Water: the most versatile and nature’s friendly media in asymmetric organocatalyzed direct aldol reactions

The aldol reaction is an excellent synthetic tool to construct β-hydroxy carbonyl skeletons. The asymmetric version of this reaction has been developed for the synthesis of enantiomerically enriched β-hydroxy carbonyl motifs, which can be extended toward the stereogenic construction of complex polyol architectures. l-Proline and other organic molecules are known to catalyze asymmetric direct aldol reactions in various solvents. Most asymmetric organocatalyzed direct aldol reactions occur in organic media, although some aldol reactions have been carried out in water, either as a co-solvent or additive. The development of highly diastereo- and enantioselective organocatalyzed direct aldol reactions between a wide variety of substrates in water without the contamination of any organic solvent is of great interest. Herein, we discuss organocatalysts based on l-proline, 4-hydroxy-l-proline, simple amino acids, enzymes etc., which have been so far applied in asymmetric aldol reactions in aqueous media. The present review describes the chronological development of asymmetric organocatalyzed aldol reactions in aqueous media considering both ‘in water’ and ‘on water’ concepts in each subsection.

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