Efficient synthetic protocol for substituted guanidines via copper(I)-mediated intermolecular amination of isothiourea derivatives

Amination of S-methyl-N,N′-bis-Boc-isothiourea with either primary or sterically hindered secondary amines promoted by copper(I) chloride and K2CO3 gave N,N′-bis-Boc protected guanidines in good to excellent yields under mild reaction conditions.

Graphical abstractAn efficient synthetic protocol for substituted guanidines using copper(I)-salts-mediated intermolecular amination was developed. The synthesis of bis-Boc protected guanidines via the amination of S-methyl-N,N′-bis-Boc-isothiourea and N,N′-bis-Boc-thiourea with a variety of primary/secondary amines and anilines proceeded under mild reaction conditions without having to use highly toxic metal salts.Figure optionsDownload full-size imageDownload as PowerPoint slide