【作者】 杨波；

【导师】 康彦彪；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2024， 博士

【摘要】 含氮芳香化合物与人类生活息息相关,含氮化合物的合成也一直深深吸引着化学家们的兴趣。在现代生产生活的各个方面,如天然产物、药品、农用化学品、有机材料和催化剂等多个领域,都可以看到芳胺、氮杂环及其相关含氮芳香化合物的存在。随着社会的发展,人们对合成的低成本、低污染、操作简便、普适性高等方面要求越来越高,开发新的更优秀的构建C-N键的方法以及合成芳胺及氮杂环化合物的反应也一直是一个值得深入研究的问题。在我们课题组对碱或光促进的自由基偶联反应的研究基础上,本论文致力于探索更高效的构建C-N键的方法,用以合成具有广泛应用价值的芳胺和氮杂环化合物。具体有以下三方面工作:(1)利用碱促进的苄位C-H活化引发的串联C(Ar)-N键偶联实现吲哚类四并环稠环化合物的高效合成。这种方法避免了传统构建吲哚类四并环稠环化合物所需的多步反应,为吲哚类稠环化合物的合成提供了一种简单高效的方法。(2)利用氢氧化钾催化的苄位C-H活化引发的串联C(Ar)-N键偶联实现了异喹啉类稠环化合物的高效合成。仅需要催化量的氢氧化钾和简单易得的原料就可以简便地通过环化方法合成异喹啉衍生物,反应条件简单,有利于实际生产工作中的大规模合成应用。(3)利用实验室发现的具有强还原能力的光还原催化剂协同镍催化剂实现了氯苯和氟苯与胺的C-N键或C-O键偶联。该方法从原理上突破了传统的零价镍对C-X键的氧化加成引发C-N偶联的模式,直接通过卤苯的SET光还原产生苯自由基,并与低价镍发生氧化加成进而实现C-N偶联。基于此策略,难以活化的氯苯甚至氟苯也能实现C-X偶联。更多还原

【Abstract】 Nitrogen-containing aromatic compounds are closely related to human life,and the synthesis of nitrogen-containing compounds has always attracted the interest of chemists.In all aspects of modern production and life,such as natural products,pharmaceuticals,agricultural chemicals,organic materials and catalysts,it is possible to observe the presence of aromatic amines and nitrogen-containing heterocycles.With the development of society,people are demanding a low-cost and environment-friendly synthesis method with simple operation and practical value.It is a worthy issue to find a new and better methods for constructing C-N bonds for the synthesis of aromatic amines and nitrogen-containing heterocyclic compounds.Based on our research about base-or photo-induced free radical coupling reactions,this paper aims to explore a more efficient method to construct C-N bonds for the synthesis of high-value arylamines and nitrogen heterocyclic compounds.Specific work in the following three aspects:(1)Efficient synthesis of indole-fused tetracyclic heteroacenes was achieved via the tandem C(Ar)-N bond coupling induced by alkali-promoted benzyl C-H activation.This method avoids the multi-step reaction to obtain tetracyclic heteroacenes,which is simple and efficient.(2)The efficient synthesis of isoquinoline-fused tetracyclic heteroacenes was achieved via the tandem C(Ar)-N bond coupling induced by benzyl C-H activation catalyzed by potassium hydroxide.Only a catalytic amount of potassium hydroxide as a simple and readily available raw materials is used for the synthesis of such derivatives by cyclization.The reaction conditions are simple,which is conducive to large-scale synthesis applications in actual production work.(3)The C-N bond or C-O bond coupling between chlorobenzene,fluorobenzene,and amine was realized by using the original photoreduction catalyst with high reductive potential and the nickel catalyst.The benzyl radical is generated from SET photoreduction of halogenated benzene and participates C-N coupling by one-electron oxidation addition of low-valence state nickel.This method breaks through the traditional mode of C-N coupling started from the two-electron pathway of C(sp~2)-X.Based on this strategy,electron-rich chlorobenzene and even fluorobenzene,which are difficult to activate,can also achieve C-X coupling.更多还原