Theoretical studies of stereoselectivities in the direct syn- and anti-Mannich reactions catalyzed by different amino acids

Abstract

Quantum mechanics calculations have been performed to study the stereoselectivities in the direct anti- and syn-Mannich reactions catalyzed by different amino acids. The effects of two kinds of amino acid catalysts, l-proline (secondary) and l-tryptophan (primary), on the diastereoselectivity and enantioselectivity of the direct Mannich reactions between α-hydroxyacetone, p-anisidine, and p-nitrobenzaldehyde have been studied. Transition states of the stereochemistry-determining C–C bond-forming step with the enamine intermediate addition to the imine for the proline- and tryptophan-catalyzed processes are reported. These theoretical calculations provide a good explanation for the opposite syn diastereoselectivities versus anti diastereoselectivities of these two types of catalysts ( syn-selectivity for the secondary cyclic amino acids such as proline and anti-selectivity for the acyclic primary amino acids such as tryptophan). Calculated and observed diastereomeric ratio and enantiomeric excess values are in good agreement.