Asymmetric catalysis by l-prolinamide based small molecules: synthesis, characterization and first principle studies on their enantioselectivity

Abstract

This paper delineates the stepwise synthesis of l-prolinamide organocatalysts and their comparative NMR studies to investigate the effect of the position and electronic nature of groups attached to the aryl ring, on the chemical shifts of l-proline's protons, particularly H7 and amide protons (-CH7CONH). The catalytic activity of these catalysts has been explored and compared for Michael and oxa-Michael-Henry reactions. This catalytic system displayed excellent catalytic efficiency for both the reactions and provided the corresponding products in high yields. The enantioselectivity of the products was found to be affected by the structure of reactants. The mechanistic routes of these reaction have also been explored by performing density functional calculations that explained the (R,R)- and (S)-enantiomer preferences for the Michael addition and oxa-Michael Henry reactions, respectively, via transition state optimization studies.