Ugi反应
羧酸,C-异腈,胺和羰基化合物进行四组分缩合得到二酰胺(二肽)的反应。
此反应反应活性很高,反应时间一般都很短。最常用的溶剂是甲醇,有时候反应中加入少量的水可以加速反应 (J. Am. Chem. Soc. 2004, 126, 444.)。Ugi反应中各个R基团可以有各种变换,生成的肽类似物可能是有用的潜在的药物中间体。此反应在构建筛选化合物的化合物库方面有很好的应用。
反应的加量顺序(Marcaccini、S.; Torroba ,T. Nature Protocols 2007, 2, 632. doi:10.1038/nprot.2007.71):
反应机理
反应实例
参考文献
1. (a) Ugi, I. Angew. Chem. Int. Ed. 1962, 1, 8–21.; (b) Ugi, I.; Offermann, K.; Herlinger, H.; Marquarding, D. Liebigs Ann. Chem. 1967, 709, 1–10.; (c) Ugi, I.; Kaufhold, G. Ann. 1967, 709, 11–28; (d) Ugi, I.; Lohberger, S.; Karl, R. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991, Vol. 2, 1083. (Review); (e) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3168. (Review); (f) Ugi, I. Pure Appl. Chem. 2001, 73, 187–191. (Review). Ivar Karl Ugi (1930-2005) earned his Ph.D. under the guidance of Prof. Rolf Huisgen. Since 1962, he worked at Bayer AG, rising through the ranks to director. But he left Bayer in 1969 to pursue his indendent academic career at the University of Southern California (USC). In 1973, he moved to the Technische Universität München, where stayed until his retirement in 1999. Ugi was one of the pioneers in multi-component recations (MCRs).
2. Endo, A.; Yanagisawa, A.; Abe, M.; Tohma, S.; Kan, T.; Fukuyama, T. J. Am. Chem. Soc. 2002, 124, 6552-6554.
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Overkleeft, H. S. Eur. J. Org. Chem. 2008, 3678–3688.
10. Williams, D. R.; Walsh, M. J. Ugi Reaction. In Name Reactions for Homologations-Part II; Li, J. J., Ed.; Wiley: Hoboken, NJ, 2009, pp 786-805. (Review).
11. Tyagi, V.; Shahnawaz Khan, S.; Chauhan, P. M. S. Tetrahedron Lett. 2013, 54, 1279– 1284.
Ivar Karl Ugi (1930-2005)在Rolf Huisgen教授指导下获得Ph.D.学位。从1962年起在拜耳公司工作,做到主管的级别。1969后在南加大(USC)进行独立的学术研究。1973年后到慕尼黑工业大学任教至1999年退休。Ugi是研究多组分化学(MCRs)的先驱。
编译自:编译自:Name Reactions (A Collection of Detailed Reaction Mechanisms), Jie Jack Li, Ugi reaction,page 608-610.