Theoretical studies of stereoselectivities in the direct organocatalytic Mannich reactions involving ketimine

Quantum mechanics calculations have been performed to study the stereoselectivities in the direct Mannich reactions catalyzed by different chiral secondary amine catalysts. The effects of two kinds of catalysts, (S)-1-(2-pyrrolidinylmethyl) pyrrolidine and proline on the diastereoselectivities of the direct Mannich reactions between ketimine and aldehyde have been studied with the aid of the BH and HLYP method. Transition states of the stereochemistry-determining CC bond-forming step with the enamine intermediate addition to the ketimine for the subject reactions are reported. These theoretical calculations provide a good explanation for the opposite diastereoselectivities of these two different kinds of catalysts. Calculated and observed diastereomeric ratio and enantiomeric excess values are in good agreement.

The effects of two kinds of chiral secondary amine catalysts on the diastereoselectivities of the direct Mannich reactions between ketimine and aldehyde have been studied theoretically. The most stable transition states of the crucial CC bond-forming step for the proline and (S)-1-(2-pyrrolidinylmethyl) pyrrolidine-catalyzed processes provide a good explanation for the opposite diastereoselectivities of these two different kinds of catalysts.Figure optionsDownload as PowerPoint slide