Catalytic Asymmetric Synthesis of Vicinally Bis(trifluoromethyl)-Substituted Molecules via Normal [3 + 2] Cycloaddition of N -2,2,2-Trifluoroethyl Benzothiophene Ketimines and β-Trifluoromethyl Enones.

An organocatalytic asymmetric [3 + 2] cycloaddition of β-trifluoromethyl enones with 3-( N -2,2,2-trifluoroethyl) benzothiophene ketimines and 2-( N -2,2,2-trifluoroethyl) benzothiophene ketimines was described for the first time. A wide spectrum of vicinally bis(trifluoromethyl)-substituted spiro pyrrolidine-benzothiophenones were obtained with excellent stereocontrol (all cases >20:1 dr and up to 99% ee). The highlight of this work is the extremely high efficiency in the construction of spirocyclic benzothiophenone derivatives possessing a vicinally bis(trifluoromethyl)-substituted pyrrolidine moiety with four contiguous stereocenters.