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Scaffold-Inspired Enantioselective Synthesis of Biologically Important Spiro[pyrrolidin-3,2′-oxindoles] with Structural Diversity through Catalytic Isatin-Derived 1,3-Dipolar Cycloadditions

Authors

  • Feng Shi,

    1. School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, 221116 (P.R. China)
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  • Zhong-Lin Tao,

    1. Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026 (P.R. China), Fax: (+86) 551-3606266
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  • Shi-Wei Luo,

    Corresponding author
    1. Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026 (P.R. China), Fax: (+86) 551-3606266
    • Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026 (P.R. China), Fax: (+86) 551-3606266
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  • Prof. Shu-Jiang Tu,

    1. School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, 221116 (P.R. China)
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  • Prof. Liu-Zhu Gong

    Corresponding author
    1. Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026 (P.R. China), Fax: (+86) 551-3606266
    • Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026 (P.R. China), Fax: (+86) 551-3606266
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Abstract

Catalytic asymmetric construction of the biologically important spiro[pyrrolidin-3,2′-oxindole] scaffold with contiguous quaternary stereogenic centers in excellent stereoselectivities (up to >99:1 d.r., 98 % ee) has been established by using an organocatalytic 1,3-dipolar cycloaddition of isatin-based azomethine ylides. This protocol represents the first example of catalytic asymmetric 1,3-dipolar cycloadditions involving azomethine ylides generated in situ from unsymmetrical cyclic ketones. In addition, theoretical calculations were performed on the transition state of the reaction to understand the stereochemistry. Preliminary bioassays with these spiro[pyrrolidin-3,2′-oxindole] revealed that several compounds showed moderate cytotoxicity to SW116 cells.

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