Highly Enantioselective Reactions of Cyclohexanone and β , γ ‐Unsaturated α ‐Keto Ester: The Tuning of Chemo‐selectivities by Secondary and Primary Amine Catalysts

A series of of amphiphilic imidazole based secondary and primary amine catalysts were synthesized and shown to be very effective with an acid cocatalyst for the asymmetric reaction of cyclohexanone to β , γ ‐unsaturated α ‐keto ester. Interestingly, primary and secondary amine catalysts show different regio‐selectivities in this reaction. Under the catalysis of secondary amine 1 , excellent enantioselectivities were observed for the products from direct 3+3 reactions of cyclohexanone with β , γ ‐unsaturated α ‐keto esters using water as the solvent. Moreover, the same reactants catalyzed by the primary amines 2 lead to the aldol reactions, affording the corresponding products with high diastereoselectivities and up to 97% ee . Theoretical studies on the transition states by using a model in gas phase revealed that steric effect plays an important role on different chemo‐selective induction between the secondary amine 1 and primary amine 2 .