Small organic molecule catalyzed enantioselective direct aldol reaction in water

Protonated pyrrolidine based small organic molecules have been designed and evaluated for the asymmetric direct aldol reaction in water. The designed organocatalysts are multifunctional in nature and exploit the combined effect of hydrogen bonding and hydrophobic interactions for enantioselective catalysis in water. As a result a unique direct asymmetric aldol reaction in water catalyzed by a small organic molecule having an amide linkage has been developed. The developed catalyst affords chiral β-hydroxyketones in good yields (93%) and enantioselectivities (upto 62%) in water.

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(S)-2-(Phenylcarbamoyl)pyrrolidinium bromideC11H15N2OBr[α]D20=-18.0 (c 0.38, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Benzylcarbamoyl)pyrrolidinium bromideC12H17N2OBr[α]D20=-29.0 (c 0.61, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Naphth-1′-ylcarbamoyl)pyrrolidinium bromideC15H17N2OBr[α]D20=-16.0 (c 0.54, MeOH)Source of chirality: commercially available l-proline

(2S,1′R/S)-2-(1′-Phenylethylcarbamoyl)pyrrolidinium bromideC13H19N2OBr[α]D20=-28.5 (c 0.56, MeOH)Source of chirality: commercially available l-proline

(2S,1′R)-2-(1′-Phenylethylcarbamoyl)pyrrolidinium bromideC13H19N2OBr[α]D20=+39.0 (c 0.34, MeOH)Source of chirality: commercially available l-proline

(2S,1′S)-2-(1′-Phenylethylcarbamoyl)pyrrolidinium bromideC13H19N2OBr[α]D20=-114.8 (c 0.25, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Piperidine-1′-carbonyl)pyrrolidinium bromideC10H19N2OBr[α]D20=-53.0 (c 0.54, MeOH)Source of chirality: commercially available l-proline

(2S,1′R/S)-2-(1′-Naphth-1″-yl-ethylcarbamoyl)-pyrrolidinium bromideC17H21N2OBr[α]D20=-17.5 (c 0.89, MeOH)Source of chirality: commercially available l-proline

(2S,1′R)-2-(1′-Phenylpropylcarbamoyl)pyrrolidinium bromideC14H21N2OBr[α]D20=+42.0 (c 0.39, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Pyridinium-2′-ylcarbamoyl)pyrrolidinium dibromideC10H15N3OBr2[α]D20=+1.5 (c 0.80, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Pyridinium-3′-ylcarbamoyl)pyrrolidinium dibromideC10H15N3OBr2[α]D20=+4.0 (c 0.70, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Pyridinium-4′-ylcarbamoyl)pyrrolidinium dibromideC10H15N3OBr2[α]D20=+2.5 (c 0.65, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Pyrrolidine-1′-carbonyl)pyrrolidinium bromideC9H17N2OBr[α]D20=-55.5 (c 0.80, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Butylcarbamoyl)pyrrolidinium bromideC9H19N2OBr[α]D20=-14.5 (c 0.29, MeOH)Source of chirality: commercially available l-proline

(S)-2-(1′-Methylheptylcarbamoyl)pyrrolidinium bromideC13H27N2OBr[α]D20=-15.5 (c 0.62, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Hexylcarbamoyl)pyrrolidinium bromideC11H23N2OBr[α]D20=-21.0 (c 0.27, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Heptylcarbamoyl)pyrrolidinium bromideC12H25N2OBr[α]D20=-29.0 (c 1.43, MeOH)Source of chirality: commercially available l-proline

(S)-2-(Octylcarbamoyl)pyrrolidinium bromideC13H27N2OBr[α]D20=-19.0 (c 0.52, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Dipropylcarbamoyl)pyrrolidinium bromideC10H23N2OBr[α]D20=-40.0 (c 0.33, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Dimethylcarbamoyl)pyrrolidinium bromideC7H15N2OBr[α]D20=-41.0 (c 0.44, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Diethylcarbamoyl)pyrrolidinium bromideC9H19N2OBr[α]D20=-41.6 (c 0.31, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Dioctylcarbamoyl)pyrrolidinium bromideC21H43N2OBr[α]D20=-26.0 (c 0.49, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Dibutylcarbamoyl)pyrrolidinium bromideC13H27N2OBr[α]D20=-38.0 (c 0.33, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Dihexylcarbamoyl)pyrrolidinium bromideC17H35N2OBr[α]D20=-17.5 (c 0.68, MeOH)Source of chirality: commercially available l-proline

(2S,1′R)-2-(1′-Phenylethylcarbamoyl)pyrrolidinium trifluoroacetateC15H18N2F3O3Br[α]D20=+29.5 (c 0.15, MeOH)Source of chirality: commercially available l-proline

(S)-2-(N,N-Diisopropylcarbamoyl)pyrrolidinium bromideC11H23N2OBr[α]D20=-18.0 (c 1.19, MeOH)Source of chirality: commercially available l-proline

(2S,1′R)-2-(1′-Phenylethylcarbamoyl)pyrrolidinium chlorideC13H19N2OCl[α]D20=-37.0 (c 0.32, MeOH)Source of chirality: commercially available l-proline

(R)-4-Hydroxy-4-(4′-nitrophenyl)butan-2-oneC10H11NO4[α]D20=+30.0 (c 1.24, CH2Cl2)Ee = 46%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(2′-nitrophenyl)butan-2-oneC10H11NO4[α]D20=-89.0 (c 0.34, CH2Cl2)Ee = 62%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(3′-nitrophenyl)butan-2-oneC10H11NO4[α]D20=+35.0 (c 1.14, CH2Cl2)Ee = 47%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(4′-chlorophenyl)butan-2-oneC10H11ClO2[α]D20=+24.4 (c 0.94, CH2Cl2)Ee = 36%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(2′-chlorophenyl)butan-2-oneC10H11ClO2[α]D20=+50.0 (c 1.07, CH2Cl2)Ee = 41%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(4′-fluorophenyl)butan-2-oneC10H11FO2[α]D20=+25.9 (c 1.24, CH2Cl2)Ee = 37%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-phenylbutan-2-oneC10H12O2[α]D20=+26.5 (c 0.40, CH2Cl2)Ee = 37%Source of chirality: asymmetric synthesis

(R)-4-Hydroxy-4-(4′-cyanophenyl)butan-2-oneC11H11NO2[α]D20=+27.0 (c 0.94, CH2Cl2)Ee = 36%Source of chirality: asymmetric synthesis