A Liquid–Liquid Biphasic Homogeneous Organocatalytic Aldol Protocol Based on the Use of a Silica Gel Bound Multilayered Ionic Liquid Phase

An innovative two stage liquid–liquid biphasic homogeneous protocol for the asymmetric organocatalytic aldol reaction isproposed, based on the use of the cis-ion-tagged proline 8 dissolved in the liquid film of a multilayered ionic liquid covalently bonded to silica gel 4. The resulting catalytically active material9 is first soaked with cyclohexanone in the presence of water, resulting in a semi-transparent gel, then the aldehyde isadded and the mixture stirred at RT. In the first stage, 4 acts as a catalyst reservoir that delivers 8 to the cyclohexanone phaseallowing the reaction to take place homogeneously. In the second stage, cyclohexanone is removed under vacuum andthe resulting slurry is extracted with anhydrous diethylether.Now 4 acts as a catalyst sponge, redissolving 8. Product extractionis extremely selective; no trace of catalyst is detected in the product-containing phase, and 9 can be easily reused several times with high cumulative productivity values (up to 523).