Synthesis of Zirconium Phosphonate Supported L-Proline as an Effective Organocatalyst for Direct Asymmetric Aldol Addition

Stable L-proline-functionalized zirconium methyl- and/or phenylphosphonates have been prepared as amorphous solids by the precipitation of (4R)-4-[(4-phosphonobenzyl)oxy]-L-proline and methyl- and/or phenylphosphonic acid with ZrOCl2. The supported L-proline catalysts were tested in the direct asymmetric aldol addition between several ketones and p-substituted benzaldehydes. High yields, diastereoselectivities (anti/syn up to 92:8) and enantiomeric excesses (up to 99%ee) have been achieved. Moreover, an easy protocol for the efficient recovery of the catalytic system by simple centrifugation has been defined, and the effective reuse of the catalyst has been reported in the representative aldol addition of cyclohexanone with p-nitrobenzaldehyde. This study has shown that these L-proline immobilized catalytic systems can be used at least six times without loss of activity and with reproducible anti/syn and ee values.