Aerobic Copper-Catalyzed Organic Reactions - …

The methyl ester of (S)-proline-(S)-tryptophan (IV) was shown to be an efficient organocatalyst for asymmetric aldol reactions of ketones with aromatic aldehydes in the presence of water by using HSBM () []. The corresponding aldol products 3 were obtained in good yield (64–90%), low to high diastereoselectivity (40:60 to 98:2 dr, anti/syn) and moderate to excellent enantioselectivity (55 to >98% ee) by using only 3 mol % of IV. A similar transition state (TS 2) to that of III could be proposed, which involves the formation of enamine and simultaneous hydrogen bonding activation of the aldehyde by amidic NH of the catalyst. The large surface area of the lipophilic residue of the tryptophan, reinforced by the hydrophobic environment created by the addition of water, appears to be responsible for the improvement in diastereoselectivity. These factors also enhance the π–π stacking between the catalyst and aldehyde to form a more rigid transition state, which induces higher stereoselectivity. In addition, the acidity of the amidic N–H bond is increased by the formation of a hydrogen bond between water molecules and amidic carbonyl, thus providing a stronger hydrogen-bonding interaction with the aldehyde.

2.3.2 Stereoselective Synthesis of 1,3 Diols: Asymmetric Aldol Reactions 88

L-Proline and its analogues have been predominantly used in amino catalysis. We initiated a research program in which primary amino acids/amines, rather than the secondary pyrrolidine moiety, were utilized as the catalyst for a range of important asymmetric transformations. We demonstrated that primary amine organic catalysts have often shown to be complementary or superior, in comparison with secondary amine-mediated processes. For instance, we discovered that natural tryptophan and silylated threonine were efficient catalysts for the direct aldol and Mannich reaction in aqueous media, respectively.


The chemistry of isatins: a review from 1975 to 1999 - …

2.3.2 Stereoselective Synthesis of 1,3 Diols: Asymmetric Aldol Reactions 88.