Research On Cycloaddition Of 3-Indolylmethanol Catalyzed By Lewis And Br?nsted Acid

Multi-substituted indoles are significant heterocyclic skeletons, which widely exist in many natural products with unique biological and pharmacological activity and phmaceutical molecules. They are not only important intermediates in fine chemicals, but also widely used in the fields of pharmaceuticals, pesticides, dyes, fragrances, forages, food and additives, the chemical syntheses of which have been receiving considerable interest from synthetic community. Therefore, it is of high significance to design novel substrates, innovate new synthetic strategies to construct multi-substituted indole and their derivatives, which is of considerably academic importance and highly valuable in industry.In this thesis, synthetic strategies of multi-substituted indoles are discussed, which are constructed with unusual substrates via simple and efficient cycloaddition and Friedel-Crafts alkylation. The research work is divided into three sections, which are briefly introduced as follows:Section I: Lewis acid catalyzed [4+3] cycloaddition of 3-indolylmethanols.With 3-indolylmethanols owning potential biological activity as substrate and under the catalysis of Lewis acids, e.g. InBr3, the [4+3] cycloaddition of alcohol and conjugated dienes was successfully accomplished, furnishing novel compounds containing indole and 7-membered cyclic skeleton.Section II: Br?nsted Acid Catalyzed Friedel-crafts alkylation reaction of 3-indolylmethanols.Similar to the first part, with isatin-derived 3-indolylmethanols owning potential biological and pharmacological activity as substrate, and under the catalysis of Br?nsted acid, i.e.(s)-camphor sulfonic acid, Friedel-crafts alkylation reaction of 3-indolylmethanols could be accomplished with various heterocyclic aromatic compounds, yielding a series of 3,3'-indolyloxindole derivatives with potential biological activities.Section III: Based on the intermediate of ortho-Quinone Methides [4+2] cycloaddition reaction.With 2-(hydroxymethyl)phenol as substrates and under the catalysis of Br?nsted acid, chroman derivatives could be achieved via [4+2] cycloaddition of the in situ generated ortho-quinone methides and a series of diene or mono-olefin. The relative configurations of products were confirmed through two-dimensional spectra(e.g. H, H-COSY and NOESY), and the reaction mechanism was verified via theoretical calculation. The products were further elaborated via several synthetic approaches. The innovation of the reaction is that cyclopentadiene and other cpnjugate dienes are employed as dienes in the normal [4+2] reaction, whereas in this reaction, cyclopentadiene and other cpnjugate dienes served as dienophiles instead and the o-QMs generated in situ was exploited as diene. In Brief, a simple and fast synthetic method was developed to construct 2-alkenyl chroman skeleton, moreover the reaction mode of cyclopentadiene is updated.