若干铜促新型Domino反应合成取代杂环化合物的研究

Substituted heterocyclic compounds are valuable in the fields of pharmaceutical, biological and material chemistry. The copper-promoted cross-coupling, C-H activation, and intramolecular addition reactions have become powerful synthetic protocols for their green features and high efficiency. And domino reaction is an important synthetic strategy due to its concise and efficient features..In this project, several substituted heterocycles of potential value would be assembled via the copper-promoted novel domino reactions with cross-coupling, C-H activation or intramolecular addition as the key process. The main contents are: (1) synthesis of heterocycles via the Cu-promoted intermolecular substitution/intramolecular double coupling process; (2) synthesis of heterocycles via the Cu-promoted intermolecular substitution/intramolecular oxidative coupling process; (3) synthesis of heterocycles via the Cu-promoted (intermolecular coupling/) intramolecular domino double addition process. The related factors of these reactions (such as reaction conditions and structures of the substrates) would be carefully investigated. And we will also study the related mechanisms and rules for these domino reactions..Certain initial experiments on the feasibilities of these reactions have been carried out during our preliminary investigation..These methods are versatile. Various substituted heterocycles with variable structures could be elaborated. There is no similar report for these Cu-promoted domino synthetic protocols to date. The Cu-promoted novel domino approaches may be useful for the synthesis of the corresponding heterocyclic molecules in the field of medicine and biology science.

取代杂环化合物在医药、生物和材料等领域有很重要的应用价值。铜促交叉偶联、C-H键活化和分子内加成由于绿色、高效而成为有力的合成工具；Domino反应具简捷、有效等特点，是当今有机合成领域的一类重要策略。.本项目拟采用较易得原料，利用铜促交叉偶联、C-H键活化、分子内加成等参与的新型Domino反应，合成若干具潜在价值的取代杂环化合物。主要包括：采用铜促进的分子间取代/分子内两次偶联、分子间取代/分子内氧化偶联、(分子间偶联/)分子内连续加成等新型策略构建若干系列取代杂环。同时仔细考察各种因素(反应条件、底物结构等)的影响，探索相关反应机理和规律。.申请者已对这些反应的可行性进行了一定的前期研究。.本项目方法具一定广适性，涉及多种取代杂环的构建，结构可变动性较大。目前尚未有相似文献报道。通过这些铜促新型反应的研究，将为合成具有相关取代杂环的医药或生物活性分子提供新的有用途径。

许多取代杂环化合物在医药、生物和材料等领域有非常重要的应用价值。铜促偶联、C-H键官能化和加成由于绿色、高效而成为有力的合成工具；Domino反应具简捷、有效等特点，是当今有机合成领域的一类重要策略。.本项目采用了较易得原料，利用铜促偶联、加成、C-H键官能化等过程参与的新型Domino反应，合成了若干类具潜在价值的取代杂环化合物。研究内容主要包括：.(1)铜促分子间取代/分子内偶联为关键步构建杂环的Domino反应研究；.(2)铜促分子间偶联/分子内偶联为关键步构建杂环的Domino反应研究；.(3)铜促分子间N-烃基化/分子内加成(/分子内C-H官能化) 为关键步构建杂环的Domino反应研究；.(4)铜促分子间加成/分子内偶联或C-H官能化为关键步构建杂环的Domino反应研究；.(5)铜促分子间加成/分子内加成/分子内偶联为关键步构建杂环的Domino反应研究；.这些方法具新颖性、简捷性和广适性，涉及多种取代杂环的构建，结构可变动性较大。通过这些铜促新型反应的研究，将为合成具有相关取代杂环的生物/医药活性或功能材料分子提供了新的有用途径。.总之，本项目成功地开发了五类新型的铜促Domino反应，丰富和发展了相关铜化学和串联方法。总体上达到了预期研究的目的，实际研究成果已经超过了预期的要求。