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1
Jain, Nikita. "Chiral hypervalent iodine mediated enantioselective oxidative dearomatization of naphthols." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62521.
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This dissertation investigates and describes the hypervalent iodine mediated dearomatization of naphthols, thereby yielding diversity of spiro-heterocyclic compounds in both racemic and chiral form.
The first part of this thesis discloses the synthesis of racemic spiropyrrolidines and spirolactams via oxidative amidation of corresponding naphtholic sulfonamides, employing DIB as the oxidant. Enantioselective variant of the same have been demonstrated by using in situ generated chiral hypervalent iodine to provide chiral spiropyrrolidines. A noteworthy side reaction discovered in the course of these studies is the asymmetric oxidative addition of meta-chlorobenzoic acid to the naphtholic sulfonamides. The resulting acyloxylated adducts were formed with a greater degree of asymmetric induction compared to spiropyrrolidines in the same reaction mixture. Based on the results obtained from optimization study and substrate scope, plausible mechanistic insights of both cyclization and acyloxylation reactions have been provided.
The second part of this thesis unravels the spiroetherification of naphtholic alcohols, thereby yielding spiroethers both in racemic and chiral form. Chiral hypervalent iodine reagents generated in situ provided a range of spiroethers with excellent ee’s and high yields. These chiral oxidants have been evaluated for kinetic resolution of naphtholic primary alcohols bearing stereogenic center at β-position in the side chain.Science, Faculty of
Chemistry, Department of
Graduate
2
Wu, Ju. "Electrochemical and Non-electrochemical Oxidative Dearomatization Reactions of Indoles." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS368.
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L'électrochimie est apparue comme un puissant outil de synthèse durable en chimie organique, qui évite l'utilisation d'un oxydant stoechiométrique externe et permet le développement de méthodes de difonctionnalisation très efficaces et sélectives des indoles dans des conditions douces. L'utilisation de médiateurs redox pour réaliser l'électrolyse indirecte a gagné en importance ces dernières année, ce qui offre de nombreux avantages par rapport à l'électrolyse directe. Les réactions de désaromatisation des hétéroarènes achiraux, et en particulier des indoles, donnent des structures tridimensionnelles d’un grand intérêt pour la synthèse totale ou la découverte de médicaments, via la génération de deux centres stéréogéniques contigus. Ainsi des efforts de synthèse intensifs ont été consacrés à la difonctionnalisation désaromatisante d’indoles. Dans ce contexte, le développement de réactions de désaromatisation des indoles a été étudié au cours de cette thèse. Dans la première partie de la thèse, une diallylation désaromatisante de N-acylindoles médiée par FeCl₃ a été développée pour obtenir des indolines tridimensionnelles sélectives possédant deux centres stéréogéniques contigus. Dans ce procédé, deux groupes allyle ont été introduits sur des N-acylindoles avec de l'allyltriméthylsilane en présence de FeCl₃, conduisant à la formation de deux liaisons carbone-carbone et de deux centres stéréogéniques contigus. La stéréosélectivité de cette transformation est contrôlée par la substitution du noyau indole. Des applications synthétiques ont permis d'obtenir des squelettes trans-tétrahydrocarbazoles et aza[4.4.3]propellanes par RCM. L'hydratation sélective de l'un des groupes allyliques a également été réalisée. Dans la deuxième partie de la thèse, une désomatisation oxydante directe des indoles a été réalisée par électrochimie, conduisant à des 2,3-dialcoxy ou des 2,3-diazido indolines avec une cellule non divisée à courant constant. Cette difonctionnalisation électrochimique des indoles évite l'utilisation d'un oxydant externe et présente une excellente compatibilité de groupes fonctionnels, ce qui devrait inspirer le développement d'autres réactions de désaromatisation afin d'accéder à des architectures à haute valeur ajoutée à partir de matériaux de départ facilement disponibles. Sur la base de l'étude mécanistique, nous pensons que la formation des deux liaisons C-O ou C-N résulte de l'oxydation des indoles en un intermédiaire radical cation. Dans la troisième partie de la thèse, une désaromatisation oxydante par électrolyse indirecte des indoles a été conçue en utilisant MgBr₂ comme médiateur redox pour éviter l'oxydation directe du noyau indole à l'anode. L’oxydation de l’indole en un ion bromonium induite par la génération d’un réactif électrophile bromé à partir de MgBr₂, conduit à des réactions de dihydroxylation, d’hydroxycyclisation et de bromocyclisation d’indoles. Aucun sous-produit organique n'est généré avec ce protocole qui ne nécessite aucun électrolyte supplémentaire. L’intérêt de cette transformation est démontré par les applications synthétiquesElectrochemistry emerged as a powerful sustainable synthetic tool in organic chemistry, which avoids the use of an external stoichiometric oxidant and enables the development of methods for the highly efficient and selective difunctionalization of indoles in mild conditions. The use of redox mediators to achieve indirect electrolysis is attaining increased significance, which offers many advantages compared to direct electrolysis. Dearomatization reactions of achiral heteroarenes and in particular of indoles, afford three-dimensional structures of high interest for total synthesis or drug discovery, through the generation of two contiguous stereogenic centers. Intensive synthetic efforts have been devoted to dearomative difunctionalization of indoles. In this context, the development of dearomatization reactions of indoles has been studied in this thesis. In the first part of the thesis, a dearomative diallylation of N-acylindoles mediated by FeCl₃ was developed to obtain selectively three-dimensional indolines possessing two contiguous-stereogenic centers. In this process, two allyl groups were introduced to N-acylindoles with allyltrimethylsilane in the presence of FeCl₃, leading to the formation of two carbon-carbon bonds and two contiguous-stereogenic centers. The stereoselectivity of this transformation is controlled by the substitution of the indole nucleus. Synthetic application allowed to obtain trans-tetrahydrocarbazoles and aza[4.4.3]propellane scaffolds by RCM. Selective hydration of one of the allyl group was achieved. In the second part of the thesis, a direct oxidative dearomatization of indoles was performed with electrochemistry, leading to 2,3-dialkoxy or 2,3-diazido indolines under undivided cell conditions at a constant current. This general difunctionalization of indoles avoids the use of an external oxidant and displays excellent functional group compatibility, which should inspire the development of other dearomatization reactions to access high added-value architectures from readily available starting materials. Based on the mechanistic study, the formation of the two C-O or C-N bonds is believed to arise from the oxidation of the indoles into radical cation intermediates. In the third part of the thesis, an indirect oxidative dearomatization of indoles was devised by using MgBr₂ as the redox mediator to avoid the direct oxidation of the indole nucleus at the anode. The oxidation of the indole into a bromonium ion induced by the generation of an electrophilic bromine reagent from MgBr₂, and lead to dihydroxylation, hydroxycyclization and bromocyclization reactions of indoles. No organic byproducts are generated with this protocol which requires no additional electrolyte. The potential of this transformation is demonstrated by synthetic applications
3
Pace, Robert David Matthew. "Catalytic enantioselective dearomatization and studies towards the total synthesis of (-)-morphine." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611683.
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Garnier, Tony. "Désaromatisation oxydante asymétrique de phénols : développements méthodologiques et application à la synthèse de la scyphostatine." Thesis, Bordeaux 1, 2010. http://www.theses.fr/2010BOR14160/document.
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Les réactifs iodés hypervalents (i.e. iodanes) et les complexes métalliques en milieu oxydant sont des outils particulièrement efficaces pour réaliser la réaction de désaromatisation oxydante de phénols et donner ainsi accès à des motifs cyclohexa-2,4-diénone. Ces travaux de thèse ont permis d'étudier le développement de versions asymétriques de cette réaction de désaromatisation contrôlée soit par le substrat dans le cas de l’utilisation d’iodanes, soit par le réactif lorsqu’un complexe métal/ligands chiraux est privilégié. Cette méthodologie a ensuite été appliquée à la synthèse de la (+)-scyphostatine, un inhibiteur naturel de la sphingomyélinase neutreAbstract
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Vitaku, Edon, and Edon Vitaku. "Strategic Oxidative Dearomatization - Rearomatization Cascades in the Synthesis of Aromatic and Heteroaromatic Synthons." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/621360.
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Four new synthetic methods employing an oxidative dearomatization - rearomatization strategy are presented. In Chapter 2, a new oxidative dearomatization - radical cyclization - rearomatization approach to form fused oxygen-containing heterocycles is presented. Origins, design, reaction, and optimizations are discussed. In Chapter 3, meta-selective alkylation of catechol mono-ethers is described employing an oxidative dearomatization - radical addition - rearomatization approach using trialkylboranes as source of alkyl radicals. In Chapter 4, a metal-free method to synthesize fluorinated indoles from aniline starting materials is described. Chapter 5 lays the groundwork for para-selective functionalization of catechol mono-ethers. Chapters 6 and 7 highlight the work related to pharmaceutical drug analyses. Chapter 6 presents the FDA approved drugs organized in Disease Focused Posters. Chapter 7.1 and 7.2 present the drug analysis of Sulfur- and Fluorine-Containing Drugs, and Nitrogen-Heterocycle Containing Drugs, respectively.
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Vo, Ngoc Tri. "A catalytic enantioselective dearomatization strategy and studies towards the total synthesis of daldinone C." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611307.
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Fischer, Theresa [Verfasser], and Mancheño Olga [Akademischer Betreuer] García. "Enantioselective Nucleophilic Dearomatization of Heteroarenes by Anion-Binding-Catalysis / Theresa Fischer ; Betreuer: Olga García Mancheño." Regensburg : Universitätsbibliothek Regensburg, 2019. http://d-nb.info/1180719484/34.
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Rousseaux, Sophie. "Palladium-Catalyzed C(sp2)-C(sp3) Bond Formation." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23058.
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Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for “palladium-catalyzed cross couplings in organic synthesis”, and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.
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Guddehalli, Parameswarappa Sharavathi. "Bifunctional cyclooctynes in copper-free click chemistry for applications in radionuclide chemistry nd 4-Alkylpyridine derivatives in intramolecular dearomatization and heterocycle synthesis." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/2710.
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Part A. Bifunctional cyclooctynes in copper-free click chemistry for applications in radionuclide chemistry: A new monofluorinated cyclooctyne (MFCO) with a reasonable kinetic profile was synthesized in three steps. We have demonstrated that MFCO can be used as a lynchpin to conjugate biomolecules to radionuclide chelators using copper-free 1,3-dipolar cycloaddition reactions with azides. Many bifunctional biomolecule-chelators were synthesized, and then radiolabelled with very high radiochemical purity and specific activity. MFCO-amine analogues were also synthesized and used in construction of chelator-biomolecule conjugates (particularly, NDP-α-MSH analogues) for applications in radioimaging. Bis-MFCO based bivalent ligands with various linker lengths were also synthesized as precursors to multivalent ligands for use in cancer diagnosis and therapy.
Part B. 4-Alkylpyridine derivatives in intramolecular dearomatization and heterocycle synthesis: 4-Alkylpyridine derivatives substituted with different carbon nucleophiles were synthesized and subjected to intramolecular spirocyclization under various conditions to afford synthetically useful diazaspiro[4.5]decanes as well as diazaspiro[5.5]undecanes in good yields. The same 4-alkyl substrates were used to synthesize anhydrobase intermediates which, then participated in aldol-like condensation in the presence of Lewis acid to yield highly conjugated dihydropyridines. Acid hydrolysis produced substituted pyridines tethered with functionalized butyro- and valero lactams. The synthesis of related azaspiro[4.5]decanes and azaspiro[5.5]undecanes from reaction of
hypervalent iodine reagents with 4-methoxy-substituted benzyl and phenethyl substrates linked to β-keto amide nucleophiles was also briefly investigated.
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El, assal Mourad. "Désaromatisation oxygénante asymétrique de phénols à l'aide d'iodanes pour la synthèse totale de substances naturelles." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0348/document.
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La réaction de désaromatisation oxygénante de phénols est une transformation très utile en tant qu’étape clé dans la synthèse de substances naturelles complexes. Elle permet de préparer des intermédiaires de type cyclohexa-2,4-diénones à partir de phénols ortho-substitués, notamment en utilisant des réactifs iodés hypervalents (i.e., iodanes) qui constituent une alternative moderne aux réactifs à base de métaux lourds toxiques (e.g., Pb, Tl, Hg). Notre équipe s’intéresse plus particulièrement à la désaromatisation hydroxylante de 2-alkylphénols (réaction HPD) par des iodanes, transformation qui engendre la création d’un centre carboné quaternaire stéréogène. Le contrôle de la configuration de ce centre chiral par l’utilisation d’un substrat ou d’un réactif approprié est un de nos objectifs. Des iodanes chiraux récemment développés au laboratoire ont permis d’atteindre des excès énantiomériques de plus de 90% dans des réactions HPD modèles. Nous avons exploité avec succès ces iodanes chiraux pour réaliser les premières synthèses totales de la (–)-bacchopétiolone et de la (+)-mayténone, ainsi que pour élaborer la tête polaire de type ortho-quinol époxydé de la (+)-scyphostatineThe oxygenative phenol dearomatization reaction is a very useful transformation, as a key step in the synthesis of complex natural substances. It gives access to cyclohexa-2,4-dienones from ortho-substituted phenols, through the use of hypervalent iodine reagents (i.e., iodanes), which constitutes a modern alternative to toxic heavy-metal-based reagents (e.g., Pb, Tl, Hg). Our team is interested in the hydroxylative dearomatization of 2-alkylphenols (HPD reaction) by iodanes, a transformation that results in the formation of one quaternary stereogenic center. Control of the absolute configuration of this chiral center through the use of an appropriate substrate or reagent is amongst our goals. Chiral iodanes recently developed in the laboratory allowed us to reach enantiomeric excesses above 90 % in model HPD reactions. Successful application of these chiral iodanes led us to achieve the first total syntheses of (–)-bacchopetiolone and (+)-maytenone, as well as that of the epoxy ortho- quinol polar head of (+)-scyphostatine
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Grossmann, Adriana [Verfasser], and Thomas [Akademischer Betreuer] Magauer. "Studies toward the total synthesis of salimabromide via dearomatization of 1-Naphthols and investigation of the Claisen Rearrangement of allyl chlorovinyl ethers / Adriana Grossmann ; Betreuer: Thomas Magauer." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1176971409/34.
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Soulard, Marine. "Approche synthétique vers la synthèse totale de l’epicocconone, étude de la réaction de désaromatisation oxydante à l’aide d’iode hypervalent (III) ou (V)." Thesis, Rouen, INSA, 2014. http://www.theses.fr/2014ISAM0005/document.
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L'epicocconone est un produit naturel tricyclique, de la famille des azaphilones, isolé en 2003 d'un champignon Epicoccum nigrum. Ce composé se lie de façon covalente aux amines, conduisant à la formation d'une énamine fluorescente. Cette réaction, réversible en fonction du pH, fait de ce composé un excellent marqueur de protéines pour la détection sur gels d'électrophorèse compatible avec une analyse de spectrométrie de masse. La synthèse de ce produit naturel a été débutée au sein de notre laboratoire en s'appuyant sur les travaux réalisés précédemment et mettant en jeu une étape clé de désaromatisation oxydante à l'aide d'iode hypervalent. Une étude méthodologique de réaction clé a permis de comparer l'efficacité et la diastéréosélectivité de l'oxydation effectuée par l'iode (III) ou l'iode (V)Epicocconone is a tricyclic natural product of the azaphilone family, isolated from the fungus Epicoccum nigrum. This compound covalently binds to primary amines, leading to a protein conjugate which is highly fluorescent. This reaction, reversible according to the pH, make this compound an excellent protein stain compatible with mass spectrometry analysis. The synthesis of this natural product has been started in our laboratory based on the previous work in involves a key oxidative dearomatization using hypervalent iodine. Methodological studies of this key reaction allowed us to compare the efficiency and diastereoselectivity of iodine (III) and iodine (V) mediated oxidations
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Boulangé, Agathe. "Synthèse d'analogues de l'épicocconone par réaction d'oxydation désaromatisante : relation structure fluorescences et application en protéomique." Phd thesis, INSA de Rouen, 2012. http://tel.archives-ouvertes.fr/tel-00735882.
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L'epicocconone est un produit naturel tricyclique de la famille des azaphilones isolé en 2003 d'un champignon Epicoccum nigrum. Ce composé se lie de façon covalente aux amines, conduisant à la formation d'une énamine fluorescente. Cette réaction, réversible en fonction du pH, fait de ce composé un excellent marqueur de protéines pour la détection sur gels d'électrophorèse compatible avec une analyse par spectrométrie de masse. La synthèse d'analogues de l'épicocconone a été engagée au sein de notre laboratoire, en basant sur une étape clé d'oxydation désaromatisante. Une étude approfondie de cette réaction a permis de mettre en évidence une haute diastéréosélectivité en fonction des conditions opératoires.Après introduction d'un cycle acylfuranonique diversement fonctionnalisé, une série d'analogues de l'épicocconone a été obtenue permettant d'établir la relation structure fluorescence et évaluer l'utilisation de ces biomarqueurs en protéomique.
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Marguerit, Mélanie. "Désaromatisation hydroxylante de phénols par des réactifs iodés hypervalents : application à la synthèse de substances naturelles." Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13924/document.
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La réaction de désaromatisation hydroxylante de phénols (HPD) est un outil puissant pour accéder de façon biomimétique, en une seule étape à partir de 2-alkylphénols, aux ortho-quinols, c’est-à-dire les 6-alkyl-6-hydroxycyclohexa-2,4-diénones. Ces synthons peuvent être présentés tels quels par de nombreux produits naturels mais peuvent aussi servir d’intermédiaires hautement fonctionnalisés pour la construction rapide d’architectures structurales complexes. L’acide o-iodoxybenzoïque (IBX), un réactif de type iodane-?5, et sa formulation stabilisée non-explosible (SIBX) se sont révélés particulièrement efficaces pour promouvoir des réactions HPD de manière ortho-sélective. Ces travaux de thèse concernent l’application de cette réaction à l’élaboration d’un intermédiaire ortho-quinolique clé hautement fonctionnalisé pour la synthèse d’un antibiotique de type angucycline, la (+)-aquayamycine, ainsi qu’à la première synthèse totale d’un ortho-quinol naturel non dimérisant, la (+)-wasabidiénone B1. Enfin, le développement d’une version asymétrique de cette réaction a été entrepris. La génération in situ de iodanes à partir de iodoarènes chiraux et de m-CPBA comme co-oxydant permet de préparer soit des ortho-quinols de façon non racémique lorsque des quantités stoechiométriques des deux réactifs sont utilisées, soit des ortho-quinols régio- et diastéréosélectivement époxydés lorsqu’une quantité catalytique de iodoarène chiral est employée. Un suivi de ces réactions par spectrométrie de masse a conduit à la détection d’espèces de type iodanyl-?3 et/ou -?5, et à la proposition d’un mécanisme pour ces réactions de désaromatisation hydroxylante asymétriqueThe hydroxylative phenol dearomatization (HPD) reaction is a powerful tool to access, in one biomimetic step from various 2-alkylphenols, ortho-quinols, i.e., 6-alkyl-6-hydroxycyclohexa-2,4-dienones. These dearomatized moieties can be found as such in few natural products or can be used as highly functionalized intermediates. The ?5-iodane 2-iodoxybenzoic acid (IBX) and its stabilized nonexplosive formulation (SIBX) have proved particularly useful and efficient in mediating HPD reactions in a strictly ortho-selective manner. This PhD work describes the application of our SIBX-mediated HPD reaction to the elaboration of a key ortho-quinolic advanced intermediate for the synthesis of the angucycline-type antibiotic (+)-aquayamycin, and to the first total synthesis of the natural non-dimerizing ortho-quinol (+)-wasabidienone B1. An asymmetric version of this HPD reaction has been also developed. In situ generation of iodanes from chiral iodoarenes and m-CPBA as co-oxidant enables the preparation of either ortho-quinols in a non racemic form when using stoechiometric amounts of both reagents, or regio- and diastereoselectively epoxidized ortho-quinols when a catalytic amount of the chiral iodoarene is used. Monitoring of these reactions by mass spectrometry allowed the detection of ?3- and/or ?5-iodanyl-type species, and the proposition of a mechanism for these asymmetric hydroxylative dearomatization reactions
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Erhard, Thomas. "Totalsynthese von (±)-Codein durch 1,3-dipolare Cycloaddition." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-69013.
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Die Nitron-Cycloaddition an ein dearomatisiertes Phenol ermöglichte den leichten Aufbau des Phenanthrengerüstes von Codein in der gewünschten Konfiguration. Weitere Schritte führten mit kompletter Diastereoselektivität zu Allopseudocodein und nach Allylverschiebung durch Hydrolyse der Chlorcodide schließlich zu (±)-Codein.
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Rkein, Batoul. "Désaromatisation d'arènes électro-appauvris par des réactions de cycloadition (4+2) The facile dearomatization of nitroaromatic compounds using lithium enolates of unsaturated ketones in conjugate additions and (4+2) formal cycloadditions." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR092.
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Les composés aromatiques sont largement accessibles, que ce soit à partir de la pétrochimie, ou de molécules naturelles. Ainsi, des efforts importants ont été faits pour convertir ces molécules simples et facilement disponibles en structures 3D complexes d’intérêts synthétiques tels que des polycycles possédant des centres tétrasubstitués, utiles par exemple dans la synthèse de produits naturels ou pharmaceutiques. Même si plusieurs méthodes efficaces de désaromatisation ont été décrites, le développement de méthodologies complémentaires reste nécessaire. Dans ce contexte, les cycloadditions (4+2) représentent une approche attrayante pour obtenir des composés polycycliques complexes à partir de substrats aromatiques simples. Au cours de ce travail, nous avons examiné la réactivité de différents composés nitroaromatiques vis-à-vis des des silyloxydiènes lors de cycloadditions de Diels-Alder à demande électronique normale. Ces réactions se font sous pression ambiante pour les dérivés du nitroindole ; tandis qu'une pression élevée est nécessaire pour les nitroaromatiques moins réactifs. Une méthodologie complémentaire basée sur l'activation nucléophile du diène, par la formation de son énolate de lithium, a été développée. La désaromatisation des nitroarènes par des énolates lithiés peut également avoir lieu dans un processus formel de cycloaddition (4+2)Aromatic compounds are common substrates, obtained either from the petrochemical industry or from natural products. Thus, important efforts have been made to convert these simple and easily available molecules into complex 3D structures of synthetic interest such as polycycles featuring tetrasubstituted centers, for example, useful in the synthesis of natural or pharmaceutical products. Even if several efficient dearomatizing methods have been reported, the development of complementary methodologies is still needed. In this context, (4+2) cycloadditions represent an attractive approach to obtain complex polycyclic compounds from simple aromatic substrates. In the course of this work, we have examined the reactivity of different nitroaromatics towards silyloxydienes in Normal Electron Demand Diels-Alder cycloadditions. These reactions showed to proceed under ambient pressure for nitroindole derivatives, while high pressure conditions were needed for more challenging nitroaromatics. A complementary methodology based on the nucleophilic activation of the diene, through the formation of its lithium enolate has been developed. The dearomatization of nitroarenes by lithiated enolates can also take place following a formal (4+2) cycloaddition process
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Cheikh, Ali Zakaria. "Études chimiques et biologiques d’Aframomum sceptrum (Zingiberaceae) et de la curcumine." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA114814/document.
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Ce travail de thèse consacré à la chimie de Zingiberaceae est divisé en deux parties distinctes.Dans la première partie, une étude phytochimique des rhizomes d’une plante africaine, Aframomum sceptrum K. Schum., couramment employée en Côte d’Ivoire, a été réalisée. Deux nouveaux composés, nommés sceptrumlabdalactone A et sceptrumlabdalactone B ont été isolés. Ce sont des composés terpéniques type labdane. Le sceptrumlabdalactone B est fortement actif contre L. donovani, avec une CI50 proche de celle de la pentamidine.L’extraction de l’huile essentielle des rhizomes a également été réalisée par hydrodistillation. L’analyse de l’huile par GC-MS a montré la présence de mono- et de sesquiterpènes avec une quasi-absence de monoterpènes aromatiques. L’évaluation des activités biologiques de l’huile a montré une activité contre les bactéries à Gram positif, et dans une moindre mesure, contre les bactéries à Gram négatif. Une forte activité trichomonicide a aussi été constatée.La deuxième partie, est consacrée à la curcumine. Ce diarylheptanoïde, est fréquent dans plusieurs Curcumas, Des analogues originaux, par exemple prénylés ont été préparés. Plusieurs activités biologiques (activités antiparasitaires, antibactériennes, anti-inflammatoires, anti-agrégation de la protéine β-amyloïde) ont été évaluées in vitro. L’activité anti-inflammatoire apparait différente de celle du produit de départ pour un des analogues.De même, la désaromatisation oxydante de la curcumine et ses analogues a permis l’accès en une ou deux étapes à des composés originaux à pharmacophore largement modifié.Des nanoparticules à base de "curcumine-squalénisée" ont également été préparées afin de surmonter le problème de la faible biodisponibilité de la curcumine. L’activité leishmanicide in vitro semble prometteuseDuring our research for fighting human African trypanosomiasis (sleeping sickness), two approaches were employed; firstly the traditional use of plants, secondly the synthesis of original derivatives of curcumin.In the first part, a bioguided fractionation of a methanolic extract of the rhizomes of Aframomum sceptrum K. Schum (Zingiberaceae) allowed the isolation of five compounds, including new labdanes, named sceptrumlabdalactone A and sceptrumlabdalactone B successively. Sceptrumlabdalactone B was reasonably active against T. brucei brucei, and strongly active against L. donovani, with IC50 close to that of pentamidine.The essential oil from the rhizomes of the species might also contribute to its biological activity. It was obtained by hydrodistillation and analyzed by GC–MS. Its major constituents were β-pinene, caryophyllene oxide and cyperene. It exhibited strong bactericidal activity against Gram-positive bacteria. It only showed moderate bacteriostatic activity against Gram-negative bacteria. Remarkable activities against T. b. brucei and Trichomonas vaginalis were also observed.The second part is devoted to curcumin. This diarylheptanoid, is common in several Curcuma spp.Structural modifications and preparation of nanoparticles of curcumin were carried out to increase its activities and/or overcome the problem of the low bioavailability of this compound.Original analogs, e.g. prenylated curcumins were prepared. Several biological activities (antiparasitic, anti-inflammation, Inhibition of β–amyloid aggregation, etc) were evaluated in vitro.Similarly, the oxidative dearomatization of curcumin and its analogues allowed the access to novel original compounds.Finally, the coupling of curcumin and squalene was achieved. The resulting molecules were able to form spherical nanoassemblies that may overcome bioavailability issues. Antiparasitic, antibacterial, and cytotoxic activities were also evaluated. The in vitro leishmanicidal activity seems promising
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Wloch, Morgan. "Synthèse totale de la (+)-strépantibine A, un ortho-quinol d’origine bactérienne, par désaromatisation hydroxylante phénolique asymétrique médiée par des iodanes-λ5 de type iodylarène." Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0035.
Full textAbstract:
La (+)-strépantibine A est un ortho-quinol (i.e., 6-alkyl-6-hydroxycyclohexa-2,4-diénone) qui a récemment été isolé à partir d’une bactérie du genre Streptomyces en association symbiotique avec les larves de la guêpe maçonne Sceliphron madraspatanum. Ce métabolite possède une activité inhibitrice prometteuse contre l'hexokinase 2, une enzyme responsable de la croissance tumorale. Parmi les nombreuses transformations chimiques qui permettent la formation d'ortho-quinols, la désaromatisation hydroxylante de phénols à l’aide d’agents de transfert d’atome d’oxygène à base de composés iodés hypervalents de type iodylarène (i.e., ArIO2) est une réaction développée dans notre laboratoire. Dans ce contexte, nous avons mis au point une réaction régio- et énantiocontrôlée en utilisant une nouvelle classe d’iodylarènes chiraux de structure pipérazinique. Cette innovation méthodologique nous a permis d’accomplir la première synthèse totale de la (+)-strépantibine A en neuf étapes avec un rendement global de 6%(+)-strepantibin A is an ortho-quinol (i.e., 6-alkyl-6-hydroxycyclohexa-2,4-dienone), which was recently isolated from a Streptomyces bacteria associated with the larvae of the mud dauber wasp Sceliphron madraspatanum. Promising in vitro inhibitory activity of this natural ortho-quinol was found against hexokinase 2, an enzyme responsible for tumor growth. Among many existing chemical transformations that allow the formation of ortho-quinols, hydroxylative phenol dearomatization using hypervalent iodine-based oxygen-atom transfer reagents, such as iodylarenes (i.e., ArIO2), is a reaction developed in our laboratory. In this context, we have set up a regio- and enantiocontrolled reaction using a novel class of chiral piperazine-based iodylarenes. This methodological innovation has allowed us to accomplish the first total synthesis of (+)-strepantibin A in nine steps with an overall yield of 6%
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Segovia, Claire. "Nouvelles approches en organocatalyse énantiosélective par paire d’ions Access to polyfluorinated tetrahydropyranyl amides via Prins‐Ritter cyclization under green conditions Enantioselective catalytic transformations of barbituric acid derivatives." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMIR16.
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L’objectif principal de ma thèse a été le développement de nouvelles réactions énantiosélectives organocatalysées impliquant une catalyse bifonctionnelle idéalement à base de paires d’ions chirales. Dans un premier temps, cette approche a été appliquée à la désaromatisation nucléophile de sels de pyridinium en mettant en œuvre un système catalytique bifonctionnel original paire d’ions/énamine. Les 1,4-dihydropyridines ont pu être obtenu de façon régiosélective avec cependant des rendements et des excès énantiomériques faibles (19% de rendement et 32% ℯℯ au maximum). Dans un deuxième temps, une réaction de déracémisation monotope organocatalysée de cétones comportant un centre stéréogène en position α a été étudiée. La première étape est une réaction de silylation conduisant à un éther d’énol silylé prochiral qui subit, dans un deuxième temps une étape clé de protonation énantiosélective catalysée par un dérivé original des alcaloïdes du Quinquina. La séquence a pu être appliquée à 13 cétones α-substituées avec des rendements allant de moyens à très bons et des excès énantiomériques allant jusqu’à 87%. Il est à noter qu’à ce jour, il s’agit de la seule méthode de déracémisation purement chimique qui ne s’appuie pas sur des équilibres rédoxThe main purpose of this PhD thesis was the development of new enantioselective organocatalyzed reactions involving bifunctional catalysis if possible by means of ion-pairing catalysts. Firstly, this approach was applied to the nucleophilic dearomatization of pyridinium salts based upon an original bifunctional system ion pair/enamine. The 1,4-dihydropyridines were obtained with good regioselectivity albeit in low yields and enantiomeric excesses (19% yield and 32% ℯℯ max). Thereafter, a one-pot organocatalysed deracemization reaction of ketones bearing a stereogenic center at their α position was studied. The first step relied on a silyation reaction to provide a silyl enolate which was in the second step, submitted to an enantioselective protonation reaction catalysed by an original Cinchona catalyst. This sequence was applied to 13 α-substituted ketones in modest to high yields and up to 87% ℯℯ. It is worthy to note that this reaction is the only method of purely chemical deracemization reaction that does not rely on redox equilibrium
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Coffinier, Romain. "Nouveaux iodanes chiraux pour des réactions d’oxygénation asymétriques." Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR14974/document.
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Ces travaux concernent le développement de nouveaux iodanes chiraux et leur application à des réactions d’oxygénation asymétriques. Ces réactifs à base d’iode hypervalent constituent une alternative intéressante aux réactifs à base de métaux lourds en termes de réactivité et de toxicité. La première partie de ce travail a été consacrée à la synthèse de nouvelles structures originales C 2 -symétriques énantiopures de type S alen. Un criblage de conditions oxydantes a ensuite montré que seul le 3,3-diméthyldioxirane (DMDO) permet une oxydation propre et sélective de ces iodoarènes en iodanes-λ5 correspondants, composés isolables par simple filtration et dont la nature a pu être déterminée sans ambiguïté par analyse spectroscopique RMN 13C. Dans un second temps, ces nouveaux iodanes-λ5 chiraux ont été appliqués à des réactions d’oxygénation asymétriques, et plus particulièrement à la désaromatisation hydroxylante (réaction HPD) de 2-alkylphénols tels que le carvacrol et le thymol. Les meilleurs excès énantiomériques (ee) sont obtenus lorsque la réaction HPD est réalisée à température ambiante dans un mélange 85:15 de dichlorométhane/ trifluoroéthanol. Le carvacrol est ainsi converti en son cyclodimère [4+2] d’ortho -quinol naturel, le biscarvacrol, avec 55% de ee, et le thymol en bisthymol avec 68% de eeThis work focuses on the development of new chiral iodanes and their application to asymmetric oxygenation reactions. These hypervalent iodine-based reagents represent an interesting alternative to heavy metal-based reagents in terms of reactivity and toxicity. The first part of this work consisted in the synthesis of new enantiopure C 2 -symmetrical Salen-type structures. A screening of oxidizing conditions then showed that only 3,3-dimethyldioxirane (DMDO) is able to mediate a clean and selective oxidation of these iodoarenes into to the corresponding λ5-iodanes, which were isolated by simple filtration and further characterized by 13C NMR spectroscopic analysis. In a second part, these new chiral λ5-iodanes were applied to asymmetric oxygenation reactions, in particular the Hydroxylative Phenol Dearomatization reaction (HPD reaction) of 2-alkylphenols such as carvacrol and thymol. Best enantiomeric excesses (ee) where obtained when the HPD reaction was performed in a 85:15 mixture of dichloromethane/ trifluoroethanol. Carvacrol was converted into its natural ortho -quinol-based [4+2] cyclodimer biscarvacrol with ee up to 55%, and thymol into bisthymol with ee up to 68%
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Bosset, Cyril. "Synthèse d’iodanes biaryliques chiraux : application à des réactions d’oxygénation asymétrique." Thesis, Bordeaux 1, 2013. http://www.theses.fr/2013BOR14983/document.
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La chimie des dérivés à base d’iode hypervalent, également appelés iodanes, connaît depuis la fin des années 1990 un essor important qui s’explique par leurs conditions d’utilisation douces et leur faible toxicité comparée à celle des réactifs à base de métaux lourds. Plus récemment, des versions chirales de ces réactifs font l’objet de nombreuses recherches. Dans ce contexte, une première partie de ces travaux de thèse a consisté à développer de nouveaux iodanes chiraux basés sur un squelette biarylique atropoiso-mériquement pur de type soit 1,1’-binaphtyle, soit 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphtyle. Plusieurs iodobiaryles ont été synthétisés, puis oxydés efficacement et sélectivement au 3,3-diméthyldioxirane (DMDO) pour donner, après une simple filtration, les iodanes correspondants purs. Le degré d’oxydation de l’atome d’iode de chacun de ces composés a été déterminé par spectroscopie RMN 13C : des iodanes-λ3 ont été isolés dans le cas des systèmes binaphtyliques ou substitués par une fonction acide carboxylique en ortho de l’atome d’iode, tandis que des iodanes-λ5 ont été obtenus pour les composés basés sur un squelette octahydro-1,1’-binaphtyle. Dans une seconde partie, ces iodanes ont été appliqués à des réactions d’oxygénation et plus particulièrement à la désaromatisation hydroxylante asymétrique de 2-alkylarénols. Le 2-méthylnaphtol a été converti en son ortho-quinol avec un excès énantiomérique (ee) atteignant 73 %. Des phénols naturels comme le carvacrol et le thymol ont conduit aux cyclodimères [4+2] d’ortho-quinols, le biscarvacrol et le bisthymol, avec des résultats encore meilleurs, respectivement 74 % ee et 94 % eeThe chemistry of hypervalent organoiodine compounds, also referred to as iodanes, has experienced an impressive development since the 1990s due to their mild oxidizing conditions and their low toxicity compared to heavy metal-based reagents. Recently, chiral versions of iodanes have been focusing several research efforts. In this context, the first part of this work was dedicated to the development of new chiral iodanes with an atropisomerically pure biarylic structure, either 1,1’-binaphthyl or 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl. Many iodobiaryls were synthesized, and then efficiently and selectively oxidized with 3,3-dimethyldioxirane (DMDO) to furnish the corresponding pure iodanes by simple filtration. The oxidation state of the iodine atom of each compound was determined by 13C NMR spectroscopic analysis: λ3-iodanes were isolated in the case of binaphthylic structures or when the iodoarene bears a carboxylic acid function ortho to the iodine atom, whereas λ5-iodanes were obtained for octahydro-1,1’-binaphthylic compounds. These iodanes were next applied to oxygenation reactions and in particular to asymmetric hydroxylative dearomatization of 2-alkylarenols. 2-Methylnaphthol was converted into its ortho-quinol with up to 73 % enantiomeric excess (ee). Natural phenols such as carvacrol and thymol gave the corresponding ortho-quinol-based [4+2] cyclodimers, biscarvacrol and bisthymol, with even better results of 74 % ee and 94 % ee, respectively
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Chang, Liang. "Sustainable Transformations of Methyl Coumalate : efficient Preparations of Unsaturated Carboxylic Acids, 2HPyrans, Trifluoromethyl Benzenes and Fluorescents Molecules." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS109.
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Dans ce travail, nous décrivons le développement de nouvelles transformations utilisant le coumalate de méthyle, composé renouvelable biosourcé. Un couplage double séquentiel d'alkyl-alkyle ou d'alkyl-hydrure one-pot conduit à des acides insaturés d’intérêt. Nous décrivons une synthèse efficace de 2H-pyranes tétrasubstitués dans des conditions douces, puis nous décrivons une réaction efficace et sans solvant avec des dicétones trifluorométhylées, pour conduire à des benzènes trifluorométhylés. Enfin, nous avons rapporté une nouvelle stratégie générale de réaction de désaromatisation de composés hétérocycliques de type pyrido [1, 2-a] bicycliquesIn this work, we have described the development of new transformations using bio-based renewable methyl coumalate as feedstock. An iron and copper catalyzed one-pot sequential double alkyl-alkyl or alkyl-hydride 1,6-addition with methyl coumalate was described. We then described an efficient synthesis of tetrasubstituted 2H-pyrans under mild condition. Later we reported a solvent-free reaction of methyl coumalate with trifluoromethyl-β-diketones, in a tBuOK-catalyzed domino sequence. A novel reaction, for efficient C-C bond formation between the bio-based methyl coumalate and a variety of imines and aldehydes via MBH pathway was reported. Finally, we reported a novel, general dearomatization strategy with an unprecedented pyrido[1, 2-a] fused heterocyclic scope
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Kumar, R. "Oxidative dearomatization using hypervalent Iodine." Thesis, 2014. http://ethesis.nitrkl.ac.in/6188/1/E-33.pdf.
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Oxidative Dearomatization with new Iodine complexes and cyclopropyl ring fragmentation strategies has opened up a new direction of unfolding molecular complexities associated with synthesis of bio-active natural products like Penostatins and pseudoguaianolides. So we trying to developed a new easy route for oxidative Dearomatization.
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Graham, Peter Michael. "Synthesis and reactivity of tungsten dearomatization agents /." 2005. http://wwwlib.umi.com/dissertations/fullcit/3169690.
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Kosturko, George William. "Dearomatization and activation of pyridines towards alkaloid frameworks /." 2009. http://wwwlib.umi.com/dissertations/fullcit/3364909.
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Kumar, Rahul. "Efforts Towards Alkyne Insertion Reactions Via Oxidative Dearomatization." Thesis, 2015. http://ethesis.nitrkl.ac.in/7315/1/2015_Efforts_Kumar.pdf.
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Development of 1,2-dihydro naphthalene precursors are considered to be one of the most important reactions as they form versatile framework for natural product synthesis. Efforts are on the way to develop dihydronapthalene, benzofuran and indene using an alkyne insertion pathway which would proceed via oxidative dearomatization of phenols.
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Pepper, Henry Patrick. "Biomimetic synthesis of meroterpenoid natural products using dearomatization strategies." Thesis, 2016. http://hdl.handle.net/2440/114063.
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Synthetic efforts towards various meroterpenoid natural products based on biosynthetic speculation were undertaken in order to gain biosynthetic insight and to develop efficient syntheses of some structurally complex, biologically active compounds. The first total synthesis of the PPAP natural product garcibracteatone was achieved in four linear steps from phloroglucinol (0.6% overall yield). The key biomimetic synthetic step was an oxidative radical cyclization cascade reaction, where four new carbon-carbon bonds, four new carbocyclic rings and five new stereocentres were formed in the one step. The first total synthesis of merochlorin A was achieved in five linear steps from methyl-3,5- dimethoxyphenylacetate (6% overall yield). The key biomimetic synthetic step was a [5 + 2] cycloaddition reaction induced be oxidative dearomatization to form the bicyclo[3.2.1]octane core. The first total synthesis of the napyradiomycin natural product naphthomevalin was achieved in 11 steps from methyl-3,5-dimethoxyphenylacetate (1.4% overall yield). The key biomimetic synthetic step was a thermal α-ketol rearrangement reaction to form the naphthoquinone core of the napyradiomycins. The synthetic naphthomevalin was additionally converted into A80915G via a biomimetic Sɴ2 epoxidation reaction, and into napyradiomycin A1 via a chemoenzymatic reaction.Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2016.
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Ghosh, Manoj Kumar. "New Synthetic Intrigues Towards Oxidative Dearomatization and Related Strategies." Thesis, 2018. http://ethesis.nitrkl.ac.in/9789/1/2018_PHD_MKGhosh_513CY1006_New_.pdf.
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The thesis entitled “New Synthetic Intrigues Towards Oxidative Dearomatization and Related Strategies” is divided into the following six chapters.
Chapter-I describes a new methodology of oxidative-dearomatization of planar phenols and naphthols. An economic, viable, one-pot, metal-free protocol for direct conversion of naphthols to α-ketols is reported. naphthols were found to undergo facile unprecedented oxidative dearomatization with regioselective hydroxylation with phenyl selenyl bromide in open air conditions. Quaternary stereocenters were developed along with formation of sterically demanding α- and γ-ketols with high yields. A thorough study of the stereo electronic demands of the unusual oxy-Selenium reactive intermediate involved in dearomatization of 1- and 2-naphthols is studied. The first instance of unprecedented phenoxy-selenium interaction leading to facile dearomatization of arenes is highlighted in this chapter.
Chapter-II entails the first recognition of Phenyl Trimethyl Ammonium Tribromide (PTAB) as an effective reagent for spiro-cyclizations proceeding via oxidative dearomatization. The experiment exhibits metal-free, ligand-free and one-pot accomplishment of these significant transformations. The presented methodology described the first generalized protocol for spiro-etherification reaction as well as brominative dearomatization of naphthols which can be applied towards various directions. Good to moderate diastereoselectivity was achieved with varied substitution in the hydroxy- naphthols in case of spiro-etherification. Also this chapter highlight the synthesis of bromo spiro-furanonaphtalones from 1-naphthol derivatives. In this chapter also we describe the lactonisation of 2-naphthol derivatives using PTAB as the effective reagent.
Chapter-III discloses a highly efficient methodology for generation of nitrogen containing quaternary carbon centres via aminative and azidative oxidative dearomatization of phenols and naphthols. The same protocol has also been successfully employed to achieve oxidative peroxidation as well as oxidative etherification of phenols and naphthols. The simplest metal free reaction conditions delineates an easy break through to the “Trio”- of oxidative amination, azidation and peroxidation. An array of diverse polyfunctionalised heterocycles has been synthesized in one pot.
Chapter-IV explored two new reagents Phenyl selenyl bromide (PhSeBr) and phenyl trimethylammonium tribromide (PTAB) as the effective reagents for oxidative C (sp2) – C (sp3) bond cleavage of 1-hydroxy alkyl 2-naphthols via oxidative dearomatization.Also the synthetically important bromo-azido ketone was first synthesized in this oxidative C (sp2) – C (sp3) bond cleavage.
Chapter-V describes a facile methodology which has successfully simplified the generation of sulfonamides, thiosulfonates and symmetric disulfanes. These excellent oxidative tendencies prompted us to study the tribromide mediated oxidative couplings in the S-N and S-S generation studies. The “trio” of reactions occur in an open metal free atmosphere and has also been scaled up to grams making it suitable for commercialization. The reactions also have been successfully carried out with asymmetric variants, thus contributing to the chiral pool. The user friendly “trio” enables easy generation of these versatile sulfur analogues and the reaction condition employed depict an economic outline.
Chapter-VI describes the first stereoselective synthesis of Heliannuol G employing an o-quinone methide intermediate. The key compound trans- dihydrobenzofuran was generated employing a reactive o-quinone methide intermediate via oxidative dearomatization. The present synthesis triumphs over all the drawbacks associated with the reported one and reveal an impressive overall yield of 12.37%.
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Sahoo, S. R. "Oxidative dearomatization of naphthols –a novel synthesis of sulphoxide templates." Thesis, 2014. http://ethesis.nitrkl.ac.in/6186/1/E-34.pdf.
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Development of facile routes to accomplish successful multistep organic synthesis, leading to the development of bioactive natural products is one of the most challenging fields in chemistry in academic and industry throughout the world. Our interest lies in Oxidative Dearomatization of unprotected systems like phenol, cresols, coumarins, napthols etc. using hyper-valent Iodine catalysts which can lead to versatile frameworks for active organic practioners. Intial approaches towards two Bioactive Natural Products namely Pseudoguaianolide (1) and Penostatin A (2) lead us to explore newer methodologies for scalable Oxidative Dearomatization. In an event of experiments leading to this methodology, a novel transformation leading to formation of sulphoxide templates have been brought under the preview of this project and elaborated in the following pages.
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Ding, Fei. "Stereoselective dearomatization of benzene, alkylated benzenes and naphthalenes by dihapto-coordination /." 2004. http://wwwlib.umi.com/dissertations/fullcit/3118387.
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Welch, Kevin David. "Coordination and activation of aromatic heterocycles by a tungsten dearomatization agent /." 2007. http://wwwlib.umi.com/dissertations/fullcit/3285311.
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Sahoo, Sushree Ranjan. "Synthetic Efforts Towards Carbon-Heteroatom Bond Generations Employing Dearomatization, Alkene and Alkyne Intrigues." Thesis, 2019. http://ethesis.nitrkl.ac.in/10139/1/2020_PhD_SRSahoo_514CY6009_Synthetic.pdf.
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Carbon-hetero bond generation has been a core interest of synthetic chemists throughout the past. The modern approach to develop these attempts in environmentally benign condition with atom economy has emerged as a frontier goal in organic synthesis. Particularly, dearomatization of cheaply available planar arenes and molecular gymnastics with alkenes and alkynes precursors has opened a new avenue for chemists with regard to efficiency and versatility. The present thesis covers some of our attempts in the generation of carbon-heteroatom bonds via dearomatization of planar phenols and pyridine derivatives in the first part, delivering the multi-functionalized spiro, indolizine molecules employing our own tri-bromides (TBrs), visible light and copper(I) catalysis. The second part of the thesis focuses on strategies like isomerisations of alkenes or alkynes, free radical reactions and multi-component reactions to synthesize these biologically important motifs.
Chapter-I:
In this chapter, we have discussed a metal free one-pot stereoselective synthesis of para-quinone monoketals and their derivatives have been reported in this present work. Tri-bromides (TBrs) have been employed as an effective reagent for intramolecular spiro-cyclizations leading to excellent yields of the monoketals. The TBrs are slowly turning out to be an important reagent for oxidative dearomatization which is further attested in the presented work. In addition, the obtained substituted para-quinone monoketals and their derivatives were readily transformed into more complex products by reaction with Pd/C under hydrogen atmosphere leading to saturated para-monoacetal, which are important building blocks in organic synthesis.
Chapter-II:
In this chapter, we metal free one pot approach towards a highly stereoselective synthesis of N-substituted spiro azacyclodienones, dihydro spiro-azacyclodienones and spiro-lactams has been reported in this present work. Phenyl tri-methyl ammonium tri-bromide (PTAB) as an effective reagent has been implied for intramolecular spiro-cyclizations via the key oxidative dearomatization reaction. Interestingly, the obtained substituted N-substituted spiro azacyclodienones was readily transformed into strained cyclopropanated spirocycles.
Chapter-III:
In this chapter, a visible light assisted dearomative selenylative carbo-spirocyclisation of aromatic homologated-ynones has been reported. The ynones deliver selenylative spiro-cyclohexadienones and spiro-diepoxides at varied temperatures. The prescribed methodology is photo-catalyst free and scalable. The combination of visible light, molecular oxygen and the products synthesized delivers a uniqueness to the designed methodology.
Chapter-IV:
In this chapter, we have discussed an efficient two-component copper-catalyzed cyclization cascade approach towards highly functionalized indolizinone heterocycles have been developed from reactions of pyridine-, isoquinoline-, and quinoline ynones, via 5-exo-dig cyclization. The catalysis involves the activation by diorgano diselenide and diorgano disulphide and also their incorporation into the indolizinone core. In addition, the obtained substituted indolizinones were readily transformed into 1 (organochalcogenyl)indolizin-2-ols, which are important building blocks in organic synthesis.
Chapter-V:
In this chapter, we have discussed the radical induced cyclopropyl ring fragmentation with encompassed olefinic and cyclopropane environment has been carried out. Interestingly, the fragmentation has occasioned onto a stereoselective synthesis of trans-3-allyl-2,3 dihydrobenzofurans (TADHBs) with impressive yields. The trans-dihydrobenzofurans are present as central core in many molecules of medicinal interest and the present protocol deliver a straight forward access to the embedded molecular architecture.
Chapter-VI:
In this chapter, we have discussed about an efficient approach for the synthesis of α-allyl α-selanyl ketone and selanyl tetra-hydrofurans has been reported in this present work. The sodium methoxide (MeONa) mediated one pot three-component synthesis lead towards a good to an excellent yield of products with a wide substrate scope. The selenylated ketones can be important point towards important organic synthons.
Chapter-VII:
In this chapter, we have discussed about a facile hydrochloride promoted regioslective synthesis of isoxazoles and pyrazoles from 1,2-allenic ketones. The reaction has been scaled upto grams. A direct 8-endo-dig ring annulations towards the first synthesis of (Z)-2-methyl-7H benzo[b]pyrazolo[5,1-d][1,5]oxazocine has been developed.
Chapter-VIII:
In this chapter, we have discussed about revisit towards regioselective addition of insitu generated negative nucleophiles to allenic ketones in the presence of a base. A wide variety of allenic ketones as well as nucleophiles are viable in this transformation. A direct ring annulation towards the challenging benzodioxin skeleton synthesis has been developed. Environmentally benign protocol and wide substrate scope are the notable features of this methodology.
Chapter-IX:
In this chapter, we have discussed about addition of boron trifluoride etherate (BF3OEt2) to allenic ketones has lead to trapping of the isolated boron-difluoride enolate. The challenging single-crystal structure of the boron-enolate has been solved. The (Z) β-difluoroboryloxy ether derivatives undergo an unpreceedented C1-C10 migration, to deliver rearranged phenol derivatives which are functionalized to C-2 alkyl-chromenones. This has been the first example where isolated boron-enolates have exhibited significant anti-cancer properties.
Chapter-X:
In this chapter, we have discussed about an efficient copper-catalyzed cyclization cascade approach towards highly functionalized methylene 4-chromanol and aurone derivatives has been developed from reactions of ynols via 6-exo-dig and 5-exo-dig cyclization respectively. The catalysis involves the alkyne activation via diorgano-diselenides and also their regioselective incorporation into the methylene 4 chromanol and aurone derivatives core and is an open-air transformation.
Chapter-XI:
In this chapter, we have discussed about a direct metal-free approach for the synthesis of alpha-cyanoalkylboronic esters from bis-diboron ester and azobis-nitrile compound is reported under ambient temperature and pressure via a free radical procedure.
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Zuliani, Christopher J., and Christopher Zuliani. "NEW STRATEGIES FOR THE PERI LITHIATION OF NAPHTHALAMIDES." Thesis, 2009. http://hdl.handle.net/10214/2098.
Full textAbstract:
Directed metalation reactions are an interesting area of synthetic chemistry. They provide a powerful regiospecific method for functionalizing complex aromatic rings. Presently, directed ortho metalations are well understood. However, there has been very little progress in the remote metalation of naphthalene derivatives.
Presently the peri lithiation of naphthalamides is a reaction that has not been solved to a level that allows for it to be deployed in a vast number of synthetic schemes. The processes by which peri functionalized naphthalamides are present obtained required several steps and give poor yields. Previously attempts directed toward the peri lithiation in the Schwan lab have met with little success.
Herein experiments were preformed to understand why the pervious attempts failed and other experiments were performed in an effort to acheive the peri lithiation of a specific naphthalamide. The mechanism of previous chemical observations was understood by trapping experiments and clearly demonstrated how problematic acidic sites can interfere with intended directed metalation. The acidic site was sterically hindered by employing strategic protecting groups. However, the steric demand of the protecting groups considered was not sufficient to eliminate the problematic acidic site. This led to the consideration of an alternative strategy for the peri lithiation by removing the acidic center of the specific substrate. This however, resulted in remote addition of lithiating reagents to the naphthalamide and clearly showed that several naphthalamides are not a suitable directed metalation group for the peri lithiation.
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Barbe, Guillaume. "Synthèse totale de la lépadine B : plate-forme pour la découverte de nouvelles tranformations chimiques." Thèse, 2009. http://hdl.handle.net/1866/3239.
Full textAbstract:
Dans ce document, serons détaillées les résultats de mes travaux de recherche d’études doctorales. Tout d’abord, nous discuterons de la synthèse totale de la lépadine B, la plus courte à paraître dans la littérature à ce jour. Cette synthèse, en plus de valoriser la synthèse asymétrique de pipéridines poly-substituées développée par l’équipe du professeur Charette, mettra à profit une utilisation originale d’une séquence de fermeture-ouverture de cycle par la réaction de métathèse d’alcènes. De plus, nous détaillerons une brève étude mécanistique de cette dernière nous ayant permis la proposition d’un mécanisme peu commun de ce type de séquence réactionnel et dont les conséquences expérimentales sont impressionnantes.
Au cours de cette synthèse, nous avons identifié un synthon d’une grande valeur synthétique. En effet, ne comportant pas moins que quatre centres chiraux, ce synthon pouvait être obtenu énantiopure en seulement trois étapes à partir de la pyridine. Ainsi, nous avons effectué une analyse structurale de ce synthon et avons envisagé une valorisation supplémentaire par une utilisation originale de la fragmentation de Grob. Dans ce contexte, nous avons développé une toute nouvelle synthèse de pipéridines 2,3,6-trisubstituées hautement régio- et diastéréosélective.
Afin de pouvoir réaliser la précédente méthodologie, nous avons dû étudier la réduction d’une amide en présence de groupements fonctionnels sensibles dans les conditions usuelles. Heureusement, l’année précédente nous avions développée une réaction hautement chimiosélective d’amides tertaires. Cette nouvelle réaction, qui a été fondamentalement inspiré par une méthodologie du professeur Charette sur l’activation d’amides, a permis la réduction d’amides tertiaires en présence de fonctions telles les cétone, ester, nitrile, époxyde, insaturations, etc.
Enfin, l’ensemble des connaissances acquises au cours de ces projets a permis l’élaboration d’une toute nouvelle stratégie de synthèse pour la préparation d’indolizidines et quinolizidines. Plus spécifiquement, nous avons développé la première séquence d’activation intramoléculaire et déaromatization asymétrique de la pyridine. Ceci permet d’avoir un accès aux squelettes indolizidine et quinolizidine avec des stéréosélectivités élevées, la nature insaturée de ces derniers laissant également place à une grande flexibilité synthétique. Dans ce contexte, nous allons détailler une très courte synthèse de trans-indolizidines.In this document, the results of Ph.D. thesis will be detailed. First, we will discuss the synthesis of alkaloid lepadin B, the shortest to appear in the literature to date. This synthesis, in addition to validating the asymmetric synthesis of polysubstituted piperidines developed earlier by the group of Professor Charette, will highlight an original use of a ring-closing ring-opening alkene metathesis sequence. Also, a brief mechanistic study of the latter reaction will be detailed, a study which led us to propose an unusual mechanism for this reaction sequence and for which the experimental concequences are impressive. During the total synthesis of lepadin B, we identified a synthon of great synthetic value. Indeed, containing not less than four chiral centres, that synthon could be obtained enantiopure through a short three-step synthesis from pyridine. We performed a structural analysis of this synthon and we envisaged an additional validating through an original use of the Grob fragmentation. Consequently, we developed a new highly regio- and diastereoselective synthesis of 2,3,6-trisubstituted piperidines. To succesfully realize the latter methodology, it was required to perform an amide reduction in the presence of sensitive functionnalities under usual reduction conditions. Fortunatly, we had recently developed a set of conditions for the highly chemoselective reduction of tertiary amides. This new reaction, fundamentaly inspired by an amide activation methodology from Charette’s group, allowed the reduction of amides in the presence of functionalities such as ketone, ester, nitrile, epoxide, unsaturations, etc. Finaly, the knowledge acquired by conducting this research allowed for the elaboration of a new methodology for the synthesis of indolizidines and quinolizidines. Specifically, we developed the first intramolecular pyridine activation-asymmetric dearomatization reaction of the pyridine. This led us to the highly stereoselective access to indolizidine and quinolizidine backbone, the unsaturated nature of which permitting a good degree of synthetic flexibility. In that context, we will detail a short synthesis of trans-indolizidines.
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Boyce, Jonathan Henry. "Total syntheses of polycyclic polyprenylated acylphloroglucinol natural products and analogs utilizing alkylative dearomatizations and cationic cyclizations." Thesis, 2017. https://hdl.handle.net/2144/24108.
Full textAbstract:
Polycyclic polyprenylated acylphloroglucinols (PPAPs) are structurally complex natural products with promising biological activities. These compounds have interesting anticancer and anti-HIV properties as well as other biological activities making them highly attractive synthetic targets. We report a stereodivergent, asymmetric total synthesis of (−)-clusianone in six steps from commercial materials. We have implemented a challenging cationic cyclization forging a bond between two sterically encumbered quaternary carbon atoms. Mechanistic studies point to the unique ability of formic acid to mediate the cyclization forming the clusianone framework.
We also present a biosynthesis-inspired, diversity-oriented synthesis approach for rapid construction of PPAP analogs via palladium-catalyzed dearomative conjunctive allylic alkylation (DCAA). These efficient palladium-catalyzed protocols construct the [3.3.1]-bicyclic PPAP core in a single step from their stable aromatic precursors.
The first syntheses of 13,14-didehydroxyisogarcinol and garcimultiflorone A stereoisomers are reported in six steps from a commercially available phloroglucinol. Lewis acid-controlled, diastereoselective cationic oxycyclizations enabled asymmetric syntheses of (−)-6-epi-13,14-didehydroxyisogarcinol and (+)-30-epi-13,14-didehydroxyisogarcinol. A similar strategy enabled production of the meso-derived isomers (±)-6,30-epi-13,14-didehydroxyisogarcinol and (±)-6,30-epi-garcmultiflorone A. A convenient strategy for gram scale synthesis of these stereoisomers was developed utilizing diastereomer separation at a later stage in the synthesis that minimized the number of necessary synthetic operations to access all possible stereoisomers.
Finally, we report cationic rearrangements of dearomatized acylphloroglucinols leading to the formation of unprecedented PPAP scaffolds. A novel type A [3.3.1]-bicyclic PPAP was produced as a major product and the structure confirmed by X-ray crystallographic analysis. A novel [3.3.1]-bicyclolactone was also produced utilizing an alternative substrate. Efforts will be described to determine the scope of these rearrangements and type A-selective cyclizations.2018-08-09T00:00:00Z
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Perreault, Christian. "Cycloaddition dipolaire [3+2] à partir d'hétérocycles aromatiques N-aminés." Thèse, 2008. http://hdl.handle.net/1866/7834.
Full text