Bond Cleavage Step Research Articles

Nondirected C–H Activation of Arenes with Cp*Ir(III) Acetate Complexes: An Experimental and Computational Study

Combined experimental and computational studies have revealed factors that influence the nondirected C–H activation in Cp*Ir complexes that contain carboxylate ligands. A two-step acetate-assisted pathway was shown to be operational where the first step involves substrate binding and the second step involves cleavage of the C–H bond of the substrate. A nonlinear Hammett plot was obtained to examine substituted arenes where a strong electronic dependence (ρ = 1.67) was observed for electron-donating groups, whereas no electronic dependence was observed for electron-withdrawing groups. Electron-donating substituents in the para position were shown to have a bigger impact on the C–H bond cleavage step, whereas electron-withdrawing substituents influenced the substrate-binding step. Although cleavage of the C–H bond was predicted to be more facile with arenes that contain substituents in the para position by DFT calculations, the cyclometalations of anisole and benzonitrile were observed experimentally. This ...

Role of magnesium ions in the reaction mechanism at the interface between Tm1631 protein and its DNA ligand.

A protein, Tm1631 from the hyperthermophilic organism Thermotoga maritima belongs to a domain of unknown function protein family. It was predicted that Tm1631 binds with the DNA and that the Tm1631–DNA complex is an endonuclease repair system with a DNA repair function (Konc et al. PLoS Comput Biol 9(11): e1003341, 2013). We observed that the severely bent, strained DNA binds to the protein for the entire 90 ns of classical molecular dynamics (MD) performed; we could observe no significant changes in the most distorted region of the DNA, where the cleavage of phosphodiester bond occurs. In this article, we modeled the reaction mechanism at the interface between Tm1631 and its proposed ligand, the DNA molecule, focusing on cleavage of the phosphodiester bond. After addition of two Mg2+ ions to the reaction center and extension of classical MD by 50 ns (totaling 140 ns), the DNA ligand stayed bolted to the protein. Results from density functional theory quantum mechanics/molecular mechanics (QM/MM) calculations suggest that the reaction is analogous to known endonuclease mechanisms: an enzyme reaction mechanism with two Mg2+ ions in the reaction center and a pentacovalent intermediate. The minimum energy pathway profile shows that the phosphodiester bond cleavage step of the reaction is kinetically controlled and not thermodynamically because of a lack of any energy barrier above the accuracy of the energy profile calculation. The role of ions is shown by comparing the results with the reaction mechanisms in the absence of the Mg2+ ions where there is a significantly higher reaction barrier than in the presence of the Mg2+ ions.Graphical abstractA protein, Tm1631 from the hyperthermophilic organism Thermotoga maritima belongs to a domain of unknown function protein family. We modeled the reaction mechanism at the interface between Tm1631 and its proposed ligand, the DNA molecule, focusing on cleavage of the phosphodiester bondElectronic supplementary materialThe online version of this article (doi:10.1186/s13065-016-0188-6) contains supplementary material, which is available to authorized users.

Density Functional Theory Study of the Mechanism of Formaldehyde Oxidation on Mn-Doped Ceria

Formaldehyde is an indoor pollutant, whose removal under mild conditions is of growing importance. Mn-doped CeO2 is a promising catalyst for the oxidation of formaldehyde to water and carbon dioxide. We have theoretically investigated the origin of the high activity of Mn-doped ceria as compared with ceria. DFT+U calculations were used to identify adsorption modes and compare different reaction mechanisms. The reaction mechanism involves HCHO adsorption, two C–H bond cleavage steps involving reactive O atoms (either structural O atoms of the support or adsorbed O2), H2O formation, and H2O and CO2 desorption. On the stoichiometric surface, a Mars–Van Krevelen mechanism occurs, which involves ceria surface O atoms. The lower coordination number of these O atoms in the stoichiometric Mn-doped ceria results in decreased barriers for C–H bond cleavage. In the presence of defects which will be ubiquitous in the Mn-doped surface, a Langmuir–Hinshelwood mechanism becomes feasible, as O2 can strongly adsorb on the...

Kinetic Compensation between Ester-Bond Cleavage, Folding and Release from the Ribosome in Protein Biogenesis

In the healthy cell, bioactive proteins fold without aggregating. However, the mechanism of protein folding and release from the ribosome after completion of protein biosynthesis is still largely unknown. In this work, we focused on two bacterial single-domain monomeric model proteins: the alpha-helical globin ApoHmpH and the beta sheet cold shock protein A (CspA). We studied the kinetics of hydrolysis of the ester bond between the nascent polypeptides and the 3' end of the tRNA. In addition, we characterized the escape and folding of the model proteins from the ribosome. Time-resolved fluorescence depolarization in the frequency domain led to insights into the compaction of ribosome-bound and -released nascent proteins. Chain release was triggered by the antibiotic puromycin at concentrations yielding rates of ester bond cleavage similar to those of the naturally occurring release factors. Surprisingly, we found that departure of apoHmpH from the ribosome is rate-limited by the bond cleavage step and that escape from the ribosomal tunnel and completion of folding occur quickly afterwards. On the other hand, for the smaller beta-sheet protein CspA ester-bond cleavage is faster, and escape from the tunnel and folding occur more slowly. Yet, the overall rate of native protein production is comparable to that of apoHmpH. Overall, the ribosomal context promotes “temporally efficient” folding upon nascent protein release. We propose that the rapid combined rate of ribosome release and folding is tuned to prevent undesirable diffusion- and concentration-dependent aggregation in the cellular environment, at physiologically relevant concentrations.

A DFT Study on the Conversion of Aryl Iodides to Alkyl Iodides: Reductive Elimination of R-I from Alkylpalladium Iodide Complexes with Accessible β-Hydrogens.

DFT calculations have been performed on the palladium-catalyzed carboiodination reaction. The reaction involves oxidative addition, alkyne insertion, C-N bond cleavage, and reductive elimination. For the alkylpalladium iodide intermediate, LiOtBu stabilizes the intermediate in non-polar solvents, thus promoting reductive elimination and preventing β-hydride elimination. The C-N bond cleavage process was explored and the computations show that PPh3 is not bound to the Pd center during this step. Experimentally, it was demonstrated that LiOtBu is not necessary for the oxidative addition, alkyne insertion, or C-N bond cleavage steps, lending support to the conclusions from the DFT calculations. The turnover-limiting steps were found to be C-N bond cleavage and reductive elimination, whereas oxidative addition, alkyne insertion, and formation of the indole ring provide the driving force for the reaction.

Mechanism of Oxygen Reduction in Cytochrome c Oxidase and the Role of the Active Site Tyrosine.

Cytochrome c oxidase, the terminal enzyme in the respiratory chain, reduces molecular oxygen to water and stores the released energy through electrogenic chemistry and proton pumping across the membrane. Apart from the heme-copper binuclear center, there is a conserved tyrosine residue in the active site (BNC). The tyrosine delivers both an electron and a proton during the O-O bond cleavage step, forming a tyrosyl radical. The catalytic cycle then occurs in four reduction steps, each taking up one proton for the chemistry (water formation) and one proton to be pumped. It is here suggested that in three of the reduction steps the chemical proton enters the center of the BNC, leaving the tyrosine unprotonated with radical character. The reproprotonation of the tyrosine occurs first in the final reduction step before binding the next oxygen molecule. It is also suggested that this reduction mechanism and the presence of the tyrosine are essential for the proton pumping. Density functional theory calculations on large cluster models of the active site show that only the intermediates with the proton in the center of the BNC and with an unprotonated tyrosyl radical have a high electron affinity of similar size as the electron donor, which is essential for the ability to take up two protons per electron and thus for the proton pumping. This type of reduction mechanism is also the only one that gives a free energy profile in accordance with experimental observations for the amount of proton pumping in the working enzyme.

DFT Studies on the Mechanism of the Rhodium(III)-Catalyzed C-H Activation of N-Phenoxyacetamide.

A density functional theory (DFT) study has been conducted to elucidate the mechanism of the rhodium(III)-catalyzed C-H activation of N-phenoxyacetamide, where the amido component of an internal oxidant serves as a leaving group. The impact of different substrates (alkynes versus cyclopropenes) on the reaction mechanism has been discussed in detail. The pathway for cyclopropene substrate proceeded via a Rh(V) nitrene, while Rh(III) remained unchanged throughout the pathway for alkyne substrate. The C-O bond-forming reductive elimination and O-N bond cleavage steps simultaneously occurred for the alkyne substrate. However, the C-O bond was formed by an electrocyclization from a Rh(III) intermediate for the cyclopropene substrate. The energy profiles for the cyclopropene substrate were accompanied by a change in spin-state because the triplet spin state of a Rh(V) nitrene complex is lower than that of the singlet spin state.

Scope and Mechanistic Studies of the Cationic Ir/Me-BIPAM-Catalyzed Asymmetric Intramolecular Direct Hydroarylation Reaction

Results of mechanistic studies on asymmetric hydroarylation of α-keto amides via direct C–H bond addition to a carbonyl group catalyzed by a cationic Ir/Me-BIPAM complex are presented in this paper. A catalytic cycle involving C–H bond cleavage to give an Ar-[Ir]+ intermediate, insertion of a carbonyl group into the aryl-iridium bond, giving iridium alkoxide, and finally reductive elimination to reproduce active [Ir]+ species is proposed. The mechanistic insight for the iridium hydride species indicated that the C–H bond cleavage is caused in a reversible manner. Furthermore, the kinetic isotope effect was measured by product analysis of the reaction to compare H/D, and it was determined that kH/kD was 1.85. These experimental results suggest that the C–H bond cleavage step is not included in the turnover-limiting step. In addition, Hammett studies of substrates (ρ = −0.99) demonstrated that electron-donating groups at the para position to the reactive C–H bond accelerate the reaction rate. This linear relationship obtained in the Hammett plot indicates that the nucleophilicity of the aryl-iridium intermediate is an important factor in this reaction. All of the data indicate that carbonyl insertion into aryl-iridium is included in the turnover-limiting step of the catalytic cycle.

ChemInform Abstract: Efficient Transition Metal‐Catalyzed Reactions of Carboxylic Acid Derivatives with Hydrosilanes and Hydrosiloxanes, Afforded by Catalyst Design and the Proximity Effect of Two Si—H Groups

AbstractReview: [89 refs.

Rhodium-catalysed C(sp(2))-C(sp(2)) bond formation via C-H/C-F activation.

Fluoroalkenes represent a class of privileged structural motifs, which found widespread use in medicinal chemistry. However, the synthetic access to fluoroalkenes was much underdeveloped with previous reported methods suffering from either low step economy or harsh reaction conditions. Here we present a RhIII-catalysed tandem C–H/C–F activation for the synthesis of (hetero)arylated monofluoroalkenes. The use of readily available gem-difluoroalkenes as electrophiles provides a highly efficient and operationally simple method for the introduction of α-fluoroalkenyl motifs onto (hetero)arenes under oxidant-free conditions. Furthermore, the employment of alcoholic solvent and the in-situ generated hydrogen fluoride are found to be beneficial in this transformation, indicating the possibility of the involvement of hydrogen bond activation mode with regards to the C–F bond cleavage step.

Oxidative Olefination of Anilides with Unactivated Alkenes Catalyzed by an (Electron-Deficient η(5) -Cyclopentadienyl)Rhodium(III) Complex Under Ambient Conditions.

The oxidative olefination of sp(2) C-H bonds of anilides with both activated and unactivated alkenes using an (electron-deficient η(5) -cyclopentadienyl)rhodium(III) complex is reported. In contrast to reactions using this electron-deficient rhodium(III) catalyst, [Cp*RhCl2 ]2 showed no activity against olefination with unactivated alkenes. In addition, the deuterium kinetic isotope effect (DKIE) study revealed that the C-H bond cleavage step is thought to be the turnover-limiting step.

Palladium-Catalyzed Asymmetric Arylation of C(sp(3))-H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids.

Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.

Efficient Transition Metal-Catalyzed Reactions of Carboxylic Acid Derivatives with Hydrosilanes and Hydrosiloxanes, Afforded by Catalyst Design and the Proximity Effect of Two Si–H Groups

The discovery of the ruthenium cluster μ3,-(η2:η3:η5-acenaphythylene)Ru3(CO)7 (1), which is active in catalytic reactions involving Si–H bond activation, and the rate enhancement by the proximity effect of two Si–H groups enabled the reduction of carboxylic acid derivatives with hydrosilanes under mild reaction conditions. A judicious choice of the hydrosilane and of the additives led to a remarkably selective reduction. Besides simple reduction, the treatment of carboxylic acid derivatives with hydrosilanes in the presence of 1 led to new reactions involving several C–O and C–C bond-forming as well as C–O bond-cleavage steps. These reactions included polymerization, rearrangement, and aromatic substitution. The use of inexpensive 1,1,3,3-tetramethyldisiloxane (TMDS) facilitated the efficient reduction of amides to amines using either 1, commercially available platinum compounds, or environmentally friendly iron complexes. The conversion of tertiary amides into aldenamines was achieved by iridium catalysis. In the ruthenium-, iridium-, platinum-, and iron-catalyzed reduction of amides, the use of the reducing reagent polymethylhydrosiloxane (PMHS) resulted in self-encapsulation of the residual metal species into the formed silicone gel to give the ‘metal-free’ product in a straightforward way. 1 Introduction 2 Two Key Preliminary Investigations 2.1 A Ruthenium Cluster for Si–H Bond Activation 2.2 Proximity Effect of Two Si–H Groups for Rate Enhancement 3 Ruthenium-Catalyzed Reduction of Carboxylic Acid Derivatives 3.1 From Ketones to Less Reactive Carboxylic Acid Derivatives 3.2 Self-Encapsulation of the Residual Metals into Silicone Gel 4 Extension to C–O and C–C Bond-Forming Reactions 4.1 Reduction versus Ring-Opening Polymerization of Cyclic Ethers 4.2 Polymerization versus Rearrangement of Vinyl Ethers 4.3 Is ‘R3Si+’ Involved in the Reactions? 4.4 Applications of ‘R3Si+’-Mediated Reactions 5 Reductions with Unique Selectivity 6 Surfing the Periodic Table 7 Concluding Remarks

Formation of a C-C double bond from two aliphatic carbons. Multiple C-H activations in an iridium pincer complex.

The search for novel, atom-economic methods for the formation of C-C bonds is of crucial importance in synthetic chemistry. Especially attractive are reactions where C-C bonds are formed through C-H activation, but the coupling of unactivated, alkane-type Csp3 -H bonds remains an unsolved challenge. Here, we report iridium-mediated intramolecular coupling reactions involving up to four unactivated Csp3 -H bonds to give carbon-carbon double bonds under the extrusion of dihydrogen. The reaction described herein is completely reversible and the direction can be controlled by altering the reaction conditions. With a hydrogen acceptor present a C-C double bond is formed, while reacting under dihydrogen pressure leads to the reverse process, with some of the steps representing net Csp3 -Csp3 bond cleavage. Mechanistic investigations revealed a conceptually-novel overall reactivity pattern where insertion or deinsertion of an Ir carbene moiety, formed via double C-H activation, into an Ir-C bond is responsible for the key C-C bond formation and cleavage steps.

Rhodium(III)-Catalyzed Hydrazine-Directed C–H Activation for Indole Synthesis: Mechanism and Role of Internal Oxidant Probed by DFT Studies

DFT calculations have been carried out to study the detailed mechanism of Rh(III)-catalyzed C–H activation/cyclization of 2-acetyl-1-arylhydrazines with alkynes leading to the formation of indoles, in which the hydrazine moiety is used as the internal oxidant. The energy profiles associated with the catalytic cycle, involving N–H deprotonation, C–H activation (a concerted metalation–deprotonation (CMD) process), alkyne insertion, ring rearrangement/isomerization, and finally N–N bond cleavage/reductive elimination to regenerate the active species, are presented and analyzed. Through analysis of the calculation results, we found that the combined processes of the CMD and alkyne insertion contribute to the overall rate-determining step. The N–N bond cleavage step was examined in detail to understand how the internal oxidant interacts with the metal center to facilitate the catalytic reactions. The factor influencing regioselectivity was also investigated. How different types of substrates (alkynes versus alkenes) and internal oxidants (−NH(NHAc) versus −NH(OAc)) influence the reaction mechanisms, Rh(III)/Rh(I) versus Rh(III)/Rh(V) catalytic cycles, was discussed.

A theoretical investigation on palladium-catalyzed one-pot coupling of aryl iodides, alkynes, and amines through CN bond cleavage for the synthesis of indole derivatives

Detailed mechanism of one-pot coupling of aryl iodides, alkynes, and amines catalyzed by a palladium complexes is studied using density functional theory. The reaction of three-component proceeds in four steps after the insertion of alkyne into CI bond. The four-component case comprises eight steps incorporating two times of nucleophilic addition. The CN bond cleavage is rate-limiting. The reaction sequence is maintained the same. The function of metal Pd is reflected by the coordination ability and electrophility of different oxidation state. The high selectivity of ligand is originated from the style of electron distribution in CN bond cleavage and amination steps. We also discuss the amination from a bonding orbital matching perspective by means of frontier molecular orbital analysis. © 2014 Wiley Periodicals, Inc.

ChemInform Abstract: Copper‐Catalyzed Oxidative Cyclization of 1,5‐Enynes with Concomitant C—C Bond Cleavage: An Unexpected Access to 3‐Formyl‐1‐indenone Derivatives.

AbstractA novel water‐induced oxygen‐insertion/β‐carbon elimination via double oxy‐cupration is proposed to be involved in the C—C bond cleavage step.

Oxidation Mechanism of Formic Acid on the Bismuth Adatom-Modified Pt(111) Surface

In order to improve catalytic processes, elucidation of reaction mechanisms is essential. Here, supported by a combination of experimental and computational results, the oxidation mechanism of formic acid on Pt(111) electrodes modified by the incorporation of bismuth adatoms is revealed. In the proposed model, formic acid is first physisorbed on bismuth and then deprotonated and chemisorbed in formate form, also on bismuth, from which configuration the C-H bond is cleaved, on a neighbor Pt site, yielding CO2. It was found computationally that the activation energy for the C-H bond cleavage step is negligible, which was also verified experimentally.

ChemInform Abstract: Nickel‐Catalyzed Direct Arylation of C(sp3)—H Bonds in Aliphatic Amides via Bidentate‐Chelation Assistance.

The Ni-catalyzed, direct arylation of C(sp3)–H (methyl and methylene) bonds in aliphatic amides containing an 8-aminoquinoline moiety as a bidentate directing group with aryl halides is described. Deuterium-labeling experiments indicate that the C–H bond cleavage step is fast and reversible. Various nickel complexes including both Ni(II) and Ni(0) show a high catalytic activity. The results of a series of mechanistic experiments indicate that the catalytic reaction does not proceed through a Ni(0)/Ni(II) catalytic cycle, but probably through a Ni(II)/Ni(IV) catalytic cycle.

Unraveling the synergy between gold nanoparticles and chromium-hydrotalcites in aerobic oxidation of alcohols

The combination of gold nanoparticles (AuNPs) with chromium-substituted hydrotalcite (Cr-HT) supports makes very efficient heterogeneous catalysts (Au/Cr-HT) for aerobic alcohol oxidation under soluble-base-free conditions. The Au-support synergy increases with increasing Cr content of the support and decreasing AuNP size. In situ UV-Raman, X-ray absorption and photoelectron spectroscopic studies firmly establish that the strong Au–Cr synergy is related to a Cr3+↔Cr6+ redox cycle at the Au/Cr-HT interface, where O2 activation takes place accompanied by electron transfer from Cr-HT to Au. The interfacial Cr6+ species can be reduced by surface Au–H hydride and negative-charged Au species to close the catalytic cycle. A study of kinetic isotope effect indicates that alcohol O–H cleavage is facilitated by the presence of Cr, making α-C–H bond cleavage step more rate-controlling. Accordingly, a dual synergistic effect of Au/Cr-HT catalysts on the activation of O2 and alcohol reactants is proposed.