Synthetic and Mechanistic Study of the Catalytic Enantioselective Preparation of Primary β‑Amino Ketones from Enones and a Fluorinated Gabriel Reagent

The salen μ-oxo complex of
aluminum 1 catalyzes
the asymmetric 1,4-addition of the novel ammonia equivalent 3,4,5,6-tetrafluorophthalimide
to unsaturated ketones. All of the reagents are inexpensive and are
readily available. The products are formed in up to 89% yield and
up to 96% ee. The tetrafluorophthalimide group is removed under mild
chemoselective conditions and in high yields to afford the free primary
amines. Mechanistic studies suggest that the reaction occurs through
a dual activation mechanism. A pre-equilibrium formation of a 1:1
complex between tetrafluorophthalimide and the catalyst is observed.
The rate-determining step is the addition of tetrafluorophthalimide
catalyst complex to the catalyst activated enone. These mechanistic
studies provide important clues for the further development of catalytic
asymmetric reactions.