| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1343565 | Tetrahedron: Asymmetry | 2015 | 11 Pages |
Direct asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone were catalysed by trans-4-hydroxy-(S)-prolinamide (10 mol %) in the presence of CH3COOH (10 mol %) as the co-catalyst under solvent-free conditions at 15 °C. (2S,4R)-4-Hydroxy-N-((S)-1-phenylethyl)pyrrolidine-2-carboxamide 2 efficiently catalysed the asymmetric aldol reaction to afford the product in >99% yield and with 95% ee with an anti/syn ratio of 88:12 after 18 h. The additional trans-hydroxyl group on (S)-prolinamide and (S)-1-phenylethylamine both influenced the ee of the predominant anti aldol product. Different benzaldehyde derivatives with cyclohexanone gave the corresponding aldol products in 38–89% yields and with 56–94% ee with anti/syn (100:0–71:29). Catalyst 2 can be used up to 5 continuous cycles for asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone with overall 91% yield and 86% yield of anti-product with anti/syn (98:2).
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
(S)-N-((S)-1-Phenylethyl)pyrrolidine-2-carboxamideC13H18N2O[α]D25 = −71.1 (c 1.10, MeOH)Source of chirality: (S)-proline and (S)-1-phenylethylamineAbsolute configuration: (S)(S)
(2S,4R)-4-Hydroxy-N-((S)-1-phenylethyl)pyrrolidine-2-carboxamideC13H18N2O2[α]D25 = −78.7 (c 1.70, MeOH)Source of chirality: (2S,4R)-4-hydroxy-proline and (S)-1-phenylethylamineAbsolute configuration: (2S,4R)(S)
(2S,4R)-4-Hydroxy-N-((R)-1-phenylethyl)pyrrolidine-2-carboxamideC13H18N2O2[α]D25 = +25.9 (c 1.00, MeOH)Source of chirality: (2S,4R)-4-hydroxy-proline and (R)-1-phenylethylamineAbsolute configuration: (2S,4R)(R)
(2S,4R)-N-Benzyl-4-hydroxypyrrolidine-2-carboxamideC12H16N2O2[α]D25 = −25.7 (c 1.29, MeOH)Source of chirality: (2S,4R)-4-hydroxy-prolineAbsolute configuration: (2S,4R)
(2R,4R)-4-Hydroxy-N-((S)-1-phenylethyl)pyrrolidine-2-carboxamideC13H18N2O2[α]D25 = −24.8 (c 0.58, MeOH)Source of chirality: (2R,4R)-4-hydroxy-proline and (S)-1-phenylethylamineAbsolute configuration: (2R,4R)(S)
