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Organocatalytic Asymmetric Conjugate Addition of 3-Monosubstituted Oxindoles to (E)-1,4-Diaryl-2-buten-1,4-diones: A Strategy for the Indirect Enantioselective Furanylation and Pyrrolylation of 3-Alkyloxindoles

Authors

  • Yu-Hua Liao ,

    1. National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (P.R. China)
    2. Graduate School of Chinese Academy of Sciences, Beijing 100049 (P.R. China)
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  • Xiong-Li Liu ,

    1. National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (P.R. China)
    2. Graduate School of Chinese Academy of Sciences, Beijing 100049 (P.R. China)
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  • Dr. Zhi-Jun Wu,

    1. Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041 (P.R. China)
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  • Prof. Xi-Lin Du,

    1. Department of General Surgery, TangDu Hospital, The Fourth Military Medical University, Xi'an 710038 (P.R. China)
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  • Prof. Dr. Xiao-Mei Zhang,

    1. National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (P.R. China)
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  • Prof. Dr. Wei-Cheng Yuan

    Corresponding author
    1. National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (P.R. China)
    • National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (P.R. China)
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Abstract

An asymmetric conjugate addition of 3-monosubstituted oxindoles to a range of (E)-1,4-diaryl-2-buten-1,4-diones, catalyzed by commercially available cinchonine, is described. This organocatalytic asymmetric reaction affords a broad range of 3,3′-disubstituted oxindoles that contain a 1,4-dicarbonyl moiety and vicinal quaternary and tertiary stereogenic centers in high-to-excellent yields (up to 98 %), with excellent diastereomeric and moderate-to-high enantiomeric ratios (up to 99:1 and 95:5, respectively). Subsequently, cyclization of the 1,4-dicarbonyl moiety in the resultant Michael adducts under different Paal–Knorr conditions results in two new kinds of 3,3′-disubstituted oxindoles—3-furanyl- and 3-pyrrolyl-3-alkyl-oxindoles—in high yields and good enantioselectivities. Notably, the studies presented here sufficiently confirm that this two-step strategy of sequential conjugate addition/Paal–Knorr cyclization is not only an attractive method for the indirect enantioselective heteroarylation of 3-alkyloxindoles, but also opens up new avenues toward asymmetric synthesis of structurally diverse 3,3′-disubstituted oxindole derivatives.

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