铜催化芳基硼酸酰胺化和富电子芳烃区域选择性C-H键磺酰氧化
发布时间：2018-11-24 09:41
【摘要】：随着过渡金属催化C-N键偶联反应的发展,涌现了许多N-芳基酰胺化合物的合成方法。相比之下,卤代芳烃的酰胺化反应通常面临着卤素取代的底物不兼容的问题,而简单芳烃的C-H键酰胺化反应往往面临选择性、需预官能团化、不得不采用特殊芳烃以及贫电子芳烃不兼容的缺点。能否以一种高效可控、符合原子经济性的方法来有效构建酰胺键,这对于药物以及天然产物中间体的合成具有重大的意义。除此之外,芳烃C-H键选择性氧化也是近年来的研究热点之一,如何在活化芳烃C-H键的同时实现其区域选择性的控制,确实面临着不小的挑战。除了特殊取代的芳烃如苯酚和苯酰胺类能实现对位C-H键选择性氧化之外,简单芳烃直接氧化通常会面临选择性的问题。另一种则是采取螯合辅助的方式,该方法虽然有效,但芳烃需要进行额外的官能团化,使得其在实用性方面受到一定的限制。本论文主要分为以下两部分:第一章,我们利用腈对芳基硼酸的酰胺化反应,发展了一种高效合成N-芳基酰胺的方法。该体系底物范围广,不仅能够同时兼容富电子官能团、贫电子官能团,而且也能适用于卤代取代的底物。第二章,我们发展了一种富电子芳烃/杂环芳烃区域选择性的C-H键磺酰氧化反应,电子效应和位阻效应使得磺酰氧化在富电子芳烃/杂环芳烃的特定位置发生。不仅如此,磺酰氧化后的产物能用于水解成酚,并且还可以作为亲电试剂应用于偶联反应中,大大拓宽了反应底物的应用范围。综上所述,本文发展了一种新的合成N-芳基酰胺的方法,高效制备了各种取代的N-芳基酰胺化合物,改善了反应的官能团兼容性,拓宽了底物范围。针对富电子芳烃C-H键氧化选择性难的问题,本文还发展了一种可控高效的方法,实现了富电子芳烃/杂环芳烃的区域选择性C-H键磺酰氧化反应。
[Abstract]:With the development of transition metal catalyzed C-N bond coupling reaction, many synthesis methods of N-aryl amides have emerged. In contrast, the amidation reaction of halogenated aromatics usually faces the problem of incompatibility of halogen-substituted substrates, while the C-H bond amidation of simple aromatics often faces selectivity and requires prefunctionalization. The disadvantage of having to use special aromatics and poor electronic aromatics is incompatibility. It is of great significance for the synthesis of drugs and intermediates of natural products to construct the amide bond effectively by a highly efficient and controllable method which accords with the atomic economy. In addition, the selective oxidation of aromatic C-H bond is one of the hot topics in recent years. How to activate the C-H bond of aromatics at the same time to realize the control of its regioselectivity is a real challenge. In addition to the selective oxidation of special substituted aromatics such as phenol and benzamide, the direct oxidation of simple aromatics usually faces the problem of selectivity. The other is chelating assisted method. Although the method is effective, the aromatics need additional functionalization, which makes it limited in practicability. This thesis is divided into two parts as follows: in Chapter 1, we developed an efficient method for the synthesis of N-aryl amide by amidation of nitrile to aryl boric acid. The system has a wide range of substrates, which can not only be compatible with electron-rich functional groups and poor electronic functional groups at the same time, but also suitable for halogenated substrates. In chapter 2, we develop a regioselective C-H bond oxidation reaction of electron-rich aromatics / heterocyclic aromatics. The electron effect and steric effect make the oxidation of sulfonyl occur in the specific position of electron-rich aromatics / heterocyclic aromatics. Moreover, the sulfonyl oxidized products can be used to hydrolyze phenol and can be used as electrophilic reagents in coupling reactions, which greatly broadens the application range of reaction substrates. In conclusion, a new method for the synthesis of N-aryl amides has been developed in this paper. Various substituted N-aryl amides have been synthesized efficiently, which improves the functional compatibility of the reaction and broadens the substrate range. Aiming at the difficulty of C-H bond oxidation selectivity of electron-rich aromatics, a controllable and efficient method has been developed to realize the regioselective C-H bond sulfonyl oxidation of electron-rich aromatics / heterocyclic aromatics.
【学位授予单位】：四川师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251
本文编号：2353186
[Abstract]:With the development of transition metal catalyzed C-N bond coupling reaction, many synthesis methods of N-aryl amides have emerged. In contrast, the amidation reaction of halogenated aromatics usually faces the problem of incompatibility of halogen-substituted substrates, while the C-H bond amidation of simple aromatics often faces selectivity and requires prefunctionalization. The disadvantage of having to use special aromatics and poor electronic aromatics is incompatibility. It is of great significance for the synthesis of drugs and intermediates of natural products to construct the amide bond effectively by a highly efficient and controllable method which accords with the atomic economy. In addition, the selective oxidation of aromatic C-H bond is one of the hot topics in recent years. How to activate the C-H bond of aromatics at the same time to realize the control of its regioselectivity is a real challenge. In addition to the selective oxidation of special substituted aromatics such as phenol and benzamide, the direct oxidation of simple aromatics usually faces the problem of selectivity. The other is chelating assisted method. Although the method is effective, the aromatics need additional functionalization, which makes it limited in practicability. This thesis is divided into two parts as follows: in Chapter 1, we developed an efficient method for the synthesis of N-aryl amide by amidation of nitrile to aryl boric acid. The system has a wide range of substrates, which can not only be compatible with electron-rich functional groups and poor electronic functional groups at the same time, but also suitable for halogenated substrates. In chapter 2, we develop a regioselective C-H bond oxidation reaction of electron-rich aromatics / heterocyclic aromatics. The electron effect and steric effect make the oxidation of sulfonyl occur in the specific position of electron-rich aromatics / heterocyclic aromatics. Moreover, the sulfonyl oxidized products can be used to hydrolyze phenol and can be used as electrophilic reagents in coupling reactions, which greatly broadens the application range of reaction substrates. In conclusion, a new method for the synthesis of N-aryl amides has been developed in this paper. Various substituted N-aryl amides have been synthesized efficiently, which improves the functional compatibility of the reaction and broadens the substrate range. Aiming at the difficulty of C-H bond oxidation selectivity of electron-rich aromatics, a controllable and efficient method has been developed to realize the regioselective C-H bond sulfonyl oxidation of electron-rich aromatics / heterocyclic aromatics.
【学位授予单位】：四川师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251
【参考文献】
相关期刊论文 前1条
1 ;Cu-catalyzed cross-couplings under ligandless conditions[J];Chinese Chemical Letters;2007年10期
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