Direct Asymmetric Aldol Reactions in Water Catalysed by a Highly Active C2-Symmetrical Bisprolinamide Organocatalyst

A novel C2-symmetrical bisprolinamide organocatalyst was synthesised and used to facilitate asymmetric direct aldol reactions in a water emulsion. Reactions were performed at room temperature with very low catalyst loadings (12.5 mol%) without the required use of additives, co-catalysts or extended reaction times (24 h). This catalyst system was then used with a variety of aldehyde substrates showing good reaction generality for benzaldehydes with cyclohexanone (dr range 77/23 to >99/1, anti/syn; ee range 33% to >99%) and moderate scope with cyclopentanone (dr range 45/55 to 76/24, anti/syn; ee range 14% to 68%). Ultra-low catalysts loadings (0.1 and 0.05 mol%) were also investigated demonstrating catalyst turnover numbers in the order of 1000.