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.