基于α-卤代腙的不对称环化反应在构建含多氮杂环手性化合物中的应用研究

具有手性的二氢吡唑、四氢哒嗪及1,2-二氮杂卓类杂环骨架广泛存在于许多天然产物以及某些具有生物活性的分子中。发展高效便捷的方法用于合成手性的二氢吡唑、四氢哒嗪及1,2-二氮杂卓类化合物分子具有非常重要的意义。基于我们之前的工作基础，此项目期望通过反应底物及催化体系的设计，实现基于α-卤代腙的催化不对称4+1、4+2、4+3环化反应及串联反应来构建手性的二氢吡唑、四氢哒嗪及1,2-二氮杂卓类杂环化合物。考察各种因素对催化不对称反应的效率及立体选择性的影响，探讨这几类不对称环化反应的机理并揭示其中的反应规律。并进一步利用发展的方法学，尝试合成一些含有多氮杂环的结构复杂的手性化合物以及天然产物AZD8165分子。此项目的开展不但可为不对称催化合成领域增加新颖的内容，丰富手性二氢吡唑、四氢哒嗪以及1,2-二氮杂卓类杂环化合物的种类，而且可为高效合成含有这几种类型骨架的杂环化合物提供新方法和新思路。

Chiral dihydropyrazole, tetrahydropyridazine and 1,2-diazepine heterocyclic skeletons are present in a wide range of natural products and biologically active molecules. Therefore, the development of more creative and convenient methods to construct these interesting molecules is highly desirable. Based on our previous studies，we plan to develop diversely catalytic asymmetric 4+1, 4+2, 4+3 cyclizations, and cascade reactions by using α-halogeno hydrazone for the construction of nitrogen-containing chiral hetereocyclic compounds. Meanwhile, we also will systemically investigate various influence factors on the reactivity, diastereo- and enantioselectivity, as well as disclose the possible reaction mechanism and law. We will also try to use the developed methodology for the synthesis of some complex heterocyclic compounds and natural product AZD8165. The realization of this project will provide a viable approach to synthesize various optically active dihydropyrazole, tetrahydropyridazine and 1,2-diazepine heterocyclic compounds.