Asymmetric N-selective Nitroso-aldol Reaction Catalyzed By Chiral Primary Amines

Recently, asymmetric organic catalysis has been the most important and interesting research topic in organic chemistry because of metal-free, environmentally benign and high atom economy. N-selective aldol reaction is one of the most important carbon-nitrogen bond forming reactions, and the products of a-nitrogenated carbonyl compounds play very important roles in the synthesis of pharmaceutical intermediates and chemical intermediates.Nitroso compounds have two reactive nitrogen and oxygen atoms. It is interesting and important to perform a nitrogen or oxygen selective reaction with interesting substrates. In this research, we designed and synthesized a series of primary amine catalysts la-lg from selected, commercially available natural amino acids in high yields. Then, the direct aldol reactions of unmodified aldehydes and nitrobenzene which were catalyzed by la-lg were tested. The results showed that N-selective nitroso-aldol adducts which were reduced in situ with NaBH4 were obtained as the only products with the highest ee up to 65% and yield up to 73% in the presence of catalyst la. To the best of our knowledge, this is the first direct enantioselective a-hydroxyamination of aldehydes with nitrosobenzene by a series of primary amine derivatives.In addition, we also discussed the mechanism of this asymmetric reaction. The bulkier substituted groups of the organocatalyst and two hydrogen bonds from the organocatalyst and the oxygen atom of nitrosobenzene make the reaction preferentially N-specific and predominantly afford R products.