基于喹喔啉衍生的新型非经典氮杂环卡宾的设计、合成及在促进金属催化性能方面的应用研究

Bulky and electron-rich N-heterocyclic carbenes (NHCs) play essential role in the improvement of stability, activity and selectivity of metal catalysts. In order to overcome the drawback that the traditional imidazole-based NHCs can hardly further improve the bulky and electron-rich properties of the ligands due to the inherent electron-withdrawing effect of the two nitrogen atoms (inductive effect) and the limitation of efficiently enlarging the bond angle of N―C(NHC)―N, this project will focus on the design and synthesis of mono-nitrogen/mono-carbon-stabilized, nonclassical ring-expanded NHCs (six-membered ring) derived from quinoxalines. These novel nonclassical NHCs have advantages of potentiality of exihibiting even more bulky and electron-rich features in comparison with the classical ones, availability of being isolated in free state, and capability of fine control of the steric and electronic effects of ligands through modification of substituents on the ligand scaffold. We will then study the coordinating behavior of these novel nonclassical ligands with a variety of transition metals (Pd, Au, Ir, Rh, Ru etc.). In addition, we will investigate and evaluate the role of the novel NHCs in the enhancement of the catalytic performance of metal catalysts by employing the palladium-catalyzed aryl chloride-participated cross-coupling and gold-catalyzed nucleophilic addition of alkynes as the model reactions. Furthermore, we will try to disclose the stabilization mechanism of the newly-designed nonclassical NHCs and elucidate the mechanism of their enhancement of the catalytic performanc of the related metal catalysts by using various analytical tools and theoretical calculation, thereby providing accumulated experimental data and laying the theoretical foundation for further application of these novel NHCs in the related fields.

具有大位阻富电子特性的氮杂环卡宾在提高金属催化剂的稳定性、活性和选择性方面发挥着至关重要的作用。针对传统咪唑型NHCs由于存在双氮吸电子作用 (诱导效应) 及N―C(NHC)―N键角不能有效变大的局限性进而制约大位阻和富电子性能进一步提高这一弊端，本项目拟以喹喔啉衍生物为母体，设计和合成单氮/单碳稳定的扩环（六元）非经典氮杂环卡宾，继而利用这种具有大位阻、富电子、游离稳定而且电子效应和空间立体效应易于通过取代基变换修饰进行精细调控等优点的新型非经典NHCs与各种过渡金属（钯、金、铱、铑、钌等）合成系列卡宾配合物，以钯催化的氯代芳烃参与的偶联和金催化的炔烃亲核加成为模板反应开展其促进金属催化性能的评价，并通过各种分析和理论计算等手段阐明卡宾稳定机制及促进金属催化性能的机理，从而为这种新型卡宾的进一步应用积累实验数据和奠定理论基础。

具有大位阻、富电子的配体对于提升过渡金属催化剂的稳定性、活性和选择性起关键作用。本项目的初衷是设计合成出基于喹喔啉衍生的新型扩环（六元）非经典氮杂环卡宾并利用这种具有潜在更大空间位阻和富电子性能的新型配体去提升过渡金属如金、铜、钯等的稳定性、活性和选择性，最后通过理论计算阐明新型卡宾的稳定机制及促进金属催化性能的机理。在项目的实际执行过程中发现，基于喹喔啉为母体骨架的单氮/单碳扩环（六元）非经典氮杂环卡宾并没有预期想象的那么稳定且难以分离得到游离稳定的目标卡宾，从而造成后续研究目标难以实现。所幸的是，在合成参照对比的相关配体过程中发现，基于远程具有碱性基团的双官能化五元环氮杂环卡宾和Buchwald联苯型膦配体在提升金催化剂稳定性和活性方面有很好的效果；同时发现基于2,9位和4,7位基团调控的菲咯啉配体对于提升P/N杂配Cu(I)光敏剂的稳定性和活性有很好效果。基于研究过程中的新发现，经向国家自然科学基金委申请，对项目研究内容和计划作相应调整，将研究重点转到开展具有双官能化五元环氮杂环卡宾配体和Buchwald联苯型膦配体的合成及提升金催化剂稳定性和活性的研究以及开展菲咯啉骨架电子效应和立体位阻效应精确调控及提升P/N杂配Cu(I)光敏剂的稳定性和活性研究。由此，相继成功开发了一系列高效、高选择性及温和的金催化反应和光催化反应，为一系列用常法难以合成或不易合成的具有潜在生理或药理活性或具有潜在功能材料应用价值的化合物的合成提供了新颖、便捷、高效地合成方法，包括-苯并[d][1,2,3]三嗪-4(1H)-酮取代苯乙酮、取代吲哚、2,5-二取代呋喃、1,5-苯并二氮杂卓、O-烯基膦酸酯、多取代降冰片烯、烯丙基芳烃、苯并芴醇、N-二氟甲基胺、-胺基酮、2-苯基乙酰胺、6-烷基菲啶、二氟烯烃、环丁烯并奎宁酮、3-胺基环戊烯砜类化合物等。至结题时，项目共发表SCI收录学术论文24篇，包括ACS Catal.1篇，Org. Lett. 3篇，Chem. Commun. 3篇，J. Org. Chem. 5篇，获得授权发明专利27项，培养研究生13名。