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.

An efficient temperature‐dependent organocatalyzed asymmetric formal [3+2] cycloaddition reaction of α‐substituted isocyanoacetates to β‐trifluoromethylated enones by cinchona alkaloid‐derived squaramide has been investigated, affording the optically active trifluoromethylated 2‐pyrrolines in excellent yields (up to 98 %) and high stereoselectivities (>20:1 dr, up to >99 % ee) under mild conditions.

Dihydroquinine-derived thiourea catalyzed asymmetric tandem conjugate addition–protonation of α-isocyanoacetates to 2-chloroacrylonitrile was developed.

Cinchona Alkaloid Squaramide-Catalyzed Asymmetric Michael Addition of -Aryl Isocyanoacetates to -Trifluoromethylated Enones and Its Applications in the Synthesis of Chiral -Trifluoromethylated Pyrrolines. -This is the first example of a successful approach of the title reaction. It works well with arylisocyanoacetates and -aryloyl-,,-trifluoroprop-2-enes depending on their steric and electronic natures. Alkyl derivatives of each reactant do no react to give the desired products. Acidic hydrolysis of Michael adducts leads to pyrrolines (IV) which are regarded as biologically attractive derivatives. The methods can also be applied in a one-pot fashion. -(ZHAO*, M.-X.; ZHU, H.-K.; DAI, T.-L.; SHI, M.; J. Org. Chem. 80 (2015) 22, 11330-11338, http://dx.