基于螺环假吲哚类中间体的新反应研究

To capture and characterize active intermediates of an organic reaction, and investigate their reactivity are the cutting-edge areas of modern organic chemistry. They hold significant positions in mechanistic research and provide rational guidance for developing novel synthetic methodologies. Spiroindolenines are not only important nitrogen-containing cyclic compounds, but also key intermediates in Pictet–Spengler reaction which finds wide application in organic synthesis. Our research group has conducted systematic studies on the chemistry of spiroindolenines, and obtained deep mechanistic insights of their transformations. Based on our previous results, this project is aiming to develop a series of new reactions of spiroindolenine-type intermediates: (1) synthesis of novel spiroindolenines, spiro-2H-pyrroles and spirocyclohexadienones by applying desymmetrization strategy; (2) novel migration reactions of spiroindolenines; (3) novel migration reactions of spirocyclohexadienones; (4) interrupted Pictet–Spengler reaction, etc. An array of aza-polycyclic compounds with novel structural motifs and multiple stereogenic centers can be assembled via these methods. In addition, the real roles played by spiroindolenines as key intermediates in catalytic asymmetric Pictet–Spengler reaction will be investigated by theoretical computations.

捕捉和表征有机反应中的活泼中间体并研究其反应性能是有机反应机理研究的重要手段，并能为设计和发展新型有机反应方法学提供理性的指导。螺环假吲哚是一类重要的含氮杂环化合物，同时也是在有机合成中具有重要应用价值的Pictet–Spengler反应的重要中间体。本项目拟发展一系列基于螺环假吲哚类中间体的新反应。主要包括：（1）利用去对称化策略合成新型螺环假吲哚、螺环-2H-吡咯、螺环己双烯酮等化合物；（2）基于螺环假吲哚的新型迁移反应；（3）基于螺环己双烯酮的新型迁移反应；（4）中断的Pictet–Spengler反应等。利用这些反应可以合成一系列结构新颖的含有多个手性中心的多环杂环化合物。此外，本项目还将利用理论计算研究螺环假吲哚作为关键中间体，其形成和转化对于催化不对称Pictet–Spengler反应的历程和立体化学的影响。

本项目的总体目标是深入研究螺环假吲哚类分子的化学，为结构多样性的多环吲哚啉类分子提供高效合成方法。项目执行期间，研究人员发展了一系列螺环假吲哚类化合物的新型不对称催化合成方法与开环重排反应，利用金属铱催化的不对称烯丙基取代反应实现多类杂芳香化合物的去芳构化，发展了可见光促进的环加成去芳构化反应等新型反应方法学。提出了Pictet–Spengler反应的统一机理模型，利用从头算分子动力学模拟研究了氢负离子转移反应和开壳层单重态双自由基重联反应中的动态学效应。本项目的研究成果推动了螺环假吲哚类分子化学的发展，具有结构多样性的复杂多环分子的合成提供了新的思路。