Asymmetric Aldol Reaction in Water Using Polystyrene-Supported Proline

Significance

Polystyrene-supported proline 3 was synthesized and found to be highly effective for the asymmetric aldol reaction in water. Thus, esterification of N-Boc-4-hydroxyproline 1 with t-BuBr followed by etherification with propargyl bromide gave 2 in 63% yield. The [3+2] cycloaddition reaction of azide-substituted Merrifield resin with alkyne 2 afforded the polystyrene-supported N-Boc-proline ester. The resulting resin was deprotected with TFA and washed with THF-Et₃N (98:2) and yielded the polystyrene-supported proline 3. Asymmetric aldol reaction of various aldehydes with cyclic ketones in the presence of 10 mol% of catalyst 3 gave the corresponding aldol products in high yield (7 examples: 70-97% yield) with high enantioselectivities (87-97% ee).