Origin of enantioselectivity in the Ru(arene)(amino alcohol)-catalyzed transfer hydrogenation of ketones

The origin of the enantioselectivity in the ruthenium-catalyzed transfer hydrogenation has been studied by means of experiment and density functional theory calculations. The results clearly show that electrostatic effects are of importance, not only in the T-shaped arene-aryl interaction in the favored transition state but also between the aryl of the substrate and the amine ligand in the disfavored TS. In addition, the electrostatic interaction between the alkyl substituent of the substrate and the catalyst is of importance to the enantioselectivity. The major cause of enantioselection is found to be of nonelectrostatic origin. This inherent property of the catalytic system is discussed in terms of dispersion forces and solvent effects. Finally, a minor but well-characterized steric effect was identified. The success of this class of catalysts in the reduction of alkyl aryl ketones is based on the fact that all factors work in the same direction.     

Room-temperature Ru(II)-catalyzed transfer hydrogenation of ketones and aldehydes in air

Transfer hydrogenation (TH) of ketones and aldehydes was efficiently carried out in 2-propanol at room temperature by means of a ruthenium(II) complex catalyst bearing a 2-(benzoimidazol-2-yl)-6-(pyrazol-1-yl)pyridine ligand. TH of the ketone substrates proceeded in air, reaching final TOFs of up to 59,400 h⁻¹, and the reduction of aldehydes proceeded under a nitrogen atmosphere to achieve final TOFs of up to 5940 h⁻¹.     

Chiral induction effects in ruthenium(II) amino alcohol catalysed asymmetric transfer hydrogenation of ketones: an experimental and theoretical approach

The enantioselective outcome of transfer hydrogenation reactions that are catalysed by ruthenium(II) amino alcohol complexes was studied by means of a systematically varied series of ligands. It was found that both the substituent at the 1-position in the 2-amino-1-alcohol ligand and the substituent at the amine functionality influence the enantioselectivity of the reaction to a large extent: enantioselectivities (ee values) of up to 95% were obtained for the reduction of acetophenone. The catalytic cycle of ruthenium(II) amino alcohol catalysed transfer hydrogenation was examined at the density functional theory level. The formation of a hydrogen bond between the carbonyl functionality of the substrate and the amine proton of the ligand, as well as the formation of an intramolecular H...H bond and a planar H-Ru-N-H moiety are crucially important for the reaction mechanism. The enantioselective outcome of the reaction can be illustrated with the aid of molecular modelling by the visualisation of the steric interactions between the ketone and the ligand backbone in the ruthenium(II) catalysts.     

"Tethered" Ru(II) catalysts for asymmetric transfer hydrogenation of ketones

Stereochemically well-defined ruthenium(II) catalysts have been applied to the asymmetric transfer hydrogenation of a series of ketones. In one case, statistical experimental design was employed to optimize the enantiomeric excess of the product. In the case of the TsDPEN-based systems, the replacement of trans-1,2-diphenyl substitution with cis-, or deletion of one of the phenyl groups, results in significant deterioration of the enantiomeric excess. A new method is described for the synthesis of tethered amino alcohol-containing catalysts.     

Chiral sulfur-containing ligands for iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones

New efficient catalyst systems, coupled with IrCl(COD)PPh₃ and chiral [SNNS]-type ligands, were employed in the asymmetric transfer hydrogenation of aromatic ketones under mild reaction conditions. The corresponding optically active alcohols were obtained in high yield and good to excellent enantioselectivities (up to 96% ee). The chiral Ir(I) complexes with the ligands of [SNNS]-type were also prepared and characterized, which showed good enantioselectivity and high activity. The reactions can be performed in air and the catalytic experiments are greatly simplified.     

Screening of chiral ferrocenyl amino alcohols as ligands for ruthenium-catalysed transfer hydrogenation of ketones

A variety of ferrocenyl amino alcohols possessing central chirality have been screened as ligands for ruthenium(II)-catalysed transfer hydrogenation of acetophenone using 2-propanol in the presence of KOH as the hydrogen source. Enantiomerically enriched 1-phenylethanol was obtained in high yield and 70% e.e. using ligand 9. This ligand was employed in the asymmetric reduction of different arylalkyl ketones and the corresponding alcohols were obtained in up to 80% e.e. A comparison of the catalytic properties of ferrocenyl amino alcohols and their phenyl analogues is discussed briefly.     

Asymmetric transfer hydrogenation of ketones using Ru(0) nanoparticles modified by Chiral Thiones

The catalytic asymmetric transfer hydrogenation (ATH) of acetophenone in isopropanol by Ru(0) nanoparticles (NPs) obtained by the in‐situ reduction of Ru (II) half‐sandwich complexes of chiral 2‐oxazolidinethiones and 2‐thiozolidinethiones was examined and compared with the catalytic activity of Ru(0) NPs formed in‐situ by the reduction of [Ru(p‐cymene)(Cl)₂]₂ in presence of optically active ligands such as (S)‐4‐isobutylthiazolidine‐2‐thione, (S)‐4‐Isopropyl‐2(?2‐pyridinyl)‐2‐oxazoline, (8S, 9R)‐(?)‐cinchonidine, (S)‐leucinol, (S)‐phenylalaninol, and (S)‐leucine. Three of the best catalytic systems were then examined for ATH of thirteen aromatic ketones with different electronic and steric properties. A maximum of 24% ee was obtained using NPs generated from the Ru (II) half‐sandwich complex with (S)‐4‐isobutylthiazolidine‐2‐thione in the TH of acetophenone. The NPs were characterized by TEM and DLS measurements. Kinetic studies and poisoning experiments confirmed that the reaction is catalyzed by the chiral NPs formed in‐situ. Complete characterization of the complexes, including the X‐ray crystallographic characterization of two complexes, was also carried out.     

[RuCl2COD)]n: A simplified source of Ru(II)-catalysts for the asymmetric hydrogenation of functionalized ketones

A simplified procedure of enantioselective ruthenium-catalyzed hydrogenation of functionalized ketones using commercially available [RuCl₂(COD)]_n, (COD = cis,cis-cycloocta-1,5 diene) mixed with the chiral diphosphines (BINAP, MeO-BIPHEP, DuPHOS) is reported. Under these conditions, C-O groups were completely hydrogenated with excellent enantiomeric excesses (up to 99 %).     

Efficient Ru(II)-catalyzed asymmetric hydrogenation of simple ketones with C2-symmetric planar chiral metallocenyl phosphinooxazoline ligands

C₂-symmetric metallocenyl planar phosphinooxazoline ligands (2 and 3) have been applied in the Ru(II)-catalyzed asymmetric hydrogenation of simple ketones. This type of ligands enjoys the advantages of dual reaction sites as well as larger steric hindrance than their corresponding C₁-symmetric counterparts. As a result, almost quantitative conversions and excellent enantioselectivities were obtained for a series of simple ketones. Under the optimal reaction conditions, up to 99.7% ee was obtained in many cases. It was also confirmed that hydrogen rather than reaction solvent i-PrOH is at work in the hydrogenation procedure.     

钌(II)-吡啶基NNN配合物催化酮的室温(不对称)氢转移反应

合成了一种基于吡啶骨架含有苯并咪唑和手性咪唑啉基团的三齿NNN配体及其二价钌(II)配合物,通过核磁共振波谱学和X射线单晶晶体结构测定确认了钌(II)配合物的分子结构.这些配合物在室温下催化酮的氢转移反应,表现出了优异的催化活性,收率和ee值最高分别可达99%和97%.     

Probing subtle ligand effects in the enantioselective transfer hydrogenation of ketones

The rational modification of an established amino-alcohol scaffold has revealed new, highly effective ligands for the enantioselective transfer hydrogenation of acetophenone that affords the product in up to 95% ee.     

Hydrogen transfer hydrogenation of nitrobenzene to aniline with Ru(acac)3 as the catalyst

Tris(acetylacetonato)ruthenium(III)(Ru(acac)₃) was synthesized with RuCl₃·nH₂O and acetylacetone as raw materials. The structure of Ru(acac)₃ was identified by FI-IR, ¹H NMR, ¹³C NMR, and elemental analysis. It was used in the catalytic hydrogen transfer hydrogenation of nitrobenzene with sodium formate as hydrogen donor. The effects of reaction conditions on the process, such as temperature, time, dosage of catalyst, and kinds of hydrogen donor, were investigated. The optimal reaction parameters were determined as follows: 80 °C, 4.0 h, the substrate nitrobenzene 20 mL, sodium formate 27.20 g, Ru(acac)₃ 0.96 g, the conversion of nitrobenzene is 100.0 %, the yield of aniline and the selectivity to aniline are 96.65 %. The reaction mechanism is proposed and analyzed. It exhibited excellent catalytic properties in the hydrogen transfer hydrogenation of nitrobenzene to aniline.     

Preparation of a series of Ru(II) complexes with N-heterocyclic carbene ligands for the catalytic transfer hydrogenation of aromatic ketones

The reaction of [RuCl(2)(p-cymene](2) with Ag-N-heterocyclic carbene (NHC) complexes yields a series of [(p-cymene)Ru(NHC)] complexes (2a-f). All synthesised compounds were characterized by elemental analysis, NMR spectroscopy and the molecular structure of 2a was determined by X-ray crystallography. All complexes have been tested as catalysts for the transfer hydrogenation of aromatic ketones, showing excellent activity in this reaction.     

Polyethylene glycol‐bound Ru catalyst for asymmetric transfer hydrogenation of aromatic ketones in water

A new polyethylene glycol‐supported chiral monosulfonamide was synthesized from (R,R)‐1,2‐diaminocyclohexane and shown to act as a ligand for ruthenium(II)‐catalyzed asymmetric transfer hydrogenation of aromatic ketones in neat water using sodium formate as the hydrogen source. Good enantioselectivities were obtained and the catalyst could be easily separated from the reaction mixture and reused several times. Copyright © 2011 John Wiley & Sons, Ltd.     

An alternative route to tethered Ru(II) transfer hydrogenation catalysts

A new route towards a series of tethered η⁶-arene/Ru(II) catalysts for use in the transfer and pressure hydrogenation of ketones and aldehydes to alcohols is reported. The route proceeds through the formation of an amide from the diamine precursor, followed by reduction, rather than the direct alkylation of the diamine. This has the advantage that dialkylation of the amine is avoided during the synthesis. Through this new route, both racemic and enantiomerically-pure η⁶-arene/Ru(II) tethered catalysts can be prepared in high yield.     

Mechanism of Pd(NHC)-catalyzed transfer hydrogenation of alkynes

The transfer semihydrogenation of alkynes to (Z)-alkenes shows excellent chemo- and stereoselectivity when using a zerovalent palladium(NHC)(maleic anhydride)-complex as precatalyst and triethylammonium formate as hydrogen donor. Studies on the kinetics under reaction conditions showed a broken positive order in substrate and first order in catalyst and hydrogen donor. Deuterium-labeling studies on the hydrogen donor showed that both hydrogens of formic acid display a primary kinetic isotope effect, indicating that proton and hydride transfers are separate rate-determining steps. By monitoring the reaction with NMR, we observed the presence of a coordinated formate anion and found that part of the maleic anhydride remains coordinated during the reaction. From these observations, we propose a mechanism in which hydrogen transfer from coordinated formate anion to zerovalent palladium(NHC)(MA)(alkyne)-complex is followed by migratory insertion of hydride, after which the product alkene is liberated by proton transfer from the triethylammonium cation. The explanation for the high selectivity observed lies in the competition between strongly coordinating solvent and alkyne for a Pd(alkene)-intermediate.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Asymmetric transfer hydrogenation of ketones with a polymer-supported chiral diamine

A new supported chiral diamine has been developed and shown to be highly effective in ruthenium-catalysed asymmetric transfer hydrogenation of simple aromatic ketones.     

Application of ferrocenylimidazolium salts as catalysts for the transfer hydrogenation of ketones

Ferrocenylimidazolium salts with methylene and phenyl groups bridging the ferrocenyl and alkylimidazolium moieties were synthesized and characterized by spectroscopic and analytical methods. Crystal structures of two new compounds are also reported. Cyclic voltammetry was used to analyze the influence of the two bridging groups or spacers on electrochemical properties of the salts relative to the shifts in the formal electrode or peak potentials (E⁰ or E_1/2) of the ferrocene/ferrocenium redox couple. Results from this study showed that all the salts exhibited higher electrode potentials relative to ferrocene, which is due to the electron‐withdrawing effect of the imidazolium ion on the ferrocenyl moiety. Application of the salts as catalysts in transfer hydrogenation of ketones resulted in high conversion of saturated ketones to corresponding alcohols and turnover numbers as high as 1880. The catalysts were chemoselective towards reduction of the C═C bonds of conjugated 3‐penten‐2‐one and 4‐hexen‐3‐one to yield saturated ketones, while unconjugated 5‐hexen‐2‐one was hydrogenated to an unsaturated alcohol. Copyright © 2012 John Wiley & Sons, Ltd.