Silver-Catalyzed Synthesis of 2-Amino-imidazole Alkaloids

Significance

Reported is the silver-mediated synthesis of 1,4,5-trisubstituted 2-aminoimidaz­oles 4 starting from secondary propargylamines 1 and thioureas 2. Silver nitrate in acetonitrile was found to be the most efficient catalyst. The guanylation and the cyclization steps can be carried out either in a stepwise manner using EDCl and the Hünig base, or in a one-pot manner using triethyl­amine as a base and a recoverable silver(I) salt as promoter and catalyst. Thus, using the Boc- and Cbz-protected S-methylthioureas 2b, a variety of secondary propargylamines 1 were converted in a single step into Boc- and Cbz-protected 2-imino­imidazolines 3 under mild conditions, in very short reaction times, and in good to excellent yields. Boc-protected products 3 were deprotected by treatment with TFA to afford the corresponding 2-aminoimidazoles 4. A mechanism involving a carbodiimide intermediate was proposed without evidence.