C-H Activation Research Articles

Synthesis, characterization and catalytic activity of a mononuclear nonheme copper(II)-iodosylbenzene adduct

Iodosylbenzene (PhIO) and its derivatives have attracted significant attention due to their various applications in organic synthesis and biomimetic studies. For example, PhIO has been extensively used for generating high-valent metal-oxo species that have been regarded as key intermediates in diverse oxidative reactions in biological system. However, recent studies have shown that metal-iodosylbenzene adduct, known as a precursor of metal-oxo species, plays an important role in transition metal-catalyzed oxidation reactions. During last few decades, extensive investigations have been conducted on the synthesis and reactivity studies of metal-iodosylbenzene adducts with early and middle transition metals including manganese, iron, cobalt. Nevertheless, metal-iodosylbenzene adducts with late transition metals such as nickel, copper and zinc, still remains elusive. Herein, we report a novel copper(II)-iodosylbenzene adduct bearing a linear ligand composed of two pyridine rings and an ethoxyethanol side-chain, [Cu(OIPh)(HN3O2)]2+ (1). The copper(II)-iodosylbenzene adduct was characterized by several spectroscopic methods including UV–vis spectroscopy, electrospray ionization mass spectrometer (ESI MS), and electron paramagnetic resonance (EPR) combined with theoretical calculations. Interestingly, 1 can carry out the catalytic sulfoxidation reaction. In sulfoxidation reaction with thioanisole under catalytic reaction condition, not only two-electron but also four-electron oxidized products such sulfoxide and sulfone were yielded, respectively. However, 1 was not an efficient oxidant towards CH bond activation and epoxidation reactions due to the steric hindrance created by the intramolecular H-bonding interaction between HN3O2 ligand and iodosylbenzene moiety.

Radial molecular property functions of CH in its ground electronic state

Effective potential energy curves of the ground electronic states of isotopomers of the methylidyne radical CH are constructed by morphing accurate ab initio potential energy curves within the framework of Jenč’s reduced potential energy curve (RPC) approach. The morphing is performed by fitting the RPC parameters to available experimental ro-vibrational data. In turn, the resulting potential energy curves are used to determine the radial property functions describing the spin-orbit and fine and hyperfine energy patterns of the spin-ro-vibrational energy levels by morphing their ab initio approximants or by a direct fitting to experiment. The resulting functions enable reliable predicting outside prospected energy regions, and a quantitative probing of the impacts of external perturbations on the observed spectra.

Easy Access to Versatile Catalytic Systems for C-H Activation and Reductive Amination Based on Tetrahydrofluorenyl Rhodium(III) Complexes.

On the basis of the 1,2,3,4-tetrahydrofluorenyl ligand, a simple approach was developed to new effective rhodium catalysts for the construction of C-C and C-N bonds. The halide compounds [(η5 -tetrahydrofluorenyl)RhX2 ]2 (2 a: X=Br; 2 b: X=I) were synthesized by treatment of the bis(ethylene) derivative (η5 -tetrahydrofluorenyl)Rh(C2 H4 )2 (1 a) with halogens. An analogous reaction of the cyclooctadiene complex (η5 -tetrahydrofluorenyl)Rh(cod) (1 b) with I2 is complicated by the side formation of [(cod)RhI]2 . The reaction of 2 b with 2,2'-bipyridyl leads to cation [(η5 -tetrahydrofluorenyl)Rh(2,2'-bipyridyl)I]+ (3). The halide abstraction from 2 a,b with thallium or silver salts allowed us to prepare sandwich compounds with incoming cyclopentadienyl, dicarbollide and mesityleneligands [(η5 -tetrahydrofluorenyl)RhCp]+ (4), (η5 -tetrahydrofluorenyl)Rh(η-7,8-C2 B9 H11 ) (5), and [(η5 -tetrahydrofluorenyl)Rh(η-mesitylene)]2+ (6). The structures of 1 b, 2 b ⋅ 2I2 , 3PF6 , 4TlI4 , 5, and [(cod)RhI]2 were determined by X-ray diffraction. Compounds 2 a,b efficiently catalyze the oxidative coupling of benzoic acids with alkynes to selectively give isocoumarins or naphthalenes, depending on the reaction temperature. Moreover, they showed moderate catalytic activity in other annulations of alkynes with aromatic compounds (such as benzamide, acetanilide, etc.) which proceed through CH activation. Compound 2 b also effectively catalyzes the reductive amination of aldehydes and ketones in the presence of carbon monoxide and water via water-gas shift reaction, giving amines in high yields (67-99 %).

C–H activation

C–H activation

C–H activation

C–H activation

Unsymmetrical Naphthyridine-Based Dicopper(I) Complexes: Synthesis, Stability, and Carbon–Hydrogen Bond Activations

Unsymmetrical Naphthyridine-Based Dicopper(I) Complexes: Synthesis, Stability, and Carbon–Hydrogen Bond Activations

DNA-encoded C[sbnd]H functionality via photoredox-mediated hydrogen atom transformation catalysis

We described a mode of catalytic activation that accomplished the α-alkylation of N-Boc saturated heterocycles with DNA-linked acrylamide via photoredox-mediated hydrogen atom transfer (HAT) catalysis. This C(sp3)-C(sp3) bond formation reaction tolerated five-, six- and seven-membered cyclic substrates, substantially streamline synthetic efforts to functionalize the α-position of heterocycles with native CH functional handle. This photoredox catalyzed CH functionalization proceeded in mild DNA-compatible condition, and suited for the construction of DNA-encoded libraries.

A radical approach for the selective C-H borylation of azines.

Boron functional groups are often introduced in place of aromatic carbon-hydrogen bonds to expedite small-molecule diversification through coupling of molecular fragments1-3. Current approaches based on transition-metal-catalysed activation of carbon-hydrogen bonds are effective for the borylation of many (hetero)aromatic derivatives4,5 but show narrow applicability to azines (nitrogen-containing aromatic heterocycles), which are key components of many pharmaceutical and agrochemical products6. Here we report an azine borylation strategy using stable and inexpensive amine-borane7 reagents. Photocatalysis converts these low-molecular-weight materials into highly reactive boryl radicals8 that undergo efficient addition to azine building blocks. This reactivity provides a mechanistically alternative tactic for sp2 carbon-boron bond assembly, where the elementary steps of transition-metal-mediated carbon-hydrogen bond activation and reductive elimination from azine-organometallic intermediates are replaced by a direct, Minisci9-style, radical addition. The strongly nucleophilic character of the amine-boryl radicals enables predictable and site-selective carbon-boron bond formation by targeting the azine's most activated position, including the challenging sites adjacent to the basic nitrogen atom. This approach enables access to aromatic sites that elude current strategies based on carbon-hydrogen bond activation, and has led to borylated materials that would otherwise be difficult to prepare. We have applied this process to the introduction of amine-borane functionalities to complex and industrially relevant products. The diversification of the borylated azine products by mainstream cross-coupling technologies establishes aromatic amino-boranes as a powerful class of building blocks for chemical synthesis.

The evolution of intra- and inter-molecular isotope equilibria in natural gases with thermal maturation

Naturally occurring hydrocarbon fluids in sedimentary basins have economic, geological and environmental significance. Connecting sedimentary basin temperature-time evolution with petroleum generation and transformation is a long-studied problem. In this study, we investigate the use of a novel tool – multiply substituted isotopologues of methane, for distinguishing between different chemical mechanisms in catagenesis and for characterizing the extent of thermal maturation of thermogenic natural gases. We analyze the stable isotope compositions of a suite of thermogenic gas samples that are globally distributed and cover a wide range in composition and thermal maturation, from dominantly unconventional shale gas formations and a few conventional gas plays. Our data show that methane generated at early thermal maturity has a stable isotope composition governed by chemical kinetics, characterized by a pronounced deficit in Δ12CH2D2; this signature can be explained by its formation chemistry that combines a more D-rich methyl radical pool and more D-poor H radical pool. Methane from higher thermal maturity fluids increases in Δ12CH2D2, reaching equilibrium at vitrinite reflectance maturity (Ro) of approximately 1.5% (equivalent to 170–210 °C peak burial temperature) and higher, which is interpreted to be the result of isotope exchange erasing the disequilibrium signature of catagenetic chemistry, mediated by CH activation during either radical chain reactions or organic-inorganic interactions on mineral surfaces. We further examined hydrogen isotope fractionations among methane, ethane and propane for a compiled global dataset and found that the intermolecular fractionation exhibits a trend similar to that seen for the Δ12CH2D2 value of methane, departing from equilibrium at low thermal maturities and moving towards equilibrium as maturity increases. These findings indicate that the inter- and intra-molecular hydrogen isotope structures of components of thermogenic natural gas transition from chemical-kinetic control at low thermal maturities toward thermodynamic control at higher thermal maturities, mediated by hydrogen exchange reactions. We propose that these systematic relationships could be used to identify the exact thermal maturation stages for natural gases and their associated fluids, especially for oil-associated gas at early maturation.

Revisited the mechanism of cobalt(III) catalyzed cyanation of arenes and heteroarenes: A DFT study

Transition metal catalyzed cyanation of arenes and heteroarenes by CH activation is an attractive process for functionalization of aromatic system. One such reaction under the catalysis of cobalt complex using N-cyano-N-phenyl-p-toluenesulfonamide as a cyanating reagent was studied theoretically. Metal mediated cyanation of aromatic ring involving one and more acetic acid have been explored. Our finding reveals that during the metal mediated activation of CH bond, presence of two acetic acid, increase the activation energy of the proton abstraction step. Comparison of the energy profile diagrams for single and double acetic acid mediated steps shows that the pathway, assisted by single acetic acid, is energetically more favorable. The calculated apparent activation barrier of the reaction is also consistent with the experimental report and it also shows high temperature (120 °C) has been needed to carry out the reaction.

Di-ortho-C[sbnd]H arylation of phenylalanine: A bimetallic interaction between Pd(IV)-Ag(I)

The direct di-ortho-arylation of substituted phenylalanines has been accomplished via methoxyiminoacyl (MIA)-mediated Pd-catalyzed CH functionalization. A diverse array of phenylalanine substrates is amenable to this protocol, providing di-ortho-arylated phenylalanine derivatives with good to high efficiency. Computational results revealed that a bimetallic interaction between Pd(IV)-Ag(I) was formed through the localized orbital, which obviously favored the reductive elimination step of the arylation process.

Functionalization of RhIII–Me Bonds: Use of “Capping Arene” Ligands to Facilitate Me–X Reductive Elimination

We show how to improve the yield of MeX from CH4 activation catalysts from 12% to 90% through the use of “capping arene” ligands. Four (FP)RhIII(Me)(TFA)2 {FP = “capping arene” ligands, including 8,8′-(1,2-phenylene)diquinoline (6-FP), 8,8′-(1,2-naphthalene)diquinoline (6-NPFP), 1,2-bis(N-7-azaindolyl)benzene (5-FP), and 1,2-bis(N-7-azaindolyl)naphthalene (5-NPFP)} complexes. These complexes and (dpe)RhIII(Me)(TFA)2 (dpe = 1,2-di-2-pyridylethane) were synthesized and tested for their performance in reductive elimination of MeX (X = TFA or halide). The FP ligands were used with the goal of blocking a coordination site to destabilize the RhIII complexes and facilitate MeX reductive elimination. On the basis of single-crystal X-ray diffraction studies, the 6-FP and 6-NPFP ligated Rh complexes have Rh–arene distances shorter than those of the 5-FP and 5-NPFP Rh complexes; thus, it is expected that the Rh–arene interactions are weaker for the 5-FP complexes than for the 6-FP complexes. Consistent with our hypothesis, the 5-FP and 5-NPFP RhIII complexes demonstrate improved performance (from 12% to ∼60% yield) in the reductive elimination of MeX. The reductive elimination of MeX from (FP)RhIII(Me)(TFA)2 can be further improved by the use of chemical oxidants. For example, the addition of 2 equiv of AgOTf leads to 87(2)% yield of MeTFA and can be achieved in CD3CN at 90 °C using (5-FP)Rh(Me)(TFA)2.

Highly basic alkyl-substituted bis(benzhydryl) CaII and YbII complexes with β-CH–M agostic interactions

The reaction between potassium derivative {[(4-ButC6H4)2CH]−K+}n and alkyl iodides gives new 1,1-bis(4-tert-butylphenyl)alkanes which can be deprotonated with BunNa to produce species [(4-ButC6H4)2CR]−Na+ (R = Me, Bui). The salt metathesis of the latter with base-free CaI2 or YbI2 affords novel bis(hydrocarbyl) complexes [(4-ButC6H4)2CR]2M(TMEDA) (M = Ca, R = Me; M = Yb, R = Bui). The hyperconjugation of the central carbanion with alkyl groups pronouncedly enhances the basic properties of the compounds which would perform CH bond activation in toluene and thiophene, in distinction to the related ‘nonalkylated’ analogues with (4-ButC6H4)2CH− ligand.

Highly basic alkyl-substituted bis(benzhydryl) CaII and YbII complexes with β-CH–M agostic interactions

The reaction between potassium derivative {[(4-Bu t C 6 H 4 ) 2 CH] − K + } n and alkyl iodides gives new 1,1-bis(4- tert -butylphenyl)alkanes which can be deprotonated with Bu n Na to produce species [(4-Bu t C 6 H 4 ) 2 CR] − Na + (R = Me, Bu i ). The salt metathesis of the latter with base-free CaI 2 or YbI 2 affords novel bis(hydrocarbyl) complexes [(4-Bu t C 6 H 4 ) 2 CR] 2 M(TMEDA) (M = Ca, R = Me; M = Yb, R = Bu i ). The hyperconjugation of the central carbanion with alkyl groups pronouncedly enhances the basic properties of the compounds which would perform CH bond activation in toluene and thiophene, in distinction to the related ‘nonalkylated’ analogues with (4-Bu t C 6 H 4 ) 2 CH − ligand.

Elucidation of the Active Phase in Pd‐Based Catalysts Supporting on Octahedral CeO2 for Low‐Temperature Methane Oxidation

AbstractPd catalysts supported on CeO2 (Pd/CeO2) are highly active towards lean methane combustion, and the catalytic behavior is substantially affected by the chemical property of surface palladium species. In this work, various Pd catalysts supported on octahedral‐CeO2 (Pd/O‐CeO2) were successfully prepared by redox interation‐engaged strategy. The oxidation state of palladium species was controlled by varying the calcination condition. X‐ray absorption characterization coupled with light‐off curves confirmed that the catalytic activity of relevant catalysts was closely related with the proportion of the metallic Pd and PdO species. Within limits, increasing Pd0/PdO ratio can bring superior catalytic behavior and the approximately equal ratio of interfacial hybrid Pd0/PdO phase exhibits the optimal catalytic activity. Importantly, in situ DRIFTS results demonstrated that the hybrid Pd0/PdO phase was recognized as the active site pair for lean methane oxidation, which is attributed to the fact that the metallic Pd0 species can adsorb and dissociate methane molecules and then the resulting intermediate species further react with the active O* of PdO, which thereby promotes CH4 activation.

Ruthenium(II)- and Palladium(II)-catalyzed position-divergent C[sbnd]H oxygenations of arylated quinones: Identification of hydroxylated quinonoid compounds with potent trypanocidal activity

A diversity-oriented synthesis of hydroxylated aryl-quinones via CH oxygenation reactions and their evaluation against Trypanosoma cruzi, the etiological agent of Chagas disease, was accomplished. With the use of ruthenium(II)- or palladium(II)-based catalysts, complementary regioselectivities were observed in the hydroxylation reactions and we have identified 9 compounds more potent than benznidazole (Bz) among these novel arylated and hydroxylated quinones. For instance, 5-hydroxy-2-[4-(trifluoromethyl)phenyl]-1,4-naphthoquinone (4h) with an IC50/24 h value of 22.8 µM is 4.5-fold more active than the state-of-the-art drug Bz. This article provides the first example of the application of CH activation for the position-selective hydroxylation of arylated quinones and the identification of these compounds as trypanocidal drug candidates.

Transition-metal complexes bearing chelating NHC Ligands. Catalytic activity in cross coupling reactions via C[sbnd]H activation

In recent years, the direct functionalization of CH bonds has become an important tool for CC or C–heteroatom cross-coupling reactions. In these reactions, homogeneous catalysts based on transition metals have demonstrated good selectivity for direct CH activation. This process is not only simple but easily leads to molecules and products of high added value through greener and more energy efficient processes. In this context, metallacyclic complexes have been very successful in CH functionalization reactions, especially with the use of transition metal compounds bearing at least one N-heterocyclic carbene (NHC). Thus, herein we highlight some of the most recent advances on the catalytic CC or C–heteroatom (B, N and O) bond formation via CH activation, using metallacyclic transition metal NHC complexes.

Cu-decorated cellulose through a three-component Betti reaction: An efficient catalytic system for the synthesis of 1,3,4-oxadiazoles via imine C[sbnd]H functionalization of N-acylhydrazones

Materials functionalization through multicomponent reactions (MCRs) has recently attracted great attention due to the generation of outstanding features in materials. Herein, an efficient novel heterogeneous catalytic system was designed and synthesized via the MCRs functionalization of the most abundant biopolymer in nature, cellulose. In this regard, cellulose was oxidized using periodate as an oxidant agent, and then the resulted carbonyl functional groups participated in the three-component Betti reaction. The ICP-OES analysis was revealed that the functionalization of cellulose via this three-component reaction effectively improved the complexing ability of functionalized cellulose with Cu(II). The synthesized biocatalyst was characterized by FT-IR, 1H NMR, XRD, SEM, EDS, ICP, and TGA techniques. The efficiency of the designed biocatalyst was investigated in the CH functionalization reaction of N-acylhydrazones to synthesize 1,3,4-oxadiazoles. This biocatalyst’s outstanding advantages are high yields, non‐hazardous catalyst, mild reaction conditions, operational simplicity, and reusability.

The effect of oxygen vacancies on the coordinatively unsaturated Al-O acid-base pairs for propane dehydrogenation

Recently, the coordinatively unsaturated metal-O Lewis acid-base pairs of metal oxides are found to be able to activate the C–H bond of light alkane efficiently. For the inert crystal Al2O3, we found that the surface oxygen vacancy amount of Al2O3 can be controlled by pretreatment of CO reduction, and the nearby coordinatively unsaturated Al-O (Alcu-O) pairs can effectively catalyze propane dehydrogenation (PDH). The C3H6 formation rate of γ/δ-Al2O3 is in line with the concentration of oxygen vacancies. The experiments and DFT calculations illuminate the importance of oxygen vacancy on the surface of Al2O3 for PDH reaction. The consumption of lattice oxygen reduces the one coordination number of the bonding Al, the formed Alcu-O as defective acid-base pairs, can be an effective way to tune the adsorption energy of the intermediates and the barriers of key steps (the first CH activation and H2 formation) to enhance the performance of PDH through both site-dependent concerted and stepwise mechanisms.

Rhodium(III)-catalyzed regioselective C[sbnd]H nitrosation/annulation of unsymmetrical azobenzenes to synthesize benzotriazole N-oxides via a RhIII/RhIII redox-neutral pathway

A Rh(III)-catalyzed regioselective CH nitrosation/annulation reaction of unsymmetrical azobenzenes with [NO][BF4] has been developed to achieve high-yielding syntheses of benzotriazole N-oxides with excellent functional group tolerance. Computational studies have revealed that this oxidative CH functionalization reaction involves an interesting redox-neutral Rh(III)/Rh(III) pathway without the change of Rh oxidation state.