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Catalytic Asymmetric Tandem Reaction of Tertiary Enamides: Expeditious Synthesis of Pyrrolo[2,1‐ a ]isoquinoline Alkaloid Derivatives
Author(s) -
Xu XinMing,
Zhao Liang,
Zhu Jieping,
Wang MeiXiang
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201600119
Subject(s) - isoquinoline , chemistry , enantioselective synthesis , synthon , diastereomer , moiety , stereochemistry , intramolecular force , tandem , combinatorial chemistry , alkaloid , cascade reaction , catalysis , organic chemistry , materials science , composite material
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.