Enantioselective Hydrogenation of Activated Aryl Imines Catalyzed by an Iron(II) P‑NH-P′ Complex

Chiral amines are
key building blocks in synthetic chemistry with
numerous applications in the agricultural and pharmaceutical industries.
Asymmetric imine hydrogenation, particularly with iridium catalysts,
is well developed. However, imine reduction still remains challenging
in the context of replacing such a precious metal with a cheap, nontoxic,
and environmentally friendly substitute such as iron. Here, we report
that an unsymmetrical iron P-NH-P′ catalyst that was previously
shown to be effective for the asymmetric hydrogenation of aryl ketones
is also a very effective catalyst for the asymmetric hydrogenation
of prochiral aryl imines activated with N-diphenylphosphinoyl
or N-tosyl groups. The P-NH-P′ abbreviation
stands for (S,S)-PPh2CHPhCHPhNHCH2CH2PiPr2. Density functional theory results suggest that, surprisingly, the
NH group on the catalyst activates and orients the imine to hydride
attack by hydrogen bonding to the PO or SO group on the imine nitrogen,
as opposed to the imine nitrogen itself. This may explain why N-Ph and N-Bu imines are not hydrogenated.