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含N杂环结构广泛存在于具有生物活性的药物或天然产物骨架中.本文开发了一个高效合成含N杂环骨架的方法,这类方法在近年来一直是研究热点.在最近几年,过渡金属催化C-H键活化并随后与不饱和键发生环化反应被认为是一种环境友好且原子经济性高的构建功能化杂环的方法.在这些金属催化的体系中,三价铑催化与炔烃的环化反应体系,被认为是一种高效且有实际意义的合成含N杂环的体系.在这类体系,特别是构建六元环的体系中,炔烃通常作为一个C2合成子被广泛应用.为了克服这一局限性,Chang课题组和本课题组分别独立报道了通过三价铑催化,炔烃与芳烃硝酮偶联合成吲哚啉化合物,其中炔烃作为一个C1合成子参与反应.另一方面,本课题组还报道了炔丙醇与吡咯烷苯甲酰胺通过C-H键活化合成1-异色满酮结构,其中由于电子效应,芳基-铑物种对于炔烃的插入是在炔烃的2位.基于上述工作,本文希望通过置换炔丙醇中芳基与烷基的位置,使芳基-铑物种对于炔烃插入的方向发生改变,进而生成联烯中间体,然后发生环化反应生成五元环内酰胺结构.异吲哚啉酮骨架结构也是一类重要的含N杂环结构,广泛存在于多种天然产物及药物分子中,其合成方法受到广泛关注.尽管此前已有三价铑催化C-H官能团化的方法来构建异吲哚啉酮骨架结构,但通常需要活性极高或易爆的化合物作为反应底物.因此,本文报道一类以简单的炔丙醇与N-甲氧基苯甲酰胺作为起始原料,通过一步[4+1]环化合成异吲哚啉酮骨架结构.本文完成了32个不同官能团取代的异吲哚啉酮骨架结构的合成,反应均可以以中等到良好的收率得到目标产物.另外还进行了放大实验,结果表明可以以克级规模制备异吲哚啉酮化合物,反应剩余的Ag2CO3以及生成的单质银可以回收(收率78%).总之,我们将N-甲氧基苯甲酰胺与炔丙醇在三价铑催化作用下通过C-H键活化的方法环化高效合成N-取代的异吲哚啉酮骨架结构,且该骨架结构含有一个手性中心.催化体系温和,官能团容忍度好.
N-containing heterocyclic structures exist widely in biologically active drugs or natural product skeleton.In this paper, we have developed an efficient method for the synthesis of N-containing heterocycle skeletons, and these methods have been the research focus in recent years.In recent years, Metal-catalyzed CH-bond activation followed by cyclization with unsaturated bonds is considered to be an environmentally friendly and atomically cost-effective method of constructing functionalized heterocycles.In these metal-catalyzed systems, the trivalent rhodium catalyzes the reaction with alkyne Hydrocarbon cyclization reaction system is considered to be an efficient and practical method for the synthesis of N-containing heterocycles.In such systems, especially in the construction of six-membered ring systems, alkynes are often used as a C2 synthon Widely used.In order to overcome this limitation, Chang group and our group separately reported independently that indole compounds were synthesized through the coupling reaction of alkyne with aromatic nitrones via trivalent rhodium catalysis, in which alkyne was involved as a C1 synthon Reaction.On the other hand, our group also reported that propargyl alcohol and pyrrolidine benzamide through CH bond activation synthesis of 1-isochromanone structure, which due to the electronic effect, aryl-rhodium species for alkyne insertion is in Hydrocarbon 2. Based on the above work, this paper hopes to replace the propargyl propargyl aryl and alkyl position, so that the aryl-rhodium species for alkyne insertion direction change, and then generate alkene intermediates, and then ring The reaction results in the formation of a five-membered ring lactam structure. Isoindolinone skeleton structure is also an important class of N-containing heterocycle structure, which exists widely in many natural products and drug molecules, and its synthesis method has drawn wide attention. There is a trivalent rhodium catalyzed CH functionalization method to construct the isoindolinone skeleton structure, but usually require highly active or explosive compounds as the reaction substrate.Therefore, this article reports a class of simple propargyl alcohol and N- Methoxybenzamide as the starting material, the isoindolinone skeleton structure was synthesized by one step [4 + 1] cyclization.The synthesis and reaction of 32 isoindolinone skeleton structures with different functional groups were completed The target product can be obtained in moderate to good yield.In addition, an amplification experiment was carried out, and the results showed that the isoindolinone compound can be prepared on a gram scale scale, and the remaining Ag2CO3 and the elemental silver generated after the reaction can be recovered (yield: 78% ) In summary, we cyclize N-methoxybenzamides with propargyl alcohol via CH bond activation catalyzed by trivalent rhodium efficiently to synthesize N-substituted isoindolinone skeletons, and the framework structure Contains a chiral center. Catalytic system is mild, functional groups tolerance is good.