Asymmetric Synthesis of 1-Aryltrifluoroethylamines

Significance

Fluorinated groups adjacent to amines are pharmacologically important for the increased metabolic stability that they provide. Although the yields are modest, the sequence is unique in the operational simplicity and rapidity with which the chiral amines 4 can be obtained. Indeed, both the trifluoroacetaldehyde hydrate (1) and Ellman’s chiral sulfinamide 2 are commercially available, and a one-pot procedure was developed to yield the chiral adduct 3 with excellent selectivity. The mild cleavage conditions released the desired enantiopure amines as the stable HCl salts 4.