Highly Enantioselective Biginelli Reaction of Aliphatic Aldehydes Catalyzed by Chiral Phosphoric Acids

Several chiral phosphoric acids were evaluated as organocatalysts for the enantioselective Biginelli reaction of aliphatic aldehydes. With a chiral phosphoric acid derived from 3,3′-bis(3,5-di- tert -butyl-4-methoxyphenyl)-1,1′-binaphthalene-2,2′-diol, and after extensive optimization of the reaction conditions, the corresponding dihydropyrimidines were obtained in moderate to high yields with 73–87% ee by a three-component reaction of an aliphatic aldehyde, urea, and a β-keto ester.