We have studied the mechanism of transfer hydrogenation (TH) in silico using density functional theory (DFT) with the Fe­(II) PNNP bis­(eneamido) model complexes Fe­(CO)­(H2PCHCHNCH2CH2NCHCHPH2) based on compounds with the general formula Fe­(CO)­(R2PCHCHN­((S,S)-CH­(R′)­CH­(R′))­NCHCHPR2) (R, R′ = alkyl, aryl). An initial activation period involving 1 equiv of isopropyl alcohol reduces the bis­(eneamido) complex by a stepwise inner-sphere mechanism. This activation step is proposed to be slow because of the high barrier calculated for the inner-sphere transfer of hydride to an imine carbon on the ligand. This bis­(eneamido) complex reacts with isopropyl alcohol to produce the active species, proposed to be the unsymmetrical amido-eneamido complex Fe­(CO)­(H2PCH2CH2NCH2CH2NCHCHPH2), which is within the catalytic cycle. The catalytic cycle propagates by addition of isopropyl alcohol to the Fe–amido half of the ligand to generate an FeH–NH unit. However, a stepwise outer-sphere mechanism has been calculated to transfer the proton and hydride in two discrete steps which are connected through a ground state involving an NH-stabilized alkoxide ion. The highest calculated barrier is hydride transfer in the activation period, while the second highest barrier involves hydride transfer during the catalytic cycle. The resting states during catalysis are the alkoxide complex Fe­(CO)­(OiPr)­(H2PCH2CH2NHCH2CH2NCHCHPH2) and/or the amino–hydrido complex FeH­(CO)­(H2PCH2CH2NHCH2CH2NCHCHPH2), on the basis of their low relative free energies. Calculated kinetic isotope effect values are in rough agreement with the experimentally determined values, which also supports the proposed mechanism of catalysis. This data complements the experimental work recently published by our group (J. Am. Chem. Soc.20121341226612280) and leads to a deeper understanding of how these highly active “green” catalysts operate under catalytic conditions.

When activated with base, the iron(II) complexes with tetradentate amine(imine)diphosphine ligands, (S,S)-trans-[FeCl(CO)(PAr 2 -NH-N-PAr′ 2 )]BF 4 (1: Ar, Ar′ = Ph; 2: Ar = Ph, Ar′ = 4-MeC 6 H 4 ; 3: Ar, Ar′ = 3,5-Me 2 C 6 H 3 ), are very active for the asymmetric transfer hydrogenation (ATH) of ketones in KO t Bu/2propanol. For ATH, better enantioselectivity, but lower catalytic activity, was observed in general when using catalyst precursors with the bulkier dixylylphosphino groups compared to those with diphenylphosphino groups. The complexes were much less active for the pressure hydrogenation of ketones, where 1 and 2 produced racemic product alcohols, while 3 yielded chiral alcohols with an enantiomeric excess of up to 70% (R) at turnover frequencies up to 80 h −1 and turnover numbers of 100 for a range of ketones at 50 °C and 20 atm H 2 . This is a rare example of asymmetric pressure hydrogenation using an iron complex. Unlike the case of ATH, there is no effect on the rate upon the addition of KO t Bu beyond the 2 equiv needed to convert the precursor complex to the active amido(ene-amido) and amine(ene-amido)hydrido forms. Both AH and ATH reactions share the same iron hydride intermediate formed by reaction of the amido(ene-amido) iron complex with either dihydrogen or 2-propanol. Kinetic studies on the H 2 hydrogenation of acetophenone catalyzed by 1, activated by base in benzene, using the method of initial rates indicated that the heterolytic splitting of the dihydrogen at the amido(ene-amido) iron complex is the turnover-limiting step of the catalytic cycle for hydrogenation. For 1 in benzene at 323 K over the ranges of concentrations [1] = (2.4−4.8) × 10 −4 M and [ketone] = (3.6−7.2) × 10 −2 M, and of H 2 pressures = 10−20 atm, the rate law is rate = k[1][H 2 ], with k = 0.16 ± 0.01 M −1 s −1 , ΔH ⧧ = 10.0 ± 0.2 kcal mol −1 , and ΔS ⧧ = −31.0 ± 0.5 cal mol −1 K −1. Detailed DFT calculations also support the finding that the barrier for H 2 splitting is the turnover-limiting step. The higher barrier for H 2 activation compared to isopropanol activation in order to generate the active amine(ene-amido)hydrido form explains why this system is biased toward ATH over AH.

The geometric constraints imposed by a tetradentate PN ligand play an essential role in stabilizing square planar Fe complexes with changes in metal oxidation state. The square pyramidal Fe(N)(PN) complex catalyzes the conversion of N to N(SiR) (R = Me, Et) at room temperature, representing the highest turnover number of any Fe-based N silylation catalyst to date (up to 65 equiv N(SiMe) per Fe center). Elevated N pressures (>1 atm) have a dramatic effect on catalysis, increasing N solubility and the thermodynamic N binding affinity at Fe(N)(PN). A combination of high-pressure electrochemistry and variable-temperature UV-vis spectroscopy were used to obtain thermodynamic measurements of N binding. In addition, X-ray crystallography, Fe Mössbauer spectroscopy, and EPR spectroscopy were used to fully characterize these new compounds. Analysis of Fe, Fe, and Fe complexes reveals that the free energy of N binding across three oxidation states spans more than 37 kcal mol.

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.

The reaction of the iron complex trans-[Fe(CO)(MeCN)(PPh 2 C 6 H 4 CHNCH 2 −) 2 -κ 4 P,N,N,P]-(BF 4 ) 2 (1) with KOiPr in benzene produced the unusual complex [Fe(CO)(PPh 2 C 6 H 4 CHNCH 2 CH 2 NHCHC 6 H 4 PPh 2 )κ 5 P,N,C,N,P][BF 4 ] (2), which has been characterized by spectroscopy and by single-crystal X-ray diffraction. The C−N bond length in this complex indicates that it is best viewed as an iron(II) ligand-folded ferraaziridine-κ 2 C,N complex instead of an iron(0) η 2 -iminium complex. Density functional theory (DFT) calculations have been employed on simplified structural models to support a mechanism of formation of this complex via the transfer of a hydride from the alkoxide complex trans-[Fe(CO)(OCHMe 2 )(PH 2 C 6 H 4 CHNCH 2 −) 2 -κ 4 P,N,N,P] + (4 DFT ) to an imine carbon on the ligand to produce the amide complex trans-[Fe(CO)(OC(CH 3 ) 2 )(PH 2 C 6 H 4 CHNCH 2 CH 2 NCH 2 C 6 H 4 PH 2 -κ 4 P,N,N,P)] + (5 DFT acet ) followed by liberation of acetone to afford 5 DFT . Two energetically similar pathways have been proposed in which deprotonation of the PNNP ligand of 5 DFT by strong base produces the experimentally observed ferraaziridinido complex Fe(CO)(PH 2 C 6 H 4 CH NCH 2 CH 2 NCHC 6 H 4 PH 2 )-κ 5 P,N,C,N,P (3 DFT ) or the square-pyramidal Fe(0) complex Fe(CO)(PH 2 C 6 H 4 CHNCH 2 −) 2κ 4 P,N,N,P (7 DFT ). Protonation of 3 DFT by free isopropyl alcohol produces the ferraaziridine complex 2 DFT . Nuclear magnetic resonance and infrared spectroscopy data show that during the transfer hydrogenation of acetophenone catalyzed by 1 in basic isopropyl alcohol, free ligand is observed along with one major iron-containing species identified as 3. On the basis of our calculations of relative free energies and a CO scale factor, we predict that 2 is easily deprotonated to form the electron-rich iron complex 3 and the square-pyramidal Fe(0) complex 7, which are responsible for the two observed CO stretches below 1900 cm −1 in catalytic mixtures. Mass balance studies indicate that the catalytically active species is not observable by NMR. Although 2 and 3 are poor transfer hydrogenation catalysts, we present experimental and theoretical evidence that ligand folding/ distortion is feasible.