Direct Asymmetric Aldol Reaction Using Polystyrene-Supported Proline Amide

Significance

Polystyrene-supported proline amide was designed, prepared, and found to promote the asymmetric aldol reaction. Thus, the reaction of l-proline derivative 3 with (2S)-2-amino-1,1,2-triphenylethanol (4) gave proline amide derivative 2 in 62% yield. Immobilization of proline amide 2 on mercaptomethyl-functionalized polystyrene and subsequent deprotection of the N-Boc group with formic acid afforded the polystyrene-supported proline amide 1 (proline amide loading = 0.74 mmol/g). Asymmetric aldol reaction of p-nitrobenzaldehyde with acetone was carried out in the presence of 10 mol% of catalyst 1 to give (S)-4-hydroxy-4-(4-nitrophenyl)butan-2-one in 96% yield with 95% ee.