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

Abstract

AbstractA 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.