Highly Diastereoselective Synthesis of alpha-Difluoromethyl Amines from N-tert-Butylsulfinyl Ketimines and Difluoromethyl Phenyl Sulfone

The first highly efficient and stereoselective difluoromethylation of structurally diverse N-tert-butylsulfinyl ketimines has been achieved with an in situ generated PhSO2CF2- anion, which provides a powerful synthetic method for the preparation of a variety of structurally diverse homochiral alpha-difluoromethyl tertiary carbinamines, including alpha-difluoromethyl allylic amines and alpha-difluoromethyl propargylamines. The stereocontrol mode of the present diastereoselective difluoromethylation of ketimines was found to be different from that of other known fluoroalkylations of N-tert-butylsulfinyl aldimines, which suggests that a cyclic six-membered transition state may be involved in the reaction.