Alan J. Lough

Amine(imine)diphosphine iron catalysts for asymmetric transfer hydrogenation of ketones and imines.

Lighter Hydrogenation Catalysts Enzymes have evolved to use abundant metals such as iron, cobalt, and nickel for redox catalysis. However, synthetic catalysis has generally relied on the rarer, heavier relatives of these elements: ruthenium, rhodium, iridium, palladium, and platinum (see the Perspective by Bullock). Friedfeld et al. (p. 1076) used high-throughput screening to show that the right cobalt precursor can be activated for asymmetric hydrogenation catalysis by using the traditional ligands developed for the precious metals. Zuo et al. (p. 1080) focused on iron, demonstrating a highly effective asymmetric transfer hydrogenation catalyst that uses a ligand rationally designed after careful mechanistic study. Jagadeesh et al. (p. 1073) prepared supported iron catalysts that selectively reduce nitro substituents on aromatic rings to amines, thereby facilitating the preparation of a wide range of aniline derivatives. Ligand design based on mechanistic insight enables highly efficient iron catalysis. [Also see Perspective by Bullock] A rational approach is needed to design hydrogenation catalysts that make use of Earth-abundant elements to replace the rare elements such as ruthenium, rhodium, and palladium that are traditionally used. Here, we validate a prior mechanistic hypothesis that partially saturated amine(imine)diphosphine ligands (P-NH-N-P) activate iron to catalyze the asymmetric reduction of the polar bonds of ketones and imines to valuable enantiopure alcohols and amines, with isopropanol as the hydrogen donor, at turnover frequencies as high as 200 per second at 28°C. We present a direct synthetic approach to enantiopure ligands of this type that takes advantage of the iron(lI) ion as a template. The catalytic mechanism is elucidated by the spectroscopic detection of iron hydride and amide intermediates.

Efficient asymmetric transfer hydrogenation of ketones catalyzed by an iron complex containing a P-N-N-P tetradentate ligand formed by template synthesis.

A distorted iron complex formed by template synthesis is the basis of a very efficient and economical catalyst system for the asymmetric transfer hydrogenation of ketones for the production of valuable enantioenriched alcohols.

Reversible, metal-free, heterolytic activation of H2 at room temperature.

The combination of the borane B(p-C(6)F(4)H)(3) and (o-C(6)H(4)Me)(3)P activates H(2) to give [(o-C(6)H(4)Me)(3)PH][HB(p-C(6)F(4)H)(3)]. This salt when placed under vacuum releases H(2) at room temperature.

Structure–Activity Relationship Analysis of Pd–PEPPSI Complexes in Cross-Couplings: A Close Inspection of the Catalytic Cycle and the Precatalyst Activation Model

A series of Pd-N-heterocyclic carbene (Pd-NHC) complexes with various NHC, halide and pyridine ligands (PEPPSI (pyridine, enhanced, precatalyst, preparation, stabilisation and initiation) precatalysts) were prepared, and the effects of these ligands on catalyst activation and performance were studied in the Kumada-Tamao-Corriu (KTC), Negishi, and Suzuki-Miyaura cross-coupling reactions. The lowered reactivity of more hindered 2,6-dimethylpyridyl complex 4 in the Negishi and KTC reactions is consistent with slow reductive dimerisation of the organometallic reaction partner during precatalyst activation. Comparative rate studies of complexes 1, 4 and 5 in the KTC and Suzuki-Miyaura reactions verify that 4 activated more slowly than the others. A potential on/off mechanism of pyridine coordination to NHC-Pd(0) is also plausible, in which the more basic pyridine stays bound for longer.

Iron(II) Complexes for the Efficient Catalytic Asymmetric Transfer Hydrogenation of Ketones

Iron(II) carbonyl compounds of the type trans-[Fe(NCMe)(CO)(P-N-N-P)][BF(4)](2) bearing the ethylenediamine-derived diiminodiphosphine ligands (R,R)- or (S,S)-1,2-diphenyl-1,2-diaminoethane were synthesized and characterized, including by their crystal structures. The new complexes are suitable precatalysts for the transfer hydrogenation of ketones at room temperature, giving turnover frequencies of up to 2600 h(-1) with low catalyst loadings (0.025-0.17%). Screening experiments showed that the precatalysts are able to produce alcohols from a wide range of simple ketones. For sterically demanding prochiral ketones, excellent enantioselectivities were obtained (up to 96% ee).

The synthesis and exchange chemistry of frustrated Lewis pair–nitrous oxide complexes

Facile activation of nitrous oxide is achieved using a series of fluoroarylboranes, B(C6F5)3, PhB(C6F5)2, MesB(C6F5)2, (C6F5)2BOC6F5, B(C6F4-p-H)3, B(C6H4-p-F)3 and 1,4-(C6F5)2BC6F4B(C6F5)2 in the presence of the basic, bulky phosphinetBu3P. Room temperature reaction yields mono- and bis-zwitterionic species of the form tBu3P(N2O)B(C6F5)2R (R = C6F51, Ph 2, Mes 3, OC6F54), tBu3P(N2O)BR3 (R = C6F4-p-H 5, C6H4-p-F 6) and tBu3P(N2O)B(C6F5)2C6F4(C6F5)2B(ON2)PtBu37. N2O activation is similarly achieved using Cy3P and B(C6F4-p-H)3 yielding the zwitterionic species Cy3P(N2O)B(C6F4-p-H)38. Reaction of 6 with [Ph3C][B(C6F5)4] results in facile transfer of the robust tBu3P(N2O) fragment to the stronger Lewis acid Ph3C+ generating [tBu3P(N2O)CPh3][B(C6F5)4] 10. Similarly exchange reactions with titanocene and zirconocene cations generate transition metal and phosphine stabilized nitrous oxide salts, of the form [tBu3P(N2O)MCp2Me][MeB(C6F5)3], (M = Zr 11, Ti 12). The alkoxy zirconocene cation [Cp*2Zr(OMe)]+ forms an FLP in the presence of tBu3P which reacts with N2O providing a direct synthetic route to the corresponding salt [tBu3P(N2O)ZrCp*2(OMe)][B(C6F5)4] 13. Kinetic studies of the self-exchange reaction of tBu3P(N2O)B(C6H4-p-F)3 with B(C6H4-p-F)3 were carried out acquiring information regarding the mechanism of exchange.

Low-Valent Ene―Amido Iron Complexes for the Asymmetric Transfer Hydrogenation of Acetophenone without Base

Examination of the role of base in the activation of our previously reported iron(II) complexes having the general formula [Fe(CO)(Br)(PNNP)][BPh(4)] revealed a five-coordinate iron(II) complex in which the tetradentate PNNP ligand had been doubly deprotonated. The new iron(II) complexes were used in the transfer hydrogenation of acetophenone in isopropanol in the absence of added base, and certain analogues showed catalytic activity.

The mechanism of efficient asymmetric transfer hydrogenation of acetophenone using an iron(II) complex containing an (S,S)-Ph2PCH2CH═NCHPhCHPhN═CHCH2PPh2 ligand: partial ligand reduction is the key.

On the basis of a kinetic study and other evidence, we propose a mechanism of activation and operation of a highly active system generated from the precatalyst trans-[Fe(CO)(Br)(Ph(2)PCH(2)CH═N-((S,S)-C(Ph)H-C(Ph)H)-N═CHCH(2)PPh(2))][BPh(4)] (2) for the asymmetric transfer hydrogenation of acetophenone in basic isopropanol. An induction period for catalyst activation is observed before the catalytic production of 1-phenethanol. The activation step is proposed to involve a rapid reaction of 2 with excess base to give an ene-amido complex [Fe(CO)(Ph(2)PCH(2)CH═N-((S,S)-C(Ph)H-C(Ph)H)-NCH═CHPPh(2))](+) (Fe(p)) and a bis(enamido) complex Fe(CO)(Ph(2)PCH═CH-N-(S,S-CH(Ph)CH(Ph))-N-CH═CHPPh(2)) (5); 5 was partially characterized. The slow step in the catalyst activation is thought to be the reaction of Fe(p) with isopropoxide to give the catalytically active amido-(ene-amido) complex Fe(a) with a half-reduced, deprotonated PNNP ligand. This can be trapped by reaction with HCl in ether to give, after isolation with NaBPh(4), [Fe(CO)(Cl)(Ph(2)PCH(2)CH(2)N(H)-((S,S)-CH(Ph)CH(Ph))-N═CHCH(2)PPh(2))][BPh(4)] (7) which was characterized using multinuclear NMR and high-resolution mass spectrometry. When compound 7 is treated with base, it directly enters the catalytic cycle with no induction period. A precatalyst with the fully reduced P-NH-NH-P ligand was prepared and characterized by single crystal X-ray diffraction. It was found to be much less active than 2 or 7. Reaction profiles obtained by varying the initial concentrations of acetophenone, precatalyst, base, and acetone and by varying the temperature were fit to the kinetic model corresponding to the proposed mechanism by numerical simulation to obtain a unique set of rate constants and thermodynamic parameters.

Synthesis and reactivity of subvalent compounds: Part 11. Oxidation, hydrogenation and hydrolysis of stable diamino carbenes

Abstract The reactivities of the two stable diamino carbenes 1,3-di-tert-butylimidazol-2-ylidene (1) and 1,3-di-tert-butylimidazolin-2-ylidene (2) toward hydrogen, oxygen, water and carbon monoxide were investigated. The carbenes do not react with O2 or CO but are attacked by water to give the respective hydrolysis products tBu–NCHCH2–N(CHO)tBu (7) and tBu–NH–CH2CH2–N(CHO)tBu (8). While 2 is hydrolyzed instantaneously, the aromatically stabilized 1 reacts only very slowly and can be handled in air for brief periods of time. The carbenes 1 and 2 are unreactive towards H2 alone but can be catalytically hydrogenated to the respective aminals 2,3-dihydro-1,3-di-tert-butylimidazole (5) and 1,3-di-tert-butylimidazolidine (6). The reaction products were characterized by single crystal X-ray crystallography, multinuclear NMR spectroscopy (1H, 13C, 17O), IR spectroscopy and DFT methods. The extent of aromatic delocalization in 1 was investigated through isodesmic hydrogenation reactions at the B3LYP/6-31G(d)//B3LYP/6-31G(d) level. At this level of theory, the ‘carbene oxide’ (2,3-dihydro-imidazol-2-one) retains ca. 50% of the aromatic delocalization energy of the carbene. The oxidation of the diamino carbenes to the ‘carbene oxides’ (ureas) is calculated to be exothermic by −79.1 kcal mol−1 (1) and −86.4 kcal mol−1 (2). The oxygen affinity of the carbenes resembles that of trimethylphosphine (−79.7 kcal mol−1) and triethyl phosphite (−88.6 kcal mol−1) and is significantly higher than that of CO (−67.6 kcal mol−1). The aminals 5 and 6 are structurally related to Thauers hydrogenase (TH2/TH+) but do not show hydrogenase activity.

Synthesis and characterization of iron(II) complexes with tetradentate diiminodiphosphine or diaminodiphosphine ligands as precatalysts for the hydrogenation of acetophenone.

Six complexes of the type trans-[Fe(NCMe)2(P-N-N-P)]X2 (X = BF4(-), B{Ar(f)}4(-)) (Ar(f) = 3,5-(CF3)2C6H3) containing diiminodiphosphine ligands and the complexes trans-[Fe(NCMe)2(P-NH-NH-P)][BF4]2 with a diaminodiphosphine ligand were obtained by the reaction of Fe(II) salts with achiral and chiral P-N-N-P or P-NH-NH-P ligands, respectively, in acetonitrile at ambient temperature. The P-N-N-P ligands are derived from reaction of ortho-diphenylphosphinobenzaldehyde with the diamines 1,2-ethylenediamine, 1,3-propylenediamine, (S,S)-1,2-disopropyl-1,2-diaminoethane, and (R,R)-1,2-diphenyl-1,2-diaminoethane. Some complexes could also be obtained for the first time in a one-pot template synthesis under mild reaction conditions. Single crystal X-ray diffraction studies of the complexes revealed a trans distorted octahedral structure around the iron. The iPr or Ph substituents on the diamine were found to be axial in the five-membered Fe-N-CHR-CHR-N- ring of the chiral P-N-N-P ligands. A steric clash between the imine hydrogen and the substituent probably determines this stereochemistry. The diaminodiphosphine complex has longer Fe-N and Fe-P bonds than the analogous diiminodiphosphine complex. The new iron compounds were used as precatalysts for the hydrogenation of acetophenone. The complexes without axial substituents on the diamine had moderate catalytic activity while that with axial Ph substituents had low activity but fair (61%) enantioselectivity for the asymmetric hydrogenation of acetophenone. The fact that the diaminodiphosphine complex has a slightly higher activity than the corresponding diiminodiphosphine complex suggests that hydrogenation of the imine groups in the P-N-N-P ligand may be important for catalyst activation. Evidence is provided, including the first density-functional theory calculations on iron-catalyzed outer-sphere ketone hydrogenation, that the mechanism is similar to that of ruthenium analogues.