Primary Amine Catalyzed Biginelli Reaction for the Enantioselective Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones

Several chiral primary amines, mainly those derived from cinchona alkaloids, were evaluated as organocatalysts for the asymmetric Biginelli reaction. With quinine-derived amine catalyst 1 and after extensive optimization of the reaction conditions, 3,4-dihydropyrimidin-2(1H)-ones were obtained in moderate to good yields and 51-78% ee from a three-component reaction of aryl and aliphatic aldehydes, urea, and acetoacetate.