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] cyclo-addition of beta-trifluoromethyl enones with 3-(N-2,2,2-trifluoroeth-yl) 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.

Automated summary

This study describes an organocatalytic asymmetric [3 + 2] cyclo-addition of beta-trifluoromethyl enones with 3-(N-2,2,2-trifluoroethyl) benzothiophene ketimines and 2-(N-2,2,2-trifluoroethyl) benzothiophene ketimines for the first time. A wide range of vicinally bis(trifluoromethyl)-substituted spiro pyrrolidine-benzothiophenones were obtained with excellent stereocontrol, including those with four contiguous stereocenters in the spirocyclic benzothiophenone moiety.