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Regio‐ and Enantioselective (3+3) Cycloaddition of Nitrones with 2‐Indolylmethanols Enabled by Cooperative Organocatalysis
Author(s) -
Li TianZhen,
Liu SiJia,
Sun YuWen,
Deng Shuang,
Tan Wei,
Jiao Yinchun,
Zhang YuChen,
Shi Feng
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202011267
Subject(s) - enantioselective synthesis , cycloaddition , organocatalysis , chemistry , reactivity (psychology) , nucleophile , catalysis , combinatorial chemistry , phosphoric acid , organic chemistry , stereochemistry , medicine , alternative medicine , pathology
The regio‐ and enantioselective (3+3) cycloaddition of nitrones with 2‐indolylmethanols was accomplished by the cooperative catalysis of hexafluoroisopropanol (HFIP) and chiral phosphoric acid (CPA). Using this approach, a series of indole‐fused six‐membered heterocycles were synthesized in high yields (up to 98 %), with excellent enantioselectivities (up to 96 % ee ) and exclusive regiospecificity. This approach enabled not only the first organocatalytic asymmetric (3+3) cycloaddition of nitrones but also the first C3‐nucleophilic asymmetric (3+3) cycloaddition of 2‐indolylmethanols. More importantly, theoretical calculations elucidated the role of the cocatalyst HFIP in helping CPA control the reactivity and enantioselectivity of the reaction, demonstrating a new mode of cooperative catalysis.