Bond Cleavage Step Research Articles

Post-Synthetic Modification of Calix[4]arene Framework by Iridium-Mediated Alkyne Insertion into an Inert C-C Bond: A Novel Strategy for Unsymmetrical Macrocycles.

As a novel synthetic method for unsymmetrical macrocycles, we herein developed a post-synthetic modification of calix[4]arenes by insertion of a terminal alkyne into an inert C(methylene)-C(aryl) bond of the macrocyclic framework. In this transformation, C-iridated calix[4]arenes, readily synthesized through C-H bond activation of the parent calix[4]arene, undergoes C(methylene)-C(aryl) bond cleavage followed by insertion of an alkyne to provide a ring-expanded calix[4]arene complex. Removal of the iridium metal from the resulting complex was readily accomplished by a simple treatment with an acid. The developed sequential method affords novel unsymmetrical, monofunctionalized macrocyclic compounds via 3 steps from the parent calix[4]arene in good yield. The unique unsymmetrical structures of the alkyne-inserted macrocycles were evaluated by X-ray single crystal analyses. On the basis of theoretical calculations, we propose a reaction mechanism involving an uncommon C-C bond cleavage step through δ-carbon elimination for the ring enlargement process.

Mechanistic Insights into the Direct Deoxygenation of Phenolic Compounds over Novel Heusler Alloy Catalysts.

The catalytic deoxygenation of phenolic compounds is a crucial step in the valorization of biomass resources, which can effectively enhance the heating value and stability of primary biofuel. In this study, the catalytic mechanism of four Heusler alloy catalysts for the direct deoxidation pathway of phenol was studied through electronic structure regulation by element occupation. We found that Heusler alloys catalysts exhibit excellent catalytic activity in the dissociation activation of H2 and the cleavage of aryl hydroxyl bond (CAr-OH) bonds. The energy barriers for the direct cleavage of the CAr-OH bond in phenol on Ni2MoAl, Co2MoAl, Ni2NbAl and Ni2MoGa catalysts are 0.86, 0.95, 1.09, and 1.28 eV, respectively. And Y element of the X2YZ catalyst has a significant impact on this reaction, while the X element has a complex influence on the hydrogenation step of the unsaturated benzene ring. Microkinetic analysis further substantiates that the phenol (CAr-OH) bond cleavage step in the reaction exhibits a fast reaction rate and high extent of reaction. The reaction of hydroxyl hydrogenation to produce water exhibits the highest energy barrier, serving as the rate-determining step of the entire reaction. This issue could potentially be addressed by further fine-tuning the electronic structure.

Decarboxylation Mechanism of iso-Orotate Decarboxylase Revisited.

iso-Orotate decarboxylase (IDCase), which is involved in the thymidine salvage pathway, has attracted considerable interest owing to its chemical similarity to a hypothetical DNA decarboxylase in mammals. Although valuable insights into the active DNA demethylation of 5-methyl-cytosine can be obtained from the decarboxylation mechanism of 5-carboxyl-uracil (5caU) catalyzed by IDCase, this mechanism remains under debate. In this study, the catalytic mechanism of 5caU decarboxylation by IDCase was studied using hybrid quantum mechanics/molecular mechanics (QM/MM) methodologies and density functional theory (DFT) calculations with a truncated model. The calculations supported a mechanism involving three sequential stages: activation of the 5caU substrate via proton transfer from an arginine (R262') to the carboxyl group of 5caU, formation of a tetrahedral intermediate, and decarboxylation of the tetrahedral intermediate to generate uracil as the product. The reaction pathways and structures obtained using the QM/MM and DFT methods coincided with each other. These simulations provided detailed insights into the unique mechanism of IDCase, clarifying various unresolved issues, such as the critical role of R262'. In addition, aspartate D323 was found to act as a general base in the tetrahedral intermediate formation step and a general acid in the later C-C bond cleavage step.

Evaluation of Retro-Aldol vs Retro-Carbonyl-Ene Mechanistic Pathways in a Complexity-Generating C-C Bond Fragmentation.

We report an experimental and computational investigation of the likely mechanism of a cascade reaction. The reaction involves an intramolecular Diels-Alder reaction, followed by a C-C bond cleavage, to afford a complex bridged bicyclic product. As multiple reaction pathways could be envisioned for the latter step, the mechanism of the C-C bond cleavage step was investigated. Two reasonable reaction pathways were evaluated. Both computations and experiments indicate that the C-C bond cleavage step proceeds by a retro-carbonyl-ene pathway rather than a retro-aldol pathway. This report underscores the synergy between computational and experimental studies and establishes the mechanism of an interesting complexity-generating transformation.

Redox-neutral depolymerization of lignin-derived aryl ethers catalyzed by Rh(III)-complexes: a mechanistic insight.

Density functional theory (DFT) calculations at the TPSSh-D3(BJ)/def2-TZVP (SMD, water) level of theory were performed to understand the mechanism of redox-neutral depolymerization of four types of lignin-derived aryl ether dimers catalyzed by rhodium-terpyridine ([Rh]) and a binuclear Rh complex ([2Rh]). The cleavage of the Cβ-O bond in the β-O-4 model compound was initiated by the dehydrogenation of the alcohol moiety into a ketone intermediate, followed by the reductive cleavage of the ether bond, producing phenol and aromatic ketone products. The [Rh]-OH intermediate, generated by the interaction between the Rh-complex and NaOH, facilitated the transformation of the alcohol group to a CO group in the lignin model compound and subsequent H-transfer, selectively forming rhodium-H active species and the ketone intermediate. The [2Rh]-H complex exhibited high reactivity, with energy barriers for a rate-determining Cβ-O bond breakage of 35.3 kcal mol-1. In contrast to 1-phenylethan-1-ol and H2, lignin itself acted as a good hydrogen source to generate [Rh]-H species. The transformation of β-O-4 model compounds with the γ-OH group occurred via the elimination of the γ-OH group, reduction of the CC bond, and Cβ-O bond cleavage steps. However, since lignin itself was unable to supply enough hydrogen to form [Rh]-H species, the aromatic products were obtained in low yields, as observed in the experiment.

Abatement of photochemical smog precursors through complete hydrocarbon oxidation over commercial Pd catalysts under fuel-lean conditions with NO promoting effect

Currently, severe environmental issues have led to a great transition in the automotive industry from internal combustion engine vehicles to electric vehicles, but this transition will take time more than 10 years, which still requires the use of internal combustion engine vehicles. However, these vehicles emit a significant amount of hydrocarbons, in addition to nitrogen oxides (NOx), due to incomplete fuel combustion. They contribute to the formation of photochemical smog when they react with NOx in the presence of sunlight. To effectively remove these hydrocarbons from the exhaust gas of turbo-gasoline engines or diesel engines, we investigated the abatement of propane and iso-pentane, two typical hydrocarbons. In particular, we studied commercial Pd catalysts and revealed how the Pd loading and aging process simulating 4k and 100k mileage affected hydrocarbon abatement abilities, and their phases were identified using characterization technique, including CO chemisorption, X-ray diffraction (XRD), and high-resolution transmission electron microscopy (HR-TEM). We also suggested the reaction pathway for the complete oxidation of propane over Pd catalyst based on the reaction orders of propane and oxygen: Propane adsorbs on O atoms of PdO, and the kinetically relevant C–H bond cleavage step occurs by the interaction with abundant neighboring O atoms of PdO. Finally, the propane and iso-pentane abatement ability of the Pd catalyst aged for 100k mileage were evaluated under realistic exhaust gas conditions, and the effect of each gas component in the realistic exhaust gas was identified; water inhibits the catalytic reaction of hydrocarbons by occupying the active sites, whereas NO catalyzes the hydrocarbon oxidation reaction by either changing the reaction pathway or active sites under fuel-lean conditions. These findings enable us to effectively reduce environmental pollution and facilitate a smoother transition from internal combustion engine vehicles to electric vehicles.

Mechanistic Investigation of the Nickel-Catalyzed Transfer Hydrocyanation of Alkynes.

The implementation of HCN-free transfer hydrocyanation reactions on laboratory scales has recently been achieved by using HCN donor reagents under nickel- and Lewis acid co-catalysis. More recently, malononitrile-based HCN donor reagents were shown to undergo the C(sp3)-CN bond activation by the nickel catalyst in the absence of Lewis acids. However, there is a lack of detailed mechanistic understanding of the challenging C(sp3)-CN bond cleavage step. In this work, in-depth kinetic and computational studies using alkynes as substrates were used to elucidate the overall reaction mechanism of this transfer hydrocyanation, with a particular focus on the activation of the C(sp3)-CN bond to generate the active H-Ni-CN transfer hydrocyanation catalyst. Comparisons of experimentally and computationally derived 13C kinetic isotope effect data support a direct oxidative addition mechanism of the nickel catalyst into the C(sp3)-CN bond facilitated by the coordination of the second nitrile group to the nickel catalyst.

Borane-Catalyzed C-F Bond Functionalization of gem-Difluorocyclopropenes Enables the Synthesis of Orphaned Cyclopropanes.

Herein, we disclose an approach to synthesize tert-alkyl cyclopropanes by leveraging C-F bond functionalization of gem-difluorocyclopropenes using tris(pentafluorophenyl)borane catalysis. The reaction proceeds through the intermediacy of a fluorocyclopropenium ion, which was confirmed by the isolation of [Ph2(C6D5)C3]+[(C6F5)3BF]-. We found that silylketene acetal nucleophiles were optimal reaction partners with fluorocyclopropenium ion intermediates yielding fully substituted cyclopropenes functionalized with two α-tert-alkyl centers (63-93% yield). The regioselectivity of the addition to cyclopropenium ions is controlled by their steric and electronic properties and enables access to 3,3-bis(difluoromethyl)cyclopropenes in short order. The resulting cyclopropene products are readily reduced to the corresponding orphaned cyclopropanes under hydrogenation conditions. Quantum chemical calculations reveal the nature of the C-F bond cleavage steps and provide evidence for catalysis by boron and not silylated oxonium ions, though Si-F bond formation is the enthalpic driving force for the reaction.

Scope and Mechanistic Studies on the Ruthenium-Catalyzed Multicomponent Deaminative C–H Coupling Reaction of Phenols with Aldehydes and Enamines for the Formation of Xanthene and Dioxacyclic Derivatives

The in situ generated catalytic system from the tetranuclear Ru–H complex [(PCy3)(CO)RuH]4(O)(OH)2 (1) with 3,4,5,6-tetrachloro-1,2-benzoquinone (L1) has been found to mediate a multicomponent deaminative coupling reaction of phenols with aldehydes and enamines to form xanthene products. The multicomponent C–H coupling reaction of phenols with 2-hydroxybenzaldehydes and cyclic enamines efficiently installed the tricyclic 1,3-dioxacin derivatives, while the analogous coupling reaction of phenols with 2-hydroxybenzaldehydes and triethylamine selectively formed bicyclic 1,5-dioxacyclic derivatives. The density functional theory (DFT) calculations established two energetically viable mechanistic pathways for the formation of xanthene products, in which both pathways identified the C–O bond cleavage step as the turnover limiting step. A Hammett plot from the coupling reaction of 3,5-dimethoxyphenol with an enamine and para-substituted benzaldehydes p-X-C6H4CHO (X = OMe, Me, H, Cl, CF3) showed a negative slope (ρ = −0.98). The calculated energy analysis showed a similar trend (ρ = −0.59) for the mechanism via the C–O cleavage rate-limiting step. The combined experimental and DFT computational results support a mechanistic path that involves the dehydrative C–H coupling of phenol with aldehyde, followed by the deaminative coupling reaction with an enamine in forming the xanthene product.

Isotopic Fractionation as a Mechanistic Probe in Light-Driven C-H Bond Exchange Reactions.

Here, we report a diagnostic framework for elucidating the mechanisms of photoredox-based hydrogen isotope exchange (HIE) reactions based on hydrogen/deuterium (H/D) fractionation. Traditional thermal HIE methods generally proceed by reversible bond cleavage and bond reformation steps that share a common transition state. However, bond cleavage and bond reformation in light-driven HIE reactions can proceed via multiple, non-degenerate sets of elementary steps, complicating both mechanistic analysis and attendant optimization efforts. Building on classical treatments of equilibrium isotope effects, the fractionation method presented here extracts information regarding the nature of the key bond-forming and bond-breaking steps by comparing the extent of deuterium incorporation into an exchangeable C-H bond in the substrate relative to the H/D isotopic ratio of a solvent reservoir. We show that the extent of fractionation is sensitive to the mechanism of the exchange process and provides a means to distinguish between degenerate and non-degenerate mechanisms for isotopic exchange. In model systems, the mechanisms implied by the fractionation method align with those predicted by thermochemical considerations. We then employed the method to study HIE reactions whose mechanisms are ambiguous on thermodynamic grounds.

Oxidative Decomposition Mechanism of Ethylene Carbonate on Positive Electrodes in Lithium-Ion Batteries

Abstract For extending the lifetime and improving the safety of lithium-ion batteries, the decomposition mechanism of electrolytes in lithium-ion batteries was kinetically and stereospecifically investigated in simplified reaction systems, which were in contact with the charged positive electrodes including Li1−xCoO2 as an active material removed from batteries. By identifying the products, mainly vinylene carbonate (VC) was detected by gas chromatography as an oxidation product of ethylene carbonate (EC). The kinetic isotope effects of the reaction were examined using EC and deuterium-labeled EC-D4. The kH/kD was found to be 2.9 suggesting the C–H bond cleavage step was irreversible and corresponds to the rate-determining step of the overall process in the reaction. Moreover, Arrhenius and Eyring plots and stereospecific studies using syn-substituted EC-D2 indicated that the transition state has a rigid structure and that the elimination of hydrogens from EC proceeds mainly via syn stereochemistry. Upon a change in the charge potential of Li1−xCoO2 from 4.5 V to 4.1 V, the rate of formation of VC decreased. PF6−, PO3F2−, and PO2F2− relating to LiPF6 promoted the generation of VC.

Temporal and spatial resolution of distal protein motions that activate hydrogen tunneling in soybean lipoxygenase

The enzyme soybean lipoxygenase (SLO) provides a prototype for deep tunneling mechanisms in hydrogen transfer catalysis. This work combines room temperature X-ray studies with extended hydrogen-deuterium exchange experiments to define a catalytically-linked, radiating cone of aliphatic side chains that connects an active site iron center of SLO to the protein-solvent interface. Employing eight variants of SLO that have been appended with a fluorescent probe at the identified surface loop, nanosecond fluorescence Stokes shifts have been measured. We report a remarkable identity of the energies of activation (Ea) for the Stokes shifts decay rates and the millisecond C-H bond cleavage step that is restricted to side chain mutants within an identified thermal network. These findings implicate a direct coupling of distal protein motions surrounding the exposed fluorescent probe to active site motions controlling catalysis. While the role of dynamics in enzyme function has been predominantly attributed to a distributed protein conformational landscape, the presented data implicate a thermally initiated, cooperative protein reorganization that occurs on a timescale faster than nanosecond and represents the enthalpic barrier to the reaction of SLO.

Computation Study on Copper-Catalyzed Aerobic Intramolecular Aminooxygenative C═C Bond Cleavage to Imides: Different Roles of Mononuclear and Dinuclear Copper Complexes

Cu-catalyzed aerobic reactions are a powerful protocol for the synthesis of value-added chemicals based on the ideal oxidant O2. Despite the long research history, the mechanistic studies clarifying the details of the whole catalytic cycle, where Cu-O2 complexes and their derivatives directly participate in the conversion of substrates, are limited, leaving the mechanisms of emerging aerobic reactions far from understanding. Herein, a computational study on the mechanism of Cu-catalyzed aerobic aminooxygenation of alkene-tethered amides to imides is reported. It is found that the Cu(I) precursor is not the active species but can generate two types of Cu(II) complexes LCu(OAc)OH and LCu(OAc)OOR to start the aminooxygenation through the successive formation of dinuclear Cu(III) oxo complex, dinuclear Cu(II) hydroxide complex, and hetero-dinuclear Cu(II)-Cu(I) complex, followed by alkylperoxo radical capture with Cu(I) species. LCu(OAc)OH catalyzes the aminooxygenation via a mononuclear mechanism, while LCu(OAc)OOR is an active intermediate therein. In the initial catalytic stage, LCu(OAc)OH transforms alkene-tethered amides to α-amidated aldehydes through N–H activation, amide isomerization, cyclization, alkyl radical release, alkyl radical capture by O2, alkylperoxo radical capture by in situ-generated Cu(I) species to LCu(OAc)OOR, acetate-assisted proton-coupled electron transfer (PCET), and concerted PCET/O–O bond cleavage. In the second catalytic stage for the generation of imides from α-amidated aldehydes, the previously proposed aldehyde Cα–H pathway is possible, but it is more likely to generate CO2 and H2 as the byproducts. Instead, a more feasible pathway involving C(O)–H activation to acyl radical, decarbonylation, and radical capture to LCu(OAc)OOR′ was discovered. The C(O)–H activation pathway generates CO and H2O as the byproducts and is consistent with the experimental observations. The concerted PCET/O–O bond cleavage steps generating α-amidated aldehydes and imides have close energy barriers and both can be the rate-determining steps. The presented outcome revised and expanded the knowledge of Cu-catalyzed aerobic conversion of C═C bonds and amide N–H bonds, highlighting the different roles of mononuclear and dinuclear copper complexes in the aerobic reactions and the in situ generation of Cu(II) catalysts, respectively.

Chemistry of a Nitrosyl Ligand κ:η-Bridging a Ditungsten Center: Rearrangement and N-O Bond Cleavage Reactions.

The novel nitrosyl-bridged complex [W2Cp2(μ-PtBu2)(μ-κ:η-NO)(CO)(NO)](BAr4) [Ar = 3,5-C6H3(CF3)2] was prepared in a multistep procedure starting from the hydride [W2Cp2(μ-H)(μ-PtBu2)(CO)4] and involving the new complexes [W2Cp2(μ-PtBu2)(CO)4](BF4), [W2Cp2(μ-PtBu2)(CO)2(NO)2](BAr4), and [W2(μ-κ:η5-C5H4)Cp(μ-PtBu2)(CO)(NO)2] as intermediates, which follow from reactions with HBF4·OEt2, NO, and Me3NO·2H2O, respectively. The nitrosyl-bridged cation easily added chloride upon reaction with [N(PPh3)2]Cl, with concomitant NO rearrangement into the terminal coordination mode, to give [W2ClCp2(μ-PtBu2)(CO)(NO)2], and underwent N–O and W–W bond cleavages upon the addition of CNtBu to give the mononuclear phosphinoimido complex [WCp(NPtBu2)(CNtBu)2](BAr4). Another N–O bond cleavage was induced upon photochemical decarbonylation at 243 K, which gave the oxo- and phosphinito-bridged nitrido complex [W2Cp2(N)(μ-O)(μ-OPtBu2)(NO)](BAr4), likely resulting from a N–O bond cleavage step following decarbonylation.

Photo-assisted reductive cleavage and catalytic hydrolysis-mediated persulfate activation by mixed redox-couple-involved CuFeS2 for efficient trichloroethylene oxidation in groundwater

Persulfate (PS, S2O82−) activation through transition metal sulfides (TMS) has gained increasing attention since it can decompose a wide variety of refractory halogenated organic compounds in groundwater and wastewater. However, the processes of PS activation by TMS and particularly the formation of •OH radical under anoxic and acidic conditions (pH ∼2.8) remain elusive. Herein, by employing mixed redox-couple-involved chalcopyrite (CuFeS2) (150 mg/L) nanoparticles for PS (3.0 mM) activation, 96% of trichloroethylene was degraded within 120 min at pH 6.8 under visible light irradiation. The combination of experimental studies and theoretical calculations suggested that the Cu(I)/Fe(III) mixed redox-couple in CuFeS2 plays a crucial role to activate PS. Cu(I) acted as an electron donor to transfer electron to Fe(III), then Fe(III) served as an electron transfer bridge as well as a catalytic center to further donate this received electron to the O–O bond of PS, thus yielding SO4•− for trichloroethylene oxidation. Moreover, for the first time, •OH radicals were found to form from the catalytic hydrolysis of PS onto CuFeS2 surface, where S2O82− anion was hydrolyzed to yield H2O2 and these ensuing H2O2 were further transformed into •OH radicals via photoelectron-assisted O–O bond cleavage step. Our findings offer valuable insights for understanding the mechanisms of PS activation by redox-couple- involved TMS, which could promote the design of effective activators toward PS decomposition for environmental remediation.

Resolving Oxygenation Pathways in Manganese-Catalyzed C(sp3)-H Functionalization via Radical and Cationic Intermediates.

The C(sp3)–H bond oxygenation of the cyclopropane-containing mechanistic probes 6-tert-butylspiro[2.5]octane and spiro[2.5]octane with hydrogen peroxide catalyzed by manganese complexes bearing aminopyridine tetradentate ligands has been studied. Mixtures of unrearranged and rearranged oxygenation products (alcohols, ketones, and esters) are obtained, suggesting the involvement of cationic intermediates and the contribution of different pathways following the initial hydrogen atom transfer-based C–H bond cleavage step. Despite such a complex mechanistic scenario, a judicious choice of the catalyst structure and reaction conditions (solvent, temperature, and carboxylic acid) could be employed to resolve these oxygenation pathways, leading, with the former substrate, to conditions where a single unrearranged or rearranged product is obtained in good isolated yield. Taken together, the work demonstrates an unprecedented ability to precisely direct the chemoselectivity of the C–H oxidation reaction, discriminating among multiple pathways. In addition, these results conclusively demonstrate that stereospecific C(sp3)–H oxidation can take place via a cationic intermediate and that this path can become exclusive in governing product formation, expanding the available toolbox of aliphatic C–H bond oxygenations. The implications of these findings are discussed in the framework of the development of synthetically useful C–H functionalization procedures and the associated mechanistic features.

Reversible C-C bond formation using palladium catalysis.

A widely appreciated principle is that all reactions are fundamentally reversible. Observing reversible transition metal-catalysed reactions, particularly those that include the cleavage of C-C bonds, is more challenging. The development of palladium- and nickel-catalysed carboiodination reactions afforded access to the cis and trans diastereomers of the iodo-dihydroisoquinolone products. Using these substrates, an extensive study investigating the reversibility of C-C bond formation using a simple palladium catalyst was undertaken. Herein we report a comprehensive investigation of reversible C-C bond formation using palladium catalysis employing diastereomeric neopentyl iodides as the starting point. It was shown that both diastereomers could be converted to a common product under identical catalytic conditions. A combination of experimental and computational studies were used to probe the operative mechanism. A variety of concepts key to understanding the process of reversible C-C bond formations were investigated, including the effect of electronic and steric parameters on the C-C bond-cleavage step.

A theoretical investigation on the hydrodesulphurisation mechanism of hydrogenated thiophene over Cu–Mo-modified FAU zeolite

ABSTRACT We have theoretically investigated the hydrodesulphurisation (HDS) mechanism of hydrogenated thiophene over Cu–Mo-modified FAU zeolite using a two-layer ONIOM (our Own N-layered Integrated molecular Orbital and molecular Mechanics) study. The thiophene is hydrogenated to 2,3-dihydrothiophene (2,3-DHT), 2,5-dihydrothiophene (2,5-DHT) and tetrahydrothiophene (THT) due to moderate free energy barriers. Hydrogenolysis desulphurisation (HYD) and concerted direct desulphurisation (DDS) are discussed. Ring-opening, hydrogen transfer and C−S bond cleavage steps of thiophene derivatives are involved in the HYD process. The rate-determining steps are the hydrogen transfer step for 2,5-DHT and C−S bond cracking step for 2,3-DHT and THT. The concerted DDS pathway is probably more favourable than the HYD pathway in the desulphurisation of 2,5-DHT. The difference charge density (DCD) analysis reveals that for the ring-opening process, the electrons are migrated from the organic chain to the Cu–Mo catalytic centre. The reduced density gradient (RDG) plots indicate that both steric hindrance and a weak van der Waals (VDW) interaction exist between organic fragment and catalytic centre for all transition states (TSs). The localised orbital locator (LOL) maps suggest that there are strong covalent interactions and weak VDW interactions between the atoms in the forming chemical bonds.

Unique regioselectivity of the Pd-catalysed cross-dehydrogenative coupling reaction of simple polyaromatic hydrocarbons with polyfluoroarenes.

A Pd-catalysed cross-dehydrogenative coupling reaction introduced two polyfluoroarenes into simple polyaromatic hydrocarbons at sterically favourable positions. An investigation of the reaction mechanism revealed that the unique regioselectivity was determined by the reductive elimination step rather than the C-H bond cleavage step.

Catalytic Activities of Low‐Coordinated Ce for Methane Conversion

AbstractIn heterogeneous catalysis, the catalytic activity of an active center strongly correlates with its coordination number. In this work, density functional theory calculations corrected by on‐site Coulomb interactions were conducted to investigate the catalytic performances of the CeO4‐terminated reconstructed CeO2(100) (CeO4‐t) and the Ca‐doped CeO4‐t surfaces. The undoped CeO4‐t surface contains single 4‐fold coordinated Ce (Ce4c) sites on its top surface layer, and the Ca‐doped CeO4‐t surface can expose even lower‐coordinated 3‐fold Ce (Ce3c) sites. We found that the empty 4f states of the single Ce3c sites on the Ca‐doped CeO4‐t surface have much lower energies than that of the single Ce4c sites on the undoped CeO4‐t surface, which can effectively boost the reduction of Ce4+ to Ce3+. We further studied the selective oxidation of CH4 to CH3OH on the two surfaces and found that the isolated nature combined with the strong electron‐reservoir character of the single Ce3c site makes it highly desirable for the selective activation of the first C−H bond of CH4, while the subsequent C−H bond cleavage step is less affected by such low‐coordinated Ce and the CH3OH formation becomes more facile on the Ca‐doped CeO4‐t surface, giving rise to the high activity and selectivity of the Ca‐doped CeO4‐t surface toward the selective oxidation of CH4 to CH3OH.