光促进的氮杂环卡宾催化偶联及加成反应研究

Light-promoted reactions could generate highly reactive radicals under mild conditions, accomplishing the activation of inert chemical bonds, and it could realize reactions that hardly proceed in an ion-type. While the problems of poor selectivity, especially the poor stereoselectivity hampered the application of light-promoted reactions in organic synthesis, related research on improving the selectivity is a challenge but highly desired. As a kind of highly efficient organocatalyst, N-heterocyclic carbenes (NHCs), with its structure diversity and broad substrate scope, met great success in the area of organic synthesis especially the asymmetric synthesis in recent years. However, there are seldom reports on utilizing the highly efficient catalytic property and excellent stereocontrol ability of NHCs to solve the selectivity problem of light-promoted reactions. We propose to use the coupling, addition and related cascade reactions between highly reactive radical intermediates generated in light-promoted reaction system and various electron-rich and/or electron-deficient intermediates generated through the addition of NHCs to the substrates, in order to enhance the stereoselectivity of light-promoted reactions, enrich the reaction type of NHC-catalysis, and accomplish precise synthesis of target molecules. The research will develop several novel, efficient and green coupling/addition reactions, providing new methodologies of light-promoted NHC-catalyzed chemical transformations, and thus advance the science of catalysis.

光促反应可在温和条件下产生高活性的自由基中间体，实现惰性键的活化,能够完成离子型反应不易实现的反应。但选择性差尤其是立体选择性差等问题限制了此类反应在合成中的应用,提高光促反应选择性的相关研究亟待突破。氮杂环卡宾是一类高效的有机小分子催化剂，其结构多样、底物广泛，近年来在有机合成，特别是不对称合成领域取得了长足发展。但是少有报道利用氮杂环卡宾的高效催化性能及优异的立体控制性解决光促反应中存在的选择性问题。氮杂环卡宾通过与底物作用形成多样的中间体，起到活化底物的作用。我们拟通过利用光促反应中产生的高活性自由基中间体与氮杂环卡宾催化中形成的富电子及缺电子中间体的偶联反应、加成反应及相关的串联反应，提高光促反应的立体选择性，丰富卡宾催化的反应类型，实现目标分子的精准合成。研究有望实现若干新颖、高效、绿色的偶联加成反应，开发光促进的氮杂环卡宾催化转化新模式，促进催化科学发展。

氮杂环卡宾是一类重要的有机小分子催化剂，催化产生的中间体类型丰富，但目前卡宾催化反应多局限于离子型反应。本项目开发了光促进氮杂环卡宾催化新策略，将光氧化还原反应与卡宾催化有机结合，发展了卡宾催化的新型自由基反应，有效拓展了卡宾催化的应用范围。项目实现了光促进卡宾催化γ-预氧化烯醛的远端烷基化反应，突破原来卡宾催化局限于C(sp2)试剂的限制，将底物范围拓展至普通的C(sp3)烷基化试剂，并首次实现卡宾催化经三烯醇中间体的ε-位烷基化反应。项目发展了系列氧气氧化的绿色反应，实现了光/卡宾协同催化的氧化Smiles重排，光促进卡宾催化的四氢异喹啉的氧化偶联，以及光促进苄位C(sp3)-H氧化官能化反应。项目实现了光催化可调控的Heck型反应和烯烃烷基化氧化反应，选择性地得到多取代烯烃和烷基芳基酮类化合物。.研究工作开发的光促进卡宾催化为协同催化提供了新策略，发展的三烯醇中间体为卡宾催化远端官能化提供了新方法。项目发表SCI论文5篇，其中Angew. Chem. Int. Ed. 1篇，Org. Lett. 1篇， Chem. Commun. 1篇，Adv. Synth. Catal. 1篇，Org. Biomol. Chem. 1篇。毕业博士研究生3名。