Catalysts For Asymmetric Transfer Hydrogenation Research Articles

Mechanistic Aspects of Using Formate as a Hydrogen Donor in Aqueous Transfer Hydrogenation

Asymmetric transfer hydrogenation of ketones is an important chemical reaction. In aqueous solution, Ru(p-cymene)[TsDPEN] is an efficient catalyst for asymmetric transfer hydrogenation via a metal–ligand bifunctional mechanism with either 2-propanol or formate as hydrogen donors. Here, we provide novel insight for two key steps in the catalytic cycle of transfer hydrogenation cycle, using a computational model of Ru(p-cymene)[TsDPEN] with an explicit aqueous solvent. Employing ab initio molecular dynamics simulations, we model the hydride transfer between formate and the protonated and deprotonated catalyst, and the dissociation of the ruthenium-formato complex. It is shown that the aqueous solvent provides a significant contribution to the reaction barriers, increasing the hydride transfer barrier, while decreasing the dissociation barrier for ruthenium-formato complex, when compared with a gas-phase model. These effects can be attributed to hydrogen-bond structure around the formate, which favors the fo...

ChemInform Abstract: Synthesis of Planar Chiral Shvo Catalysts for Asymmetric Transfer Hydrogenation.

AbstractSeveral examples for transfer hydrogenations are given which may proceed with high yields and moderate enantiomeric excesses.

ChemInform Abstract: Asymmetric Transfer Hydrogenation of Ketones with Modified Grubbs′ Metathesis Catalysts: On the Way to a Tandem Process.

AbstractUpon addition of a chiral amine ligand, an alcohol and a base, the 1st generation Hoveyda—Grubbs catalyst is in situ transformed into an asymmetric transfer hydrogenation catalyst, promoting the enantioselective reduction of acetophenone to 1‐phenylethanol.

Synthesis of Planar Chiral Shvo Catalysts for Asymmetric Transfer Hydrogenation

AbstractA new type of planar chiral Shvo catalysts, where the chirality is based solely on different substitution flanking the CO function, was prepared and used for transfer hydrogenation of imines and ketones. The reduction of ketimines represented by N‐(1‐phenylethylidene)aniline and prochiral ketones such as phenyl trifluoromethyl ketone with 2‐propanol was efficiently catalyzed by 0.5 mol% of the chiral Shvo catalyst to give high yields of the corresponding reduction products with the enantioselectivities in the range 45% to 64% ee.magnified image

N-Functionalised TsDPEN catalysts for asymmetric transfer hydrogenation; synthesis and applications

A series of Ru(II)/arene complexes containing N-alkylated derivatives of TsDPEN were prepared and tested in the asymmetric transfer hydrogenation (ATH) of ketones. The results demonstrated that a wide variety of functionality were tolerated on the basic amine of the TsDPEN ligand, without significantly disrupting the ability of the catalyst to catalyse hydrogen transfer reactions.

ChemInform Abstract: Silica‐Supported Chiral Catalysts for Asymmetric Transfer Hydrogenation

AbstractReview: 50 refs.

ChemInform Abstract: Simple 1,3‐Diamines and Their Application as Ligands in Ruthenium(II) Catalysts for Asymmetric Transfer Hydrogenation of Aryl Ketones.

In this research work simple unsymmetrical 1,3-diamines were studied. The synthesis of the diamines started from non-commercial available compounds. S-5a and S,S-5c were obtained by biocatalysis with non conventional yeast, Rhodotorula rubra MIM 147, with excellent 99% e.e. and d.e. up to 90%. Different approaches of synthesis were applied to the same backbone to study both the steric and electronic effects of the ligands. The reactivity of the corresponding ruthenium complexes was evaluated in the asymmetric hydrogen transfer reduction of acetophenone as a standard substrate and of other different aryl ketones, highlighting the flexibility of the six membered chelating ring. A screening of the reaction conditions indicated aqueous media in the presence of HCOONa as a hydrogen donor to be the best system for overcoming the lack of stereocontrol thus allowing us to obtain 56% e.e. in the reduction of acetophenone with the complex in which the ligand was diamine 1, revealed as the best in terms of reactivity and stereoselectivity also in the reduction of the other different aryl ketones, in particular for α-tetralone, i (63% e.e.).

Silica-Supported Chiral Catalysts for Asymmetric Transfer Hydrogenation

Developments of mesoporous silica materials for use as supports to construct silica-supported chiral heterogeneous catalysts and explorations of their applications in asymmetric transfer hydrogenation represent an important branch of organic chemistry, in which understanding the supports role and controlling chiral environment are critical during the catalytic process. In this review, we briefly introduce the basic concepts with respect to general immobilization strategies and preparation methods. Main considerations focus on the preparation of heterogeneous catalysts according to the type of mesoporous silica supports and summarize their applications in asymmetric transfer hydrogenation. This paper also provides a perspective for further developing the design of silica-supported chiral heterogeneous catalysts. Keywords: Asymmetric catalysis, immobilization, mesoporous material, silica, supported catalyst.

Easy To Synthesize, Robust Organo-osmium Asymmetric Transfer Hydrogenation Catalysts.

Asymmetric transfer hydrogenation (ATH) is an important process in organic synthesis for which the Noyori‐type RuII catalysts [(arene)Ru(Tsdiamine)] are now well established and widely used. We now demonstrate for the first time the catalytic activity of the osmium analogues. X‐ray crystal structures of the 16‐electron OsII catalysts are almost identical to those of RuII. Intriguingly the precursor complex was isolated as a dichlorido complex with a monodentate amine ligand. The OsII catalysts are readily synthesised (within 1 h) and exhibit excellent enantioselectivity in ATH reactions of ketones.

Synthesis and use of an asymmetric transfer hydrogenation catalyst based on iron(II) for the synthesis of enantioenriched alcohols and amines.

The catalytic hydrogenation of prochiral ketones and imines is an advantageous approach to the synthesis of enantioenriched alcohols and amines, respectively, which are two classes of compounds that are highly prized in pharmaceutical, fragrance and flavoring chemistry. This hydrogenation reaction is generally carried out using ruthenium-based catalysts. Our group has developed an alternative synthetic route that is based on the environmentally friendlier iron-based catalysis. This protocol describes the three-part synthesis of trans-[amine(imine)diphosphine]chlorocarbonyliron(II) tetrafluoroborate templated by iron salts and starting from commercially available chemicals, which provides the precatalyst for the efficient asymmetric transfer hydrogenation of ketones and imines. The use of the enantiopure (S,S) catalyst to reduce prochiral ketones to the (R)-alcohol in good to excellent yields and enantioenrichment is also detailed, as well as the reduction to the amine in very high yield and enantiopurity of imines substituted at the nitrogen with the N-(diphenylphosphinoyl) group (-P(O)Ph2). Although the best ruthenium catalysts provide alcohols in higher enantiomeric excess (ee) than the iron complex catalyst used in this protocol, they do so on much longer time scales or at higher catalyst loadings. This protocol can be completed in 2 weeks.

Simple 1,3-diamines and their application as ligands in ruthenium(ii) catalysts for asymmetric transfer hydrogenation of aryl ketones

A new efficient synthesis of 1,3-diamines was realized and their ruthenium(ii) complexes were studied in ATH in aqueous media.

Rhodium complex with unsymmetrical vicinal diamine ligand: excellent catalyst for asymmetric transfer hydrogenation of ketones

New unsymmetrical vicinal diamine ligands with systematic variation in the regio and stereo positions in the amine and sulphonamide groups were synthesized from cheap starting material such as norephedrine.

Exploring the decomposition pathways of iron asymmetric transfer hydrogenation catalysts.

Our group has developed a series of iron-based asymmetric transfer hydrogenation (ATH) catalysts for the reduction of polar double bonds. The activation of the precatalysts as well as the catalytic mechanism have been thoroughly investigated, but the decomposition pathways of these systems are poorly understood. Herein, we report a study of the deactivation pathways for an iron ATH catalyst under catalytically relevant conditions. The decomposition pathways were examined using experimental techniques and density functional theory (DFT) calculations. The major decomposition products that formed, Fe(CO)((Et)2PCH2CH2CHCHNCH2CH2P(Et)2) (3a) and Fe(CO)((Et)2PCH2CH2C(Ph)C(Ph)NCH2CH2P(Et)2) (3b), had two amido donors as well as a C=C bond on the diamine backbone of the tetradentate ligand. These species were identified by NMR studies and one was isolated as a bimetallic complex with Ru(II)Cp*. Two minor iron hydride species also formed concurrently with 3a, as determined by NMR studies, one of which was isolated and contained a fully saturated ligand as well as a hydride ligand. None of the compounds that were isolated were found to be active ATH catalysts.

Insight into the role of fluorinated dendrimers in ruthenium(II) catalyst for asymmetric transfer hydrogenation: The stabilizing effects from experimental and DFT approach

A series of fluorinated dendritic chiral ligands have been designed and synthesized. These fluorinated dendrimers are capable of forming a well-defined semi-rigid structure, which was revealed to play a vital role in the ruthenium(II) bifunctional catalyst for asymmetric transfer hydrogenation of prochiral ketone substrates. In contrast to the classical non-fluorinated dendrimer carrier, both NMR and DFT study exhibit that the introduction of fluorine atoms leads to considerable intramolecular weak interactions such as π–π stacking and hydrogen bonding interactions, which make the dendritic backbone exist with a semi-rigid structure in the catalyst. This influences the performance of the catalytic center in terms of the stability and reusability. This concept was employed as a strategy to design a new Ru(II)-complex catalyst Ru-G-2′-F, which demonstrated obviously improved recycling ability up to fifteen times. Significantly enhanced activity, high enantioselectivity and outstanding recycling ability have also been achieved even at high reaction temperature with Ru-G-2-F.

Rational development of iron catalysts for asymmetric transfer hydrogenation

The asymmetric reduction of ketones and imines by transfer of hydrogen from isopropanol as the solvent catalyzed by metal complexes is a very useful method for preparing valuable enantioenriched alcohols and amines. Described here is the development of three generations of progressively more active iron catalysts for this transformation. Key features of this process of discovery involved the realization that one carbonyl ligand was needed (as in hydrogenases), the synthesis of modular ligands templated by iron, the elucidation of the mechanisms of catalyst activation and action, as well as the rational synthesis of precursors that lead directly and easily to the species in the catalytic cycle. The discovery that iron, an abundant element that is essential to life, can form catalysts of these hydrogenation reactions is a contribution to green chemistry.

Chiral Ir(I) complex supported on external surface passivated SBA-15 as heterogeneous catalyst for asymmetric transfer hydrogenation of aromatic ketones

Chiral 9-amino epi-cinchonine was anchored on external surface passivated SBA-15 as well as calcined SBA-15. The two resulting materials were used as catalysts for the asymmetric transfer hydrogenation of aromatic ketones after complexing with [Ir(COD)Cl]2. Higher enantioselectivities were obtained over the passivated SBA-15 supported catalyst compared with the catalyst based on calcined SBA-15 as well as the homogeneous counterpart. Especially for the substrate of acetophenone, an obviously high enantiomeric excess (ee) of 74% (homogeneous ee: 60%) was achieved with comparable conversion to the homogeneous catalyst (97% vs. 98%). Furthermore, the passivated SBA-15 supported catalyst demonstrated higher stability during the asymmetric transfer hydrogenation reaction as compared with the catalyst based on calcined SBA-15.

A new efficient bis(phosphinite)-ruthenium(II) catalyst system for the asymmetric transfer hydrogenation of aromatic ketones

Many chiral ligands bearing phosphorus donor atoms were developed and applied in the area of metal catalyzed asymmetric catalysis. A new chiral bis(phoshinite) ligand was successfully synthesized from optically active (1S,8S)-3,6-[N-(S)-α-phenylethyl]diaza-1,8-diphenoxymethyl-1,8-octanediol in high yield. A ruthenium(II) complex generated in situ from [Ru(η6-p-cymene)(μ-Cl)Cl]2, bis(phosphinite) ligand and KOH acts as an active catalyst for asymmetric transfer hydrogenation (ATH) of acetophenone derivatives in isopropyl alcohol (IPA) as both solvent and hydrogen source. The catalytic reaction proceeds cleanly to give enantiomerically enriched secondary alcohols up to 90% or 89% ee’s at 50 or 82°C, respectively.

Amine(imine)diphosphine Iron Catalysts for Asymmetric Transfer Hydrogenation of Ketones and Imines

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.

Nanoscale Fe 2 O 3 -Based Catalysts for Selective Hydrogenation of Nitroarenes to Anilines

Production of anilines--key intermediates for the fine chemical, agrochemical, and pharmaceutical industries--relies on precious metal catalysts that selectively hydrogenate aryl nitro groups in the presence of other easily reducible functionalities. Herein, we report convenient and stable iron oxide (Fe2O3)-based catalysts as a more earth-abundant alternative for this transformation. Pyrolysis of iron-phenanthroline complexes on carbon furnishes a unique structure in which the active Fe2O3 particles are surrounded by a nitrogen-doped carbon layer. Highly selective hydrogenation of numerous structurally diverse nitroarenes (more than 80 examples) proceeded in good to excellent yield under industrially viable conditions.

Cobalt Precursors for High-Throughput Discovery of Base Metal Asymmetric Alkene Hydrogenation Catalysts

Asymmetric hydrogenation of alkenes is one of the most widely used methods for the preparation of single enantiomer compounds, especially in the pharmaceutical and agrochemical industries. For more than four decades, precious metal complexes containing rhodium, iridium, and ruthenium have been predominantly used as catalysts. Here, we report rapid evaluation of libraries of chiral phosphine ligands with a set of simple cobalt precursors. From these studies, base metal precatalysts have been discovered for the hydrogenation of functionalized and unfunctionalized olefins with high enantiomeric excesses, demonstrating the potential utility of more earth-abundant metals in asymmetric hydrogenation.