叔胺（膦）催化的串联扩环反应合成含氮杂环化合物的研究

Nitrogen-containing heterocyclic molecules have attracted much attention from organic chemists due to their potential biological activity or pharmaceutical significance. In this item, tertiary amine (phosphine) catalyzed tandem ring-expansion reactions of sulfonyl aziridine to synthesize five-, six-, seven- and eight-membered nitrogen-containing heterocyclic compounds will be investigated，and a new efficient and high selective organic synthesis method will be developed. The studies are focus on dipolar intermediates, which are produced by tertiary amine (phosphine) and active alkynes, reacted with N-tosylaziridine to synthesize various of nitrogen-containing heterocyclic compounds through diverse tandem ring-expansion reactions; explore the impact of structural changes in organic base and active alkyne on the tandem ring-expansion reaction, [3+2], [3+3], [4+3] and [5+3] cycloaddition reactions will be obtained with selectivity by controlling the structures of catalyst and substrate; summarize reaction rule, the mechanisms of the ring expansion reactions and the reasons for the chemoselectivity of cycloaddition reactions will be discussed by isotopic labeling experiment, controlled experiment and theoretical computation, research scope of the cycloaddition reaction catalyzed by tertiary amine (phosphine) will be broaden. Finally, an efficient, simple, environmentally friendly synthetic method will be developed to synthesize potential biological active nitrogen-containing heterocyclic compounds.

含氮杂环分子具有潜在生物活性，以及在制药领域具有的重要意义，受到化学家们的广泛关注。本项目研究叔胺（膦）催化磺基氮杂环丙烷的串联扩环反应合成五元、六元、七元和八元含氮杂环化合物，发展新型高效、高选择性的有机合成方法。重点研究叔胺（膦）与活泼炔形成的偶极中间体与磺基氮杂环丙烷的反应，以实现通过不同的串联扩环反应合成各种含氮杂环化合物；探索有机碱自身结构的特异性以及活泼炔的结构改变对串联扩环反应的影响，通过控制催化剂和底物的结构，导向性地进行[2+3]、[3+3]、[4+3]和[5+3]环加成反应；总结反应规律，并以同位素标记实验、控制实验和理论计算为研究手段，合理解释扩环反应机理和产生环加成化学选择性的原因，开拓叔胺（膦）催化环加成的研究范围。最终期待发现高效、操作简单、绿色的合成潜在生物活性含氮杂环化合物的合成方法。

有机碱催化的环加成反应是高效构建碳（杂）环的重要方法。项目探索了氮杂环丙烷在有机碱催化作用下与贫电子炔的环加成反应，但未能实现期望的预期研究结果，可能主要由于氮杂环丙烷自身亲电活性问题所导致的。项目研究发现以Bu3P为催化剂，实现了磺基偶氮和MBH加成物的去磺基化[3+2]环加成反应，生成吡唑化合物；发展了DMAP催化的联烯酸酯与偶氮酮的[2+4]环化反应，合成系列噁二嗪类化合物。另一方面研究可见光促进，以有机染料为光敏化剂，基于烯烃（炔烃）的有机光化学反应：发展了可见光促进下，以吖啶为光催化剂，芳基烯烃在氧气存在条件下的自身环化反应，直接构建4-芳基四氢萘酮；发展了以吡喃盐为光催化剂，可见光驱动下芳炔和腈[2+2+2]环加成反应，在温和绿色以及无金属条件下制备了三取代吡啶化合物；实现了可见光促进下，以Na2-Eosin Y为催化剂，烷基溴代物对芳基炔烃的立体和区域选择性的双官能团化反应。目前项目已发表SCI论文5篇（IF > 6.0的4篇）。