基于酰胺亲电活化的反应研究

基于酰胺亲电活化的有机化学反应因其底物简单易得、化学选择性高的优势，长期以来受到化学家的广泛关注。特别是近年来的多项重要突破使得该领域再次成为研究亮点。通过酰胺的亲电活化，化学家开发了多种类型的酰胺转换过程，实现了结构多样的杂环化合物、酮、亚胺的高化学选择性制备。然而有关α,β不饱和酰胺亲电活化的反应却未见报道。本项目拟通过酰胺中氮原子上取代基的合理选择以及亲电活化体系的优化实现α,β不饱和酰胺的亲电活化，并进一步探索活化后亲电中间体的环加成反应。另一方面，本项目将以近期发现的偶极型烯胺盐为研究对象，设计并开发基于这一中间体的新反应，包括酰胺与亲核试剂在酰胺α位的偶联反应、偶极型烯胺盐与不同亲电官能团的环加成反应。综上所述，我们期待开发一系列新颖酰胺亲电活化反应，实现杂环化合物的制备以及酰胺α位官能团化的新方法，解决传统合成中化学选择性的问题。

Reactions based on the amide electrophilic activation have received considerable attention in a long time due to their merits of readily available substrates and highly chemical selectivity. Particularly, a number of significant progresses made in recent few years highlight this field again. By means of the electrophilic activation of amide, a variety of amide transformations have been developed allowing the highly chemical selective synthesis of heterocycles, ketones and imines. Nevertheless, to our knowledge, the electrophilic activation of α,β-unsaturated amides have not been reported so far. In this project, we will develop methods for the electrophilic activation of α,β-unsaturated amides through the rational choice of substituents on the amide nitrogen and the optimization of the electrophilic activation conditions. Cycloaddition reactions with resulted intermediates will then be investigated. In another aspect, this project will cover the development of new reactions by making use of a newly discovered dipolar enamine-like intermediate. Reactions in this aspect will include the cross coupling reaction of amides with nucleophiles at the α position of amide and the cycloaddition reaction of the enamine-like intermediate with different electrophilic functional groups. In summary, we anticipate a few novel amide electrophilic transformations will be realized in this project. It will prompt the synthesis of heterocycles and α-functionalized amides which in turn solving the chemical selectivity issues in the traditional synthesis.