Direct Asymmetric Aldol Reaction Co-catalyzed by Amphiphilic Prolinamide Phenol and Lewis Acidic Metal on Water

An approach based on combinations of various water compatible Lewis acids and lipophilic group containing amphiphilic prolinamide co‐catalysts has been evaluated for the direct asymmetric Aldol reaction. From the broad screening of chloride salts from alkali metal to transition metal, LiCl, ZnCl₂ and SnCl₂ lead to the highest stereoselectivities. The optimized catalytic conditions (10 mol% prolinamide with 10 mol% MCl₂ or 20 mol% LiCl at room temperature on water) gave anti‐products with improved enantioselectivities (up to 99% ee) compared to the moderately stereoselective procedure based on prolinamide activation only.