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Organocatalytic Michael/Michael Cycloaddition Enabled Asymmetric Construction of Hexahydroxanthones with Skeletal Diversity
Author(s) -
Liu XiongLi,
Wei QiDi,
Zuo Xiong,
Xu ShengWen,
Yao Zhen,
Wang JunXin,
Zhou Ying
Publication year - 2019
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201900119
Subject(s) - stereocenter , michael reaction , chemistry , isoxazole , cycloaddition , domino , stereochemistry , combinatorial chemistry , enantioselective synthesis , oxindole , catalysis , organic chemistry
Abstract A highly efficient strategy for stereocontrolled construction of potentially bioactive and structurally rigid isoxazole‐fused spirocyclohexane oxindole‐based hexahydroxanthones via an organocatalytic domino Michael/Michael cycloaddition of multifunctional chromone‐based oxindole as a 4C building block and 3‐methyl‐4‐nitro‐5‐alkenyl‐isoxazole as an activated Michael acceptor is reported. Complex and skeleton‐diversified hexahydroxanthones bearing five continuous stereocenters including one spiro quaternary carton center were smoothly afforded in up to 92% yield, >20:1 d.r. and >99% ee. Further transformation of the product into other potentially bioactive molecules has also been demonstrated. This method could also forge the libraries of medicinally relevant molecules with skeletal diversity, thus to facilitate the search for new bioactive entities.