| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1348310 | Tetrahedron: Asymmetry | 2011 | 12 Pages |
Novel β-homoproline derivatives, 2-hydroxy-2-(pyrrolidin-2-yl)acetic acids (R,S)- and (S,S)-1a–d, were synthesized. All of the prepared compounds were used as organocatalysts in the direct asymmetric aldol reaction of 4-nitrobenzaldehyde with several ketones. Among these catalysts, (R)-2-hydroxy-2-((S)-pyrrolidin-2-yl)acetic acid (R,S)-1a showed good catalytic ability in the formation of aldol product 13 (up to 69% ee, 95% yield), which was similar to the results catalyzed by l-proline (71% ee, 96% yield). Relatively low yields and low enantioselectivities were observed in aldol reactions catalyzed by (S,S)-1a, for example, 13 was obtained in 55% yield and 13% ee. The aldol reaction catalyzed by the methyl-protected carboxylic acid 1b and esters 1c,d produced much lower chemical yields and enantioselectivities during the formation of 13. The cooperative effect of the (R)-configured hydroxyl group and the carboxyl group was found to play an important role in inducing enantioselectivity in the aldol reaction. Relatively high diastereoselectivities (anti:syn = 85:15) and enantioselectivity (anti, 83% ee) were observed in the aldol reactions of 4-nitrobenzaldehyde with cyclohexanone, which was catalyzed by (R,S)-1a.
Graphical abstractThe novel β-homoproline derivatives 1 were prepared and found to catalyze the direct asymmetric aldol reactions of 4-nitrobenzaldehyde with several ketones. The cooperative effect of the hydroxyl and the carboxyl group in the catalyst (R,S)-1a was observed on the enantioselectiviy.Figure optionsDownload full-size imageDownload as PowerPoint slide
(2S)-tert-Butyl 2-(2′-methoxy-2′-oxoacetyl)pyrrolidine-1-carboxylateC12H19NO5[α]D25=-32.8 (c 0.884, CHCl3)Source of chirality: l-prolineAbsolute configuration: (S)
(2S,1′R)-tert-Butyl 2-(1′-hydroxy-2′-methoxy-2′-oxoethyl)pyrrolidine-1-carboxylateC12H21NO5[α]D25=-49.4 (c 0.516, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′R)
(2S,1′S)-tert-Butyl 2-(1′-hydroxy-2′-methoxy-2′-oxoethyl)pyrrolidine-1-carboxylateC12H21NO5[α]D25=-37.8 (c 0.344, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′S)
(2R,2′S)-2-[1′-(tert-Butoxycarbonyl)pyrrolidin-2′-yl]-2-hydroxyacetic acidC11H19NO5[α]D25=-35.8 (c 1.47, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(1S,2′S)-2-[1′-(tert-Butoxycarbonyl)pyrrolidin-2′-yl]-2-hydroxyacetic acidC11H19NO5[α]D25=-44.4 (c 0.394, CH3OH)Source of chirality: l-prolineAbsolute configuration: (1S,2′S)
(2S,1′R)-tert-Butyl 2-(1′,2′-dimethoxy-2′-oxoethyl)pyrrolidine-1-carboxylateC13H23NO5[α]D25=-74.2 (c 1.51, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,1′′R)
(2S,1′S)-tert-Butyl 2-(1′,2′-dimethoxy-2′-oxoethyl)pyrrolidine-1-carboxC13H23NO5[α]D25=-78.5 (c 0.789, CHCl3)Source of chirality: l-prolineAbsolute configuration: (2S,2′S)
(2R,2′S)-2-[1′-(tert-Butoxycarbonyl)pyrrolidin-2′-yl]-2-methoxyacetic acidC12H21NO5[α]D25=-36.3 (c 0.564, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(2S,2′S)-2-[1′-(tert-Butoxycarbonyl)pyrrolidin-2′′-yl)-2-methoxyacetic acidC12H21NO5[α]D25=-62.2 (c 0.740, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2S,2′S)
(2R,2′S)-2-Hydroxy-2-(pyrrolidin-2′-yl)acetic acidC6H11NO3·TFA[α]D25=-9.2 (c 0.546, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(2R,2′S)-2-Hydroxy-2-(pyrrolidin-2′-yl)acetic acidC6H11NO3[α]D25=-13.6 (c 1.03, H2O)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(2S,2′S)-2-Hydroxy-2-(pyrrolidin-2′-yl)acetic acidC6H11NO3·TFA[α]D25=-9.0 (c 0.558, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2S,2′S)
(2R,2′S)-2-Methoxy-2-(pyrrolidin-2′-yl)acetic acidC7H13NO3·TFA[α]D25=-32.7 (c 2.26, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(2S,2′S)-2-Methoxy-2-(pyrrolidin-2′-yl)acetic acidC7H13NO3·TFA[α]D25=-35.8 (c 0.950, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2S,2′S)
(2R,2′S)-Methyl 2-hydroxy-2-(pyrrolidin-2′-yl)acetateC7H13NO3·TFA[α]D25=-22.5 (c 0.778, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(2S,2′S)-Methyl 2-hydroxy-2-(pyrrolidin-2′-yl)acetateC7H13NO3·TFA[α]D25=-17.7 (c 1.24, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2S,2′S)
(2R,2′S)-Methyl 2-methoxy-2-(pyrrolidin-2′-yl)acetateC8H15NO3·TFA[α]D25=-32.8 (c 0.442, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2R,2′S)
(2S,2′S)-Methyl 2-methoxy-2-(pyrrolidin-2′-yl)acetateC8H15NO3·TFA[α]D25=-42.9 (c 0.198, CH3OH)Source of chirality: l-prolineAbsolute configuration: (2S,2′S)
