Hydrazides and hydrazones as versatile Michael-Donors for iminium-catalyzed conjugate addition reactions

396 : il., graf.

Activación de aldehídos a,b-insaturados mediante aminocatálisis en procesos enantioselectivos. Cicloadiciones (3+2) y reacciones en cascada Michael/Henry

During the research that it is summarized in the present memory, the activation of enals via iminium ion catalysis in different transformations has been studied. Firstly, a 1,3-dipolar cycloaddition between stable azomethine ylides and a,b-unsaturated aldehydes catalyzed by a chiral imidazolidinone derivative has been optimized. Employing this methodology we have synthesized a large range of densely substituted pyrroloisoquinolines and pyrrolophthalazines with good yields and high values of diastereo- and enantioselectivity. Moreover, a mechanistic study has been carried out based on DFT calculations and experimental data which have allowed us to propose that the (3+2) cycloaddition reaction follows a sequential Michael addition/Mannich cyclization pathway. The formation of the iminium ion as a result of the condensation between the a,b-unsaturated aldehyde and the catalyst plays an essential role, regarding both reactivity and stereoselectivity. On the other hand we have developed a methodology to carry out a cascade Michael/Henry reaction followed by a sequential dehydration. Starting from simple substrates (2-nitromethylacrilates and a,b-unsaturated aldehydes) and employing a prolinol-derivative catalyst a series of quiral nitrocyclohexadienes have been synthesized.

Asymmetric organocatalytic cascade reactions

302 p. : gráf.

Ring-opening metathesis of bulky norbornene monomers and the radical-mediated hydrophosphonation of olefins

This thesis discusses two major topics: the ring-opening metathesis polymerization (ROMP) of bulky monomers and the radical-mediated hydrophosphonation of olefins. The research into the ROMP of bulky monomers is further divided into three chapters: wedge-shaped monomers, the alternating copolymerization of 1-methyloxanorbornene derivatives with cyclooctene, and the kinetic resolution polymerization of 1-methyloxanorbornene derivatives. The wedge-shaped monomers can be polymerized into diblock copolymers that possess photonic crystal properties. The alternating copolymerization of 1-methyloxanorbornene derivatives with cyclooctene is performed with > 90% alternation via two different routes: typical alternating copolymerization and a sequence editing approach. The kinetic resolution polymerization of these same 1-methyloxanorbornene monomers achieves only modest selectivity (S=4), but there is evidence that the growing polymer chain forms a helix that influences the selectivity of the resolution. The last topic is the radical-mediated hydrophosphonation of olefins. This synthetic method provides access to Wittig reagents that are capable of highly cis-selective olefinations of aldehydes.

The electrocatalytic and stoichiometric oxidation chemistry of binuclear ruthenium complexes incorporating the anionic tripod ligand {(η5-C5H5)Co[P(OCH3)2(=O)]3}-

The anionic tripod ligand NaLoMe (L_(oMe) - = [(η^5-C_5H_5)Co{P(O)(OCH_3)_2}_3]^-) reacts with RuO_4 in a biphasic reaction mixture of 1% H_2SO_4 and CCI_4 to afford [(L_(oMe) (HO)Ru^(IV) (µ-O)_2Ru ^(IV)(OH)(L_(oMe)] (1), which is treated with aqueous CF_3S0_3H to generate [(L_(oMe)(H_2O)Ru^(IV) (µ-O)_2R^(IV) (OH_2)(L_(oMe)][CF_3SO_3]_2 ([H_21][CF_3SO_3]_2). Addition of iodosobenzene to an acetonitrile solution of this salt yields [(L_(oMe)(O)Ru^v(µ-0)2Ru^v-(O)(_(LoMe)] (2). The dimer 1 can be reduced chemically or electrochemically to the Ru^(III)- Ru^(III) dimers [(L_(oMe)(H_20)Ru^(III) (µ-OH)_2Ru^(III) (OH_2)(L_(oMe)) ]^2+ and [(L_(oMe)) ^(III) (µ-0Hh(µ-0H2)Ru^(III) (L_(oMe)]^2+ which interconvert in aqueous media. Two electron processes dominate both the bulk chemistry and the electrochemistry of 1. Among these processes are the quasi-reversible Ru^(IV) - Ru^(IV)/Ru^(III)- Ru^(III) and Ru^(III)- Ru^(III)/ Ru^(II)- Ru^(II) reductions and a largely irreversible Ru^(V) - Ru^(V)/ Ru^(IV) - Ru^(IV)/oxidation. The dioxo dimer 2 oxidizes alcohols and aldehydes in organic media to afford 1 and the corresponding aldehydes and acids. Analogously, the Ru^(V) - Ru^(V)/ Ru^(IV)- Ru^(IV) redox wave mediates the electrooxidation of alcohols and aldehydes in aqueous buffer. In this system, substrates can be oxidized completely to CO_2. The kinetic behavior of these oxidations was examined by UV-vis and chronoamperometry, respectively, and the chemistry is typical of metal-oxo complexes, indicating that electronic coupling between two metal centers does not dramatically affect the metal-oxo chemistry. Dimer [H_21]^(2+) also reacts with alcohols, aldehydes, and triphenylphosphine in CH_3CN to afford Ru^(III)- Ru^(III) products including [(L_(oMe))CH_3CN) Ru^(III) (µ-OH)_2 Ru^(III) (NCCH_3)( L_(oMe))][CF_3SO_3]2 (characterized by X-ray crystallography) and the corresponding organic products. Reaction of 1 with formaldehyde in aqueous buffer quantitatively affords the triply bridged dimer [(L_(oMe)Ru^(III) (µ-OH)2- (µ-HCOO) Ru^(III) (L_(oMe)][CF_3SO_3] (characterized by X-ray crystallography). This reaction evidently proceeds by two parallel inner-sphere pathways, one of which is autocatalytic. Neither pathway exhibits a primary isotope effect suggesting the rate determining process could be the formation of an intermediate, perhaps a Ru^(IV) - Ru^(IV) formate adduct. The Ru^(III)- Ru^(III)formate adduct is easily oxidized to the Ru^(IV) - Ru^(IV) analog [(L_(oMe)Ru^(IV)(µ-OH)_2-(µ-HCOO) Ru^(IV) (L_(oMe)][CF_3SO_3], which, after isolation, reacts slowly with aqueous formaldehyde to generate free formate and the Ru^(III)- Ru^(III) formate adduct. These dimers function as catalysts for the electrooxidation of formaldehyde at low anodic potentials (+0.0 V versus SCE in aqueous buffer, pH 8.5) and enhance the activity of Nafion treated palladium/carbon heterogeneous fuel cell catalysts.

A Convergent Synthetic Route to the Tunicamycin Antiobiotics. Synthesis of (+)-Tunicamycin V

A concise synthetic route to the tunicamycin antibiotics is described, illustrated by the preparation of (+)-tunicamycin-V (1-V). Key features of the synthesis include: (1) the development and application of a silicon-mediated reductive coupling of aldehydes and allylic alcohols to construct the undecose core of the natural product; and (2) the development of an efficient procedure for the synthesis of the trehalose glycosidic bond within the antibiotic. These innovations allow for the coupling of a uridine-derived aldehyde fragment with a preformed trehalose-linked disaccharide allylic alcohol to form the carbohydrate core (1) of the natural product in a highly convergent manner. The resultant amino polyol is a versatile intermediate for the synthesis of any of the homologous tunicamycin antibiotics.

Synthetic applications of intramolecular aza-Wittig reaction for the preparation of heterocyclic compound

[EN] A review focused on recent advances in intramolecular aza-Wittig reaction of phosphazenes with several carbonyl or analogous compounds is reported. Phosphazenes afford intramolecular aza-Wittig reaction with different groups within the molecule as aldehydes, ketones, esters, thioesters, amides, anhydrides and sulfimides. One of the most important applications of this reaction is the synthesis of a wide range of heterocyclic compounds, ranging from simple monocyclic compounds to complex polycyclic and macrocyclic systems.

Selective hydroxylation of small alkanes by the particulate methane monooxygenase

The particulate methane monooxygenase (pMMO) catalyzes the oxidation of methane to methanol under ambient temperatures and pressures. Other small alkanes and alkenes are also substrates of this enzyme. We measured and compared the initial rate constants of oxidation of small alkanes (C1 to C5) catalyzed by pMMO. Both primary and secondary alcohols were formed from oxidation of n-butane and n-pentane. The alcohols produced from alkane oxidation can be further oxidized, probably by pMMO, to aldehydes and ketones. The apparent regioselectivity for n-butane and n-pentane is 100% 2-alcohols because the formation of primary alcohols is slower than further oxidation of these alcohols. The hydroxylation at the secondary carbons is highly stereoselective: (R)-alcohols are preferentially formed. The enantiomeric excess increases slightly with decreasing reaction temperature. The steric course of hydroxylation on primary carbons was also studied by using isotopically substituted ethane: (S)- or (R)-CH_3-CHDT, and (S)- or (R)-CD_3- CHDT and the reactions were found to proceed with 100% retention of configuration. A primary isotopic effect of k_H/k_D=5.0 was observed in these experiments.

Use of pseudoephedrine as a practical chiral auxiliary for asymmetric synthesis

The use of pseudoephedrine as a practical chiral auxiliary for asymmetric synthesis is describe. Both enantiomers of pseudoephedrine are inexpensive commodity chemicals and can be N-acylated in high yields to form tertiary amides. In the presence of lithium chloride, the enolates of the corresponding pseudoephedrine amides undergo highly diastereoselective a1kylations with a wide range of alkyl halides to afford α-substituted products in high yields. These products can then be transformed in a single operation into highly enantiomerically enriched carboxylic acids, alcohols, and aldehydes. Lithium amidotrihydroborate (LAB) is shown to be a powerful reductant for the selective reduction of tertiary amides in general and pseudoephedrine amides in particular to form primary alcohols.

Investigations of group IVA transition metal mediated carbon-carbon bond forming reactions

Zirconocene aldehyde and ketone complexes were synthesized in high yield by treatment of zirconocene acyl complexes with trimethylaluminum or diisobutylaluminum hydride. These complexes, which are activated by dialkylaluminum chloride ligands, inserted unsaturated substrates such as alkynes, allenes, ethylene, nitriles, ketenes, aldehydes, ketones, lactones, and acid chlorides with moderate to high conversion. Insertion of aldehyde substrates yielded zirconocene diolate complexes with up to 20:1 (anti:syn) diastereoselectivity. The zirconocene diolates were hydrolyzed to afford unsymmetrical 1,2-diols in 40-80% isolated yield. Unsymmetrical ketones gave similar insertion yields with little or no diastereoselectivity. A high yielding one-pot method was developed that coupled carbonyl substrates with zirconocene aldehyde complexes that were derived from olefins by hydrozirconation and carbonylation. The zirconocene aldehyde complexes also inserted carbon monoxide and gave acyloins in 50% yield after hydrolysis.

The insertion reaction of aryl epoxides with the trimethylphoshine adduct of titanocene methylidene was examined. The resulting oxytitanacyclopentanes were carbonylated and oxidatively cleaved with dioxygen to afford y-lactones in moderate yields. Due to the instability and difficult isolation of titanocene methylidene trimethylphoshine adducts, a one-pot method involving the addition of catalytic amounts of trimethylphosphine to β,β-dimethyltitanacyclobutane was developed. A series of disubstituted aryl epoxides were examined which gave mixtures of diastereomeric insertion products. Based on these results, as well as earlier Hammett studies and labeling experiments, a biradical transition state intermediate is proposed. The method is limited to aryl substituted epoxide substrates with aliphatic examples showing no insertion reactivity.

The third study involved the use of magnesium chloride supported titanium catalysts for the Lewis acid catalyzed silyl group transfer condensation of enol silanes with aldehydes. The reaction resulted in silylated aldol products with as many as 140 catalytic turnovers before catalyst inactivation. Low diastereoselectivities favoring the anti-isomer were consistent with an open transition state involving a titanium atom bound to the catalyst surface. The catalysts were also used for the aldol group transfer polymerization of t-butyldimethylsilyloxy-1-ethene resulting in polymers with molecular weights of 5000-31,000 and molar mass dispersities of 1.5-2.8. Attempts to polymerize methylmethacrylate using GTP proved unsuccessful with these catalysts.

Complexity and Uniqueness of the Aromatic Profile of Smoked and Unsmoked Herreno Cheese

In this work, the volatile fraction of unsmoked and smoked Herreno cheese, a type of soft cheese from the Canary Islands, has been characterized for the first time. In order to evaluate if the position in the smokehouse could influence the volatile profile of the smoked variety, cheeses smoked at two different heights were studied. The volatile components were extracted by Solid Phase Microextraction using a divinylbenzene/carboxen/polydimethylsiloxane fiber, followed by Gas Chromatography/Mass Spectrometry. In total, 228 components were detected. The most numerous groups of components in the unsmoked Herreno cheese were hydrocarbons, followed by terpenes and sesquiterpenes, whereas acids and ketones were the most abundant. It is worth noticing the high number of aldehydes and ketones, and the low number of alcohols and esters in this cheese in relation to others, as well as the presence of some specific unsaturated hydrocarbons, terpenes, sesquiterpenes and nitrogenated derivatives. The smoking process enriches the volatile profile of Herreno cheese with ketones and diketones, methyl esters, aliphatic and aromatic aldehydes, hydrocarbons, terpenes, nitrogenated compounds, and especially with ethers and phenolic derivatives. Among these, methylindanones or certain terpenes like a-terpinolene, have not been detected previously in other types of smoked cheese. Lastly, the results obtained suggest a slightly higher smoking degree in the cheeses smoked at a greater height.

Research on operating conditions at the catalytic reactor for the combined removal of NOx and PCDD/PCDFs from MWI plants

The management of municipal solid waste (MSW), particularly the role of incineration, is currently a subject of public debate. Incineration shows to be a good alternative of reducing the volume of waste and eliminating certain infectious components. Moreover, Municipal Waste Incinerators (MWI), are reported to be highly hygienic and apart from that MWIs are immediately effective in terms of transport (incinerators can be built close to the waste sources) and incineration's nature. Nevertheless, the emissions of many hazardous substances make the Municipal Waste Incineration (MWI) plants to be unpopular. Metals (especially lead, manganese, cadmium, chromium and mercury) are concentrated in fly and bottom ashes. Furthermore, incomplete combustion produces a wide variety of potentially hazardous organic compounds, such as aldehydes, polycyclic aromatic hydrocarbons (PAH), chlorinated hydrocarbons including polychlorinated dibenzodioxins (PCDD) and dibenzofurans (PCDF), and even acid gases, including NOx. Many of these hazardous substances are carcinogenic and some have direct systemic toxicity.

Monitoramento das concentrações de aldeídos e BTEX como precursores de ozônio e o efeito final de semana das concentrações de ozônio na região de Bangu.

O ozônio é um poluente secundário formado pela presença de poluentes atmosféricos primários e secundários formados a partir de uma sequência de reações entre o dióxido de nitrogênio e de compostos orgânicos voláteis (COV). No grupo de compostos orgânicos voláteis estão os aldeídos e os BTEX. Os COVS são emitidos, no Rio de Janeiro, principalmente por veículos automotores. O presente estudo realizou então coletas de aldeídos e BTEX no período de 2013. Além disso, com dados de 2012 e 2013 de poluentes de uma rede automática de monitoramento analisou o possível efeito fim de semana existente na região. O efeito fim de semana é caracterizado por altas concentrações de ozônio no final de semana mesmo com a redução da frota das emissões de NOx e COVs neste período.

Enzimas antioxidantes em sangue de peixes expostos à hipoxia e hiperoxia

O oxigênio é importante não só por sua participação no metabolismo energético, mas também por sua conversão em derivados parcialmente reduzidos, as espécies reativas de oxigênio (ERO). ERO participam de funções importantes em diversas vias do metabolismo, entretanto, em concentrações desequilibradamente elevadas deflagram a peroxidação lipídica, processo deletério que forma aldeídos tóxicos, como o 4-hidroxi-2-nonenal (4-HNE). A manutenção de concentrações não deletérias das ERO é realizada por moléculas componentes do sistema antioxidante. Peixes podem ser expostos a grandes variações das concentrações de oxigênio, o que provoca ciclos oxidantes. A maioria dos estudos usa fígado e rim para avaliar estresse oxidante por meio de ensaios das atividades antioxidantes, o que requer o sacrifício dos animais. Contudo, o sangue sofre efeitos das ERO e avaliações no sangue podem permitir o estudo de antioxidantes no mesmo animal, sem a necessidade de sacrifício. Em consequência, foram nossos objetivos estabelecer uma técnica de cateterismo branquial em peixes, a padronização dos ensaios e a avaliação em sangue de componentes do sistema antioxidante de duas espécies de teleósteos em diferentes tensões de oxigênio. Pacus e tilápias foram avaliados em 6,0 mg de O2.L-1 e em hipoxia a 0,5 mg de O2.L-1 por 42 horas . Para os ensaios de hiperoxia os animais foram avaliados em 6,0 mg de O2.L-1, depois de 6 horas em 9,5 mg de O2.L-1 e depois de 30 horas de recuperação a 6,0 mg de O2.L-1. A utilização de materiais para o cateterismo de humanos permitiu a implantação de um acesso branquial. Infelizmente, houve formação de trombo após 24 horas. Mesmo assim, a observação de fluxo sanguíneo no interior da cânula e a sobrevida dos animais testados, confirmam a viabilidade da técnica. Verificamos em sangue uma maior atividade da enzima glutationa S-transferase (GST) sobre o 4-HNE em relação ao 1-cloro-2-dinitrobenzeno (CDNB). Isto reflete a importância de avaliações de atividade de enzimas, como a GST, sobre substratos endógenos. As respostas enzimáticas de tilápias mostraram-se mais sensíveis que as dos pacus quando comparadas em diferentes tensões de oxigênio.

Evaluation of biochemical characteristics of a traditional salt fermented fish product of northeast India with special reference to its flavour components

'Lona ilish', is a traditional salt fermented fish product, widely consumed and very popular in north-east part of India and Bangladesh. It is prepared exclusively from a high fat fish, Hilsa (Tenualosa) ilisha. 'Lona ilish' was prepared in the laboratory following traditional process. After 150 days of fermentation, a better quality 'lona ilish' was obtained. Biochemical characteristics of market sample was estimated and compared with the laboratory prepared one. A variation in biochemical composition was observed. Sensory quality of the final product of laboratory prepared 'lona ilish' was compared with the market sample and found that the laboratory prepared product scored better than the market sample. The moisture (49.89%) and salt (15.48%) of the final product was found to be satisfactory for stability of the 'lona ilish' at ambient temperature. Analysis of volatile compounds of 'lona ilish' was done using GC-MS. It was concluded that, aldehydes, ketones and esters may possibly contribute characteristic aromas to the overall flavour of the salt fermented hilsa.