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

Abstract

The excellent ketone asymmetric transfer hydrogenation (ATH) systems using the precatalysts (S,S)-trans-[FeCl(CO)-(PPh 2 CH 2 CH 2 NHCHPhCHPhNCHCH 2 PAr 2 )]BPh 4 (Ar = Ph (1), ptolyl (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)(PPh 2 CH 2 CH 2 NHCHPhCHPhNCHCHPAr 2 )] (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 1 H 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 C 6 D 6 in the presence of BF 4 − . 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.

Optimum bifunctionality in a 2-(2-pyridyl-2-ol)-1,10-phenanthroline based ruthenium complex for transfer hydrogenation of ketones and nitriles: impact of the number of 2-hydroxypyridine fragments

“…7,8 Remarkably, bio-inspired complexes have emerged as a privileged class of compounds in organometallic chemistry. Inspired by the pioneering work in this field of Noyori, [11][12][13][14] Shvo,15,16 Morris, [17][18][19][20][21] and Milstein, [22][23][24][25] new generations of bifunctional catalysts have been developed. Inspired by the pioneering work in this field of Noyori, [11][12][13][14] Shvo,15,16 Morris, [17][18][19][20][21] and Milstein, [22][23][24][25] new generations of bifunctional catalysts have been developed.…”

Iron Group Hydrides in Noyori Bifunctional Catalysis

“…It is clear from the transition state structures shown in Figure that the acetophenone fits better over the HFeNH motif when the small Me on the ketone is against the “phenyl wall” from PPh 2 groups while the phenyl on the ketone lies flat over the ene‐amido part. This is calculated to be 2 kcal/mol lower in energy than the alternative transition state that leads to the ( S ) product where the large phenyl group on the ketone is pushing against the phenyl wall 89…”

“…The resulting amido complex reacts with isopropanol to generate the iron hydride complex of interest. This highly reactive and oxygen sensitive yellow diamagnetic Fe(II) complex has only been characterized in solution85 and by DFT calculations 89. The 1 H NMR spectrum has a doublet of doublet pattern at −2.2 ppm.…”

“…A NOESY experiment demonstrated that the hydride is in close contact with the N‐H amine proton as shown in Scheme . The actual structure of the hydride complex can be surmised by replacing the chloride in the X‐ray‐diffraction‐derived structure of the complex ( S,S )‐FeCl(CO)(Ptol 2 CH=CHNCHPhCHPhNHCH 2 CH 2 Ph 2 )89 (Figure ) with a hydride ligand. The structure of the hydride as determined by DFT calculations is shown on the right.…”

Studies on the Reactivity of the [W3S4Br3(edpp)3]+ [edpp = (2‐aminoethyl)diphenylphosphine] Cluster Cation towards Bases: The Active Role of the Amino Group

“…Bases are critically important for hydrogenation and transfer hydrogenation reactions catalyzed by aminophosphine metal complexes , . This fact has led us to investigate the reactivity of the cuboidal [W 3 S 4 Br 3 (edpp) 3 ] + complex towards bases, in particular sodium hydroxide, tetrabutylammonium hydroxide and triethylamine.…”