Construction of Axially Chiral Indoles by Cycloaddition-Isomerization via Atroposelective Phosphoric Acid and Silver Sequential Catalysis
Construction of Axially Chiral Indoles by Cycloaddition-Isomerization via Atroposelective Phosphoric Acid and Silver Sequential Catalysis
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DOI：
10.1021/acscatal.2c02574
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发表时间：
2022-06-22
期刊：
影响因子：
12.9
通讯作者：
Shao, Zhihui
中科院分区：
文献类型：
--
作者：
Wang, Yingcheng;Zhou, Xue;Shao, Zhihui
轴向手性吲哚基骨架存在于天然产物、生物活性分子和手性配体中。因此，开发从头构建这些框架的催化不对称atroposelective方法是非常有价值的。在这里，atroposelective有机/金属组合的双重催化策略从头构建有价值的轴向手性吲哚框架已被开发。该方案利用两种手性磷酸（1摩尔%）与硝酸银（1摩尔%）的组合的催化剂系统，是基于我们最近引入的C-炔基N，O-缩醛和2-萘胺的未报道的分子间环加成-异构化反应。以良好的产率和对映选择性合成了一类重要的C-N轴手性吲哚衍生物。所获得的轴向手性吲哚也为催化剂控制的具有两个C-N轴的轴向手性吲哚的阻转选择性合成提供了平台，这是通过现有方法难以获得的。本工作也是2-萘胺在环加成反应中用作1，3-二亲核试剂和三原子（CCN）配体的一个实例。
Axially chiral indole-based frameworks occur in natural products, bioactive molecules, and chiral ligands. Thus, the development of catalytic asymmetric atroposelective approaches for de novo construction of these frameworks is highly valuable. Here, the atroposelective organo/metal combined dual catalysis strategy for de novo construction of valuable axially chiral indole frameworks has been developed. This protocol utilized a catalyst system of two chiral phosphoric acids (1 mol %) in combination with AgNO3 (1 mol %) and was based on the unreported intermolecular cycloaddition-isomerization reaction of our recently introduced C-alkynyl N,O-acetals and 2-naphthylamines. An important class of hitherto inaccessible axially chiral indoles with a C-N axis were obtained in good yields and enantioselectivities. The axially chiral indoles obtained also provided a platform for the catalyst-controlled atroposelective synthesis of axially chiral indoles bearing two C-N axes, which are difficult to access by the existing methods. This work is also an example of 2-naphthylamines used as 1,3-dinucleophiles and three-atom (CCN) synthons in cycloadditions.