Poly(ethylene glycol)-supported proline: A versatile catalyst for the enantioselective aldol and iminoaldol reactions

(2S,4R)-4-Hydroxyproline has been anchored to the monomethyl ether of poly(ethylene glycol), M-w 5000, by means of a succinate spacer to afford a soluble, polymer-supported catalyst (PEG-Pro) for enantioselective aldol and iminoaldol condensation reactions. This organic catalyst can be considered as a minimalistic version of a type I aldolase enzyme, with the polymer chain replacing the enzyme's peptide backbone, and the proline residue acting as the enzyme's active site. In the presence of PEG-Pro (0.25 - 0.35 mol equiv.), acetone reacted with enolizable and non-enolizable aldehydes and imines to afford beta-ketols and beta-aminoketones in good yield and high enantiomeric excess (ee), comparable to those obtained using non-supported proline derivatives as the catalysts. Extension of the PEG-Pro-promoted condensation to hydroxyacetone as the aldol donor opened an access to synthetically relevant anti-alpha,beta-dihydroxyketones and syn-alpha-hydroxy- beta-aminoketones, that were obtained in moderate to good yields, and good to high diastereo- and enantioselectivity. Exploiting its solubility properties, the PEG-Pro catalyst was easily recovered and recycled to promote all of the above-mentioned reactions, that occurred in slowly diminishing yields but virtually unchanged ee's.