One-pot synthesis of dihydropyrimidines via eco-friendly phosphorus derivatives catalysis

A straightforward, cost effective and eco-friendly protocol for the Biginelli reaction relying on the use of readily available hypophosphorous acid is presented. The methodology developed displays improvements compared to existing methods, is high-yielding, robust and was applied to a panel of dihydropyrimidines and thio-derivatives with various substituents. Related urea derivatives such as guanidines, benzimidazoles and benzothiazoles also reacted efficiently to afford more complex scaffolds. Thus, this rapid and convenient catalysis allows access to a wide diversity of structures including original biologically relevant heterocycles.