Thermoresponsive Polymer-Supported l-Proline Micelle Catalysts for the Direct Asymmetric Aldol Reaction in Water

Abstract

l-Proline moieties bound to a thermoresponsive polymer nanoreactor efficiently directed the asymmetric aldol reaction in water with excellent yields and enantioselectivity (ee). The reactions were efficient at higher temperatures in direct contrast to the low yields and ee values found when the reaction was carried out in a DMF/water mixture due to the location of the l-proline moieties within the hydrophobic pocket inside the core of the nanoreactors. This ideal environment formed for catalysis allows control over the water content as well as enhancing interactions between the carboxylic acid of l-proline and the aldehyde substrate. The nanoreactors were disassembled to fully water-soluble polymers by lowering the temperature to below the lower critical solution temperature (LCST) of the polymer, resulting in precipitation of the product in near pure form. The product was isolated by centrifugation and the polymer/water solution reused in additional catalytic cycles by heating the polymer above its LCST and thus reforming the nanoreactors. Although a small decrease in yield after five cycles was observed, the selectivity (anti/syn ratio and ee) remained high.

Synthesis and properties of novel helical 3-vinylpyridine polymers containing proline moieties for asymmetric aldol reaction

“…Benzene (AR, Beijing Chemical Co.) and toluene (AR, Beijing Chemical Co.) were washed with oil of vitriol three times, water three times, saturated brine once, dried with magnesium sulfate, and then refluxed over sodium and distilled out before use. 35 Measurements. 1 H-NMR (400 MHz) and 13 C-NMR (100 MHz) spectra were recorded on a Bruker ARX400 spectrometer, and 1 H-NMR (300 MHz) spectra were recorded on a Varian Mercury Plus spectrometer at room temperature in CDCl 3 with 40 tetramethylsilane (TMS) as an internal standard.…”

“…[5][6][7][8] Apart from aldolization, proline and its derivatives via enamine catalysis are widely 30 utilized in asymmetric Mannich reactions, [9][10][11] Michael reactions, 12-14 D-A reactions, [15][16][17] and α-aminations. 18,19 Moreover, their nitrogen dioxides are used as organocatalysts or the chiral ligands of organometallic catalyst in various asymmetric transformations, 20 including α-chlorinations, 21 35 cycloadditions, 22 Roskamp-Feng reactions, 23 Friedel-Crafts reactions, 24 homologations of carbonyl compounds, 25 Ene 26 and Aza-Ene reactions. 27 In order to facilitate the recyclability and reduce the cost, great efforts have been made to tether proline-based small molecule 40 catalysts onto polymer matrix.…”

“…Some well-defined polymer 50 aggregates, which could be switched by solvent, 31 pH, 34 and temperature, 35,36 were prepared to promote aldol reaction performance. Dendrimers instead of linear or cross-linked polymers were also used as the matrix to immobilize aldolases.…”

Polymer-immobilized chiral catalysts

“…15 (S)-Proline moieties bound to a thermoresponsive polymer nanoreactor efficiently directed the asymmetric aldol reaction between cyclohexanone and p-nitrobenzaldehyde in water with excellent yields and enantioselectivities. 16 An (S)-proline structure was attached to a crosslinked polymer using an azide-acetylene click reaction. The resulting polymeric proline 13 was used as a catalyst in the asymmetric aldol reaction between aromatic aldehyde 14 and 2 to form 15 in a flow system (Scheme 5 The most reactive peptidic organocatalysts developed to date for the aldol 29 …”

Nuevos materiales basados en SILLPs (Supported Ionic Liquid-like Phases) para aplicaciones avanzadas en la Química y la Ingeniería Sostenible

“…[66 ] They can also be useful in catalysis as they allow catalyst separation just by changing the temperature of the solution. [67] Lu et al obtained by RAFT polymerization a "smart" material based on a PIL copolymer possessing thermoresponsive properties being able to facilitate the separation of natural products. In particular, they were used as extractants of tocopherols showing a good recyclability (Figure 1.8.).…”