Osmium pyme complexes for fast hydrogenation and asymmetric transfer hydrogenation of ketones

The osmium compound trans,cis-[OsCl2(PPh3)2(Pyme)] (1) (Pyme=1-(pyridin-2-yl)methanamine), obtained from [OsCl2(PPh3)3] and Pyme, thermally isomerizes to cis,cis-[OsCl2(PPh3)(2)(Pyme)] (2) in mesitylene at 150 degrees C. Reaction of [OsCl2(PPh3)3] with Ph2P(CH2)(4)PPh2 (dppb) and Pyme in mesitylene (150 degrees C, 4 h) leads to a mixture of trans-[OsCl2(dppb)(Pyme)] (3) and cis-[OsCl2(dppb)(Pyme)] (4) in about an 1:3 molar ratio. The complex trans-[OsCl2(dppb)(Pyet)] (5) (Pyet=2-(pyridin-2-yl)ethanamine) is formed by reaction of [OsCl2(PPh3)3] with dppb and Pyet in toluene at reflux. Compounds 1, 2, 5 and the mixture of isomers 3/4 efficiently catalyze the transfer hydrogenation (TH) of different ketones in refluxing 2-propanol and in the presence of NaOiPr (2.0 mol %). Interestingly, 3/4 has been proven to reduce different ketones (even bulky) by means of TH with a remarkably high turnover frequency (TOF up to 5.7 x 10(5) h(-1)) and at very low loading (0.05-0.001 mol %). The system 3/4 also efficiently catalyzes the hydrogenation of many ketones (H2, 5.0 atm) in ethanol with KOtBu (2.0 mol %) at 70 degrees C (TOF up to 1.5 x 10(4) h(-1)). The in-situ-generated catalysts prepared by the reaction of [OsCl2(PPh3)3] with Josiphos diphosphanes and (+/-)-1-alkyl-substituted Pyme ligands, promote the enantioselective TH of different ketones with 91-96 % ee (ee=enantiomeric excess) and with a TOF of up to 1.9 x 10(4) h(-1) at 60 degrees C.     

Continuous homogeneous asymmetric transfer hydrogenation of ketones: lessons from kinetics

Is polymer enlargement of homogeneous catalysts a tedious task? Is not batch operation with homogeneous catalysts the optimum performance point for homogeneous catalysis? Is kinetic modelling relevant to more than academic questions in homogeneous catalysis? Can all answers for a given system be answered satisfactory? In the authors’ view, answers to these questions are no, no, yes, and depends. Polymer enlargement allowed the continuous operation of transfer hydrogenation in a chemical membrane reactor with total turnover numbers of up to 2.6×10³ and a space–time yield of 0.58 kg L^?1 d^?1 with an enantiomeric ratio of 26.8 (enantiomeric excess 92.8 %) for a conversion level of 80 %. This was predicted from simulation conducted with a model from kinetic batch experiments adopted for continuous application. These simulations for the polymer‐enlarged and the unmodified catalyst show that achieving comparable performance cannot be obtained by batch operation.     

A multilateral mechanistic study into asymmetric transfer hydrogenation in water

The mechanism of aqueous-phase asymmetric transfer hydrogenation (ATH) of acetophenone (acp) with HCOONa catalyzed by Ru-TsDPEN has been investigated by stoichiometric reactions, NMR probing, kinetic and isotope effect measurements, DFT modeling, and X-ray structure analysis. The chloride [RuCl(TsDPEN)(p-cymene)] (1), hydride [RuH(TsDPEN)(p-cymene)] (3), and the 16-electorn species [Ru(TsDPEN-H)(p-cymene)] (4) were shown to be involved in the aqueous ATH, with 1 being the precatalyst, and 3 as the active catalyst detectable by NMR in both stoichiometric and catalytic reactions. The formato complex [Ru(OCOH)(TsDPEN)(p-cymene)] (2) was not observed; its existence, however, was demonstrated by its reversible decarboxylation to form 3. Both 1 and 3 were protonated under acidic conditions, leading to ring opening of the TsDPEN ligand. 4 reacted with water, affording a hydroxyl species. In a homogeneous DMF/H(2)O solvent, the ATH was found to be first order in the concentration of catalyst and acp, and inhibited by CO(2). In conjunction with the NMR results, this suggests that hydrogen transfer to ketone is the rate-determining step. The addition of water stabilized the ruthenium catalyst and accelerated the ATH reaction; it does so by participating in the catalytic cycle. DFT calculations revealed that water hydrogen bonds to the ketone oxygen at the transition state of hydrogen transfer, lowering the energy barrier by about 4 kcal mol(-1). The calculations also suggested that the hydrogen transfer is more step-wise in nature rather than concerted. This is supported to some degree by the kinetic isotope effects, which were obscured by extensive H/D scrambling.     

Rapid ketone transfer hydrogenation by employing simple, in situ prepared iridium(I) precatalysts supported by "non-N--H" P,N ligands

The catalytic utility in ketone transfer hydrogenation (TH) of the preformed complexes [Ir(cod)(kappa(2)-2-NMe(2)-3-PiPr(2)-indene)](+)X(-) ([2 a](+)X(-); X: PF(6), BF(4), and OTf; cod: eta(4)-1,5-cyclooctadiene; OTf: trifluoromethanesulfonate), [Ir(cod)(kappa(2)-1-PiPr(2)-2-NMe(2)-indene)](+)OTf(-) ([2 b](+)OTf(-)), [Ir(cod)(kappa(2)-2-NMe(2)-3-PiPr(2)-indenide)] (3), and [Ir(cod)(kappa(2)-o-tBu(2)P-C(6)H(4)-NMe(2))](+)PF(6) (-) ([4](+)PF(6) (-)), as well as of related mixtures prepared from [{IrCl(cod)}(2)] and various P,N-substituted indene or phenylene ligands, was examined. Whereas [2 a](+)X(-), [2 b](+)OTf(-), 3, and related in situ prepared Ir catalysts derived from P,N-indenes proved to be generally effective in mediating the reduction of acetophenone to 1-phenylethanol in basic iPrOH at reflux (0.1 mol % Ir; 81-99 % conversion) in a preliminary catalytic survey, the structurally related Ir catalysts prepared from (o-R(2)P-C(6)H(4))NMe(2) (R: Ph, iPr, or tBu) were observed to outperform the corresponding P,N-indene ligands under similar conditions. In the course of such studies, it was observed that alteration of the substituents at the donor fragments of the supporting P,N ligand had a pronounced influence on the catalytic performance of the derived catalysts, with ligands featuring bulky dialkylphosphino donors proving to be the most effective. Notably, the crystallographically characterized complex [4](+)PF(6) (-), either preformed or prepared in situ from a mixture of [{IrCl(cod)}(2)], NaPF(6), and (o-tBu(2)P-C(6)H(4))NMe(2), proved to be highly effective in mediating the catalytic transfer hydrogenation (TH) of ketones in basic iPrOH, with near quantitative conversions for a range of alkyl and/or aryl ketones and with very high turnover-frequency values (up to 230 000 h(-1) at >50 % conversion); this thereby enabled the use of Ir loadings ranging from 0.1 to 0.004 mol %. Catalyst mixtures prepared from [{IrCl(cod)}(2)], NaPF(6), and the chiral (alphaS,alphaS)-1,1'-bis[alpha-(dimethylamino)benzyl]-(R,R)-2,2'-bis(dicyclohexylphosphino)ferrocene (Cy-Mandyphos) ligand proved capable of mediating the asymmetric TH of aryl alkyl ketones, including that of the hindered substrate 2,2-dimethylpropiophenone with an efficiency (0.5 mol % Ir; 95 % conversion, 95 % ee) not documented previously in TH chemistry.     

Manganese catalyzed asymmetric transfer hydrogenation of ketones

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral P_xN_y-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)₅] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP₂N₄ (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.     

Chiral iridium(I) bis(NHC) complexes as catalysts for asymmetric transfer hydrogenation

The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L ‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley & Sons, Ltd.     

Ir-catalysed asymmetric hydrogenation: Ligands, substrates and mechanism

Relatively air and moisture tolerant cationic iridium complexes, with chiral non-racemic N,P-ligands and weakly coordinating counter ions, are efficient catalysts in the asymmetric hydrogenation of olefins. Unfunctionalised olefins are particularly difficult substrates because, in general, a polar group adjacent to the alkene bond is required for high catalytic activity and enantioselectivity. The applicability towards a variety of substrates and choice of ligands reported thus far in the literature, as well as the mechanism, selectivity issues and the importance of the anion are also discussed.     

Mechanistic insights into iridium-catalyzed asymmetric hydrogenation of dienes

Hydrogenation of 2,3-diphenylbutadiene (1) with the chiral carbene-oxazoline-iridium complex C has been studied by means of a combined experimental and computational approach. A detailed kinetic profile of the reaction was obtained with respect to consumption of the substrate and formation of the intermediate half-reduction products, 2,3-diphenylbut-1-ene (2) and the final product, 2,3-diphenylbutane (3). The data generated from these analyses, and from NMR experiments, revealed several facets of the reaction. After a brief induction period (presumably involving reduction of the cyclooctadiene ligand on C), the diene concentration declines in a zero-order process primarily to give monoene intermediates. When all the diene is consumed, the reaction accelerates and compound 3 begins to accumulate. Interestingly, the prevalent enantiomer of the monoene intermediate 2 is converted mostly to meso-3 so the enantioselectivity of the reaction appears to reverse. The reaction seems to be first-order with respect to the catalyst when the catalyst concentration is less than 0.0075 M; diffusion of hydrogen across the gas-liquid interface complicates the analysis at higher catalyst concentrations. Similarly, these diffusion effects complicated measurements of reaction rate versus applied pressure of dihydrogen; other factors like stir speed and flask geometry come into play under some, but not all, the conditions examined. Density functional theory (DFT) calculations, using the PBE method, were used to probe the reaction. These studies indicate a transoid-eta(4)-diene-dihydride complex forms in the first stages of the catalytic cycle. Further reaction requires dissociation of one alkene ligand to give a eta(2)-diene-dihydride-dihydrogen intermediate. A catalytic cycle that features Ir(3+)/Ir(5+) seems to be involved thereafter.     

Hydrogenation versus transfer hydrogenation of ketones: two established ruthenium systems catalyze both

The established standard ketone hydrogenation (abbreviated HY herein) precatalyst [Ru(Cl)(2)((S)-tolbinap)[(S,S)-dpen]] ((S),(S,S)-1) has turned out also to be a precatalyst for ketone transfer hydrogenation (abbreviated TRHY herein) as tested on the substrate acetophenone (3) in iPrOH under standard conditions (45 degrees C, 45 bar H(2) or Ar at atmospheric pressure). HY works at a substrate catalyst ratio (s:c) of up to 10(6) and TRHY at s:c<10(4). Both produce (R)-1-phenylethan-1-ol ((R)-4), but the ee in HY are much higher (78-83 %) than in TRHY (4-62 %). In both modes, iPrOK is needed to generate the active catalysts, and the more there is (1-4500 equiv), the faster the catalytic reactions. The ee is about constant in HY and diminishes in TRHY as more iPrOK is added. The ketone TRHY precatalyst [Ru(Cl)(2)((S,S)-cyP(2)(NH)(2))] ((S,S)-2), established at s:c=200, has also turned out to be a ketone HY precatalyst at up to s:c=10(6), again as tested on 3 in iPrOH under standard conditions. The enantioselectivity is opposite in the two modes and only high in TRHY: with (S,S)-2, one obtains (R)-4 in up to 98 % ee in TRHY as reported and (S)-4 in 20-25 % ee in HY. iPrOK is again required to generate the active catalysts in both modes, and again, the more there is, the faster the catalytic reactions. The ee in TRHY are only high when 0.5-1 equivalents iPrOK are used and diminish when more is added, while the (low) ee is again about constant in HY as more iPrOK is added (0-4500 equiv). The new [Ru(H)(Cl)((S,S)-cyP(2)(NH)(2))] isomers (S,S)-9 A and (S,S)-9 B (mixture, exact structures unknown) are also precatalysts for the TRHY and HY of 3 under the same conditions, and (R)-4 is again produced in TRHY and (S)-4 in HY, but the lower ee shows that in TRHY (S,S)-9 A/(S,S)-9 B do not lead to the same catalysts as (S,S)-2. In contrast, the ee are in accord with (S,S)-9 A/(S,S)-9 B leading to the same catalysts as (S,S)-2 in HY. The kinetic rate law for the HY of 3 in iPrOH and in benzene using (S,S)-9 A/(S,S)-9 B/iPrOK or (S,S)-9 A/(S,S)-9 B/tBuOK is consistent with a fast, reversible addition of 3 to a five-coordinate amidohydride (S,S)-11 to give an (S,S)-11-substrate complex, in competition with the rate-determining addition of H(2) to (S,S)-11 to give a dihydride [Ru(H)(2)((S,S)-cyP(2)(NH)(2))] (S,S)-10, which in turn reacts rapidly with 3 to generate (S)-4 and (S,S)-11. The established achiral ketone TRHY precatalyst [Ru(Cl)(2)(ethP(2)(NH)(2))] (12) has turned out to be also a powerful precatalyst for the HY of 3 in iPrOH at s:c=10(6) and of some other substrates. Response to the presence of iPrOK is as before, except that 12 already functions well without it at up to s:c=10(6).     

Zwitterionic iridium complexes with P,N-ligands as catalysts for the asymmetric hydrogenation of alkenes

Several zwitterionic iridium complexes based on chiral P,N-ligands with imidazoline or oxazoline donors and anionic tetraarylborate or aryltrifluoroborate substituents have been synthesized. The corresponding cationic analogues have also been prepared, to evaluate the effect of the covalent linkage between the anion and the cationic metal complex in catalytic reactions. The respective pairs of structurally analogous precatalysts have been compared for their efficacies in the asymmetric hydrogenation of unfunctionalized olefins. In most cases, the anionic derivatization has virtually no influence on the asymmetric induction of the iridium complex. This is in accordance with X-ray structural studies, which have shown that the chiral environment of the cationic metal center is not affected by the anionic substituent. Depending on the nature of the counterion employed, the zwitterionic catalysts proved to be significantly more reactive than their cationic counterparts in nonpolar solvents.     

新型手性环状胺膦配体的设计合成及在酮的不对称还原中的应用

新型手性配体的设计合成是不对称催化研究的重要内容,其中手性胺膦配体因同时含有"软"的磷原子和"硬"的氮原子而具有丰富的配位化学性能和优秀的不对称诱导能力.本文总结了本研究组最近设计合成的手性环状胺膦配体的制备、表征及其在铁催化酮的不对称还原中的应用.手性1,2-环己二胺与双(2-甲酰基苯基)苯基膦通过[2+2]环缩合反应能够顺利获得手性22元环的亚胺膦配体21,该配体经Na BH4还原后生成大环胺膦配体22.利用手性大环胺膦配体22与Fe3(CO)12原位生成的催化体系,能够高活性、高对映选择性地实现包括杂环芳香酮在内50多种酮的不对称转移氢化和不对称氢化反应,其S/C(底物与催化剂的摩尔比)最高可达5000:1,产物手性芳香醇的光学纯度高达99%ee.     

Rhodium-complex-catalyzed asymmetric hydrogenation: transformation of precatalysts into active species

The use of diolefin-containing rhodium precatalysts leads to induction periods in asymmetric hydrogenation of prochiral olefins. Consequently, the reaction rate increases in the beginning. The induction period is caused by the fact that some of the catalyst is blocked by the diolefin and thus not available for hydrogenation of the prochiral olefin. Therefore, the maximum reaction rate cannot be reached initially. Due to the relatively slow hydrogenation of cyclooctadiene (cod) the share of active catalysts increases at first, and this leads to typical induction periods. The aim of this work is to quantify the hydrogenation of the diolefins cyclooctadiene (cod) and norborna-2,5-diene (nbd) for cationic complexes of the type [Rh(ligand)(diolefin)]BF(4) for the ligands Binap (1,1'-binaphthalene-2,2'-diylbis(phenylphosphine)), Me-Duphos (1,2-bis(2,5-dimethylphospholano)benzene, and Catasium in the solvents methanol, THF, and propylene carbonate. Furthermore, an approach is presented to determine the desired rate constant and the resulting respective pre-hydrogenation time from stoichiometric hydrogenations of the diolefin complexes via UV/Vis spectroscopy. This method is especially useful for very slow diolefin hydrogenations (e.g., cod hydrogenation with the ligands Me-Duphos, Et-Duphos (1,2-bis(2,5-diethylphospholano)benzene), and dppe (1,2-bis(diphenylphosphino)ethane).     

Mixtures of chiral and achiral monodentate ligands in asymmetric Rh-catalyzed olefin hydrogenation: reversal of enantioselectivity

The recently described method of combinatorial asymmetric transition metal catalysis based on the use of mixtures of chiral monodentate P-ligands has been extended to include mixtures of chiral and achiral monodentate P-ligands, reversal of enantioselectivity in Rh-catalyzed olefin hydrogenation being possible in appropriate cases.