不饱和炔醛在有机催化反应和合成中的研究

The research program involves the discovery of novel reactivity through exploration of an ignored class of compounds ‒ α，β-unsaturated alkynals (ynals). Iminium catalysis currently dominated by using α，β-unsaturated aldehydes (enals) as essential substrates has enjoyed great success. Nevertheless, reactions with ynals have emerged slowly as results of their similar reaction behavior to enals people thought. However, the ynals are full of unexpected new reactivities and chemistries which are completely different from enals beyond our expection. During the funding period, we strive to explore novel reactivities of ynals in iminium catalysis with a series of very weak nucleophiles such as halogen ions, and “O” and “N” centered nucleophilic species, which are impossible in enals related iminium catalysis. Furthermore, formidably challenging organocatalytic 1,6-addition reactions and 1,6-addition-initiated cascade reactions will significantly expand the scope of organocatalysis. Realization of new valuable transformations will offer unprecedented approaches to structurally diverse building blocks and intermediates, which are highly important in organic synthesis.

针对α，β-不饱炔醛在有机催化中的研究相当有限，本课题从炔醛自身结构特性出发，探索新的化学活性，开展新的有机反应研究和应用。发展特有的有机胺催化炔醛的1,4-和1,6-共轭加成反应，而这些化学转化在烯醛为反应物的反应中是难以实现的。这些反应包括aza-Michael-Michael串联反应，立体选择的炔醛与亲核性弱的卤素离子、羧酸、磷酸、磺酸和简单的苯酚及酰胺、磺酰胺等共轭加成及相关的串联反应以及1,6-共轭加成反应和aza-1,6-共轭加成-D-A串联反应等。运用这些方法合成有重要合成价值的砌块和高效合成具有重要生物活性的骨架和天然产物。这些结构包括1,4-二氢喹啉的优势结构，天然产物strychnos等生物碱的核心结构，indenols和indenes以及５步全合成Norfluorocurarine等。此项目的成功实施，将拓展有机胺催化的范围，提供新的合成方法，丰富现代有机合成化学。

针对α，β-不饱炔醛在有机催化合成反应中的研究和应用相当有限，本课题从α，β-不饱炔醛中碳碳三键的自身结构特性出发，利用其相对缺电性的sp杂化独特结构特点，开展相关的新的有机反应基础研究。发展新颖的、立体选择的有机催化不饱和炔醛的1,4-和1,6-共轭加成反应，特别是亲核性极弱的试剂像卤素离子等及高效的、对映选择性的串联反应，并运用这些方法高效合成结构复杂、具有重要生物活性的1,4-dihydroquinolines和quinolines的药物优势结构，天然产物strychnos、aspidosperma、iboga生物碱、喜树碱，和药物sulindac的核心结构。此项目的成功实现，将大大拓展有机催化的范围，为现代有机合成提供新有力的合成工具和有机化学增加崭新的内容，因而具有重要的理论和应用价值。