醌亚胺参与的有机催化不对称合成轴手性吲哚化合物

轴手性吲哚是一类普遍存在于天然产物、药物和生物活性分子中的核心骨架，在不对称催化领域具有广泛应用。目前，尽管已经报道了一些合成方法，但其不对称合成仍然面临着反应体系复杂、底物类型受限、需要特定的活化基团等挑战。因此，开发简单高效的轴手性吲哚骨架构建策略具有重要的现实意义。醌亚胺作为一类高效的合成砌块，能够参与到多种功能化合物的不对称合成中。本文旨在以醌亚胺和吲哚为反应底物，在手性磷酸的催化下，通过引入不同的保护基来调节亚胺氮上电子云密度，从而调控反应的化学选择性，高效构建出三种轴手性吲哚骨架。

首先，以手性磷酸为催化剂，通过 N-酰基保护的醌亚胺与叔丁基吲哚
进行不对称偶联反应，高效构建轴手性 3-芳基吲哚骨架（共 27 个例子）。
该方法具有原料易得、底物范围广、反应产率高（最高达 94%）和对映选择性优异（ee 最高达 95%）等优点。对产物进行了多种衍生化实验，成功合成了同时具有中心手性和轴手性的吲哚化合物以及轴手性二酚化合物。实验证实了醌亚胺氮上保护基种类是控制化学选择性的关键因素。

其次，通过在醌亚胺的氮上引入磺酰基来改变氮的电子云密度，使氮由亲核位点变为亲电位点。在手性磷酸的催化下，其与吲哚发生不对称亲电胺化反应，以最高达 90%的收率和 94% ee 构建了一系列轴手性磺酰胺吲哚骨架（共 30 个例子）。实验结果表明：相较于酰基，引入的磺酰基使亚胺氮更具亲电性，从而实现了亚胺的极性反转。该反应底物范围广，官能团的兼容性好，为不对称合成轴手性磺酰胺吲哚提供了一种高效简便的方法。

最后，在手性磷酸的催化下，磺酰基取代的双亚胺与 2-芳基吲哚发生不对称亲电胺化反应，高效构建了轴手性 2-芳基吲哚骨架（14 个例子，收率最高达 95%，ee 最高达 94%）。该反应为轴手性 2-芳基吲哚化合物的催化不对称合成提供了一种新策略。

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