Asymmetric Synthesis Of 3-substituted-3-hydroxy-2-carbonyl Indole Compounds

Isatin is a natural oxoindole derivative,which is widely found in many natural products.Due to their unique structure and broad spectrum of biological activities,isatin derivatives have become one of the hot topics in synthetic chemistry and pharmaceutical chemistry in recent years.Among them,oxoindoles containing chiral centers,especially 3-substituted-3-hydroxy-2-carbonyl indoles containing chiral centers at 3-position,are one kind of important natural product intermediates and drug leading targets,showing extensive biological activities.Therefore,asymmetric synthesis of these compounds have received more and more attentions.The asymmetric synthesis of 3-hydroxyl-3-(2-oxypropyl)-2-carbonyl indoles and 3hydroxyl-3-indoles-2-carbonyl indoles were investigated in this thesis.1?Asymmetric synthesis of 3-hydroxy-3-(2-oxypropyl)-2-carbonyl indole compoundsInspired by the Aldol condensation enzyme Aldolase II,a mental salt of Zn(OAc)2·2H2O was combined with prolinamide-based small organic catalyst(L1)system to synergistically catalyze the asymmetric aldol reaction of isatin and acetone.Different from organic small molecule catalysts,this is a new kind of catalysis system.It was found that the reaction rates and product selectivities were significantly improved compared with that of the organic small molecule catalytic system.The experimental results showed that at-20?,the best results could be obtained by using 2.5 mol%catalyst with isopropyl alcohol as solvent.The yields of 3-hydroxy-3-(2-oxypropyl)-2-carbonyl indoles were between 82%and 99%,and the ee values of the products were up to 92%.2?Asymmetric synthesis of 3-hydroxyl-3-indolyl-2-carbonyl indole compoundsIt was found that the chiral proline ligand L7a could catalyze the asymmetric Friedel-Crafts alkylation reaction between isatins and indole.The results showed that with 20 mol%catalyst and isopropanol as solvent,the yields of indole and isatins with different substituents were between 80%and 99%,however,the highest ee value is only 65%.Bisedes,no by-products 3,3-diindolyl-2-carbonyl indoles were produced.