Asymmetric Aldol Reaction with Polystyrene-Supported Proline-Based Catalysts

Significance

Polystyrene-supported prolinamide was prepared and applied to the asymmetric direct aldol reaction in water. Thus, etherification of N-Boc-protected trans-4-hydroxy-proline 1 with vinylbenzyl chloride followed by condensation with (1S,2R)-(-)-1-amino-2-indanol gave dipeptide 3 in 40% yield over two steps. The thiolene coupling reaction of the dipeptide 3 with mercaptomethyl-polystyrene resin afforded the polymer-supported dipeptide, which was deprotected with TFA and washed with THF-Et₃N to furnish the polystyrene-supported prolinamide 4. Asymmetric aldol reaction of cyclohexanone (5) with 4-nitro-benzaldehyde (6) was carried out with the polymeric catalyst 4 to give the aldol product 7 in high yield with 72% ee. This catalyst was recovered and reused three times without any loss of catalytic activity.