During my PhD I was involved in many studies concerning the nucleophilic (SNAr) and electrophilic (SEAr) aromatic substitution reactions. My research activity was focused on the study of different electrophile/nucleophile combinations between strongly activated species, with the purpose to investigate on their reactivity, to detect new intermediates of the aromatic substitution reaction and to obtain new higly conjugated structures bearing contemporaneously electron donor and acceptor moieties on the same unit for application in different fields. Different reactions between both neutral or charged electrophilic and nucleophilic species were performed and from their combinations new products for applications in different fields (e.g. medicine, biology and materials) were obtained and new intermediates of the aromatic substitution reactions [e.g. Wheland (W), Meisenheimer (M), and even Wheland-Meisenheimer (WM)], were detected and characterized, mainly using NMR spectroscopic techniques. In particular the involved nucleophilic species were: tri- and diaminobenzene derivatives, trihydroxybenzene, trimethoxybenzene, anisole derivatives and aminothiazole derivatives; whereas the selected electrophilic species were: aryldiazonium ions, benzofuroxan and benzofurazan derivatives, thiophene derivatives and benzhydrylium ions. Furthermore, the last year of my PhD course, I spent a period in the Department of Chemistry, Ludwig-Maximilians-University of Munich, in collaboration with Prof. Herbert Mayr’s group, with the aim to investigate on the nucleophilic reactivities of di- and triaminobenzene derivatives performing their combination with different reference electrophiles, selected from the Mayr’s reactivity scales.

Questa tesi è mirata ad essere un lavoro che racchiude alcuni dei vari aspetti rilevanti che collegano la Green Chemistry alla sostenibilità ambientale. La tesi riguarda lo sviluppo sostenibile attraverso capitoli che concorrono alla progettazione di processi chimici eco-compatibili innovativi e approcci verdi per ridurre al minimo e/o rimediare l'inquinamento ambientale. In questo contesto, il mio progetto di dottorato ha affrontato tre temi principali: 1. Progettazione, sintesi e caratterizzazione di nuove molecole di tensioattivo che impiegano materie prime rinnovabili, acido itaconico e ammine lipofile, come materiali di partenza; il Capitolo 2 descrive questo argomento. 2. Sviluppo di una procedura sostenibile finalizzata alla sintesi multicomponente a cascata di biarilcalconi in acqua pura o in condizioni di catalisi micellare; in quest'ultimo caso, uno dei tensioattivi precedentemente sintetizzati è stato ampiamente impiegato; il Capitolo 5 descrive questo argomento. Capitolo 3 e Capitolo 4 descrivono il contesto scientifico e le innovazioni più importanti che hanno aperto la strada a i risultati conseguiti durante il 2 ° anno del corso di dottorato; il primo è una panoramica sull'uso dell'acqua come solvente per reazioni organiche; il secondo è una panoramica sulle reazioni di cross-coupling e lo sfruttamento in questo contesto della catalisi micellare. 3. Progettazione, sintesi e impiego di ligandi di tipo fenantrolinico deuterati per l'ossidazione aerobica palladio catalizzata del metil-glucoside, consentendo un elevato miglioramento della prestazione in questa reazione impegnativa; il Capitolo 7 raccoglie i risultati ottenuti, mentre il capitolo 6 riassume i più importanti progressi ottenuti negli ultimi anni nelle ossidazioni aerobiche di alcoli palladio-catalizzate. / This thesis is intended to be a work that encompasses some of the various relevant aspects linking the Green Chemistry practice to environmental sustainability. The thesis covers sustainable development through chapters that contribute to the design of novel environmentally benign chemical processes and green approaches to minimize and/or remediate environmental pollution. In this context, my PhD project has faced three main topics: 1. Design, synthesis and characterization of new surfactant molecules employing renewable feedstocks, itaconic acid and fatty amines, as starting materials; Chapter 2 describes this topic. 2. Development of a sustainable procedure aimed to the multicomponent cascade synthesis of biaryl-based chalcones in pure water or under micellar catalysis conditions; in the latter case, one of the surfactants previously synthesized has been widely employed; Chapter 5 describes this topic. Chapter 3 and Chapter 4 describe the scientific context and the most important innovations that have paved the way to the results achieved during the 2nd year of PhD course; the former is an overview on the use of water as solvent for organic reactions; the latter is an overview on cross-coupling reactions and the exploitation in this context of micellar catalysis. 3. Design, synthesis and exploitation of deuterated phenanthroline-type ligands for the aerobic palladium-catalyzed oxidation of methyl glucoside, allowing a high performance improvement in this challenging reaction; Chapter 7 collects the obtained results, while Chapter 6 summarizes the most important advances obtained in the last years in the palladium-catalyzed aerobic oxidations of alcohols.

Os estoques de carbono orgânico do solo (ECOS) nos ecossistemas naturais normalmente podem se manter em equilíbrio por longos períodos, porém as atividades antrópicas, especialmente a expansão da agricultura, usualmente provoca diminuição nos ECOS, com implicações nas funções ecossistêmicas e produtivas dos solos. Assim, a estimativa dos ECOS nos solos sob condições naturais e em agroecossistemas e a distribuição desses estoques na paisagem são questões científicas atuais. Este trabalho teve como objetivo amostrar solos para estimar os ECOS, compilar estudos sobre ECOS já publicados e avaliar comparativamente ECOS nas regiões dos Campos de Cima de Serra e na parte central do Planalto do Rio Grande do Sul. Para estabelecer os ECOS nestas áreas foram utilizados dados primários (coleta de amostras a campo e análises laboratoriais) e dados secundários (levantamentos, estudos e projetos de pesquisa já realizados), prioritariamente em camadas superficiais (0-30cm). A consolidação de dos resultados obtidos do campo e de estudos possibilitaram comparar os estudos existentes de forma tabular e visualizar em mapas considerando classes de solos e usos das terras. Considerando a camada mais superficial de 0-30 cm, os estoques médios (média geral dos valores medidos) na região dos Campos de Cima da Serra (173,5 Mg C ha-1) foram três vezes maiores que na região central do Planalto do Rio Grande do Sul (59,5 Mg C ha-1). De maneira similar, os ECOS nas camadas mais superficiais (0-10 e 0-20cm) também consideradas neste estudo também foram pelo menos duas vezes maiores nos Campos de Cima da Serra. Os mapas produzidos permitem visualizar a distribuição espacial destes estoques nas regiões. Estas informações podem ser usadas para definir políticas públicas no âmbito de agricultura conservacionista e auxiliar na atualização dos inventários nacionais de gases de efeito estufa. / Organic carbon stocks in soils under natural conditions are usually in equilibrium, but human intervention specially with the expansion of agriculture and silviculture leads to SOC (soil organic C) stocks losses. Thus, SOC stocks estimation and their distribution in the landscape is a crucial scientific topic. This study aimed to measure and benchmark current SOC stocks in fields from the Campos de Cima da Serra and the central part of the Planalto do Rio Grande do Sul. To update the SOC stocks in the study areas, primary data were assessed derived from field sampling and laboratory analysis) and secondary data (obtained from published surveys and research projects). Data from 0-30cm soil layer were primarily considered in this study. The consolidation of results from field and studies allowed to compare SOC stocks in tabular form and view maps considering soil types and land of uses. Considering the upper soil layer (0-30 cm), the average SOC stock (173.5 Mg C ha-1 - overall means of the measured values) in the region of Campos de Cima da Serra was three times higher than in the central section of the Planalto of Rio Grande do Sul (59.5 Mg C ha- 1). Similarly, SOC stocks in the shallower layers (0-10 and 0-20 cm) were at least twice as high in the Campos de Cima da Serra. The maps produced display the spatial distribution of measured or calculated SOC stocks. This information can be used to guide public policy for conservation agriculture programs and assist in conducting national greenhouse gas inventories.

A partir do (-)-epoxilimoneno (127) desenvolveu-se a preparação enantiosseletiva da dienona (5R)-4,8-dimetilbiciclo[3.3.0]octa-1(8),3-dien-2-ona (128), que representa um bloco de construção versátil para a síntese de produtos naturais e não-naturais opticamente ativos. A etapa-chave da síntese corresponde à conversão do aldeído quiral 163 na cianoidrina bicíclica 165, através da alquilação intramolecular da cianoidrina TMS-éter 164, conforme metodologia de Stork-Takahashi. A hidrogenação estereosseletiva da dienona 128 conduziu ao produto monossaturado 20, um intermediário avançado na preparação do ent-kelsoeno. Da mesma forma, a hidrogenação catalítica das duas ligações duplas C=C de 128 produziu o intermediário 129a, que representa a síntese formal do iridóide cis,cis-dihidronepetalactona (13). Além da preparação e funcionalização da dienona 128, investigou-se a cloração alílica de olefinas terminais, através de uma nova metodologia que emprega InCl3 na presença de NaClO. Este novo método de cloração alílica foi aplicado a diferentes substratos e forneceu cloretos alílicos com bons rendimentos. / This work describes the enantioselective preparation of (5R)-4,8-dimethylbicyclo[3.3.0]oct-1(8),3-dien-2-one (128) from (-)-limonene oxide (127). This compound holds the prospect of serving as useful building block or intermediate to prepare a variety of compounds having a bicyclo[3.3.0]octane framework. The key step is the conversion of the chiral aldehyde 163 to bicyclic cyanohydrin 165, through intramolecular alkylation of cyanohydrin TMS eter 164, according to Strok-Takahashi protocol. The stereoselective hydrogenation of dienone 128 led to monosaturated product 20, which is a important intermediate on the ent-kelsoene preparation. Also, catalytic hydrogenation of the two carbon-carbon double bonds of 128, produced 129a, which is a intermediate to formal synthesis of iridoid cis,cis-dihydronepetalactone 13. Further, a new methodology to allylic chlorination of terminal olefins which employ InCl3 in the presence of NaClO was developed. This method was applied to different compounds and furnished allylic chlorides in satisfactory yields.

A tacrina (4, 9-amino-1,2,3,4-tetraidroacridina), primeira droga aprovada nos EUA para o tratamento paliativo da doença de Alzheimer, apresenta elevada atividade farmacológica contra os sintomas dessa doença. Entretanto, devido aos efeitos colaterais apresentados pelo uso contínuo desse fármaco, como distúrbios gastrointestinais e hepatotoxicidade, várias pesquisas recentes evidenciam a importância da preparação de análogos da tacrina, com o objetivo de aumentar a eficiência do fármaco e minimizar seus efeitos colaterais. Neste trabalho estudou-se a reação de ciclodesidratação entre antranilonitrila (40) e ciclocetonas 26 na presença de diferentes ácidos de Lewis não-reportados na literatura, para a obtenção de 9-amino-1,2,3,4-tetraidroacridinas 41. A eficiência dos ácidos de Lewis em promover a reação de ciclodesidratação entre a antranilonitrila e a cicloexanona foi verificada na seguinte sequência: InCl3 > AlCl3 ~ BF3.Et2O > FeCl3 > BiCl3 ~ SbCl3 ~ SnCl2.2H2O. Este comportamento também foi verificado, de maneira geral, quando se utilizaram outras cetonas como substratos. Outros ácidos de Lewis testados, tais como RuCl3, CeCl3.7H2O, NiCl2, CoCl2.2H2O, CsCl, CrCl3.6H2O, MnCl2.4H2O, SrCl2.6H2O e Pd(OAc)2, não foram eficientes. As reações de ciclodesidratação foram realizadas empregando-se diferentes solventes e também na ausência de solvente levando à obtenção dos produtos em bons a excelentes rendimentos. Neste trabalho também foi apresentada uma racionalização mecanística para a reação de ciclocondensação entre 2-aminobenzonitrilas e cetonas cíclicas na presença de ácidos de Lewis. / Tacrine (4, 9-amino-1,2,3,4-tetrahydroacridine) is currently one of the major approved drugs for treatment of Alzheimer’s disease. Because of the serious side effects such as hepatotoxicity, a large number of its derivatives have been synthesized. The scope of Lewis acid-promoted cyclodehydratation reactions between anthranilonitrile (40) and several ketones 26, to afford tacrine and its derivatives, was expanded to include the use of various metal chloride salts not reported in the literature. The ability of the Lewis acids to effectively promote the cyclodehydratation between anthranilonitrile and cyclohexanone as the ketone was found to be the following order: InCl3 > AlCl3 ~ BF3.Et2O > FeCl3 > BiCl3 ~ SbCl3 ~ SnCl2.2H2O. The reactions were performed under both solvent and solvent-free conditions in good to excellent yields. Other Lewis acids screened, such as RuCl3, CeCl3.7H2O, NiCl2, CoCl2.2H2O, CsCl, CrCl3.6H2O, MnCl2.4H2O, SrCl2.6H2O and Pd(OAc)2 were not effective. In this work a mechanistic rationalization is given for the cyclodehydratation reaction of 2-aminobenzonitriles with cycloketones in the presence of Lewis acids.

A procura por novas tecnologias tem movido a ciência em todos seus setores. Na química um campo tecnológico que tem sido muito procurado nos últimos tempos é o dos compostos miméticos de produtos naturais. A busca de métodos simples e eficientes de síntese veio ao encontro desta busca com a click chemistry e sua cicloadição 1,3-dipolar catalisada por cobre, com a qual é possível a síntese de 1,2,3-triazóis-1,4-dissubtituídos de forma rápida e eficiente. Neste trabalho foi produzido um novo catalisador de cobre através do método sol-gel denominado Cu-sílica e testado o mesmo na cicloadição 1,3-dipolar frente a diferentes substratos e fontes de energia. Quando utilizados brometos de benzila em sistema one pot multicomponete obtivemos rendimentos de até 95% em sistema com fonte de calor após 12 horas de reação ou irradiação por microondas durante 10 minutos. Com o uso de ácidos borônicos azida e acetinelos como substrato chegamos a rendimentos de 91% com aquecimento e um tempo reacional de 48 horas a 50º C, outras fontes de energia não lograram êxito para este substrato. Finalmente foi desenvolveida uma metodologia one pot para síntese dos 1,2,3-triazóis a partir de álcoois, esta consiste de um sistema em 2 etapas reacionais que englobam três tranformações em 25 horas de reação com rendimento de 60%. / The search for new technologies has inspired the science in all areas of chemistry and one of the most studied research fields lays on the search for natural product's mimetics. A good example, among different efforts for simple and efficient new methods of synthesis, is the click chemistry and its Cu catalysed 1,3-dipolar cycloaddition, once this reaction permits quick acess to 1,4-disubstituted-1,2,3-triazoles. In this work we synthesized a copper catalyst through the sol-gel methodology, so called Cu-silica and tested it in the 1,3-cycloaddition reaction, using different starting materials and energy sources. At first we applied this catalyst in a multicomponent reaction in which benzyl bromides, sodium azide and different acetylenes and the reaction was heated for 12 hours or 10 minutes under microwave irradiation (50W), providing the 1,2,3-triazoles with 95% of yield. Further we changed the benzyl halides for boronic acids; we didn’t have success using non-classical heating systems (microwave or ultrasound), however under traditional heating at 50º C for 48 hours we got the product in 91% yield. Finally we developed a new one-pot metodology to obtain 1,2,3-triazoles from alchools. This procedure consists in a two-step continuous system embracing three transformations wihtin 25 hours with an overall yield of 60%.

Neste trabalho foi explorado o emprego de um catalisador heterogêneo à base de cobre na reação multicomponente para a obtenção de heterociclos imidazo[1,2-a]piridinas substituídos, que são moléculas com potencial aplicação farmacológica. O catalisador Cu/SiO2 foi sintetizado através do processo sol-gel, com a adição de cloreto de cobre (II) na hidrólise e policondensação do precursor alcóxisilano em meio ácido. A reprodutibilidade na síntese do material foi estudada através de variações de parâmetros de reação do sol-gel. Foram realizadas análises de microscopia eletrônica de varredura acoplada a EDS, isotermas de BET e BJH, cálculo teórico DFT e espectroscopia de absorção atômica de chama, visando a obtenção de um material de composição, área e porosidade compatível com um catalisador heterogêneo eficiente. Foi comprovada a atividade catalítica do compósito Cu/SiO2 na reação entre 2-aminopiridina, fenilacetileno e aldeídos diversos, para a obtenção de imidazo[1,2-a]piridinas com bons rendimentos. O mecanismo da reação foi proposto e os produtos caracterizados através de cromatografia gasosa acoplada a espectrômetro de massas e ressonância magnética nuclear de hidrogênio e carbono-13. / In this work it was explored the application of a copper based heterogeneous catalyst on multicomponent reaction for obtention of substituted imidazo[1,2- a]pyridine heterocyles, molecules with interesting pharmacological applications. The catalyst Cu/SiO2 was synthesized through the sol-gel process, by adding copper chloride (II) on hydrolysis and polycondensation of an alcoxysilane precursor in acidic media. Reproducibility of the synthesis of this material was studied by variation of sol-gel parameters. Analysis of scanning electronic microscopy with energy-dirpersive spectroscopy, BET and BJH isotherms, DFT theoretical calculation and flame atomic absorption spectroscopy aiming to achieve a material with composition, surface and porosity feasible with an efficient heterogeneous catalyst. It was proven the catalytic activity of the composite Cu/SiO2 in the reaction between 2- aminopyridine, phenylacethylene and diverse aldehydes furnishing imidazo[1,2-a]pyridines with good yields. The reaction mechanism was proposed and the products characterized by gas chromatography with mass spectrometer and nuclear magnetic resonance of hydrogen and carbon-13.

During the last fifteen years organocatalysis emerged as a powerful tool for the enantioselective functionalization of the most different organic molecules. Both C-C and C-heteroatom bonds can be formed in an enantioselective fashion using many types of catalyst and the field is always growing. Many kind of chiral catalysts have emerged as privileged, but among them Proline, cinchona alkaloids, BINOL, and their derivatives showed to be particularly useful chiral scaffolds. This thesis, after a short presentation of many organocatalysts and activation modes, focuses mainly on cinchona alkaloid derived primary amines and BINOL derived chiral Brønsted acids, describing their properties and applications. Then, in the experimental part, these compounds are used for the catalysis of new transformations. The enantioselective Friedel-Crafts alkylation of cyclic enones with naphthols using cinchona alkaloid derived primary amines as catalysts is presented and discussed. The results of this work were very good and this resulted also in a publication. The same catalysts are then used to accomplish the enantioselective addition of indoles to cyclic enones. Many catalysts in combination with many acids as co-catalysts were tried and the reaction was fully studied. Selective N-alkylation was obtained in many cases, in combination with quite good to good enantioselectivities. Also other kind of catalysis were tried for this reaction, with interesting results. Another aza-Michael reaction between OH-free hydroxylamines and nitrostyrene using cinchona alkaloid derived thioureas is briefly discussed. Then our attention focused on Brønsted acid catalyzed transformations. With this regard, the Prins cyclization, a reaction never accomplished in an enantioselective fashion until now, is presented and developed. The results obtained are promising. In the last part of this thesis the work carried out abroad is presented. In Prof. Rueping laboratories, an enantioselective Nazarov cyclization using cooperative catalysis and the enantioselective desymmetrization of meso-hydrobenzoin catalyzed by Brønsted acid were studied.

During the course of my Ph.D. in the laboratories directed by Prof. Alfredo Ricci at the Department of Organic Chemistry “A. Mangini” of the University of Bologna, I was involved in the study and the application of a number of organocatalytic systems, all coming from the natural chiral pool. The first part of this thesis will be devoted to new homogeneous organocatalytic reactions promoted by Cinchona alkaloid-based organocatalysts. Quinine based catalysts were found to be a very effective catalyst for Diels-Alder reactions involving 3-vinylindoles. Excellent results in terms of yields and enantioselectivities were achieved, outlining also a remarkable organocatalytic operational mode mimicking enzymatic catalysis. The same reaction with 2-vinylindoles showed a completely different behaviour resulting in an unusual resolution-type process. The asymmetric formal [3+2] cycloaddition with in situ generated N-carbamoyl nitrones using Cinchona-derived quaternary ammonium salts as versatile catalysts under phase transfer conditions, outlines another application in organocatalysis of this class of alkaloids. During the seven months stage in the Prof. Helma Wennemers’ group at the Department of Chemistry of the University of Basel (Switzerland) I have been involved in organocatalysis promoted by oligopeptides. My contribution regarded the 1,4-addition reaction of aldehydes to nitroolefins. In the work performed at the Department of Organic Chemistry “A. Mangini” of the University of Bologna, in collaboration with the ‘Institut Charles Gerhardt-Montpellier, of Montpellier (France) the possibility of performing for the first time heterogeneous organocatalysis by using a natural polysaccharide biopolymer as the source of chirality was disclosed. With chitosan, derived from deacetylation of chitin, a highly enantioselective heterogeneous organocatalytic aldol reaction could be performed. The use of an eco-friendly medium such as water, the recyclability of the catalytic specie and the renewable nature of the polysaccharide are assets of this new approach in organocatalysis and open interesting perspectives for the use of biopolymers.

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