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.