Li Tian-Zhen, Liu Si-Jia, Sun Yu-Wen, Deng Shuang, Tan Wei, Jiao Yinchun, Zhang Yu-Chen, Shi Feng
School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, China.
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China.
Angew Chem Int Ed Engl. 2021 Feb 1;60(5):2355-2363. doi: 10.1002/anie.202011267. Epub 2020 Dec 4.
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.
通过六氟异丙醇（HFIP）和手性磷酸（CPA）的协同催化，实现了硝酮与2-吲哚甲醇的区域和对映选择性（3+3）环加成反应。采用这种方法，一系列吲哚稠合的六元杂环化合物得以高产率（高达98%）合成，具有优异的对映选择性（高达96% ee）和专一的区域特异性。这种方法不仅实现了首例硝酮的有机催化不对称（3+3）环加成反应，还实现了首例2-吲哚甲醇的C3-亲核不对称（3+3）环加成反应。更重要的是，理论计算阐明了助催化剂HFIP在帮助CPA控制反应的活性和对映选择性方面的作用，展示了一种新的协同催化模式。
