Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines

A convenient synthetic strategy toward N-acylguanidines via a sequential one-pot multicomponent carbonylation/amination reaction has been developed. The compounds were readily obtained via an N-cyanobenzamide intermediate formed from the Pd(0)-catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides. Subsequent amination with a large variety of amines provided the final N-acylguanidines, with the overall formation of one C–C and two C–N bonds, in moderate to excellent yields. The substrate scope was found to be wide and the methodology was used to produce over 50 compounds, including 29 novel molecules. Furthermore, three separate nitrogen-containing heterocycles were prepared from the N-acylguanidines synthesized using the developed multicomponent, carbonylative method.