Details of the Mechanism of the Asymmetric Transfer Hydrogenation of Acetophenone Using the Amine(imine)diphosphine Iron Precatalyst: The Base Effect and The Enantiodetermining Step

The excellent ketone asymmetric transfer
hydrogenation (ATH) systems
using the precatalysts (S,S)-trans-[FeCl­(CO)­(PPh2CH2CH2NHCHPhCHPhNCHCH2PAr2)]­BPh4 (Ar = Ph (1), p-tolyl (2)) have a fascinating dependence
of activity on the base concentration, which is investigated here.
The reaction of complex 1 or 2 with 1 equiv
of the strong base potassium tert-butoxide in THF
for 2–7 days produces the neutral amine­(ene-amido) complexes
[FeCl­(CO)­(PPh2CH2CH2NHCHPhCHPhNCHCHPAr2)] (8 and 9). These monodeprotonated
complexes have been completely characterized by NMR, EA, and FT-IR
spectroscopy and mass spectrometry, and the structure of 9 has been further confirmed by single-crystal X-ray diffraction to
reveal a structure with the NH and FeCl bonds parallel and the proton
and chloride ligands next to each other. The structures of 8 and 9 and their 1H NMR patterns are similar
to those of the active catalyst for the ATH of ketones that is postulated
to have NH and FeH bonds parallel with the protonic and hydridic hydrogens
adjacent. Identical key nuclear Overhauser effect (NOE) correlations
in both 8 and the hydrido complex provide further evidence
for the postulated structure of the amine iron hydride intermediate.
The catalyst system is not active for the transfer hydrogenation of
acetophenone, unless greater than 2 equiv of base is added to activate
the precatalyst. The addition of base (up to 8 equiv per iron) increases
the reaction rate, while a further increase of the base concentration
shows a reduction of activity. The loss of activity with less than
2 equiv of base results from a side reaction of the active amido­(ene-amido)
complexes with 2-propanol to form an inactive neutral bis­(amido) iron
complex, which was characterized by NMR spectroscopy. Structural evidence
for this was provided by the X-ray crystal structure determination
of an analogous bis­(amino) iron­(II) complex, generated from the reaction
of the amine­(ene-amido) iron complex with methanol in C6D6 in the presence of BF4–. The presence of excess base prevents this side reaction, thereby
favoring the reaction which forms the active amine iron hydride species
that is in the catalytic cycle. The structure of the transition state
for the reaction of the amine hydrido iron catalyst with acetophenone
has been successfully modeled using density functional theory (DFT)
calculations. The (R) configuration of the product
1-phenylethanol is induced by the position of the phenyl groups on
the catalyst and a π–π stabilizing interaction
between the aryl ring on the ketone and the ene-amido moiety on the
ligand.