A novel trifunctional organocatalyst for the asymmetric aldol reaction: a facile enantioselective synthesis of β-hydroxyketones

A new l-prolinamide trifunctional catalyst has been developed for the enantioselective aldol reaction of various aromatic and aliphatic aldehydes with acetone. This method provides high yields of β-hydroxyketones (up to 90%) with good enantioselectivity (up to 92%) at a low catalyst loading (10 mol %).

Figure optionsDownload as PowerPoint slide

(R)-4-Hydroxy-4-(2-nitrophenyl)butan-2-oneC10H11NO4Ee = 92% from HPLC[α]D = −107 (c 1.20 CHCl3)Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(3-nitrophenyl)butan-2-oneC10H11NO4Ee = 77% from HPLC[α]D = +53.2 (c 0.42 CHCl3)Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(4-nitrophenyl)butan-2-oneC10H11NO4Ee = 70% from HPLC[α]D = −21.8 (c 0.40 CHCl3)Source of chirality: asymmetric synthesis

(R)-4-(2,4-Dichlorophenyl)-4-hydroxybutan-2-oneC10H01Cl2O2Ee = 73% from HPLC[α]D = +39.5 (c 0.44, CHCl3)Source of chirality: asymmetric synthesis

(R)-4-(4-Chlorophenyl)-4-hydroxybutan-2-oneC10H11ClO2Ee = 65% from HPLC[α]D = +33.2 (c 0.70, CHCl3)Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(naphthalene-1-yl)butan-2-oneC14H14O2Ee = 62% from HPLC[α]D = +72 (c 0.20, CHCl3)Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(2,4-dinitrophenyl)butan-2-oneC10H10N2O6Ee = 70% from HPLC[α]D = −21.8 (c 0.40, CHCl3)Source of chirality: asymmetric synthesis

3-((R)-1-Hydroxy-3-oxobutyl)benzonitrileC11H11NO2Ee = 72%[α]D = +21 (c 0.60 CHCl3, 72% ee from HPLC)Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-5-methylhexan-2-oneC7H14O2Ee = 52%[α]D = +53.2 (c 0.40 CHCl3, 52% ee from HPLC)Source of chirality: asymmetric synthesis

(R)-4-Cyclohexyl-4-hydroxybutan-2-oneC10H18O2Ee = 51%[α]D = −33.4 (c 0.70 CHCl3, 51% ee from HPLC)Source of chirality: asymmetric synthesis

(R)-Hydroxy-4-phenylbutan-2-oneC10H12O2Ee = 63%[α]D = +65 (c 0.40 CHCl3, 63% ee from HPLC)Source of chirality: asymmetric synthesis

(4R)-Hydroxy-4(4-methoxyphenyl)-butan-2-oneC11H14O3Ee = 50%[α]D = +42 (c 0.45 CHCl3, 50% ee from HPLC)Source of chirality: asymmetric synthesis