Direct Asymmetric Aldol Reactions in Water Catalysed by a Highly Active C 2 ‐Symmetrical Bisprolinamide Organocatalyst

A novel C 2 ‐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 (1–2.5 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.