基于三元杂环与卡宾和乃春的杂环化合物合成

杂环化合物是药物的重要结构单元，其合成方法一直是有机化学的研究热点之一。通过卡宾或乃春与四元杂环化合物形成叶立德并扩环的反应是近年来发展起来的合成普通环、中环及大环杂环化合物的新方法，但相关的研究工作非常有限。该类反应到目前为止尚未应用于三元杂环化合物的反应中。在本项目中，我们拟研究通过卡宾或乃春与三元杂环化合物形成叶立德的扩环反应来合成小环四元杂环化合物，以及中环和大环冠醚类化合物。同时探讨控制成环选择性的因素，以便控制选择性地实现四元杂环化合物，以及中环和大环冠醚类化合物的合成。并探索通过形成的叶立德原位与缺电子烯烃发生串联反应合成六元杂环化合物。还将探索在手性催化剂存在下的四元和六元杂环的不对称合成。设计的方法所需原料简单易得，可为四元和六元杂环类化合物的合成提供一种简单易行的新方法。该方法还可能会成为合成中环和大环冠醚、硫冠醚和氮冠醚类化合物的新方法。

Heterocyclic compounds are crucial structural elements of drugs. Their synthesis is always one of the most important issues in organic chemistry. It is becoming one of the new and important synthetic methods of common heterocycles, even medium and large heterocycles that the reactions of carbenes and nitrenes with four-membered heterocyclic compounds via the generated ylide expansions. The methods attract much attention recently. However, the related research work is very limited and the reactions have not been applied in the reactions involving three-membered heterocycles to date. In the current proposal, we plan to investigate synthesis of small ring four-membered heterocycles mainly, even medium heterocycles and large crowns and their analogues through reactions of carbenes and nitrenes with three heterocycles via the generated ylide expansions. We will investigate on the controlling factors of the cyclization selectivity to realize the selective synthesis of four-membered heterocycles, medium heterocycles and large crowns and their analogues, respectively. Meanwhile, the in-situ reactions of the generated ylides with electron-deficient olefins will be studied to prepare six-membered heterocycles via a tandem mode. The asymmetric synthetic versions of four- and six-membered heterocycles will be attempted under the catalysis of enantiopure catalysts. The starting materials are commercially available or easily prepared in the current project. The designed strategy will be facile and novel methods for synthesis of four- and six-membered heterocycles, even medium heterocycles, large crowns, thiacrowns, and azacrowns.