Organocatalytic enantioselective SN1-type dehydrative nucleophilic substitution: access to bis(indolyl)methanes bearing quaternary carbon stereocenters |
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| Authors: | Wen-Run Zhu Qiong Su Xiao-Yi Deng Jia-Sheng Liu Tao Zhong Shan-Shui Meng Ji-Tao Yi Jiang Weng Gui Lu |
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| Institution: | Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 P. R. China, |
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| Abstract: | A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized via 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 er). 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 SN1-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−1).A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized via enantioconvergent dehydrative nucleophilic substitution. |
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