Dual stereocontrol in aldol reactions catalysed by hydroxyproline derivatives in the presence of a large amount of water

• Published in: Tetrahedron: asymmetry Vol. 27; no. 19; pp. 936 - 942
• Main Authors: Gurka, András A., Szőri, Kornél, Bartók, Mihály, London, Gábor
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.10.2016; Elsevier
• Subjects: Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Chemistry, Physical; Physical Sciences; Science & Technology; KETONES; ENANTIOSELECTIVITY; AMINO-ACIDS; STEREOCHEMISTRY; ORGANOCATALYSIS; ALDEHYDES; DIHYDROXYACETONE; EFFICIENT; ASYMMETRIC ALDOL
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/j.tetasy.2016.08.009

[Display omitted] Parameters influencing dual stereocontrol in aldol reactions of water miscible acetone with aromatic aldehydes in the presence of a large amount of water using hydroxyproline based catalysts were studied. Stereocontrol was achieved by changing the acidity and basicity of the reaction media by the addition of achiral salts in the presence of a single chiral catalyst. Under acidic conditions (NH4Cl salt) the (R)-aldol product was formed in excess while basic aqueous media (carboxylate salts) led to the enrichment of the (S)-enantiomer. Reaction conditions under which the reaction is feasible were optimised and the effect of the structure of the hydroxyproline-based catalysts was investigated. The results show that the formation of a biphasic micellar system and the presence of an appropriate catalyst are both crucial for the reaction to occur. Although the catalyst structure influenced the formation and stabilisation of the micellar system to a large extent, its effect on the enantioselectivities were found to be less pronounced.