研究室工作进展 Jul. 8th, 2015
Synthesis and Mechanistic Study of Cyclic Oxoguanidines via Zn(OTf)2-Catalyzed Guanylation/Amidation from Readily Available Amino Acid Esters and Carbodiimides
Chi, Yue; Xu, Ling; Du, Shanshan; Yan, Haihan; Zhang, Wen-Xiong*; Xi, Zhenfeng
Chem. Eur. J. 2015, 21, 10369-10378. (Cover Paper)
Recent years have witnessed a rapid growth in the area of catalytic guanylation reaction of amines with carbodiimides (CGAC reaction). This is because CGAC reaction will provide a straightforward and atom-economical method to prepare substituted guanidines, which have unique value in pharmacy, organometallic and coordination chemistry, and organic synthesis. In this work, we will report a tandem Zn(OTf)2-catalyzed guanylation/amidation process from readily available amino acid ester hydrochlorides and carbodiimides to efficiently construct various cyclic oxoguanidines, including 2-amino-1H-imidazol-5(4H)-ones and 2-aminoquinazolin-4(3H)-ones in medium to high yields. It is the first time to use the ammonium salt in guanylation reaction. Application of cyclic oxoguanidines is also explored to provide the conjugated heterocyclic compounds via oxidative C–N formation or aldol reaction. The reaction mechanism is well elucidated by the isolation and characterization of three important intermediates.
亮点介绍
胍作为一类重要的含氮有机化合物，是许多生物活性物质的结构单元，同时也作为碱性催化剂在有机合成中有广泛应用。胺对碳二亚胺的催化成胍（CGAC）反应，是一种直接的、原子经济性的方法制备胍。本课题组一直致力于胍类化合物的合成和应用研究，并对该反应的发现，发展现状与重要性进行了评述（Organometallics 2015, 34, 1787; Chem. Commun. 2015, 51, 254），虽然该成胍反应发展迅速，然而通过串联成胍反应合成环状胍的报道却较少。在此基础上，我们发展了一种Zn(OTf)2催化的成胍/酰胺化串联反应合成了一系列环状胍类化合物。该串联反应第一次使用简单易得的氨基酸酯盐酸盐，操作简单，效率高，并通过三个重要的反应中间体的分离与结构表征，对反应机理及催化剂Zn(OTf)2的作用进行了详细的研究。该文被欧洲化学杂志选为Cover Paper。