Asymmetric Catalytic Conjugate Addition of Cyanide to Chromones and ?-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. KEYWORDS: asymmetric catalysis, conjugate addition of cyanide, cyclic a,fi-unsaturated ketones, repinotan, sarizotan, Lewis acids