过渡金属催化不饱和含氮化合物参与的杂-环加成反应

Hetero-cycloaddition reaction of unsaturated nitrogen-containing substrates is one of the most efficient methods for the synthesis of azacyclic compounds. In our previous work, highly efficient iron and other transition metal-catalyzed [2+2+2] hetero-cycloaddition reactions of alkynes and nitriles or aldehyde oximes to form pyridines was developed. Following this avenue, transition metal-catalyzed other hetero-cycloaddition reactions will be studied in this research proposal. The application of iron catalyst on the new hetero-cycloaddition reactions, the generation and the catalytic reactivity of active iron species will be investigated. In addition, the transition metal-catalyzed hetero-cycloaddition reactions of unsaturated nitrogen-containing compounds such as imines and methyleneaziridines will be carried out. Substrate activation strategies will be applied to tackle the low reactivity issue of imines and other related substrates in the cycloaddition reactions. New catalytic systems with high activity and selectivity will be developed. Furthermore, studies on the interaction between the catalyst and the reactant, and the control factors on the regioselectivity of reactions on the basis of ligand design will provide insights into the mechanism of the hetero-cycloaddition reactions. In view of the fact that cycloaddition reaction is one of the most important issue in organic chemistry, and transition metal catalysis is a powerful tool in synthetic chemistry, the successful implementation of this project will make a significant contribution to the field of transition metal catalysis as well as the discovery of new reaction patterns and catalytic systems for the synthesis of important nitrogen-containing heterocycles.

不饱和含氮化合物参与的杂-环加成反应是构建含氮杂环化合物非常有效的手段之一。在前期工作中，我们利用铁和其它过渡金属高效地催化炔与腈或醛肟的杂-[2+2+2]环加成反应合成了吡啶化合物。由此本项目将继续深入研究过渡金属催化不饱和含氮化合物参与的其它杂-环加成反应。探索铁催化体系在杂-环加成新反应中的应用，阐明铁催化剂的产生过程及其对反应活性的影响；发现亚甲基氮杂环丙烷等不饱和环状底物参与的杂-环加成新反应；解决亚胺等含C=N双键底物难以参与环加成反应的问题；发展出高活性和高选择性的新催化体系；探索如何利用配体的选择来控制反应的区域选择性。通过深入理解催化剂与反应物之间的作用模式，揭示催化杂-环加成反应的机理。环加成反应是有机化学重要的研究方向之一,而过渡金属催化始终是合成化学中的重要工具，本项目的成功实施将会对过渡金属催化化学、环加成反应新催化体系的研究和新反应的发现作出贡献。

不饱和含氮化合物参与的杂-环加成反应是构建含氮杂环化合物非常有效的手段之一。在自然科学基金面上项目（21372219）的资助下，本项目研究了金属催化亚甲基氮杂环丙烷、环丙亚胺、硝酮等含氮小分子参与的环加成或环化反应，高选择性地构建了吡咯、吖庚因、吲哚、均三嗪等一系列杂环化合物。通过深入理解催化剂与反应物之间的作用模式，揭示金属催化杂-环加成反应的机理。本项目培养毕业了4位博士，发表了10篇研究论文（含3篇Angew. Chem. Int. Ed.），申请了12件中国专利。