Transformações de cetonas α,β- e α,β,γ,δ-insaturadas. Novas rotas de síntese de 2,3-diarilxantonas

Esta dissertação é constituída por duas partes: na primeira parte reportam-se estudos de epoxidação em cetonas α,β- e α,β,γ,δ-insaturadas, catalisados por um complexo de salen Mn(III), conhecido como catalisador de Jacobsen; na segunda parte desenvolvem-se novas rotas de síntese de 2,3-diarilxantonas em que se recorre à reacção de Heck de cromonas bromadas com estirenos. Os estudos de epoxidação apresentados na primeira parte desta dissertação foram efectuados em três sistemas carbonílicos α,β- e α,β,γ,δ-insaturados: (E)-calconas, (E,E)-cinamilidenoacetofenonas e (E)-2-estirilcromonas e utilizando o peróxido de hidrogénio e o iodosilbenzeno como oxidantes. As reacções de epoxidação de (E)-calconas originaram os respectivos trans-epóxidos em bons rendimentos enquanto que nas (E)-2’-hidroxicalconas isolaram-se os produtos de ciclização dos respectivos trans-epóxidos, as trans-3-hidroxiflavanonas em rendimentos moderados. As reacções de epoxidação de (E,E)-cinamilidenoacetofenonas proporcionaram a formação dos respectivos γ,δ-trans-monoepóxidos e α,β:γ,δ- trans,trans-diepóxidos. De referir que no caso da (E)-4-nitrocinamilidenoacetofenona foi também possível isolar o α,β-trans-monoepóxido. Para as (E,E)-2’-hidroxicinamilidenoacetofenonas, além dos γ,δ-trans-monoepóxidos, isolaram-se os produtos resultantes da ciclização de α,β-trans-monoepóxidos, as (E)-2,3-trans-3-hidroxi-2-estiril-4-cromanonas. A epoxidação de (E,E)-γ-metilcinamilidenoacetofenonas originou uma mistura diasteriomérica dos γ,δ-trans-monoepóxidos, o que leva a considerar um mecanismo radicalar para este tipo de reacção. As reacções de epoxidação de (E)-2-estirilcromonas e (E)-5-hidroxi-2-estirilcromonas originaram os respectivas α,β-epóxidos, tendo sido necessário recorrer à técnica de HPLC para isolar os resultantes da epoxidação de (E)-5-hidroxi-2-estirilcromonas. Estudos de RMN e HPLC revelaram que apesar de ter sido utilizado um catalisador quiral na reacção de epoxidação, este não conseguiu induzir quiralidade em quaisquer dos produtos obtidos dos três tipos de compostos estudados. Na segunda parte desta dissertação aborda-se a síntese de novos derivados de xantona, nomeadamente 2,3-diarilxantonas. Para o efeito foram desenvolvidas duas rotas sintéticas. A primeira via de síntese utiliza como reagente de partida a 3-bromo-2-metilcromona e a segunda envolve a utilização de (E)-3-bromo-2-estirilcromonas.preparação de 3-bromo-2-metilcromonas envolveu; i) acetilação de 2’-hidroxiacetofenonas seguida de transposição do grupo acetilo; ii) bromação dos compostos cetónicos formados e ciclização do produto obtido, num passo único, originando as 3-bromo-2-metilcromonas. O derivado não substituído foi obtido em bom rendimento, os derivados 4’-benziloxilo e 6’-benziloxilo foram obtidos em rendimentos moderados, nao tendo sido possível isolar a 4’,6’-dibenziloxi-3-bromo-2-metilcromona. A preparação de (E)-3-bromo-2-estirilcromonas foi efectuada recorrendo ao método de Baker-Venkataraman, partindo de 2’-hidroxiacetofenonas e derivados de ácidos cinâmicos, ambos adequadamente substituídos. Os ésteres assim obtidos foram tratados com base originando as 3-hidroxi-1,4-pentadieno-4-onas que foram sujeitas, num só passo, a condições de bromação e ciclização do produto obtido, de forma a originar as pretendidas (E)-3-bromo-2-estirilcromonas. A síntese de 2,3-diarilxantonas partindo da 3-bromo-2-metilcromona envolveu reacções de Heck com estirenos comerciais e catalisadas por reagentes de paládio, obtendo-se (E)-2-metil-3-estirilcromonas. Por condensação aldólica destas com benzaldeídos originaram (E,E)-2,3-diestirilcromonas, que após refluxo em 1,2,4-triclorobenzeno dão origem às pretendidas 2,3-diarilxantonas. A reacção de Heck de (E)-3-bromo-2-estirilcromonas e estirenos levou à formação directa de 2,3-diarilxantonas. Esta transformação explica-se pela formação de (E,E)-2,3-diestirilcromonas, seguida de processos de electrociclização e oxidação. Foi também possível isolar neste tipo de reacção 2,3-diaril-3,4-di-hidroxantonas, intermediários semi-oxidados das xantonas obtidas. A última etapa deste trabalho consistiu na desalquilação das benziloxi- e metoxi-2,3-diarilxantonas sintetizadas. Na caracterização estrutural dos compostos sintetizados recorreu-se a técnicas analíticas actuais, em especial através de estudos de espectroscopia de ressonância magnética nuclear (RMN) [espectros de 1H, de 13C e estudos bidimensionais de correlação espectroscópica homo e heteronuclear e de efeito nuclear de Overhauser (NOESY)]. Estes estudos foram também essenciais no estabelecimento da estereoquímica presente na maioria dos compostos sintetizados. Os novos produtos obtidos foram igualmente caracterizados por espectrometria de massa recorrendo em alguns casos à técnica de impacto electrónico noutros, à técnica de “electrospray” e sempre que possível acompanhados de microanálise elementar ou espectrometria de massa de alta resolução.This dissertation is constituted by two parts: in the first one we report the epoxidation studies of α,β-and α,β,γ,δ-unsaturated ketones, catalysed by the well-known Jacobsen catalyst; in the second one novel routes of 2,3-diarylxanthones were developed, in which we use the Heck reaction of bromochromones with styrenes. The epoxidation studies presented in the firs part of this dissertation were accomplished in three α,β-unsaturated carbonylic systems: (E)-chalcones, (E,E)-cinnamylideneacetophenones and (E)-2-styrylchromones using hydrogen peroxide and iodosylbenzene as oxidants. Good yields were obtained in the synthesis of chalcone trans-epoxides; concerning the (E)-2’-hydroxychalcones, the cyclisation products of the epoxides, trans-3-hydroxyflavanones, were obtained in moderated yields. The epoxidation of (E,E)-cinnamylideneacetophenones leads to the formation of the respective γ,δ-trans-monoepoxides and α,β:γ,δ-trans,trans-diepoxides. In the case of the (E)-4-nitrocinnamylideneacetophenone it was also possible to isolate the α,β-trans-monoepoxide. For (E,E)-2’-hydroxycinnamylideneacetophenones besides the γ,δ-trans-monoepoxides it was also possible to isolate the cyclisation products of the α,β-trans-monoepoxides, (E)-2,3-trans-3-hydroxy-2-styryl-4-chromanones. The epoxidation of (E,E)-γ-methylcinnamylideneacetophenones gives a diasteriomeric mixture of γ,δ-trans-monoepoxides which lead us to propose a stepwise radicalar mechanism. The epoxidation of (E)-2-styrylchromones and (E)-5-hydroxystyrylchromones leads to the formation of the respective α,β-trans-epoxides, being necessary the use of HPLC to separate those obtained from (E)-5-hydroxystyrylchromones. NMR and HPLC studies showned that no chirality were induced in the epoxidation products of any of the studies, in spite of the use of chiral catalyst. The second part of this dissertation is dedicated to the synthesis of novel xantone derivatives, mainly 2,3-diarylxanthones. To achive the target, two synthetic routes were developed: The first uses the 3-bromo-2-methylchromone as starting material and the second one uses (E)-3-bromo-2-styrylchromones.This dissertation is constituted by two parts: in the first one we report the epoxidation studies of α,β-and α,β,γ,δ-unsaturated ketones, catalysed by the well-known Jacobsen catalyst; in the second one novel routes of 2,3-diarylxanthones were developed, in which we use the Heck reaction of bromochromones with styrenes. The epoxidation studies presented in the firs part of this dissertation were accomplished in three α,β-unsaturated carbonylic systems: (E)-chalcones, (E,E)-cinnamylideneacetophenones and (E)-2-styrylchromones using hydrogen peroxide and iodosylbenzene as oxidants. Good yields were obtained in the synthesis of chalcone trans-epoxides; concerning the (E)-2’-hydroxychalcones, the cyclisation products of the epoxides, trans-3-hydroxyflavanones, were obtained in moderated yields. The epoxidation of (E,E)-cinnamylideneacetophenones leads to the formation of the respective γ,δ-trans-monoepoxides and α,β:γ,δ-trans,trans-diepoxides. In the case of the (E)-4-nitrocinnamylideneacetophenone it was also possible to isolate the α,β-trans-monoepoxide. For (E,E)-2’-hydroxycinnamylideneacetophenones besides the γ,δ-trans-monoepoxides it was also possible to isolate the cyclisation products of the α,β-trans-monoepoxides, (E)-2,3-trans-3-hydroxy-2-styryl-4-chromanones. The epoxidation of (E,E)-γ-methylcinnamylideneacetophenones gives a diasteriomeric mixture of γ,δ-trans-monoepoxides which lead us to propose a stepwise radicalar mechanism. The epoxidation of (E)-2-styrylchromones and (E)-5-hydroxystyrylchromones leads to the formation of the respective α,β-trans-epoxides, being necessary the use of HPLC to separate those obtained from (E)-5-hydroxystyrylchromones. NMR and HPLC studies showned that no chirality were induced in the epoxidation products of any of the studies, in spite of the use of chiral catalyst. The second part of this dissertation is dedicated to the synthesis of novel xantone derivatives, mainly 2,3-diarylxanthones. To achive the target, two synthetic routes were developed: The first uses the 3-bromo-2-methylchromone as starting material and the second one uses (E)-3-bromo-2-styrylchromones.The preparation of 3-bromo-2-methylchromones was made through: i) acetylation of 2’-hydroxyacetophenones followed by the transposition of the acetyl group, ii) bromination of the formed ketonic compounds and cyclisation in one step, giving the desired 3-bromo-2-methylchromones. The unsubstituted derivative was obtained in good yield, the 4’-benzyloxy and 6’-benzyloxy derivatives were obtained in moderate yields and it was not possible to isolate 4’,6’-dibenzyloxy-3-bromo-2-methylchromone. (E)-3-Bromo-2-styrylchromones were obtained by the Baker-Venkataraman method, starting with 2’-hydroxyacetophenones and cinnamic acid derivatives, both appropriated substituted. The formed esters were treated with base giving 3-hydroxy-1,4-pentadiene-1-ones which were submitted to bromination and cyclisation in one step in order to achive the desired (E)-3-bromo-2-styrylchromones. The synthesis of 2,3-diarylxanthones starting from the 3-bromo-2-methylchromones involved a Heck reaction with commercial styrenes, catalysed by palladium catalysts, to afford (E)-2-methyl-3-styrylchromones. The aldol condensation of these products with benzaldehydes leads to (E,E)-2,3-distyrylchromones, which after reflux in 1,2,4-trichlorobenzene gives the desired 2,3-diarylxanthones. A Heck reaction between (E)-3-bromo-2-styrylchromones and commercial styrenes aforded directly the desired 2,3-diarylxanthones. This transformation is explained by the formation of (E,E)-2,3-distyrylchromones followed by electrocyclisation and oxidation processes. It was also possible to isolate in this type of reaction 2,3-diaryl-3,4-di-hidroxanthones, semi-oxidized intermediates of the obtained xanthones. Finally the dealkylation of the benzyloxy- and methoxy-2,3-diarylxanthones synthetized were performed in order to prepare hydroxy-2,3-diarylxanthones. All the synthesised compounds were characterised using modern analytical techniques, with special emphasis on exhaustive nuclear magnetic resonance (NMR) spectroscopic studies [1H and 13C spectra, two dimensional homonuclear and heteronuclear spectroscopy and NOESY]. All the new compounds were also characterized by mass spectrometry, in some cases using electronic impact and in others electrospray ionization technique and as long as possible elemental analysis or high resolution mass spectrometry were also carried on