Asymmetric Intramolecular Oxa-Michael Addition of ε- and ζ-Hydroxy-α,β-Unsaturated Esters Enabled by Chiral Crown Ether-Coordinated Potassium Base Catalysts

To develop catalysts using earth-abundant metals for sustainable asymmetric synthesis, we synthesized a series of chiral potassium catalysts consisting of chiral crown ethers and potassium tert-butoxide. These catalysts demonstrated exceptional efficiency in the asymmetric intramolecular oxa-Michael addition of α,β-unsaturated esters containing an alcoholic OH group, a reaction that is difficult to proceed using an organocatalyst. Notably, the ester moiety in the resulting products can be readily transformed into various valuable functional groups without compromising the enantiomeric purity. To gain insight into the origin of the observed enantioselectivity, we analyzed the transition-state structure computationally. These findings highlight the potential of chiral potassium catalysts as a sustainable and highly effective alternative to conventional organocatalysts for asymmetric synthesis.