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

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.