Asymmetric Direct Stoichiometric Aldol Reactions in Water

Significance

The authors report an organocatalytic asymmetric direct aldol reaction that only requires stoichiometric amounts of the substrates, in water mediated by sulfated β-cyclodextrin (β-CD). tert-Butylphenoxy proline catalyst 1 was found to be effective for this reaction. The sulfated β-CD binds with the catalyst 1 and acts as an inverse phase-transfer reagent (i.e., it allows water-insoluble molecules to react in aqueous medium). With 2 mol% of catalyst 1 and 10 mol% of sulfated β-CD good to high diastereoselectivities (dr = 84:16 to >99:1) and excellent enantioselectivities (er = 98:2 to >99:1) are obtained for different aldehydes.