(S)-Histidine-based dipeptides as organic catalysts for direct asymmetric aldol reactions

The structure/activity relationships for some (S)-histidine-based dipeptide catalysts in direct aldol reactions have been examined. The reactivities and stereoselectivities are shown to be dependent upon the intramolecular cooperation of side-chain functional groups and the presence of a suitable combination and sequence of amino acids. Good yields (up to 96%) and enantioselectivities (up to 76% ee) were obtained with electron-deficient aromatic aldehydes in the presence of H-Leu-His-OH. The influence of different chiral and achiral co-catalysts on the reaction rates, yields and enantioselectivities has also been evaluated. Significant increases in the acceleration of the reaction, most remarkable for achiral trans-2,5-dimethylpiperazine as co-catalyst and the improved yields, were demonstrated. (c) 2005 Elsevier Ltd. All rights reserved.