Prolinamides versus Prolinethioamides as Recyclable Catalysts in the Enantioselective Solvent-Free Inter- and Intramolecular Aldol Reactions

A solvent-free asymmetric and direct anti-aldol reaction of aliphatic ketones with aromatic aldehydes catalyzed by recyclable L-proline-amides and L-prolinethioarnides 3 is studied. The L-prolinethioamide 3d (5 mol%), derived from L-Pro and (R)-1-aminoindane, is the most efficient catalyst for this process affording the anti-aldol adducts in high yields with excellent diastereo- and enantio-selectivities (up to > 98/2 dr, up to 98% ee) at 0 degrees C or room temperature. Prolinethioamide 3d is an effective organocatalyst for the first asymmetric, solvent-free, intramolecular Hajos-Parrish-Eder-Sauer-Wiechert reaction with comparable or higher levels of enantioselectivity (up to 88% ee) to reported catalysts in organic solvents. Moreover, organocatalyst 3d can be easily recovered and reused by a simple acid/base extraction.