Highly efficient primary amine organocatalysts for the direct asymmetric aldol reaction in brine

Organocatalytic systems made up of six primary amine organocatalysts, derived from natural primary amino acids, in combination with 2,4-dinitrophenol (DNP) have proven to be efficient in the presence of brine without further addition of organic solvents. The system formed by 1f and DNP was the most efficient one; it can catalyze the direct aldol reaction with a broad range of ketones and aromatic aldehydes, giving the corresponding aldol products in high yields with up to nearly perfect diastereo- and enantioselectivities (up to 99/1 syn/anti, >99% ee).

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(S,S)-2-Amino-N-(2-hydroxy-1,2,2-triphenylethyl)propanamideC23H24N2O2[α]D20=-190 (c 1.0, DMSO)Source of chirality: (S)-Ala and (S)-phenylglycineAbsolute configuration: (S,S)

(S,S)-2-Amino-N-(1-hydroxy-1,1,3-triphenylpropan-2-yl)propanamideC24H26N2O2[α]D20=-18 (c 1.0, DMSO)Source of chirality: (S)-Ala and (S)-PheAbsolute configuration: (S,S)

(S,S)-2-Amino-N-(1-hydroxy-4-methyl-1,1-diphenylpentan-2-yl)propanamideC21H28N2O2[α]D20=-54 (c 1.0, DMSO)Source of chirality: (S)-Ala and (S)-LeuAbsolute configuration: (S,S)

(S,S)-2-Amino-N-(1-hydroxy-4-methyl-1,1-diphenylpentan-2-yl)-3-methylbutanamideC23H32N2O2[α]D20=-49 (c 1.0, DMSO)Absolute configuration: (S, S)Source of chirality: (S)-Val and (S)-Leu

(S,S)-2-Amino-N-(2-hydroxy-1,2,2-triphenylethyl)-4-methylpentanamideC26H30N2O2[α]D20=-155 (c 1.0, DMSO)Source of chirality: (S)-Leu and (S)-phenylglycineAbsolute configuration: (S, S)

(S,S)-2-Amino-N-(1-hydroxy-1,1,3-triphenylpropan-2-yl)-4-methylpentanamideC24H34N2O2[α]D20=-44 (c 1.0, DMSO)Source of chirality: (S)-Leu and (S)-LeuAbsolute configuration: (S, S)