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

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.

The most stable transition states of the crucial C–C bond-forming step for the proline- and tryptophan-catalyzed direct Mannich reaction involving hydroxyacetone, p-anisidine, and p-nitrobenzaldehyde.Figure optionsDownload as PowerPoint slide