title: Catalytic Asymmetric Tandem Reaction of Tertiary Enamides: Expeditious Synthesis of Pyrrolo[2,1-a]isoquinoline Alkaloid Derivatives.
abstract: 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.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Xu
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH 5304, 1015, Lausanne, Switzerland.
authors.forename: Jieping
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China. wangmx@mail.tsinghua.edu.cn.|Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, 300072, China. wangmx@mail.tsinghua.edu.cn.
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D007546:Isoquinolines / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis*
chemical_list: D000470:Alkaloids; D000577:Amides; D007546:Isoquinolines; D011758:Pyrroles; C560364:pyrrolo(2,1-a)isoquinoline
keywords: alkaloids; asymmetric catalysis; copper; cyclizations; synthetic methods