Cicloadiciones tándem de isonitrilos para la síntesis de sistemas heterocíclicos

Resumo

Multicomponent reactions constitute a very efficient methodology for the synthesis of complex molecules from simple starting materials. In this Thesis we have developed a novel multicomponent methodology based on the trapping of unstable intermediate 2-aminofurans for the synthesis of diverse polyheterocyclic systems. Thus, the multicomponent coupling of isocyanides, 3-carbonylchromones and dienophiles affords straightforwardly 4-aminoxanthones in one-pot. This tandem process involves the [4+1] cycloaddition of the isocyanide and 3-carbonylchromone leading to a 2-aminofuran, which suffers an immediate [4+2] cycloaddition with the dienophile present in the reaction medium, followed by aromatization of the cycloadduct. Interestingly, the use of non-symmetric dienophiles allows the isolation of non-aromatized 1-hydroxydihydroxanthones, structurally related to bioactive ergochromes. Furthermore, when natural sugar-derived nitroalkenes are used as dienophiles the reaction takes place with high diastereoselectivity, constituting a new highly convergent procedure for the synthesis of homochiral mycotoxin derivatives. To probe the scope of this novel methodology other a,ß-unsaturated carbonyl compounds were investigated. Thus the reaction of 3-carbonylcoumarins, isocyanides and dienophiles readily leads to 6H-benzo[c]chromen-6-ones through a similar mechanism. In summary, the trapping of reactive 2-aminofurans have shown to be an efficient and high yielding strategy for the synthesis of complex both aromatic and non-aromatic heterocycles with biological interest.