Organocatalytic enantioselective S1-type dehydrative nucleophilic substitution: access to bis(indolyl)methanes bearing quaternary carbon stereocenters.

Journal: Chemical science
Published Date:

Abstract

A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized enantioconvergent dehydrative nucleophilic substitution. A broad range of 3,3'-, 3,2'- and 3,1'-BIMs were obtained under mild conditions with excellent efficiency and enantioselectivity (80 examples, up to 98% yield and >99 : 1 ). By utilizing racemic 3-indolyl tertiary alcohols as precursors of alkyl electrophiles and indoles as C-H nucleophiles, this organocatalytic strategy avoids pre-activation of substrates and produces water as the only by-product. Mechanistic studies suggest a formal S1-type pathway enabled by chiral phosphoric acid catalysis. The practicability of the obtained enantioenriched BIMs was further demonstrated by versatile transformation and high antimicrobial activities (3al, MIC: 1 μg mL).

Authors

  • Wen-Run Zhu
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Qiong Su
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Xiao-Yi Deng
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Jia-Sheng Liu
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Tao Zhong
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Shan-Shui Meng
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Ji-Tao Yi
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Jiang Weng
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.
  • Gui Lu
    Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University Guangzhou 510006 P. R. China wengj2@mail.sysu.edu.cn lugui@mail.sysu.edu.cn.

Keywords

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