Chemoselective Transfer Hydrogenation Research Articles

Homobimetallic Ruthenium(II) Complexes Catalysed Selective Transfer Hydrogenation of Aldehydes in Water.

Herein we report chemoselective transfer hydrogenation (TH) of aldehydes in aqueous medium using a series of homobimetallic Ru(II) catalysts. Two homobimetallic complexes (Ru1 and Ru3) and one monometallic complex (Ru2) have been employed in the catalytic reduction of aldehydes. Bimetallic complex [(p-cymene)2(RuCl)2L3] (Ru3) is obtained from the reaction of Schiff base ligand 2,2'-((1E,1'E)-((3,3',5,5'-tetraisopropyl-[1,1'-biphenyl]-4,4'diyl)bis(azaneylylidene))bis(methaneylylidene))bis(4-bromophenol) (H2L3) and characterized by various spectroscopic and analytical techniques. The use of formic acid/formate buffer as the hydride source and a catalyst loading of 0.01 mol% of Ru1 or Ru3 resulted in the conversion of various aldehydes to the corresponding alcohols in good to excellent yield. This method is very efficient for selective reduction of aldehydes in the presence of other reducible functional groups. A loading of 0.0001 mol% of Ru1 catalyst is sufficient to achieve a turnover frequency (TOF) of 5.5× 105 h-1. Furthermore, the catalyst can been recycled and reused for six consecutives cycles without sacrificing the efficiency. A comparison of results obtained between bimetallic and monometallic complexes offers valuable insights into the distinct reactivity patterns of the bimetallic complexes, presumably originating from a cooperative effect. We have explored the mechanistic pathway using DFT methods.

Ruthenium‐Catalyzed Chemoselective Olefin Transfer Hydrogenation of alpha, beta‐Unsaturated Carbonyl Systems By Using EtOH as Hydrogen Source

AbstractThe use of EtOH as hydrogen donor is remarkably under explored in transfer hydrogenation reactions, even though EtOH represents an appealing hydrogen source. With the cationic ruthenium complex [Ru(PYA)(cymene)]+, 1, containing a N,N‐bidentate amino‐functionalized pyridinium amidate (PYA) ligand as catalyst precursor, we here demonstrate the first example of chemoselective room temperature transfer hydrogenation of the C═C bond in α,β‐unsaturated ketones using EtOH as benign hydrogen source to yield a variety of functionalized ketones. The reaction proceeds under mild conditions with K2CO3 as base and conventiently at room temperature. A broad substrate scope, including various functionalized α,β‐unsaturated carbonyl groups, demonstrates the general applicability of this method. Preliminary mechanistic studies suggest the formation of an alkoxide complex [1]–OEt as an initially formed species, and the requirement for EtOH to induce hydride transfer, suggesting a protic activation of the catalyst.

Iron-Catalyzed Chemoselective Transfer Hydrogenation of α,β-Unsaturated Ketones Using H2O as a Surrogate of Hydrogen.

Sustainable and highly economical iron-catalyzed chemoselective reduction of C═C of α,β-unsaturated ketones has been established under mild reaction protocols. Water is used as a green and abundant surrogate of hydrogen and is scarcely used in organic synthetic transformations as a source of hydrogen. The developed protocol offers a broad spectrum for chemoselective transfer hydrogenation of α,β-unsaturated ketones. Moreover, the method was found to be highly effective for aryl and ferrocenyl α,β-unsaturated ketones consisting of one or two double bonds and with multiple functionalities. Moreover, the present method avoids prolonged reaction time, provides a wide range of substrates with excellent yield, and circumvents the tedious chromatographic workup.

(Invited) Thermal and Plasmon-Mediated Catalytic Transfer Hydrogenation Reactions on Nanostructured Metal Surfaces

Catalytic hydrogenation reactions play crucial roles in fine chemical production and pharmaceutical synthesis. Compared to direct hydrogenation of organic compounds with pressurized hydrogen gas, catalytic transfer hydrogenation reactions using inexpensive and readily accessible small molecules as hydrogen-donors has been considered as a more versatile, scalable, and sustainable pathway toward enhanced chemoselectivity under mild reaction conditions. Noble metal nanoparticles, especially those within the sub-5 nm size regime, can efficiently catalyze the dehydrogenation of a series of hydrogen-storing molecules, such as ammonia borane, hydrazine, formaldehyde, formic acid, and isopropanol, to produce surface-adsorbed hydrogen species that actively hydrogenate a variety of organic substrate molecules. The transfer hydrogenation/hydrogenolysis reactions are mechanistically complex, and may occur selectively along multiple distinct pathways, exhibiting kinetic features signifying the Langmuir–Hinshelwood, Eley–Rideal, autocatalysis, and reversible reaction mechanisms, respectively, depending on the compositions of the metal catalysts and the chemical nature of the hydrogen donors. In this talk, I will share with the audience some new insights concerning the detailed mechanisms of transfer hydrogenation reactions over metal nanocatalyst surfaces. We employ surface-enhanced Raman scattering (SERS) as an in situ fingerprinting spectroscopic tool to precisely resolve the detailed structural evolution of molecular adsorbates during catalytic reactions, based upon which the key intermediates along different reaction pathways are unambiguously identified. The results of deliberately designed in situ SERS measurements show that the chemoselective transfer hydrogenation of nitrophenyl isocyanide by ammonia borane may proceed on noble metal nanocatalyst surfaces selectively through either a unimolecular or a bimolecular pathway, depending on how the nitrophenyl isocyanide adsorbates interact with the metal nanoparticle surfaces. The experimental observations are corroborated by density functional theory calculations, which shed light on the underlying relationships between catalyst-adsorbate interactions and reaction pathway selection. We have further demonstrated that the photoexcited plasmonic hot carriers in the metal nanoparticles can be effectively harnessed to fine-regulate the activation energy barriers associated with the rate-limiting steps for the transfer hydrogenation of nitrophenyl isocyanide on Pd nanocatalyst surfaces when ammonium formate serves as the hydrogen donor. Our results clearly demonstrate the feasibility of using plasmonic hot carriers to kinetically modulate catalytic molecule-transforming processes.

MgO Modified by X2, HX, or Alkyl Halide (X = Cl, Br, or I) Catalytic Systems and Their Activity in Chemoselective Transfer Hydrogenation of Acrolein into Allyl Alcohol.

A new type of catalyst containing magnesium oxide modified with various modifiers ranging from bromine and iodine, to interhalogen compounds, hydrohalogenic acids, and alkyl halides have been prepared using chemical vapor deposition (CVD) and wet impregnation methods. The obtained systems were characterized using a number of methods: determination of the concentration of X- ions, surface area determination, powder X-ray diffraction (PXRD), surface acid-base strength measurements, TPD of probe molecules (acetonitrile, pivalonitrile, triethylamine, and n-butylamine), TPD-MS of reaction products of methyl iodide with MgO, and Fourier transform infrared spectroscopy (FTIR). The catalysts' activity and chemoselectivity during transfer hydrogenation from ethanol to acrolein to allyl alcohol was measured. A significant increase in the activity of modified MgO (up to 80% conversion) in the transfer hydrogenation of acrolein was found, while maintaining high chemoselectivity (>90%) to allyl alcohol. As a general conclusion, it was shown that the modification of MgO results in the suppression of strong basic sites of the oxide, with a simultaneous appearance of Brønsted acidic sites on its surface. Independently, extensive research on the reaction progress of thirty alkyl halides with MgO was also performed in order to determine its ability to neutralize chlorinated wastes.

Chemoselective Transfer Hydrogenation of Nitroarenes with Ammonia Borane Catalyzed by Copper N‐heterocyclic Carbene Complexes

Comprehensive SummaryHerein, we present a method for the homogeneous hydrogenation of nitroarenes to produce anilines using low catalyst loading (1 mo%) of copper N‐heterocyclic carbene complexes as the catalyst and ammonia borane as the source of hydrogen. A wide range of nitroarenes, featuring diverse functional groups, were selectively transformed into their corresponding primary aromatic amines with high yields. This process can be readily scaled up and exhibits compatibility with various sensitive functional groups, including halogen, trifluoromethyl, aminomethyl, alkenyl, cyano, ester, amide, and hydroxyl. Notably, this catalytic methodology finds application in the synthesis of essential drug compounds. Mechanistic investigations suggest that the in‐situ‐generated Cu‐H species may serve as active intermediates, with reduction pathways involving species such as azobenzene, 1,2‐diphenylhydrazine, nitrosobenzene, and N‐phenylhydroxylamine.

Nanocatalysts Based on Ni Nanoparticles in Functionalized Ionic Liquids for Chemoselective Hydrogenation and Transfer Hydrogenation of α,β‐unsaturated Carbonyl Compounds

AbstractFor the development of catalytically active and selective Ni nanoparticle (NP) catalysts both the choice of the synthesis method and the selection of stabilizer are key parameters. A series of Ni NPs were synthesized in various ionic liquids (Ni/ILs) and applied as catalysts for the chemoselective reduction of 2‐cyclohexen‐1‐one (1), as a representative of the group of α,β‐unsaturated carbonyl compounds with industrial relevance. The Ni/ILs systems were found to be efficient catalysts for the selective hydrogenation of 1 to cyclohexanone (2) under quite mild reaction conditions (130‐170 °C, 10 bar H2, 1/Ni molar ratio of 100/1), achieving high conversions in a short reaction time (1 h). The oxidized counterparts (Ni‐NiO/ILs) showed to be active for the selective catalytic transfer hydrogenation (CTH) of 1 to 2‐cyclohexen‐1‐ol (3) with 2‐propanol, also under mild reaction conditions (150 °C, 48 h, 1/Ni ratio of 50/1).

Highly chemoselective transfer hydrogenation of the C[dbnd]C bonds of α-Keto substituted acrylate compounds catalyzed by an Iridium-TsEN complex in water

Highly chemoselective transfer hydrogenation of the CC bonds of α-keto substituted acrylate compounds catalyzed by an [IrCl2Cp*]2-TsEN Complex (Cp* = η5-C5Me5) in water using sodium formate as hydride source has been developed. A variety of α-keto substituted acrylate compounds were reduced smoothly under 0.5 mol% of Iridium catalyst with 1.0 mol% ligand TsEN and 3 equiv. of sodium formate providing the desired product α-alkyl-β-keto esters in high to excellent yields (80–99 %). The procedure presented is simple and makes this method suitable for practical use.

Nickel-Catalyzed Chemo- and Enantioselective Hydrogenation and Deuteration of α,β-Unsaturated Ketimines Using Alcohols: Synthesis of Deuterated Chiral Allylic Amines.

A nickel-catalyzed chemoselective asymmetric transfer hydrogenation of α,β-unsaturated ketimines using ethanol as a hydrogen donor under mild conditions that avoid using high-pressure hydrogen gas was developed. With this catalyst, C1-selective deuterated chiral allylic amines were efficiently synthesized using only stoichiometric 2-propanol-d8. Mechanism studies demonstrated the formation of a nickel hydride intermediate.

Manganese(I)-Catalyzed Chemoselective Transfer Hydrogenation of the C=C Bond in Conjugated Ketones at Room Temperature.

Chemoselective transfer hydrogenation of C=C bond in α,β-unsaturated ketones is demonstrated at room temperature employing a manganese(I) catalyst and half an equivalent of ammonia-borane (H3 N-BH3 ). A series of mixed-donor pincer-ligated Mn(II) complexes, (tBu2 PN3 NPyz )MnX2 [κP ,κN ,κN -(N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine)MnX2 ] {X=Cl (Mn2), X=Br (Mn3), X=I (Mn4)} were synthesized and characterized. Amongst the Mn(II) complexes, (Mn2, Mn3, Mn4) and Mn(I) complex, (tBu2 PN3 NPyz )Mn(CO)2 Br (Mn1) screened; the Mn1 acts as an efficient catalyst for the chemoselective C=C bond reduction in α,β-unsaturated ketones. Various synthetically important functionalities like halides, methoxy, trifluoromethyl, benzyloxy, nitro, amine, and unconjugated alkene and alkyne groups, including heteroarenes, were compatible and provided saturated ketones in excellent yields (up to 97 %). A preliminary mechanistic study highlighted the crucial role of metal-ligand (M-L) cooperation through the dearomatization-aromatization process in catalyst Mn1 for the chemoselective C=C bond transfer hydrogenation.

Highly selective catalytic transfer hydrodeuteration of cyclic alkenes.

Selective deuterium installation into small molecules is becoming increasingly desirable not only for the elucidation of mechanistic pathways and studying biological processes but also because of deuterium's ability to favorably adjust the pharmacokinetic parameters of bioactive molecules. Fused bicyclic moieties, especially those containing heteroatoms, are prevalent in drug discovery and pharmaceuticals. Herein, we report a copper-catalyzed transfer hydrodeuteration of cyclic and heterocyclic alkenes, which enables the synthesis of chromans, quinolinones, and tetrahydronaphthalenes that are precisely deuterated at the benzylic position. We also demonstrate the ability to place one deuterium atom at the homobenzylic site of these scaffolds with high regioselectivity by swapping transfer reagents for their isotopic analogs. Furthermore, examples of chemoselective transfer hydrogenation and transfer deuteration are disclosed, allowing for the simultaneous incorporation of two vicinal hydrogen or deuterium atoms into a double bond.

Utilization of methanol for condensation interrupted chemoselective transfer hydrogenation of CC, CO, and CN bonds under low catalyst loading

Selective transfer hydrogenation (TH) of unsaturated molecules using methanol is challenging as the in situ generated formaldehyde is prone to react with the active methylene (C-methylation) or amine (N-methylation) core of the desired product.

Homogenous nickel-catalyzed chemoselective transfer hydrogenation of functionalized nitroarenes with ammonia-borane.

Homogeneous Ni-catalyzed highly selective transfer hydrogenation of nitroarenes was successfully established using NH3BH3as a hydrogen source. A broad range of functional groups were selectively reduced to provide the corresponding anilines in good to high yields. Further, pharmaceutically active compounds can be prepared that would otherwise be challenging to access.

Catalyst-Free Transfer Hydrogenation of Activated Alkenes Exploiting Isopropanol as the Sole and Traceless Reductant.

Both metal-catalyzed and organocatalytic transfer hydrogenation reactions are widely employed for the reduction of C=O and C=N bonds. However, selective transfer hydrogenation reactions of C=C bonds remain challenging. Therefore, the chemoselective transfer hydrogenation of olefins under mild conditions and in the absence of metal catalysts, using readily available and inexpensive reducing agents (i.e. primary and secondary alcohols), will mark a significant advancement towards the development of green transfer hydrogenation strategies. Described herein is an unconventional catalyst-free transfer hydrogenation reaction of activated alkenes using isopropanol as an eco-friendly reductant and solvent. The reaction gives convenient synthetic access to a wide range of substituted malonic acid half oxyesters (SMAHOs) in moderate to good yields. Mechanistic investigations point towards an unprecedented hydrogen bond-assisted transfer hydrogenation process.

Umpolung Reactivity of Imine Ester: Visible-Light Mediated Transfer Hydrogenation of α-Aryl Imino Esters by Phenylsilane and Water.

A visible-light mediated chemoselective transfer hydrogenation of α-aryl imino esters was demonstrated. The methodology allowed the efficient and practical preparation of α-amino acid esters. The mechanism of the reaction was probed by DFT calculations, and deuteration experiments indicated deuterium was introduced into amino acid esters efficiently (up to 99 % D ratio), enabling a feasible way to obtain deuterated amino acids using D2 O as a cheap deuterium source.

Chemoselective Transfer Hydrogenation of Enamides Using Ru Pincer Complexes for the Synthesis of α-Amino Acids.

The chemoselective reduction of enamides to α-amino acids with iPrOH and EtOH as H-donors and solvents catalyzed by Ru pincer complexes is demonstrated. A range of α-amino acids is synthesized in good to excellent yields. Applications, large scale, and a one-pot experiment are also reported. Finally, deuterium-labeling experiments show high regioselectivity between the α- and β-positions of the alkene unit.

Iridium-catalyzed chemoselective transfer hydrogenation of α, β-unsaturated ketones to saturated ketones in water

A chemoselective iridium-catalyzed transfer hydrogenation of α, β-unsaturated ketones was realized in water. The CC double bonds of 2-benzylidene indanones and analogues were hydrogenated exclusively catalyzed by an iridium complex (0.1 mol%) bearing a pyridine-imidazoline ligand, using a mixture of formic acid/triethyl amine (molar ratio: 5/2) as a hydrogen source in water. A series of 2-benzyl indanones and analogues were obtained with good functional group tolerance and good yields. The practicability of this approach is also demonstrated by a gram-scale synthesis.

Methanol as a hydrogen source: room-temperature highly-selective transfer hydrogenation of α,β-unsaturated ketones.

The described system offers an ideal, user-friendly protocol for the chemoselective homogeneous hydrogenation of α,β-unsaturated ketones at room temperature using methanol as a liquid organic hydrogen carrier. Excellent yields were achieved with an in situ-prepared phosphine-free Cp*Ir(III)/bipyridonate complex. Chemoselective reduction with other reducible functionalities and late-stage functionalization were also explored.

A hassle-free and cost-effective transfer hydrogenation strategy for the chemoselective reduction of arylnitriles to primary amines through in situ-generated nickelII dihydride intermediate in water

In this paper, we have introduced a new, simple, efficient, inexpensive, and chemoselective transfer hydrogenation strategy for the straightforward reduction of arylnitriles to corresponding primary amines using sodium borohydride (NaBH4) and nickel acetate tetrahydrate (Ni(OAc)2•4H2O) through in situ-generated nickelII dihydride intermediate in the water medium at 50 ᵒC. The presented methodology features moderate reaction conditions, nickel boride (Ni2B)-free trajectory, good-to-excellent yields of the products, relatively short reaction times, satisfactory chemoselectivity, and does not involve the use of toxic organic solvent and also any base or ligand.

Photocatalytic Chemoselective Transfer Hydrogenation of Quinolines to Tetrahydroquinolines on Hierarchical NiO/In2O3–CdS Microspheres

Photocatalytic Chemoselective Transfer Hydrogenation of Quinolines to Tetrahydroquinolines on Hierarchical NiO/In₂O₃–CdS Microspheres