O trabalho de tese é dividido em dois capítulos e visou explorar a química das diazocetonas α,β-insaturadas bem como dos ilídeos β-cetosulfoxônios. No primeiro capítulo é apresentado o emprego das diazocetonas α,β-insaturadas como novos aceptores em reações de aza-Michael. A adição conjugada de aminas primárias e secundárias foi explorada, assim como o uso de aminas quirais para avaliar a versão assimétrica da reação. Além da formação desses adutos, também foram investigadas estratégias para a construção de heterocíclicos nitrogenados a partir destes ou via protocolos \"one-pot\" (partindo das diazocetonas α,β-insaturadas) levando à formação de 2- e 3-pirrolidinonas. Por fim, foi avaliada a aplicação da metodologia desenvolvida na síntese do produto natural Barmumicina. O segundo capítulo se dispôs a investigar o emprego dos ilídeos β-cetosulfoxônios como substitutos de compostos diazocarbonílicos em reações de inserção. Num primeiro momento, avaliaram-se reações de inserção S-H intermolecular, visando a construção do fragmento β-cetotioéter. Alguns estudos competitivos e mecanísticos, bem como estratégias assimétricas também compõem o escopo. Num segundo momento, os ilídeos foram empregados em reações de inserção N-H intramolecular, no qual, a partir de sulfoxônios derivados de aminoácidos, vislumbrou-se a formação de 3-azetidinonas. / This thesis is divided into two chapters which are related to the chemistry of α,β-unsaturated diazoketones and β-ketosulfoxonium ylides. The first chapter presents the utility of α,β-unsaturated diazoketones as new aza-Michael acceptors. Conjugate addition of primary and secondary amines was explored, as well as the use of chiral amines to evaluate the asymmetric version of the reaction. In addition to the formation of these adducts, it was also investigated some strategies for the synthesis of 2- and 3-pyrrolidinones via the \"one-pot\" protocols (starting directly from the α,β-unsaturated diazoketones). Finally, the synthesis of the natural product Barmumicyn was evaluated from this methodology. The second chapter aimed to investigate the use of β-ketosulfoxonium ylides as diazocarbonyl compounds substitutes in insertion reactions. At first, the intermolecular S-H insertion reaction was studied aiming the construction of the β-ketothioether fragment. Some competitive and mechanistic studies, as well as asymmetric versions are also part of the scope. Secondly, some ylides were also employed in intramolecular N-H insertion reactions (from sulfoxonium amino acid derivatives) aiming the formation of 3-azetidinones.

The work presented in this thesis has broadly established a few findings about the structure¬hyperpolarizability relation in molecular compounds: First, by measuring βHRS of an organic keto-enol tautomer, benzoylacetanilide in a binary solvent, I have shown that the first hyperpolarizability can be manipulated favourably by changing the composition of the solvent or by altering the pH of the solution. BA which exists in the pure keto form in water and as a keto-enol tautomer in ethanol, co-exists in equilibrium with the keto and enol forms at pH 11 in aqueous solution. The β value of the anion form is 709 x 10¬30 esu , whereas that of the enol is 232 x 10-30 esu and of the keto is 88 x 10-30 esu. There is an enhancement of β by ~ 8 times for the anion and ~3 times for the enol compared to the keto form. This opens up the possibility of finding large nonlinearities in organic molecules by simply ionizing it. Second, in organometallic complexes of divalent Ru, the first hyperpolarizability could be manipulated by altering the valence state of the metal center by oxidation or reduction or by introducing highly polarisable halogen atoms as substitutions in ligands attached to the metal center. The enhancement of first hyperpolarizability was observed in mononuclear [RuII(acac)2(CH3CN)2] complex by 1.7 times when the metal center was oxidized from RuII to RuIII. As it is already known that the complexes like [(acac)2Ru-bptz-Ru(acac)2] produce stable mixed valent compound, the enhancement of β by ~1.6 times is appearing because of that species only. Exploring Large Nonlinearity in Tautomers In this thesis I have taken a linear ketone for studying the effect of structure on β via the enol and anion formation mediated by solvent and pH of the medium. In the present study the proton transfer in BA took place in the ground state of the ketone and the enol or anion are produced in the ground states. The proton transfer reaction (tautomerism) can also happen in the excited state as well in some molecules where there is a substantial barrier to the proton transfer reaction in the ground state. In such systems, once the ketone is excited using ultraviolet light the barrier to proton transfer in the medium is overcome and a proton transfer in the excited state takes place and the enol is produced. Since such a system will be at higher energy, it will be interesting to do a two-laser experiment where the excited state hyperpolarizability is measured in a time resolved manner and the β value is determined in the excited state. Building Molecular Nonlinearity in Step-by-Step Electron Transfer In this thesis, I have dealt with a binuclear complex of Ru(II) which in one-step electrochemical oxidation produced a mixed valence compound which had substantially higher β value compared to the unoxidized complex. In this way it is possible to build a multicentered complex and see if sequential one-electron transfer and subsequent oxidation/reduction of the metal centers produce a mixed-valent metal compound with large molecular nonlinearity. The indication from the present study is that such a scheme should double the β value in each one-electron transfer step. Also the linker group/moiety between the successive metal centers will play an important role in dictating the efficiency of electron transfer. If the metal d-electrons in a multinuclear complex are linked through a π-conjugation, one would expect manifold enhancement of β. Such metal arrays can also be designed in 2 or 3 dimensions. The dimensionality of the multinuclear metal complexes can easily be changed by supramolecular design and synthesis strategy. Such metal networks may or may not generate large β molecules since electronic polarization in such systems may not be superimposable in a coherent fashion and may not add in a positive sense. All these remain to be tested and explored in the future.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Due to the high chemical versatility of β-keto esters and the β-enamino carbonylic compounds as synthetic precursors, our research group has investigated and developed methodologies for their synthesis and reactivity. In the present work, we aim to establish a methodology for the transesterification of β-keto esters using montmorillonite (K-10) as a support or catalyst by itself or together with microwave irradiation (MW). We used the methodology to evaluate the synthesis and reactivity of β-enamino esters. The cyclic β-keto ester ethyl-2-oxo-1-cyclopentanecarboxilate was synthesized by ethanol esterification followed by Dieckmann Cyclization of adipic acid. To obtain the series of the cyclic β-keto esters derived from ethyl-2-oxo-1-cyclopentanecarboxilate by transesterification reaction with allylic and benzylic alcohol and (1S, 2R, 5S)-(+)-menthol, montmorillonite (K-10) as catalyst with microwaves was used. To validate the methodology chosen for our work, we compared microwave irradiation to the use of reflux in toluene. The use of K-10/MW in the absence of solvent was shown to be more efficient than refluxing in toluene, giving higher yields with a much reduced reaction time. Cyclic β-enamino esters were obtained by condensation of the previously synthesized β-keto esters with primary amines, using the same K-10/MW methodology adapted to a sealed flask. This step gave excellent results. For the study of the β-enamino esters reactivity evaluation we tried several reduction systems for ethyl 2-allylamino-1-cyclopentene-1-carboxylate, without success. For the evaluation of the β-keto esters reactivity we chose ethyl 2-oxo-1-cyclopentanecarboxylate and allyl 2-oxo-1-cyclopentanecarboxylate. They were used in the condensation reaction with secondary amines and also for cyclization using Mn(OAc)3, to give a cyclic amide and a spiro compound, respectively. / Devido à grande versatilidade química como precursores sintéticos, os β-cetoésteres e os compostos β-enamino carbonílicos, têm sido alvo de estudos em nosso grupo de pesquisa no desenvolvimento de metodologias para a síntese e reatividade desses compostos. Neste trabalho buscamos estabelecer metodologias para transesterificação de β-cetoésteres, utilizando montmorillonita (K-10), como suporte ou catalisador associado ou não ao uso de energia de microondas e avaliar a obtenção e a reatividade de β-enamino ésteres. Visando tais objetivos, sintetizamos o β-cetoéster cíclico, 2-oxo-1-ciclopentanocarboxilato de etila a partir do ácido adípico, através da esterificação em etanol, seguida de uma Ciclização de Dieckmann. Na obtenção de uma série de β-cetoésteres cíclicos derivados do 2-oxo-1-ciclopentanocarboxilato de etila, pela reação de transesterificação deste frente a álcool alílico, benzílico e (1S, 2R, 5S)-(+)-mentol, elegeu-se a metodologia utilizando montmorillonita (K-10) como catalisador associada a energia de microondas. Para validação desta metodologia, comparou-se a utilização de energia de microondas com o emprego de refluxo em tolueno. A metodologia empregando K-10/MO na ausência de solvente mostrou-se, mais eficiente, pois apresentou melhores rendimentos e tempos reacionais bastante reduzidos em relação à outra metodologia avaliada. Foram obtidos β-enamino ésteres cíclicos pela condensação dos β-cetoésteres sintetizados com aminas primárias empregando a metodologia de suporte sólido (K-10), associada à energia de microondas adaptada para vaso vedado obtendo ótimos resultados. Para a avaliação da reatividade dos β-enamino ésteres, vários sistemas redutores foram empregados para o 2-alilamino-1-ciclopenteno-1-carboxilato de etila, sem sucesso. Para o estudo da reatividade de β-cetoésteres, elegemos o 2-oxo-1-ciclopentanocarboxilato de etila e o 2-oxo-1-ciclopentanocarboxilato de alila, que foram submetidos à reação de condensação frente à amina secundária e à reação de ciclização promovida por Mn(OAc)3, obtendo-se, respectivamente, uma amida cíclica e um composto espiro.

O trabalho de tese é dividido em dois capítulos e visou explorar a química das diazocetonas α,β-insaturadas bem como dos ilídeos β-cetosulfoxônios. No primeiro capítulo é apresentado o emprego das diazocetonas α,β-insaturadas como novos aceptores em reações de aza-Michael. A adição conjugada de aminas primárias e secundárias foi explorada, assim como o uso de aminas quirais para avaliar a versão assimétrica da reação. Além da formação desses adutos, também foram investigadas estratégias para a construção de heterocíclicos nitrogenados a partir destes ou via protocolos \"one-pot\" (partindo das diazocetonas α,β-insaturadas) levando à formação de 2- e 3-pirrolidinonas. Por fim, foi avaliada a aplicação da metodologia desenvolvida na síntese do produto natural Barmumicina. O segundo capítulo se dispôs a investigar o emprego dos ilídeos β-cetosulfoxônios como substitutos de compostos diazocarbonílicos em reações de inserção. Num primeiro momento, avaliaram-se reações de inserção S-H intermolecular, visando a construção do fragmento β-cetotioéter. Alguns estudos competitivos e mecanísticos, bem como estratégias assimétricas também compõem o escopo. Num segundo momento, os ilídeos foram empregados em reações de inserção N-H intramolecular, no qual, a partir de sulfoxônios derivados de aminoácidos, vislumbrou-se a formação de 3-azetidinonas. / This thesis is divided into two chapters which are related to the chemistry of α,β-unsaturated diazoketones and β-ketosulfoxonium ylides. The first chapter presents the utility of α,β-unsaturated diazoketones as new aza-Michael acceptors. Conjugate addition of primary and secondary amines was explored, as well as the use of chiral amines to evaluate the asymmetric version of the reaction. In addition to the formation of these adducts, it was also investigated some strategies for the synthesis of 2- and 3-pyrrolidinones via the \"one-pot\" protocols (starting directly from the α,β-unsaturated diazoketones). Finally, the synthesis of the natural product Barmumicyn was evaluated from this methodology. The second chapter aimed to investigate the use of β-ketosulfoxonium ylides as diazocarbonyl compounds substitutes in insertion reactions. At first, the intermolecular S-H insertion reaction was studied aiming the construction of the β-ketothioether fragment. Some competitive and mechanistic studies, as well as asymmetric versions are also part of the scope. Secondly, some ylides were also employed in intramolecular N-H insertion reactions (from sulfoxonium amino acid derivatives) aiming the formation of 3-azetidinones.

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No description available.

In dieser Arbeit wird die Synthese neuartiger 5-monosubstituierter Barbituratfarbstoffe mit elektronenziehenden Substituenten in 5-Position beschrieben. Durch diese Funktionalisierung entstehen schaltbare Farbstoffe mit einer farblosen Ketoform und einer farbigen Enolform. Die Einflüsse verschieden stark elektronenziehender Substituenten sowie unterschiedlich großer konjugierter π-Systeme auf die Keto-Enol-Tautomerie wurden untersucht. Dies erfolgt einerseits mittels Röntgeneinkristallstrukturanalysen der Festkörper und andererseits mit solvatochromen Untersuchungen in Lösung. Durch die Keto-Enol-Tautomerie der Barbituratfarbstoffe wird die Wasserstoffbrücken¬bindungssequenz beim Übergang zwischen Keto- und Enol-Form verändert. Es wurde gezeigt, dass durch Zugabe von Rezeptoren mit komplementärer Wasserstoffbrückenbindungssequenz zur Enol-Form das tautomere Gleichgewicht der Barbitursäuren hin zur Enol-Form verschoben werden kann. Um hierzu verlässliche Aussagen zu erhalten wurden vergleichende Experimente mit N,N´-dialkylierten Barbituratfarbstoffen durchgeführt. Aufgrund der Synthesestrategie der Barbituratfarbstoffe, welche ausgehend von Barbituratanionen über nukleophile aromatische Substitutionsreaktionen hergestellt wurden, war es zweckmäßig die Nukleophilieparameter der Barbituratanionen zu ermitteln. Dazu wurde der Ansatz von Mayr gewählt und die Nukleophilie von vier Barbituratanionen bestimmt. Weiterhin konnte in dieser Arbeit die Charakterisierung von ionischen Flüssigkeiten nach der 4-Parameter-Gleichung von Catalán umgesetzt werden. Dabei gelang es erstmal für eine vielzahl verschiedener ionischer Flüssigkeiten die Polarisierbarkeit und Dipolarität getrennt voneinander mit Hilfe zweier solvatochromer Farbstoffe zu ermitteln.

Les travaux décrits dans ce mémoire de thèse ont pour objet d'une part l'étude de la réactivité de céto-3-alcynoates et de céto-sulfonylynamides. Les céto-3-alcynoates conduisent à la formation d'allénoates bi- ou tricycliques par catalyse au carbonate de césium. La sélectivité est totale au niveau de l'allénoate bicyclique obtenu. Il est également possible d'effectuer cette réaction de cyclisation de façon monotope au départ de l'alcynyl-cétone correspondante, dans ce cas les allénoates tricycliques sont obtenus avec de très bons rendements. Les 3-alcynoates peuvent également être utilisés pour la synthèse de dérivés oxydés de l'acide jasmonique. Ainsi deux composés énantiomériquement enrichis, le (-)-12-COOH-JA et le (-)-12-COOH-JA-Ile, observés dans les plantes blessées on été synthétisés. Ces composés ont permis d'élucider deux voies cataboliques : une voie oxydative et une voie hydrolytique. L'étude de la réactivité de céto-sulfonylynamides en présence de triflimide d'argent a conduit à l'obtention d'aza-bicyclo[n.m.1]alcanones. Cette réaction de Conia-ène formelle s'applique à différentes cycloalcanones, ainsi qu’à une grande variété d’ynamides fonctionnalisés / The work described in this manuscript involved the reactivity of keto-3-keto-alkynoates and and keto-sulfonamides. Keto-3-alkynoates led to bi- or tricyclic allenoates in the presence of a catalytic amount of cesium carbonate. Cyclization proceeds in a totally stereoselective manner in the case of the two-carbon linker chain. A one-pot reaction starting from alkynyl ketones afforded tricyclic fused ring systems with good yields. Enantiomerically enriched, oxidized, conjugated or non-conjugated jasmonate derivatives were obtained through 3-alkynoates, in particular (-)-12-COOH-JA and (-)-12-COOH-JA-Ile found in wounded leaves. The availability of those synthetic compounds allowed deeper exploration of the complex regulation of JA-Ile hormone homeostasis and unraveled an oxidative and a hydrolytic pathway. Aza-bicyclo[n.m.1]alkanone frameworks could be obtained when keto-sulfonylynamides were treated under silver catalysis. This formal Conia-ene reaction was compatible with various cycloalkanones, as well as a wide range of functionalized ynamides.

In dieser Arbeit wird die Synthese neuartiger 5-monosubstituierter Barbituratfarbstoffe mit elektronenziehenden Substituenten in 5-Position beschrieben. Durch diese Funktionalisierung entstehen schaltbare Farbstoffe mit einer farblosen Ketoform und einer farbigen Enolform. Die Einflüsse verschieden stark elektronenziehender Substituenten sowie unterschiedlich großer konjugierter π-Systeme auf die Keto-Enol-Tautomerie wurden untersucht. Dies erfolgt einerseits mittels Röntgeneinkristallstrukturanalysen der Festkörper und andererseits mit solvatochromen Untersuchungen in Lösung. Durch die Keto-Enol-Tautomerie der Barbituratfarbstoffe wird die Wasserstoffbrücken¬bindungssequenz beim Übergang zwischen Keto- und Enol-Form verändert. Es wurde gezeigt, dass durch Zugabe von Rezeptoren mit komplementärer Wasserstoffbrückenbindungssequenz zur Enol-Form das tautomere Gleichgewicht der Barbitursäuren hin zur Enol-Form verschoben werden kann. Um hierzu verlässliche Aussagen zu erhalten wurden vergleichende Experimente mit N,N´-dialkylierten Barbituratfarbstoffen durchgeführt. Aufgrund der Synthesestrategie der Barbituratfarbstoffe, welche ausgehend von Barbituratanionen über nukleophile aromatische Substitutionsreaktionen hergestellt wurden, war es zweckmäßig die Nukleophilieparameter der Barbituratanionen zu ermitteln. Dazu wurde der Ansatz von Mayr gewählt und die Nukleophilie von vier Barbituratanionen bestimmt. Weiterhin konnte in dieser Arbeit die Charakterisierung von ionischen Flüssigkeiten nach der 4-Parameter-Gleichung von Catalán umgesetzt werden. Dabei gelang es erstmal für eine vielzahl verschiedener ionischer Flüssigkeiten die Polarisierbarkeit und Dipolarität getrennt voneinander mit Hilfe zweier solvatochromer Farbstoffe zu ermitteln.

Neste trabalho apresenta-se o estudo do comportamento eletroquímico anódico - direto (oxidação na superfície do eletrodo) e indireto (oxidação através de um oxidante eletrogerado, ou mediador) de β-ceto-sulfetos e βhidróxi-sulfetos de estruturas variadas. Foram utilizadas as técnicas de voltametria cíclica (anodo:pérola de Pt; referência: Ag/AgI; solvente: MeCN anidra e NaClO4 0,1 M como eletrólito de suporte) e de oxidações anódicas preparativas (potencial controlado ou corrente constante; eletrodos de Pt polida 4 cm2; solvente:MeCN/H2O (9:1v/v); NaClO4 0,2 M). Foram sintetizadas e estudadas as seguintes cetonas α-sulfeniladas: 2-etiltio- (I.1), 2-etiltio-2-metil (I.2) e, 2-feniltio-(I.3)-ciclo-hexano-1-onas; 2-metiltio-(II.1) e 2-metiltio-2-metil-(II.2)-1-tetralonas; 1-fenil-2-metiltio-butano-1-ona (III.1); 2-etiltio-1,2-difenil-etano-1-ona (IV.1) e três derivados aril-substituídos [4.4-OMe (IV.2); 4-OMe (IV.3); 2.2-Cl (IV.3); 2,2-Cl (IV.4)]. Os mediadores preparados e eletroquimicamente investigados foram os derivados bromados da trifenilamina (V.1): tris(4-bromofenil)amina (V.2) e tris(2,4-dibromo-fenil)amina (V.3). Os álcoois correspondentes foram preparados por redução direta das cetonas. Os resultados dos estudos eletroquímicos das cetonas demonstraram que o diferente comportamento eletroquímico deve-se a fatores estereoeletrônicos. Somente (III.1) e (IV.1, 2 e 3) eram oxidados indiretamente. As oxidações anódicas diretas dos β-hidróxi-sulfetos mostraram-se mais seletivas que as das cetonas relativas. Além do mais, a comparação entre as oxidações direta e indireta destes álcoois revelou que enquanto diretamente obtem-se dois ou três produtos, indiretamente os sulfóxidos correspondentes são obtidos. Como único produto, de todos álcoois exceto daqueles relativos às cetonas (IV. 2, 3 e 4). Também foi observado que a estereoquimica cis entre os grupos hidroxila e alquiltio é fator determinante para as oxidações eletroquímicas indiretas. Os estereoisômeros trans não eram oxidados indiretamente. Um intermediário cíclico, formado durante o processo de oxidação, é sugerido como explicação para estes fatos. Também foi observado que ocorre clivagem da ligação carbono-carbono entre os grupos hidroxila e alquiltio na oxidação anódica, quando os carbonos substituídos são terciários (no caso de 2-etiltio-1,2-dimetil-ciclohexan-1-ol), ou estão ligados a grupos fenila (IV.1, 2, 3 e 4). São obtidos os compostos carbonílicos correspondentes em bons rendimentos. / In the present work a study of the electrochemical oxidation behaviour under direct (oxidation at the electrode) and indirect (oxidation by on in situ electrogenerated species, a mediator) conditions of several β-keto and β-hydroxysulphides is reported. Cyclic voltammetry (anode: Pt bead, reference: Ag/AgI, 0.1 M NaClO4) in anhydrous acetonitrile) and preparative scale electrolysis under controlled potential or at constant current (anode: Pt 2 x 2 cm, 0.2 M NaClO4 in acetonitrile - water (9:1 v/v) were employed. The studied mediators were tris-(4-bromophenyl) and tris-2,4-dibromophenyl)amines. The following α-sulphenylated ketones were synthesized: 2-ethylthio-(I.1), 2-ethylthio-2-methyl (I.2) and 2-phenylthio-(I.3)-cyclohexan-1-ones; 2-methylthio-(II.1) and 2-methylthio-2-methyl-(II.2)-1-tetralones; 1-phenyl-2-methylbutan-1-one (III.1); 2-ethylthio-1,2-diphenylethan-1-one (IV.1) and three aryl derivatives [4,4\'-OMe (IV.2), 4\'-Ome (IV.3), 2,2\'-Cl (IV.3)]. The corresponding alcohols were prepared by direct reduction of the ketones. The results of the electrochemical studies for the investigated ketones demonstrated that their different behaviour is due to stereoelectronic effects. Only (III.1, IV.1, IV.2 and IV.3) were indirectly oxidized. The direct anodic oxidations of the β-hydroxy-sulphides were more selective than those of the corresponding ketones. Moreover, a comparison between direct and indirect oxidations of such alcohols reveal that while the former can give two or three products, the latter yields the relatives sulphoxides as the only products with all the alcohols except the ones related to (IV.2, 3 and 4). It was also noticed that the cis stereochemistry between hydroxyl and alkylthio groups is the determining feature in the indirect electrochemical oxidation of cyclic alcohols. No oxidation was observed in the case of the trans stereoisomers. A cyclic intermediate, formed during the oxidation process, is suggested to explain these facts. In addition, a cleavage of the carbon-carbon bond between the hydroxyl and alkylthio groups was observed in the anodic oxidation, when the substituted carbons are tertiary (in the case of 2-ethylthio-1,2- dimethylciclohexan-1-ol), or linked to phenyl groups (IV.1, 2, 3 and 4). In these cases, the corresponding carbonyl compounds were obtained in good yields.