Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

We report here the tridentate, P-stereogenic, C₂-symmetric PNP pincer ligand (S_P,S_P)-2,6-bis­((cyclohexyl­(methyl)­phosphanyl)­methyl)­pyridine (1a) and its iron­(II) complexes [FeBr₂(CO)­(1a)] (2a), [FeHBr­(CO)­(1a)] (3a), and [FeH₂(CO)­(1a)] (4a). In the presence of base, bromocarbonylhydride 3a catalyzes the hydrogenation of acetophenone to (S)-1-phenylethanol with 48% ee. The transition states of the enantiodetermining transfer of hydride from 3a to the carbonyl group of acetophenone were studied by density functional theory (DFT) with a full conformational analysis of the PNP ligand for the three different mechanistic models recently proposed for a related achiral catalyst. The DFT calculations show that the outer-sphere monohydride mechanism originally proposed by Milstein reproduces the experimentally observed sense of induction (S) and enantioselectivity, whereas the dihydride and inner-sphere pathways predict the formation of the R enantiomer.