Research News, July 20th, 2012

 Metal-free Synthesis of Cyclic Di-oxoguanidines via One-pot Sequential Transformation of Amines, Carbodiimides and Acid Dichlorides 

Fei Zhao, Yang Wang, Wen-Xiong Zhang,* and Zhenfeng Xi.* 

Org. Biomol. Chem. 2012, 10, 6266–6270. (Inside Front Cover)

Metal-catalyzed two-component guanylation reaction of amines and carbodiimides is a well-established process to prepare acyclic guanidines. However, it is a challenging objective how the third unknown component can be incorporated into guanylation reaction to construct some important N-containing compounds. The effect of the above process generally requires more than one step and needs usually the presence of the second catalyst or one new challenging catalyst. The paper provides a new protocol: the third component can activate a certain component to make all components coupled without catalyst. Surprisely, we find acid dichlorides can not only serve as the third component but also activate carbodiimides to let this sequential reaction among amines, carbodiimides and acid dichlorides go smoothly under the metal-free conditions. This coupling provides a simple and general method to cyclic di-oxoguanidines. The unexpected 2,2-dichloro-imidazolidindione intermediate is considered to be essential for realizing such a useful and metal-free transformation. In sharp contrast, the AlMe3-catalyzed sequential reaction from the same substrates gives the isomer.