Stereoselectivity of Proline-catalyzed Mannich Reaction: a Density Functional Study

摘要

The stereoselective step of (S)-proline catalyzed Mannich reaction of cyclohexanone, formaldehyde, and aniline were theoretically investigated using density functional theory, B3LYP, with 6-31＋＋g(d,p) basis set. From the proposed mechanism, cyclohexane and (S)-proline generate enamine and formaldehyde and aniline generate imine. The activation energies of the reaction between the enamine and imine which yield (S)- and (R)-intermediate are 8.5 and 12.4 kcal/mol, respectively. This is in agreement with experimental result that (S)-intermediate upon hydrolyzed yields major (S)-Mannich base product.