New organocatalysts derived from tartaric and glyceric acids for direct aldol reactions

The synthesis of several new pyrrolidine based asymmetric organocatalysts derived from tartaric, glyceric acids and a pyrrolidine moiety is described with a study of their application in the development of an enantioselective aldol protocol. The influence of different proton donor groups, such as a primary hydroxyl or a carboxylic acid group, or their absence, on the efficiency of the organocatalyst was studied. The configuration of the tartrate derived catalysts and the presence of the rigid butane-2,3-diacetal were found to have a strong influence on the stereoselective outcome of the aldol reaction.

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(2S)-Prolinyl-[(2R,3R,5R,6R)-3-hydroxymethyl-2-aminomethyl-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane]-amideC15H28N2O6[α]D20=-157.3 (c 1.0, CH2Cl2).Source of chirality: l-tartaric acid and l-prolineAbsolute configuration: (2S) (proline), (2R,3R,5R,6R) (tartrate)

(2S)-Prolinyl-[(2R,3R,5R,6R)-3-hydroxycarbonyl-2-aminomethyl-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane]-amideC15H26N2O7[α]D20=-131.1 (c 0.37, CH2Cl2).Source of chirality: l-tartaric acid and l-prolineAbsolute configuration: (2S) (proline), (2R,3R,5R,6R) (tartrate)

(2S)-Prolinyl-[(2S,3S,5S,6S)-3-hydroxymethyl-2-aminomethyl-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane]-amideC15H28N2O6[α]D20=+109.0 (c 0.3, CH2Cl2).Source of chirality: d-tartaric acid and l-prolineAbsolute configuration: (2S) (proline), (2S,3S,5S,6S) (tartrate)

(2S)-Prolinyl-[(2S,3S,5S,6S)-3-hydroxycarbonyl-2-aminomethyl-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane]-amideC15H26N2O7[α]D20=+112.3 (c 0.26, CH2Cl2).Source of chirality: d-tartaric acid and l-prolineAbsolute configuration: (2S) (proline), (2S,3S,5S,6S) (tartrate)

(2S)-Prolinyl-[(2R,3S,5R,6R)-3-hydroxymethyl-2-aminomethyl-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane]-amideC15H28N2O6[α]D20=-122.7 (c 0.30, CH2Cl2).Source of chirality: l-tartaric acid and l-prolineAbsolute configuration: (2S) (proline), (2R,3S,5R,6R) (tartrate)

(2S)-Prolinyl-[(1R,2S,4R,5R)-2-aminomethyl-4-methoxy-4,5-dimethyl-3,6,8-trioxabicyclo[3.2.1]octane]-amideC14H24N2O5[α]D20=-103.7 (c 0.43, acetone).Source of chirality: l-tartaric acid and l-prolineAbsolute configuration: (2S) (proline), (1R,2S,4R,5R) (tartrate)

(2S)-Prolinyl-[(2S,5R,6R)-2-aminomethyl-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane]-amideC14H26N2O5[α]D20=-150.8 (c 0.80, CH2Cl2).Source of chirality: l-glyceric acid and l-prolineAbsolute configuration: (2S) (proline), (2S,5R,6R) (glycerate)