Highly Enantioselective Michael Addition of Cyclic Diketones to β,γ-Unsaturated α-Keto Esters Catalyzed by Squaramide Organocatalyst

A new tertiary amine-squaramide organocatalyst has been developed and applied to the asymmetric Michael addition of cyclic diketones to β,γ-unsaturated α-keto esters. The catalyst system performed well with a low catalyst loading of 1 mol% under mild reaction conditions. A series of synthetically and pharmaceutically useful chiral bicyclic compounds were obtained in high yields (up to 97%) with excellent enantioselectivities (up to 99 % ee). Furthermore, this catalytic system can be used efficiently in large-scale reactions with the yields and enantioselectivities being maintained.

Helical Polycarbenes Bearing D-Prolinol Ester Pendants: An Efficient Catalyst for Asymmetric Michael Addition Reaction

a novel diazoacetate monomer (1) carrying tert-butyloxycarboryl (Boc) protected D-prolinol ester was designed and synthesized successfully. Molecular weight-controlled polymerization of 1 using the complex of π-allylPdCl coordinated Wei-phos (LR) ligand gives a series of helical polycarbenes (poly-1ms) with well-defined molecular weights (Mns) and low polydispersity (Mw/Mns). Removing the protecting Boc groups on the D-prolinol ester pendants leads to the formation of helical poly-1m-As, which showed high optical activity. Furthermore, the poly-1m-As showed high catalytic ability on asymmetric Michael addition reaction (up to 76% ee and 94/6 dr). Both the enantioselectivity and diastereoselectivity of the Michael addition reaction were increased comparing to D-prolinol as catalyst. Moreover, the helical polycarbene catalyst can be easily recovered and reused at least four times without significant loss of its enantioselectivity and diastereoselectivity.

Organocatalytic Asymmetric Michael Addition in Aqueous Media by a Hydrogen-Bonding Catalyst and Application for Inhibitors of GABAB Receptor

Catalysts based on (R, R)-1,2-diphenylethylenediamine are, as chiral organic catalysts, applied to the asymmetric Michael addition to α, β-unsaturated nitroalkenes under neutral conditions. The role of an aqueous medium for organic catalytic activity can be reversed concerning hydrophilic-hydrophobic function depending on the reaction conditions. In this study, to provide an environmentally friendly system, the thiourea-based catalyst substituted with 3,5-(CF3)2-Ph was used in water solvents. The hydrophobic effect of the substituent provided fast reaction, high chemical yield, and mirror-image selectivity. This reaction allowed the preparation of GABAB agonists in an optically pure manner. Additionally, GABA (γ-aminobutyric acid) analogs such as baclofen and phenibut were synthesized as R-type S-type with high optical purity.