Les molécules polycycliques, et notamment les éthers spirocycliques, sont des structures présentant un fort intérêt dans le domaine de la chimie des parfums. Cette thèse est dédiée au développement de nouvelles cycloisomérisations de dérivés d’éthers d’énol catalysées par le triflate de bismuth(III). Une étude bibliographique a ainsi été consacrée aux réactions de cyclisation catalysées par Bi(OTf)3. Une réaction de cycloisomérisation d’éthers d’énol alléniques permettant la formation rapide de produits cyclopenténiques et dihydrofuraniques a été développée. Des dérivés oxaspirocycliques ont été obtenus à partir de substrats trifonctionnels possédant un éther d’énol cyclique et une fonction alcool additionnelle. La chimiodivergence de ces réactions a été étudiée avec l’activation préférentielle de l’allène par des catalyseurs à base d’or(I) menant à d’autres structures cyclopenténiques. Une réaction de double cyclisation a été développée donnant un accès privilégié à des produits polycycliques pontés comportant un motif oxaspirocyclique. Des études mécanistiques ont été effectuées et une nouvelle cyclisation tandem impliquant un transfert d’hydrure-1,5 a été étudiée. La réaction de double cyclisation de dérivés du campholénal énantioenrichis a ensuite été développée pour la formation de bis-éthers tétracycliques et de cétones tricycliques. La plupart de ces nouveaux composés présentent des notes remarquables, principalement dans les familles olfactives aromatiques et boisées. / Polycyclic compounds and more specifically, spirocyclic ethers are of particular interest in fragrance chemistry. This thesis is dedicated to the development of new cycloisomerisations of enol ether derivatives by bismuth(III) triflate catalysis. In this way, a bibliographic study has been carried out on cyclisations catalysed by bismuth(III) triflate. A cycloisomerisation of allenic enol ethers has been developed for the straightforward synthesis of cyclopentene and dihydrofuran derivatives. New oxaspirocyclic compounds have been obtained starting from trifunctional substrates containing a cyclic enol ether and an additional hydroxyl group. The chemodivergence of this reaction has been studied by means of gold(I) catalysis to access different cyclopentenic structures via the preferential activation of the allene. A double cyclisation reaction has been developed leading to bridged polycyclic compounds featuring an oxaspirocyclic moiety. Mechanistic studies have been performed and a tandem cyclisation involving a 1,5-hydride shift has been studied. The double cyclisation of enantioenriched campholenic aldehyde derivatives has been investigated for the formation of tetracyclic diethers and tricyclic ketones. Most of the new compounds presented interesting notes, mainly in the aromatic and woody olfactory family.

No description available.

L’utilisation de méthodologies de synthèse toujours plus performantes et respectueuses de l’environnement est un axe de recherche majeur de la chimie moderne. L’apport de la catalyse, avec l’utilisation de superacides de Lewis, a permis d’améliorer de nombreux processus synthétiques. Nous avons pu développer dans ce manuscrit des réactions de cycloisomérisation de type réaction de Friedel-Crafts qui donnent accès à un ensemble de structures polycycliques intéressantes avec de bons rendements et sélectivités. L’utilisation d’une quantité catalytique, entre 1 et 10 mol% de Bi(OTf)3, permet l’activation d’oléfines et d’allènes non activés ainsi que de systèmes 1,3-diéniques. Ce type de méthodologie, à économie d’atomes maximale, a permis de limiter la formation de sous-produits, le catalyseur pouvant être recyclé et réutilisé sans perte d’activité. Des approches intra- et intermoléculaires, des réactions cascades et tandems ainsi qu’une étude mécanistique ont été effectuées afin de mieux comprendre la réactivité et ses limitations, et ainsi atteindre une plus large gamme de structures. Les méthodologies développées ont été appliquées au domaine des arômes et parfums pour la synthèse d’analogues de la Calone 1951®, de chromanes, d’indanes et de tétralines fonctionnalisés, posant les bases de travaux futurs pour une meilleur compréhension des relations structures-odeurs / Efficient and ecofriendly synthetic methodologies have always constituted an important area of research in modern organic chemistry. Lewis superacid catalysis has contributed in the improvement of many synthetic processes. We have developed some cycloisomerization reactions including Friedel-Crafts type reaction, giving access to a set of interesting polycyclic structures with good yields and selectivities. The use of a catalytic amount of Bi(OTf)3 (1 to 10 mol%), has allowed the activation of olefins, non-activated allenes and of 1,3-dienic systems. This atom economy methodology can prevent the formation of by-products and the catalyst can be recycled without loss of activity. Intra- and intermolecular approaches, tandem and cascades reactions, as well as mechanistic studies were conducted to enable a better understanding of the reactivity and its limitations to reach a wider range of structures. The developed methodologies were applied to the field of flavors and fragrances in the synthesis of Calone 1951® analogues, and for the preparation of chromans, indanes and tetralins type functionalized structures, for a better understanding of the structure/odor relationship.

<p>Crystallographic and spectroscopic studies have been performed of structures, coordination and chemical bonding for series of trivalent metal ions solvated by two oxygen-coordinating solvents, water and dimethyl sulfoxide (DMSO). The hydrated scandium(III) and lanthanoid(III) ions, La to Lu, are surrounded by tricapped trigonal prisms of aqua ligands in the isomorphous series of trifluoromethanesulfonates, [M(H₂O)_n](CF₃SO₃)₃. For the smallest ions, M = Er, Tm, Yb, Lu, Sc, the hydration numbers decrease, <i>n</i> = 8.96(5), 8.8(1), 8.7(1), 8.5(1), 8.0(1), respectively, with decreasing size of the ion. The crystal structures at ambient temperature indicate randomly distributed vacancies of the capping oxygen atoms, and ²H solid-state NMR of the diamagnetic [M(H₂O)_n](CF₃SO₃)₃, M = Sc, Lu, Y and La compounds revealed increasing mobility of the water ligands in the coordination sphere with increasing temperature, also for the fully nonahydrated La^III and Y^III ions. The stretching force constants of the Ln-O bonds, evaluated from vibrational spectroscopy, increased from 0.81 to 1.16 N cm^-1 for the Ln-6O trigonal prism in a smooth correlation with the bond distances from La to Lu. For the capping Ln-3O bonds the increase from 0.49 to 0.65 N cm^-1 reflects the increased ligand-ligand repulsion with decreasing ion size. This is also the reason for the water deficiency of the Er, Tm, Yb, Lu and Sc salts, and for [Sc(H₂O)_8.0](CF₃SO₃)₃ the repulsion induced a phase transition at about 185 K that, by low temperature crystallography, was found to distort the coordination of water molecules toward a monocapped trigonal prism around the scandium(III) ion.</p><p>All crystal structures of the octakis(dimethyl sulfoxide)lanthanoid(III) iodides comprise discrete [Ln(dmso)₈]³⁺ complexes surrounded by iodide ions. The lanthanum(III) and praseodymium(III) compounds crystallize in the orthorhombic space group <i>Pbca</i> with more efficient packing than for the heavier and smaller ions in the lanthanoid series, which crystallize in the monoclinic space group <i>P2</i>₁/<i>n</i>. The group 13 metal ions, aluminium(III), gallium(III), indium(III), thallium(III), and also scandium(III) of group 3, form crystalline hexakis(dimethyl sulfoxide) solvates in the space group <i>R</i> 3, with octahedral MO₆ coordination entities, which are increasingly compressed along one threefold axis for increasing ionic size. EXAFS measurements on the solvated ions display similar M-O bond distances in dimethyl sulfoxide solution as in the solid solvates. For all the solid dimethyl sulfoxide solvates the strength and nature of the metal-oxygen bond has been evaluated by normal coordinate analysis of vibrational spectra, and correlated with the S-O stretching vibrational mode.</p><p>Distortions from regular octahedral six coordination are discussed for the hydrated isoelectronic soft mercury(II) and thallium(III) ions in the solid bisaquamercury(II) and trisaquatallium(III) trifluoromethanesulfonates, in terms of pseudo Jahn-Teller effects (PJTE). Mercury(II), generally more strongly influenced by PJTE distortions, displays a 2 + 4 Hg-O coordination forming chains that are held together in sheets by hydrogen bonds and in layers by van der Waals interactions, which explain the fragile structure of the crystals.</p>

Crystallographic and spectroscopic studies have been performed of structures, coordination and chemical bonding for series of trivalent metal ions solvated by two oxygen-coordinating solvents, water and dimethyl sulfoxide (DMSO). The hydrated scandium(III) and lanthanoid(III) ions, La to Lu, are surrounded by tricapped trigonal prisms of aqua ligands in the isomorphous series of trifluoromethanesulfonates, [M(H2O)n](CF3SO3)3. For the smallest ions, M = Er, Tm, Yb, Lu, Sc, the hydration numbers decrease, n = 8.96(5), 8.8(1), 8.7(1), 8.5(1), 8.0(1), respectively, with decreasing size of the ion. The crystal structures at ambient temperature indicate randomly distributed vacancies of the capping oxygen atoms, and 2H solid-state NMR of the diamagnetic [M(H2O)n](CF3SO3)3, M = Sc, Lu, Y and La compounds revealed increasing mobility of the water ligands in the coordination sphere with increasing temperature, also for the fully nonahydrated LaIII and YIII ions. The stretching force constants of the Ln-O bonds, evaluated from vibrational spectroscopy, increased from 0.81 to 1.16 N cm-1 for the Ln-6O trigonal prism in a smooth correlation with the bond distances from La to Lu. For the capping Ln-3O bonds the increase from 0.49 to 0.65 N cm-1 reflects the increased ligand-ligand repulsion with decreasing ion size. This is also the reason for the water deficiency of the Er, Tm, Yb, Lu and Sc salts, and for [Sc(H2O)8.0](CF3SO3)3 the repulsion induced a phase transition at about 185 K that, by low temperature crystallography, was found to distort the coordination of water molecules toward a monocapped trigonal prism around the scandium(III) ion. All crystal structures of the octakis(dimethyl sulfoxide)lanthanoid(III) iodides comprise discrete [Ln(dmso)8]3+ complexes surrounded by iodide ions. The lanthanum(III) and praseodymium(III) compounds crystallize in the orthorhombic space group Pbca with more efficient packing than for the heavier and smaller ions in the lanthanoid series, which crystallize in the monoclinic space group P21/n. The group 13 metal ions, aluminium(III), gallium(III), indium(III), thallium(III), and also scandium(III) of group 3, form crystalline hexakis(dimethyl sulfoxide) solvates in the space group R 3, with octahedral MO6 coordination entities, which are increasingly compressed along one threefold axis for increasing ionic size. EXAFS measurements on the solvated ions display similar M-O bond distances in dimethyl sulfoxide solution as in the solid solvates. For all the solid dimethyl sulfoxide solvates the strength and nature of the metal-oxygen bond has been evaluated by normal coordinate analysis of vibrational spectra, and correlated with the S-O stretching vibrational mode. Distortions from regular octahedral six coordination are discussed for the hydrated isoelectronic soft mercury(II) and thallium(III) ions in the solid bisaquamercury(II) and trisaquatallium(III) trifluoromethanesulfonates, in terms of pseudo Jahn-Teller effects (PJTE). Mercury(II), generally more strongly influenced by PJTE distortions, displays a 2 + 4 Hg-O coordination forming chains that are held together in sheets by hydrogen bonds and in layers by van der Waals interactions, which explain the fragile structure of the crystals.

The thesis entitled “Studies on the Stereoselective Geminal and Vicinal Heterodifunctionalization of Alkenes” consists of three chapters. Chapter 1: Part A: Bromonium Ion Mediated Stereoselective Geminal Aminooxygenation of Vinylarenes In this part (part-A) of Chapter 1, the development and mechanistic studies of the first method for the non-Wacker intermolecular geminal aminooxygenation of vinylarenes (styrenes) has been presented (Scheme 1). Sheme 1 The role of the substituent on controlling the competitive vicinal and geminal addition pathways has been studied. It was found that the unsubstituted amino alcohol takes both the vicinal addition pathways, whereas, the introduction of substituent on the aminoalcohols was found to favour only the geminal addition route (Scheme 2). Scheme 2 The diastereomeric alkenes were found to show stereoconvergence on the product formation. The migration of the phenyl group in the semipinacol rearrangement was confirmed by deuterium labeling studies. This highly stereoselective oxidative geminal addition is found to involve a semipinacol rearrangement (Scheme 3). Scheme 3 Chapter 1: Part B: Bromonium Ion Mediated Stereoselective Anti-Markovnikov Geminal Diamination and Dioxygenation of Vinylarenes In this part (part-B) of Chapter 1, the development of a facile straightforward method for the stereoselective intermolecular geminal diamination of vinylarenes under the bromonium ion mediated conditions is discussed (Scheme 4). Scheme 4 The addition of unsubstituted diamine was found to follow both geminal and vicinal addition routes, while the introduction of the substituent on the diamine was found to favour only geminal addition (Scheme 5). Scheme 5 The stoichiometric geminal dioxygenation of vinylarenes using 1,2 and 1,3 -diols was also found to work well. The substituent on the nucleophile and the nucleophilicity of the heteroatom was found to control the competitive geminal and vicinal addition pathways. The stereoselectivity of geminal dioxygenation is dependent on the ring size of the product formed and on the position of the stereo-inducing substituent. Unlike the unsubstituted diamine and the unsubstituted aminoalcohol, irrespective of the substituents attached to it, the 1,2-diols furnished only the geminal addition product (Scheme 6). Scheme 6 Interestingly, the α-methyl substituted 1,3-diols provided the corresponding 2,4-disubstituted 1,3-dioxanes with very high stereoselectivity. The β-propyl substituted 1,3-diol gave the 2,5-disubstituted 1,3-dioxane as a mixture of diastereomers (Scheme 7). Scheme 7 The phenyl migration in the semi-pinacol rearrangement in the geminal addition process was confirmed from the deuterium labelling studies (Scheme 8). Scheme 8 Chapter 1: Part C: Straightforward Synthesis of 1,3-Dioxolan-4-ones through Geminal Difunctionalization of Vinylarenes The development of a straightforward method for the synthesis of important chiral synthon, 1,3-dioxolan-4-ones by the geminal addition of α-hydroxy carboxylic acids to vinylarenes has been presented in the final part of this chapter (part-C, Chapter 1) (Scheme 9). Scheme 9 The effect of substituents on the α-hydroxy carboxylic acid on controlling the stereoselectivity of the reaction has been studied. In the case of α-hydroxy carboxylic acid derived from isoleucine containing the chiral substituent at the α position, it exclusively forms a single diastereomer of the corresponding 1,3-dioxolan-4-one (Scheme 10). Scheme 10 The reactions of α-hydroxy carboxylic acids with styrenes containing a variety of substituents have been found to work well, including the styrenes containing the electron withdrawing groups and the β-substituted styrenes. The migration of the phenyl group in the semi-pinacol rearrangement in the geminal oxidative reaction has been confirmed by deuterium labelling studies (Scheme 11). Scheme 11 Simple carboxylic acids are found to form only the vicinal addition products on reaction with styrenes. However, the alcohols under the same conditions formed only the geminal addition product, thereby demonstrating the role of nucleophilicty of heteroatom being added that control the competitive vicinal and geminal addition pathways (Scheme 12 Scheme 12 Chapter 2: Reagent-Switch Controlled Metal-Free Geminal Difunctionalization of Vinylarenes In this Chapter, the development of two new methods for the geminal oxyamination of vinylarenes and the detailed studies to understand their mechanism are presented. A novel reagent-switch for the control of migrating group by controlling the two independent, distinct pathways of the two reagent systems has been reported for this geminal addition (Scheme 13). Scheme 13 We have developed the first general method for the geminal diamination of vinylarenes with excellent stereoselectivity mediated by a hypervalent iodine reagent (Scheme 14). Scheme 14 This method is also found to be very efficient for the stoichiometric metal-free geminal dioxygenation of vinylarenes (Scheme 15). Scheme 15 The substituent on the nucleophile and the nucleophilicity of the heteroatom was found to control the competitive geminal and vicinal addition pathways. Chapter 3: Studies on the Synthesis of Enantiopure Morpholine Derivatives Mediated by Dimethyl (Methylthio) Sulfonium Triflate (DMTST) In this chapter, the development of a sulfonium ion mediated cylco-etherification methodology for the construction of biologically important molecules such as morpholines, morpholine carboxylates and morpholine methylthio ethers in good yields under mild conditions using DMTST has been presented. This method was also found to work well for the synthesis of 1,4-oxazepane (Scheme 16). (For figures pl refer the abstract pdf file)

In this thesis, the discharge products formed at the cathode and the performance and cell chemistry of sodium-oxygen batteries have been studied. This was carried out using different NaOTf salt concentrations. The influence of different salt concentrations on sodium-oxygen batteries was investigated since it has been shown that increasing the salt concentration beyond conventional concentrations could result in advantages such as increased stability of the electrolytes towards decomposition, higher thermal stability and lower volatility. An increase in salt concentration has also been shown to influence the electrochemical potential window. The solubility of NaOTf was investigated in two different solvents, DME and diglyme. NaOTf was found to be more soluble in DME compared to diglyme but due to the volatile nature of DME, three different concentrations of NaOTf were prepared with diglyme as solvent. Experimentation involved discharging the batteries to either maximum or limited capacity. The discharge products were examined and characterized using XRD and SEM. The main discharge product was identified as sodium superoxide although sodium peroxide dihydrate was also identified in one battery. A trend of higher capacity and voltage plateaus with higher salt concentration was also found. The influence of trace amounts of water was suggested as one explanation as it works as a catalyst, promoting sodium superoxide cube growth due to improved transportation of superoxide. Another or contributing explanation could be a possible change in donor number with increased salt concentration, resulting in higher solubility and longer lifetime of superoxide, promoting the growth of sodium superoxide cubes.

Micelas são agregados coloidais formados por moléculas anfifílicas i.e., moléculas com uma região hidrofóbica e uma porção hidrofílica (surfactantes). Efeitos específicos de íons (EEIs) são observados em micelas iônicas, uma vez que as propriedades físico-químicas de agregado micelares, como tamanho e geometria, dependem da natureza do contra-íon. Diferentes ânions inorgânicos produzem alterações modestas nas propriedades de agregados micelares catiônicos, mas ânions orgânicos podem induzir efeitos mais pronunciados, como transições de forma do agregado ou separações de fase. Em sistemas micelares, os EEIs podem estar relacionados a: (a) diferenças na localização dos ânions nas micelas; (b) diferenças na hidratação micellar e de íons; e (c) possível formação de pares iônicos entre surfactantes e contra-íons na interface micelar. Diversos modelos foram desenvolvidos para descrever a formação e estabilidade de agregados micelares, considerando diferentes termos energéticos que possivelmente contribuem para a formação/estabilidade de micelas. Contudo, os termos descritos acima (a - c) geralmente não são incluídos nos modelos micelares. Assim, não deve ser possível predizer as propriedades de micelas catiônicas, usando os modelos atuais, caso o contra-íon seja pequeno, desidratado e capaz de formar pares iônicos, como o ânion trifluorometilsulfonato (triflato, Tf). Tendo isso em vista, determinamos as propriedades micelares de triflato de dodeciltrimetilamônio (DTATf) e comparamos com micelas análogas formadas por brometo, cloreto e metanosulfonato, visando identificar diferenças estruturais das micelas e suas origens. Para determinação de propriedades micelares, utilizamos uma série de técnicas experimentais: fluorescência resolvida no tempo, espalhamento de raio-X de baixo ângulo, condutometria, cinética química, ressonâncias paramagnética eletrônica e magnética nuclear e espectroscopia de relaxação dielétrica, entre outras. Observamos que o agregado de DTATf possui uma estrutura discoidal altamente empacotada, ordenada e desidratada e estas propriedades foram reproduzidos em simulações de dinâmica molecular. A análise do conjunto de resultados obtidos para DTATf demonstrou que a formação de pares iônicos na interface micelar induz severas alterações nas propriedades micelares, como a desidratação dos agregados. Os dados obtidos com DTATf demonstram claramente que, para um modelo teórico de sistemas micelares ser capaz de predizer propriedades micelares de diferentes agregados, a possibilidade de formação de pares iônicos na interface micelar e as interações específicas entre contra-íons e surfactantes devem ser modeladas. Adicionalmente, devido aos resultados aqui reportados e analisando outros sistemas interfaciais, propomos um papel mais fundamental para a água (interfacial ou de hidratação) nas propriedades micelares / Micelles are colloidal aggregates formed by amphiphilic monomers i.e., molecules with a hydrophobic and a hydrophilic moiety (surfactants). Specific ion effects (SIEs) are observed in cationic micelles, because the physicochemical properties of the micellar aggregates, such as size and shape, depend on the nature of the counterion. Different inorganic counterions lead to small changes in micellar properties of cationic aggregates, but organic counterions can induce more pronounced effects, such as shape transitions of the aggregates or phase separation. In micellar systems, the SIEs can be related with: (a) differences in the location of anions in micelles; (b) differences in the hydration of micelles and ions; and (c) possible ion-pair formation between surfactants and counterions at the micellar interface. Several models have been developed to describe the formation and stability of micellar aggregates, considering different energy terms that possibly contribute to the formation/stability of micelles. However, the terms described above (a - c) are generally not included in micellar models. Thus, it should not be possible to predict the properties of cationic micelles, using the current models, if the counterion is small, dehydrated and capable of forming ion-pairs, such as the trifluoromethylsulfonate anion (triflate, Tf). In this context, we have determined the micellar properties of dodecyltrimethylammonium triflate (DTATf) micelles and we have compared the results with similar micelles formed by bromide, chloride and methanesulfonate, aiming to identify their structural differences and its origins. To determine the micellar properties, we have used several techniques: time resolved fluorescence, small angle X-ray scattering, conductometry, kinetic assays, electron paramagnetic and nuclear magnetic resonances and dielectric relaxation spectroscopy, among others. We have observed that the DTATf aggregate presents a highly packed, ordered and dehydrated disk-like geometry and these properties were reproduced in molecular dynamics simulations. The analysis of the DTATf properties showed that the formation of ion-pairs at the micellar interface induces severe changes in micellar properties, such as micellar dehydration. The DTATf properties clearly demonstrate that for a theoretical model of micellar system to be accurate and general, the possibility of ion-pair formation at the micellar interface and the counterions-surfactant specific interactions must be modeled. Additionally, due to the results reported herein and by analyzing other systems, we suggest a more fundamental role of water (interfacial or hydrating water) in the micellar properties.

Micelas são agregados coloidais formados por moléculas anfifílicas i.e., moléculas com uma região hidrofóbica e uma porção hidrofílica (surfactantes). Efeitos específicos de íons (EEIs) são observados em micelas iônicas, uma vez que as propriedades físico-químicas de agregado micelares, como tamanho e geometria, dependem da natureza do contra-íon. Diferentes ânions inorgânicos produzem alterações modestas nas propriedades de agregados micelares catiônicos, mas ânions orgânicos podem induzir efeitos mais pronunciados, como transições de forma do agregado ou separações de fase. Em sistemas micelares, os EEIs podem estar relacionados a: (a) diferenças na localização dos ânions nas micelas; (b) diferenças na hidratação micellar e de íons; e (c) possível formação de pares iônicos entre surfactantes e contra-íons na interface micelar. Diversos modelos foram desenvolvidos para descrever a formação e estabilidade de agregados micelares, considerando diferentes termos energéticos que possivelmente contribuem para a formação/estabilidade de micelas. Contudo, os termos descritos acima (a - c) geralmente não são incluídos nos modelos micelares. Assim, não deve ser possível predizer as propriedades de micelas catiônicas, usando os modelos atuais, caso o contra-íon seja pequeno, desidratado e capaz de formar pares iônicos, como o ânion trifluorometilsulfonato (triflato, Tf). Tendo isso em vista, determinamos as propriedades micelares de triflato de dodeciltrimetilamônio (DTATf) e comparamos com micelas análogas formadas por brometo, cloreto e metanosulfonato, visando identificar diferenças estruturais das micelas e suas origens. Para determinação de propriedades micelares, utilizamos uma série de técnicas experimentais: fluorescência resolvida no tempo, espalhamento de raio-X de baixo ângulo, condutometria, cinética química, ressonâncias paramagnética eletrônica e magnética nuclear e espectroscopia de relaxação dielétrica, entre outras. Observamos que o agregado de DTATf possui uma estrutura discoidal altamente empacotada, ordenada e desidratada e estas propriedades foram reproduzidos em simulações de dinâmica molecular. A análise do conjunto de resultados obtidos para DTATf demonstrou que a formação de pares iônicos na interface micelar induz severas alterações nas propriedades micelares, como a desidratação dos agregados. Os dados obtidos com DTATf demonstram claramente que, para um modelo teórico de sistemas micelares ser capaz de predizer propriedades micelares de diferentes agregados, a possibilidade de formação de pares iônicos na interface micelar e as interações específicas entre contra-íons e surfactantes devem ser modeladas. Adicionalmente, devido aos resultados aqui reportados e analisando outros sistemas interfaciais, propomos um papel mais fundamental para a água (interfacial ou de hidratação) nas propriedades micelares / Micelles are colloidal aggregates formed by amphiphilic monomers i.e., molecules with a hydrophobic and a hydrophilic moiety (surfactants). Specific ion effects (SIEs) are observed in cationic micelles, because the physicochemical properties of the micellar aggregates, such as size and shape, depend on the nature of the counterion. Different inorganic counterions lead to small changes in micellar properties of cationic aggregates, but organic counterions can induce more pronounced effects, such as shape transitions of the aggregates or phase separation. In micellar systems, the SIEs can be related with: (a) differences in the location of anions in micelles; (b) differences in the hydration of micelles and ions; and (c) possible ion-pair formation between surfactants and counterions at the micellar interface. Several models have been developed to describe the formation and stability of micellar aggregates, considering different energy terms that possibly contribute to the formation/stability of micelles. However, the terms described above (a - c) are generally not included in micellar models. Thus, it should not be possible to predict the properties of cationic micelles, using the current models, if the counterion is small, dehydrated and capable of forming ion-pairs, such as the trifluoromethylsulfonate anion (triflate, Tf). In this context, we have determined the micellar properties of dodecyltrimethylammonium triflate (DTATf) micelles and we have compared the results with similar micelles formed by bromide, chloride and methanesulfonate, aiming to identify their structural differences and its origins. To determine the micellar properties, we have used several techniques: time resolved fluorescence, small angle X-ray scattering, conductometry, kinetic assays, electron paramagnetic and nuclear magnetic resonances and dielectric relaxation spectroscopy, among others. We have observed that the DTATf aggregate presents a highly packed, ordered and dehydrated disk-like geometry and these properties were reproduced in molecular dynamics simulations. The analysis of the DTATf properties showed that the formation of ion-pairs at the micellar interface induces severe changes in micellar properties, such as micellar dehydration. The DTATf properties clearly demonstrate that for a theoretical model of micellar system to be accurate and general, the possibility of ion-pair formation at the micellar interface and the counterions-surfactant specific interactions must be modeled. Additionally, due to the results reported herein and by analyzing other systems, we suggest a more fundamental role of water (interfacial or hydrating water) in the micellar properties.

<p>In medicinal chemistry, there is a constant need for new preparative methods, both to make the synthesis process more effective, and to increase the accessibility to a wide variety of compounds. A number of different approaches can be used to attain these goals. Transition metal catalysis is generally performed under mild conditions, providing both regio- and chemoselective reactions. Thus, it offers an attractive means of preparation of complex drug candidates. Two additional methodologies used to increase the preparative efficiency are one-pot protocols and controlled microwave heating. One-pot and multi-component reactions are less time consuming than step-by-step reactions, and microwave heating has been used to considerably shorten the reaction times. </p><p>This thesis describes a new palladium-catalyzed, one-pot reaction producing racemic acetal-protected 3-hydroxy-1-indanones from ethylene glycol vinyl ether and triflates of salicylic aldehydes. The triflates were prepared using controlled microwave heating. The reaction sequence starts with a regioselective internal Heck coupling, followed by an annulation cascade. By including secondary amines in the reaction mixture, the reaction was further developed into a three-component reaction delivering racemic acetal-protected 3-amino-1-indanones. This new method was utilized for the synthesis of primary, secondary and tertiary aminoindanones. Finally, by using enantiopure t-butyl sulfinyl imines, derived from salicylic aldehyde triflates and ethylene glycol vinyl ether as starting materials in a closely related type of palladium coupling–annulation sequence, a stereoselective protocol providing enantiomerically pure 3-amino-1-indanones was developed. To demonstrate an application in medicinal chemistry, the enantiopure 3-amino-1-indanones were incorporated as P2 and/or P2´ substituents into active HIV-1 protease inhibitors.</p>