Outer-sphere Mechanism Research Articles

Experimental and Computational Studies for the Synthesis of Functionalized Cyclopropanes from 2-Substituted Allylic Derivatives with Ethyl Diazoacetate.

The catalytic asymmetric synthesis of highly functionalized cyclopropanes from 2-substituted allylic derivatives is reported. Using ethyl diazo acetate, the reaction, catalyzed by a chiral ruthenium complex (Ru(II)-Pheox), furnished the corresponding easily separable cis and trans cyclopropanes in moderate to high yields (32-97 %) and excellent ee (86-99 %). This approach significantly extends the portfolio of accessible enantioenriched cyclopropanes from an underexplored class of olefins. DFT calculations suggest that an outer-sphere mechanism is operative in this system.

Mechanism and Stereoselectivity Control of Terminal Alkyne Dimerization Activated by a Zr/Co Heterobimetallic Complex: A DFT Study.

Heterobimetallic complexes have recently garnered considerable attention in organic synthesis owing to their high activity and selectivity, which surpass those of monometallic complexes. In this study, the detailed mechanisms of terminal alkyne dimerization activated by the heterobimetallic Zr/Co complex, as well as the different stereoselectivities of Me3SiC≡CH and PhC≡CH dimerization, were investigated and elucidated by using density functional theory calculations. After excluding the three-molecule reaction and outer-sphere mechanisms, the inner-sphere mechanism was determined as the most optimal process. The inner-sphere mechanism involves four processes: THF dissociation and coordination of the first alkyne; ligand migration and C-H activation; N2 dissociation and insertion of the second alkyne; and reductive elimination. The stereoselectivity between the E-/Z- and gem-isomers is determined by the C-C coupling mode of the two alkynes and that of the E- and Z-isomers is determined by the sequence of the C-C coupling and hydrogen migration in the reductive elimination process. Me3SiC≡CH dimerization yields only an E-isomer owing to the large differences in the distortion and interaction energies, whereas PhC≡CH dimerization produces an E-, Z-, and gem-isomers owing to the reduced interaction energy differences.

The crucial role of ligand deprotonation in manganese catalyzed hydrogenation reactions

Hydrogenation catalysts based on the abundant early transition metal manganese recently received growing attention. A common motif found in most of the reported systems is a deprotonatable hydrogen atom in the ligand, usually considered necessary within an outer-sphere mechanism. Here we investigated the mechanism of the catalytic hydrogenation of ketones, focusing on the crucial function of the deprotonatable H atom in the ligand. Therefore, we synthesized phosphine-free Mn(I) complexes of the type [(L)MnBr(CO)3)] utilizing pyridyl-imidazole ligands, having a deprotonatable H atom within the imidazole ring. They were found to be active catalysts for the hydrogenation of ketones with molecular hydrogen. Kinetic and spectroscopic studies together with DFT calculations point towards an inner-sphere mechanism with the hydride transfer to the substrate being the rate determining step. Most importantly, we demonstrate that the NH-motif remains deprotonated throughout the catalytic cycle maintaining an anionic manganese species. Thereby, the anionic ligand is a more potent electron donor which enhances the rate determining hydride transfer.

Cation-induced changes in the inner- and outer-sphere mechanisms of electrocatalytic CO2 reduction

The underlying mechanism of cation effects on CO2RR remains debated. Herein, we study cation effects by simulating both outer-sphere electron transfer (OS-ET) and inner-sphere electron transfer (IS-ET) pathways during CO2RR via constrained density functional theory molecular dynamics (cDFT-MD) and slow-growth DFT-MD (SG-DFT-MD), respectively. Our results show without any cations, only OS-ET is feasible with a barrier of 1.21 eV. In the presence of K+ (Li+), OS-ET shows a very high barrier of 2.93 eV (4.15 eV) thus being prohibited. However, cations promote CO2 activation through IS-ET with the barrier of only 0.61 eV (K+) and 0.91 eV (Li+), generating the key intermediate (adsorbed CO{}_{2}^{delta -}). Without cations, CO2-to-CO{}_{2}^{delta -}(ads) conversion cannot proceed. Our findings reveal cation effects arise from short-range Coulomb interactions with reaction intermediates. These results disclose that cations modulate the inner- and outer-sphere pathways of CO2RR, offering substantial insights on the cation specificity in the initial CO2RR steps.

Mechanistic insights into excited-state palladium catalysis for C–S bond formations and dehydrogenative sulfonylation of amines

Photocatalytic selective C(sp3)–H activation/cross-coupling reactions are appealing in organic synthesis. In this manuscript, we describe the development of photoexcited-state Pd-catalyzed dehydrogenative β-sulfonylation reactions using amines and aryl sulfonyl chlorides via intermolecular hydrogen atom transfer and C−S cross-coupling processes at room temperature. The transformation can be achieved by the direct generation of two distinct Pd-radical hybrid species and their capability to promote two different reactivities from Pd(0) and aryl sulfonyl chlorides, allowing for the efficient conversion of readily available amines into stable sulfonyl-substituted enamines at room temperature. The in-depth experimental, computational, and transient optical spectroscopic study and catalytic applications of a dehydrogenative functionalization event provide evidence for both static and dynamic quenching, as well as inner-sphere and outer-sphere mechanisms.

Synthesis of Allenes by Hydroalkylation of 1,3-Enynes with Ketones Enabled by Cooperative Catalysis.

A method for the synthesis of allenes by the addition of ketones to 1,3-enynes by cooperative Pd(0)Senphos/B(C6F5)3/NR3 catalysis is described. A wide range of aryl- and aliphatic ketones undergo addition to various 1,3-enynes in high yields at room temperature. Mechanistic investigations revealed a rate-determining outer-sphere proton transfer mechanism, which was corroborated by DFT calculations.

Theoretical insight into the acceptorless dehydrogenation catalyzed by the transition metal bifunctional catalysts: Mechanism and metal effect

In this paper, the density functional theory study was performed to investigate the reaction mechanism of acceptorless dehydrogenation catalyzed by bifunctional catalysts. The calculation results indicate that the catalyst bearing the Co(III) center adopts the inner-sphere stepwise dehydrogenation mechanism. The H2 formation was found to be the rate-determining step, and the proton-shuttle type transition state effectively reduces the activation energy barrier. Furthermore, the catalytic activities of the noble metals (Rh and Ir) were investigated and compared. The results suggest that the noble metals prefer the outer-sphere bifunctional transfer mechanism for the dehydrogenation reaction. Frontier molecular orbital analysis shows that the HOMO-LUMO gap of the active species increases along with the periodic number, which leads to a weakening of the coordination strength of the substrate to the metal center, resulting in the different mechanistic selectivity toward dehydrogenation reaction. In addition, based on the distortion-interaction analysis, the different activation energy barrier in the H2 formation step is illuminated. The reduced ionic radii of the Co result in lower deformation energies of the catalyst and substrate structures in the H2 formation transition state, thus lowering the activation energy barrier. Our results reveal the advantages of base metal in dehydrogenation reactions, which is expected to provide theoretical guidance for future catalyst design.

Premicellar effects on the reduction of N, N′-phenylenebis(salicylideneiminato)iron(III) by thioglycolic acid: Kinetic study and mechanism

The reduction kinetics of N,N′-phenylenebis(salicylideneiminato)iron(III), [Fe(salphen)]+ by thioglycolic acid (TSH) has been carried out in mixed aqueous medium (DMSO:H2O; 1:4) in pseudo-first order condition at 26 ± 1 °C. A CORNING colorimeter 253 was used to monitor the reaction rates by detecting the absorbance reduction of the reaction at 435 nm. The reaction was acid independent, second order overall and demonstrated zero Brønsted-Debye salt effect. Ions such as Mg2+ and CH3COO- catalyzed the reaction. The thermodynamic parameters indicated an activated complex that is much ordered and a highly solvated transition state. Reaction catalysis was observed in the case of sodium dodecylsulphate (SDS) and cetyltrimethylammonium bromide (CTAB) inclusion. The critical micelle concentrations obtained for SDS were 8.0 × 10−3 and 3.3 × 10−3 mol dm−3 whereas that observed for CTAB were 2.0 × 10−3 and 2.8 × 10−3 mol dm−3 in water and [Fe(salphen)]+ reaction media respectively. Piszkiewicz model was used to analyze the results which indicated the existence of pre-micellar aggregates and significant electrostatic and hydrophobic interactions between the metal complex and the pre-micellar aggregates of the surfactants. The cooperativity index and binding constants obtained were n = 1.22, K = 4.78 × 104 dm3 mol−1, n = 1.27 and K = 4.55 × 104 dm3 mol−1 respectively for SDS and CTAB. A plausible mechanism suggesting an outer-sphere mechanism has been postulated.

Kinetic study of Ru(III) – catalyzed oxidation of L-phenylalanine by hexacyanoferrate(III) in an anionic surfactant medium

Abstract The kinetic investigation of Ru(III) promoted oxidation of L-phenylalanine (L-PheAla) by [Fe(CN)6]3− has been performed in anionic sodium dodecyl sulfate (SDS) micellar medium by recording the decrease in absorbance at 420 nm corresponding to [Fe(CN)6]3− using an UV–visible spectrophotometer. Using the pseudo-first-order condition, the course of the reaction was studied as a function of [Fe(CN)6 3−], ionic strength, [OH−], [SDS], [Ru3+], [L-PheAla] and temperature by changing one variable at a time. The results exhibit that [OH−], [SDS], and [L-PheAla] are the crucial parameters that have an appreciable influence on the reaction rate. The reaction exhibits first-order kinetics in concentration ranges of Ru(III), [Fe(CN)6]3− and at low [L-PheAla] and [OH−] concentrations. The incremental trend observed in the reaction rate with electrolyte concentration shows a positive salt effect. The reaction rate is almost 10 times faster in SDS micellar medium than in aqueous medium. [Fe(CN)6]3− has no appreciable effect on the CMC of SDS, since the polar head of SDS and [Fe(CN)6]3− are both negatively charged. The K+ obtained from K3[Fe(CN)6] and KNO3 decreases the repulsion between the negatively charged heads of the surfactant molecules, which decreases the CMC of SDS. The activation parameters also support the outer-sphere electron transfer mechanism.

Spectrophotometric Study of Kinetics of Redox Reaction between Caffeine and Permanganate Ion in Aqueous Acidic Medium

The kinetics of redox reaction between caffeine (hereafter referred to as CAF) and permanganate ion [MnO4-] has been studied spectrophotometrically in aqueous sulfuric acid medium. One mole of CAF was oxidized by one mole of [MnO4-].The reaction showed first-order kinetics with respect to both [CAF] and [MnO4-]. The investigation was carried out under pseudo-first order condition atI= 0.5 mol dm–3, (Na2SO4), T = 24± 0.1℃ and [H+] = 1.0 × 10–1mol dm-3. The reaction obeys the rate law: -d[MnO4-]/dt = (a+b [H+]) [CAF ] [MnO4-]. The reaction was retarded by increased in ionic strength of the reaction medium. The rate of the reaction showed dependence on acid (in the range used).Added anions and cations were observed to catalyze the reaction rate. Spectroscopic investigation and kinetic study did not suggest intermediate complex formation. An outer–sphere mechanism is proposed for the reaction.

Effects of support material and electrolyte on a triphenylamine substituted cobalt porphyrin catalytic oxygen reduction reaction

The interfacial charge transfer conditions are crucial for understanding the catalytic mechanism and thus developing high performing electrocatalysts. To justify the effects of support material and electrolyte on metalloporphyrin catalytic oxygen reduction reaction (ORR), we synthesize a symmetric triphenylamine (TPA) substituted cobalt porphyrin, nominated as s-TPA-CoP, and select carbon black and multi-walled carbon nanotubes as the supports to fabricate composite catalysts. The ORR performances are measured in both acidic and alkaline solutions. While the support material affects negligibly on reduction potentials, the stronger π-π stacking in s-TPA-CoP/CNT, as revealed by X-ray photoelectron spectroscopy measurements, leads to greater limiting current densities and larger electron transfer numbers as compared to s-TPA-CoP/XC in either electrolyte. Both composites perform better ORR activity but poorer 4-electron selectivity in base than in acid, whose origins are discussed from the aspects of interfacial charge states and inner- / outer-sphere electron transfer mechanisms. Strikingly, s-TPA-CoP/CNT exhibits an electron transfer number of 3.8 in acid, demonstrating the privilege of TPA as the substitution on monometallic cobalt porphyrins in chasing 4-electron transfer oxygen reduction.

Mechanism of Pd/Senphos-Catalyzed trans-Hydroboration of 1,3-Enynes: Experimental and Computational Evidence in Support of the Unusual Outer-Sphere Oxidative Addition Pathway.

The reaction mechanism of the Pd/Senphos-catalyzed trans-hydroboration reaction of 1,3-enynes was investigated using various experimental techniques, including deuterium and double crossover labeling experiments, X-ray crystallographic characterization of model reaction intermediates, and reaction progress kinetic analysis. Our experimental data are in support of an unusual outer-sphere oxidative addition mechanism where the catecholborane serves as a suitable electrophile to activate the Pd0-bound 1,3-enyne substrate to form a Pd-η3-π-allyl species, which has been determined to be the likely resting state of the catalytic cycle. Double crossover labeling of the catecholborane points toward a second role played by the borane as a hydride delivery shuttle. Density functional theory calculations reveal that the rate-limiting transition state of the reaction is the hydride abstraction by the catecholborane shuttle, which is consistent with the experimentally determined rate law: rate = k[enyne]0[borane]1[catalyst]1. The computed activation free energy ΔG‡ = 17.7 kcal/mol and KIE (kH/kD = 1.3) are also in line with experimental observations. Overall, this work experimentally establishes Lewis acids such as catecholborane as viable electrophilic activators to engage in an outer-sphere oxidative addition reaction and points toward this underutilized mechanism as a general approach to activate unsaturated substrates.

Mechanisms of Docking of Superoxide Ions in the Catalytic Cycle of Manganese and Iron Superoxide Dismutases

n this paper, we propose an approach to resolving some questions about the catalytic action of manganese and iron superoxide dismutases. At the level of a pure quantum-chemical calculation using an ORCA 5.0.3 program, a PBE functional and a def2-SVP and def2-TZVP basis sets, the possible mechanisms of superoxide ions binding to the active sites of enzymes, the electron transfer distances and their characteristics were established. It is shown that the initial form of the fifth ligand in both active sites is the hydroxide ion OH–. Before the primary electron transfer, active sites are protonated, the hydroxide ion is converted into a water molecule H2O. Primary electron transfers from the superoxide ion to Mn3+-SOD and Fe3+-SOD occur by the associative mechanism, with the formation of an octahedral complex, at a transfer distance of 1.95 Å and 2.56 Å, respectively. At the second stage, the superoxide ion accepts the electron by the substitution mechanism from Mn2+- SOD at the transfer distance of 2 Å to form bonds with the water molecule and a tyrosine. The superoxide ion accepts the electron from Fe2+-SOD through the outer-sphere mechanism, where it binds to a histidine and the water molecule at the transfer distance of 4.24 Å.

A syn outer-sphere oxidative addition: the reaction mechanism in Pd/Senphos-catalyzed carboboration of 1,3-enynes.

We report a combined experimental and computational study of Pd/Senphos-catalyzed carboboration of 1,3-enynes utilizing DFT calculations, 31P NMR study, kinetic study, Hammett analysis and Arrhenius/Eyring analysis. Our mechanistic study provides evidence against the conventional inner-sphere β-migratory insertion mechanism. Instead, a syn outer-sphere oxidative addition mechanism featuring a Pd-π-allyl intermediate followed by coordination-assisted rearrangements is consistent with all the experimental observations.

Reactivity of Ir(I)-aminophosphane platforms towards oxidants.

The iridium(I)-aminophosphane complex [Ir{κ3C,P,P'-(SiNP-H)}(cod)] has been prepared by reaction of [IrCl(cod)(SiNP)] with KCH3COO. DFT calculations show that this reaction takes place through an unexpected outer sphere mechanism (SiNP = SiMe2{N(4-C6H4Me)PPh2}2; SiNP-H = CH2SiMe{N(4-C6H4Me)PPh2}2). The reaction of [IrCl(cod)(SiNP)] or [Ir{κ3C,P,P'-(SiNP-H)}(cod)] with diverse oxidants has been explored, yielding a range of iridium(III) derivatives. On one hand, [IrCl(cod)(SiNP)] reacts with allyl chloride rendering the octahedral iridium(III) derivative [IrCl2(η3-C3H5)(SiNP)], which, in turn, reacts with tert-butyl isocyanide yielding the substitution product [IrCl(η3-C3H5)(CNtBu)(SiNP)]Cl via the observed intermediate [IrCl2(η1-C3H5)(CNtBu)(SiNP)]. On the other hand, the reaction of [Ir{κ3C,P,P'-(SiNP-H)}(cod)] with [FeCp2]X (X = PF6, CF3SO3), I2 or CF3SO3CH3 results in the metal-centered two-electron oxidation rendering a varied assortment of iridium(III) compounds. [Ir{κ3C,P,P'-(SiNP-H)}(cod)] reacts with [FeCp2]+ (1 : 2) in acetonitrile affording [Ir{κ3C,P,P'-(SiNP-H)}(CH3CN)3]2+ isolated as both the triflato and the hexafluorophosphato derivatives. Also, the reaction of [Ir{κ3C,P,P'-(SiNP-H)}(cod)] with I2 (1 : 1) yields a mixture of iridium(III) derivatives, namely the mononuclear compound [IrI(κ2P,P'-SiNP)(η2,η3-C8H11)]I, containing the η2,η3-cycloocta-2,6-dien-1-yl ligand, and two isomers of the dinuclear derivative [Ir2{κ3C,P,P'-(SiNP-H)}2(μ-I)3]I, the first species being isolated in low yield. DFT calculations indicate that [IrI(κ2P,P'-SiNP)(η2,η3-C8H11)]I forms as the result of a bielectronic oxidation of iridium(I) followed by the deprotonation of the cod ligand by iodide and the protonation of the methylene moiety of the [Ir{κ3C,P,P'-(SiNP-H)}] platform by the newly formed HI. Finally, the oxidation of [Ir{κ3C,P,P'-(SiNP-H)}(cod)] by methyl triflate proceeds via a hydride abstraction from the cod ligand, with the elimination of methane and the formation of the η2,η3-cycloocta-2,6-dien-1-yl ligand with the concomitant two-electron oxidation of the iridium centre. The crystal structures of selected compounds have been determined.

Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinones via Rh-thiourea catalyzed asymmetric hydrogenation.

Chiral tetrahydroquinoxalines and dihydroquinoxalinones represent the core structure of many bioactive molecules. Herein, a simple and efficient Rh-thiourea-catalyzed asymmetric hydrogenation for enantiopure tetrahydroquinoxalines and dihydroquinoxalinones was developed under 1 MPa H2 pressure at room temperature. The reaction was magnified to the gram scale furnishing the desired products with undamaged yield and enantioselectivity. Application of this methodology was also conducted successfully under continuous flow conditions. In addition, 1H NMR experiments revealed that the introduction of a strong Brønsted acid, HCl, not only activated the substrate but also established anion binding between the substrate and the ligand. More importantly, the chloride ion facilitated heterolytic cleavage of dihydrogen to regenerate the active dihydride species and HCl, which was computed to be the rate-determining step. Further deuterium labeling experiments and density functional theory (DFT) calculations demonstrated that this reaction underwent a plausible outer-sphere mechanism in this new catalytic transformation.

Robust and efficient transfer hydrogenation of carbonyl compounds catalyzed by NN-Mn(I) complexes.

A series of manganese(I) carbonyl complexes bearing structurally related NN- and NNN-chelating ligands have been synthesized and assessed as catalysts for transfer hydrogenation (TH). Notably, the NN-systems based on N-R functionalized 5,6,7,8-tetrahydroquinoline-8-amines, proved the most effective in the manganese-promoted conversion of acetophenone to 1-phenylethanol. In particular, the N-isopropyl derivative, Mn1, when conducted in combination with t-BuONa, was the standout performer mediating not only the reduction of acetophenone but also a range of carbonyl substrates including (hetero)aromatic-, aliphatic- and cycloalkyl-containing ketones and aldehydes with especially high values of TON (up to 17 200; TOF of 3550 h-1). These findings, obtained through a systematic variation of the N-R group of the NN ligand, are consistent with an outer-sphere mechanism for the hydrogen transfer. As a more general point, this Mn-based catalytic TH protocol offers an attractive and sustainable alternative for producing alcoholic products from carbonyl substrates.

Energetics of key Au(III)-substrate adducts relevant to catalytic hydroarylation of alkynes.

(P,C)-cyclometalated Au(III) complexes have shown remarkable ability to catalyze the intermolecular hydroarylation of alkynes. Evidence of an outer-sphere mechanism has been provided in a previous study and is confirmed here by analysing the experimental data and DFT calculations. In this work, we propose evaluation of critical energies of dissociation of Au(III) complexes with different substrates via energy-resolved mass spectrometry (ERMS) experiments and kinetic modelling. The kinetic model is based on a multi-collisional approach. On the one hand, the classification confirms the mechanism previously proposed; on the other hand, it supports the collisional model and its application to particularly fragile adducts.

Biphasic oxidation of diaquadichloro(1,10‐phenanthroline)chromium(III) by N‐bromosuccinimide and the formation of chromium(IV) and chromium(V)

AbstractThe kinetics of oxidation of diaquadichloro(1,10‐phenanthroline)chromium(III) complex, [CrIII(phen)(H2O)2Cl2]+, by N‐bromosuccinimide (NBS) is biphasic. The first faster step involves the oxidation of Cr(III) to Cr(IV). The second slower step is due to the oxidation of Cr(IV) to Cr(V). The reaction product is isolated and characterized by electron spin resonance (ESR), IR, and elemental analysis. The chromium(V) product is consistent with the formula [CrV(phen)Cl2(O)]Br. The rate constants kf and ks, for the faster and the slower steps respectively, were obtained using an Origin 9.0 software program. Values of both kf and ks, varied linearly with [NBS] at constant reaction conditions. The effect of pH on the reaction rate is investigated over the pH (4.11–6.01) range at 25.0°C. The rate constants kf and ks increased with increasing pH. This is consistent with hydroxo forms of the chromium species being more reactive than the aqua forms. Chromium(III) complexes, more often than not, are inert. The oxidation of the Cr(III) complex to Cr(IV), most likely, proceeds by an outer sphere mechanism. Since chromium(IV) is labile the mechanism of its oxidation to chromium(V) is not certain.

Anticancer Activity, Reduction Mechanism and G-Quadruplex DNA Binding of a Redox-Activated Platinum(IV)-Salphen Complex.

Aiming at reducing the unselective cytotoxicity of Pt(II) chemotherapeutics, a great deal of effort has been concentrated into the design of metal-containing drugs with different anticancer mechanisms of action. Inert Pt(IV) prodrugs have been proposed to be a valid alternative as they are activated by reduction directly into the cell releasing active Pt(II) species. On the other hand, a promising strategy for designing metallodrugs is to explore new potential biological targets rather than canonical B-DNA. G-quadruplex nucleic acid, obtained by self-assembly of guanine-rich nucleic acid sequences, has recently been considered an attractive target for anticancer drug design. Therefore, compounds capable of binding and stabilizing this type of DNA structure would be greatly beneficial in anticancer therapy. Here, computational analysis reports the mechanism of action of a recently synthesized Pt(IV)-salphen complex conjugating the inertness of Pt(IV) prodrugs with the ability to bind G-quadruplexes of the corresponding Pt(II) complex. The reduction mechanism of the Pt(IV) complex with a biological reducing agent was investigated in depth by means of DFT, whereas classical MD simulations were carried out to shed light into the binding mechanism of the released Pt(II) complex. The results show that the Pt(IV) prodrug may be reduced by both inner- and outer-sphere mechanisms, and the active Pt(II) complex, as a function of its protonation state, stabilizes the G-quadruplex DNA prevalently, either establishing π-stacking interactions with the terminal G-tetrad or through electrostatic interactions along with H-bonds formation.