研究室工作進展 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.
亮點介紹
胍作為一類重要的含氮有機化合物，是許多生物活性物質的結構單元，同時也作為堿性催化劑在有機合成中有廣泛應用。胺對碳二亞胺的催化成胍（CGAC）反應，是一種直接的、原子經濟性的方法制備胍。本課題組一直緻力于胍類化合物的合成和應用研究，并對該反應的發現，發展現狀與重要性進行了評述（Organometallics 2015, 34, 1787; Chem. Commun. 2015, 51, 254），雖然該成胍反應發展迅速，然而通過串聯成胍反應合成環狀胍的報道卻較少。在此基礎上，我們發展了一種Zn(OTf)2催化的成胍/酰胺化串聯反應合成了一系列環狀胍類化合物。該串聯反應第一次使用簡單易得的氨基酸酯鹽酸鹽，操作簡單，效率高，并通過三個重要的反應中間體的分離與結構表征，對反應機理及催化劑Zn(OTf)2的作用進行了詳細的研究。該文被歐洲化學雜志選為Cover Paper。