Asymmetric Catalytic Conjugate Addition of Cyanide to Chromones and β-Substituted Cyclohexenones

A highly enantioselective conjugate cyanation of cyclic a,fi-unsaturated ketones was achieved with dual catalysis of chiral Lewis acids and achiral organic bases. A variety of chromones and fi-substituted cyclohexenones were transformed into the desired fi-cyano ketone derivatives in good yields with high enantioselectivities under mild conditions. The metal salts Ce(OTf)3 and Ba(OTf)2 in combination with chiral N,N '-dioxides facilitated the reaction well, revealing a close connection between the outcome of the reaction and the Lewis acidity with metal ion radii. The application of the methods was highlighted by the facile synthesis of the bioactive compounds repinotan and sarizotan.

Automated summary

A highly enantioselective conjugate cyanation of cyclic a,fi-unsaturated ketones was successfully achieved using chiral Lewis acids and achiral organic bases as dual catalysts. Various chromones and fi-substituted cyclohexenones were efficiently converted into the desired fi-cyano ketone derivatives with good yields and high enantioselectivities under mild reaction conditions. The combination of metal salts Ce(OTf)3 and Ba(OTf)2 with chiral N,N'-dioxides proved to be effective in facilitating the reaction, showing a strong correlation between the reaction outcome and the Lewis acidity influenced by the metal ion radii. The practical utility of this methodology was demonstrated through the facile synthesis of the bioactive compounds repinotan and sarizotan.