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Organocatalytic properties of polyhydroxylated prolines
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1  Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares and Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Academic Editor: Julio A. Seijas

https://doi.org/10.3390/ecsoc-27-16117 (registering DOI)
Abstract:

The development of enantioselective reactions using water as a reaction medium and small organic molecules as organocatalysts is an important current goal.1 Proline is a suitable organocatalyst, because its conformational rigidity, its ability to act as a base and as a Brönsted acid, both allowing it to act as an efficient bifunctional catalyst.2 Nevertheless, it is not efficient in aqueous media, which require prolines substituted with hydrophobic groups, because most of the reactions take place in the interphase of biphasic systems.3. A representative example is the aldol condensation of p-nitrobenzaldehyde with cyclohexanone, using (2S,4R)-4-((tert-butyldimethylsilyl)oxy)pyrrolidine-2-carboxylic acid (proline 1) as the catalyst and water as the solvent, Four stereoisomers resulted, with an overall yield of 86%, an anti/syn diastereomeric ratio of 20:1 and an enantiomeric excess of greater than 99%.

The organocatalytic properties of the similar (2S,3R,4R)-3,4-bis((tert-butyldimethylsilyl)oxy)pyrrolidine-2-carboxylic acid (proline 2), with two OH groups protected as OTBS, were now studied for the aldolic condensation of p-nitrobenzaldehyde with cyclohexanone, in the same conditions as for proline 1. The results obtained were almost similar. The enantiomeric yields and the enantiomeric excesses were also 86% and greater than 99%, respectively. But the diastereomeric anti/syn excess was now higher (25:1 versus 20:1)

Keywords: Organocatalysis, prolines, aldol condensation, stereoselective synthesis

 
 
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