Polymer-Supported Asymmetric Aldol Catalysts

Poly(ethylene glycol) grafted on crosslinked polystyrene (PEG-PS) resin has often been used as a polymer support for chiral catalysts of reactions performed in aqueous media. Peptides immobilized to PEG-PS resin have been developed and used as a catalyst for direct asymmetric aldol reactions in aqueous media (Scheme 3.19) [42]. When tripeptide-supported PEG-PS 67 was used as chiral catalyst in the reaction between 70 and acetone, the corresponding aldol product 69 was obtained with 73% ee. Kudo further developed the one-pot sequential reaction of acidic deacetalization and enanhoselective aldol reaction by using an Amberhte and PEG-ST-supported peptide catalyst 67 [43]. The enantioenriched aldol product 72 was obtained in 74% isolated yield from acetal 70 in a one-pot reaction (Scheme 3.20). 

Catalyzed enantioselective Mukaiyama-aldol reactions have been developed extensively [101] and chiral polymer-supported Lewis acids are the catalysts of choice. Polymer-supported chiral A(-sulfonyloxazaborohdinones 86 and 87, prepared by copolymerization of styrene, divinylbenzene, and chiral monomers derived from L-valine and L-glutamic acid, respectively, have been used for aldol reactions [102]. The rates of reaction using the polymeric catalysts were slow and enantioselectivity was lower than was obtained by use of the low-molecular-weight counterpart (88). The best ee obtained by use of the polymeric catalyst was 90 % ee with 28 % isolated yield in the asymmetric aldol reaction of benzaldehyde with 89 (Eq. 27). 

Optically active l,l -binaphthols are among the most important chiral ligands of a variety of metal species. Binaphthol-aluminum complexes have been used as chiral Lewis acid catalysts. The l,T-binaphthyl-based chiral ligands owe their success in a variety of asymmetric reactions to the chiral cavity they create around the metal center [107,108]. In contrast with the wide use of these binaphthyls, the polymer-supported variety has been less popular. The optically active and sterically regular poly(l,l -bi-naphthyls) 96 have been prepared by nickel-catalyzed dehalogenating polycondensation of dibromide monomer 95 (Sch. 7) [109] and used to prepare the polybinaphthyl aluminum(III) catalyst 97 this had much greater catalytic activity than the corresponding monomeric catalyst when used in the Mukaiyama aldol reaction (Eq. 29). Unfortunately no enantioselectivity was observed in the aldol reaction. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Wennemers found that tripeptide H-Pro-Pro-Asp-NH2 was a highly active and selective catalyst for asymmetric aldol reactions [44]. This peptide was immobihzed to a polymer support and used as a catalyst for the aldol reaction of p-nitrobenzal-dehyde 73 and acetone (Scheme 3.21). By using a TentaGel-supported peptide 73 the aldol adduct 69 was obtained in 89% yield with 75% ee, while a polyethylene glycol-polyacrylamide (PEGA)-supported peptide gave the same adduct in 93% yield and 79% ee [45]. 

Very recently, Portnoy et al. described the design and synthesis of insoluble polymer-supported dendrimers bearing proline end groups for asymmetric aldol reachons [123]. The zeroth- to third-generahon supported dendrimer catalysts were prepared by ahaching (2S,4R)-4-hydroxyproline onto the insoluble PS-bound... 

The polymer-supported Zr catalyst (12) is useful for asymmetric aza-Diels-Alder cycloaddition of benzaldehyde imine to Danishefsky diene [9]. The 6-substituted BINOL-Zr(IV) catalyst is useful for the enantioselective anft -preferred aldol reaction of benzaldehyde with ketene silyl thioacetal (15) (Scheme 5.5) [ 10]. The calculated charge densities on the oxygen atoms of the BINOL derivatives revealed that there is a good correlation between the charge density and the reactivity of 6-substituted BINOL [ 10]. 

Polymer-supported organocatalysts are valuable materials for conducting catalytic asymmetric transformations under simple and environmentally begnin conditions [275]. A novel polymer-supported diphenylprolinol trimethylsilyl ether was synthesized by Hansen et oi. [276], and further applied as catalyst to induce a diastereo- and enantioselective three-component domino Michael/Michael/aldol... 

In 2008, Gruttadauria and coworkers synthesised prolinamide derivatives 54a and 54b, in which prolinamide units were anchored to a polystyrene support via thiol-ene coupling reactions. In the presence of these heterogeneous catalysts, cyclic ketones or acetone 8 reacted with atyl aldehydes 9 to afford corresponding chiral aldols 10 (Scheme 10.l). The best yields of 10 and stereoselectivity of the reactions (dr antilsyn) 96 4-98 2 and 89-99% ee) were attained in a 1 2 (v/v) water/chloroform solvent system, in which water pushed reagents to the concentrated organic phase where asymmetric reactions occurred, meanwhile chloroform ensured swelling of the polymer chain. However, the activity of catalysts 54a and 54b became... 

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