Organocatalytic Direct Asymmetric Aldol Reactions in Water

Abstract

We have developed direct asymmetric cross-aldol reactions that can be performed in water without addition of organic solvents. A bifunctional catalyst with a long hydrophobic alkyl chain efficiently catalyzed the reactions and afforded the desired aldol products in excellent yield with high enantiomeric excess, even when only an equal molar ratio of the donor and acceptor was used. These results reveal an effective design strategy for the development of aqueous organocatalytic systems.

A supramolecular hydrogel as a reusable heterogeneous catalyst for the direct aldol reaction

“…9 In particular, Barbas has described related amphiphilic catalysts that form an emulsion in water and act as efficient catalysts for this reaction. 10 In the case reported here, an additional advantage appears, owing to the fact that a hydrogel can be easily recycled and recovered as a solid-like heterogeneous phase. Furthermore, due to their dynamic reversible nature, supramolecular hydrogels can be disassembled in response to slight environmental changes like temperature or pH, allowing on-off switching of catalytic activity.…”

“…The results described indicate that this supramolecular heterogeneous catalytic system uses one of the most important non-covalent interactions in the biological context, the hydrophobic effect, both for the self-construction of the catalyst as well as for the approach of the substrate to the catalytic center. As reported for direct aldol reactions catalyzed by L-proline derivatives, [8][9][10] the reaction is meant to take place following an enamine-based mechanism, and accordingly, the supramolecular hydrogel would be acting as an effective type I aldolase mimetic. Further work will be carried out in the study of the scope of substrate selectivity and the influence of co-solvent on the reaction rate.…”

Acid controlled diastereoselectivity in asymmetric aldol reaction of cycloketones with aldehydes using enamine-based organocatalysts

“…Chiral primary amine compounds had been discovered to be suitable catalysts for the asymmetric aldol reaction. [35][36][37][38][39][40] Different kinds of chiral amines (Scheme 1) were chosen as catalysts for the aldol reactions using 4-nitrobenzaldehyde and cyclohexanone as the model substrates (Table S1, ESIw).Our catalyst screening studies clearly demonstrated that chiral amine 1a combined with TFA could efficiently catalyze the asymmetric aldol reaction under solvent-free condition togive an ee of 97% and syn/anti ratio of 11/89. When the loading of chiral amine was reduced to as low as 2 mol%, the product was obtained with moderate yield (58%) and good enantioselectivity (83% ee).…”

“…Chiral primary amine compounds had been discovered to be suitable catalysts for the asymmetric aldol reaction. [35][36][37][38][39][40] Different kinds of chiral amines (Scheme 1) were chosen as catalysts for the aldol reactions using 4-nitrobenzaldehyde and cyclohexanone as the model substrates (Table S1, ESIw).…”

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

“…141 In their extensive research efforts in this area, Barbas III and coworkers recently developed a new type of diamine catalyst 23 bearing hydrophobic aliphatic side chains. 142 Thus, the diamine 23/CF 3 COOH bifunctional catalyst system showed excellent reactivity, diastereoselectivity, and enantioselectivity in asymmetric aldol reaction in water (yield up to 99%, anti/ syn up to 91 : 9, ee up to 99%) (Scheme 41). In this case, there is again some possibility that the straight chain alkyl groups acted as an effective surfactant to cause favorable interactions of the catalyst with the substrates.…”