Transfer Hydrogenation Conditions Research Articles

Primary alcohols as killers of Ni-based catalysts in transfer hydrogenation

The effect of different types of alcohols used as hydrogen donors on the activity of a metal Ni-based catalyst in the hydrogenation of benzofuran as a model substrate under transfer hydrogenation conditions has been studied. The hydrogenation process of benzofuran using 2-PrOH as a hydrogen donor leads sequentially to dearomatization and then to deoxygenation of the substrates. At the same time, the use of primary alcohols such as MeOH, EtOH and 1-PrOH as hydrogen donors leads to irreversible deactivation of the Ni-containing catalyst. A clear mechanism of deactivation of Ni-based metal catalysts by primary alcohols has been established. The interaction of the catalyst with primary alcohols at a temperature of 250 °C leads to the formation of an inactive Ni3C carbide phase, as well as sintering and segregation of metal particles on the surface of the alumina support.

Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism.

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(μ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.

Enantioselective Parallel Kinetic Resolution of Aziridine-Containing Quinoxalines via Chiral Phosphoric Acid-Catalyzed Transfer Hydrogenation.

This article describes the asymmetric synthesis of chiral aziridinoquinoxalines using (R)-TRIP-catalyzed parallel kinetic resolution under transfer hydrogenation conditions. This resolution was successfully accomplished for 16 different substrates and led to highly enantioenriched diastereomers with the (R)-configuration of the newly formed stereocenter (32-61% yield and 64-99% ee for the (R,R,R)-diastereomers and 7-46% yield and 97-99% ee for the (S,S,R)-diastereomers). This process could be coupled to ring-opening of the (S,S,R)-diastereomer with thiophenol to produce chiral tetrahydroquinoxalines with three contiguous stereocenters.

Reductive Transformation of O-, N-, S-Containing Aromatic Compounds under Hydrogen Transfer Conditions: Effect of the Process on the Ni-Based Catalyst.

The influence of the reaction medium on the surface structure and properties of a Ni-based catalyst used for the reductive transformations of O-, N-, and S-containing aromatic substrates under hydrogen transfer conditions has been studied. The catalysts were characterized by XRD, XPS, and IR spectroscopy and TEM methods before and after the reductive reaction. It has been shown that the conversion of 1-benzothiophene causes irreversible poisoning of the catalyst surface with the formation of the Ni2S3 phase, whereas the conversion of naphthalene, 1-benzofuran, and indole does not cause any phase change of the catalyst at 250 °C. However, after the indole conversion, the catalyst surface remains enriched with N-containing compounds, which are evenly distributed over the surface.

Substituent Effects and Mechanistic Insights on the Catalytic Activities of (Tetraarylcyclopentadienone)iron Carbonyl Compounds in Transfer Hydrogenations and Dehydrogenations.

(Cyclopentadienone)iron carbonyl compounds are catalytically active in carbonyl/imine reductions, alcohol oxidations, and borrowing hydrogen reactions, but the effect of cyclopentadienone electronics on their activity is not well established. A series of (tetraarylcyclopentadienone)iron tricarbonyl compounds with varied electron densities on the cyclopentadienone were prepared, and their activities in transfer hydrogenations and dehydrogenations were explored. Additionally, mechanistic studies, including kinetic isotope effect experiments and modifications to substrate electronics, were undertaken to gain insights into catalyst resting states and turnover-limiting steps of these reactions. As the cyclopentadienone electron density increased, both the transfer hydrogenation and dehydrogenation rates increased. A catalytically relevant, trimethylamine-ligated iron compound was isolated and characterized and was observed in solution under both transfer hydrogenation and dehydrogenation conditions. Importantly, it was catalytically active in both reactions. Kinetic isotope effect data and initial rates in transfer hydrogenation reactions with 4'-substituted acetophenones provided evidence that hydrogen transfer from the catalyst to the carbonyl substrate occurred during the turnover-limiting step, and NMR spectroscopy supports the trimethylamine adduct as an off-cycle resting state and the (hydroxycyclopentadienyl)iron hydride as an on-cycle resting state. In transfer dehydrogenations of alcohols, the use of electronically modified benzylic alcohols provided evidence that the turnover-limiting step involves the transfer of hydrogen from the alcohol substrate to the catalyst. The trimethylamine-ligated compound was proposed as the primary catalyst resting state in dehydrogenations.

RuCl2(DPEphos)(N-N)] (DPEphos = bis[(2-diphenylphosphino)phenyl]ether; N-N = 2-aminomethylpyridine or ethylenediamine): synthesis, characterization and transfer hydrogenation of aryl-ketones

The complexes trans/cis-[RuCl2(DPEphos)(ampy)] (trans – 1a; cis – 1b) and trans/cis-[RuCl2(DPEphos)(en)] (trans – 2a; cis – 2b) were obtained from the reactions of mer-[RuCl2(DPEphos)(PPh3)] (PPh3 = triphenylphosphine) with the corresponding amine in CH2Cl2. The isomer 1a was observed in situ when the reaction was carried out at r.t.; isolation leads to mixtures with 1b, while the latter was isolated when the reaction was performed under reflux. On the other hand, trans-[RuCl2(DPEphos)(en)] (2a) was obtained at r.t., in good yield and the cis-isomer 2b was observed when the reaction was carried out under reflux or when a CH2Cl2 solution of 2a is exposed to ambient light, but 2b was not isolated in pure form even under reflux for one week. Cyclic voltammetry studies revealed the presence of one reversible process with E1/2 0.57 and 0.40 V for 1b and 2a, respectively. Both 1b and 2a were used as pre-catalysts for reduction of acetophenone and p-substituted acetophenones (F–, Me– and MeO–) in transfer-hydrogenation conditions (isopropanol, 82 °C, and pre-catalyst:KOH:acetophenones in molar ratio 1:20:500 and/or 1:20:1000) showing conversions of 93–99% and TOF values up to 4.2 104 h−1.

Applying green chemistry principles to iron catalysis: mild and selective domino synthesis of pyrroles from nitroarenes.

An efficient and general cascade synthesis of pyrroles from nitroarenes using an acid-tolerant homogeneous iron catalyst is presented. Initial (transfer) hydrogenation using the commercially available iron-Tetraphos catalyst is followed by acid catalysed Paal-Knorr condensation. Both formic acid and molecular hydrogen can be used as green reductants in this process. Particularly, under transfer hydrogenation conditions, the homogeneous catalyst shows remarkable reactivity at low temperatures, high functional group tolerance and excellent chemoselectivity transforming a wide variety of substrates. Compared to classical heterogeneous catalysts, this system presents complementing reactivity, showing none of the typical side reactions such as dehalogenation, debenzylation, arene or olefin hydrogenation. It thereby enhances the chemical toolbox in terms of orthogonal reactivity. The methodology was successfully applied to the late-stage modification of multi-functional drug(-like) molecules as well as to the one-pot synthesis of the bioactive agent BM-635.

New palladium(II) complexes with ferrocenyl Schiff bases in the hydrogenation of aromatic ketones

Two new palladium complexes with chelating phosphorus-free ferrocenyl-imine ligands derived from 1,2-diaminocyclohexane and 1,2-diphenylethylenediamine were investigated in the hydrogenation of aromatic ketones. It was found that these catalysts are active in reactions performed with H2 as well as in transfer hydrogenation using 2-propanol/NaOH as a hydrogen donor. In the hydrogenation of acetophenone (APh), two products could be formed, 1-phenylethanol (PhE) and ethylbenzene (EtB), and the reaction selectivity in the studied system was controlled by the kind of solvent and the amount of free ligand excess. In the hydrogenation of acetophenone derivatives, higher selectivity to 1-arylethanol was achieved under hydrogen transfer conditions than under 10 bars of H2 and some ketones were hydrogenated only using this method.

Upgradation of sugarcane bagasse lignin: Fractionation to cyclic alcohols production

Reductive catalytic fractionation (RCF) is a new class of process that produces mono phenolics close-to-theoretical maximum yield by preserving the biomass polysaccharides as solid residues under hydrogen atmosphere or hydrogen transfer conditions. Herein, hydrous ruthenium oxide deposited on carbon (HRO@C) and HY-zeolite (HRO@HYZ) catalysts are prepared and characterized by different analytical techniques (TGA, TPD, TPR, XRD, TEM, XPS, physisorption and chemisorption). Both catalysts have been used for the RCF of sugarcane bagasse (SCB). Effects of catalyst acidity, reaction time, pressure, temperature, and solvent on the RCF of SCB have been investigated. Solid residues after RCF are characterized by FT-IR, TGA, XRD, and fibertec to identify the effects of reaction conditions on lignin-first delignification efficiency (LFDE). High acidity of HRO@HYZ favors a high degree of LFDE (81.2 %) than HRO@C (55.8 %). However, alkyl-substituted phenolic monomers (ASPMs) selectivity is 69 % for HRO@C and 55.7 % for HRO@HYZ, respectively, under the same reaction conditions. NMR and GC-FID/GC-MS analysis indicate the presence of ASPMs in the resulted lignin bio-oil. Moreover, fractionated lignin bio-oil is used for upgradation and the upgraded product analysis confirms > 95 % conversion of lignin bio-oil, in which over 90 % selectivity is towards alkylated cyclic alcohols.

Poisoning effect of N-containing compounds on performance of Raney® nickel in transfer hydrogenation

The effect of amines, imines and heterocycle compounds on conversion has been studied in transfer hydrogenation of camphor and 2-PrOH catalyzed by Raney® nickel. Small amount (5 mol% to nickel) of N-containing compound significantly decreases catalyst activity. It has been shown that the poisoning effect mostly depends on molecular size of amines and heterocyclic compounds. For aniline and cyclohexylamine the dependence of camphor conversion on poison/nickel ratio was obtained. Additionally, benzaldehyde, cinnamaldehyde demonstrated higher reactivity compared corresponding imines under transfer hydrogenation conditions. Obtained data explain low activity of nickel-based catalysts when N-containing compounds are presented in reaction mixture.

Asymmetric Transfer Hydrogenation of Aryl Heteroaryl Ketones using Noyori‐Ikariya Catalysts

AbstractA range of ketones flanked by a combination of an aromatic and a heterocyclic ring (furan, thiophene, N‐methylimidazole) were reduced under asymmetric transfer hydrogenation (ATH) conditions. Using a range of [(arene)Ru(TsDPEN)Cl] precatalysts, including tethered derivatives, the reduction enantioselectivity was high (up to 99 % ee) in cases where the aromatic ring contained an ortho‐substituent. The enantioselectivity is influenced by a combination of steric and electronic factors which for the furan and thiophene series, follow literature precedents. In the case of the N‐methylimidazole‐containing ketones, an unexpected switch in enantioselectivity took place upon variation of the opposing aromatic group. Pyrrole‐ containing ketones were resistant to reduction. This study demonstrates the asymmetric transfer hydrogenation (ATH) of a range of hindered heterocyclic ketones, in high conversion and ee, using Noyori‐Ikariya catalysts.

Copper-Catalyzed Formal Transfer Hydrogenation/Deuteration of Aryl Alkynes.

A copper-catalyzed reduction of alkynes to alkanes and deuterated alkanes is described under transfer hydrogenation and transfer deuteration conditions. Commercially available alcohols and silanes are used interchangeably with their deuterated analogues as the hydrogen or deuterium sources. Transfer deuteration of terminal and internal aryl alkynes occurs with high levels of deuterium incorporation. Alkyne-containing complex natural product analogues undergo transfer hydrogenation and transfer deuteration selectively, in high yield. Mechanistic experiments support the reaction occurring through a cis-alkene intermediate and demonstrate the possibility for a regioselective alkyne transfer hydrodeuteration reaction.

Hydrocarbon hydrogen carriers for catalytic transfer hydrogenation of guaiacol

Polycyclic hydrocarbons are known to be efficient hydrogen carriers capable of yielding high purity H2 upon dehydrogenation. Due to their high hydrogen density, high boiling point, and stability, these compounds demonstrate the potential to be used as hydrogen donors under catalytic transfer hydrogenation (CTH) conditions. In this work, the potential of a suite of hydrogen carriers to donate hydrogen, as well as the mechanisms affecting their hydrogen transfer, are assessed through the CTH of guaiacol, on Pd/Al2O3, as a model system. The results indicated the following descending order of transfer hydrogenation rate: bicyclohexyl > tetralin » hydrogenated terphenyl (HTP) > cyclohexylbenzene. Among the products, cyclohexanone and phenol are the most abundant, directly resulting from CTH. Detailed analysis of the hydrogen carrier conversion and selectivity clearly shows that the potential for CTH is highly linked to the molecular structure of the donor, rather than the amount of hydrogen available for transfer. A density functional theory (DFT) study, supported by experimental data, reveals that when unsaturated hydrocarbons are utilized, such as tetralin, cyclohexylbenzene, and HTP, the effective CTH rate to guaiacol is limited, despite dehydrogenation being more favorable for those molecules than from fully saturated donors, such as bicyclohexyl.

Catalyzed transfer hydrogenation by 2-propanol for highly selective PAHs reduction

Catalytic hydrogenation of mono-, di- and trinuclear aromatic compounds has been studied under hydrogen transfer conditions at 150 °C and 82 °C in 2-PrOH as a hydrogen donor and with Raney® nickel as a catalyst. In contrast to conjugated or condensed aromatic rings, isolated ones demonstrated low reactivity in transfer hydrogenation (TH) that can be used to increase the hydrogenation selectivity of the reaction. So, naphthalene and biphenyl are partially hydrogenated into tetralin and cyclohexylbenzene, respectively, with excellent conversion (≥ 96 %) and selectivity (≥ 98 %) for 5–6 h at 82 °C. Increasing the reaction temperature to 150 °C results expectedly in the hydrogenation of second aromatic ring, which occurs slowly enough. Only 8 % of decaline and 42 % of dicyclohexyl, correspondingly, were obtained after 5 h at 150 °C. At the same time, TH of trinuclear anthracene and phenanthrene at 150 °C resulted in the formation of deeper hydrogenated octahydro-anthracenes and -phenanthrenes, respectively.

Asymmetric Transfer Hydrogenation of o-Hydroxyphenyl Ketones: Utilizing Directing Effects That Optimize the Asymmetric Synthesis of Challenging Alcohols.

A systematic range of o-hydroxyphenyl ketones were reduced under asymmetric transfer hydrogenation conditions using the C3-tethered catalyst 2. Two directing effects, i.e., an o-hydroxyphenyl coupled to a bulky aromatic on the opposite side of the ketone substrate, combine in a matched manner to deliver reduction products with very high enantiomeric excess.

Reductive Amination of Ketonic Compounds Catalyzed by Cp*Ir(III) Complexes Bearing a Picolinamidato Ligand.

Cp*Ir complexes bearing a 2-picolinamide moiety serve as effective catalysts for the direct reductive amination of ketonic compounds to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source. The clean and operationally simple transformation proceeds with a substrate to catalyst molar ratio (S/C) of up to 20,000 at relatively low temperature and exhibits excellent chemoselectivity toward primary amines.

Raney® nickel-catalyzed hydrodeoxygenation and dearomatization under transfer hydrogenation conditions—Reaction pathways of non-phenolic compounds

Abstract Catalytic reduction of oxygen-containing aromatic compounds has been studied under transfer hydrogenation (TH) conditions at 150 °C in 2-PrOH as a hydrogen donor. Raney® nickel is used as a heterogeneous catalyst. The reaction of aromatic non-phenolic carbonyl compounds is most likely to proceed through the pathway “aromatic ketone (aldehyde)→aromatic alcohol→alkylaromatics→saturated alkylcyclohexane”. One of the main reactions under the TH conditions is a hydrodeoxygenation (HDO) process. Unexpectedly, the hydrodeoxygenation of aromatic ketones to alkylaromatics (C O → CH2) occurs faster than of corresponding aromatic alcohols (HC OH → CH2) that means either additional reaction pathway of its hydrodeoxygenation missing for the corresponding aromatic alcohols or specific interaction of OH functionality with Raney® nickel surface obstructing (hindering) the further reduction. Benzaldehyde is shown to be less reactive than the aromatic ketones under the same reaction conditions. The main reason is proposed to be carbon monoxide release resulted from the decarbonylation of the aldehyde. Carbon monoxide demonstrates a poisoning effect on Raney® nickel surface that is evidenced in the catalyzed TH reaction of acetophenone. The HDO reaction of anisole under the same reaction conditions was a little slowly than of oxygen-containing non-phenolic aromatics.

Pyridine‐Stabilized Rhodium Nanoparticles in Ionic Liquids as Selective Hydrogenation and Transfer Hydrogenation Catalysts

Rhodium nanoparticles (RhNPs) stabilized with pyridine‐based ligands in the ionic liquid [BMIM][BF4] (RhNPs‐I to III) were synthesized from the organometallic precursor [Rh(µ‐OMe)COD]2 under dihydrogen pressure. The pyridine‐stabilized RhNPs showed smaller size compared to the ligand free RhNPs‐V and presented higher activity and selectivity in the hydrogenation of acetophenone to 1‐phenylethanol. In the case of pyridine‐capped RhNPs‐I, the system was reused for several runs without loss of activity and selectivity. Nitrobenzene was reduced to aniline with dihydrogen in the presence of RhNPs‐I with moderate activity. When the hydrogen source was formic acid‐Et3N azeotrope (transfer hydrogenation) the reaction was completed within minutes with high selectivity. Under transfer hydrogenation conditions, it was possible to apply the catalytic system RhNPs‐I in multistep processes for the generation of substituted arylic amines through the reductive N‐alkylation of nitrobenzene and benzaldehyde; and the synthesis of substituted pyrroles through the nitroarene reduction/Paal‐Knorr condensation.

The reductive deaminative conversion of nitriles to alcohols usingpara-formaldehyde in aqueous solution

We report herein, for the first time, the application ofpara-formaldehyde (pFA) to the reductive deamination of both aliphatic and aromatic nitriles in aqueous solution under transfer hydrogenation conditions.

Ruthenium(II)-Arene Complexes of the Water-Soluble Ligand CAP as Catalysts for Homogeneous Transfer Hydrogenations in Aqueous Phase

The neutral Ru(II) complex κP-[RuCl2(η6-p-cymene)(CAP)] (1), and the two ionic complexes κP-[RuCl(η6-p-cymene)(MeCN)(CAP)]PF6 (2) and κP-[RuCl(η6-p-cymene)(CAP)2]PF6 (3), containing the water-soluble phosphine 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP), were tested as catalysts for homogeneous hydrogenation of benzylidene acetone, selectively producing the saturated ketone as product. The catalytic tests were carried out in aqueous phase under transfer hydrogenation conditions, at mild temperatures using sodium formate as hydrogen source. Complex 3, which showed the highest stability under the reaction conditions applied, was also tested for C=N bond reduction from selected cyclic imines. Preliminary NMR studies run under pseudo-catalytic conditions starting from 3 showed the formation of κP-[RuH(η6-p-cymene)(CAP)2]PF6 (4) as the pivotal species in catalysis.