Cinchona Alkaloid Squaramide-Catalyzed Asymmetric Michael Addition of alpha-Aryl Isocyanoacetates to beta-Trifluoromethylated Enones and Its Applications in the Synthesis of Chiral beta-Trifluoromethylated Pyrrolines

摘要

Cinchona alkaloid squaramide can effectively catalyze the asymmetric Michael addition of alpha-aryl isocyanoacetates to beta-trifluoromethylated enones, affording the corresponding adducts, with an adjacent chiral tertiary carbon center bearing a CF3 group and a quaternary carbon center in moderate to good yields along with excellent stereo-selectivities. The adduct can be easily transformed into biologically attractive chiral beta-trifluoromethylated pyrroline carboxylate in high yield via an isocyano group hydrolysis/cyclization/dehydration cascade reaction by treating with acid. The one-pot enantioselective Michael addition/isocyano group hydrolysis/cyclization/dehydration sequential protocol has also been investigated.