Prolinamides <i>versus</i> Prolinethioamides as Recyclable Catalysts in the Enantioselective Solvent‐Free Inter‐ and Intramolecular Aldol Reactions

Abstract

Abstract A solvent‐free asymmetric and direct anti ‐aldol reaction of aliphatic ketones with aromatic aldehydes catalyzed by recyclable L ‐prolineamides and L ‐prolinethioamides 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 enantioselectivities (up to &gt;98/2 dr , up to 98% ee ) at 0 °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.