酸催化不饱和含氮分子的环加成反应

Cycloaddition reaction of unsaturated nitrogen-containing substrates is one of the most efficient methods for the synthesis of azacyclic compounds. To date, most of the cycloaddition reactions rely on transition metal catalysis. Therefore, the development of metal-free catalytic cycloadditions is of highly important in view of the limitations of metal catalysis. In our preliminary study, we have developed an efficient approach toward aminooxazoles via Tf2NH-catalyzed formal [3+2] cycloaddition of ynamides with dioxazoles. Following this avenue, acid-catalyzed cycloaddition reactions of ynamides with other unsaturated nitrogen-containing compounds will be investigated in this research proposal. The application of acid catalysts on the new cycloaddition reactions will be explored. The influence of acid catalysts on the reaction reactivity will be elucidated. In addition, the acid-catalyzed cycloaddition reactions of ynamides with unsaturated nitrogen-containing compounds such as oxadiazolones will be carried out. The role of water in the reaction with 3,5-dimethylisoxazoles will be also investigated. Furthermore, studies on the interaction between the acid catalyst and the reactant, and the control factors on the regioselectivity of reactions will provide insights into the mechanism of the cycloaddition reactions. In view of the fact that cycloaddition reaction is one of the most important issue in organic chemistry, and metal-free catalysis is one of the powerful tools in synthetic chemistry, the successful implementation of this project will make a significant contribution to the field of metal-free 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环加成反应是构建含氮杂环化合物非常有效的手段之一。但迄今为止，大部分催化体系都依赖于过渡金属催化剂。因而，基于金属催化剂的某些限制，发展高效的非金属催化体系具有很重要的意义。在前期工作中，我们利用Tf2NH高效地催化炔酰胺和二噁唑的[3+2]形式环加成反应，合成了氨基噁唑化合物。由此本项目将继续深入研究酸催化炔酰胺和其它不饱和含氮化合物的环加成反应。探索酸催化体系在环加成反应中的应用，阐明酸催化剂对反应活性的影响；发现噁二唑酮等不饱和含氮化合物参与的环加成新反应；探索水在3,5-二甲基异噁唑参与的反应中的作用。通过深入理解酸催化剂与反应物之间的作用模式，揭示催化环加成反应的机理。环加成反应是有机化学重要的研究方向之一，而非金属催化是合成化学中的重要工具之一，本项目的成功实施将会对非金属催化化学、环加成反应新催化体系的研究和新反应的发现作出贡献。

含氮杂环化合物由于其独特的生理、药理活性而广泛存在于众多天然产物、农药和医药分子中。因此，含氮杂环的合成方法学一直是有机化学的前沿科学。本项目主要探索新型高效的不饱和分子参与的环加成反应，来快速构建含氮杂环化合物。主要进展包括，1）酸催化炔酰胺和不饱和含氮分子的环加成反应，二噁唑/噁二唑酮可以作为三原子合成子参与反应，合成氨基噁唑与氨基咪唑；炔酰胺与异噁唑及水可以发生[5+2+1]环加成反应，构建氧桥-1,4-氧氮七元环。2）钌催化高烯丙基磺酰胺和炔的环化反应，证实反应可能经历了炔烃对π-烯丙基钌的迁移插入过程。3）钴催化酰胺与炔烃的脱羰环化反应，烷基芳基取代的不对称炔烃均能顺利反应，有着高的区域选择性。4）可见光诱导铑催化酰亚胺与炔烃的脱羰环化反应，铑催化剂用量可以低至1%，底物分子和铑催化剂原位生成铑类光敏剂。