably modified to contain an olefin tether.
Chapter One introduces olefin metathesis, describes the mechanism of cross metathesis (CM) and ring-closing metathesis (RCM), and outlines the catalysts that can be used for these transformations. The application of CM and RCM to amino acid and peptide-based systems is reviewed.
Chapter Two describes the CM coupling between modified lysine- (2.34 - 2.37, 2.43), serine- (2.45, 2.46), and cysteine-based (2.48, 2.49a, 2.51) amino acids and dipeptides (2.54, 2.57) to a terminal alkene (2.61, 2.65), carbohydrate (1.51b), or fatty acid (2.76) target compound using catalyst 1.17. The amino acid and dipeptide-based CM substrates were prepared by side-chain acylation of the parent amino acid with carboxylic acids containing variable but controllable olefin tether lengths. A CM model study in which these amino acid-based substrates were coupled to terminal alkene 2.61 and 2.65 gave CM products 2.66 - 2.74. CM was then carried out between amino acid-based substrates and a carbohydrate (1.51b) or fatty acid derivative (2.76), that afforded a novel series of glycoamino acids (2.80 - 2.85) and lipoamino acids (2.94 - 2.101).
Chapter Three describes the synthesis of amino acid dimers by CM. Two serine-based (3.22 - 3.23) and two cysteine-based (3.24 - 3.25) symmetrical dimers along with two unsymmetrical serine-cysteine dimers (3.26 - 3.27) were prepared from the same side-chain acylated amino acid substrates described in chapter 2. These compounds are examples of novel cross-linked amino acid-based dimers, and further illustrate the versatility of the CM methodology developed in this thesis.
Chapter Four describes the synthesis of cyclic amino acids and dipeptides via RCM of acyclic precursors that are suitably modified with acyl olefin tethers of variable length. Cyclic compounds based on lysine (4.6, 4.13), serine (4.31, 4.33), and cysteine (4.40, 4.42) single amino acid residues, and compounds based on lysine (4.16, 4.21, 4.27), serine (4.37), and cysteine (4.45, 4.46) dipeptides were prepared. All these compounds were constructed using the same, versatile general method, which involves acylation of the natural amino acid substrate with a carboxylic acid of controllable olefin tether length followed by RCM with catalyst 1.17 to give cyclic products containing variable ring sizes.
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Nam, Youn Hee. "Development of Ru-Catalyzed Tandem Sequences Involving Ring-Closing Metathesis." Thesis, Boston College, 2013. http://hdl.handle.net/2345/3036.
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Thesis advisor: Marc L. SnapperTandem processes can have several advantages over multiple single step processes. Non-metathesis transformations of ruthenium alkylidenes were studied and applied to tandem processes. Ruthenium catalyzed tandem RCM/hydroacylation that allows access to tricyclic ring systems from readily available substrates was developed. Mechanistic investigations indicated that this reaction may proceed through a mechanism involving [Ru]-H species. A Ru-catalyzed tandem RCM/olefin isomerization/C-H activation sequence that provides significant advantages in terms of rapid elaboration of simple reaction partners to more complex entities was developed
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Letort, Aurelien. "Ring-closing metathesis cascade toward a formal synthesis of taxol." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6677/.
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TaxolTM and its derivatives are the largest selling anticancer drugs of all time. Numerous synthetic works and total syntheses have been published since its discovery, but to date no high yielding synthesis with less than 37 steps has been achieved. In this thesis is presented our synthetic efforts toward such a robust and efficient synthesis of Taxol. The optimisation of the Shapiro coupling fragments syntheses were investigated to enhance the robustness of our strategy. Then the C7-deoxy model ABC tricycle ring-system of Taxol, which lacks the oxygenated substituent at C7, has been efficiently synthesised by a dienyne ring-closing metathesis cascade (RCDEYM). This cascade closed the AB 6/8 membered ring system in a single operation. Other dienyne ring-closing metathesis cascades with similar substrates were also performed, assessing the influence of ruthenium catalysts, C1-C2 diol protecting groups (R1, R2), and substitution of the alkene at C13. Synthetic efforts were also devoted to apply such a powerful method toward a formal synthesis of Taxol from an intermediate Holton and co-workers synthesised. During our studies, the C7-oxy group was found to be critical to access the ABC tricyclic core of Taxol by metathesis cascade. Understanding of the importance of this C7-oxy group was undertaken and led to the conception of a metathesis cascade prediction model. Once the metathesis cascade was optimised, differentiation of the three trisubstituted alkenes present on the ABC tricyclic ring system was studied and elaboration of a formal synthesis was endeavoured.
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Blackwell, Helen Elizabeth Grubbs Robert H. "New synthetic applications for ring-closing metathesis and cross-metathesis employing well-defined ruthenium alkylidenes /." Diss., Pasadena, Calif. : California Institute of Technology, 1999. http://resolver.caltech.edu/CaltechETD:etd-09262005-133922.
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White, John William. "An Evans-Tishchenko/ring closing metathesis approach towards the medium ring lactone, octalactin A." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/11557.
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Medium-ring lactones have become important targets for synthesis as they have been isolated in an increasing number of biologically active natural products. The studies towards two 8-membered ring lactone natural products, octalactins A 1 and B 2, will be described. The first section of this thesis examines the application of key methodology (anti aldol reaction, Homer Wadsworth Emmons olefination, intermolecular Evans- Tishchenko coupling and Ring Closing Metathesis) towards the octalactins via the synthesis of a model lactone 3 (Chapter 2). The second section (Chapter 3) discusses the extension of the aldol methodology from Chapter 2 towards the development of a novel chiral auxiliary 4 to mediate the anti aldol reaction. The generality of this new auxiliary in anti aldol reactions will also be discussed. The final part of this thesis describes the synthesis of the octalactins based on the application of the methodology developed from the model studies using the key functionalised fragments: aldehyde 5, 3-ketophosphonate ester 6 and aldehyde 7.
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Feng, Gaofeng. "Total synthesis of 24-demethylbafilomycins using diester-tethered ring-closing metathesis /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202010%20FENG.
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Astle, Christopher John. "The synthesis of tropane alkaloids using ring closing and cross metathesis." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408999.
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Klanchantra, Mutita. "Design and synthesis of beta-strand conformationally constrained calpain inhibitors for cataract treatment via metathesis ring closure." Thesis, University of Canterbury. Chemistry, 2006. http://hdl.handle.net/10092/1609.
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This thesis summarises the progress made in the design and synthesis of conformationally constrained β-strand peptidomimetic compounds using ring closing metathesis methodology under microwave irridation conditions. The best macrocycle were elaborated into an inhibitor for a specific protease target. Calpain was used as an example of protease targeting cataract disease. Chapter One introduces proteases in general centring on the general context of protease inhibitor design. The significant of the β-strand 'bioactive' conformation is discussed in details in particular the exploitation of conformationally constrained to potential lock the 'bioactive' conformation. Chapter Two illustrates in silico methods used to design a series of β-strand macrocycle 2.1-2.7. The analysis of these is performed using molecular modelling software Schrodinger suite (2005). A brief discussion of ring closing metathesis methodology is also included. Chapter Three describes the synthesis of the precursor required for RCM reactions (tripeptides dienes). Various types of allylated amino acid side chains were synthesised. The tripeptides were obtained using standard peptide coupling methodology utilising reagents such as HATU, EDC and HOAT. Chapter Four describes the application of ring closing metathesis for the synthesis of β-strand macrocycles. The development of a new reaction conditions to optimise the ring closing metathesis reaction is discussed. In particular the effect of the use of a Lewis acid (chlorodicyclohexylborane) additive in RCM reactions is investigated. Chapter Five discusses the mechanism of cataract formation, cataract treatment and the potential development of calpain inhibitors. One of the macrocycles synthesised in chapter 4 is elaborated into a calpain inhibitor. The in-vitro assay result of this is presented and this compound is currently undergoing in vivo evaluation.
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Mitchell, Lisa. "The interplay of structure and reactivity on a ring closing metathesis reaction." Thesis, University of Leicester, 2008. http://hdl.handle.net/2381/30003.
Full textAbstract:
This Thesis describes investigations of how structure affects a cyclooctannulation of a difluorinated diene via ruthenium-catalysed ring closing metathesis (RCM). The study originated in attempts to optimise these reactions towards the synthesis of novel difluorinated analogues of sugars.;A range of difluorinated dienes have been synthesised in order to study the effects of allylic protecting group on cyclisation efficiency, using the CF2 group as a probe to reaction outcomes via 19F NMR. We identified a 102 fold difference in cyclisation efficiency depending on which allylic protecting group was used. However, kinetic studies have shown us that allylic protecting groups have only a moderate effect on cyclisation rate. Kinetic studies have also shown us that the cyclisation is affected by the presence of gem-dialkyl groups, which accelerate the rate---an effect which has not been quantified for the formation of medium rings by RCM previously.;1H NMR kinetics has enabled the identification of the most significant catalytic species on the reaction timescale, including identification of catalytic decomposition products. This has led to the development of a kinetic data model to which all kinetic data were fitted, using simulation software, and has allowed a deeper analysis and understanding of how olefin structure affects reactivity in RCM.;Based on the kinetic data, RCM substrates, which prolong catalytic lifetime and simplify reaction kinetics have been synthesised and examined. In addition to this, the effects of reaction solvent, temperature, catalyst and catalyst loading on the cyclisation rate have been studied in order to identify the optimum conditions for synthesis of the desired difluorinated cyclooctenones.
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Doodeman, Robin. "Synthesis of oxygen and nitrogen heterocycles via stabilized carbocations and ring-closing metathesis." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/65801.
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Nelson, David James. "The interplay of structure and reactivity in ruthenium-catalysed alkene ring-closing metathesis." Thesis, University of Strathclyde, 2012. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=18035.
Full textAbstract:
Alkene ring-closing metathesis (RCM) has fundamentally changed the way that chemists consider the construction of molecules. However, quantitative understanding has not progressed at the same rate as synthetic application. There is still not a firm quantitative understanding of the relationship between pre-catalyst and diene structure and reaction rate or efficiency; measurements reported are typically yield measurements, which are sensitive to the work-up and isolation methods employed. Work towards a detailed quantitative understanding of the interplay between structure and reactivity is presented. A variety of classical and modern physical organic chemistry tools such as spectroscopy, kinetic studies, density functional theory, and reaction simulation are employed. Kinetic studies were applied to investigate the effect of ring size on RCM rate. The order of reactivity in prototypical dienes, in reactions shown to be under thermodynamic control, was established qualitatively an d some quantification of this order of reactivity is presented. Attempts to quantify kinetic EMs were unsuccessful. Additionally, 1,5-hexadiene was revealed to be a metathesis inhibitor. Reaction simulation approaches were explored for the quantification of outcomes from kinetic experiments and for comparison of substrates. An existing model for RCM was tested and several flaws were identified; overcoming these flaws allowed successful application of the model to substrate and pre-catalyst evaluation. Significant substrate isomerisation encountered in small-scale reactions was probed using kinetic experiments under a number of reaction conditions. Benzoquinone suppressed this isomerisation but reduced the rate of productive RCM. A number of potential isomerisation agents were prepared and benchmarked, and one was detected in very small quantities in a metathesis reaction. This work contributes to better quantitative understanding of RCM. In addition, the small-scale metathesis reaction simulation approaches are excellent means by which to rapidly identify suitable reaction conditions for metathesis reactions.
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Wybrow, Robert Anthony James. "Investigations towards the synthesis of (-)-histrionicotoxin via a tandem ring closing metathesis technique." Thesis, University of Sheffield, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419328.
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Margue, Robert Germain. "Mechanistic investigations of enyne ring-closing metathesis reactions catalysed by ruthenium based systems." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431634.
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Basu, Kallol. "New aspects in ring closing metathesis reactions studies toward the synthesis of mangicol A." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1093973365.
Full textAbstract:
Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xviii, 228 p.; also includes graphics. Includes bibliographical references (p. 128-137).
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Edwards, Andrew. "The application of tandem ring closing metathesis : studies towards the total synthesis of (-)-histrionicotoxin." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269348.
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Mak, Xiao Yin. "Tandem benzannulation-ring closing metathesis strategy for the synthesis of benzo-fused nitrogen heterocycles." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/46034.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008.Vita.
Includes bibliographical references.
A tandem benzannulation-ring closing metathesis strategy for the efficient synthesis of benzo-fused nitrogen heterocycles such as dihydroquinolines, benzazepines, and benzazocines has been developed. This strategy is based on the benzannulation reaction of ynamides with cyclobutenones or [alpha]-diazo ketones to generate highly-substituted aniline derivatives, which then participate in ring-closing metathesis reactions to form nitrogen heterocycles. The synthetic utility of this strategy has been demonstrated by its successful application in a formal synthesis of the natural product (+)-FR900482. In addition, an environmentally-friendly approach to the synthesis of amides and lactams has been developed using supercritical carbon dioxide as a 'green' replacement solvent. The amide products are generated from the addition of amines to ketenes, which are formed in situ from the retro-ene reaction of alkynyl ethers.
by Xiao Yin Mak.
Ph.D.
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Wu, Xiao. "New routes to 2,5-disubstituted tetrahydropyrans and P-stereogenic heterocycles via ring-closing metathesis." Thesis, University of York, 2013. http://etheses.whiterose.ac.uk/4494/.
Full textAbstract:
New methodologies have been developed for the synthesis of 2,5-disubstituted tetrahydropyrans and for the asymmetric synthesis of P-stereogenic phospholene boranes. Synthesis of 2,5-disubstituted tetrahydropyrans in a racemic fashion was achieved via Grignard addition, O-alkylation, ring-closing metathesis and hydrogenation. Using this route, seven potential perfumery compounds were produced in good overall yield. Olfactory evaluation of the potential perfumery molecules accessed the majority of products as having a predominant characteristic of citrus note and others having a floral note. In addition, asymmetric synthesis of two saturated cyclic ethers was achieved using an asymmetric deprotonation approach. An alternative route to an enantioenriched alcohol using catalytic asymmetric deprotonation and trapping with Andersen’s sulfinate was briefly studied and proved successful. The asymmetric synthesis of P-stereogenic phospholene boranes was investigated. First, three chiral diamines were synthesised and their asymmetric induction was tested in the asymmetric lithiation of t-butyl phosphine boranes. Subsequently, the asymmetric synthesis of P-stereogenic vinylic phospholene boranes was carried out. Using s-BuLi/(_)-sparteine as a base, alkylated phosphine boranes were isolated with good yield and high enantioselectivity. A telescoped regioselective deprotonation/trapping of paraformaldehyde and elimination reaction was developed to gain access to the dienes. Finally, ring-closing metathesis afforded the desired vinylic phospholene boranes. The application represents the first example of asymmetric synthesis of P-stereogenic vinylic phospholene boranes.
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Dorgan, Philip D. "An Evans-Tishchenko/ring-closing alkyne metathesis approach towards the synthesis of Disorazole C₁." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/13692.
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Courtney, Anne Kathleen. "Studies of substituted olefins in ring closing olefin metathesis and approaches toward a synthesis of manzamine A /." Digital version accessible at:, 2000. http://wwwlib.umi.com/cr/utexas/main.
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Xu, Chaofan. "New Ru-Based Catalysts and Strategies for Kinetically Controlled Stereoselective Olefin Metathesis:." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:109015.
Full textAbstract:
Thesis advisor: Amir H. HoveydaChapter 1. In Situ Methylene Capping: A Key Strategy in Catalytic Stereoretentive Olefin MetathesisA general approach for in situ methylene capping that significantly expands the scope of catalyst-controlled stereoselective olefin metathesis is presented. By incorporation of stereodefined 2-butene as the capping reagent, the catechothiolate Ru complex is enabled to catalyze olefin metathesis reactions of terminal alkenes. Substrates bearing a carboxylic acid, an aldehyde, an aryl substituent, an α substituent were thus converted to the desired products in 47–88% yield and 90:10–98:2 Z:E selectivity. The capping strategy was also applied in ring-closing metathesis reactions leading to 14- to 21-membered macrocyclic alkenes (96:4–98:2 Z:E). The utility of this method was highlighted through synthesis of a platelet aggregate inhibitor and two members of the prostaglandin family compounds by cross-metathesis reaction, as well as a strained 14-membered ring stapled peptide by macrocyclic ring-closing metathesis. Examples of the corresponding E-selective cross-processes are provided as well. Chapter 2. Synthesis of Z- or E-Trisubstituted Allylic Alcohols and Ethers by Kinetically Controlled Catalytic Cross-MetathesisKinetically controlled Ru-catalyzed cross-metathesis reactions that generate Z- or E-trisubstituted alkenes are discussed. Reactions were catalyzed by catechothiolate Ru complex to generate trisubstituted allylic alcohols and ethers in up to 81% yield and >98% stereoisomeric purity. The approach is applicable to synthesis of products containing an alcohol, an aldehyde, a carboxylic acid or an alkenyl substituent. Mechanistic models that account for the observed trends in efficiency and stereoselectivity will be provided. Chapter 3. A New Ru-Based Catechothiolate Complex Bearing an Unsaturated NHC Ligand for Synthesis of Z-α,β-Unsaturated Carbonyl Compounds by Cross Metathesis Design and development of a new Ru catechothiolate complex that may be used to promote Z-selective cross-metathesis transformations that afford Z-α,β-unsaturated esters, acids, and amides (including Weinweb amides) are discussed. Comparison between Ru catechothiolate complexes with an unsaturated NHC and a saturated NHC ligand will be provided. Utility of the approach is demonstrated by an eight-step synthesis (15% overall yield) of an intermediate for synthesis of stagonolide E, and a five-step synthesis of a precursor to dihydrocompactin
Thesis (PhD) — Boston College, 2020
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
32
Satcharoen, Vachiraporn. "The ring-closing metathesis of vinyl fluoro- and bromo-containing dienes synthesis of (±)-deoxygalanthamine." Thesis, University of Southampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430673.
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Moriggi, Jean-Dominique Francois Michel. "Solid-phase synthesis of cyclic sulfonamides and sulfamides employing a ring-closing metathesis cleavage strategy." Thesis, London South Bank University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342638.
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Chen, Zhong-Ren Kornfield Julia A. Grubbs Robert H. "I. Dynamics of block copolymer nanostructures. : II. Polymerizability of cyclic olefins and ring-closing metathesis /." Diss., Pasadena, Calif. : California Institute of Technology, 1998. http://resolver.caltech.edu/CaltechETD:etd-01242008-095827.
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Alexander, John Bryson 1972. "Chiral molybdenum and tungsten imido alkylidene complexes as catalysts for asymmetric ring-closing metathesis (ARCM)." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/44898.
Full textAbstract:
Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999.Includes bibliographical references (leaves 172-179).
Chapter 1. The synthesis and resolution of sterically encumbered biphenols is presented. -- Chapter 2. The synthesis of molybdenum(VI) imido alkylidene complexes containing racemic and optically pure biphenoxides (Biphen and Biad) is reported. -- Chapter 3. The 1H NMR spectroscopic data for molybdenum(VI) imido alkylidene biphenoxide complexes prepared in Chapter 2 are presented. -- Chapter 4. The application of catalysts prepared in Chapter 2 in asymmetric ring-closing metathesis (ARCM) is described. -- Chapter 5. Synthesis, characterization and reactivity of (±)(Me2)W(Neo) and (±)(iPr 2)W(Neo) . PMe2Ph is discussed.
by John Bryson Alexander.
Ph.D.
36
Méndez-Andino, José Luis. "New fields in organic chemistry : developments in aqueous organoindium chemistry and ring closing olefin metathesis /." The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488204276534782.
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Wang, Yikai. "Studies on Application of Silyl Groups in Ring-Closing Metathesis Reactions and Fragment-Based Probe Discovery." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10115.
Full textAbstract:
In efforts to search for tool compounds that are capable of probing normal and disease-associated biological processes, both quality and identity of the screening collection are very important. Towards this goal, diversity-oriented synthesis (DOS) has been explored for a decade, which aims to populate the chemical space with diverse sets of small molecules distinct from the traditional ones obtained via combinatorial chemistry. In the practice of DOS, macrocyclic ring-closing metathesis (RCM) reactions have been widely used. However, the prediction and control of stereoselectivity of the reaction is often challenging; chemical transformation of the olefin moiety within the product is in general limited. Chapter I of this thesis describes a methodology that addresses both problems simultaneously and thus extends the utility of the RCM reactions. By installing a silyl group at the internal position of one of the olefin termini, the RCM reaction could proceed with high stereoselectivity to afford the (E)-alkenylsiloxane regardless of the intrinsic selectivity of the substrate. The resulting alkenylsiloxane can be transformed to a variety of functionalities in a regiospecific fashion. The conversion of the (E)-alkenylsiloxanes to alkenyl bromides could proceed with inversion of stereochemistry for some substrates allowing the selective access of both the E- and Z-trisubstituted macrocyclic alkenes. It was also found that the silyl group could trap the desired mono-cyclized product by suppressing nonproductive pathways. Chapter II of this thesis describes the application of the concept of DOS in the area of fragment-based drug discovery. Most fragment libraries used to date have been limited to aromatic heterocycles with an underrepresentation of chiral, enantiopure, \(sp^3\)-rich compounds. In order to create a more diverse fragment collection, the build/couple/pair algorithm was adopted. Starting from proline derivatives, a series of bicyclic compounds were obtained with complete sets of stereoisomers and high \(sp^3\) ratio. Efforts are also described toward the generation of diverse fragments using methodology described in Chapter I. The glycogen synthase kinase \((GSK3\beta)\) was selected as the proof-of-concept target for screening the DOS fragments.Chemistry and Chemical Biology
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Mann, Tyler J. "Stereoselective Olefin Metathesis Reactions Catalyzed by Molybdenum Monoaryloxide Monopyrrolide Complexes." Thesis, Boston College, 2016. http://hdl.handle.net/2345/bc-ir:104995.
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Thesis advisor: Amir H. HoveydaChapter 1: Efficient Z-Selective Cross-Metathesis of Secondary Allylic Ethers Efficient Z-selective cross-metathesis of secondary allylic ethers were catalyzed by monoaryloxide monopyrrolide molybdenum complexes. Reactions involving both silyl and benzyl protected ethers were demonstrated, as well as ethers containing alkyl, aryl and alkynyl substituents. Mechanistic studies were performed, and the reactions were applied to the total synthesis of several ene-diyne natural products. Chapter 2. Stereoselective Total Synthesis of Disorazole C1 The stereoselective total synthesis of disorazole C1 is reported. The synthesis was completed in 12 longest linear steps. Our synthesis demonstrates the utility of Z-selective cross-metathesis to form both alkenyl borons and alkenyl halides. Another key transformation was a one-pot Suzuki-dimerization reaction to form a symmetric 30 membered ring in relatively high yield. Chapter 3. Stereoselective Cross-Metathesis to Form Trisubstituted Alkenes Initial studies into the stereoselective formation of trisubstituted olefins through molybdenum catalyzed cross-metathesis have been performed. Our mechanistic understanding of the reaction lead us to focus on the synthesis of alkenyl halides, which can be obtained in up 90% yield and 75:25 E:Z selectivity. Chapter 4: Ring-Closing Metathesis in the Synthesis of Natural Products Development of highly efficient and selective ring-closing metathesis reactions have enabled collaborators to successfully implement routes in total synthesis endeavors. A diastereoselective seven-membered ring-closing metathesis enabled the successful synthesis of (±)-tetrapetalone A methyl-aglycon. An enantioselective ring-closing metathesis to form a six membered ring has provided access to enantioenriched aspidosperma alkaloids
Thesis (PhD) — Boston College, 2016
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
39
Cayir, Merve. "Synthesis Of Chiral Diene Systems Via Ring Closing Enyne Metathesis And Their Applications In Diels-alder Reactions." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/3/12612149/index.pdf.
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The main subject of this thesis is synthesis of chiral diene systems via Ring Closing Enyne Metathesis (RCEM). Furan and thiophene carbaldehydes were chosen as starting compounds. As a result of allylation and propargylation reaction of these aldehydes targeting racemic heteroaryl substituted homoallylic and homopropargylic alcohols were synthesized. Enantiomerically enriched alcohols were obtained by enzymatic resolution method with different enzymes (PS-II, Lipozyme) with the high enantiomeric excess values. Absolute configurations of all alcohols are known. O-allylation and O-propargylation reactions of enantiomerically pure alcohols, afforded feasible enyne units for RCEM were synthesized successfully. All RCEM reactions were performed by using Grubbs‟
1st generation catalyst. The absolute configuration of all chiral diene systems were known since during the course of the all reactions, configurations were preserved. As a last step, Diels-Alder reactions were applied to some of these chiral diene systems to get bicyclic compounds and comment on the stereoselectivity. Only one diastereomeric cycloadduct was observed as a result of Diels-Alder applications.
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Liu, Shiqi. "Mechanical Generation of Depolymerizable Poly(2,5-dihydrofuran)." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1619002348147551.
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Zunic, Valentin B. "Diastereoselective ring closing metathesis as an approach to cycloalkenes and symmetrical bicyclodienes and their functionalization through desymmetrization reactions." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58764.pdf.
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Yu, Miao. "Stereoselective Olefin Metathesis Reactions for Natural Product Synthesis." Thesis, Boston College, 2014. http://hdl.handle.net/2345/3861.
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Thesis advisor: Amir H. HoveydaChapter 1. The first examples of highly Z- and enantioselective ring-opening/cross-metathesis reactions are disclosed. Transformations involve meso cyclic olefin substrate and styrenes or enol ethers as olefin cross partners. A stereogenic-at-Mo monoaryloxide monopyrrolide (MAP) complex, prepared and used in situ, is discovered for the efficient formation of Z olefins. Such complex, bearing a relatively smaller adamantylimido and a larger chiral aryloxide ligand, leads to kinetic Z-selectivity due to the size differential. In most cases, the resulting disubstituted Z olefins are formed with excellent stereoselectivity (>95% Z). Chapter 2. The protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Stereoselective cyclizations are performed with either Mo- or W-based monoaryloxide monopyrrolide (MAP) complex at 22 oC. Synthetic utility of such broadly applicable transformation is demonstrated by synthesis of several macrocyclic natural products: relatively simpler molecules such as epilachnene (91% Z) and ambrettolide (91% Z), as well as advanced precursors to epothilones C and A (97% Z) and nakadomarin A (94% Z). Several principles of catalytic stereoselective olefin metathesis reactions are summarized based on the studies: 1) Mo-based catalysts are capable of delivering high activity but can be more prone to post-RCM isomerization. 2) W-based catalysts, though furnish lower activity, are less likely to cause the loss of kinetic Z selectivity by isomerization. 3) Reaction time is critical for retaining the stereoselectivity gained from kinetic, which not only applicable with MAP complexes but potentially with other complexes as well. 4) By using W-based catalyst, polycyclic alkenes can be accessed with sequential RCM reactions, without significant erosion of the existing Z olefins in the molecule. Chapter 3. An enantioselective total synthesis of anti-proliferative agent (+)-neopeltolide is presented. The total synthesis is accomplished in 11 steps for the longest linear sequence and 28 steps in total, including 8 catalytic reactions. Particularly, several Mo- or Ru-catalyzed stereoselective olefin metathesis reactions as well as N-hetereocyclic carbene (NHC)-catalyzed enantioselective boron conjugate addition to an acyclic enoate have proven to be effective for convergent construction of the molecule. The most important novelty of the study incorporates the explorations of feasibility of Z-selective cross-metathesis reactions to solve the challenge of installing two Z olefins with excellent selectivity
Thesis (PhD) — Boston College, 2014
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
43
Foley, Anne M. "Studies in alkene selective ring-closing metathesis and chromium(II)-mediated E-alkenylstannylation : a formal synthesis of (-)-periplanone-B." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302063.
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Stengel, Jason H. "The Application of Tandem O-H Insertion/Ring-Closing Metathesis to the Synthesis of Unsaturated Cyclic Ethers: Approaches to Rogioloxepane and Isolaurepinnacin." Ohio : Ohio University, 2010. http://www.ohiolink.edu/etd/view.cgi?ohiou1260473764.
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Goldring, William Peter Donald. "Application of ring-closing metathesis to the synthesis of unsaturated 14-membered lactams and the marine alkaloids motuporamines A-C." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0018/NQ56551.pdf.
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Cusak, Alen. "Temporary silicon-tethered ring-closing metathesis approach to polyketide fragments : Asymmetric synthesis of the C1-C30 fragments of amphidinol 3." Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511068.
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Demirci, Sema. "Synthesis Of Heteroaryl Substituted Dihydrofuran And Dihydropyran Derivatives By Green Chemistry Approach." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/2/12610966/index.pdf.
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The thesis subject is mainly involved in Green Chemistry approach. Thiophene, furan and pyridine carboxaldehydes were chosen as starting compounds and vinylation and allylation with Grignard reaction afforded the corresponding racemic heteroaryl substituted allylic and homoallylic alcohols. Subsequent resolution with enzymes (PS-Amano II, Lipozym and Novazym 435) gave enantiomerically enriched alcohols with the e.e. values varied between 65 and 99%. The absolute configurations of all substrates are known. As a result of O-allylation with the common procedure formed the feasible carbon backbone for the ring closing metathesis reaction. All ring closing metathesis reactions were performed by Grubbs&rsquocatalyst with just 5% catalyst loading. The absolute configurations of dihydrofuran and dihydropyran derivatives are known, since the chiral center configurations of all substrates are preserved throughout all the applied processes.
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Sieng, Bora. "Synthesis of six- and seven-membered cyclic ethers by ring-closing metathesis and synthesis of the A-D fragment of gambieric acid A." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2523/.
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Over the past thirty years, numerous fused polycyclic ether natural products have been isolated from small marine organisms. These compounds revealed a variety of interesting biological properties, which has attracted the interest of many synthetic groups. The common structural characteristic of these compounds is an array of trans-fused ether rings. Several iterative strategies have been reported to build six- and seven-membered cyclic ethers, which are the two most common units in these natural products. The objective of work described in the first part of this thesis was to develop new synthetic methodology to access these motifs. Each unit must be built in the minimum number of steps and the new methodology must be flexible enough to obtain both six- and seven-membered rings from a common precursor. They key reaction of the strategy will be ring-closing metathesis, as previous work in our group showed that this is a powerful reaction to create cyclic ethers. The second part of this thesis focus on the total synthesis of one of the marine polyether natural products, gambieric acid A. This compound was isolated in 1992 and has so far eluded total synthesis. First, the synthesis of the tricyclic B-D core, which has been developed in our group, was optimised and performed on a large scale. The synthetic route relies on the ring-closing metathesis reaction to construct two of the cyclic ethers from a commercially available glucose derivative. Several strategies for the coupling with the tetrahydrofuran A ring were then investigated. The initial method envisioned for the fragment coupling was a nucleophilic substitution of an alkyl iodide by a lithiated dithiane. However, this strategy revealed unsuccessful. Instead, a more converging approach using a diastereoselective Tsuji reaction was developed, which allowed the formation of the complete carbon skeleton of the A-D fragment.
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Parulekar, Sumedh. "A novel approach to manipulate cavity size In resorcinarenes." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001810.
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Wang, Jian-Xin. "Total synthesis of plakortones A, B & E : synthesis of cyclic peroxides by ring-closing metathesis and synthesis and stereochemistry of (+)-zerumin B & beyond." Doctoral thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24203/24203.pdf.
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