New N-terminal prolyl-dipeptide derivatives as organocatalysts for direct asymmetric aldol reaction

A series of new N-terminal prolyl-dipeptide derivatives have been synthesized and evaluated as organocatalysts for the direct asymmetric aldol reaction of acetone with electron-deficient aromatic aldehydes. At room temperature, the presence of 10 mol % of catalysts 2 and 5 efficiently catalyzes the direct asymmetric aldol reaction to give the aldol adducts with modest to excellent enantiomeric excesses (ee) values, which are up to 96%.     

Felkin-Anh selectivity in Rh(bisoxazolinylphenyl)-catalyzed reductive aldol coupling reaction: asymmetric synthesis of stereotriads

The catalytic reductive aldol coupling of 2-phenylpropionaldehyde and acrylate derivatives with rhodium-bisoxazolinyl catalysts resulted in high Felkin-Anh selectivity (β,γ-syn) up to 98% accompanied by α,β-anti diastereoselectivity and high enantiomeric excesses up to 99%.     

Rationally designed organocatalyst for direct asymmetric aldol reaction in the presence of water

A rationally designed organocatalyst for direct asymmetric aldol reaction in the presence of water has been developed. High yield (up to 99%), diastereoselectivity (up to 99:1) and enantioselectivity (up to 97%) were obtained under optimal conditions.     

Highly efficient prolinamide-based organocatalysts for the direct asymmetric aldol reaction in brine

Four prolinamide-based organocatalysts were readily synthesized and applied to the direct asymmetric aldol reactions of ketones and aromatic aldehydes in brine. When 2,4-dinitrophenol (DNP) was used as an acidic additive, 1 mol % low loading of 2b afforded aldol products with excellent diastereoselectivity of up to 98/2 dr and high enantioselectivity of up to 97% ee.     

Carbohydrate-based organocatalysts in direct asymmetric aqueous aldol reaction

Aldol reaction involving chiral amines as organocatalysts through enamine formation, like class-I aldolases, is one of the thriving areas of general interest and widely applicable asymmetric reactions. There are many natural and synthetic chiral templates known to work as efficient organocatalysts, but using carbohydrate templates for chiral induction in asymmetric aldol reactions is a relatively new area developed in the recent years. This review focuses on carbohydrates alone or their conjugates with previously known chiral moieties as organocatalysts for asymmetric aldol reactions.     

Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water

A rationally designed 4-phenoxy substituted prolinamide phenols as an efficient hydrophobic organocatalyst for direct asymmetric aldol reaction in water has been developed. High yield (up to 99%), diastereoselectivity (up to 99:1), and enantioselectivity (up to 97%) were obtained under optimal condition. The influence of substituent groups on the reactivity of catalysts was studied in detail.     

Chiral 1,2-diaminocyclohexane as organocatalyst for enantioselective aldol reaction

A simple and commercially available chiral 1,2-diaminocyclohexane as catalyst, hexanedioic acid as co-catalyst could efficiently catalyze the asymmetric aldol reaction in MeOH-H₂O. Cyclic ketones as aldol substrates gave the anti-β-hydroxyketone products with moderate to good yields, diastereoselectivity and enantioselectivity (up to 78% yield, >20:1 anti/syn, 94% ee). Hydroxyacetone as aldol substrate afforded the syn-α, β-dihydroxyketones as major products in up to 85% yield with good enantioselectivity (up to >20:1 syn/anti, 93% ee).     

Application of high pressure, induced by water freezing, to the direct asymmetric aldol reaction

High pressure, induced by water freezing, has been successfully applied to the direct catalytic asymmetric aldol reaction, in which higher yield and better enantioselectivity can be realized than in the reaction at room temperature under 0.1 MPa.     

壳聚糖负载辛可宁催化剂的制备及其在水中催化不对称Aldol反应

以丁二酸酐为连接臂,经两步反应制备了壳聚糖负载辛可宁有机催化剂(CTS-SA-CN),并研究了CTS-SA-CN在水体系中对酮与多种芳香醛的直接不对称aldol反应的催化性能。结果表明,在CTS-SA-CN催化下,酮与多种芳香醛发生直接不对称aldol反应,可得到99%的产率和96%的ee值。另外, CTS-SA-CN可通过简单过滤实现回收,重复使用5次活性并没有明显下降。     

壳聚糖负载辛可宁催化剂的制备及其在水中催化不对称Aldol反应

以丁二酸酐为连接臂,经两步反应制备了壳聚糖负载辛可宁有机催化剂(CTS-SA-CN),并研究了CTS-SA-CN在水体系中对酮与多种芳香醛的直接不对称aldol反应的催化性能。结果表明,在CTS-SA-CN催化下,酮与多种芳香醛发生直接不对称aldol反应,可得到99%的产率和96%的ee值。另外, CTS-SA-CN可通过简单过滤实现回收,重复使用5次活性并没有明显下降。     

Chiral spiroborate esters catalyzed highly enantioselective direct aldol reaction

Asymmetric catalysis of chiral spiroborate esters with an O₃BN framework toward the direct aldol reaction of acetone and aromatic aldehydes was examined, and a new, efficient chiral catalyst was discovered. In the presence of the novel catalyst, acetone was allowed to react with aromatic aldehydes at 0 °C for 50 h to afford chiral β-hydroxyketone in up to >99% ee and 92% yield. The catalyst, which is readily synthesized, is highly stable to hydrolysis, thermolysis, oxidation, and racemization, can be conveniently recovered.     

Chiral ytterbium complex-catalyzed direct asymmetric aldol-Tishchenko reaction: synthesis of anti-1,3-diols

The asymmetric aldol-Tishchenko reaction of aromatic aldehydes with aliphatic and aromatic ketones has been developed as an efficient strategy for the synthesis of anti-1,3-diols in good yield with high diastereocontrol and good levels of enantioselectivity. This domino-type reaction is catalyzed by a chiral ytterbium complex that promotes both the aldol reaction through enolization of the carbonyl compound and the Evans-Tishchenko reduction of the aldol intermediate. The stereochemistry of the resulting diols is also investigated and finally proved by using CD techniques.     

Sequential oxidation/asymmetric aldol reaction of primary alcohols by resin-supported catalysts

The sequential reaction including alcohol oxidation by TEMPO/Cu system and the asymmetric aldol reaction by peptide catalysis was realized using resin-supported catalysts. The step of oxidizing primary alcohols to the corresponding aldehydes could be dramatically enhanced through the introduction of triglycyl peptide to supported TEMPO and the method of pre-adsorbing a Cu-complex into resin beads.     

Cp*rhodium complexes with salicyloxazolines: Diastereoselective synthesis, configurational stability and use as asymmetric catalysts for a Diels-Alder reaction

Reaction of [RhCl₂Cp*]₂ (Cp* = η-C₅Me₅) with salicyloxazolines in the presence of NaOMe gives complexes [RhCl(R-saloxaz)Cp*] (1-4) which have been fully characterised. The diastereoselectivity of complexation depends on the substituents and the absolute configuration at the metal centre is unstable in solution. Treatment of 2 with 4-methylpyridine and NaSbF₆ in methanol at reflux gave [Rh(4-Mepy){(S)-ⁱPr-saloxaz}Cp*][SbF₆] (5) whilst [Rh(OH₂)(Me₂-saloxaz)Cp*][SbF₆] (6) was prepared by reaction of 1 with AgSbF₆. Three complexes, [RhCl(Me₂-saloxaz)Cp*] (1), [RhCl{(S)-ⁱPr-saloxaz}Cp*] (2), and [Rh(OH₂)(Me₂-saloxaz)Cp*][SbF₆] (6) have been characterised by X-ray crystallography. Some of the complexes, after treatment with AgSbF₆, have been tested as enantioselective catalysts for the Diels-Alder reaction of methacrolein with cyclopentadiene.     

Noncovalently supported heterogeneous chiral amine catalysts for asymmetric direct aldol and Michael addition reactions

A new strategy for the immobilization of asymmetric organocatalysts by combining polystyrene (PS)/sulfonic acids and chiral amines in situ through acid-base interactions is presented. The PS/sulfonic acids play a dual role as catalyst anchors and modulators for activity and stereoselectivity. Different types of polymeric sulfonic acids were examined and 1% divinylbenzene (DVB) cross-linked PS/sulfonic acid 1 e with a medium loading of sulfonic acid moieties was found to be the optimal support. Furthermore, the noncovalency of this system allows combinatorial screening of optimal catalysts for the targeted reactions. In this regard, highly efficient and enantioselective heterogeneous catalysts were identified for the asymmetric direct aldol and Michael addition reactions. The catalysts could be easily recovered by filtration and reused for six cycles with similar stereoselectivity but slightly decreased activity. Significantly, the deactivated catalysts could be regenerated following an acidic washing/amine recharging procedure.     

Prolinamides derived from aminophenols as organocatalysts for asymmetric direct aldol reactions

N-(2-Hydroxyphenyl)-prolinamides were synthesized with the aim to introduce an additional hydrogen bonding site to the prolinamide structure. These compounds were evaluated as organocatalysts for asymmetric aldol reactions between aromatic aldehydes and cyclohexanone. Very good yields, diastereoselectivities, and enantioselectivities were achieved in both organic solvents and water. The importance of the additional hydrogen bonding site was confirmed by comparative experiments with prolinamide derivatives without the hydroxyl group.     

A recyclable non-immobilized siloxy serine organocatalyst for the asymmetric direct aldol reaction

A recyclable siloxy-l-serine organocatalyst has been developed to catalyze asymmetric direct aldol reactions in [bmim][BF₄], furnishing the β-hydroxy carbonyl scaffold in high enantio- and diastereoselectivities using a selection of aromatic aldehydes and cycloalkanes. The siloxy serine organocatalyst in the ionic liquid can be reused for up to four successive cycles with comparable enantioselectivities.     

Dipeptide-catalyzed direct asymmetric aldol reactions in the presence of water

The l-proline-based dipeptide has been discovered and developed as an efficient catalyst for the direct asymmetric aldol reactions of unmodified ketones with various aldehydes including aromatic, aliphatic, heteroaromatic, and unsaturated aldehydes in the presence of water at 0 °C. The resulted methodology and optimal conditions led to the corresponding aldol products with high yields (up to 94%) and good enantioselectivities (up to 97% ee).     

N-Prolinylanthranilic acid derivatives as bifunctional organocatalysts for asymmetric aldol reactions

Several N-prolinylanthranilic acid derivatives were prepared and tested as bifunctional organocatalysts in the direct asymmetric aldol reaction of cyclohexanone with p-nitrobenzaldehyde. It was found that methyl substitution ortho to the carboxylic acid improves enantioselectivity, but substitution ortho to the anilide group does not. The catalyst derived from 2-amino-6-methylbenzoic acid was tested over a range of direct asymmetric aldol reactions and its overall performance is equal to or better than many of the known prolinamide catalysts in terms of yield, diastereoselectivity, and enantioselectivity.