L'isosorbide est un dianhydrohexitol chiral obtenu énantiomériquement pur par double déshydratation du sorbitol, un des produits majoritaires de l'industrie amidonnière résultant de l'hydrogénation du glucose. L'intérêt croissant pour l'isosorbide ces deux dernières décennies s'explique notamment grâce à sa production industrielle par des entreprises comme Roquette (20 000 tonnes par an). Cette disponibilité a permis la valorisation de l isosorbide dans divers domaines : polymères (polyéthylène isosorbide téréphtalate), tensioactifs, solvants (diméthyl isosorbide) et pharmaceutique (isosorbide dinitrate). Les propriétés de l'isosorbide ont ouvert la voie à des applications en induction chirale comme ligand, auxiliaire ou catalyseur par transfert de phase. D'autres isohexides (isomannide et isoidide) ont été moins étudiés. Leur structure conformationnelle rigide offre une grande diversité de modifications afin de moduler leurs propriétés électroniques et stériques. Les isohexides sont des candidats prometteurs pour le développement d'organocatalyseurs biosourcés. Très récemment, l'alkylation énantiosélective d'indole catalysée par des dérivés thiourées basées sur le squelette isohexide a été décrite. Au cours de cette thèse, la fonctionnalisation des isohexides en dérivés aminés est rapportée. La synthèse d'une première série d'amino-alcools, amino-éthers et diamines est décrite. Une seconde génération d'α-amino-amides et 1,2-diamines est obtenue par amidation. Ces dérivés aminés sont engagés comme organocatalyseurs dans la synthèse asymétrique de la warfarine (avec des résultats atteignant 20% de rendement et 28% d'e.e.) et l'aldolisation de l'isatine (jusqu'à 73% de rendement et 33% d'e.e.) / Isosorbide is a chiral dianhydrohexitol obtained in enantiomerically pure form by double dehydration of sorbitol, a major product of the starch industry resulting from hydrogenation of glucose. Isosorbide has been increasingly studied these last twenty years, mainly thanks to industrial companies, such as Roquette (France) that implemented the production to 20,000 tons a year. This availability allowed the promotion of isosorbide applications in various fields: polymers (polyethylene isosorbide terephthalate), surfactants, solvents (dimethyl isosorbide) and pharmacy (isosorbide dinitrate). Isosorbide structural properties opened its investigation as a chiral inducer either as a ligand, an auxiliary or a phase transfer catalyst. Other isohexides (isomannide, isoidide) were much less studied. These diastereomeric conformationally rigid structures offer a large diversity of functionalizations to tune their electronic and steric properties. Isohexides are promising candidates for the development of biosourced organocatalysts. Very recently, Friedel-Crafts enantioselective alkylation of indole mediated by thiourea organocatalysts derived from isohexides has been described. In this thesis, the functionalization of isohexides into amino derivatives is reported. A first serie of amino-alcohols, amino-ethers and diamines is reported. A second generation of α-amino amides and 1,2-diamines is then obtained via amidation. These nitrogenfunctionalized derivatives are screened as organocatalysts for the asymmetric synthesis of warfarin (with results up to 20% of yield and 28% of e.e.) and for isatin aldolisation (with results up to 73% of yield and 33% of e.e.)

In der vorliegenden Dissertation konnten erfolgreich neben der Entwicklung und Optimierung neuer Methoden in der Kettenverlängerung von Aldosen und Ketosen auch neue Farbstoffe zur Untersuchung von Protonierungs- und Wasserdynamiken designt und synthetisiert werden. Die Erweiterung des Verständnisses im Zusammenspiel von Aminosäuren und Kohlenhydraten hat einen großen Einfluss in der wissenschaftlichen Gesellschaft der Kohlenhydratchemie. Die Kontrolle im Aufbau von Stereotetraden und -pentaden führt zu einer Ausweitung der bekannten Möglichkeiten in der stereoselektiven Synthese von Naturstoffen und Biomimetika. Außerdem konnten durch eine einfache Methode die C-Glykoside seltener Kohlenhydrate dargestellt werden. Einbau von Aminosäuren in Kohlenhydratstrukturen konnten in hohen Stereoselektivitäten und der Möglichkeit der Stereomanipulation durch Wahl des Isocyanides erreicht werden. Die Synthese des zellgängigen Farbstoffes PAc-SNARF, sowie des Biolinkers IA-SNARF ermöglicht eine bildgebenden ratiometrischen pH-Untersuchungen in Zellen und auf Proteinoberflächen. Die Verallgemeinerung der Synthese der Farbstoff-Precursor für die SNARF-Derivate über eine Friedel-Crafts-Acylierung erlaubt eine kostengünstige Darstellung einer großen Bandbreite von Farbstoffen. Mithilfe der neu synthetisierten sterisch anspruchsvollen N-Methyl-6-oxychinoliniumbetain-Derivate verbunden mit der Fluoreszenzaufkonvertierungs-Spektroskopie konnte eine Verlangsamung von Wasser an hydrophoben Oberflächen bewiesen werden. Die gesammelten Ergebnisse und Erkenntnisse in diesen verschiedenen Themengebieten werden in Zukunft einen großen Einfluss in der Wissenschaftswelt haben. / In the presented dissertation new methods in the chain elongation of carbohydrates could be established and optimized. Besides that, new probes for the investigation of protonation and water dynamics could be designed and synthesized. The extension of comprehension in the interaction between amino acids and carbohydrates through hydrogen bonds has a great impact in the scientific community of carbohydrate research. The stereochemical control in the construction of stereotetrads and –pentads leads to a considerable extension of known methods in the synthesis of natural compounds and biomimetics. Additionally the C-glycosides of rare carbohydrates could be synthesized through simple methods. Installation of amino acids into carbohydrate structures could be achieved with very high stereoselectivity and the potential of manipulating the stereochemical course through the choice of different isocyanides. The synthesis of the cell permeable PAc-SNARF and the cysteine-bioapplicable IA-SNARF allow the ratiometric pH-imaging of cells and protein surfaces. The generalization of the synthesis of dye-precursors for SNARF-derivatives through friedel-crafts-acylation allow an inexpensive approach in synthesizing a broad spectrum of dyes. Through deployment of newly developed sterical demanding N-Methyl-6-oxyquinolinium betaine-derivates together with the fluorescence upconversion spectroscopy a deceleration of water reorientation near hydrophobic surfaces could be proven. The here summarized results and insights in the different topics will have a considerable influence in academic sciences.

No description available.

No description available.

Ziel der Arbeit war es, Katalysatoren zu entwickeln, in Modellsystemen zu testen und Rückschlüsse auf deren Aktivität und Verbesserungspotential zu ziehen. Dabei standen sowohl theoretische Betrachtungen mittels quantenmechanischer Berechnungen, aber auch experimentelle Arbeiten im Mittelpunkt. Die Untersuchungen wurden an ausgewählten Beispielen der Claisen-Umlagerung und der Morita-Baylis-Hillmann-Reaktion sowie verbrückter Bis(NHC)metallkomplexe auf der Basis von Triazolen in der Mizoroki-Heck-Reaktion durchgeführt. Claisen-Umlagerung. Die Wechselwirkung zwischen Substrat und dem Katalysator sollte hierbei auf eine bidendate Ausbildung von Wasserstoffbrücken zum Substrat entsprechend dem Design nach Jørgensen[1-4] abzielen. Die Auswahl der „Organokatalysatoren“ erstreckte sich von den Thioharnstoffen, über L-Milchsäure, einem Phosphorsäure-Derivat bis hin zu 2,2,2-Trifluorethanol (TFE). Mit dem Allyl Vinyl Ether (AVE) 83 wurden die theoretischen Betrachtungen der Wechselwirkung und der sich daraus ergebende Einfluss auf die Umlagerungs-geschwindigkeit durchgeführt. Der Thioharnstoff 1 und dessen Wechselwirkung mit 83 standen dabei im Mittelpunkt der Betrachtungen. Es wurden zwei mögliche entscheidende Übergangszustände postuliert. Im Vergleich zum konkurrierenden Übergangszustand [s-cis-83b•1A]# war [s-trans-83b•1A]# in Summe bevorzugt. Gegenüber der thermischen Claisen-Umlagerung von 83 war [s-trans-83b•1A]# für ΔG#[3,3] um +3,1 Kcal mol-1 erniedrigt, was einer leichten Erhöhung der Umlagerungsgeschwindigkeit entsprach. Dies konnte durch experimentelle Untersuchungen bestätigt werden. Das Phosphorsäure-Derivat 94 war im Vergleich zur L-Milchsäure 91 besser in der Lage, die Barriere des sigmatropen Umlagerungsschrittes abzusenken. Es zeigte sich, dass die Kombination von 91 mit einem Wassermolekül 8 zu dem Komplex 92 zu einer verbesserten Stabilisierung des Übergangszustandes führte. Bei beiden Systemen wurde jedoch beobachtet, dass die Barrieren über den Gesamtverlauf der Reaktion nicht ausreichend stark abgesenkt werden konnten. Für die Berechnungen mit dem Lösungsmittel TFE wurde gezeigt, dass die Betrachtung der Wechselwirkung einzelner TFE-Moleküle mit dem Substrat 83 nicht ausreichte. Morita-Baylis-Hillman-Reaktion. Mit der Morita-Baylis-Hillman-Reaktion[5, 6] (MBH) kann im Sinne einer C-C-Verknüpfungs-reaktion neben der atomökonomischen Durchführung zusätzlich ein Stereozentrum erzeugt werden. Basierend auf den Ergebnissen von Cheng et al.[7] wurde ein systematischer Zusammenhang zwischen dem eingesetzen Vermittler/Katalysator und Ausbeute/Umsatz hergestellt. Die aus der Literatur bekannte pH-Wert-Abhängigkeit der Reaktion konnte auf einen Bereich zwischen 8 und 9 eingegrenzt werden. Unter Verwendung verschiedener Substitutionsmuster am Imidazol konnte gezeigt werden, dass 1H-substituierte Imidazole die Reaktion wesentlich langsamer als die in 1-Position unsubstituierten Imidazole vermittelten, was durch DFT-Rechnungen unterstrichen werden konnte. Im weiteren Verlauf der experimentellen Untersuchungen stellte sich heraus, dass TFE als Lösungsmittel ohne Zusatz einer weiteren Base für die Vermittlung der Reaktion gut geeignet ist. Verbrückte Bis(NHC)metallkomplexe auf der Basis von Triazolen. Die Synthese der Bis(NHC)metallkomplexe und deren Einsatz in der Katalyse wurde von Straßner et al.[8-15] sehr intensiv studiert. Teil dieser Arbeit war es, die Bandbreite der Katalysatoren zu erweitern und den Einfluss von einem Stickstoffatom im (NHC)-Rückgrat zu untersuchen. Die synthetische Zugänglichkeit der Konstitutionsisomere wurde bereits bei der Darstellung der aromatischen Triazole gewährleistet. Die sich anschließende Darstellung der entsprechenden Salze konnte für die Methoxy-Gruppe am Aromaten erfolgreich durchgeführt werden. Die Unterscheidung von Konstitutionsisomeren eines Komplexes wurde am Beispiel von 126 und 128 durchgeführt. Hierbei zeigten sich bereits im 1H-NMR-Spektrum feine Unterschiede in den Kopplungskonstanten und auch in den Signalen für die Methylenbrücke. Der tatsächliche Beweis wurde mit der 2D-Methode, der sogenannten „Heteronuclear Multiple Bond Correlation“ – HMBC, erbracht. Der Einsatz der dargestellten Palladium(II)komplexe zeigte für p-Bromacetophenon analoge Ergebnisse zu den Imidazol-Derivaten bei „gleicher“ Konzentration. Für die Komplexe, ausgehend von den asymmetrischen Triazolen (zum Beispiel 128), wurde eine erhöhte Reaktivität beobachtet. Weiterhin wurde ein signifikanter Unterschied in der Ausbeute bei Reaktionen mit p-Chloracetophenon beobachtet. Literatur. [1] D. L. Severance, W. L. Jorgensen, Journal of the American Chemical Society 1992, 114, 10966. [2] C. J. Cramer, D. G. Truhlar, Journal of the American Chemical Society 1992, 114, 8794. [3] W. L. Jorgensen, J. F. Blake, D. Lim, D. L. Severance, Journal of the Chemical Society, Faraday Transactions 1994, 90, 1727. [4] M. M. Davidson, I. H. Hillier, Journal of Physical Chemistry 1995, 99, 6748. [5] A. B. Baylis, M. E. D. Hillman, (Celanese Corp.). Application: DE DE, 1972, p. 16 pp. [6] K. Morita, Z. Suzuki, H. Hirose, Bulletin of the Chemical Society of Japan 1968, 41, 2815. [7] S. Luo, P. G. Wang, J.-P. Cheng, Journal of Organic Chemistry 2004, 69, 555. [8] S. Ahrens, A. Zeller, M. Taige, T. Strassner, Organometallics 2006, 25, 5409. [9] M. A. Taige, A. Zeller, S. Ahrens, S. Goutal, E. Herdtweck, T. Strassner, Journal of Organometallic Chemistry 2007, 692, 1519. [10] A. Meyer, T. Strassner, unpublished results 2010. [11] M. Taige, TU Dresden (Dresden), 2009. [12] S. Ahrens, E. Herdtweck, S. Goutal, T. Strassner, European Journal of Inorganic Chemistry 2006, 1268. [13] S. Ahrens, T. Strassner, Inorganica Chimica Acta 2006, 359, 4789. [14] T. Strassner, M. Muehlhofer, A. Zeller, E. Herdtweck, W. A. Herrmann, Journal of Organometallic Chemistry 2004, 689, 1418. [15] M. Muehlhofer, T. Strassner, W. A. Herrmann, Angewandte Chemie, International Edition 2002, 41, 1745.

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 interne. / The 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.

The thesis entitled “Controlling Stereochemistry at the Quaternary Center Using Bifunctional (Thio)urea Catalysis” is divided into five chapters. Chapter 1: Catalytic Enantioselective Construction of Quaternary Stereocenters through Direct Vinylogous Michael Addition of Deconjugated Butenolides to Nitroolefins The direct use of deconjugated butenolides in asymmetric C–C bond forming reaction is a powerful but challenging task because of the additional problem of regioselectivity along with the issues of diastereo- and enantioselectivity. In this chapter, a direct asymmetric vinylogous Michael addition of deconjugated butenolides to nitroolefins has been demonstrated for the construction of quaternary stereocenter at the γ-position of butenolides. A novel thiourea-based bifunctional organocatalyst, containing two elements of chirality, was synthesized starting from commercially available quinine and (S)-tert-leucine. Remarkably, the sense of stereoinduction in this process is dominated by the tert-leucine segment of the catalyst. Synthetically versatile & highly functionalized γ-butenolides with contiguous quaternary and tertiary stereocenters were synthesized stereoselectively. The reaction was found to be general and a wide range of nitroolefins, with both electron-rich and electron-deficient substituents, underwent smooth reaction under these mild conditions. Similarly, deconjugated butenolides, having various substituents at the γ-position were well tolerated under these reaction conditions and the products were obtained in excellent yields and with uniformly high diastereo- and enantioselectivities. Reference: Manna, M. S.; Kumar, V.; Mukherjee, S. Chem. Commun. 2012, 48, 5193–5195. Chapter 2: Catalytic Asymmetric Direct Vinylogous Michael Addition of Deconjugated Butenolides to Maleimides for the Construction of Quaternary Stereogenic Center In this chapter, a mild and operationally simple protocol for the direct vinylogous Michael addition of deconjugated butenolides to maleimides has been illustrated. Using bifunctional tertiary amino thiourea organocatalyst, derived from a ‘matched’ combination of trans-(1R,2R)-diaminocyclohexane (DACH) and (S)-tert-leucine, the Michael adducts were obtained in excellent yields and with good to high diastereoselectivities and outstanding enantioselectivities. Application of the corresponding diastereomeric catalyst indicated the dominance of the ‘DACH’ unit over the chiral side chain in determining the sense of stereoinduction. The practicality of this protocol is illustrated by substantial low catalyst loading (down to 5 mol%) and one-pot catalyst recycling. Based on the X-ray structure of the catalyst and observed stereochemistry of the Michael adduct, a stereochemical model is proposed which was further supported by additional experiment. Reference: Manna, M. S.; Mukherjee, S. Chem.–Eur. J. 2012, 18, 15277–15282. Chapter 3: Enantioselective Desymmetrization of Cyclopentenedione through Direct Catalytic Vinylogous Michael Addition of Deconjugated Butenolides Five-membered carbocycles containing one or more stereogenic centers on the ring are privileged structural motifs found in many biologically active natural and non-natural compounds. Among various methods for accessing these enantioenriched carbocyclic frameworks, desymmetrization of prochiral or meso-compounds through catalytic enantioselective transformations represents a powerful strategy. The biggest advantage of such asymmetric desymmetrization reactions lies in their ability in controlling stereochemistry remote from the reaction site. This chapter deals with a highly efficient desymmetrization protocol for 2,2-disubstituted cyclopentene-1,3-diones via direct vinylogous nucleophilic addition of deconjugated butenolides with the help of a tertiary amino thiourea bifunctional catalyst. In contrast to the existing desymmetrization protocols, this method represents a unique example where quaternary stereocenter is generated not only within the ring but also outside the cyclopentane ring. Densely functionalized products are obtained in excellent yields and with outstanding diastereo- and enantioselectivities. The robustness screening indicated that the reaction is highly tolerant to a variety of competing electrophiles and nucleophiles. The remarkable influence of the secondary catalyst site on the enantioselectivity points towards an intriguing mechanistic scenario. To the best of our knowledge, this is the first time such an effect is observed in the context of asymmetric catalysis. Reference: (1) Manna, M. S.; Mukherjee, S. Chem. Sci. 2014, 5, 1627–1633. (2) Manna, M. S.; Mukherjee, S. Org. Biomol. Chem. 2015, 13, 18–24. (Perspective) Chapter 4: Enantioselective Desymmetrization of Cyclopentenediones through Organocatalytic C(sp2)–H Alkylation Organic compounds are characterized by the presence of various C–H bonds. Functionalization of a specific C–H bond in a molecule with a selected atom or group are among the most straightforward and desirable synthetic transformations in organic chemistry. In this chapter, a simple protocol for the direct alkylation of olefinic C(sp2)–H bond has been developed, not only enantioselectively using an organocatalyst but more importantly without using any directing group. This alkylative desymmetrization of prochiral 2,2-disubstituted cyclopentene-1,3-diones is catalyzed by a dihydroquinine-based bifunctional urea derivative. Using easily accessible, inexpensive and air-stable nitroalkanes as the alkylating agent, this C(sp2)−H alkylation represents a near-ideal desymmetrization and delivers products containing an all-carbon quaternary stereogenic center in good to excellent yields and with high enantioselectivities. The mild reaction conditions allow for the introduction of various functionalized alkyl groups. The possibility of a second alkylation and its applications has also been demonstrated. This protocol is the first example of the use of nitroalkane as the alkyl source in an enantioselective transformation. It is expected that, these findings would have broader consequences and applications to other alkylative and related transformations. Reference: Manna, M. S.; Mukherjee, S. J. Am. Chem. Soc. 2015, 137, 130–133. (Highlighted in Synform 2015, 67–70) Chapter 5: Enantioselective Desymmetrization of Cyclopentenediones through Organocatalytic Formal C(sp2)–H Vinylation The development of catalytic enantioselective C(sp2)–H vinylation reactions remained relatively underexplored for a long time because of various challenges associated with it. As C(sp2)–H functionalization reactions do not generate any stereocenter at the reaction site, development of enantioselective C(sp2)−H functionalization must rely on desymmetrization of prochiral or meso-substrates. More important issue is the identification of a suitable directing group which can efficiently control the regioselectivity during the activation of C(sp2)−H bond. In this chapter, an efficient formal C(sp2)−H vinylation of prochiral 2,2-disubstituted cyclopentene-1,3-dione is developed without using any directing group. This formal C(sp2)−H vinylation of 2,2-disubstituted cyclopentene-1,3-dione is realized using a two-step operation: catalytic enantioselective Michael addition of deconjugated butenolides followed by a base mediated decarboxylation. The vinylated products, containing a remote all-carbon quaternary stereogenic center, are obtained in good yields and with good to high enantioselectivities. Synthetic utility of this protocol is demonstrated by converting the resulting chiral electron-deficient diene into various important building blocks. Significant erosion in enantioselectivity during the decarboxylation process was explained by a plausible mechanism, which was further supported by control experiments. Reference: Manna, M. S.; Sarkar, R.; Mukherjee, S. manuscript under preparation.

Made available in DSpace on 2015-05-14T13:21:17Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 2697470 bytes, checksum: 43857465b95f5bc745fef7fb91591233 (MD5) Previous issue date: 2012-08-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This study was performed in order to synthesize and evaluate a new chiral tertiary amine, (S)-2-hydroxypropanoate 2-N, N-dimetilaminoetila according to the concept of multifunctional catalyst, which allows one same molecule presents various characteristics such as Bronsted acid and Lewis base. Allied to the interests of organocatalysis of simplicity and low operating costs, resulting in products that do not have contaminants like metals, designed in order to be able to catalyze / promote the reaction of Morita-Baylis-Hillman (MBH). The synthesis was performed starting from cheap raw materials and good commercial availability, S-lactic acid and 2-N, Ndimetilaminoetan-1-ol in one step reaction (98%). Based on current mechanistic proposal of the MBH reaction, the mechanism of Cantillo and Kappe, we investigated the reaction conditions, where there is a hydrogen transfer in aprotic media and also in the presence of phenols as additives, checking the influence speeds, reaction yields and asymmetric induction. We investigated the reaction between pnitrobenzaldehyde and acrylonitrile as reaction MBH pattern, varying experimental conditions such as solvent, quantity of (S)-2-hydroxypropanoate 2-N, Ndimetilaminoetila time, temperature and addition of phenolic additives. In addition, a new method was developed for the separation of enantiomers for the racemic compound antiparasitic 2 - [Hydroxy (4-nitrophenyl) methyl] acrylonitrile by gas chromatography with high resolution capillary columns packed with chiral phases. Chemical yields were obtained 2 - [hydroxy (4-nitrophenyl) methyl] <1 to 98% and enantiomeric excesses up to 20.5%. Mechanistic aspects are discussed in this paper, based on the results and computations, using the theory DFT and QTAIM. / Este trabalho foi realizado com o intuito de sintetizar e avaliar uma nova amina terciária quiral, o (S)-2-hidroxipropanoato de 2-N,N-dimetilaminoetila de acordo ao conceito de catalisador multifuncional, o qual permite que uma mesma molécula apresente várias características como os de ácido de Bronsted e base de Lewis. Aliado aos interesses da organocatálise de simplicidade e baixo custo operacional, resultando em produtos que não apresentam metais como contaminantes, projetamos no intuito de ser capaz de catalisar/promover a reação de Morita-Baylis-Hilman (MBH). A síntese de foi efetuada a partir de matérias-primas baratas e de boa disponibilidade comercial; o ácido S-lático e o 2-N,Ndimetilaminoetan- 1-ol em uma etapa reacional (98%). Baseado na atual proposta mecanística da reação de MBH, o mecanismo de Cantillo e Kappe, foram investigados as condições reacionais, onde há a transferência de hidrogênio em meio aprótico e também na presença de fenóis como aditivos, verificando a influência nas velocidades, rendimentos de reação e indução assimétrica. Investigamos a reação entre o p-nitrobenzaldeído e a acrilonitrila como reação de MBH padrão, variando condições experimentais como: solvente, quantidade do(S)-2-hidroxipropanoato de 2-N,N-dimetilaminoetila, tempo, temperatura e adição de aditivos fenólicos. Em adição, foi desenvolvido um novo método de separação de enantiômeros para o composto racêmico antiparasitário 2-[Hidroxi(4-nitrofenil)metil] acrilonitrila via cromatografia gasosa com colunas capilares de alta resolução empacotadas por fases quirais. Foram obtidos rendimentos químicos do 2-[Hidroxi(4- nitrofenil)metil] <1 à 98% e excessos enantioméricos até 20,5%. Aspectos mecanísticos são discutidos neste trabalho, baseados nos resultados obtidos e em cálculos computacionais, usando a teoria DFT e QTAIM.

Bien que thermodynamiquement et cinétiquement stable, le dioxyde de carbone est une molécule qui peut être convertie en carbonates cycliques à cinq ou six atomes respectivement au départ d’époxydes ou d’oxétanes moyennant l’utilisation d’un catalyseur approprié. Ces carbonates cycliques sont utilisés comme solvants verts, électrolytes pour les batteries au lithium ou comme intermédiaires pour la synthèse de polymères. Cependant, les performances catalytiques doivent être améliorées en particulier pour lecouplage du CO2 avec les huiles végétales époxydées ou les oxétanes. Dans ce contexte, nous avons développé un nouveau catalyseur homogène bicomposant organique composé d’un sel d’ammonium jouant le rôle de catalyseur et d’un co-catalyseur fluoré simple ou double donneur de liaison hydrogène. Dans un premier temps, l’efficacité de ces nouveaux catalyseurs a été évaluée et optimisée pour le couplage entre un époxyde terminal et le CO2 via des études cinétiques par spectroscopie FTIR ou Raman in-situ sous pression. Ces études ont démontré que l’utilisation combinée de sels d’ammonium et d’alcools fluorés induit un effet synergique permettant la fixation rapide et sélective du CO2 sur les époxydes modèles et les huiles végétales époxydées dans des conditions douces et sans solvant. L’utilisation de cette plateforme catalytique performante a ensuite été exploitée pour la synthèse d’oligocarbonates hydroxyles téléchéliques au départ d’oxétanes nettement moins réactifs que les époxydes. Ces oligocarbonates ont finalement été valorisés pour la synthèse de polyuréthanes CO2-sourcés par extension de chaines en présence de diisocyanates. En complément de ces travaux, une compréhension fine des mécanismes réactionnels a été réalisée via calculs DFT qui ont mis en évidence que l’efficacité catalytique de ces catalyseurs était liée à la stabilisation multiple des intermédiaires et états de transition par liaisons hydrogènes. A ce jour, via une étude comparative, nous avons mis en évidence que ce système catalytique bicomposant constitue un des catalyseurs organiques les plus performants pour le couplage du CO2 et d’époxydes et le seul système organique permettant la conversion d’oxétanes en synthons d’intérêt. / Although it is a thermodynamically and kinetically stable molecule, carbon dioxide can beconverted into five- and six-membered cyclic carbonates by coupling with epoxides or oxetanes, respectively, using appropriate catalysts. Cyclic carbonates are used as green solvents, electrolytes for Liion batteries or intermediates for the synthesis of polymers. However, the catalytic performance must be further enhanced in particular for the coupling of CO2 with epoxidized vegetable oils or oxetanes. In this context, we developed a new highly efficient bicomponent homogeneous organocatalyst composed of anammonium salt as the catalyst and fluorinated single or double hydrogen bond donors as co-catalysts. First,a screening of onium-based catalysts and hydrogen-bond donors was performed. Performances of thecatalysts and optimization of the reaction was realized through detailed kinetics studies using in-situ FTIR/Raman spectroscopy under pressure. We demonstrated that fluorinated alcohols showed unexpected co-catalytic activity due to synergisms between the onium salt and fluorinated co-catalysts enabling the fast and selective addition of CO2 on to model epoxides and epoxidized vegetable oils under solvent-free and mild experimental conditions. The use of this powerful dual catalyst was then extended to the first organocatalytic coupling of CO2 with less reactive oxetanes to produce hydroxyl telechelic oligocarbonates that were used asprecursor of CO2-based polyurethanes by chain-extension with a diisocyanate. In addition, a fine comprehension of the mechanisms was investigated by DFT calculations highlighting that the co-catalytic performance of the onium salt/fluorinated alcohol binary catalyst arose from the strong stabilization of the intermediates and transitions states by hydrogen-bonding. To date, through comparative studies, we evidenced that this new catalyst is one

Cette thèse décrit la Chimie Covalente Dynamique (CCD) des échanges imine/imine, Knoevenagel/imine et Knoevenagel/Knoevenagel. La L-proline est un excellent organocatalyseur pour la formation de Bibliothèques Covalentes Dynamiques (BCDs). Cependant, l’interconversion entre des dérivées Knoevenagel de l’acide diméthylbarbiturique et des imines se déroule rapidement sans catalyseur. Une nouvelle classe de CCD basée sur des échanges par substitutions nucléophiles (SN2/SN2’) entre des sels d’ammonium quaternaires et des amines tertiaires est développée, impliquant la catalyse par l’iodure. Les réactions d’échange entre des sels de pyridinium et un dérivé de pyridine génèrent des liquides ioniques dynamiques. Enfin, la sélection cinétique et thermodynamique de la formation d’imines dans la CCD est réalisée en solution aqueuse e ten solvant organique. / This thesis describes the dynamic covalent chemistry (DCC) of imine/imine, Knoevenagel/imine, and Knoevenagel/Knoevenagel exchange. L-proline is shown to be an excellent organocatalyst to accelerate the formation of dynamic covalent libraries (DCLs). The interconversion between Knoevenagel derivatives of dimethylbarbituric acid and imines is found to occur rapidly in the absence of catalyst. A new class of DCC based on nucleophilic substitution (SN2/SN2’) component exchange between quaternary ammonium salts and tertiary amines is developed, by the use of iodide as a catalyst. The exchange reactions between pyridinium salts and a pyridine derivative generate dynamic ionic liquids. Finally, kinetic and thermodynamic selection of imine formation in a DCC is perfomed in aqueous solution and organic solvent.