PEG-supported proline

PEG-supported proline 92 was designed to catalyze the asymmetric Michael addition of ketones to nitrostyrene (Scheme 3.26) [53]. Using 5mol% of the polymeric catalyst, the Michael adduct 95 was obtained in good yields (up to 94%) and moderate to good enantioselectivities (up to 86% ee). A high level of diastereose-lectivities (>98/2, syn/anti) was also observed. The enantiomeric excesses obtained... 

This overview about developments in the field of proline-catalysis unfortunately cannot take into full account the vast field of proline-derived catalysts, such as diarylprolinols, 4-silo)yprolines or proline-silyl-ether, to name only a few. These are covered in subsequent chapters of this volume. Furthermore, other great improvements have been made by using immobilised proline catalysts, such as PEG-supported proline or polyelectrolyte-bound pro-line. Going one step further, supported proline catalysts are then applicable in the striving field of continuous-flow reactions. Recent examples include aldol, a-amination reactions and Michael reactions under such conditions. ... 

Commercially available Amberlite IR-120 (H -form) was used as an acid catalyst this resin is a divinylbenzene-crosslinked partially sulfonated gel-type polystyrene. As a base catalyst, PEG-PS resin-supported proline was employed. The reaction was performed in water-acetone-tetrahydrofuran (1 1 1 v/v/v) at room temperature in the presence of 20 mol. % of resin-supported proline and Amberlite. After 20 h, the reaction mixture contained the starting 4-nitro-benzaldehyde dimethyl acetal, 4-nitrobenzaldehyde and the corresponding aldol product with acetone in a ratio of 4 9 87. This means that both the... 

OH) with aldehydes 9 in the homogeneous conditions (DMF or DMSO) (Scheme 10.1). Furthermore, PEG-supported catalyst 20a could be recovered by precipitation from the DMF solution with ether and reused in the same reactions without reduction of enantiomeric excesses of products 10 (R = OH). It also appeared applicable to asymmetric iminoaldol (Mannich) reactions to afford p-aminoketones 16 (R = Ar) (Scheme 10.3) and to the enantioselective Michael/aldol cascade reaction resulting in the S3mthesis of Wieland-Mischler ketone 28b, an important precursor of some other natural compounds (Scheme 10.6). Diastereo- and enantioselectivities of these reactions were close to the corresponding data for proline-catalysed reactions. 

Systems have been developed that allow the recycling of catalysts. The first case study involved simple adsorption of proline onto silica gel [6], but the system suffered from a loss in enantioselectivity. More recently, promising results have been obtained with fluorous proline derivatives [64] used for aldol reactions the recycling of fluorous catalysts has been demonstrated using fluorous solid-liquid extraction. Solid phase-supported catalysts through covalent bonds [65] and through noncovalent interactions [66] were also used for aldol reactions. Proline and other catalysts can be recycled when ionic liquids or polyethylene glycol (PEG) were used as reaction solvents [67]. 

For example, onium ion-tagged prolines have been synthesized and their catalytic activity in direct asymmetric aldol condensation was initially studied in molecular solvents.The observed superior performance of IL-proline relative to Peg-proline or free proline, in terms of yields and enantiomeric excess, evidenced that the ionic moiety in IL-proline plays more than a silent or simply supporting role in the reaction (Scheme 4.4). ... 

The direct asymmetric aldol reaction has been studied with different di- and tri-peptides sequences supported in PEG-polystyrene resins by two different groups. In both cases the peptides contained proline at the N-terminus. In one case the other components of the sequence were aromatic amino acids. Thus, polymer 146 (20mol.%) displaying the sequence H-D-Pro-Tyr-Phe-PS produced the aldol product in 90% yield and 33% ee. The enantioselectivity was improved to 73% ee with the addition of 20 mol.% ZnCl2, but required longer reaction times. In the second case, a higher variation of amino acids was considered. Resin 147... 

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