氮杂环丙烷作为烷基化试剂在Catellani反应中的应用研究

The Catellani-type reaction is a powerful strategy that allows the expeditious synthesis of highly substituted arenes, which is widely used in contemporary organic synthesis. Recent efforts in this area have expanded the scope of terminating reagents substantially, as a gamut of functionalities can be appended at the ipso-position. In contrast, the electrophilic reagents developed for ortho C–H functionalization are quite limited. In this project, we’d like to utilize aziridines as the alkylating reagents in the Catellani reaction and develop several novel protocols for the synthesis of nitrogen-containing heterocyclic compounds like indolines and tetrahydroisoquinolines. To this end, we will investigate: 1) Direct annulation between aryl iodides and aziridines; 2) Catellani/aza-Michael addition cascade reaction; 3) Catellani/hydroamination cascade reaction; 4) Total synthesis of Dysoxylum and Aporphine alkaloids with the above developed cascade reactions as the key step. The performance of these studies will not only expand the existing paradigm of Catellani reaction, but also provide a new and efficient route to nitrogen-containing heterocycles. More importantly, it will also open a new avenue for the total synthesis of natural alkaloids that possess remarkable bioactivities.

Catellani反应是一类高效制备多取代芳香化合物的催化合成方法，被广泛地应用于有机合成当中。目前，前人对该反应的研究主要集中在碳-碘键本位终止试剂的开发，对邻位碳-氢键官能团化所用的亲电试剂则关注较少。针对这一问题，本项目拟以氮杂环丙烷作为新的烷基化试剂，发展基于Catellani反应的新型串联反应，高效合成吲哚啉、四氢异喹啉等含氮杂环化合物。重点研究：1）芳基碘代物与氮杂环丙烷的直接环化反应；2）Catellani/aza-Michael加成串联反应；3）Catellani/分子内氢胺化串联环化反应；4）以上述反应为关键步骤合成㭴木属和阿朴啡类生物碱。该项目的实施对进一步拓展Catellani反应的适用范围、高效构建氮杂环化合物具有重要意义，同时为若干具有显著活性的生物碱的全合成提供新的合成路径。

Catellani反应是一类高效制备多取代芳香化合物的催化合成方法，被广泛地应用于有机合成当中。目前，人们对该反应的研究主要集中在碳-碘键本位终止试剂的开发，对邻位碳-氢键官能团化所用的亲电试剂研究较少。..在本项目的支持下，我们以氮杂环丙烷作为新的烷基化试剂，应用于Catellani反应中，发展了钯和降冰片烯协同催化的芳基碘化物、氮杂环丙烷和缺电子烯烃之间的三组分Catellani/aza-Michael串联环化反应，高效构建了1-烷基取代的四氢异喹啉化合物；将钯和降冰片烯协同催化的芳基碘化物、氮杂环丙烷和炔烃之间的三组分Catellani反应和金催化的环化反应相结合，高效合成了1-烯基取代的四氢异喹啉类化合物。以上述反应为关键步骤，我们成功实现了天然产物dactyllactone A，korupensamine A和B，michellamine B的全合成以及8-oxypseudopalmatine的形式合成。..在该项目资助下，共发表13篇SCI论文，其中第一作者或者共同通讯作者论文9篇。