Nickel-catalyzed Hydrogenation Research Articles

Regio- and enantioselective hydrofluorination of internal alkenes via nickel-catalyzed hydrogen atom transfer

Regio- and enantioselective hydrofluorination of internal alkenes via nickel-catalyzed hydrogen atom transfer

Selective Hydrofunctionalization of Alkenyl Fluorides Enabled by Nickel-Catalyzed Hydrogen Atoms and Group Transfer: Reaction Development and Mechanistic Study.

Due to the unique effect of fluorine atoms, the efficient construction of high-value alkyl fluorides has attracted significant interest in modern drug development. However, enantioselective catalytic strategies for the efficient assembly of highly functionalized chiral C(sp3)-F scaffolds from simple starting materials have been underutilized. Herein, we demonstrate a nickel-catalyzed radical transfer strategy for the efficient, modular, asymmetric hydrogenation and hydroalkylation of alkenyl fluorides with primary, secondary, and tertiary alkyl halides under mild conditions. The transformation provides facile access to various structurally complex secondary and tertiary α-fluoro amide products from readily available starting materials with excellent substrate compatibility and distinct selectivity. Furthermore, the utility of this method is demonstrated by late-stage modifications and product derivatizations. Detailed mechanistic studies and DFT calculations have been conducted, showing that the rate-determining step for asymmetric hydrogenation reaction is NiH-HAT toward alkenyl fluorides and the stereo-determining step is alcohol coordination to Ni-enolates followed by a barrierless protonation. The mechanism for the asymmetric hydroalkylation reaction is also delivered in this investigation.

Electrochemical Nickel-Catalyzed Hydrogenation.

Olefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal-catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal-hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well-established HER. Using an inexpensive and bench-stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large-scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre-coordination of the substrate to the nickel center.

Nickel-catalyzed regioselective hydrogen isotope exchange accelerated by 2-pyridones.

A nickel-catalyzed hydrogen isotope exchange has been developed with acetone-d6 as the deuterium source. The reaction showed an improved kinetic feature of H/D exchange under the assistance of 2-pyridones, efficiently affording regioselective labeled aryl and alkyl carboxamides.

Optimized Synthesis of a Key Intermediate of Nirmatrelvir

In this study, the development of a concise alternative process for synthesis of a key nirmatrelvir intermediate cyclic glutamine analog is described. The process proceedes via α-cyanomethylation of dimethyl N-BocGlu in the presence of NdCl3, followed by one-pot Raney nickel-catalyzed hydrogenation of the cyano group with concomitant cyclization and ammonolysis and subsequent deprotection of N-Boc to deliver the target intermediate cyclic glutamine analog in three steps with an 82% overall yield and 99.4 A% high-performance liquid chromatography (HPLC) purity. This study resulted in improved synthetic efficiency and stereoselectivity of α-cyanomethylation for production of a key nirmatrelvir intermediate cyclic glutamine analog.

Nickel-Catalyzed Hydrocarboxylation and Enantioselective Transfer Hydrogenation of Alkynes

Nickel-Catalyzed Hydrocarboxylation and Enantioselective Transfer Hydrogenation of Alkynes

Recent advances in nickel-catalyzed C-C and C-N bond formation via HA and ADC reactions.

In recent times, earth-abundant 3d-transition-metal catalysts have attracted much attention in contemporary catalysis. They have been widely employed as suitable alternatives to their counterparts noble metals. In particular, nickel catalysts provide distinctive redox properties; thus, their efficiency in sustainable organic transformations is manifold. In this review article, recent advances in nickel-catalyzed hydrogen auto-transfer (HA) and acceptorless dehydrogenative coupling (ADC) reactions for the construction of C-C and C-N bonds have been discussed.

Nickel-Catalyzed Hydrogenation to Form α-Amino Acid Derivatives

Nickel-Catalyzed Hydrogenation to Form α-Amino Acid Derivatives

Site-Selective Nickel-Catalyzed Hydrogen Isotope Exchange in N-Heterocycles and Its Application to the Tritiation of Pharmaceuticals

A nickel-catalyzed method for the site-selective hydrogen isotope exchange (HIE) of C(sp2)–H bonds in nitrogen heteroarenes is described and applied to the tritiation of pharmaceuticals. The α-diim...

Synthesis of Lactones and Lactams by Nickel-Catalyzed Transfer Hydrogenation

Synthesis of Lactones and Lactams by Nickel-Catalyzed Transfer Hydrogenation

Air-Stable α-Diimine Nickel Precatalysts for the Hydrogenation of Hindered, Unactivated Alkenes

Treatment of a mixture of air-stable nickel(II) bis(octanoate), Ni(O2CC7H15)2, and α-diimine ligand, iPrDI or CyADI (iPrDI = [2,6-iPr2–C6H3N═C(CH3)]2, CyADI = [C6H11N═C(CH3)]2) with pinacolborane (HBPin) generated a highly active catalyst for the hydrogenation of hindered, essentially unfunctionalized alkenes. A range of tri- and tetrasubstituted alkenes was hydrogenated and a benchtop procedure for the hydrogenation of 1-phenyl-1-cyclohexene on a multigram scale was demonstrated and represents an advance in catalyst activity and scope for the nickel-catalyzed hydrogenation of this challenging class of alkenes. Deuteration of 1,2-dimethylindene with the in situ-generated nickel catalyst with iPrDI exclusively furnished the 1,2-syn-d2-dimethylindane. With cyclic trisubstituted alkenes, such as 1-methyl-indene and methylcyclohexene, deuteration with the in situ generated nickel catalyst under 4 atm of D2 produced multiple deuterated isotopologues of the alkanes, signaling chain running processes that are co...

Exploring the Reactivity of Nickel Pincer Complexes in the Decomposition of Formic Acid to CO2/H2 and the Hydrogenation of NaHCO3 to HCOONa

AbstractThe nickel‐catalyzed decomposition of formic acid to yield molecular hydrogen and the nickel‐catalyzed hydrogenation of bicarbonate as a carbon dioxide mimic have been examined. Well‐defined nickel complexes modified by a PCP‐pincer ligand, especially nickel hydride and nickel formate complexes, revealed catalytic activity with turnover numbers of up to 626 (decomposition) and 3000 (hydrogenation). Thus, a formal hydrogen storage and release cycle performed by a well‐defined nickel catalyst was accomplished.

Raney Nickel–Catalyzed Hydrogenation of Unsaturated Carboxylic Acids with Sodium Borohydride in Water

A mild, selective, and green method for the reduction of unsaturated carboxylic acids with sodium borohydride–Raney nickel (W6) system in water is reported. This method is practical and safe and avoids use of organic solvents.

Convenient and Scalable Process for the Preparation of Indole via Raney Nickel–Catalyzed Hydrogenation and Ring Closure

An efficient and practical method for the synthesis of indole as a key starting material for many useful chemicals is described. Using 2-nitrotoluene as starting material, hydroxymethylation with formaldehyde under alkaline conditions gave 2-(2-nitrophenyl)ethanol on a large scale. Raney Ni catalyst was used for both reduction of the nitro group as well as for the indole formation. The overall yield was 78% from 2-nitrotoluene.

Impact of nitrogen doping of carbon nanospheres on the nickel-catalyzed hydrogenation of butyronitrile

Three nickel catalysts supported on carbon and nitrogen-doped carbon nanospheres have been prepared by deposition-precipitation (DP) with urea (ca. 2% w/w). The nanospheres were prepared by thermal pyrolysis of benzene (CNS B), aniline (CNS A) and nitrobenzene (CNS N) and characterized by transmission electron microscopy (TEM), N 2 adsorption–desorption, temperature-programmed oxidation (TPO), X-ray diffraction (XRD), elemental (CHN) analysis, X-ray photoelectron spectroscopy (XPS), temperature-programmed decomposition (TPD) and acid/base titrations, revealing different graphitic characteristics and different distribution of nitrogen (when present) functionalities. Upon Ni introduction, the catalysts were characterized by temperature-programmed reduction (TPR), XRD and TEM. Surface area weighted mean Ni particle diameters (post activation at 603 K) were in the range 10.5–18.2 nm. Ni particle size exhibited a big dependence on CNS nitrogen doping, where nitrogen introduction, essentially in the quaternary form, enhanced metal sintering by enriching the surface electron density of the support. The catalysts were tested in the gas phase hydrogenation of butyronitrile ( T = 493 K). Extracted specific reaction rates in the steady state followed the sequence: Ni/CNS B < Ni/CNS A < Ni/CNS N. When the active metal was physically mixed with the support, the following sequence was obtained: Ni + CNS B < Ni + CNS A < Ni + CNS N. Our results demonstrate that doping carbon nanospheres with nitrogen strongly impacts on reactant adsorption and metal sintering, both critical aspects in the hydrogenation of nitriles. Selectivity was not sensitive to the support (or the physical mixture) employed and was in all cases close to 100% to the primary amine.

Ames test evaluation of two commercially available zero-valent nickel compounds

Zero-valent nickel compounds are organometallic chemicals that are used in synthetic applications and may also occur as intermediates in nickel-catalyzed hydrogenation reactions used in food processing. Few studies have been performed on their possible genotoxic actions. We have tested two commercially available examples of this class of compounds. Solubility and stability were examined. Mutagenicity testing did not confirm a previous report that bis(1,5-cyclooctadiene)nickel is positive in the Ames assay. No stimulation of lipid peroxidation was observed in studies of bovine erythrocytes exposed in vitro. Our results do not indicate that zero-valent nickel compounds have genotoxic effects.

Direct synthesis of nitrogen-containing filamentous carbon on a high-percentage Ni-Cu catalyst

Nitrogen-containing catalytic filamentous carbon (N-CFC) of chemical composition NC18-NC104 has been synthesized by the decomposition of pyridine (Py) from gaseous mixtures with argon or H2 at 550–800°C on Ni/Al2O3 (Ni) and Ni-Cu/Al2O3 (Ni-Cu) high-percentage catalysts. The activity of the Ni-Cu catalyst in Py decomposition in mixtures with H2 is about one order of magnitude higher than its activity in Py/Ar mixtures (more than 70 g N-CFC per metal gram in 4.5 h at 750°C), which is interpreted as arising from the nickel-catalyzed hydrogenation of Py. The formation and growth of carbon fibers occurs through the decomposition of Py (from Ar/Py mixtures) and/or Py hydrodenitrification products (from H2/Py mixtures). The carbon material has been characterized by elemental analysis, low-temperature nitrogen adsorption, high-resolution transmission electron microscopy (HRTEM), and X-ray photoelectron spectroscopy (XPS). The effect of the noncatalytic reactions of Py and its transformation products on the composition and texture of N-CFC is discussed.

Reduction of substituted spiro[cyclopropane-3-(1-pyrazolines)] to spiro[cyclopropane-3-pyrazolidines] and 1-(2-aminoethyl)cyclopropylamine derivatives

Raney nickel-catalyzed hydrogenation of 5-substituted spiro[cyclopropane-3-(1-pyrazoline)]-5-carboxylates occurs with N—N bond cleavage with simultaneous cyclocondensation to give 3-aminopyrrolidin-2-ones containing a spirocyclopropane fragment. The presence of the second ester group in the pyrazoline side chain, in the position ensuring the formation of a five-membered ring results in 6,11-diazadispiro[2.1.4.2]undecane-7,10-dione, the product of double cyclocondensation of the intermediate diamine. Hydrogenation of the aryl-substituted spiro[cyclopropane-3-(1-pyrazolines)] in the presence of acetone affords hexahydrospiro[cyclopropane-4-pyrimidines], which can be converted into the cyclopropane-containing 1,3-diamines in the individual state or as salts.

Kinetics of the hydrogenation of 1-octene catalyzed by [Ni( o-MeO-dppp)(OAc) 2

The kinetics of the nickel-catalyzed hydrogenation of 1-octene have been studied using nickel(II) acetate in combination with the ligand 1,3-bis(di( o-methoxyphenyl)phosphanyl)propane ( o-MeO-dppp). The effects of temperature and dihydrogen pressure, as well as the influence of the nickel and substrate concentrations have been studied ( T=30–60°C, p(H 2)=30–60 bar, [Ni]=0.35–2.81 mM, [1-octene]=0.98–3.91 M, ligand/Ni=1.1 in a mixture of dichloromethane and methanol). The kinetic study results in the surprisingly simple rate law r= k cat[Ni][1-octene] p(H 2). The kinetic data are consistent with a mechanism in which the terminating hydrogenolysis step of the nickel–alkyl complex is the rate-determining step of the catalytic cycle with all preceding steps at equilibrium. The first-order dependence on the substrate is confirmed by the results with other substrates, as the hydrogenation rate strongly depends on the nature of the substrate.

Supported Nickel-Catalyzed Hydrogenation of Aromatic Nitriles under Low Pressure Conditions

Hydrogenation of aromatic nitriles takes place under the mild conditions using supported nickel catalysts to afford aminomethyl-substituted aromatics in good yields.