Xu Xin-Ming, Zhao Liang, Zhu Jieping, Wang Mei-Xiang
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH 5304, 1015, Lausanne, Switzerland.
Angew Chem Int Ed Engl. 2016 Mar 7;55(11):3799-803. doi: 10.1002/anie.201600119. Epub 2016 Feb 16.
Reported is a new and efficient strategy for rapid construction of the chiral tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one structure from unique tertiary enamide synthons. A Cu(OTf)2 /chiral Pybox complex catalyzes the intramolecular enantioselective addition of tertiary enamides to ketonic carbonyls with subsequent diastereoselective interception of the resulting acyliminium by tethered electron-rich aryl moiety. The tandem reaction produces diverse tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one derivatives as the sole diastereoisomers in good to excellent yields with up to 98.5 % ee. The transformations of the resulting heterocycles into various hexahydropyrrolo[2,1-a]isoquinoline derivatives were also demonstrated. The cyclization products, which are difficult to obtain by other synthetic means, are structural motifs found in many bioactive alkaloids.
报道了一种从独特的叔烯酰胺合成子快速构建手性四氢吡咯并[2,1-a]异喹啉-3(2H)-酮结构的新型高效策略。Cu(OTf)₂/手性Pybox配合物催化叔烯酰胺与酮羰基的分子内对映选择性加成，随后通过连接的富电子芳基部分非对映选择性地捕获生成的酰基亚胺离子。该串联反应以良好至优异的产率（高达98.5% ee）生成多种四氢吡咯并[2,1-a]异喹啉-3(2H)-酮衍生物作为唯一的非对映异构体。还展示了所得杂环向各种六氢吡咯并[2,1-a]异喹啉衍生物的转化。这些环化产物难以通过其他合成方法获得，是许多生物活性生物碱中的结构基序。
