氮氧杂烯丙基阳离子中间体参与的不对称环加成反应研究

Nitrogen-containing heterocycles have been widely used in pesticides, medicines and many fine chemicals. Consequently, the development of high efficient method towards the construction of those heterocycles has attracted considerable attentions in synthetic organic chemistry. The cycloaddition reaction involving azaoxyallyl cation as the key intermediate provides an efficient route to those heterocycles. However, the substrate types of reported reactions are somewhat limited and the combination of azaoxyallyl cation with other catalytic modes are not reported yet. Moreover, how to realize the catalytic asymmetric version of this cycloaddition process is waiting for further exploration. Consequently, the research contents of this project is trying to combine azaoxyallyl cations with chiral tertiary amine catalysis, NHC catalysis, Lewis acid catalysis and Palladium catalysis. We want to use chiral catalyst to activate another reaction component and use the in-situ formed chiral intermediate to accomplish the catalytic asymmetric cycloaddition reactions of azaoxyallyl cations. The designed reactions can not only greatly enrich the cycloaddition reaction types of azaoxyallyl cation intermediates, but also provide novel and efficient routes to various biologically important chiral heterocycles.

含氮杂环化合物在农药，医药以及众多精细化学品中有着非常广泛的应用。因此，发展新型高效的含氮杂环化合物的合成方法一直吸引着化学家们的广泛研究兴趣。氮氧杂烯丙基阳离子中间体参与的环加成反应为氮杂环化合物的构建提供了一条有效的途径。然而，目前所报道的反应底物类型较为局限，而且将氮氧杂烯丙基阳离子中间体与其他催化模式相结合的反应迄今还未被开发。不仅如此，如何实现该类型环加成反应的催化不对称过程是一个亟待解决的科学问题。基于此，本项目拟将氮氧杂烯丙基阳离子中间体分别与手性三级胺催化、氮杂环卡宾催化、路易斯酸催化和过渡金属钯催化相结合。期望通过催化剂活化另一反应组分，并与之形成手性中间体，实现氮氧杂烯丙基阳离子在上述四种催化体系下的不对称环加成反应。这些反应的实现不仅可以极大丰富氮氧杂烯丙基阳离子参与的环加成反应类型，而且为许多重要含氮杂环化合物的不对称合成提供新途径，具有重要意义和研究价值。

氮氧杂烯丙基阳离子中间体参与的环加成反应为氮杂环化合物的构建提供了一条有效的途径。然而，目前所报道的反应底物类型较为局限。在过去的三年时间内，项目组紧密围绕氮氧杂烯丙基阳离子参与的[3+m]环加成这一研究方向，相继完成了一系列氮氧杂烯丙基阳离子的[3+2]、[3+3]和[3+4]-环加成反应。这些反应不仅为许多重要含氮杂环化合物的合成提供了新型有效的方法，方法学还被用作关键步骤应用于天然产物和活性药物分子的骨架修饰中。.另外，我们还发展了烯炔自由基串联环化反应，这些反应为结构多样、多官能化的-内酰胺和萘衍生物的高效、高选择性合成提供了新的方法和策略。.基于可见光作为绿色能源，课题组在光致氧化还原催化和单一可见光诱导的功能有机分子合成方面也取得了一定的研究进展。相继实现了色螨酮、1,2,4-噁二唑、3-烷基-喹喔啉酮、3-酰基喹喔啉酮、多取代烯烃以及酰胺类化合物的绿色高效合成。.在本项目资助下，共发表SCI论文17篇，其中包括CCS Chem. (1篇)、 Sci. China. Chem. (1 篇)、 Org. Lett. (4篇)，在Chem. Commun., Sci Bull.和Chem. Soc. Rev.上撰写发表综述论各1篇。