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

Chris Seo (1) , Thibault Tannoux (2) , Samantha Smith (1) , Alan Lough (1) , Robert Morris (1)

1 Department of Chemistry [University of Toronto]
2 ISCR - Institut des Sciences Chimiques de Rennes

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.

Domains: Chemical Sciences; Organic chemistry; Chemical Sciences; Catalysis

Chris Seo, Thibault Tannoux, Samantha Smith, Alan Lough, Robert Morris. Enantioselective Hydrogenation of Activated Aryl Imines Catalyzed by an Iron(II) P-NH-P′ Complex. Journal of Organic Chemistry, 2019, 84 (18), pp.12040-12049. ⟨10.1021/acs.joc.9b01964⟩. ⟨hal-02473966⟩