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1
Millet, Julien. "Approaches towards a stereoselective Nicholas reaction." Thesis, Kingston University, 2006. http://eprints.kingston.ac.uk/20379/.
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This programme of work has focused on developing ways of inducing stereoselectivity into the Nicholas reaction towards the synthesis of natural products. The first chapter of the thesis reviews the developments ofthe Nicholas reaction since its discovery in 1972 as well as other applications of cobalt clusters. The following chapter describes chirality and various approaches towards asymmetric synthesis. Chapter 3 details our investigations as well as the results that we achieved in the two ' areas we explored. The first part of the project attempted to determine which oxazolidinone derivative would provide optimum levels of selectivity in 1, 4-conjugate addition reactions, and then investigate such derivatives in the Nicholas reaction. It was found that oxazolidinones bearing a phenyl group at the C4 position induced much higher levels • ,rof stereoselectivity than those with benzyl or methyl groups at the C4 position. Although 4-phenyl-2-oxazolidinone provided optimum levels of diastereoselectivity in the asymmetric conjugate addition reaction of pentenyl organometallic reagents, it proved less efficient when applied sequencially in an intermolecular Nicholas reaction. In contrast, 4-methyl-2-oxazolidinone provided poor selectivity in an asymmetric conjugate addition reaction; however it was the auxiliary of choice for the corresponding Nicholas reaction providing optimum levels ofdiastereoselectivity. In the second part of our project, we focused on studying the intramolecular Nicholas reaction carried out upon optically active propargyl alcohols derived from citronella!. These were prepared from two different approaches. In the first approach, racemic propargyl alcohols were prepared via a Grignard reaction, then oxidised to the corresponding ketone before being reduced to the optically pure alcohol via a stereoselective reduction using alpine borane®. In the second approach, optically active propargyl alcohols were prepared via zinc catalysed asymmetric alkynylation reactions. After complexation of these propargyl alcohols to cobalt octacarbonyl, the addition of a Lewis acid led to the intramolecular Nicholas cyclisation reaction providing tri-substituted six membered rings in 55% yield. The results show that the reactions carried out on opposite diastereoisomers or racemic mixture provided the same mixture of diastereoisomers of the cyclised products. The final chapter describ~s all the experimental procedures that were carried out as well as the characterisation of every compound presented in this document.
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Rutherford, Alistair Peter. "Stereoselective synthesis of #Beta#-hydroxycyclohexanones using the anionic oxy-cope rearrangement." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299981.
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LOPS, CARMINE. "Development of organocatalytic and stereoselective reactions." Doctoral thesis, Università degli Studi di Trieste, 2018. http://hdl.handle.net/11368/2918472.
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Il focus di questo dottorato è stato lo sviluppo di due reazioni organocatalitiche e stereoselettive: le addizioni di sulfa-Michael e le condensazioni di Darzens poiché rappresentano degli approcci sintetici interessanti per la sintesi di farmaci chirali e, nell’ambito farmaceutico, ci sono pochi principi attivi (API) sintetizzati con reazioni di SMAs e/o di Darzens organocatalitiche e stereoselettive. Nell’ambito delle addizioni di sulfa-Michael (SMAs), la catalisi mediata da molecole bifunzionali donatrici di legami ad idrogeno (HBD) rappresenta un approccio interessante per l'attivazione sia della componente nucleofila che di quella elettrofila di una reazione. Gli esempi di SMA stereoselettive catalizzate da HBD bifunzionali e aventi il trans-chalcone come accettore di Michael sono pochi. Con l’obiettivo di ottimizzare l’attivitá dei catalizzatori HBD, la letteratura suggerisce come l'aumento dell'acidità dei protoni tioureici NH abbia effetti positivi sulle velocità di alcune reazioni. Spinto da queste informazioni, si è deciso di eseguire un'analisi comparativa di alcuni catalizzatori HBD in SMA stereoselettive aventi il trans-calcone come accettore di Michael. All’inizio, abbiamo studiato l'effetto della quantitá di catalizzatore, del solvente e della temperatura nella reazione modello: l'addizione del fenilmetantiolo al trans-calcone. Successivamente, con le condizioni di reazione ottimizzate, abbiamo valutato la capacità di indurre stereoselezione da parte di alcuni catalizzatori HBDs nelle SMAs stereoselettive del benzentiolo, fenilmetantiolo e 2-feniletantiolo al trans-calcone. L'aumento dell'acidità di Brønsted nella porzione donatrice di legami ad idrogeno ha dato, in alcuni casi, reazioni più rapide ma, in generale, ha avuto un impatto negativo sulla stereoselettività. Inoltre, il prodotto ottenuto dall’addizione del benzentiolo al trans-calcone è risultato stereochimicamente instabile, poiché subisce una reazione di retro-Michael quando lasciato in presenza di catalizzatori, come nel caso di un ritardato work-up della reazione. Per quanto riguarda le condensazioni di Darzens, generalmente, sono condotte in presenza di basi forti come idrossidi o alcossidi di metalli alcalini, sodio ammide, LDA, LiHMDS o n-butil-litio. In letteratura, non ci sono esempi di reazioni di Darzens condotte in presenza di basi organiche neutre. Quindi, si è deciso di studiare la reazione di Darzens in presenza di basi organiche neutre aventi una diversa pKBH+. La reazione, in presenza di una quantità stechiometrica di fosfazene P1-t-Bu, genera gli epossidi cis e trans con una buona resa e con un breve tempo di reazione. Tuttavia, sia i problemi di stabilità che le difficoltà di preparazione delle basi fosfazeniche, rendono importante l’obiettivo di identificare nuove superbasi. A tal fine, è stata valutata la ciclopropenimmina, con una pKBH+ simile a quella di P1-t-Bu. Con l’impiego di una quantità stechiometrica di ciclopropenimmina, l'epossido è stato ottenuto con una resa fino al 34% e 1/0.85 d.r. cis/trans. Usando una quantità catalitica di ciclopropenimmina (30 mol%), i composti α,β-epossicarbonilici sono stati ottenuti con una resa fino all'86% e 1/0.6 d.r. cis/trans; dimostrando di essere tollerante sia alle variazioni strutturali che alle proprietà elettroniche delle aldeidi aromatiche e dei composti carbonilici impiegati.
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Thomas, Jermaine D. O. "Highly regio and stereoselective hydroxy-directed Diels-Alder reaction." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6123.
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The Diels-Alder reaction has proven to be an invaluable tool in the arsenal of the synthetic organic chemist for the relatively facile construction of cyclic cores. However, the utility of this reaction is not without its shortcomings. Lack of regio and stereoselectivity are two problems that are often encountered with asymmetric dienophiles. Although Lewis acids have been successfully employed to control the selectivity of Diels-Alder reactions involving activated dienophiles, there is little precedent in the literature for their use with dienes containing a tertiary alcohol functionality, due to elimination complications. To this end, a new method has been developed, and reported herein, for the control of both the regio and facial selectivity of the Diels-Alder reaction via a Lewis acid tether to the dienophile directed by the tertiary alcohol on the diene.* *Please refer to dissertation for diagrams.
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Dawson, Graham John. "Studies on the stereoselective palladium-catalysed allylic substitution reaction." Thesis, Loughborough University, 1995. https://dspace.lboro.ac.uk/2134/31866.
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This thesis contains the preparation of a new design of ligand for the palladium catalysed allylic substitution reaction. The phosphine oxazoline ligands detailed in the thesis give high levels of enantiocontrol when used in conjunction with symmetrical allyl systems in the palladium catalysed allylic substitution reaction. For unsymmetrical allyl systems the palladium catalysed allylic substitution process proceeds with complete regiocontrol and high levels of stereocontrol are again observed. The products from the palladium catalysed allylic substitution reaction can be readily converted to succinic acids, γ-lactones and aryl propanoic acids.
6
Beligny, Samuel Daniel Charles. "Stereoselective synthesis of tetrahydropyridines using the Diels-Alder reaction." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414751.
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Takano, Toshiyuki. "SYNTHESIS OF CELLO-OLIGOSACCHARIDES -INFLUENCE OF SUBSTITUENT GROUPS ON STEREOSELECTIVE GLYCOSYLATION REACTION-." Kyoto University, 1990. http://hdl.handle.net/2433/78226.
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Cresswell, Mark. "The stereoselective Pictet-Spengler reaction and studies towards the total synthesis of ajmaline." Thesis, Keele University, 2013. http://eprints.keele.ac.uk/3816/.
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Due to their extensive and important medicinal properties, the indole alkaloids are an important class of natural products. A key step towards the total synthesis of indole alkaloids is the diastereoselective Pictet-Spengler reaction, which has enabled the total syntheses of a number of these natural products to be reported, one of which is the medicinally-important alkaloid ajmaline. Ajmaline is well studied and the previous attempts towards its synthetic preparation are described. During our investigations towards the asymmetric syntheses of ajmaline and other related indole alkaloids, it was found that the kinetically-controlled Pictet-Spengler cyclisations of L-tryptophan allyl ester gave cis-3,5-disubstituted tetrahydro-β- carbolines with enhanced stereoselectivities of up to 20:1. The Pictet-Spengler reaction of L-tryptophanamide was also studied and the cis/trans tetrahydro-β- carbolines were formed in a ratio of 3:1, typical of that for other ineticallycontrolled Pictet-Spengler cyclisations reported previously. Studies towards our total synthesis of ajmaline are also described. The synthesis features the kinetically-controlled Pictet-Spengler reaction, a highly stereoselective intramolecular Michael cyclisation and a one-pot indole cyclisation/reduction procedure, which was used to introduce three stereocentres simultaneously. It was found that the nitrogen protecting group has a defining role to play in both the indole cyclisation step, and during reduction of the subsequent iminium ion through remote steric induction. Despite installing seven of the nine stereocentres with high levels of stereocontrol, an inability to remove the robust nitrogen amide protecting group prevented completion of a total synthesis. The final ring-closing protocol could be carried out using semi-synthetic material derived from ajmaline. Cyclisation was achieved by the selective oxidation of a primary alcohol to the aldehyde, which spontaneously ring closed under the conditions of the reaction to complete the ajmaline framework.
9
Herlé, Bart. "Stereoselective Cyclopropanations via Gold(I)-Catalyzed Retro-Buchner Reactions." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/454770.
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La formació de carbens bencílics d’or(I) a partir de cicloheptatriens substituïts en la posició 7, a través de la reacció de retro-Buchner, ha aparegut recentment com una alternativa segura i versàtil a la descomposició de diazocompostos. No obstant, la formació de dits carbens requereix altes temperatures, limitant la seva aplicació. El treball d’aquest tesi doctoral s’ha dedicat a superar aquesta desavantatge i millorar la versatilitat de la transformació.
Els derivats de 1H-ciclopropa[l]fenantrè, que s’assemblen al tautòmer norcaradiè del cicloheptatriè, es descomponen per donar lloc a carbens lliures mitjançant la irradiació amb llum. Es va investigar la formació de carbens d’or(I) amb derivats de fenantrè mitjançant la reacció de retro-Buchner. No obstant, no es va trobar cap millora significativa amb respecte l’ús de derivats de cicloheptatriè.
Per altre banda, la generació de carbens al·lílics d’or(I) a partir de 7-alquenilcicloheptatriens, té lloc a temperatures significativament més baixes. Tenint en compte aquest fet, es va desenvolupar una reacció de ciclopropanació d’olefines per donar vinil-ciclopropans i vinil-aminociclopropans amb bons rendiments i elevada selectivitat per donar l’isòmer cis. Els derivats de 7-alquenil-cicloheptatriè es formen en un sol pas a partir d’aldehids i cetones emprant un nou reactiu del tipus Julia-Kocienski.
Addicionalment, utilitzant tècniques experimentals i computacionals, es van estudiar els mecanismes mediats per or(I) de la reacció de retro-Buchner, de la ciclopropanació i de la reacció de epimerització dels vinil-ciclopropans. Això va permetre el desenvolupament d’un model esteroquímic avançat per a les reaccions de ciclopropanació catalitzades per or(I).
El coneixement aportat per els estudis mecanístics i la síntesi millorada de derivats de cicloheptatriè van permetre la síntesi de derivats de cicloheptatriè més congestionats estèricament, què donen lloc a carbens d’or(I) a temperatura ambient i són el punt de partida per al desenvolupament d’una ciclopropanació enantioselectiva de gran aplicació.La formación de carbenos bencílicos de oro(I) a partir de cicloheptatrienos sustituídos en la posición 7, a través de la reacción de retro-Buchner, ha surgido recientemente como una alternativa segura y versátil a la descomposición de diazocompuestos. Sin embargo, la formación de dichos carbenos tiene lugar a altas temperaturas, limitando su aplicación. El trabajo de esta tesis doctoral se dedicó a superar esta desventaja y a mejorar la versatilidad de la transformación. Los derivados de 1H-ciclopropa[l]fenantreno, que se asemejan al tautómero norcaradieno del cicloheptatrieno, se descomponen para dar lugar a carbenos libres mediante irradiación con luz. Se investigó la formación de carbenos de oro(I) con derivados de fenantreno, a través de la reacción de retro-Buchner. No obstante, no se encontró ninguna mejora significativa con respecto al uso de derivados de cicloheptatrieno. Por otro lado, la generación de carbenos alílicos de oro(I) a partir de 7-alquenil-cicloheptatrienos, tiene lugar a temperaturas significativamente más bajas. Dada esta observación, se desarrolló una reacción de ciclopropanación de olefinas para dar vinil-ciclopropanos y vinil-aminociclopropanos en buenos rendimientos y con elevada selectividad para el isómero cis. Los derivados de 7-alquenil-cicloheptatrieno son formados en un sólo paso a partir de aldehídos y cetonas utilizando un nuevo reactivo de tipo Julia-Kocienski. Adicionalmente, utilizando técnicas experimentales y computacionales, se estudiaron los mecanismos mediados por oro(I) de la reacción de retro-Buchner, de la ciclopropanación y de la reacción de epimerización de los vinilciclopropanos. Esto permitió el desarrollo de un modelo estereoquímico avanzado para las reacciones de ciclopropanación catalizadas por oro(I). El conocimiento aportado por los estudios mecanísticos y la síntesis mejorada de derivados de cicloheptatrieno, permitieron la síntesis de derivados de cicloheptatrieno más estéricamente congestionados, que dan lugar a carbenos de oro(I) a temperatura ambiente y son el punto de partida para el desarrollo de una ciclopropanción enantioselectiva de gran aplicación.
The formation of benzylic gold(I) carbenes from 7-substituted cycloheptatrienes via a retro-Buchner reaction has recently emerged as a safe and versatile alternative to decomposition of diazo compounds. However, the carbene formation takes places at high temperatures, which puts a limit on its application. The work in this thesis is dedicated to overcome this drawback and enhance the versatility of this transformation. Free carbenes can be generated from light-induced decomposition of 1H-cyclopropa[l]phenanthrenes, which bear great resemblance to the norcaradiene tautomer of cycloheptatriene. Therefore, the propensity to form gold(I) carbenes via the retro-Buchner reaction of phenanthrene derivatives was investigated, albeit without finding significant improvements over the cycloheptatriene derivatives. The formation of allylic gold(I) carbenes from 7-alkenyl cycloheptatrienes takes place at significantly lower temperatures. Based on this observation, a highly cis-selective olefin cyclopropanation reaction has been developed, affording vinylcyclopropanes and vinyl-aminocyclopropanes in moderate to good yield. The 7-alkenyl cycloheptatriene derivatives can be formed in a single step from aldehydes and ketones by a novel Julia-Kocienski reagent. The mechanisms of the gold(I)-mediated retro-Buchner, cyclopropanation, and epimerization reactions for vinylcyclopropanes have been studied experimentally and computationally, which led to the development of an advanced stereomodel for gold(I)-catalyzed cyclopropanation reactions. Owing to the mechanistic insights, and the improved strategy for the synthesis of cycloheptatriene reagents, a sterically encumbered cycloheptatriene derivative was developed, which allows the formation of gold(I) carbenes at room temperature, paving the way for a broad-scope enantioselective cyclopropanation reaction.
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Peace, Simon. "The stereoselective nitro-Mannich reaction and its application towards the synthesis of vicinal diamines." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287661.
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Horsfall, L. R. "Stereoselective synthesis of pyrrolidinones via nitro-Mannich reaction : towards the synthesis of popolohuanone E." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1324535/.
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Part 1: The first section of this thesis details the stereoselective synthesis of pyrrolidinones via the nitro-Mannich reaction. Expanding on previous work within the Anderson group, conjugate addition of a diorganozinc species to nitroacrylate 141 was carried out successfully. Subsequent in situ nitro-Mannich reaction was then followed by spontaneous lactamisation to afford the desired five-membered ring pyrrolidinone structure. The reaction was performed in one pot, generating three contiguous stereocentres in a highly diastereoselective manner. The scope of the reaction was investigated by varying substituents on the imine partner. This led to the synthesis of a broad range of analogues incorporating alkyl, aryl and heteroaryl functional groups, each isolated as a single diastereoisomer in 48-84% yield. Studies to develop an asymmetric variant of the reaction were performed, with Feringa’s phosphoramidite ligand 299 enabling formation of the pyrrolidinone with a moderate 52% e.e. Analysis of the reaction mechanism and the origin of the observed diastereoselectivity have been investigated, followed by further functionalisation of the pyrrolidinone structure to yield a wide range of synthetically useful building blocks. Anderson, J. C.; Stepney, G. J.; Mills, M. R.; Horsfall, L. R.; Blake, A. J.; Lewis, W. J. Org. Chem. 2011, 76, 1961 (featured article). Part 2: This section describes work towards the total synthesis of popolohuanone E (1), a marine natural product isolated from the Dysidea sp. sponge in 1990. The molecule contains a unique trihydroxylated dibenzofuran-1,4-dione core and two identical sesquiterpene units. The complex molecular structure and interesting biological activity of popolohuanone E (1) has made this compound a particularly interesting target. Synthesis of model system 132 was successfully achieved, which allowed investigations into the key oxidative dimerisation reaction. Extensive studies led to isolation of the desired bis-quinone 133 in 40% yield, followed by acid catalysed cyclisation to form the dibenzofuran core present in popolohuanone E (1), in 26% yield. Focus then turned to the synthesis of the proposed precursor to popolohuanone E (1), 6’-hydroxyarenarol (7), based on the route developed within the Anderson group. Studies began with the enantioselective synthesis of intermediate iodide 83 utilising Myers’ pseudo-ephedrine auxillary. The remaining stereocentres were subsequently installed via an intramolecular Hosomi-Sakurai reaction in high yield and diastereoselectivity. With the cis-decalin framework in hand, construction of the phenolic portion was achieved by addition of lithiated 1,2,4-trimethoxybenzene to neo-pentyl aldehyde 74, followed by deoxygenation using Barton-McCombie conditions. Installation of the exo-cyclic alkene, followed by removal of the three methyl ether protecting groups, then afforded the required precursor 6’- hydroxyarenarol (7). Finally, dimerisation was attempted as developed previously on model system 132, however none of the desired bis-quinone (18) was observed.
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Gilley, Cynthia Brooke. "New convertible isocyanides for the Ugi Reaction application to the stereoselective synthesis of omuralide /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3328498.
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Thesis (Ph. D.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed November 5, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Dogan, Sengul Dilem. "Regioselectivity In The Ene Reaction Of Singlet Oxygen With Cyclic Alkenes And Application Of Ene Reaction To Stereoselective Synthesis Of Carbaheptopyranose Derivatives." Phd thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612648/index.pdf.
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In the first part of this thesis is related to the regioselectivity in ene reaction of singlet oxygen with cyclic alkenes. The photooxygenation of 1-methyl-, 2,3-dimethyl-, 1,4-dimethylcyclohexa-1,4-dienes, 1,2,3,4,5,8-hexahydronaphthalene (16) and 2,3,4,7-tetrahydro-1H-indene (17) which are readily available through Birch reduction, yielded the ene products. The formed endocyclic dienes were trapped by the addition of singlet oxygen to give corresponding bicyclic endoperoxy-hydroperoxides. In the case of 1-methylcyclohexa-1,4-diene (13) and 1,4-dimethyl-cyclohexa-1,4-diene (15), cis-effect determined the product distribution. Photooxygenation of 2,3-dimethylcyclohexa-1,4-dienes (14) gave mainly exocyclic olefin, which was attributed to the lowered rotational barrier of the methyl group and increased reactivity of the methyl groups. Photooxygeneation of 1,2,3,4,5,8-hexahydronaphthalene (16) and 2,3,4,7-tetrahydro-1H-indene (17) shows importance of the geometry of the allylic hydrogen in the ground state.
In the second part of this thesis is related to the stereoselective synthesis of carbaheptopyranose derivatives. Two new carbaheptopyranoses, 5a-carba-6-deoxy-&alpha-DL-galacto-heptopyranose (184) and 5a-carba-6-deoxy-&alpha
-DL-gulo-heptopyranose (185) have been prepared starting from cyclohexa-1,4-diene. The addition of dichloroketene to cyclohexa-1,4-diene followed by subsequent reductive elimination and Baeyer-Villiger oxidation formed the bicyclic lactone 188. Reduction of the lactone moiety followed by acetylation gave the diacetate 182b with cis-configuration. Introduction of additional acetate functionality into the molecule was achieved by singlet oxygen ene-reaction. The formed hydroperoxide 189 was reduced and then acetylated. The double bond in triacetate was further functionalized either by direct cis-hydroxylation using OsO4 or epoxidation followed by ring-opening reaction to give the hepto-pyranose derivatives 184 and 185.
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Karak, Milandip. "A stereoselective vinylogous aldol reaction of tetronamides and the synthesis of rubrolides and beta- substituted butenolides." Universidade Federal de Viçosa, 2017. http://www.locus.ufv.br/handle/123456789/13425.
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Os butenolídeos, que apresentam em sua estrutura o núcleo lactona α, -insaturada, são encontrados em produtos naturais e não naturais com diversas propriedades biológicas. Devido à prevalência dos butenolídeos substituídos, muitos esforços têm sido direcionados para explorar metodologias eficientes para suas sínteses e transformações. Entre elas, o acesso estereosseletivo dos derivados de butenolídeos -substituídos utilizando o conceito de vinilogia, o qual envolve a formação de ligação carbono-carbono com um eletrófilo apropriado na posição do butenolídeo, tem provocado um interesse crescente. Portanto, esta tese apresenta uma reação aldólica viníloga estereosseleva (VAR) eficiente, simples, escalável e diretamente estereosseletiva de butenolídeos -amino-substituídos (tetronamidas) com aldeídos. Esta tese também descreve as sínteses totais de butenolídeos contendo metabólitos naturais marinhos rubrolídeos pela bromação altamente regiosseletiva de fase tardia a partir de intermediários apropriados. Além disso, a tese inclui uma desalogenação redutiva de butenolídeos α-halo- -substituídos sob condições suaves com rendimentos elevados e regiosseletivos. Uma introdução ao contexto geral, incluindo estratégias sintéticas versáteis, sínteses totais e propriedades biológicas dos butenolídeos substituídos estão documentadas na seção: Capítulo 1. Sendo seguida por uma ilustração dos métodos selecionados para a construção do núcleo de butenolídeos. São também discutidos os vários métodos para a preparação de alguns produtos naturais selecionados que possuem o núcleo de butenolídeo ou sintetizados a partir de butenolídeos que atuam como “building blocks”. Finalmente, foram descritos alguns butenolídeos sintéticos que são comercializados como medicamentos ou agroquimicos recentemente. Os resultados da VAR estereosseletiva de tetronamidas estão apresentatos no Capítulo 2. O procedimento descrito, simples e escalável, funciona bem com aldeídos aromáticos e alifáticos, proporcionando principalmente os adutos correspondentes de syn-aldol. Em muitos casos, estes últimos são obtidos isentos dos seus isômeros anti com rendimentos elevados. Foi também realizado um estudo computacional detalhado. Os estudos experimentais e computacionais sugerem que a diastereosseletividade observada surge através da interconversão do isômero anti-syn, através da reação reversível retro-aldólica. No Capítulo 3, as estruturas cristalinas de alguns produtos aldólicos de tetronamida com dois estereocentros foram descritos. Os compostos relacionados revelaram tendências conformacionais e supramoleculares com padrões de substituição do anel aromático/heteroaromático. Tais tendências foram racionalizadas com base nos perfis energéticos dos principais confôrmeros. A principal contribuição deste estudo refere-se ao controle sobre a conformação molecular de tetronamidas que apresentam várias ligações que permitem giros, além da elevada liberdade conformacional através do padrão de substituição de um único anel. As primeiras sínteses totais de produtos naturais marinhos, os rubrolídeos I e O e alguns de seus derivados não naturais são relatadas no Capítulo 4. Uma versátil estratégia de bromação na última etapa permitiu a funcionalização dos anéis aromáticos de maneira altamente regiosseletiva, permitindo o acesso rápido aos alvos, rubrolídeos, a partir de precursores comuns. Posteriormente, a cloração regiosselectiva foi também aplicada à preparação de análogos sintéticos biologicamente importantes a partir de precursores facilmente acessíveis. No Capítulo 5, foi relatado a desalogenação redutiva catalisada por paládio binário de butenolídeos α-halo- -substituídos. O procedimento sintético permitiu o acesso rápido aos butenolídeos substituídos sob condições suaves, com rendimentos elevados e excelente regiosseletividade. Além disso, uma nova proposta para a síntese dos rubrolídeos E, F e composto com a estrutura correspondente à descrita para 3"-bromorubrolídeo F de ocorrência natural utilizando este mesmo protocolo.
Butenolides are α, -unsaturated lactone and are found in many natural and unnatural products with diverse biological properties. Owing to the prevalence of the substituted butenolides, much effort has been directed towards developing efficient methodologies for their synthesis and transformations. Among them, stereoselective access of the -substituted butenolide derivatives by utilizing the concept of vinylogy, which usually involves the carbon– carbon formation with an appropriate electrophile at the -position of butenolides, has triggered increasing interest. This thesis presents an efficient, simple, scalable and direct stereoselective vinylogous aldol reaction (VAR) of -aminosubstituted butenolides (tetronamides) with aldehydes. In addition, this thesis also describes the total syntheses of butenolide core bearing marine natural metabolites, rubrolides by using a highly regioselective late-stage bromination from appropriate intermediates, and apprises a facile reductive dehalogenation of α-halo- -substituted butenolides. An introduction to the general background, including versatile synthetic strategies, total syntheses, and biological properties of substituted butenolides is documented in Chapter 1. It is followed by an illustration of selected methods for construction of the butenolide core. Also discussed are the various methods for preparation of some selected natural products which either possess a butenolide core or synthesized from butenolide building blocks. Finally, some synthetic butenolide derivatives are described which are recently marketed as either medicines or agrochemicals. The results of the stereoselective VAR of tetronamides are compiled in Chapter 2. The described procedure, is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers in high yields. A detailed computational study was also carried out to establish the reaction mechanism. The experimental and computational studies suggest that the observed diastereoselectivity arises through anti–syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction. In Chapter 3, the crystal structures of several tetronamide aldol products with two stereocenters are described. Those compounds revealed conformational and supramolecular trends with the substitution pattern of a side aromatic/ heteroaromatic ring. The major contribution of this study concerns the control over the molecular conformation of tetronamide aldolates bearing several rotatable bonds and the high conformational freedom through the substitution pattern of a single ring. The first total syntheses of the marine natural products rubrolides I and O and some of their unnatural congeners are reported in Chapter 4. A versatile late-stage bromination strategy allowed functionalization of the aromatic rings in a highly regioselective fashion, enabling rapid access to the target rubrolides from common precursors. Next, the regioselective chlorination was also applied to the preparation of biologically important synthetic analogous of rubrolides from easily accessible precursors. In Chapter 5, a binary palladium catalyzed reductive dehalogenation of α-halo- -substituted butenolides is documented. The synthetic procedure allowed rapid access to the -substituted butenolides under mild conditions with high yields and excellent regioselectivity. In addition, a protecting group free step-economical synthesis of rubrolides E, F and γ”-bromorubrolide F has been reported by employing this protocol.
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Crossman, Julia Stephanie, and julia crossman@flinders edu au. "Biomimetic Approaches to the Synthesis of Polyketide Derived Marine Natural Products; (-)-Maurenone and the Spiculoic Acids." Flinders University. SoCPES, 2007. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20080212.134949.
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This thesis describes the total synthesis of the polyketide derived marine natural product (-)-maurenone (14) and synthetic studies of a model system for the marine polyketides, the spiculoic acids (20, 22-24). A biomimetic approach involving cyclisation of linear polyketide precursors to install the complex chemical frameworks was employed.
Maurenone is a polypropionate derived metabolite isolated from pulmonate molluscs collected off the coast of Costa Rica. While structural assignment following isolation revealed a relatively uncommon tetra-substituted dihydropyrone moiety the only stereochemical information deduced was the trans-relative relationship between the C8 and C9 protons. The total synthesis of a series of eight stereoisomeric putative structures was achieved in order to assign the stereochemistry of (-)-maurenone (14), as that depicted above. A time and cost efficient strategy was developed utilising common intermediates providing access to the eight stereoisomeric structures in a convergent manner. Six key fragments, four aldehydes (109) and two ketones (110), were synthesised using highly diastereoselective syn- and anti-boron aldol reactions and were coupled using a lithium-mediated aldol reaction. Trifluoroacetic acid-promoted cyclisation/dehydration enabled installation the ×-dihydropyrone ring. All eight isomers of one enantiomeric series were synthesised by coupling two ketones with each of four aldehydes. By comparison of the NMR data for the eight isomers with that reported for the natural product, the relative stereochemistry was established as shown. The (-)-enantiomer of maurenone was synthesised in nine linear steps (13 % overall yield) from (R)-2-benzylpentan-3-one ((R)-40) and (R)-2-benzoyloxypentan-3-one ((R)-39).
The spiculoic acid family of polyketide derived natural products, isolated from plakortis sponges, possess a unique [4.3.0]-bicyclic core which is proposed to be formed via an enzyme catalysed Intramolecular Diels-Alder (IMDA) cycloaddition reaction of linear polyene precursors 25. Model linear precursors (114), possessing various olefin geometries at C2 and both stereochemical orientations of the C5 stereocentre, were synthesised in order to examine stereoselectivity of the thermally induced IMDA cycloaddition reaction.
The two alternative C4-C6 stereotriads of the linear precursors 114 were achieved by employing highly diastereoselective substrate-controlled aldol reactions; an anti-boron aldol reaction, controlled by the facial preference of (R)-2-benzoyloxypentan-3-one ((R)-39), and a syn-titanium aldol reaction, under the control of chiral N-acylthiazolidinethione ((R)-43a). The diene and dienophile moieties were installed using either standard Wittig, H.W.E. or ¡§modified¡¨ Julia olefination reactions.
A thorough stereochemical assignment of the cycloadducts of the thermally induced IMDA reaction of each linear precursor was accomplished employing 2D NMR techniques. Comparison of the stereochemistry of each of the cycloadducts with the spiculoic acids revealed that the linear precursor (2E,5S)-114 produced a cycloadduct 232 with stereochemistry analogous to the natural products in 94 % diastereoselectivity. Thus, a synthetic approach to the spiculoic acids via synthesis of a linear precursor 285 possessing a TBS ether at C5 in the S configuration was proposed. Unfortunately, problems encountered in the synthesis of the proposed linear precursors to the spiculoic acids ultimately prevented the total synthesis from being achieved.
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Guerrera, Cessandra. "Stereoselective Synthesis of alpha,alpha-Disubstituted Amino Acids Utilizing Porcine Liver Esterase and the Petasis Borono-Mannich Reaction." Thesis, Southern Connecticut State University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10283110.
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Arginase is a manganese-containing enzyme that catalyzes the hydrolysis of L-arginine to yield L-ornithine and urea. It has been suggested that inhibition of arginase could be of therapeutic utility, and an arginase inhibitor is currently in phase I clinical trials for a variety of cancer subtypes. To date, the most promising inhibitors reported in the literature are α,α-disubstituted arginine analogs with a boronic acid warhead in place of the substrate guanidine group. However, the stereoselective approaches reported to date for this class of compounds have significant limitations and novel methods are needed. This research investigates two approaches: a route towards α,α-disubstituted amino acids via the enzyme-catalyzed desymmetrization of a meso diester and the utilization of the Petasis borono-Mannich reaction as an alternate enantioselective route for mono-substituted analogs.
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Laws, Stephen William. "Total Synthesis of (+)-Malbrancheamide B Utilizing a Stereoselective Domino Reaction Sequence to Establish the Bicyclo[2.2]diazaoctane Core." W&M ScholarWorks, 2013. https://scholarworks.wm.edu/etd/1539626719.
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Danielsson, Jakob. "Stereoselective Nucleophilic Additions to Aldehydes and Synthesis of α-Amino-β- Hydroxy-Esters." Licentiate thesis, KTH, Organisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-95467.
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This thesis deals with the development of new reaction methodology as well as stereochemical investigations. The first part concerns the investigation of 1,2- and merged 1,2- and 1,3- asymmetric induction in Mukaiyama aldol additions to α-heteroatom and α,β- heteroatom substituted aldehydes respectively. In particular, the unexpected 1,2-syn selectivity obtained in the addition of sterically hindered nucleophiles to α-chloroaldehydes is examined, and an explanation for the observed stereochemical trends is proposed. The second part describes the development of a novel entry to α-amino-β- hydroxy esters by a 1,3-dipolar cycloaddition reaction of aldehydes and azomethine ylides, generated by thermolysis of aziridines. The third part deals with our efforts to develop a novel entry to vicinal all- carbon quaternary centers, based on an intramolecular domino Heck- carbonylation reaction using tetrasubstituted olefins.QC 20120611
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Penwell, Andrea J. "Sequential cycloadditions for the synthesis of taxoid mimics and stereoselective synthesis of tamoxifen analogues via a new carbomagnesiation-palladium coupling reaction." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26342.
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Studies towards the synthesis of TaxolRTM mimics 19 and 20 are described. The strategy involved two sequential Diels-Alder reactions to form the ABC ring system. The synthesis of aromatic analogue 19 was abandoned due to the lack of regioselectivity and low yields in the Diels-Alder reaction. More progress was made in the synthesis of norbornane analogue 20. In situ oxidation of methyl-2,5-dihydroxybenzoate, followed by cycloadditions with 2-triisopropylsilyl-1,3-butadiene and cyclopentadiene, respectively, gave the tetracyclic skeleton 56 in good yield. Further manipulations afforded compounds 69, 71, and 73, which were subsequently sent for biological testing with the hopes that they will display Taxol-like effects on microtubules.
A sequential carbomagnesiation-palladium (0) coupling reaction was investigated. Treatment of a propargyl alcohol with vinyl magnesium chloride generated a magnesium-chelate intermediate, which was capable of undergoing a palladium-catalyzed cross coupling with aryl halides. The reaction was used in a stereoselective three-step synthesis of new analogues (99 and 100) of the breast cancer drug tamoxifen (74).
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ROUX, BRUNO. "Synthese regio et stereoselective d'acides alpha-amines par la reaction enique application a la preparation d'analogues de conformation restreinte de l'acide diaminopimelique." Paris 6, 1990. http://www.theses.fr/1990PA066676.
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Nous avons entrepris la preparation d'analogues de conformation restreinte de l'acide gamma-methylene diaminopimelique, afin de determiner la conformation bioactive de cette molecule qui possede une activite antibiotique notable envers les bacteries gram negatif mais dont le mecanisme d'action n'est pas encore elucide. Pour synthetiser les acides alpha-amines beta, gamma-et/ou gamma, delta-insatures vises, nous avons choisi d'utiliser la reaction enique, du fait de ses possibilites de regio et de diastereoselectivite. L'utilisation d'olefines cycliques fonctionnalisees, domaine encore peu etudie dans le cas de la reaction enique, a conduit a des adduits possedant 3 ou 4 centres asymetriques. Plusieurs de ces centres peuvent etre simultanement controles au cours de la reaction. La regio et la diastereoselectivite importantes, observees experimentalement a partir de cyclohexene glycinates ou de cyclohexenes alaninates, ont pu etre expliquees en examinant la conformation des olefines de depart et l'accessibilite des hydrogenes allyliques de ces molecules. La preparation de la 2-methylcyclohex-2-ene glycine optiquement pure permet, du fait de l'enantioselectivite de la reaction enique, d'envisager l'acces a des adduits optiquement actifs. L'utilisation de la reaction enique a l'echelle preparative a pu etre testee avec succes. L'ensemble des isomeres projetes n'ayant pas ete prepare, les resultats pharmacologiques negatifs obtenus sur un nombre restreint d'isomeres doivent encore etre analyses avec precaution
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Datta, Gopal K. "Heck Reactions with Aryl Chlorides : Studies of Regio- and Stereoselectivity." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9202.
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Duchesne, Jean-Pierre. "Nouvelle voie d'acces aux aldehydes terpeniques : synthese stereoselective des isomeres 11-trans du retinal a l'aide de sulfones." Paris 6, 1987. http://www.theses.fr/1987PA066347.
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Burke, Elizabeth Diane. "Stereoselective carbon-carbon bond forming reactions : improving the stereoselectivity of a catalytic homoaldol reaction and the development of a general method to access the [alpha]-quaternary carbon [beta]-hydroxy carbonyl motif." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85054.
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The following thesis describes two stereoselective carbon-carbon bond forming processes---the aldol reaction and its one-carbon homologue, the homoaldol reaction. The first chapter describes our efforts to increase the stereoselectivity of a catalytic homoaldol reaction. This methodology features a second generation Binol titanium (IV) fluoride catalyst capable of opening a silyloxycyclopropane ring to form discrete homoenolates. These homoenolates react with a variety of aldehydes to form 1,4-hydroxy carbonyl compounds. The catalyst was prepared by a literature method and has improved the stereoselectivity of this reaction compared to the first generation Binol titanium (IV) triflate catalyst. A variety of substituted Binol ligands were studied to determine the effect of steric and electronic modifications on reaction selectivity.In the second chapter, a general method for the asymmetric synthesis of alpha,alpha-disubstituted-beta-hydroxy carbonyl compounds is described. This methodology relies on the stereoselective formation of acyclic alpha,alpha-disubstituted amide enolates. These enolates were prepared using methodology developed in the Gleason laboratory. Transmetallation of the initially formed lithium enolate was necessary to achieve high relative and absolute product stereocontrol. The E- and Z-enolate isomers were investigated. The Z-enolate reacted with high stereocontrol, whereas the E-enolate was not able to provide the anti isomer selectively. An X-ray crystal structure confirmed the absolute configuration of the product.
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Gallanti, M. "STEREOSELECTIVE SYNTHESIS OF A-AMINO ACIDS B-SUBSTITUTED WITH A 4,5-DIHYDROISOXAZOLE NUCLEUS AND OF TERTIARY AND QUATERNARY ALLYLSILANES." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/168366.
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In the section A of the thesis is presented a stereoselective synthesis of b-hydroxy-a -amino acids b-substituted with a 4,5 dihydroisoxazole nucleus through an aldol type reaction between Schollkopf reagent and isoxazolynil aldehydes and ketones. In the section B is presented the preparation of allyl- or crotylsilane in high dr and er via the lithiation-borylation reaction of alkylcarbamates with silaboronates.The synthesis of quaternary allylsilane through a related strategy is also presented.
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MRIDHA, MD MONIRUZZAMAN. "HIGHLY STEREOSELECTIVE ALDOL REACTION BY THE COMBINATION OF AMINOACID AND HYDROGEN BOND DONATING CATALYSTS IN WATER AND APPLICATION FOR CONCISE SYNTHESIS OF D-Lyxo-PHYTOSPHINGOSINE." Thesis, Uppsala universitet, Institutionen för kemi - BMC, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-328534.
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Tiong, Erica. "Stereoselective formation of all carbon quaternary centers: synthesis of alpha,alpha-disubstituted beta-amino carbonyl compounds via the Mannich reaction and total synthesis of (-)-puraquinonic acid." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104585.
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A bicyclic thioglycolate lactam chiral auxiliary was previously developed in our group for the asymmetric formation of quaternary carbon stereocenters via enolate alkylation. This method is notable for the stereocontrolled generation of alpha, alpha-disubstituted amide enolates, without reliance on the steric differences of the alpha-substituents. Coupled with excellent facial discrimination in electrophilic approach, this led to a general and practical method for enantioselective preparation of quaternary carbon centers via alkylation reactions. This thesis describes the extension of this methodology to the stereoselective formation of alpha, alpha-disubstituted beta-amino carbonyl compounds via the Mannich reaction and also the application of the alkylation method to the total synthesis of (-)-puraquinonic acid.alpha,alpha-Disubstituted lithium enolates, stereoselectively generated from alpha,alpha-disubstituted bicyclic thioglycolate lactams, undergo Mannich addition to benzenesulfonyl imines to form beta-amino acid derivatives with high yield and diastereoselectivity. The reaction is general for a number of aromatic imines, including those with electron rich and electron poor substituents, heteroaromatic, and alpha, beta-unsaturated imines. alpha-Substituents on the amide enolate can be varied to include methyl, ethyl, propyl, benzyl, and allyl groups. The addition occurs via a closed Zimmerman-Traxler transition state with anti/syn relationships controlled by enolate geometry. Methods for N-deprotection and removal of the auxiliary to afford beta-amino acids and alcohols are described. A concise synthesis of (-)-puraquinonic acid is accomplished using the bicyclic lactam chiral auxiliary to set the lone quaternary center at an early stage. A tandem ring-closing cross metathesis process followed by Diels-Alder cycloaddition generates a dihydroindene, which makes up the bicyclic system of puraquinonic acid. The central quinone is formed by a Curtius rearrangement/Fremy's salt oxidation sequence. Upon completion, the auxiliary is removed via acidic hydrolysis to give the required carboxylic acid functionality. The synthesis is completed in 14 steps from commercially available lactam in 21% overall yield, and represents a 24 step improvement over the previous asymmetric synthesis.Un auxiliaire chiral de type lactame thioglycolate bicyclique permettant la formation de carbones asymétriques quaternaires via une alkylation d'énolates fut développé précédemment par notre groupe de recherche. Cette méthode est remarquable puisqu'elle permet la génération stéréocontrôlée d'énolates d'amide alpha, alpha-disubstitués, sans égard à la différence stérique entre les substituants alpha Démontrant également une excellente discrimination faciale lors de l'approche de l'électrophile, ce protocole est maintenant devenu une méthode générale et pratique pour la préparation énantiosélective de carbones quaternaires par alkylation. Cette thèse rapporte l'application de cette méthode à la formation stéréosélective de composés beta-amino carbonyles alpha, alpha-disubstitués via la réaction de Mannich, ainsi que son utilisation dans la synthèse totale de l'acide (-)-puraquinonique.Les énolates alpha, alpha-disubstitués de lithium, générés de façon stéréosélective à partir de lactames thioglycolates bicycliques alpha, alpha-disubstituées, réagissent avec des imines benzènesulfoniques pour créer des acides beta-aminés avec grande efficacité et diastéréosélectivité. La réaction est générale pour une panoplie d'imines aromatiques, incluant celles comportant des substituants pauvres en électrons, riches en électrons, hétéroaromatiques, ainsi que des imines alpha, beta-insaturées. Les substituants alphades énolates d'amides peuvent être des groupements méthyle, éthyle, propyle benzyle et allyle. L'addition emploie un état de transition de type Zimmerman-Traxler où la géométrie de l'énolate contrôle le ratio d'addition anti/syn. Des méthodes de déprotection du groupe amino libérant des acides beta-aminés et des alcools sont décrites.Une courte synthèse de l'acide (-)-puraquinonique a été réalisée en utilisant l'auxiliaire chiral de type lactame thioglycolate bicyclique pour créer l'unique centre quaternaire présent tôt dans la séquence. Par la suite, un processus tandem fermeture de cycle par métathèse - cycloaddition de Diels-Alder produit un dihydroindene constituant le sytème bicyclique de l'acide puraquinonique. La quinone centrale est formée via une séquence comprenant un réarrangement de Curtius et une oxydation par le sel de Fremy. Lorsque la synthèse est complétée, l'auxiliaire est enlevé par une hydrolyse acide, révélant la fonctionnalité acide carboxylique nécessaire. La synthèse est complétée avec un rendement de 21 % à partir d'une lactame commercialement disponible, et ce, en 14 étapes. Cette synthèse représente donc une amélioration de 24 étapes par rapport à la synthèse asymétrique précédente.
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Trejos, Alejandro. "Palladium-Catalysed Couplings in Organic Synthesis : Exploring Catalyst-Presenting Strategies and Medicinal Chemistry Applications." Doctoral thesis, Uppsala universitet, Avdelningen för organisk farmaceutisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-173068.
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Palladium-catalysed coupling reactions have been embraced by synthetic chemists as one of the preferred means for smooth formation of new carbon-carbon bonds: a truly ubiquitous methodology of synthesizing complex molecules. This thesis describes the study of a series of palladium(0)-catalysed C2-arylations of a 1-cyclopentenyl ether, equipped with a chiral (S)-N-methyl-pyrrolidine auxiliary. The investigated olefin was demonstrated to undergo Si-face insertion, providing (R)-configuration of the arylated C2-carbon. In addition, the mild and novel palladium(II)-catalysed dominoHeck/Suzuki β,α-diarylation-reduction of a dimethylaminoethyl-substituted chelating vinyl ether was developed using arylboronic acids as arylating agents in combination with 1,4-benzoquinone (BQ). Further, highly regioselective palladium(II)-catalysed α-and β-monoarylation of the chelating vinyl ether was achieved using either a bidentate ligand or by employing ligand-less conditions. These studies demonstrate that the choice of ligands has a profound effect on the reaction outcome, as productive β,α-diarylation could only be obtained by suppressing the competing β-hydride elimination using BQ as the stabilising ligand and terminal reoxidant. The pivotal role of BQ in the reaction was studied using computer-aided density functional theory calculations. The calculations highlight the crucial role of BQ as a Pd(II)-ligand. In addition of serving as an oxidant of palladium, the calculations support the view that the coordination of BQ to the Pd(II)-centre in the key σ-alkyl complex leads to a low-energy pathway, aided by a strong η2 Pd-BQ donation-back-donation interaction. Furthermore, an investigation of the scope and limitations of novel stereoselective and BQ-mediated palladium(II)-catalysed domino Heck/Suzuki β,α-diarylation reactions, involving metal coordinating cyclic methylamino vinyl ethers and a number of electronically diverse arylboronic acids, conducted. In addition, a set of 4-quinolone-3-carboxylic acids, structurally related to elvitegravir and bearing different substituents on the condensed benzene ring, was designed and synthesized as potential HIV-1 integrase inhibitors. Finally, in an effort to identify a new class of HIV-1 protease inhibitors, four different stereopure β-hydroxy γ-lactam-containing inhibitors were synthesized, biologically evaluated, and co-crystallized with the enzyme.The time 12:05 for the public defense mentioned in the thesis is incorrect. It will take place at 09:15, 2012-06-08.
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Alabdullah, Basil. "Stereoselective organoborate rearrangement reactions." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/75961/.
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This thesis describes the use of organoborate rearrangement reactions to generate quaternary carbon centres, with the ultimate goal of exploring new procedures for the asymmetric synthesis of chiral quaternary carbon centres. Chapter One: this chapter contains a historical review of the use of organoboranes in organic synthesis, focusing mainly on the use of boronic esters in asymmetric organic synthesis. Chapter Two: this chapter focuses on attempts at developing a catalytic method for the generation of quaternary stereocentres using migration reactions of boronic esters with n-butyllithium in the presence of chiral catalysts. This study showed that the reaction is stoichiometric in the absence of the Lewis acid. However, there were strong indications of catalytic turn over in some experiments. Chapters Three and Four: these chapters focus on attempts at designing a chiral version of the DCME reaction using sulfur compounds. Chapter Three focuses on attempts at evaluating a heterocyclic system, specifically a dithiane, as a stereocontrol agent in its reaction with trialkylboranes. The study showed that using 2-methoxy-1,3-dithiane-oxide achieved formation of the double and triple migration product but in poor yield. Chapter Four contains a detailed investigation into the synthesis and evaluation of non-cyclic sulfur compounds such as sulfoxides, sulfoximines, sulfilimines and sulfones for generation of chiral tertiary alcohols. The study of the reaction of dichloromethyl phenyl sulfoxide with trialkylboranes showed a new type of aldol-like reaction. This reaction was utilised to synthesise a series of new compounds. Also, the study of the reaction of dichloromethyl-p-tolyl sulfone with trialkylboranes showed a new type of reaction by replacing the hydrogen with the alkyl group from the trialkylborane. Finally, the study of the reaction of N-methyl-S-(dichloromethyl)-S-phenylsulfoximine with trialkylboranes showed production of the desired triple migration product in moderate to very good yield.
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Prasad, K. R. "Stereoselective carbonyl addition reactions." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 1996. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/3010.
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NOGUE, DENISE. "Synthese regio et stereoselective d'heterocycles azotes via la reaction d'imino diels alder. Analyse conformationnelle de decahydroquinolein-4-ones et de piperidin-4-ones par correlation rmn #1h, m. M. Et rx." Paris 11, 1993. http://www.theses.fr/1993PA112254.
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Le travail rapporte dans ce memoire concerne d'une part la synthese d'heterocycles azotes tels que les n-aryl-2-aryl decahydroquinolein-4-ones et les n-aryl-2-aryl piperidin-4-ones et, d'autre part, leur analyse conformationnelle. L'etude de la reaction d'imino diels alder du 1-(1-trimethylsilyloxyethenyl)-cyclohexene et d'imines catalysee par des acides de lewis a permis d'obtenir selectivement ou tres majoritairement les enoxysilanes exo ou endo selon la nature des groupes aryles ar et ar lies respectivement au carbone et a l'azote de l'imine. Ainsi, l'utilisation du t-butyldimethylsilyle trifluoromethanesulfonate en quantite catalytique conduit a une forte selectivite exo lorsque ar est le groupe p-methoxyphenyle ou o,o,p-trimethylphenyle. Nous avons par ailleurs montre que la reaction d'addition procede selon un mecanisme concerte asynchrone. Le traitement par meoh/et#3n des cycloadduits exo et endo a permis d'obtenir stereospecifiquement les cetones bicycliques a jonction de cycle cis exo ou cis endo. Le traitement par hcl(1n)/meoh des cycloadduits a conduit aux enones alicyliques correspondantes qui evoluent ensuite vers la cetone bicyclique a jonction de cycle trans endo. Nous avons ensuite applique la reaction d'imino diels alder au 1-methoxy-3-trimethylsilyloxy buta-1,3-diene et aux imines afin de preparer les tetrahydropyridin-4-ones. Celles-ci ont conduit apres reduction aux piperidin-4-ones. L'analyse conformationnelle des cetones mono et bicycliques, realisee par correlation rmn #1h, modelisation moleculaire et dans certains cas analyse de diffraction de rx, a revele l'etroite relation entre l'hybridation sp#2 ou sp#3 de l'azote dans un groupement n-aryle et la conformation bateau ou chaise de l'heterocycle
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Marín, Ferré Irene. "Stereoselective reactions in carbohydrate synthesis." Doctoral thesis, Universitat Rovira i Virgili, 2012. http://hdl.handle.net/10803/76720.
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La Tesis que se presenta trata sobre el desarrollo de nuevos métodos selectivos de síntesis de carbohidratos. En la primera parte de la tesis se estudió la epoxidación de glicales utilizando catalizadores de Mo y ácido meta-cloroperbenzoico (MCPBA), en relación con la obtención de mano-oligosacáridos. En todos los casos estudiados, el epóxido formado se abría in situ para dar lugar al correspondiente diol o glicósido. Se observó un efecto director por parte de los hidroxilos libres, lo que permitía obtener derivados de manosa a partir de glucosa. En el caso del Mo, los resultados figuran entre los mejores descritos para epoxidación de glicales con catalizadores. Los resultados con MCPBA fueron excelentes, aplicándose este último procedimiento a la síntesis ortogonal de dadores de glicosilo. En la segunda parte, relacionado con la síntesis del cardiotónico digitoxina, se estudiaron dos metodologías sintéticas para obtener 2-desoxi-glicósidos mediante reacción de olefinación-ciclación-glicosilación y a través de síntesis asimétrica.This thesis deals with two topics connected with carbohydrate chemistry. The first part presents epoxidation and dihydroxylation reactions of glycals using Mo-catalysts and m-chloroperbenzoic acid (MCPBA) towards the synthesis of manno oligosaccharides. The oxidation of glycals afforded in all cases the corresponding diols or glycosides, as a consequence of the in situ opening of the epoxides initially formed. Free hydroxyl groups were observed to direct the stereoselectivity of the epoxidation, and then manno derivatives were obtained from unprotected or partially protected glucals. The results using Mo-catalysts are among the best described for the catalytic epoxidation of glycals. The results using MCPBA were excellent, and this methodology was applied to the synthesis of orthogonally protected glycosyl donors. The second part is related to the synthesis of the cardiotonic digitoxin. Two different strategies were studied in order to obtain 2-deoxy-glycosides through olefination-cyclization-glycosylation reaction and using asymmetric synthesis.
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Yan, Ni. "Stereoselective carbometallation reactions of cyclopropenes." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 207 p, 2008. http://proquest.umi.com/pqdweb?did=1456289621&sid=2&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Maberly, T. R. "Stereoselective reactions of iron complexes." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375266.
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Peverall, S. F. "Investigation of novel stereoselective reactions." Thesis, Swansea University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.638517.
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Chapter 1 reviews the field of asymmetric synthesis with special emphasis on stereoselective enolate formation and reaction. The physical and chemical characteristics of [2.2]paracyclophane derivatives and other planar chiral compounds are examined and their role in asymmetric synthesis mentioned. Chapter 2 investigates the role of [2.2]paracyclophanes as planar chiral auxiliaries. The stereoselective production and α-substitution of [2.2]paracyclophane ester enolates is investigated. Chapter 3 introduces the field of boron stabilised carbanion chemistry and investigates the diastereoselective synthesis of erythro-1,2-diols by condensation/oxidation of boron stabilised carbanions with aromatic aldehydes. Phenylboronates are generated from the 1,2-diols in an attempt to determine stereochemistry.
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Massolo, E. "NOVEL SYNTHETIC ORGANOCATALYTIC METHODOLOGIES." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/330262.
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The objective of this PhD study was to apply organocatalytic synthetic methods for the regio- and stereoselective synthesis of highly functionalized compounds. We exploited different organocatalytic activation modes to peculiar substrates we identified as suitable building blocks for versatile products in enantiomerically enriched form. In particular the developed projects relied on stereoselective amino- and hydrogen bonding organocatalysis, employing beta-nitroacrylates, beta-trifluoromethylated nitroalkenes and 2,2,2-trifluoroethyl 2-[(1,3-dithian)-2-yl]-ethanthioate in combination with various reaction partners, thus finding entries to valuable intermediates suitable for further subsequent transformations.
The first Chapter of this thesis aim to give a general overview on those fields of organocatalysis related to the research topics studied in this PhD program, the second Chapter offers a literature background of the employed substrates. Following five Chapters (3-7) and Appendix report the discussion on the obtained results.
According to our opinion, this PhD study offers solid examples of robustness, versatility and effectiveness of stereoselective organocatalytic strategies, which have been applied to interesting starting materials and in innovative reaction media, thus giving a reliable contribution to expand the boundaries of this field.
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RIGUET, ERIC. "Reaction de couplage aryl-aryle, entre un organometallique et un bromure ou un chlorure aromatique, catalysee par un complexe du palladium ou du nickel. Cyclisation stereoselective utilisant un nouveau systeme catalytique mn/cu." Paris 6, 1997. http://www.theses.fr/1997PA066715.
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La reaction de couplage aryl-aryle, nouvellement developpee, permet l'acces a un nombre important de diphenyles dissymetriques fonctionnalises diversement substitues a partir de bromures d'aryles. Les conditions reactionnelles sont douces (+20 a +65\c), les rendements sont bons (>90%) et les temps de reaction sont courts (environ 2 heures). - l'utilisation d'un compose organomanganeux, en presence d'une quantite catalytique d'un complexe du palladium puis d'un co-solvant tel que le dme, a permis le bon deroulement d'une telle reaction. - de la meme facon, avec les iodures et triflates d'aryle nous obtenons de tres bons rendements en produits de couplage. - cette reaction a de plus ete etendue aux chlorures d'arylzinc avec d'excellents resultats. - au cours de ce travail nous montrons, pour la premiere fois, que l'utilisation d'un chlorure d'arylmagnesium est chimioselective. - c'est enfin en presence d'un complexe catalytique du nickel que le couplage de chlorures d'aryle diversement substitues a pu etre realise. Encore une fois, le dme permet d'ameliorer les resultats. - diverses applications, telles que les couplages vinyl-aryle, vinyl-vinyle, vinyl-r et aryl-r (r= aryle), ont ete realisees. - une autre partie concerne la cyclisation 5-exo-trig stereoselective d'alcenes, d'aldehydes et de cetones -bromees. Nous avons montre que l'utilisation du systeme catalytique mn/cu en presence d'et 2zn permet a cette reaction de cyclisation d'avoir lieu dans des conditions reactionnelles douces (+60\c). Les temps de reactions peuvent de plus etre tres courts (6 minutes a 12 heures).
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RAEPPEL, STEPHANE. "Synthese stereoselective de dienediynes tricycliques analogues structuraux du chromophore de la neocarzinostatine et approche synthetique du coeur de ce puissant anticancereux naturel. Nouvelle voie de synthese d'enediynes macrocycliques par la reaction s#nar." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13167.
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Au cours de ce travail de these nous avons etudie et realise : - la synthese stereoselective et convergente de dienediynes tricycliques analogues structuraux du chromophore de la neocarzinostatine, a partir de diynes aromatiques et du (z)-bis(triflate d'enol). - une approche synthetique du cur de ce puissant anticancereux naturel. Pendant ce projet nous avons elabore une synthese alternative des deux enantiomeres de la trans-3,4-bis(benzyloxy)cyclopentanone en sept etapes a partir du diethyl tartrate comme substrat chiral non racemique et ouvert une nouvelle voie d'acces a des cycles a cinq chainons hautement fonctionnalises et diastereoisomeriquement purs par cycloisomerisation de type trost-lautens des 1,6-eneynes acycliques. - le developpement d'un nouveau mode d'activation de systemes diyniques aromatiques possedant un dispositif de gachette intramoleculaire dans l'objectif de creer une nouvelle famille de prodrogues antitumorales. - une nouvelle exploration de la reaction de substitution nucleophile aromatique. Pendant ce projet nous avons montre qu'il etait possible de creer la liaison aryl-propargyl ether par une reaction s#nar au cours d'un processus intermoleculaire. Puis cette reaction a ete utilise avec succes au cours de la construction en onze etapes d'un analogue oxygene comme modele du macrocycle de l'adduit methanolique du chromophore de la maduropeptine. Finalement nous avons developpe une nouvelle famille d'enediynes macrocycliques par une reaction de cyclisation tandem inter-intramoleculaire de type s#nar double en une seule operation. Ces systemes bi- et tricycliques s'averent tres stables thermiquement.
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Bender, Christoph. "Stereoselektive Synthese neuartiger 1,2-Dihydroisochinoline als Vorstufen für die Alkaloidsynthese." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2008. http://dx.doi.org/10.18452/15728.
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Ausgangspunkte der vorliegenden Arbeit waren stereoselektive Synthesen von Reissert-Verbindungen über chirale N-Acylisochinoliniumsalze. Es galt die Konfiguration der erhaltenen Produkte zu beweisen und deren Synthesepotential zu erforschen. Ein Ziel dieser Arbeit war es, weiterführende Reaktionen für die Synthese von alkaloidanalogen Substanzen zu entwickeln. Es gelang, die Reissert-Reaktion mit Chlorameisensäurementhylester erfolgreich auf andere Heterocyclen als Isochinolin auszudehnen. Die Annahme eine stereoselektiven Verlaufes mußte korrigiert werden. Das Reissert-Produkt konnte mit einer großen Anzahl von Alkylhalogeniden in 1-Position alkyliert werden. Die Cyanogruppe konnte in zwei Verfahren abgewandelt werden. Die Behandlung des Reissert-Produktes und der alkylierten Verbindungen mit Säuren, Halogen und Grignard-Reagenzien führte zu verschiedenen interessanten Cyclisierungen. Es gelang, die Reissert-Reaktion auf elektronenreiche Aromaten und metallorganische Reagenzien als Nucleophile zu erweitern. Es gelang eine asymmetrische C-C-Knüpfung mit Zink-Nucleophilen sowie Grignard-Verbindungen. 4-Bromsubstituierte Mannich-Produkte konnten erfolgreich in einer Suzuki-Kupplung zu 4-arylsubstituierten Isochinolinaddukten umgesetzt werden. Es gelang die Hydrierung der Enamindoppelbindung und die Abspaltung des chiralen Auxiliars auf zwei verschiedenen Wegen. Während Additionsreaktionen an die 1-Position von 2-Menthyloxcarbonylisochinoliniumsalzen im wesentlichen nicht stereoselektiv verliefen, konnte beim Einsatz von geschützten Aminosäurefluoriden als chirale Auxiliare Diastereoselektivitäten bis zu 6:1 erzielt werden. Der Einsatz der elektronenreichen Aromaten als Nucleophile führte zu Mannich-Produkten in guten Ausbeuten. Auch der Einsatz von Grignard-Reagenzien als Nucleophile konnte erfolgreich getestet werden. Hiermit ist die erste stereoselektive Addition von elektronenreichen Aromaten an cyclische Iminiumsalze gelungen.Starting points of the present work were stereoselective syntheses of Reissert compounds about chiral N-acylisoquinoliniumsalts. It was a matter of proving the configuration of the preserved products and of investigating synthesis potential. A purpose of this work was to develop continuing reactions for the synthesis of alkaloide-analogous substances. One succeeded in expanding the Reissert reaction with menthylchloroformat successfully to other heterocycles than isoquinoline. The acceptance a stereoselective course had to be corrected. The Reissert product could be alkylated with a big number of alkylhalides in 1 position. The Cyanogroup could be modified in two procedures. The treatment of the Reissert product and the alkylated compounds with acids, halogens and Grignard reagents led to different interesting cyclisations. One succeeded in extending the Reissert reaction to electronrich aromatic and heteroaromatic compounds and metal-organic reagents as nucleophiles. An asymmetrical C-C-bondformation with Zink-nucleophiles as well as Grignard compounds succeeded. 4-Bromine-substituted Mannich products could be transformed successfully in a Suzuki coupling to 4-arylsubstituted isoquinolineadducts. The hydrogenation of the enamindoublebond and the splitting off chirale auxiliary on two different ways succeeded. While addition reactions ran to the 1 position of 2-Menthyloxcarbonylisoquinoliniumsalts basically not stereoselectively, could be achieved by the application by protected Aminosäurefluoriden as chirale auxiliaries slide stereo selectivities up to 6:1. The application of the electronrich aromatics as nucleophiles led to Mannich products in good exploiting. Also the application of Grignard reagents as nucleophiles could be tested successfully. Herewith the first stereoselective addition from electronrich aromatics to cyclic iminiumsalts has succeeded.
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PUGNAUD, SYLVIE. "Etude theorique de reactions stereoselectives : - reaction de diels-alder a demande inverse d'electrons - hydrogenation de cycloalcenes." Paris 6, 2000. http://www.theses.fr/2000PA066389.
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La these comporte deux parties : partie a : la stereochimie de la cycloaddition du nitroethene, pris comme modele du 6-nitrobenzofuroxane, avec l'ethenol et la vinylamine a ete etudiee au niveau dft. L'analyse des om montre que cette reaction a demande inverse d'electrons est sous controle des orbitales frontalieres. Un chemin reactionnel en une etape avec un etat de transition dissymetrique est plus probable qu'un mecanisme en deux etapes dans lequel l'intermediaire a un caractere essentiellement biradicalaire. L'etude de reactions d'une serie de 6-nitrobenzofuroxanes substitues en position 4 avec divers ethers d'enol et enamines au niveau am1, montre que dans ce cas un mecanisme en deux etapes avec un intermediaire radicalaire a tres courte duree de vie est prefere. Les vitesses relatives et les stereoselectivites de ces reactions en fonction de la nature des reactifs ont aussi ete etudiees. Partie b : l'hydrogenation de cycloalcenes substitues soit par voie chimique par le (z)-1,2-diazene soit par voie catalytique a ete etudiee au niveau am1. Les exemples choisis presentent une stereoselectivite differente selon que l'hydrogenation se fait par voie chimique ou par voie catalytique. Pour l'hydrogenation chimique, les resultats experimentaux (rapport cis/trans) ont ete retrouves. Nous avons pu expliquer la stereoselectivite de la reaction par les interactions conformationelles internes du substrat. Pour l'hydrogenation catalytique, nous avons mis au point un modele pour l'etude de cette reaction. Ce modele repose sur les hypotheses suivantes : - l'etat de transition des additions d'hydrogene sur les cycloalcenes garde la meme geometrie que dans l'hydrogenation chimique. - la surface du catalyseur est modelisee par un tapis de molecules h 2 qui simule son encombrement sterique. Ce modele permet d'interpreter les differences de stereoselectivite observees experimentalement par rapport a l'hydrogenation chimique.
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Blumenthal, Haiko. "Struktur und Reaktivität ausgewählter chiraler N-Acylaminohydroperoxide und -peroxide." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2009. http://dx.doi.org/10.18452/15868.
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Ausgangspunkte der vorliegenden Arbeit waren stereoselektive Synthesen von Reissert-analogen N-Acylaminohydroperoxiden über chirale N-Acylisochinoliniumsalze. Edukte waren Isochinolin(derivaten), Menthylchloroformiat und Wasserstoffperoxid. Es galt die Konfiguration der erhaltenen Produkte zu beweisen und deren Sauerstoffübertragungspotential zu erforschen. Ein zweites Ziel dieser Arbeit war es, von bekannten Diketopiperazinhydroperoxiden ebenfalls das Sauerstoffübertragungspotential zu überprüfen, weil sie die gleiche N-Acylaminohydroperoxidstruktur aufweisen aber bisher wenig untersucht wurden. Es gelang durch NMR-Untersuchungen und Vergleich mit ähnlichen Reaktionen die Annahme eines stereoselektiven Verlaufes zu widerlegen. Weiterhin wurde gezeigt, dass anstelle von Hydroperoxiden Peroxide vorliegen. Es konnte eine in situ Methode entwickelt werden, um mit dem vorgegebenen Substanzen unter Zusatz eines Metallkatalysators wie Vanadium(V)triisopropylat und Titan(IV)tetraisopropylat eine Sauerstoffübertragung auf Methylphenylsulfid zu erzielen. In Abhängigkeit der eingesetzen Isochinolinderivate gelang eine kinetische Racematspaltung, so dass eine stereoselektive Sulfoxidation möglich wurde. Das günstigste Ergebnis betrug 51 % Sulfoxid bei 73 % Enantiomerenüberschuss. Mit einem bekannten Diketopiperazinhydroperoxid konnte Methylphenylsulfid direkt in 62 % Sulfoxid mit 32 % Enantiomerenüberschuss überführt werden. Dies sind die ersten erfolgreichen stereoselektiven Sulfoxidationen mit N-Acylaminohydroperoxiden.Starting points of the present work were stereoselective syntheses of Reissert analogous N-acylaminohydroperoxides derived from chiral N-acylisochinoliniumsalts. Starting materials were isochinoline (and derivates), menthylchloroformiate and hydrogen peroxide. It was a matter of proving the configuration of the preserved products and of investigating the oxygen transfer potential. The second purpose of this work was to check the oxygen transfer potential of known diketopiperazinehydroperoxides likewise because they show the same N-acylaminohydroperoxide structure, however, up to now they were only examined scarcely. One succeeded by NMR investigations and comparison with similar reactions in disproving the acceptance of a stereoselective course. Furthermore it was shown that there are peroxides instead of hydroperoxides. We developed an in situ method to achieve with the given substances under addition of a metal catalyst like vanadium(V)triisopropylate and titanium(IV)tetraisopropylate an oxygen transfer to methylphenylsulfide. In dependence of the used isochinoline derivates a kinetic resolution was observed, so that a stereoselective sulfoxidation became possible. The most favorable result amounted to 51% sulfoxide with 73% enantiomeric excess. With a known diketopiperazinehydroperoxide methylphenylsulfide could be directly transfered into 62% sulfoxide with 32% enantiomeric excess. These are the first successful stereoselective sulfoxidations with chiral N-acylaminohydroperoxides.
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Easton, R. J. C. "Stereoselective synthesis via iron acyl complexes." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379991.
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Smith, Elin Hopcyn. "Stereoselective Hex-5-enyl radical cyclisations." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259644.
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Xie, Jianing. "Advancing Pd-catalyzed Stereoselective Allylic Substitution Reactions." Doctoral thesis, Universitat Rovira i Virgili, 2020. http://hdl.handle.net/10803/670221.
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Aquesta tesi doctoral se centra principalment en el desenvolupament de nous mètodes catalítics (dòmino) basats en la substitució al·lílica catalitzada per Pd per a la síntesi estereoselectiva de petites molècules funcionals i heterocicles utilitzant un disseny detallat de lligants i substrats. Aquesta tesi està organitzada en cinc capítols: el primer capítol és una introducció general sobre els aspectes bàsics de la química al·lílica. El segon capítol il·lustra el primer mètode general per a la preparació d'èters arílics al·lílics terciaris enantioenriquits mitjançant una eterificación regio- i enantio-selectiva catalitzada per Pd dels VCCs en presència de nucleòfils fenòlics. La regioselectivitat de la reacció pot ajustar-se selectivament al producte lineal Z canviant el lligant fosforamidit a un lligant monofosfina, demostrant així el paper crucial del disseny adequat del lligant. El tercer capítol descriu el disseny d'un nou alcohol al·lílic terciari equipat amb un grup carboxil, que s'utilitza en primer lloc per a la síntesi de γ-lactames α,β-insaturades mitjançant una aminació al·lílica estereoselectiva catalitzada per Pd, seguit d’un procés de ciclació intramolecular. Els estudis mecanístics suggereixen que el grup carboxil és crucial per a aquesta transformació i actua com un grup funcional activador i estereodirector. El quart capítol presenta un enfocament estereodivergent controlat pel lligant per a la síntesi de γ-aminoàcids amb configuració Z o E derivats d'alcohols al·lílics terciaris i amines secundàries. Els resultats experimentals destaquen el paper crucial del lligant de suport i l'angle de mossegada de la difosfina. El cinquè capítol informa sobre un mètode general per a la síntesi de caprolactames insaturades substituïdes a través d'un procés d'aminació / ciclació en cascada utilitzant vinil γ-lactones com a substrats mitjançant l'ús d'un lligant fosforamidito recentment desenvolupat. Finalment, s'extreu una conclusió general per a cada capítol i també es discuteix l’aplicació potencial d'aquestes metodologies desenvolupades.Esta tesis doctoral se centra principalmente en el desarrollo de nuevos métodos catalíticos (dominó) basados en la sustitución alílica catalizada por Pd para la síntesis estereoselectiva de pequeñas moléculas funcionales y heterociclos utilizando un diseño detallado de ligandos y sustratos. Esta tesis está organizada en cinco capítulos: el primer capítulo es una introducción general sobre los aspectos básicos de la química alílica. El segundo capítulo ilustra el primer método general para la preparación de éteres arílicos alílicos terciarios enantioenriquecidos mediante una eterificación regio- y enantio-selectiva catalizada por Pd de los VCCs en presencia de nucleófilos fenólicos. La regioselectividad de la reacción puede ajustarse selectivamente al producto lineal Z cambiando el ligando fosforamidito a un ligando monofosfina, demostrando así el papel crucial del diseño adecuado del ligando. El tercer capítulo describe el diseño de un nuevo alcohol alílico terciario equipado con un grupo carboxilo, que se utiliza en primer lugar para la síntesis de γ-lactamas α,β-insaturadas mediante una aminación alílica estereoselectiva catalizada por Pd, seguido por un proceso de ciclación intramolecular. Los estudios mecanisticos sugieren que el grupo carboxilo es crucial para esta transformación y actúa como un grupo funcional activador y estereodirector. El cuarto capítulo presenta un enfoque estereodivergente controlado por el ligando para la síntesis de γ-aminoácidos con configuración Z o E derivados de alcoholes alílicos terciarios y aminas secundarias. Los resultados experimentales destacan el papel crucial del ligando de soporte y el ángulo de mordedura de la difosfina. El quinto capítulo informa sobre un método general para la síntesis de caprolactamas insaturadas sustituidas a través de un proceso de aminación / ciclación en cascada utilizando vinil γ-lactonas como sustratos mediante el uso de un ligando fosforamidito recientemente desarrollado. Finalmente, se extrae una conclusión general para cada capítulo y también se discute la aplicación potencial de estas metodologías desarrolladas.
This doctoral thesis is mainly focused on the development of novel catalytic (domino) synthesis methods based on Pd-catalyzed allylic substitution for the stereoselective synthesis of functional small molecules and heterocycles utilizing a detailed ligand engineering and substrate design. The scope of this thesis is organized into five chapters: the first chapter is a general introduction on the regular aspects of allylic chemistry. The second chapter illustrates the first general method for the preparation of enantioenriched tertiary allylic aryl ethers through a Pd-catalyzed regio- and enantio-selective etherification of VCCs in the presence of phenolic nucleophiles. The regioselectivity of the reaction can be finely tuned to the Z-selective linear product by switching the phosphoramidite ligand to a monophosphine ligand, thus proving the crucial role of proper ligand engineering. The third chapter describes a newly designed tertiary allylic alcohol equipped with a carboxyl group, which is firstly used for α,β-unsaturated γ-lactams synthesis through Pd-catalyzed stereoselective allylic amination and intramolecular cyclization process. Mechanistic studies suggest that the carboxyl group is crucial for this transformation, and acts as an activating and stereodirecting functional group. The fourth chapter presents a ligand-controlled stereodivergent approach for the synthesis of either Z or E-configured γ-amino acids derived from tertiary allylic alcohols and secondary amines. The experimental results highlight the crucial role of the supporting ligand and the diphosphine bite angle. The fifth chapter reports a general method for substituted unsaturated caprolactam synthesis through a cascade amination/cyclization process using vinyl γ-lactones as substrate by using a newly developed phosphoramidite ligand. Finally, a general conclusion for each chapter is given and potential applications for these developed methodologies are also discussed.
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Baar, Cliff Robert. "Stereoselective reactions of organoplatinum and organopalladium complexes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0019/NQ58394.pdf.
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Joensuu, Pekka Matias. "Development of catalytic stereoselective reductive aldol reactions." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/2576.
Full textAbstract:
The chemistry of enolates can be considered one of the cornerstone areas in organic chemistry. Regioselective generation of an enolate in the presence of several enolisable sites can often prove to be a difficult task. Discoveries in recent years have led to new areas of enolate formation in the presence of other carbonyl groups. These include reductive aldol chemistry where direct reductive aldol coupling of an alpha,beta - unsaturated carbonyl group in presence of a carbonyl electrophile enables often perfectly regioselective reactions to occur. This tandem conjugate reductionelectrophilic trapping process enables the reaction to be performed in a “one-pot” manner. The first examples of asymmetric copper-catalysed reductive aldol reactions have been developed for the formation of a range of beta-hydroxylactone products. A combination of Cu(OAc)2.H2O with different bisphosphine ligands catalyses these intramolecular reductive aldol reactions. TMDS (1,1,3,3-tetramethylhydrosiloxane) is used as a stoichiometric hydride source. The reaction proceeds with high relative stereocontrol (>19:1 dr), while absolute stereocontrol remains modest (up to 83% ee). The yields range from moderate to good. A continuous search for improved reaction conditions led to the discovery that cobalt-catalysed reductive aldol reactions have an advantage over the coppercatalysed reaction in the cases where 4-hydroxypiperidin-2-one products are formed. When Co(acac)2·H2O is used together with Et2Zn as the stoichiometric reductant, an increased substrate scope is observed while the diastereoselectivity of the reaction remains high. Yields are also remarkably higher compared to the results obtained with the copper catalyst. These reaction conditions are also used to perform intermolecular reductive aldol reactions between a range of alpha,beta-unsaturated amides and ketones. The reactions proceed readily with high diastereoselectivities (up to >19:1 syn:anti) and good yields. Asymmetric variants have been studied by the use of a chiral oxazolidine auxiliary. Although good selectivities have been obtained, this method currently suffers from the fact that the chiral auxiliary is difficult to cleave. Ni(acac)2 was also found to perform the intramolecular reductive aldol reaction. Et2Zn was again used as the stoichiometric reductant. The nickel-catalysed reaction increased the reaction scope still further. This time both beta-hydroxylactone and 4-hydroxypiperidin-2-one products were readily formed. The former proceeded with increased yields compared to those obtained with the copper catalyst, and, the latter with comparable results to those obtained with the cobalt catalyst.
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Goodfellow, Craig L. "Stereoselective reactions of arene chromium tricarbonyl complexes." Thesis, University of Oxford, 1989. http://ora.ox.ac.uk/objects/uuid:e2833156-aec2-42e5-b835-e9ddca4fa27c.
Full textAbstract:
This thesis describes the application of (arene)Cr(CO)3 methodology to the Stereoselective and enantioselective synthesis of substituted arenes. Chapter one reviews the main methods of preparation and decomplexation of (arene)Cr(CO)3 complexes and the electronic and steric influences of the Cr(CO)3 unit on the arene. Chapter two demonstrates that the benzylic oxygen directing effect in complexation reactions operates via a direct oxygen bond to the incoming metal unit. Attachment of bulky ft-acceptor groups, such as t-butyldimethylsilyl, to the benzylic oxygen overrides this directing effect. Chapter three describes the regioselective Cl functionalisation of the cryptopine skeleton. Complexation of dihydrocrytopine gives only a single product, the relative configuration of the product being determined using an X-ray crystal structure analysis. Subsequent alkylation of the O-methyl derivative gives Cl alkylated products. Chapter four describes the regioselective ortho functionalisation of ephedrine and pseudoephedrine derivatives. Treatment of (1S,2R)-(N,O-dimethylpseudoephedrine) Cr(CO)3 with n-butyllithium leads to exclusive removal of the pro-(R) ortho proton. The observed stereoselectivity arises via3. Complexation of 1-methylhydrocotarnine occurs to give exclusively the exo-1-methyl derivative. Further functionalisation to give the 1,5- and 4,5-dimethyl products is also described. Chapter six describes the synthesis of ortho substituted (benzaldehyde)Cr(CO)3 complexes. Chiral material is available via preferential kinetic hydrolysis of, or classical separation of, the L-valinol derived imines. Chapter seven describes the Stereoselective addition of nucleophiles to (o-anisaldehyde) Cr(CO)3 and (o-trialkylsilylbenzaldehyde)Cr(CO)3. With (o-anisaldehyde)- Cr(CO)3 the additions are completely stereoselective giving the (RR,SS) diastereoisomer. With (o-trialkylsilylbenzaldehyde)Cr(CO)3 the ratio of products is influenced by the nature of Lewis acidic species present. Chapter eight describes the Stereoselective benzylic elaboration of (o-methoxybenzyl methyl ether)Cr(CO)3 achieved via selective removal of the exo benzylic proton from transition states with the methoxy groups anti to each other.
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Kaiser, Delene Anne. "Stereoselective reactions of 16-Methylene 19-Norsteroids." Master's thesis, University of Cape Town, 1991. http://hdl.handle.net/11427/22136.
Full textAbstract:
The influence of the 17-substituent upon epoxidation of 3-methoxy-16-methylene-estra- 1,3,5(10)-trien-17-one and the derived 17β-hydroxy and 17β-acetoxy compounds was investigated. Alkaline hydrogen peroxide epoxidation of 3-methoxy-16-methyleneestra- 1,3,5(10)-trien-17-one occurred in good yields, but poor stereoselectivity was obtained due to mechanistic considerations. Poor stereoselectivity was also obtained for the peracid epoxidation of 3-methoxy-16-methylene-estra-1,3,5(10)-trien-17β-ol, due to the pseudo-equatorial position of the 17β-hydroxyl group. However, excellent stereoselectivity was obtained using Sharpless conditions (vanadium catalyst), which gave only the epoxide syn to the hydroxyl group, in good yields. Surprisingly, peracid epoxidation of 3-methoxy-16-methylene-estra-1,3,5(10)-trien-17β-yl acetate favoured equatorial attack resulting in a 2:1 ratio of the (16R)- and (16S)-epoxide isomers, instead of the expected axial approach by the peracid.
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Guiteras, Capdevila Montserrat <1980>. "Development of Organocatalytic stereoselective SN1 type reactions." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4370/1/Guitera_Capdevila_Montse_tesi.pdf.
Full textAbstract:
The proposal in my thesis has been the study of Stereoselective α-alkylation through SN1 type reaction. SN1 type reaction involves a stabilized and reactive carbocation intermediate By taking advantages of stability of particular carbocations, the use of carbocations in selective reactions has been important. In this work has been necessary to know the stability and reactivity of carbocations. And the work of Mayr group has helped to rationalize the behaviour and reactivity between the carbocations and nucleophiles by the use of Mayr’s scale of reactivity.
The use of alcohols to performed the stable and reactive carbocations have been the key in my thesis. The direct nucleophilic substitution of alcohols has been a crucial scope in the field of organic synthesis, because offer a wide range of intermediates for the synthesis of natural products and pharmaceutics synthesis. In particular the catalytic nucleophilic direct substitution of alcohols represents a novel methodology for the preparation of a variety of derivatives, and water only as the sub-product in the reaction.
The stereochemical control of the transformation C-H bond into stereogenic C-C bond adjacent to carbonyl functionalized has been studied for asymmetric catalysis. And the field of organocatalysis has introduced the use of small organic molecule as catalyst for stereoselective transformations.
Merging these two concepts Organocatalysis and Mayr’s scale, my thesis has developed a new approach for the α-alkylation of aldehydes and ketones through SN1 type reaction.La proposta della mia tesi è stato lo studio stereoselettiva di α-alchilazione attraverso la reazione di tipo SN1. SN1 reazione tipo comporta un stabilizzato e reattivo carbocatione intermedio Prendendo vantaggi della stabilità dei carbocationi particolari, l'uso di carbocationi in reazioni selettive è stato importante. In questo lavoro è stato necessario conoscere la stabilità e reattività dei carbocationi. E il lavoro di Mayr gruppo ha contribuito a razionalizzare il comportamento e reattività tra i carbocationi e nucleofili con l'uso della scala Mayr di reattività. L'uso di alcool ai eseguito i carbocationi stabili e reattive sono state la chiave nella mia tesi. La sostituzione nucleofila diretta di alcoli è stata portata cruciale nel campo della sintesi organica, poiché offrono un'ampia gamma di intermedi per la sintesi di prodotti naturali e di sintesi farmaceutica. In particolare il catalizzatore sostituzione nucleofila diretta di alcoli rappresenta una nuova metodologia per la preparazione di una varietà di derivati, e l'acqua come unico sottoprodotto nella reazione. Il controllo stereochimica del legame CH trasformazione in legame C-C stereogenico adiacente al carbonile funzionalizzata è stata studiata per la catalisi asimmetrica. E il campo dell'organocatalisi ha introdotto l'uso di piccola molecola organica come catalizzatore per trasformazioni stereoselettive. L'unione dell'organocatalisi questi due concetti e la scala Mayr, la mia tesi ha sviluppato un nuovo approccio per la α-alchilazione di aldeidi e chetoni, attraverso reazione di tipo SN1
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Guiteras, Capdevila Montserrat <1980>. "Development of Organocatalytic stereoselective SN1 type reactions." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4370/.
Full textAbstract:
The proposal in my thesis has been the study of Stereoselective α-alkylation through SN1 type reaction. SN1 type reaction involves a stabilized and reactive carbocation intermediate By taking advantages of stability of particular carbocations, the use of carbocations in selective reactions has been important. In this work has been necessary to know the stability and reactivity of carbocations. And the work of Mayr group has helped to rationalize the behaviour and reactivity between the carbocations and nucleophiles by the use of Mayr’s scale of reactivity.
The use of alcohols to performed the stable and reactive carbocations have been the key in my thesis. The direct nucleophilic substitution of alcohols has been a crucial scope in the field of organic synthesis, because offer a wide range of intermediates for the synthesis of natural products and pharmaceutics synthesis. In particular the catalytic nucleophilic direct substitution of alcohols represents a novel methodology for the preparation of a variety of derivatives, and water only as the sub-product in the reaction.
The stereochemical control of the transformation C-H bond into stereogenic C-C bond adjacent to carbonyl functionalized has been studied for asymmetric catalysis. And the field of organocatalysis has introduced the use of small organic molecule as catalyst for stereoselective transformations.
Merging these two concepts Organocatalysis and Mayr’s scale, my thesis has developed a new approach for the α-alkylation of aldehydes and ketones through SN1 type reaction.La proposta della mia tesi è stato lo studio stereoselettiva di α-alchilazione attraverso la reazione di tipo SN1. SN1 reazione tipo comporta un stabilizzato e reattivo carbocatione intermedio Prendendo vantaggi della stabilità dei carbocationi particolari, l'uso di carbocationi in reazioni selettive è stato importante. In questo lavoro è stato necessario conoscere la stabilità e reattività dei carbocationi. E il lavoro di Mayr gruppo ha contribuito a razionalizzare il comportamento e reattività tra i carbocationi e nucleofili con l'uso della scala Mayr di reattività. L'uso di alcool ai eseguito i carbocationi stabili e reattive sono state la chiave nella mia tesi. La sostituzione nucleofila diretta di alcoli è stata portata cruciale nel campo della sintesi organica, poiché offrono un'ampia gamma di intermedi per la sintesi di prodotti naturali e di sintesi farmaceutica. In particolare il catalizzatore sostituzione nucleofila diretta di alcoli rappresenta una nuova metodologia per la preparazione di una varietà di derivati, e l'acqua come unico sottoprodotto nella reazione. Il controllo stereochimica del legame CH trasformazione in legame C-C stereogenico adiacente al carbonile funzionalizzata è stata studiata per la catalisi asimmetrica. E il campo dell'organocatalisi ha introdotto l'uso di piccola molecola organica come catalizzatore per trasformazioni stereoselettive. L'unione dell'organocatalisi questi due concetti e la scala Mayr, la mia tesi ha sviluppato un nuovo approccio per la α-alchilazione di aldeidi e chetoni, attraverso reazione di tipo SN1
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Porta, R. "STEREOSELECTIVE CATALYTIC REACTIONS UNDER CONTINUOUS FLOW CONDITIONS." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/479336.
Full textAbstract:
This PhD Thesis deals with the application of different catalytic methodologies under continuous flow conditions. In particular, the combination of flow chemistry with different enabling technologies is explored.
In Chapter 1 the combination of continuous flow processes with the use of different solid supported chiral organocatalysts is described. The fabrication of chiral, packed-bed and monolithic, organocatalytic reactors and their use in stereoselective transformations are reported. The possibility to recycle the immobilized chiral catalysts is also discussed.
- In section 1.2 the use of polystyrene- and silica-supported chiral imidazolidinones to perform continuous flow stereoselective Diels-Alder cycloadditions and stereoselective aldehydes alkylation is studied.
- In section 1.3 the immobilization onto different materials of primary amines derived from Cinchona alkaloids and the application under flow conditions are explored.
- In section 1.4 chiral picolinamides for the continuous stereoselective reduction of imines with trichlorosilane are studied.
Chapter 2 describes the application of different synthetic strategies using flow micro(meso)-reactors, aimed to the synthesis of chiral active pharmaceutical ingredients or immediate advanced precursors of compounds of industrial interest. In particular,
- in section 2.2 the organocatalytic, stereoselective synthesis of (S)-Pregabalin and (S)-Warfarin within microreactors is investigated.
- Section 2.3 presents the continuous flow synthesis of primary amines through a metal-free reduction of nitro compounds with trichlorosilane.
- In section 2.4 a catalytic strategy for a multistep synthesis of chiral, biological active 1,2-amino alcohols using 3D-printed flow reactors is highlighted.
Chapter 3 covers the research work carried out during my research period in Aachen, Germany which was focused on the development of a new synthetic methodology using photoredox catalysis. In particular, the photocatalytic reductive coupling of imine with olefins for the preparation of -amino esters and its application under continuous flow conditions are discussed.