Atom economic and highly syn-selective prolinamide-catalyzed cross-aldol addition of hydroxyacetone to aromatic aldehydes

The highly selective cross-aldol addition of hydroxyacetone (HA) to p-nitro and m-nitrobenzaldehyde is reported; the reaction is catalyzed by three different di- or tripeptides all containing D-Pro in the N-terminal position and one or two residues of β3-homophenylglycine (β3-hPhg): H-D-Pro-(R)-β3-hPhg-OBn, H-D-Pro-(R)-β3-hPhg-(S)-β3-hPhg-OBn and H-D-Pro-[(S)-β3-hPhg]2-OBn. Several reaction conditions have been tested, always in the absence of a protecting group on the HA hydroxyl. This reaction affords the desired compounds with complete regioselectivities being the other regioisomer completely avoided. Furthermore high enantioselectivities and satisfactory diastereoselectivities, always favouring the syn diastereoisomers, were obtained. The stereochemistry of the diols was further confirmed by the analysis of the 1H NMR spectrum of the corresponding carbonates, obtained by reaction of the syn/anti mixtures with triphosgene in presence of dimethylamino-pyridine (DMAP). Copyright © Taylor & Francis Group, LLC.