双功能氮杂环卡宾催化不对称Vinylogous加成反应研究

As an important type of nucleophilic organocatalysts, N-hetrocyclic carbenes(NHCs)have been widely used in asymmetric synthesis.In this project, a novel chiral bifunctional NHCs bearing both Br?nsted-acidic site and Lewis- basic site will be designed and prepared. The asymmetric vinylogous addition of aldehyde, ketone and imine with O-silylated dienolates under catalysis of bifunctional NHCs will be investigated. The thio(urea)hydrogen activate electrophile as a Br?nsted acid via the interation of hydrogen-bond,while the carbene center activate nucleophile as a Lewis base. Due to the proximity effect, the catalytic efficiency and enantioselectivity will be increased dramatically through concerted catalysis of Lewis base and br?nsted acid, which will provide a valuable organocatalytic method for the preparation of optical active δ-hydroxy(amino)-α,β-unsaturated carbonyl compounds. Through the implementation of the project, bifunctional NHCs will be synthesized and the asymmetric vinylogous addition promoted by this new type of organocatalyst will realize, and these will push the progress of organocatalysis chemistry.

氮杂环卡宾是一类重要的亲核性有机小分子催化剂，在催化不对称合成中用途广泛。本项目在前期工作的基础上，设计、合成具有硫脲等Br?nsted酸基团的新型双功能手性氮杂环卡宾催化剂，研究在其催化下，醛、酮、亚胺等亲电试剂与共轭烯醇硅醚的不对称vinylogous加成反应。硫脲等Br?nsted酸基团，以分子间氢键作用活化亲电试剂；亲核卡宾则通过亲硅进攻活化亲核试剂，利用Lewis 碱-Br?nsted酸协同催化，提高催化效率，实现对反应的手性控制，解决vinylogous加成反应中存在的催化效率低、反应选择性差等问题，发展合成光学活性δ-羟基（氨基）-α,β-不饱和羰基化合物的不对称有机催化方法。通过本项目的实施，合成新型双功能氮杂环卡宾催化剂，实现有机催化的不对称vinylogous加成反应，可以促进氮杂环卡宾及有机催化化学的发展。

氮杂环卡宾是一类重要的有机催化剂，在不对称合成中有着广泛应用。本项目利用氮杂环卡宾的Leweis碱性和Brønsted碱性，对氮杂环卡宾催化的选择性vinylogous-Michael加成反应、vinylogous-Mukaiyama aldol反应、vinylogous-Mukaiyama Michael反应、C-S键的构筑反应、不对称去对称化反应等反应开展了系统研究，发展了选择性合成 γ, γ-双取代丁烯内酯、γ-单取代丁烯内酯、α–硫代烯醛、多手性中心苯并环己酮、手性环戊酮等重要合成中间体的新方法，目前已经发表SCI论文14篇 (包括 J. Org. Chem.; Chem. Commun.; Synthesis; Asian J. Org. Chem.; Tetrahedron等)，主要研究内容包括以下几个方面：.(1) 氮杂环卡宾催化当归酯、呋喃硅醚与羰基化合物、烯酮的选择性Vinylogous类型的加成反应.(2) 氮杂环卡宾催化C-S键的构筑反应.(3) 氮杂环卡宾催化不对称去对称化反应.(4) 氮杂环卡宾催化硅试剂与醛、酮的加成反应.(5) 氮杂环卡宾催化的其他反应