Iodine-Catalyzed Regioselective Synthesis of Multisubstiuted Pyrrole Polyheterocycles Free from Rotamers and Keto–Enol Tautomers

A highly regioselective iodine-mediated cascade reaction for the synthesis of multifunctional polyheterocyclic systems is developed by employing 3-(2-oxo-2-arylethylidene)­oxindoles and 1,4-benzoxazinone as starting materials. The polyheterocycles are skillfully embraced with oxindole, pyrrole, and coumarin scaffolds, which are well-known for their enriched biological activity. The current approach worked under mild reaction conditions. The reaction afforded a single product, and no rotameric and keto–enol isomeric products are formed. The method is environmentally benign and atom-economical, and the only side product of this reaction is water. This protocol obviates the purification techniques such as column chromatography for the isolation of the products. The products were isolated by decantation of the solvent or by recrystallization. The reaction proceeds through inter- and intramolecular C–C and C–N bond formation.

本研究以3-(2-氧代-2-芳基亚乙基)羟吲哚(3-(2-oxo-2-arylethylidene)­oxindoles)和1,4-苯并恶嗪酮(1,4-benzoxazinone)为起始原料，开发了一种区域选择性优异的碘介导级联反应，用于构建多功能多杂环体系。所获得的多杂环化合物巧妙整合了羟吲哚(oxindole)、吡咯(pyrrole)与香豆素(coumarin)骨架，这类骨架因具备丰富的生物活性而广受关注。该方法可在温和反应条件下顺利进行，反应仅生成单一产物，未产生旋转异构及酮-烯醇异构副产物。此方法环境友好且原子经济性高，反应唯一的副产物为水，且无需借助柱色谱等纯化手段即可分离产物，仅通过溶剂倾析或重结晶便可得到目标化合物。反应过程涉及分子间与分子内的C-C键、C-N键形成步骤。