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

Abstract

Cinchona alkaloid squaramide can effectively catalyze the asymmetric Michael addition of α-aryl isocyanoacetates to β-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 stereoselectivities. The adduct can be easily transformed into biologically attractive chiral β-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.