基于重氮酮酸酯的杂环分子高效合成方法研究
发布时间：2021-05-20 06:53
杂环化合物在自然界中广泛存在。由于其在药物结构中被广泛应用,吸引了科学界的很多注意,用以开发新的方法学来合成杂环化合物。在这些研究中,包含重氮化合物的反应是构建多种具有生物活性的杂环化合物的有力工具。通过含卡宾中间体的过渡金属催化模式,已经开发出了一系列方法来合成杂环,尤其是多组分反应,为我们提供了一种直接的方式,能够高立体选择性的来构建结构多样性的复杂骨架。这种策略包含了通过金属卡宾来生成氧鎓叶立德以及两性离子中间体,在此类中间体形成之后,在亲电试剂的存在下,会通过“延迟质子化”来发生亲电捕捉,来生成多种新型的多组分产物。作为我们研究兴趣的一部分,我们发表了多篇通过多种不同重氮化合物作为卡宾前体的多组分反应来构建杂环化合物的工作。本论文介绍了一种全新的方法,以重氮酮酸酯与苯胺为底物来构建杂环化合物,与之前报道的通过亲电试剂捕捉氨基叶立德的捕捉方式不同。我们在反应中引入了包含额外羰基的新型酮酸酯重氮。该策略提供了快速构建生物活性杂环化合物的方法,且原料简易可得,反应条件温和。在第二章中,我们介绍了一种以苯胺与重氮酮酸酯为原料,针对多取代吡咯烷与吲哚的结构多样性合成。在钌催化剂作用下,苯...
【文章来源】：华东师范大学上海市 211工程院校 985工程院校 教育部直属院校
【文章页数】：185 页
【学位级别】：博士
【文章目录】：
摘要
Abstract
Chapter1 Introduction
1.1 An Overview of Heterocycles and Their Biological Significance
1.2 Introduction of Diazo Compounds
1.2.1 Background
1.2.2 Stability and Reactivity
1.3 Synthesis of Heterocycles from Diazo Compounds
1.3.1 Synthesis of Heterocycles from Diazo Compounds Involving Allene Intermediate
1.3.2 Synthesis of Heterocycles from Diazo Compounds via Carbene/Alkyne Metathesis
1.3.3 Synthesis of Heterocycles from Diazo Compounds and Enyne
1.3.4 Synthesis of Heterocycles from Diazo Compounds via Transition Metal-Catalyzed C-H Functionalization
1.3.5 Synthesis of Heterocycles via N-H/O-H/C-H Diazo Carbene Insertion
1.3.6 Synthesis of Heterocycles from Diazo Compounds via Transition Metal-Catalyzed Multicomponent Reaction
1.4 Research Design and Objective
Chapter2 Diversity-Oriented Synthesis of Multisubstituted Pyrrolidine and Indole from Anilines and Diazopyruvates
2.1 Research Background
2.2 Introduction
2.2.1 Diversity-Oriented Synthesis(DOS)
2.2.2 Importance of Pyrrolidine and Indole
2.2.3 Strategies for Construction of Pyrrolidine and Indole
2.2.4 Design Reaction
2.3 Initial Investigation and Reaction Optimization
2.4 Substrate Scope of the Reaction
2.5 Mechanistic Study
2.6 Synthetic Application of the Developed Method
2.7 Proposed Transition State for the Diastereoselectivity
2.8 Summary
Chapter3 A Facile Synthesis of1,4 Oxazine fromα-Amino Ketones and Diazopyruvates
3.1 Research Background and Reaction Design
3.2 Biological Significance of1,4-Oxazine
3.3 Strategies towards1,4-Oxazine
3.3.1 Synthesis of1,4-Oxazine via Hydroamination
3.3.2 Synthesis of1,4-Oxazine via Hydroalkoxylation
3.3.3 Synthesis of1,4-Oxazine from SnAP Reagents
3.3.4 Synthesis of1,4-Oxazine from SLAP Reagents
3.3.5 Synthesis of1,4-Oxazine from Olefin Amine(OLA)Reagents
3.3.6 Synthesis of1,4-Oxazine from Metal Carbene
3.3.7 Miscellaneous Strategies
3.4 Initial Investigation and Reaction Optimization
3.5 Substrate Scope of the Reaction
3.6 Possible Mechanism
3.7 Summary
Chapter4 Conclusion
Chapter5 Experimental
5.1 General Information
5.2 Experimental Procedures
5.2.1 Procedure for the Preparation of Diazopyruvates (2)
5.2.2 Procedure for the Preparation of Fully-Substituted Pyrrolidine 3 (P-1)
5.2.3 Procedure for the Preparation of Pyrrolidine 3v
5.2.4 Procedure for the Preparation of Enol Intermediates (4)
5.2.5 Procedure for the Synthesis of Substituted Indole 5
5.2.6 Procedure for the Synthesis of Substituted Pyrrole 6
5.2.7 Procedure for the Preparation of 1,4-oxazine (3)
5.2.8 CCK-8 Assay
5.3 Characterization Data of Products
References
AppendixⅠ: NMR Spectra of Products
AppendixⅡ:X-ray Diffraction analysis
The Author's Resume and Publications
Acknowledgement
本文编号：3197305
【文章来源】：华东师范大学上海市 211工程院校 985工程院校 教育部直属院校
【文章页数】：185 页
【学位级别】：博士
【文章目录】：
摘要
Abstract
Chapter1 Introduction
1.1 An Overview of Heterocycles and Their Biological Significance
1.2 Introduction of Diazo Compounds
1.2.1 Background
1.2.2 Stability and Reactivity
1.3 Synthesis of Heterocycles from Diazo Compounds
1.3.1 Synthesis of Heterocycles from Diazo Compounds Involving Allene Intermediate
1.3.2 Synthesis of Heterocycles from Diazo Compounds via Carbene/Alkyne Metathesis
1.3.3 Synthesis of Heterocycles from Diazo Compounds and Enyne
1.3.4 Synthesis of Heterocycles from Diazo Compounds via Transition Metal-Catalyzed C-H Functionalization
1.3.5 Synthesis of Heterocycles via N-H/O-H/C-H Diazo Carbene Insertion
1.3.6 Synthesis of Heterocycles from Diazo Compounds via Transition Metal-Catalyzed Multicomponent Reaction
1.4 Research Design and Objective
Chapter2 Diversity-Oriented Synthesis of Multisubstituted Pyrrolidine and Indole from Anilines and Diazopyruvates
2.1 Research Background
2.2 Introduction
2.2.1 Diversity-Oriented Synthesis(DOS)
2.2.2 Importance of Pyrrolidine and Indole
2.2.3 Strategies for Construction of Pyrrolidine and Indole
2.2.4 Design Reaction
2.3 Initial Investigation and Reaction Optimization
2.4 Substrate Scope of the Reaction
2.5 Mechanistic Study
2.6 Synthetic Application of the Developed Method
2.7 Proposed Transition State for the Diastereoselectivity
2.8 Summary
Chapter3 A Facile Synthesis of1,4 Oxazine fromα-Amino Ketones and Diazopyruvates
3.1 Research Background and Reaction Design
3.2 Biological Significance of1,4-Oxazine
3.3 Strategies towards1,4-Oxazine
3.3.1 Synthesis of1,4-Oxazine via Hydroamination
3.3.2 Synthesis of1,4-Oxazine via Hydroalkoxylation
3.3.3 Synthesis of1,4-Oxazine from SnAP Reagents
3.3.4 Synthesis of1,4-Oxazine from SLAP Reagents
3.3.5 Synthesis of1,4-Oxazine from Olefin Amine(OLA)Reagents
3.3.6 Synthesis of1,4-Oxazine from Metal Carbene
3.3.7 Miscellaneous Strategies
3.4 Initial Investigation and Reaction Optimization
3.5 Substrate Scope of the Reaction
3.6 Possible Mechanism
3.7 Summary
Chapter4 Conclusion
Chapter5 Experimental
5.1 General Information
5.2 Experimental Procedures
5.2.1 Procedure for the Preparation of Diazopyruvates (2)
5.2.2 Procedure for the Preparation of Fully-Substituted Pyrrolidine 3 (P-1)
5.2.3 Procedure for the Preparation of Pyrrolidine 3v
5.2.4 Procedure for the Preparation of Enol Intermediates (4)
5.2.5 Procedure for the Synthesis of Substituted Indole 5
5.2.6 Procedure for the Synthesis of Substituted Pyrrole 6
5.2.7 Procedure for the Preparation of 1,4-oxazine (3)
5.2.8 CCK-8 Assay
5.3 Characterization Data of Products
References
AppendixⅠ: NMR Spectra of Products
AppendixⅡ:X-ray Diffraction analysis
The Author's Resume and Publications
Acknowledgement
本文编号：3197305
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