Zhao Hao-Wen, Jiang Fei, Chen Sihan, Hu Jingliang, Xiang Shao-Hua, Ding Wei-Yi, Lu Wei, Tan Bin
Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.
Angew Chem Int Ed Engl. 2025 Mar 17;64(12):e202422951. doi: 10.1002/anie.202422951. Epub 2025 Jan 9.
Spiro skeletons have emerged as a privileged class of chiral carriers across various research fields, including asymmetric catalysis and functional materials, due to their remarkable configurational rigidity. However, limited structural diversity of spiro frameworks significantly restricts the expansion of their applications. Here we present a new class of axially chiral spiro-bisindole frameworks and report their first enantioselective construction via a chiral phosphoric acid-catalyzed intramolecular dehydrative cyclization reaction. Unlike the classical SPINOL backbone, incorporation of indole moieties in place of phenol enhances the nucleophilicity of ketone substrates, thereby eliminating the need for a tedious pre-activation process. By leveraging the retained active sites of indole, the resulting highly enantioenriched spiro-bisindoles can be rapidly transformed into other valuable structures. More importantly, axially chiral fluorescent molecules with good asymmetry factors and quantum fluorescence efficiency are readily accessed, opening a new avenue for developing chiral fluorescent materials. Control experiments demonstrate the pivotal role of both unmasked N-H bonds in achieving good efficiency and enantiocontrol.
由于其显著的构型刚性，螺骨架已成为包括不对称催化和功能材料在内的各个研究领域中一类重要的手性载体。然而，螺环骨架有限的结构多样性严重限制了其应用的扩展。在此，我们展示了一类新型的轴向手性螺双吲哚骨架，并报道了通过手性磷酸催化的分子内脱水环化反应首次对其进行对映选择性构建。与经典的SPINOL骨架不同，用吲哚部分取代苯酚增强了酮底物的亲核性，从而无需繁琐的预活化过程。通过利用吲哚保留的活性位点，所得的高度对映体富集的螺双吲哚可以快速转化为其他有价值的结构。更重要的是，可以很容易地获得具有良好不对称因子和量子荧光效率的轴向手性荧光分子，为开发手性荧光材料开辟了一条新途径。对照实验证明了未掩蔽的N-H键在实现良好效率和对映体控制方面的关键作用。
