L-Prolinamides Derived from Chiral and Achiral 1,2-Diamines as Useful Bifunctional Organocatalysts for Direct Diastereo- and Enantioselective Aldol Reaction

Diastereomeric catalysts 5 and epi-5, which differ in the configuration of the stereocenter at the amino component, have been prepared from L-proline and (S)-N-2,N-2-dibenzyl-3-methylbutane-1,2-diamine or (R)-N-1,N-1-dibenzyl-3-methylbutane-1,2-diamine, respectively. Diastereomeric prolinamides 10 and epi-10, which are regioisomers of 5 and epi-5, respectively, were obtained from the same starting compounds. All of the catalysts promoted high diastereo- and enantioselectivity in the cross-aldol reaction between aromatic aldehydes and cyclohexanone using acetic acid as cocatalyst. A small match/mismatch effect over the stereoselection was observed, depending on the configuration of the stereocenters at the proline and diamine components. In general, the best results were obtained with catalyst 5, which has the same configuration at both stereocenters. Under the same reaction conditions, prolinamide 20, which was synthesized from L-proline and ethylene dial-nine, without stereocenters at the diainine component, behaved as an excellent enantioselective organocatalyst, giving the aldol products in very high diastereo- and enantioselectivity.