Asymmetric Aldol Reaction in Water Catalyzed by Polystyrene-Supported Proline

Significance

The polystyrene (PS) resin supported proline-catalyzed asymmetric aldol reaction in water was described. Thus, the reaction of 4-hydroxy-l-proline with 4-chloromethylstyrene gave styrene derivative 1 in 80% yield. The radical reaction of 1 with polystyrene-supported thiol followed by cleavage of the Boc group with TFA afforded PS resin supported proline 2 (eq. 1). The asymmetric aldol reaction of cyclohexanone with 4-cyanobenzaldehyde was carried out in the presence of 10 mol% of 2 in water to give the aldol product 3 (98% conversion, anti/syn = 95:5, 98% ee) (eq. 2). Although less conversion was observed, catalyst 2 can be reused four times without loss of ­diastereoselectivity and enantio­selectivity.