Dissertations / Theses on the topic 'Chiral organocatalyst'
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1
Ortayli, Oytun. "Asymmetric Synthesis Of 1,4-diamine Based Chiral Ligand And Organocatalyst And Their Applications." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612335/index.pdf.
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Novel 1,4-chiral diamine ligand possessing a trans-9,10-dihydro-9,10-ethanoanthracene backbone was synthesized. The synthetic plan involves first LiAlH4 reduction of the Diels-Alder adduct obtained by reaction of dimenthyl fumarate and anthracene, which is followed by reacting the corresponding alcohol and subsequent attachment of mesylate and triflate units to get good leaving groups which are available substances for introducing nitrogen units via SN2 type reactions. Consequently, by using dimesyl ester and ditriflate esters five catalysts 27, 29, 30, 33 and 38 were synthesized. The first four catalysts 27, 29, 30 and 33 were used in transfer hydrogenation reactions with transition metal whereas catalyst 38 used as an organocatalyst in direct aldol reaction between acetone and p-nitrobenzaldehyde.
2
Joyce, Jesse Jo. "The Development and Use of Chiral 4-Dimethylaminopyridine-N-Oxide as an Organocatalyst." Thesis, North Dakota State University, 2018. https://hdl.handle.net/10365/29269.
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Document incorrectly classified as a dissertation on title page (decision to classify as a thesis from NDSU Graduate School)Organocatalysis is a field that has bloomed over the last decades. With the field’s promise of being able to mimic nature and afford products in a synergistic manner to traditional Lewis acid catalysis, several interesting discoveries have been made. Owing to the vastness of the field as it exists today, this document will focus on two main aspects; cinchona alkaloid (and derivatives) as used in common carbon-carbon bond forming reactions and kinetic resolution via 4-dimethyl aminopyridine-N-oxide derivative driven acylation. Kinetic resolution via organocatalysis has the potential to react one enantiomer of a racemic mixture without affecting the other. The highlight of this screening was an s factor of 9 which was produced using optimized conditions using a catalyst designated DMAPO-IV. There remains much to do in improving the system and elucidating the scope of this catalytic system this report details the efforts made thus far.
3
Kucukdisli, Murat. "Asymmetric Synthesis Of Chiral Camphor Fused Pyridine Type Novel Organocatalysts." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12610790/index.pdf.
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Chiral pyridines as organocatalysts have been used in asymmetric organic synthesis in recent years. The asymmetric synthesis of camphor fused pyridine type novel organocatalysts were perfomed starting from cheap and easily available natural (+)-camphor. Using camphor fused pyridine skeleton, six organocatalysts 29, 32, 33, 38, 40, and 41were successfully synthesized. The first four nucleophilic and Lewis base catalysts 29, 32, and 33 are different P-oxides and P,N-dioxides which were tested in allylation of aldehydes via allyltrichlorosilane. L-proline amide 38 and D-proline amide 40 can be named as secondary amine catalyst. They were tested in direct aldol reaction between acetone and aromatic aldehydes in aqueous medium. Final group of catalyst is hydrogen bonding type catalyst which is thiourea based 41.
4
Lamprianidis, Panagiotis. "Photoredox catalysis with 10-phenyl-10H- phenothiazine and synthesis of a photocatalytic chiral proline-based organocatalyst." Thesis, KTH, Organisk kemi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-293510.
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Photoredox catalysis applications for the purpose of new synthetic routes in organic and sustainable chemistry are hot topics in organic synthesis today. In the present study, the synthesis of a chiral proline-based organocatalyst functionalized with 10-phenyl-10H phenothiazine (PTH) photocatalytic moietiesis investigated and attempted for the first time. PTH, an organic photocatalyst, isstudied for its photocatalytic activity in different organic reactions, such as dehalogenation of aromatic halides and the pinacol coupling reaction between aromatic aldehydes. These transformations are otherwise difficult to achieve without a suitable catalyst and the reactions were performed with moderate to high yields.Applikationer av photoredox-katalys med syftet att generera nya syntetiska vägar inom organisk och hållbar kemi är populära ämnen i organisk syntes idag. I denna studien undersöktes för första gången syntesen av en kiral prolinbaserad organokatalysator som är funktionaliserad med fotokatalytiska enheter (10-fenyl-10H-fenotiazin (PTH)). Den fotokatalytiska aktiviteten av PTH studerades för olika organiska reaktioner, såsom t.ex. dehalogenering av aromatiska halider och pinacolkopplingar mellan aromatiska aldehyder. Dessa transformationer är annars svåra att uppnå utan en lämplig fotokatalysator och reaktionerna utfördes med måttliga till höga utbyten.
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Jackson, Daniel Paul. "Synthesis, Characterization, and Applications of Chiral Amino Acid Derived Pyrrolines." University of Akron / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=akron1430819653.
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Matsumoto, Akira. "Studies on Organocatalytic Asymmetric Construction of Chiral Carbinols." Kyoto University, 2019. http://hdl.handle.net/2433/242517.
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Curati, Federico. "Synthesis of a chiral, water soluble porphyrin containing a pyrrolidine unit and initial study of its catalytic activity." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amslaurea.unibo.it/16731/.
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Asymmetric organocatalysis have taken hold in the last decades due to affordability and lack of toxicity of their catalysts. Unfortunately, organocatalytic enantioselective reactions in an environmentally friendly and safe solvent as water are still scarce. During the training internship our aim has been to find an effective water soluble organocatalyst able to drive in an enantioselective fashion a reaction, to maximize the diasteromeric and the enantiomeric excess. Pursuing this objective we synthesized a meso 3-sulfonatophenyl porphyrin with a chiral aminoaldehyde substituent, with the sulfonate-groups allowing its solubilization in water and the chiral group which should improve the enantioselectivity.
The chiral aldehyde has been prepared starting from L-proline, a widely used organocatalyst, and finally tried in an aldol reaction, giving excellent yield, moderate diastereoselectivity and very low enantiomeric excess.
The reaction products can be easily removed washing in organic solvent and the catalyst can be recovered by aggregation in acidic medium.
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Nakatsu, Hiroki. "Studies on Chiral Bronsted Acid-Catalyzed Activation of Imino Functionalities." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188505.
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Sugimoto, Hisashi. "Studies on Control of Stereo- and Regioselectivity in Conjugate Additions of Aldehydes Catalyzed by Axially Chiral Biaryl-Based Amines." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/199123.
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Beck, Daniel Antony Speedie, and beckautomatic@gmail com. "Stereoselective intramolecular Michael addition reactions of pyrrole and their application to natural product syntheses." The Australian National University. Research School of Chemistry, 2006. http://thesis.anu.edu.au./public/adt-ANU20070130.130009.
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Chapter one; (-)-Rhazinilam and (-)-Rhazinal: Alkaloids with Anti-mitotic Properties Derived from Kopsia teoi, provides the background information behind the motives that initiated this research project. The plant alkaloid (-)-rhazinilam [(-)-1] and its naturally-occurring derivative (-)-rhazinal [(-)-13] both exhibit potent anti-mitotic activities and, as such, are interesting targets for total synthesis. Chapter one is a review of the literature regarding these two compounds and discusses the occurrence, proposed biosynthetic origins, structural elucidation and biological activites of compound (-)-1 and that of its analogues including alkaloid (-)-13. Previous total syntheses of these two compounds are then examined, concluding with the only reported total synthesis of compound (-)-13. Developed within the Banwell research group, this total synthesis produced the racemic modification of alkaloid (-)-13 due to a lack of any stereocontrol in the key intramolecular Michael addition step. This unprecedented key step, involving cyclisation of the C2 of pyrrole onto an N-tethered and ?,?-disubstituted acrylate to produce a quaternary-carbon stereogenic centre, would be of greatly enhanced utility if it could be achieved in a catalytic-enantioselective fashion. The realisation of this goal is the central aim of the research conducted within this thesis.
¶
Chapter two; Investigating Asymmetric Induction in the Intramolecular Michael Addition of pyrrole to N-Tethered Acrylates and Related Species, introduces the model study used to direct research towards achieving the goal of asymmetric induction in the title process. The model is a somewhat simplified version of the original process used in the total synthesis of compound (-)-13 involving cyclisation of the C2 of pyrrole onto an N-tethered and ?-monosubstituted Michael acceptor, to produce a tertiary-carbon stereogenic centre. This simplification allows the rapid synthesis of a broad range of potential substrates for use in the title process, thus enabling the investigation of various different approaches to inducing asymmetry therein. High levels of asymmetric induction are observed with the use of chiral substrates or catalysts, facilitating the synthesis of both 6- and 7-membered rings annulated to pyrrole with construction of the relevant tertiary-carbon stereogenic centre in enantio-enriched form. For the reactions producing a 6-membered ring annulated to pyrrole, unambiguous proof of the absolute sense of asymmetric induction observed in the intramolecular Michael addition event is established using a chemical correlation study involving elaboration of a key indolizine-type cyclisation product, to the plant alkaloid of known absolute stereochemistry, (-)-tashiromine [(-)-75]. For the reaction producing a 7-membered ring annulated to pyrrole, the same information is obtained via X-ray crystallographic analyses of a dibrominated derivative of a key pyrroloazepine-type cyclisation product.
¶
Chapter three An Enantioselective Total Synthesis of the Alkaloid (-)-Rhazinal: An Anti-mitotic Agent Isolated from Kopsia teoi., focuses on the application of methodology developed in the previous chapter, to the original goal of inducing asymmetry in the intramolecular Michael addition reaction, involving cyclisation of the C2 of pyrrole onto an N-tethered and ?,?-disubstituted acrylate to produce a quaternary-carbon stereogenic centre. This is ultimately achieved in a catalytic-enantioselective fashion, resulting in the first such total synthesis of the anti-mitotic alkaloid (-)-rhazinal [(-)-13].
¶
Chapter four Extending the Reaction Manifold to the Syntheses of Related Natural Products: A Formal Total Synthesis of (+)-Aspidospermidine and Syntheses of (-)-Rhazinilam and (-)-Leuconolam from (-)-Rhazinal, describes three extensions to the reaction manifold used in the enantioselective total synthesis of alkaloid (-)-13:
The acquisition in an enantioselective manner, of an intermediate previously obtained in racemic form, en route to the racemic modification of the natural product (±)-aspidospermidine [(±)-134], constitutes a formal and enantioselective total synthesis of (+)-aspidospermidine
[(+)-134].
The direct deformylation of (-)-rhazinal [(-)-13], is carried out, to produce the parent alkaloid
(-)-rhazinilam [(-)-1].
The pyrrole ring present in (-)-rhazinilam [(-)-1] is oxidised, to produce the related natural product (-)-Leuconolam [(-)-12] which has not, hitherto, been prepared by total synthesis.
¶Chapter five contains the experimental procedures and characterisation data associated with compounds described in chapters two to four.
11
Strutt, Ian. "New axially chiral amine organocatalysts." Thesis, University of East Anglia, 2014. https://ueaeprints.uea.ac.uk/53435/.
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Organocatalysis has become one of the most popular areas of research within organic chemistry over the past 15 years. This is due to the fact that, usually under mild conditions, it is possible to access either highly functionalized or previously inaccessible structural motifs using this relatively new type of catalysis. Firstly, methodology is reported for the synthesis and use of tertiary amine organocatalysts based on the now ubiquitous binaphthyl backbone. The tertiary amines synthesized were shown to be effective nitrogen transfer reagents in the asymmetric aziridination of chalcone substrates, with enantiomeric excesses of up to 37% seen. The first example of an isolated chiral hydrazinium salt being used as a nitrogen transfer reagent for the aziridination of enones is also described. Secondly, a range of α-substituted secondary amines based on the binaphthyl backbone has been synthesized from easily accessible iminium salts. Preliminary catalyst testing showed them to be interesting alternatives to the more commonly seen proline-derived catalysts for asymmetric conjugate additions reactions between cyclic enones and malonates, with enantiomeric excesses of 24% seen using optimized conditions.
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Gelis, Coralie. "Développement de réactions énantiosélectives organocatalysées pour la synthèse de molécules cycliques énantioenrichies." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS430.
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Le développement de méthodes de synthèse asymétrique est très important pour l’accès à des molécules à visées thérapeutiques. Dans ce contexte, nous nous sommes intéressés à l’utilisation d’organocatalyseurs chiraux pour la synthèse de molécules cycliques énantioenrichies. Dans une première partie sont présentées des réactions de cycloadditions formelles (3+2), (4+2) et (4+3) à partir d’ènecarbamates ou de diènecarbamates catalysées par des acides phosphoriques chiraux. Ces derniers étant bifonctionnel, ils permettent l’activation des deux partenaires de cycloaddition menant à la synthèse d’indolines, de 2,3-dihydrobenzofuranes, de benzoquinones carbonannulées, de cyclohepta[b]indoles et de tétrahydroquinolines de façon hautement stéréosélective. Dans une seconde partie, nous nous sommes intéressés à l’utilisation de composés d’iode hypervalent chiraux comme organocatalyseurs. En effet, ces composés présentent une réactivité intéressante tout en étant stable et faiblement toxique. Ainsi, leur utilisation dans une réaction de lactonisation à partir de substrats flexibles a permis l’obtention de divers hétérocycles avec de bons résultatsThe development of new enantioselective methodologies is essential for the synthesis of bioactive compounds. In this context, we were interested in using organocatalysts for the synthesis of enantioenriched cyclic molecules. In a first part will be describe chiral phosphoric acid catalyzed (3+2), (4+2) and (4+3) formal cycloadditions using enecarbamate or dienecarbamate. These catalysts are bifunctional and can interact with both cycloaddition partners leading to the synthesis of 2,3-dihydrobenzofuranes, carboannulated benzoquinones, cyclohepta[b]indoles and tetrahydroquinolines with high stereocontrol. In a second phase, we were interested in using chiral hypervalent iodine as organocatalyst. Theses compounds present interesting reactivity while being stable and not very toxic. Their use permits us to develop a lactonisation starting from flexible substrate and led to the synthesis of various heterocycles with good results
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Milbéo, Pierre. "Synthèse de bicycles contraints originaux pour l’élaboration de nouveaux catalyseurs chiraux et de nouveaux foldamères." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT209.
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Les travaux présentés dans cette thèse ont eu pour objectif la valorisation d’une structures bicyclique bifonctionnelle à géométrie contrainte, celle de l’acide 2-aminobicyclo[2.2.2]octane 1-carboxylique (ABOC). La contrainte conformationnelle est une caractéristique particulièrement recherchée dans la conception d’agent chiraux pour la synthèse asymétrique ainsi que dans la synthèse de macromolécules se structurant spontanément (foldamères). Un travail sur la synthèse de petits peptides incorporant le (R) ou (S)-ABOC, a dans un premier temps conduit à l’identification d’un nouvel organocatalyseur bifonctionnel de la réaction d’aldolisation. Ce tripeptide incorporant en plus de l’ABOC un résidu proline en position N-terminale et un résidu Asp-OMe en position C-terminale a permis l’obtention d’excès énantiomérique élevés (jusqu’à 87%). Les analyses structurales ainsi que des calculs théoriques ont montré l’importance du bicycle de l’ABOC induisant la formation d’un coude dans la molécule et permettant la proximité des fonctions acide carboxylique (Asp) et amine secondaire (Pro) intervenant dans la catalyse. Dans un second temps, l’optimisation de la synthèse du (R) ou (S)-1,2-diaminobicyclo[2,2,2]octane (DABO) a permis de mettre en évidence l’impact important d’une double liaison endo-cyclique dans la réactivité de l’amine en tête de pont lors du réarrangement de l’acide carboxylique de l’ABOC en amine primaire. En effet, seules les conditions d’Hofmann appliqué au substrat présentant une insaturation dans le squelette bicyclique ont permis d’obtenir la diamine chirale avec de bon rendement. Cette nouvelle diamine vicinale chirale contrainte par un bicycle carboné a d’abord permis la synthèse de composés thiourée-amine autour du bicycle pour l’organocatalyse de la réaction d’addition de Nitro-Michael asymétrique. Cependant, et malgré les nombreux efforts d’optimisation, l’utilisation de ces molécules n’a jamais permis l’obtention d’excès énantiomériques supérieurs à 39%. En revanche, la synthèse de nouveaux ligands chiraux salen, salan et diamines secondaires basés sur le DABO et l’application des complexes de cuivre correspondants dans la catalyse de la réaction de nitroaldolisation asymétrique a abouti à l’obtention de bons rendements et d’une stéréosélectivité allant jusqu’à 86% d’excès énantiomériques. Le complexe donnant les meilleurs résultats a fait l’objet d’une étude DFT approfondie permettant de proposer la structure de l’état de transition le plus stable et de rationaliser la stéréosélectivité observée. Enfin la synthèse du DABO a permis d’entreprendre la synthèse de nouvelles oligourées mixtes homochirales se structurant en hélice-12/14 stables, alors qu’aucune structuration n’avait été observée lors de l’étude d’oligourées mixtes homochirales synthétisées à partir de l’ABOCThe work presented in this thesis was aimed at the valorisation of a bicyclic bifunctional structure with constrained geometry, the 2-aminobicyclo[2.2.2]octane 1-carboxylic acid (ABOC). Conformational restriction is a particularly sought characteristic in chiral agent designed for asymmetric synthesis as well as in the synthesis of spontaneously structuring macromolecules (foldamers). A work on the synthesis of small peptides incorporating (R) or (S)-ABOC, initially led to the identification of a novel bifunctional organocatalyst for the aldolization. This tripeptide incorporating in addition to ABOC a proline residue in the N-terminal position and an Asp-OMe residue in the C-terminal position allowed to obtain high enantiomeric excess (up to 87%). Structural analysis as well as theoretical calculations showed the importance of the ABOC bicycle, inducing the formation of a turn in the molecule and allowing the proximity of the carboxylic acid (Asp) and secondary amine (Pro) functions involved in catalysis. The optimization of the synthesis of (R) or (S)-1,2-diaminobicyclo[2,2,2]octane (DABO) allowed to demonstrate the important impact of an endo-cyclic double bond in the reactivity of the bridgehead amine during the rearrangement of the carboxylic acid of the ABOC to the primary amine. Indeed, only the Hofmann conditions applied to the substrate exhibiting unsaturation in the bicyclic skeleton allowed to obtain the chiral diamine in good yield. This novel chiral vicinal diamine conformationally restricted by a carbon bicycle first allowed the synthesis of thiourea-amine compounds around the bicycle for the organocatalysis of the asymmetric nitro-Michael addition. However, despite many optimization efforts, the use of these molecules has never led to enantiomeric excesses greater than 39%. On the other hand, the synthesis of new chiral salen, salan and secondary diamines ligands based on DABO and the application of the corresponding copper complexes for the catalysis of the asymmetric nitroaldolization reaction resulted in good yields and a stereoselectivity up to 87% enantiomeric excess. The best-performing complex was subjected to a DFT study to propose the structure of the most stable transition state and to rationalize the high stereoselectivity. Finally, the synthesis of DABO allowed to undertake the synthesis of new homochiral mixed oligoureas structuring as stable 12/14-helices, while no structure had been observed during the study of homochiral mixed oligoureas synthesized from the ABOC
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Kinsey, Francesca. "Novel axially chiral amines as organocatalysts." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/67099/.
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Novel axially chiral amines as organocatalysts Keywords: Axial chirality, asymmetric organocatalysis, Reformatsky reaction, Diels- Alder reaction, amino acid. This body of research describes the recent developments our group has contributed towards the synthesis of novel axially chiral α- and β-functionalized amino acids and their application in asymmetric catalysis. This thesis is divided into three sections. The first chapter contains a review of the discovery and development of organocatalysis and includes key examples of its progression in terms of widening applications and improving selectivities. The second chapter consists of the results and discussion section of this thesis and it is divided into two parts. Part one contains works relating to the synthesis of a series of binaphthyl and biphenyl organocatalysts and describes key selective synthetic steps: a diastereoselective Reformatsky addition and asymmetric lithiation and chloroformate/carboxylation addition steps. Part two focuses on the observed enantio- and diastereoselectivity of these catalysts in the aldol, Michael and Diels- Alder reactions. Key steps: i) 10 mol% 239.HCl, MeOH:H2O, 0 °C ii) LiAlH4 reduction Section three contains the experimental data for the compounds described in chapter two.
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Gregory, Alexander William. "Cyclisation cascades via reactive iminium intermediates." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:8e633fee-3457-4c31-939c-4421fac2fb8f.
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The aim of this D.Phil was to develop a range of cyclisation cascades, which initially form a reactive iminium intermediates that can then be attacked by a pendant nucleophile resulting in novel polycyclic structures. This concept has been applied to the development of three methodologies and has resulted in the discovery of new reactivity as well as the synthesis of a wide range of interesting novel structures Chapter 1: Enantioselective chiral-BINOL-phosphoric acid catalysed reaction cascade A highly enantioselective hydroamination / N-sulfonyliminium cyclisation cascade using a combination of Au(I) and chiral phosphoric acid catalysts has been developed. Proceeding by an initial 5-exo-dig hydroamination and a subsequent phosphoric acid catalysed Pictet- Spengler cyclisation, the reaction provides access to complex sulfonamide scaffolds in excellent yields and with high levels of enantiocontrol. The scope can be extended to lactam derivatives, with excellent yields and enantiomeric excesses of up to 93% ee. Chapter 2: Iridium catalysed nitro-Mannich cyclisation A new chemoselective reductive nitro-Mannich cyclisation reaction sequence of nitroalkyltethered lactams has been developed. An initial rapid and chemoselective iridium(I) catalysed reduction of lactams to the corresponding enamine is subsequently followed by intra molecular nitro-Mannich cyclisation. This methodology provides direct access to important alkaloid, natural product-like structures in yields up to 81% and in diastereoselectivities that are typically good to excellent. An in-depth understanding of the reaction mechanism has been gained through NMR studies and characterisation of reaction intermediates. The new methodology has been applied to the total synthesis of (±)-epi-epiquinamide in 4 steps. Chapter 3: Iridium catalysed reductive interrupted Pictet-Spengler cyclisation A novel reductive interrupted Pictet-Spengler cyclisation reaction cascade has been created. An iridium(I) catalyzed partial reduction of lactams/amides to the corresponding iminium is subsequently trapped by a pendant indole nucleophile. Interruption of the Pictet-Spengler reaction by indolium reduction provides a wide range of novel spirocyclic indoline moieties in excellent yield and diastereoselectivity.
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Néel, Mathilde. "Synthèse et utilisation de nouveaux catalyseurs phosphorés à noyau ferrocénophane." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA112222.
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La catalyse est par définition l’utilisation d’une quantité sous stœchiométrique d’un composé accélérant une réaction, sans entrer dans son bilan réactionnel. Si le catalyseur est une molécule organique chirale, nous pouvons effectuer des réactions d’organocatalyse asymétrique. D’autre part, si les phosphines trivalentes sont largement employées comme ligands en catalyse organométallique, elles présentent également une réactivité complémentaire aux amines en organocatalyse. Une nouvelle phosphine chirale à noyau ferrocénophane, le FerroPHANE, a été récemment développée et utilisée avec succès au laboratoire. C’est dans ce contexte que s’inscrivent mes travaux de thèse portant à la fois sur l’étude de nouveaux processus catalytiques et la synthèse de nouveaux dérivés phosphorés chiraux. Tout d’abord, une réaction de cyclisation [3+2] entre des oléfines et des allénylphosphonates catalysée par le FerroPHANE a été développée (excès énantiomériques compris entre 84 et 91%). Dans un second temps, des groupements aryles ont été introduits sur le noyau ferrocénique du FerroPHANE afin de moduler sa réactivité et son énantiosélectivité. Enfin, une nouvelle famille de phosphoramidites chiraux à noyau ferrocénique a été synthétisée et utilisée dans la synthèse de complexes de platineCatalysis is the acceleration of a reaction by addition of a sub-stœchiometric amount of a compound. When catalyst is a chiral organic derivative, it is possible to obtain enantioenriched products by asymmetric organocatalysis. Moreover, if trivalent phosphines have been widely developed as ligand for organometallic catalysis, their reactivity is complementary to amines in organocatalysis. A new planar chiral phosphine with ferrocenophane scaffold was recently developed and successfully used in organocatalysed reactions by our team: FerroPHANE. In this context, we have been interesting both in the development of new enantioselective [3+2] cyclization reactions catalyzed by chiral trivalent phosphines and the development of new chiral phosphorus derivatives with ferrocenophane scaffolds. In a first part, new enantioselective [3+2] cyclization reactions between olefins and allenylphosphonates, catalyzed by FerroPHANE, have been successfully developed (enantiomeric excesses between 84 to 91%). In a second part, to modify the reactivity and the enantioselectivity of this new family of phosphines, aryl groups were introduced on the ferrocenyl scaffold. Finally, a new family of chiral phosphoramidites with ferrocenyl scaffold have been synthesized and applied to the synthesis of chiral platinum complexes
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Hermeke, Julia. "Chiral phosphonium ion tagged and spiroindane-based organocatalysts." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hdl.handle.net/10722/205871.
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The research on asymmetric organocatalysis has been intensifying since the
beginning of 2000. The growing interest in this research area is driven by the
importance of the chemical synthesis of enantiomerically pure products. While
the general field of asymmetric organocatalysis has been explored intensively, the
recyclability of organocatalysts has not really been considered.
The attachment of phosphonium ion phase tags to chiral binaphthyl-based
phosphoric acid catalyst and the use of these materials in a range of
organocatalytic asymmetric Friedel-Crafts reactions of indoles have been studied.
Placement of tags at the 3 and 3’ positions of the binaphthyl core, so that they
could serve as steric blocking groups, failed to produce an active catalyst.
However, moving the phosphonium ion groups to the 6 and 6’ positions produced
an efficient and enantioselective catalyst. Aided by the presence of the phase tags,
the chiral catalyst was easily recovered at the end of the reactions, and could be
reused several times, albeit with somewhat decreased efficiency and
enantioselectivity.
Furthermore, the synthesis of 1,1’-spirobiindane-7,7’-diol and their
spiroindane-based derivatives have been explored. The (R)-1,1’-spirobiindane-
7,7’-diamine was successfully applied in exo selective asymmetric Diels-Alder
reactions of -unsaturated aldehyde with cyclopentadiene. However, moderate
results aspire further studies in assay of (R)-1,1’-spirobiindane-7,7’-diamine
derivatives, which bear various bulky groups at the 6 and 6’ positions. Moreover,
the conversion of the SPINOL into a spiroindane ketone unfortunately failed,
which was caused by the sterically crowded structure of the SPINOL skeleton.published_or_final_version
Chemistry
Master
Master of Philosophy
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Alsenani, Nawaf. "Organocatalysis using novel axially chiral secondary amines." Thesis, University of East Anglia, 2018. https://ueaeprints.uea.ac.uk/69912/.
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The field of organocatalysis has grown rapidly in the last 20 years. Moreover it is a big challenge in modern chemistry due to the rewards that can be gained from its efficiency, low cost and low toxicity. In addition, organocatalysis has many advantages in industrial chemistry it can save time and money by avoiding the use of large amounts of solvents and thus minimizing waste. This Thesis is broken down into three chapters, the first one presents a review of organocatalysis including recent updates and developments, and introduces the different organocatalyst classes, their modes of activation, and a number of examples which show the selectivity improvements obtained. The second chapter is divided into two parts. The first part descries the synthesis of certain binaphthyl organocatalysts and a description of the key steps of their synthesis: a diastereoselective Reformatsky addition and asymmetric lithiation and chloroformate/carboxylation addition steps. The second part focuses on the applications and the results obtained when these catalysts were used in aldol and Mannich reactions. The third chapter contains the experimental data for the products that are discussed in chapter two.
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Cormack, Maria. "Investigation of New Organocatalysts Based on Chiral Biaryl Azepines." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523212.
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Guo, Jiawen, and 郭嘉雯. "Chiral spirodiphosphine dioxides organocatalysis and hydrogen transfer reduction." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196023.
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Recently, during the past10 years, with the intensified attention paid to the environment and industrial development, there has been growing interest in organocatalysis. One important area of the organocatalysis is the development of new designs of chiral catalysts for the synthesis of optically pure products. Another important area is to develop methods to simplify the purification of multi-component reactions.
A chiral spirobiindane-based bisphosphine oxide catalyst was synthesized and employed in various reactions including Abramov-type phosphonylation reactions, reductive aldol reactions, direct aldol reactions, allylations, reductive cyclizations and C=N reduction reactions. The rigid and axially chiral spirobiindane skeleton of the bisphosphine oxide introduces steric hindrance and results in moderate to good enantioselectivity in Abramov phosphonylation and reductive cyclization reactions. However, the great steric hindrance of the catalyst also imposes negative effects on catalyst activity and yields of reactions. The observed slow reaction rates may possibly have led to the undesired, non-selective background reactions and therefore a lowered enantioselectivity.
Secondly, the success of polymer-supported reagents in facilitating product purification prompted our attempt to prepare and examine two different types of polymer-supported benzothiazolines for hydrogen transfer reduction. An in situ generated self-supported polybenzothiazoline proved to be a rapidly formed polymer under mild conditions and could be applied to hydrogenation transfer reduction reactions with active alkenes. A rasta resin-supported benzothiazoline was also synthesized and examined in similar transformations. Both of the two polymer reagents afforded the desired reduction products, but further optimizations may be required to suppress the formation of byproducts and to improve their reactivity.published_or_final_version
Chemistry
Master
Master of Philosophy
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Patrikeeva, Liudmila. "Immobilization of BINOL-based organocatalysts for the asymmetric synthesis of amino acids." Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20264/document.
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L'objectif du projet est de synthétiser et de tester de nouveaux catalyseurs organiques supportés qui servont à la préparation d'amines chirales par la réaction de réduction de ketimines et à la préparation d'acides aminés phosphoniques par la réaction de Pudovik. La présence d'un support facilite la récupération et le recyclage du catalyseur. Le projet est basé sur le développement de nouveaux types de catalyseurs organiques, comme les acides de Bronsted chiraux, sur support polymérique – polyéthylène glycol, possédant une activité catalytique et de stéréodifférentiation élevée, facilement récupérables d'un mélange réactionnel pour une utilisation dans plusieurs cycles catalytiques. Les diesters de l'acide phosphorique, dérivés de bisphenols, ont étés utilisés comme catalyseurs acides. Une série de dérivés polymériques basés sur des PEG monofonctionnalisés de différentes tailles ont été préparée. Ces catalyseurs ont testés dans plusieurs réactions énantiosélectives d'addition de différents nucléophiles sur liaisons C = N permettant l'accès à des précurseurs importants, que sont les amines chirales et les acides α-aminés phosphorésAsymmetric organocatalysis has emerged recently as a powerful tool for the preparation of chiral molecules. The aim of the project was to design, synthesize and test new supported organocatalysts for the preparation of molecules by transfer hydrogenation reaction of ketimines and by Pudovik reaction for the amino phosphonic acid. The presence of a soluble support provided homogeneous conditions for catalysis and facilitated recovery and recycling of the catalyst. A series of derivatized polymers based on monofunctional PEG's with different sizes were prepared. These catalysts were tested in several enantioselective addition reactions of various nucleophiles to multiple C=N-bond leading to precursors of practically important compounds such as chiral amines, amino phosphonic acids
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Perry, Benjamin Garfield. "Planar chiral (2.2) paracyclophanediols as metal-free hydrogen-bonding organocatalysts." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406740.
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Rampalakos, Konstantinos. "Asymmetric synthesis with vapol derivatives and novel chiral thiourea organocatalysts." Diss., Connect to online resource - MSU authorized users, 2008.
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Claraz, Aurélie. "Nouvelles applications de paires d’ions coopératifs chirales en organocatalyse : réactions énantiosélectives de protonation, de déprotonation et d’aldolisation directes vinylogues." Thesis, Rouen, INSA, 2012. http://www.theses.fr/2012ISAM0015.
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Le développement de nouvelles méthodologies énantiosélectives organocatalysées est au centre des projets de cette thèse. Nous avons plus particulièrement considéré le potentiel de "paires d'ions coopératifs" chirales possédant une partie ammonium dérivée des alcaloïdes de quinquina et une partie anionique à caractère nucléophile permettant d'activer un réactif. Dans un premier temps, nous avons employé un amidure d'ammonium chiral (généré in situ par réaction entre un amide N-silylé et un phénolate de quininium) comme base de Brønsted délivrée en quantité catalytiques en deux réactions distinctes. Initialement, cette stratégie nous a permis de mettre au point un procédé de désymétrisation de cétones prochirales par déprotonation éniantosélective. Bien que les excès énantiométriques obtenus restent modestes, notre approche constitue la première version organocatalysée. Puis, nous avons pu développer avec succès une nouvelle réaction d'aldolisation directe vinylogue énantiosélective de (5H)-furan-2-ones avec de bons rendements et diastérosélectivités anti et des excès énantiométriques allant jusqu'à 94 %. Dans un second temps, nous avons décrit deux nouveaux cycles catalytiques de protonation énantiosélective d'énolates masqués. Tout d'abord, l'utilisation d'hydrogénocarbonate de potassium et d'une amine chirale a conduit à l'obtention de cétones énantioenrichies α-substituées avec des excès énantiométriques allant jusqu'à 93 % à partir des trifluoacétates d'énols correspondants. Puis, les propriétés de base de Lewis de nos phénolates d'ammoniums quaternaires chiraux ont été valorisés lors de la protonation énantiosélectives d'éthers d'énols silylés en présence de phénolsThis work deals with the development of new asymetric organocatalyzed methodologies. More particularly we were focused on using "cooperative chiral ion pairs" having an ammonium moiety derived from cinchona alkaloids and an anionic moiety with nucleophilic properties able to activate a reagent.Firstly, we used an in situ generated chiral ammonium amide (from the combination of an aminosilane and a quininium aryloxide) as a Brønsted base in two distinct reactions. Initially, this strategy was applied to an organocatalyzed desymmetrization of prochiral ketones by enantioselective deprotonation. Despite modest enantiometric excesses, this report constitutes the first example of an enantioselective orgonacatalyc approach. Then, an anti-selective direct vinylogous asymmetric aldol reaction of (5H)-furan-2-ones was achieved in good yields and enantioselectivities up to 94%.Secondly, we described two new catalytic cycles for the enantioselective protonation of latent enolates. By means of cinchona alkaloids and hydrogenocarbonates, enantioenriched α-substituted ketones were obtained with good enantiometric excesses up to 93% starting from the corresponding enol trifluoacetates. Finally, the nucleophilic properties of our ammonium phenoxide catalysts prompted us to develop an enantioselective protonation reaction of silyl enol ethers in the presence of phenol as achiral proton source
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Chen, Lingyan. "CaSH (camphor sulfonyl hydrazine) and CSI (chiral sulfonimide) organocatalysis." HKBU Institutional Repository, 2010. http://repository.hkbu.edu.hk/etd_ra/1186.
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Isik, Murat. "Chiral 2-aminodmap/sulfonamides And Squaramides Asbifunctional Acid/base Organocatalysts In Asymmetriccatalysis." Phd thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613444/index.pdf.
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Synthesis and evaluation of catalytic performances of novel bifunctional 2-
aminoDMAP-Thiourea/ Sulfonamide/ Squaramide organocatalysts derived from
trans-(R,R)-cyclohexane-1,2-diamine forms the main goal of this thesis. For this
purpose, direct selective mono-N-pyridilization of trans-(R,R)-cyclohexane-1,2-
diamine via Pd and Cu catalysis is described successfully first. Facile preparation of
chiral 2-aminoDMAP core catalaphore led to the development of various 2-
aminoDMAP- Thiourea/ Sulfonamides/ Squaramides as bifunctional acid/base
organocatalyst libraries (most in two-steps overall) which showed good results in
asymmetric conjugate addition of 1,3-dicarbonyls to trans-(&beta)-nitrostyrene. Enantiomeric excesses (ee) up to 93% were attained.
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Dagousset, Guillaume. "Etude de la réaction de Povarov : synthèse énantiosélective de composés diaminés organocatalysée par des acides phosphoriques chiraux." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00802712.
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Ce travail porte sur l'étude de la réaction de Povarov, une réaction de type aza-Diels-Alder à demande inverse d'électrons entre un diène de type 2-aza-diène (généralement une imine dérivée d'une aniline) et un diénophile tel qu'une oléfine riche en électrons, aboutissant ainsi à la formation de tétrahydroquinoléines. Nous sommes parvenus à réaliser cette réaction dans sa version multicomposants, c'est-à-dire en formant in situ l'imine à partir de l'aldéhyde et de l'aniline correspondants. De plus, cette réaction multicomposants a pu être effectuée de manière énantiosélective, en utilisant comme catalyseur des organocatalyseurs de type acides phosphoriques chiraux, et en choisissant judicieusement comme diénophile des ène-carbamates, qui possèdent une liaison N-H capable d'interagir avec l'acide phosphorique. Cette méthodologie a ainsi permis la synthèse de 4-amino-tétrahydroquinoléines avec une diastéréosélectivité totale, de bons rendements, et d'excellents excès énantiomériques. L'utilisation de diénophiles de type ène-thiourées a permis selon la même stratégie d'accéder à des composés hexahydropyrroloquinoléines avec des sélectivités similaires.Nous nous sommes également intéressés au mécanisme de cette réaction de Povarov, qui s'est révélé se dérouler en deux étapes distinctes, l'intermédiaire immonium pouvant être piégé, soit de manière intermoléculaire par l'éthanol, conduisant après réduction à des 1,3-diamines chirales, soit de manière intramoléculaire dans le cas particulier de l'utilisation du phénylacétaldéhyde, conduisant alors à des 1,3-diaminotétralines.
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Levitre, Guillaume. "Photocatalyse et organocatalyse comme outils innovants pour la synthèse de molécules complexes." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS380.
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Face aux enjeux environnementaux actuels, la catalyse est devenue un outil majeur pour la synthèse de molécules complexes et à visées thérapeutiques. Dans ce contexte, nous nous sommes intéressés au développement de nouvelles méthodes de synthèses innovantes, efficaces, sans métaux ou activées par la lumière visible. Ainsi, mes travaux de thèse ont fait appel à deux thématiques largement étudiées au sein de notre laboratoire que sont la catalyse photorédox et l'organocatalyse. Dans ce manuscrit, la première partie porta sur la conception de réactions multicomposants photocatalysées pour la synthèse de structures trifluorométhylées avec de bons rendements. La partie suivante a été consacrée au développement et à l’évaluation de nouveaux photocatalyseurs supportés, robustes et recyclables. La troisième partie présenta l’élaboration de réactions de cyloadditions formelles (4+3) et (4+2), catalysées aux acides phosphoriques chiraux pour une synthèse efficace, énantiosélective et diastéréosélective de cyclohepta[b]indoles et de spiroindolines. Dans la quatrième partie, une stratégie combinant l’organocatalyse asymétrique et la photocatalyse pour la synthèse de tryptamines α-substituées β-aminées potentiellement biologiquement actives a été décrite. Enfin, l’élaboration de nouveaux composés d’iode hypervalent chiraux et leur évaluation en tant qu’organocatalyseurs fût rapportées dans la dernière partie de ce manuscrit de thèseIn front of current environmental challenges, catalysis has become a major tool for the synthesis of complex and therapeutic molecules. In this context, we have focused on the development of new synthesis methods that are innovative, efficient, metal-free or activated by visible light. Thus, my thesis work has involved two themes that have been widely studied in our team: photoredox catalysis and organocatalysis. In this manuscript, the first part focused on the conception of photocatalyzed multicomponent reactions for the synthesis of trifluoromethylated structures with good yields. The following section devoted to the design and evaluation of new supported, robust and recyclable photocatalysts. The third part presented the formulation of formal (4+3) and (4+2) cyloaddition reactions, catalyzed with chiral phosphoric acids for an effective, enantio- and diastereo-selective synthesis of cyclohepta[b]indoles and spiroindolines. In the fourth part, a strategy combining asymmetric organocatalysis and photocatalysis for the synthesis of potentially biologically active α-substituted β-amino tryptamines was described. Finally, the elaboration of new chiral hypervalent iodine compounds and their evaluation as organocatalysts was reported in the last part of this thesis manuscript
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Rasappan, Ramesh. "Synthesis and exploration of chiral aza-bis(oxazolines) and organocatalysts in asymmetric reactions." kostenfrei, 2009. http://epub.uni-regensburg.de/13388/.
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Wagner, Mathieu. "Synthèse de polyamines fonctionnalisées et de macrocycles polyazotes chiraux : application à l'organocatalyse de la réaction d'aldolisation et de nitro-Michael." Paris 6, 2009. http://www.theses.fr/2009PA066119.
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Les polyazamacrocycles fonctionnalisés utilisés comme ligands dans de nombreux domaines possèdent des structures qui pourraient leur conférer un rôle d’organocatalyseur. Le potentiel organocatalytique de deux séries de catalyseurs, les polyazamacrocycles et diverses polyamines linéaires, a été étudié. Dans un premier temps, une voie de synthèse efficace et généralisable a été mise au point pour produire une variété de polyazamacrocycles lactame et d'analogues diversement fonctionnalisés. Sur la base du même pool chiral diaminocyclohexane, leurs squelettes ont été modulés en y incorporant diverses entités susceptibles de modifier leurs propriétés catalytiques. Leur aptitude potentielle à réaliser des catalyses covalentes par la formation d'intermédiaires énamine, a ensuite conduit à les appliquer à la réaction directe d'aldolisation. Ces composés ont démontré leur efficacité vis-à-vis de cette réaction avec toutefois de faibles énantiosélectivités. La synthèse d'une série de polyamines chirales linéaires, pour une large part précurseurs des macrocycles, a également été réalisée afin d’évaluer leur potentiel organocatalytique. Parmi les différents composés élaborés, les dérivés de la L-proline se sont montrés les plus performants à catalyser la réaction d'aldolisation ou la réaction de nitro-Michaël. Pour chacune de ces deux réactions, une étude approfondie a permis de sélectionner un nouvel organocatalyseur efficace et sélectif permettant d'obtenir d'excellentes énantiosélectivités.
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Ngo, Thi Thuy Duong. "Chiral thioureas, thiourea-phosphines and amines derived from biomass : synthesis and applications in asymmetric organocatalysis." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS476.
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Cette thèse porte sur la préparation de nouveaux catalyseurs chiraux à partir de composés naturels issus de la biomasse, et leurs applications en organocatalyse asymétrique. La première partie décrit la synthèse de thiourées énantiomériquement pures dérivées de l'isosorbide et l’isommanide. Ces thiourées ont été évaluées comme catalyseurs organiques dans des réactions asymétriques de Friedel-Crafts, d’alkylation, d’addition de type aza-Michael, d’hydroamination et de type Morita-Baylis-Hillman (MBH). Les meilleurs résultats en termes de réactivité et d’induction asymétrique, ont été obtenus dans le cas de la réaction de Friedel-Crafts. La deuxième partie est consacrée à la conception et la synthèse de thiourée-phosphines chirales à partir de la L-proline. Ces thiourée-phosphines sont capables de promouvoir la formation de liaisons C-N et C-S, selon un processus de substitution allylique énantiosélectif d’adduits modifiés de MBH. De très bons rendements (jusqu’à 98%) et énantiosélectivités (jusqu'à 93%) ont été obtenus. Dans la troisième partie, nous avons développé le premier exemple de cyclisation [4 + 2] entre un allénoate et un alcène tétrasubstitué, catalysée par une amine tertiaire. Nous avons montré que des composés de type 4H-pyranniques peuvent être sélectivement obtenus, avec d’excellents rendements, en utilisant le DABCO comme catalyseur. Dans le cas de catalyseur organique de type alcaloïde, le β-ICD conduit sélectivement aux composés 2H-pyranniques avec des excès énantiomériques jusqu’à 71 % eeThe thesis focused on the preparation of new chiral catalysts derived from biomass and their applications in asymmetric organocatalysis. The first part described the synthesis of chiral thioureas derived from isosorbide and isomanide, naturally renewable resource, in moderate to good overall yields. These thioureas were evaluated in asymmetric reactions such as Friedel-Crafts alkylation, aza-Michael addition, hydroamination, Morita-Baylis-Hillman reaction. Good yields and enantioselectivities were obtained. The second part of our work went on the design and synthesis of chiral thiourea-phosphines from L-Proline. These thiourea-phosphines promoted C-N and C-S bond formation via the asymmetric allylic substitution of tert-butoxycarbonyloxy adducts. Good yields (up to 98 %) and enantioselectivities (up to 93 %) were observed. In the third part, we have developed the first example [4+2] annulation of allenoate and all-carbon tetrasubstituted alkenes catalyzed by an amine. In the case of DABCO catalyst, 4H-pyrans were isolated exclusively in good to excellent yield under mild reaction conditions. While employing β-ICD as catalyst, the enantioenriched 2H-pyran derivatives were obtained with enantiomeric excess up to 71 % ee
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Postikova, Svetlana. "New developments in organocatalyzed formal anionic [3+2] cycloadditions and novel tropos phase-transfer organocatalysts." Thesis, Rouen, INSA, 2013. http://www.theses.fr/2013ISAM0016.
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L’organocatalyse est reconnue comme une approche attractive dans la synthèse énantiosélective, offrant de nombreux avantages par rapport à la métallo-catalyse et biocatalyse. Dans la première partie de cette thèse, nous nous sommes intéressés dans le développement de nouveaux catalyseurs tropos de transfert de phase, basée sur les dérivés de dibenzazepinium et leurs applications en synthèse asymétrique. Nous avons mis en évidence la possibilité d’utiliser le principe de transfert de chiralité centrale-axiale. La deuxième partie de cette thèse a été consacrée à l'élaboration de méthodologies organocatalytiques en utilisant la catalyse par transfert de phase ou de base de Brønsted. Notre nouvelle approche, basée des réactions organocatalytiques de cycloaddition formelles [3 + 2], ouvre l'accès aux différents cycles chiraux comme des cyclopentènes, pyrrolidines ou isoxazolidinones. Toutes ces molécules sont potentiellement intéressantes pour leur évaluation comme des ligands bioactifOrganocatalysis is recognized as a versatile and attractive tool in enantioselective synthesis, offering a number of advantages over metal-based and bioorganic methods. During the first part of this thesis, we were interested in development of novel tropos Phase-Transfer catalysts, based on the dibenzazepinium derivatives and their applications in asymmetric synthesis. Their design was tackled by anoriginal central-axial chirality transfer principal. The second part of this thesis was devoted to the elaboration of novel organocatalytic methodologies under chiral PTC or Brønsted base organocatalysis. Based on formal organocatalytic [3+2]cycloaddition reactions our novel approach opens the access to various chiral cycles like cyclopentenes, pyrrolidines or isoxazolidinones. All these molecules are potentially interesting for their evaluation as bio-ligands
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Karpus, Andrii. "Calix[4]arènes chiraux contenant des groupes phosphine comme ligands pour la catalyse." Thesis, Toulouse 3, 2017. http://www.theses.fr/2017TOU30045/document.
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La thèse est consacrée à la développement de méthodes efficaces pour la synthèse d'une nouvelle classe d'intrinsèquement chiral calix[4]arènes contenant du phosphore, phosphines et acides phosphoriques avec une certaine disposition mutuelle des groupes fonctionnels sur le bord inférieur du macrocycle, avec un potentiel activité catalytique. La façon optimale fot la synthèse de calix[4]arènes contenant du phosphore par la substitution progressive des hydroxyles phénoliques a été développé afin de concevoir des intrinsèquement chiral calix[4]arènes avec des types de remplacement ABHH et ABCH au bord inférieur du macrocycle. En utilisant ces techniques, la synthèse de la six catalyseurs et efficaces avec chiralité planaire a été réalisée. En utilisant des études de diffraction des rayons X a permis d'étudier la localisation spatiale des groupes fonctionnels. L'utilisation de la réaction de Mitsunobu autorisé à fournir une synthèse de la nouvelle "poche" -comme ligands - calix[4]arènes portant des fragments ferrocényle-phosphines chirales. L'efficacité des nouveaux ligands phosphine synthétisés a été confirmé par l'exemple du modèle de réaction Tsuji-Trost. intéressante dépendance du niveau de sélectivité de la taille du cation de métal de base ajoutée, en raison de l'effet de ligand de chélation du supramoléculaire a été observée. Calix[4]arènes acides phosphoriques a d'abord été appliqués comme organocatalyseurs la série de réactions modèles: aza-Diels-Alder, aza-Mukayiama réaction asymétrique et réaction d'ouverture d'époxydes anneau. Il a été constaté que la plupart des composés synthétisés présentent un degré notable de activitydue catalytique à des caractéristiques de chiralité interneThe thesis is devoted to the developing of effective methods for the synthesis of new class of inherently chiral phosphorus-containing calix[4]arenes, phosphines and phosphoric acids with a certain mutual arrangement of functional groups on the lower rim of the macrocycle, with potential catalytic activity. The optimal way fot the synthesis of phosphorus-containing calix[4]arenes by the stepwise substitution of the phenolic hydroxyls was developed in order to design inherently chiral calix[4]arenes with ABHH and ABCH replacement types at the lower rim of the macrocycle. By using these techniques, synthesis of six analogues of known and effective catalysts with planar chirality was performed. Using X-ray diffraction studies allowed to investigate spatial location of functional groups. Using of Mitsunobu reaction allowed to provide synthesis of the new "pocket"-like ligands - calix[4]arenes bearing chiral ferrocenyl-phosphines moieties. The effectiveness of the synthesized new phosphine ligands was confirmed by the example of the model Tsuji-Trost reaction. Interesting dependence of the selectivity level on the metal cation size of added base, due to chelation effect of supramolecular ligand was observed. Calix[4]arenes phosphoric acids was first applied as organocatalysts the series of model reactions: aza-Diels-Alder reaction, aza-Mukaiyama asymmetric reaction and epoxides ring opening reaction. It was found that most of the synthesized compounds exhibit a noticeable level of catalytic activitydue to features of internal chirality
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Flores, Ferrándiz Jesús. "Chiral Aminocarbamates Derived from trans-Cyclohexane-1,2-Diamines as Organocatalysts in Conjugate Addition Reactions." Doctoral thesis, Universidad de Alicante, 2017. http://hdl.handle.net/10045/73589.
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The thesis has been divided in two chapters: Chapter I describes the preparation of primary-amine monocarbamates from enantiopure trans-cyclohexane-1,2-diamines and their use as chiral organocatalysts in the enantioselective Michael addition reaction of aldehydes and ketones to maleimides, to synthesize enantiomerically enriched substituted succinimides. In the conjugate addition reaction of aldehydes to maleimides in conventional volatile organic solvents, it has been found that these organocatalysts are able to generate both enantiomers of the corresponding succinimide using only one enantiomeric form of the catalyst, just by changing the polarity of the solvent. Theoretical calculations justify the mechanism through which this inversion of enantioinduction occurred. In addition, these organocatalysts were used in the enantioselective Michael addition reaction of aldehydes to maleimides, using Deep Eutectic Solvents (DES) as recyclable and environmentally sustainable reaction medium, yielding the corresponding succinimides with excellent yields and high enantioselectivities (up to 94%). The succinimides can be extracted from the DES, which retains the chiral organocatalyst, allowing to reuse both solvent and catalyst. Moreover, the conjugate addition of ketones to maleimides using conventional solvents, allows obtaining the corresponding succinimides with excellent yields but with moderate enantioselectivities (up to 66%). Chapter II shows the results obtained in the enantioselective Michael addition reaction of aldehydes and ketones to nitroalkenes, using the former trans-cyclohexane-1,2-diamine-derived aminocarbamates as chiral organocatalysts, obtaining enantioenriched γ-nitrocarbonyl compounds. In the conjugate addition of isobutyraldehyde to nitroalkenes, the corresponding γ-nitroaldehydes were obtained with enantioselectivities up to 84%. In addition, the enantioselective conjugate addition reaction of ketones to nitroalkenes allowed to obtain interesting γ-nitroketones with high enantioselectivities (up to 96%). Theoretical calculations justify the mechanism involved during this enantioselective process.
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Mellberg, Annika. "Chiral Carbocations as Lewis Acid Catalysts in Diels-Alder Reactions." Thesis, KTH, Skolan för kemivetenskap (CHE), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-156209.
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Lewis acids can be used as catalysts in different reactions, but the term Lewis acid catalysts often refers to metal salts. Metal complexes have been widely used for asymmetric catalysis. Asymmetric synthesis can however be performed in a metal-free way by using organocatalysis. New Lewis acid catalysts that are more effective, enantioselective and environmental friendly is of interest. This new type of Lewis acid catalysts could for example be of carbocation based character. The aim of this project was to synthesize chiral carbocations with different degree of sterical hindrance and investigate their catalytic ability in Diels-Alder reactions. It was presumed that the Diels-Alder reactions were going to be performed in an asymmetric way since the carbocation catalysts were achiral. Two chiral carbocations were synthesized successfully. The first synthesized carbocation, the less sterical hindered compound 8, was formed as a racemic mixture. The second carbocation, compound 16, could be formed as an enatiomeric pure compound. Both carbocations showed catalytic ability in Diels-Alder reactions and compound 8 was comparable with some common Lewis acid catalysts. In general, when using compound 8 as catalyst, higher catalyst amount gave higher conversions. Higher concentrations also gave higher conversions, but up to a certain level. No trend between polarity of different solvents and conversions could be seen. However, an increased temperature leads to faster reactions. The more rigid and sterical hindered compound 16 catalyzed the reactions slower than compound 8. The longer reaction time may indicate that the reaction occurs with higher selectivity, but no method to measure the ee of the product was found. An attempt to synthesize a third even more sterical hindered chiral carbocation, compound 19, resulted in a product contaminated by impurities that showed a catalytic ability lower than compound 8 and compound 16 in Diels-Alder reactions. The synthesis and the use of carbocations as Lewis acid catalysts in Diels-Alder reactions seem promising as a new type of catalysts even though there are questions that are still unanswered, e.g. counter ions effects, possible side reactions, selectivity etc.
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Nakayama, Keiji. "Design of Practical Asymmetric Organocatalysts from a Single Chiral Source for Obtaining Both Enantiomeric Products." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120721.
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Visco, Michael David. "Chiral Silanediols Designed for Enantioselective Heterocycle Functionalization." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492438099945523.
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Martin, Anthony. "Polymères chiraux par polymérisation par étapes asymétrique organocatalysée." Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14732/document.
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Depuis une quinzaine d’années, les polymères chiraux sont utilisés dans de nombreuses applications, comme phases stationnaires pour la séparation d’énantiomères ou encore en tant que catalyseurs en synthèse asymétrique. Aux vues de ces intérêts grandissants, de nombreuses méthodes ont émergé afin de les synthétiser. Nous nous sommes concentrés sur des méthodes organocatalytiques originales de synthèse de polymères chiraux par réaction de polyaldolisation et par désymétrisation de bis-anhydrides. Nous avons ainsi développé des processus de désymétrisation itératifs et ainsi généré une chiralité C-centrée sur la chaine polymérique. Des polyesters chiraux ont ainsi été obtenus avec de très bonnes séléctivitésChiral polymers are used in many applications such as stationary phases for chiral HPLC and catalysts in asymetric synthesis. The synthesis of chiral polymers traditionally deals with metal catalysts-based methodologies and often involved sensitive substrates. On the other hand, only a limited number of publications has been reported through environmentally-friendly organocatalytic pathways.The goal of this Ph.D. studies was devoted to the design of new routes toward chiral polymers under organocatalysis. We chose polyaldolisations and anhydride desymmetrizations with alcohols as key reactions to obtain original polymers with a C-centered chirality in the main polymer chain
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Slater, Natasha H. "The synthesis and functionalisation of chiral cleft molecules and their application as asymmetric hydrogen bond organocatalysts." Thesis, Loughborough University, 2015. https://dspace.lboro.ac.uk/2134/16855.
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Didier, Delphine. "Functionalized analogues of Tröger's base: synthesis, enantioseparation, and application as a chiral scaffold in organocatalysis." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210277.
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Jusqu’à très récemment, les catalyseurs pour la synthèse asymétrique étaient limités aux enzymes et aux complexes de coordination. Depuis les années 2000, une troisième approche a vu le jour: l’organocatalyse asymétrique. Il est assez surprenant de constater que parmi la multitude de catalyseurs organiques développés chaque année, une minorité d’entre eux seulement est basée sur de nouveaux squelettes chiraux. En effet, l’introduction d’une nouvelle entité chirale pourrait mener à la découverte de nouvelles combinaisons de substrats ainsi qu’à de nouvelles réactions catalytiques hautement stéréosélectives. C’est pourquoi, nous nous sommes proposé de préparer une série de nouveaux catalyseurs organiques bifonctionnels incluant des fonctions thiourées et basée sur le squelette chiral de la base de Tröger.L’accès aux dérivés énantiopures de la base de Tröger reste un défi majeur. C’est pourquoi, nous avons décidé de mettre au point une méthode efficace et prévisible, pour la résolution des analogues de la base de Tröger. Dans la mesure où l’élaboration d’une telle méthode nécessite un grand nombre de molécules, nous avons synthétisé une série de dérivés de la base de Tröger.
La condensation d’anilines variablement substituées avec du paraformaldehyde dans de l’acide trifluoroacétique a été étudiée, conduisant à la synthèse d’analogues symétriques de la base de Tröger. L’utilisation de paraformaldehyde n’étant pas compatible avec tous les groupements fonctionnels, d’autres voies de synthèse ont également été explorées. Ainsi, des dérivés amino et cyano ont été préparés par l’intermédiaire de réactions organométalliques. Ensuite, une voie de synthèse menant aux analogues non-symétriques de la base de Tröger a été mise au point. Finalement, une série de dérivés présentant un pont –NCH2CH2N- a été préparée.
La résolution de l’ensemble des composés a été systématiquement étudiée par chromatographie sur la phase stationnaire chirale commerciale Whelk O1. Des relations structure vs. énantioséléctivité ont pu être établies permettant de prédire la séparation par notre méthode. Une corrélation entre l’ordre d’élution et la configuration absolue a également pu être mise en évidence.
Enfin, l’activité catalytique des dérivés thiourées de la base de Tröger a été évaluée dans la réaction d’addition de Michael de différents dérivés de l’acide malonique au trans-nitrostyrene. Compte tenu de la faible basicité de la base de Tröger, il a été démontré que l’issue de la réaction est fortement dépendante du pKa du nucléophile. De plus, aucune stéréosélectivité n’a pu être mise en évidence dans cette réaction d’addition.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Porcar, Tost Oriol. "Chiral cyclobutane scaffolds: their application in the the development of new functionalized organogelators, organocatalysts and MRI contrast agents." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458683.
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En aquesta tesi, diferent sistemes basats en la estructura del ciclobutà s’han sintetitzat i estudiat com a gelificadors, catalitzadors i agents de contrast. Els resultats d’aquesta tesi estan dividits en tres capítols.
1) Dos gelificadors basats en pèptids estudiats prèviament en el nostre grup de recerca han estat funcionalitzats amb un derivat de la terpiridina. La influencia d’aquesta nova funció en la habilitat gelificant ha estat investigada. Per a aquest estudi s’ha utilitzat el test de la inversió del tub, microscòpia electrònica, dicroisme circular i càlculs teòrics, suggerint que la agregació d’aquests nou compostos segueix una estructura helicoïdal. Finalment, els nous gelificadors s’han complexat amb alguns ions metàl·lics, però els complexos resultants no son capaços de gelificar cap dissolvent. Aquests resultats confirmen que el disseny racional de metal·logelificadors és un gran repte.
2) Diferents tripètids hídrids que contenen dos unitats de prolina i un aminoàcid ciclobutànic s’han sintetitzat i estudiat com a organocatalitzadors per a la reacció aldòlica. Notablement, la enantioselectivitat de la reacció aldòlica va ser invertida en la presència d’aigua. Els resultats s’han racionalitzat amb estudis conformacionals i mecanístics utilitzant RMN, dicroisme circular i càlculs teòrics. Els rendiments gairebé quantitatius i les bones enantioselectivitats aconseguides confereixen a aquests pèptids amb propietats interessants ha ser utilitzats en reaccions aldòliques i a ser estudiats més profundament en altres processos químics.
3) Dos nous lligands que contenen una diamina ciclobutànica s’han sintetitzat i complexat amb diferents ions metàl·lics paramagnètics. La estabilitat termodinàmica, la inertesa cinètica i el numero de hidratació d’aquests complexos s’ha investigat utilitzant diferent tècniques. Finalment, s’han estudiat com a potencials agents de contrast per a ressonància magnètica d’imatge utilitzant diferent metodologies de RMN. Globalment, els resultats suggereixen que un d’ells es un bon candidat per ser utilitzat clínicament.In this thesis, different systems containing a cyclobutane-based scaffold were synthesized and studied as gelators, catalysts or contrast agents. Results of this thesis are divided in three chapters. 1) Two peptide-based low molecular weight gelators previously studied in our group were functionalized with a terpyridine derivative. The influence of this added moiety was determined in the final gelation behavior. This study was performed by tube inversion test, scanning electron microscopy, circular dichroism and theoretical calculations, suggesting that the aggregation of both compound followed a helical-like structure. These new gelators were complexed with some metal ions in order to obtain metallogelators, but the obtained complexes were not able to gelate any solvent, confirming that the rational design of metallogelators is still a big challenge. 2) Different new hybrid tripeptides containing two proline units and a cyclobutane-based amino acid were synthesized and studied as organocatalysts for aldol reactions. Noteworthy, the enantioselectivity in aldol reactions was reversed in the presence of water. Results were rationalized by conformational and mechanistic studies using NMR, circular dichroism and theoretical calculations. The almost quantitative yields and good enantioselectivities achieved under easy reaction conditions, confers these peptide catalysts with interesting properties to be employed in aldol reactions and to be further explored in other chemical processes. 3) Two new linear ligands containing a cyclobutane-based diamine were synthesized and complexed with different paramagnetic metal ions. The thermodynamic stability, kinetic inertness, and the hydration number of these complexes were investigated using different techniques. They were studied as potential contrast agents for magnetic resonance imaging (MRI) using different NMR methodologies. Overall, results suggested that one of them is a good and safe candidate to be used as contrast agent for clinical MRI.
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Kaplan, Matthew Jon. "Chiral Phosphoric Acid-Catalyzed Acetalization and Iso-Pictet-Spengler Reactions." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4515.
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The development of novel asymmetric reaction methodologies has been invaluable in both the academic and industrial world. In just 15 years, organocatalysis has provided a new means of developing asymmetric reaction methodologies using catalysts that are environmentally benign, relatively inexpensive, bench stable, and non-toxic. One development in organocatalysis that is important to our group in particular is chiral phosphoric acid-catalysis. BINOL-derived and VAPOL-derived phosphoric acids have proven to be excellent catalysts for a number of reactions.
The two projects I will discuss my efforts on are acetalization and iso-Pictet-Spengler reactions. These were projects that I performed during my first two years as a graduate student. The acetalization was particularly fascinating as only one literature report existed for the catalytic asymmetric variant of a reaction that makes such important compounds--O,O-acetals. The acetalization reaction proved to be a formidable opponent, and to this date no research report has been published documenting the intra-, or intermolecular catalytic asymmetric acetalization of vinyl ethers or the intermolecular catalytic asymmetric transacetalization.
The iso-Pictet-Spengler reaction is one that is interesting because exhaustive research has been conducted into the development of catalytic asymmetric Pictet-Spengler reactions, but at the time of my research, not a single catalytic asymmetric method existed to synthesize tetrahydro-γ-carbolines, the product of the iso-Pictet-Spengler reaction. Structurally, the tetrahydro-γ-carboline is isomeric to the tetrahydro-β-carboline, the product of the Pictet-Spengler reaction. They differ only in the position of nitrogen in the annulated product. This reaction seemed attractive to investigate, since independent elegant reports by Professors Benjamin List, Henk Hiemstra, and Darren Dixon documented the excellent control over enantioselectivity that chiral phosphoric acid have in the Pictet-Spengler reaction. Concurrent with the beginning stages of this project, Professor Eric Jacobsen reported the enantioselective thiourea-catalyzed iso-Pictet-Spengler reaction. The results were very good but not as great as the Pictet-Spengler work he pioneered. Around the time this report came out I commenced my reaction studies, and this thesis is the sum of just two projects I worked on. There were many more including halolactonization, VAPOL synthesis, chiral phosphoric acid synthesis, catalytic asymmetric hydroamination, and others.
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Schäfer, Philipp. "Enantioselective synthesis of chiral building blocks with non-stabilized nucleophiles." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:d69d1861-5368-495a-932d-7e1aa6bc5dfb.
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This thesis describes the combination of non-stabilized nucleophiles and prochiral/racemic electrophiles in transition metal catalyzed asymmetric transformations. These enantioselective reactions have tremendous potential for the formation of chiral building blocks and new structural motifs that can be found in a variety of natural products and their derivatives. The first part of the thesis focuses on the synthetic approach towards anti-cancer active diterpenoid structures. The two key steps involve a Cu-catalyzed asymmetric conjugate addition of alkylzirconocenes to enones and an intramolecular oxidative cyclisation. Particular investigations into the cyclisation are made with organocatalysis, transition metal catalysis and electrochemistry for the formation of these tricyclic scaffolds. In the second part this work builds on the Rh-catalyzed asymmetric Suzuki-Miyaura coupling of benzeneboronic acids and cyclic allyl chlorides, which has been developed in our group. Here, the main point is to use more challenging coupling partners, such as heteroaromatic boronic acids, which are coupled to racemic cyclic allyl halides. The utility of this method is demonstrated by performing further transformations and an asymmetric synthesis of the natural product (+)- isoanabasine. The last chapter describes the development of a new asymmetric Hiyama coupling of arylsiloxanes with racemic cyclic allyl chloride. Attempts are made to generate substrates that are not accessible via the asymmetric Suzuki - Miyaura reaction. After extensive optimisation a variety of arylsiloxanes is generated and tested with the best conditions to prove its utility in comparison to the asymmetric Suzuki-Miyaura coupling.
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Friedlein, Florian Karl. "New concepts for enantioselective organocatalysis and transition-metal catalysis chiral-at-rhenium donor ligands as design elements /." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=979598354.
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Turockin, Aleksej [Verfasser]. "Applications of guanidines as novel multifunctional organocatalysts and studies of new synthetic routes towards chiral bicyclic guanidinium salts / Aleksej Turockin." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/1059797615/34.
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Pair, Etienne. "De l'acide de Meldrum aux hétérocycles chiraux azotés d'intérêt biologiqie potentiel : synthèse domino organocatalysée de pyrazolidinones, pyrimidinones et isoxazolidinones." Thesis, Rouen, INSA, 2015. http://www.theses.fr/2015ISAM0009/document.
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Dans le cadre de cette thèse, nous nous sommes tournés vers l'utilisation de l'acide de Meldrum en tant que plateforme pour la synthèse d'hétérocycles chiraux par organocatalyse. De nouvelles voies d'accès, diastéréo- et/ou énantiosélectives, à des pyrazolidinones, pyrimidinones et isoxazolidinones ont été mises au point, via une réaction domino de type Knoevenagel/aza Michael/Cyclocondensation. La problématique du contrôle de la stéréochimie au sein de ces molécules a été d'autant plus étudiée que ce type de structures peut être retrouvé dans des composés d'intérêt biologique. Un intérêt tout particulier a été porté à l'étude des mécanismes réactionnels. Notamment dans le cadre d'une collaboration entre notre groupe et l'équipe « Analyse et Modélisation » du laboratoire COBRA pour l'étude de la réaction d'annélation [3+2] entre l'acide de Meldrum et des nitrones, par spectrométrie de masseIn the course of this thesis, we focused our efforts on developing the use of Meldrum's acid as a platform for the organocatalyzed synthesis of chiral heterocycles. In the end, we managed to access various pyrazolidinone, pyrimidinone and isoxazolidinone moieties in a diastero- and/or enantioselective fashion. We found these reactions to proceed via a navel domino Knoevenagel/aza Michael/Cyclocondensation reaction. The stereocontrol issue was particularly studied, as our final compounds can be found as part of biologically relevant structures. We also put much effort in probing reaction mechanisms. In the latter, we worked in collaboration with the "Analyse et Modélisation" team of laboratoire COBRA to get insights on the [3+2] annulation reaction between Meldrum's and nitrones, using mass spectrometry
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Yazicioglu, Emre Yusuf. "Development Of Novel Asymmetric Catalysts For Various Transformations And Investigation Of A Rearrangement Reaction." Phd thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612536/index.pdf.
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A new class of pyridine and sulfur containing chiral compounds are synthesized. Camphor sulfonyl chloride is chosen as a valuable chiral starting compound. In our synthetic strategy, sulfonylchloride moiety is first reduced to corresponding thiol compound by using triphenylphosphine and then the resultant thiol will be converted to various alkyl, aryl substituted derivatives. The second part of our strategy includes the pyridine ring construction on the carbonyl side of camphor with the formation of &beta-hydroxymethylene moiety followed by further reaction with various enamines. The resultant chiral ligands are characterized and used as a chiral ligand in asymmetric transfer of hydrogenation. Also novel class of organocatalysts synthesized from C2-symmetrical chiral diamine backbones and halopyridine derivatives are also synthesized and tested for their performance in kinetic resolution of racemic secondary alcohols. Also, a base mediated aromatization reaction is investigated in terms of both scope and mechanism.
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Liang, Tao. "Chiral Phosphoric Acids and Alkaline Earth Metal Phosphates Chemistry." Thesis, University of South Florida, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3632228.
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Asymmetric synthesis and catalysis is one of the leading research areas in chemistry society, for its versatility and efficiency in obtaining chiral molecules that found the vast majority in natural active compounds and synthetic drugs. Developing asymmetric catalytic methodology is at the frontier in both industrial and academic research laboratories. Enantioselective organocatalysis has emerged as a powerful synthetic tool that is complementary to metal-catalyzed transformations. The development of chiral phosphoric acid and metal phosphate as catalysts has been a breakthrough in recent years. Chiral phosphoric acids have been shown to be powerful catalysts in many organic transformations. Moreover, chiral metal phosphates, which formed by simply replacing the proton in phosphoric acid with metals, have introduced new catalytic activations and broaden the scope of phosphoric acids. This thesis details new highly enantioselective chiral phosphoric acid-catalyzed Pinacol rearrangement and robust alkaline phosphates catalytic system, which utilizes novel carbonyl activation.
The Pinacol rearrangement has long been known to be difficult to control in terms of regioselectivity and stereoselectivity. The initial studies found that indolyl-diol compounds can be treated with chiral phosphoric acids to afford the Pinacol rearrangement with high regio- and enantioselectivity. Over 16 chiral phosphoric acids were screened, and it was found an H8-BINOL-phosphoric acid variant with 1-naphthyl groups at 3 and 3' position was the excellent catalyst. This asymmetric transformation is tolerant toward variety of substituents both on the indole ring and migrating groups.
During the study, it was found that different ways to generate the catalyst had critical effect on this catalytic transformation. Only those phosphoric acids washed with HCl after column chromatography afforded the rearrangement products with high enantioselectivity. And those without treating with HCl were found contaminated by alkaline metals. These "contamination" catalysts were also found active with carbonyl activations.
A highly enantioselective catalytic hetero-Diels-Alder reaction of alpha-keto esters has been developed with chiral alkaline metal phosphates. A calcium 1-naphthyl-BINOL phosphate was found to be the optimum catalyst. A large range of alpha-keto esters as well as isatins can be applied in this alkaline phosphates catalytic system with high efficiency and selectivity. The structure of the catalyst is detailed for the first time by X-ray crystal structure analysis. A proposed Transition state model is provided based on the catalyst crystal structure and Raman spectroscopy analysis.
This methodology was further developed with an asymmetric Mukaiyama-Michael addition of beta,gamma-unsaturated alpha-keto ester. The best catalyst was found to be a magnesium chiral phosphate. And the transformation was found capable of tolerating a wide variety of beta,gamma-unsaturated alpha-keto esters.
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Nimmagadda, Sri Krishna. "Asymmetric Transformations Catalyzed By Chiral BINOL Alkaline Earth Metal Phosphate Complexes." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6554.
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Small molecule hydrogen bond donors have emerged as versatile catalysts in asymmetric synthesis. Within this class, chiral BINOL phosphoric acid is regarded as one of the pioneer catalysts used in several asymmetric transformations. The ability of the catalyst to activate the substrates could be controlled in two different ways. (1) Dual activation/bifunctional activation of substrate by hydrogen bond interactions or ion pairing with phosphoric acid or (2) By forming chiral BINOL phosphate metal complex that could significantly alter the interactions in chiral space. In particular, chiral alkaline earth metal phosphate complexes have unique advantages as catalysts owing to the ubiquitous availability of alkaline earth metals, strong Brønsted basicity of their counterions, mild but significant Lewis acidity of the metal and their ability to coordinate at multiple reactive sites due to large ionic radius.
Chapter 1 summarizes the recent development of alkaline earth metal complexes in asymmetric catalysis. My thesis dissertation is focused on the application of chiral alkaline earth metal phosphate complexes in novel asymmetric reactions.
In Chapter 2, we disclosed an efficient asymmetric one-pot synthesis of chiral 1,3-oxazolidines and chiral 1,3-oxazinanes. Chiral oxazolidines and oxazinanes are widely used as auxiliaries in asymmetric transition metal catalysis and also key structural motifs in natural products with biological activities. We developed a new synthetic method for chiral 1,3-oxazolidines which follows the enantioselective addition of alcohols to imines catalyzed by chiral 3,3’-(triisopropylphenyl)-derived BINOL magnesium phosphate to form hemiaminal intermediate, which then undergoes mild base mediated intramolecular nucleophilic substitution to afford highly enantioselective 1,3-oxazolidines and 1,3-oxazinanes in good yields.
In Chapter 3, we developed the first catalytic enantioselective desymmetrization process for the synthesis of novel axially chiral cyclohexylidene oxime ethers. Even though these molecules were found to be optically active in 1910, methods to synthesize these molecules are scarce. We have developed an efficient desymmetrization process of 4-phenyl cyclohexanones with phenoxyamines catalyzed by chiral BINOL strontium phosphate complex to afford highly enantioselective products. We then extended this methodology to the dynamic kinetic resolution of 2-substituted cyclohexanones to form chiral 2-substituted cyclohexyl oximes in good enantioselectivities, as demonstrated in Chapter 4. We further demonstrated the utility of these compounds by converting them to chiral 2-aryl cyclohexylamines which are important synthetic intermediates.
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Pham, Hoai Thu. "New approaches to functionalized dihydropyridines and application in cycloaddition." Caen, 2014. http://www.theses.fr/2014CAEN2042.
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Les systèmes cycliques incorporant des azotes sont des éléments clés d’une vaste gamme de composés naturels biologiquement actifs, et sont également souvent intégrés dans des structures privilégiées par les chimistes médicinaux. Par conséquent, de nouvelles voies de synthèse rapides et stéréosélectives permettant d’accéder à ces dérivés font l’objet d’un intérêt croissant. Parmi les différentes approches pour atteindre ces composés, la réaction d’organocatalyse asymétrique à plusieurs composants s’est révélée être un outil puissant. Les organocatalyseurs ne contiennent pas de métaux, sont stables dans une large gamme de conditions réactionnelles et sont insensibles à l'humidité. Dans cette thèse, nous présentons nos derniers développements sur la synthèse des dihydropyridines asymétriques par une réaction entre des aldéhydes α,β-insaturés et des enaminoesters. Les catalyseurs employés dans ces réactions sont des dérivés de type proline et des sels de phosphate chiraux. Dans ce travail, nous avons démontré que les 1,4- et les 1,2-dihydropyridines pouvaient être préparées avec de bons rendements, et des régio- et stéréosélectivités allant de moyennes à hautes. L’étendue et les limites de ce processus ont également été définies. Les DHP ont ensuite été engagées dans des réactions de cycloaddition visant à synthétiser des piperidines fonctionnalisées. Nous nous sommes efforcés de contrôler l’ensemble des centres stéréogéniques à travers des transformations diastéréosélectives. Les DHP ont été étudiées en tant que diènes ou diénophiles sous activation thermique, à haute pression, par micro-ondes ou par catalyse avec des acides de Lewis. La richesse électronique des DHP a été montrée en présence d'acroléine, agissant comme un heterodiene, et de l’organocatalyseur de MacMillan. Un mécanisme multiétape a été proposé pour expliquer la formation de produits d'addition. Ce nouveau type de réactivité ouvre la voie à de nouvelles méthodes de fonctionnalisation et de synthèse de composés polycycliquesNitrogen containing ring systems are key structural elements in a vast array of natural products as well as in a large class of biologically active natural products, being also often embedded within scaffolds recognized as privileged structures by medicinal chemists. Accordingly, new efficient and stereoselective (when possible) routes to these derivatives are of widespread interest. Among the approaches to these compounds, the organocatalyzed asymmetric multicomponent reaction has emerged as a powerful tool. Nowadays, organocatalysis is a powerful tool in enantioselective synthesis. These catalysts do not contain any metals; they are stable under a large set of reaction conditions and are moisture insensitive. In this thesis, we report our latest developments on the synthesis of non symmetrical dihydropyridines via a reaction between α,β-unsaturated aldehydes and enaminoesters. As catalysts, we used proline type derivatives and chiral phosphate salts. In this work, we demonstrated that 1,4- and 1,2-dihydropyridines could be prepared in good yields, moderate to high regio- and stereoselectivities. The scope and limitation of this process were also defined. Then, the DHPs were engaged in cycloaddition reactions to synthesize functionalized piperidines. With such sequence, we endeavoured to control all the stereogenic centres through highly diastereoselective transformations. DHPs were studied in cycloaddition reactions as dienophiles or dienes under thermal, high pressure, microwave activation or Lewis acid catalysis. The electron-rich dienophilicity of DHPs has been proven in the presence of acrolein, acting as an heterodiene, and MacMillan organocatalyst. A stepwise mechanism is proposed to account for the formation of the adducts. This new type of reactivity opens the way to new functionalization and new types of polycyclic compounds