基于喹唑啉氮氧偶极子导向的碳氢键活化串联反应合成新型功能杂环分子的反应及其应用研究

Metal-catalyzed C-H activation has been widely recognized as a step-economic strategy in organic synthesis. We plan to develop a new N-oxide directing catalytic C-H activation tandem reaction. In this reaction, two kinds of new functional heterocyclic molecules were selective synthesized under various conditions. In aqueous solvent, 1-[2-(3,4-diaryl-isoquinolin-1-yl)-phenyl]-benzamides were obtained in excellent yields by the reactions of 2,4-diarylquinazoline-N-oxides with alkynes. Under anhydrous condition, 2,4-diarylquinazoline-N-oxides reacted with two mole alkynes to selective produce (2,3-diaryl-inden-1-ylidene)-(1,3,4-triaryll-isoquinolin-8-yl)-amines in one step. More new functional isoquinoline contained heterocyclic molecules, such as fused heterocyclic compounds, N,N- chelating ligands and their organoboron complex, were obtained deriving from 1-[2-(3,4-diaryl-isoquinolin-1-yl)-phenyl]-benzamides and (2,3-diaryl-inden-1-ylidene)-(1,3,4-triaryll-isoquinolin-8-yl)-amines. The photo-physical properties of these synthesized functional heterocyclic molecules were evaluation. Good organic opto-electronic functional molecules were screen out by these evaluations and their application in aggregation induced emission (AIE), solvatochromism, ion sensing, cell imaging, photodynamic therapy(PDT) were investigated.

金属催化导向C-H键活化反应被认为是有机合成中最经济有效的手段。本课题拟发展一种新的氮氧偶极子导向催化碳-氢键活化串联反应，在不同条件下分别高选择性构建两类新型异喹啉功能杂环分子。在有水条件下，2,4-二芳基喹唑啉氮氧偶极子与一分子芳炔反应高产率合成1-(2-N-酰胺基)苯基-2,3-二芳基异喹啉衍生物。而在无水条件下，2,4-二芳基喹唑啉氮氧偶极子与二分子芳炔反应，高产率合成8-氨基-1,3,4-三芳基异喹啉-2,3-二芳基茚酮亚胺; 我们将对上述两类异喹啉化合物进一步衍生化，合成新的稠环杂环分子、含氮双齿配体及其氟硼化合物。对这些功能杂环分子的光物理性质进行评价，筛选出效果好的化合物分子，研究它们在金属离子的识别、金属离子检测、有机发光二极管、聚集诱导发光、溶致变色、离子传感、细胞成像、光动力学治疗等领域中的应用。

喹唑啉衍生物表现出多种生物活性。金属催化导向C-H键活化反应被认为是有机合成中最经济有效的手短。在本国家基金项目的支持下，经过四年的研究，项目取得了如下几方面的进展：.(1) 发展了一种选择性合成喹唑啉N1和N3氮氧偶极子的通用方法及水相合成喹唑啉酮的方法；.(2) 发展了喹唑啉氮氧偶极子的导向C-H活化与炔、烯、醚、吲哚等化合物反应合成多样性杂环化合物的方法，并对其反应机理进行了详细探究；.(3) 发展了喹唑啉酮的碳-氢活化衍生化合成多样性含喹唑啉骨架的衍生物;.(4) 发展了几种2,4-二取代的喹唑啉的导向C-H活化衍生化合成分子中含喹唑啉骨架的衍生物；.(5) 对合成的新的喹唑啉衍生物的生物活性及其光物理性质进行了研究。结果发现一些化合物是有效的酪氨酸酶混合型激活剂，而另一些化合物在固态和溶液中都表现出很好的光致发光现象，溶致变色效应，而具有成为生物成像的潜在应用。.(6) 通过不对称还原或加成反应，合成了几种具有潜在生物活性的α-氟代手性胺。.本课题的研究结果极大地丰富了我们关于氮氧偶极子有机反应的化学知识，拓展了氮氧偶极子在有机合成中的应用，为有机合成提供新的手段和新型结构多样性的功能杂环分子。研究结果在the Journal of Organic Chemistry, Organic Chemistry Frontiers, Synthesis, Bioorganic & Med. Chemistry 等期刊发表相关学术论文22篇，授权专利3项.