Nucleophilic Attack Pathway Research Articles

Mechanism and Origins of Nucleophile‐Controlled Regioselectivity of Palladium‐Catalyzed Allylic C−H Amination of 1,4‐Dienes: A Computational Study

AbstractDensity functional theory calculations have been conducted to investigate the palladium‐catalyzed allylic C−H amination of 1,4‐dienes with commonly available amines. The computations indicate that the reaction begins with the allylic C−H bond cleavage through the concerted proton and two‐electron transfer process to forge the η3‐allyl Pd(II) species. The ensuing C−N bond formation was found to be highly dependent on the basicity of the nucleophile, enabling the regioselectivity switch upon change of the nucleophile. With the weakly basic aromatic amine, the reaction occurs through the hydrogen‐bonding enabled inner‐sphere nucleophilic attack pathway. The distance between the reacting carbon atom and the terminal carbon atom is responsible for the Z/E‐selectivity. The regioselectivity is primarily due to steric repulsion between the allyl group and the ligand. On the other hand, the outer‐sphere nucleophilic attack pathway is favored for the reaction with the more basic aliphatic cyclic amine. The change of the coordinating mode of the allylic moiety was found to play a crucial role in determining the regioselectivity.

Mechanistic Insights into Oxidation of Benzaldehyde by Co-Peroxo Complexes.

Transition metal-peroxide complexes play a crucial role as intermediates in oxidation reactions. To unravel the mechanism of benzaldehyde oxidation by the Co-peroxo complex, we conducted density functional theory (DFT) calculations. The identified competing mechanisms include nucleophilic attack and hydrogen atom transfer (HAT). The nucleophilic attack pathway involves Co-O cleavage and nucleophilic attack, leading to the formation of the benzoate product. And the HAT pathway comprises O-O cleavage and HAT, ultimately resulting in the benzoate product. DFT calculations revealed that the formation of the end-on Co-superoxo complex 2 through Co-O cleavage, starting from the side-on Co-peroxo complex 1, is much more favorable than the formation of the two-terminal oxyl-radical intermediate 3 through O-O cleavage. Compared with the nucleophilic attack of benzaldehyde by 2, the abstraction of a hydrogen atom from benzaldehyde by 3 requires higher energy. The nature of the nucleophilicity of 2 and 3 accounts for the reactivity of the reaction.

Exploring the Cooperation of the Redox Non-Innocent Ligand and Di-Cobalt Center for the Water Oxidation Reaction Catalyzed by a Binuclear Complex.

Water oxidation is a crucial reaction in the artificial photosynthesis system. In the present work, density functional calculations were employed to decipher the mechanism of water oxidation catalyzed by a binuclear cobalt complex, which was disclosed to be a homogeneous water oxidation catalyst in pH=7 phosphate buffer. The calculations showed that the catalytic cycle starts from the CoIII,III-OH2 species. Then, a proton-coupled electron transfer followed by a one-electron transfer process leads to the generation of the formal CoIV,IV-OH intermediate. The subsequent PCET produces the active species, namely the formal CoIV,V=O intermediate (4). The oxidation processes mainly occur on the ligand moiety, including the coordinated water moiety, implying a redox non-innocent behavior. Two cobalt centers keep their oxidation states and provide one catalytic center for water activation during the oxidation process. 4 triggers the O-O bond formation via the water nucleophilic attack pathway, in which the phosphate buffer ion functions as the proton acceptor. The O-O bond formation is the rate-limiting step with a calculated total barrier of 17.7 kcal/mol. The last electron oxidation process coupled with an intramolecular electron transfer results in the generation of O2.

Supramolecular catalyst with [FeCl4] unit boosting photoelectrochemical seawater splitting via water nucleophilic attack pathway

Propelled by the structure of water oxidation co-catalysts in natural photosynthesis, molecular co-catalysts have long been believed to possess the developable potential in artificial photosynthesis. However, the interfacial complexity between light absorber and molecular co-catalyst limits its structural stability and charge transfer efficiency. To overcome the challenge, a supramolecular scaffold with the [FeCl4] catalytic units is reported, which undergo a water-nucleophilic attack of the water oxidation reaction, while the supramolecular matrix can be in-situ grown on the surface of photoelectrode through a simple chemical polymerization to be a strongly coupled interface. A well-defined BiVO4 photoanode hybridized with [FeCl4] units in polythiophene reaches 4.72 mA cm−2 at 1.23 VRHE, which also exhibits great stability for photoelectrochemical seawater splitting due to the restraint on chlorine evolution reaction by [FeCl4] units and polythiophene. This work provides a novel solution to the challenge of the interface charge transfer of molecular co-catalyst hybridized photoelectrode.

Mechanistic Regulation by Oxygen Vacancies in Structural Evolution Promoting Electrocatalytic Water Oxidation

Introduction of oxygen vacancies (Vo) has been considered an effective strategy for promoting the oxygen evolution reaction (OER) performance of electrocatalysts. However, the role of Vo in improving OER activity is unclear. Herein, a Vo-rich spinel Co3O4 was used as a model catalyst to explore the mechanism of Vo in structural evolution during OER. The results suggest that the Vo-rich environment facilitates the reconstruction of Co3O4 to the Co(OH)2 intermediate with proton vacancies (Co(II)Ox(OH)y), which is favorable for the formation of the active species of CoOOH. Correlative operando characterizations and electrokinetic analyses indicate that a moderate Vo density can switch the O–O bond formation pathway, from a water nucleophilic attack to an intramolecular nucleophilic attack pathway, which is more kinetically favorable for water oxidation. However, a high Vo density quenches the formation of highly valent active intermediates. This study provides significant insights into the crucial role of vacancy defects during OER.

Antioxidase‐Like Nanobiocatalysts with Ultrafast and Reversible Redox‐Centers to Secure Stem Cells and Periodontal Tissues

AbstractExploration of efficient antioxidase‐like reactive oxygen nanobiocatalysts (ROBCs) is a major challenge in combating oxidative stress‐related diseases. Herein, the molecularly well‐defined Ru‐porphyrin‐networks (Ru‐Por‐Net)‐based ROBCs with ultrafast and reversible redox‐centers for catalytic elimination of reactive oxygen species (ROS) are reported. Owing to the large π‐conjugated networks, Ru–N coordination structures, and unique electronic and redox properties of atomic Ru sites, the Ru‐Por‐Net‐based ROBCs exhibit exceptional catalytic ROS‐scavenging activities. It is considerably more efficient than recently reported state‐of‐the‐art anti‐ROS biocatalysts. Notably, a new nucleophilic attack pathway to eliminate H2O2 and produce O2 is proposed via theoretical calculations, and the desorption of the OO* process is identified as the rate‐determining step of atomic Ru centers. Cellular studies reveal that the new ROBCs can efficiently secure the survival, adhesion, spreading, and differentiation of the stem cells in high‐ROS‐level microenvironments. In vivo rat periodontitis treatments further demonstrate their superior anti‐ROS therapeutic effects. This study provides significant insights into the crucial functions of Ru–N coordinated porphyrin‐networks in catalytic ROS‐scavenging and offers a new strategy to engineer high‐performance antioxidase‐like nanobiocatalysts for stem cell‐based therapies and inflammatory diseases.

Engineering a molecular ruthenium catalyst into three-dimensional metal covalent organic frameworks for efficient water oxidation.

The water oxidation reaction plays an important role in clean energy conversion, utilization, and storage, but mimicking the oxygen-evolving complex of photosystem II for designing active and stable water oxidation catalysts (WOCs) is still an appealing challenge. Here, we innovatively engineered a molecular ruthenium WOC as a metal complex building unit to construct a series of three-dimensional metal covalent organic frameworks (3D MCOFs) for realizing efficient oxidation catalysis. The resultant MCOFs possessed rare 3D interlocking structures with inclined interpenetration of two-dimensional covalent rhombic nets, and the Ru sites were periodically arranged in the crystalline porous frameworks. Impressively, these MCOFs showed excellent performance towards water oxidation (the O2 evolution rate is as high as 2830 nmol g-1 s-1) via the water nucleophilic attack pathway. Besides, the MCOFs were also reactive for oxidizing organic substrates. This work highlights the potential of MCOFs as a designable platform in integrating molecular catalysts for various applications.

Gold(I)-Catalyzed Tandem Cyclization/Hydroarylation of o-Alkynylphenols with Haloalkynes.

A convenient and mild protocol for the gold-catalyzed intermolecular coupling of o-alkynylphenols with haloalkynes to give vinyl benzofurans is reported. In this work, the gold catalyst SIPrAuCl and the co-catalyst NaBARF would corporately promote the intramolecular cyclization of the o-alkynylphenol to benzofuran, and then a selective hydroarylation of benzofuran to haloalkyne was catalyzed by the same catalysts. Computational studies suggest that the hydroarylation process takes place via a concerted nucleophilic attack pathway of the benzofuran to the C2 carbon of the activated haloalkyne, and reveal the original driving force of this hydroarylation process.

Intramolecular hydroxyl nucleophilic attack pathway by a polymeric water oxidation catalyst with single cobalt sites

Exploration of efficient water oxidation catalysts (WOCs) is the primary challenge in conversion of renewable energy into fuels. Here we report a molecularly well-defined heterogeneous WOC with Aza-fused, π-conjugated, microporous polymer (Aza-CMP) coordinated single cobalt sites (Aza-CMP-Co). The single cobalt sites in Aza-CMP-Co exhibited superior activity under alkaline and near-neutral conditions. Moreover, the molecular nature of the isolated catalytic sites makes Aza-CMP-Co a reliable model for studying the heterogeneous water oxidation mechanism. By a combination of experimental and theoretical results, a pH-dependent nucleophilic attack pathway for O-O bond formation was proposed. Under alkaline conditions, the intramolecular hydroxyl nucleophilic attack (IHNA) process with which the adjacent -OH group nucleophilically attacks Co4+=O was identified as the rate-determining step. This process leads to lower activation energy and accelerated kinetics than those of the intermolecular water nucleophilic attack (WNA) pathway. This study provides significant insights into the crucial function of electrolyte pH in water oxidation catalysis and enhancement of water oxidation activity by regulation of the IHNA pathway.

A Water-Soluble Highly Oxidizing Cobalt Molecular Catalyst Designed for Bioinspired Water Oxidation.

Herein, we present a stable water-soluble cobalt complex supported by a dianionic 2,2'-([2,2'-bipyridine]-6,6'-diyl)bis(propan-2-ol) ligand scaffold, which is a rare example of a high-oxidation species, as demonstrated by structural, spectroscopic and theoretical data. Electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements revealed that the CoIV center of the mononuclear complex in the solid state resides in the high spin state (sextet, S=5/2). The complex can effectively catalyze water oxidation via a single-site water nucleophilic attack pathway with an overpotential of only 360 mV in a phosphate buffer with a pH of 6. The key intermediate toward water oxidation was speculated based on theoretical calculations and was identified by in situ spectroelectrochemical experiments. The results are important regarding the accessibility of high-oxidation state metal species in synthetic models for achieving robust and reactive oxidation catalysis.

A Water‐Soluble Highly Oxidizing Cobalt Molecular Catalyst Designed for Bioinspired Water Oxidation

Herein, we present a stable water-soluble cobalt complex supported by a dianionic 2,2′-([2,2′-bipyridine]-6,6′-diyl)bis(propan-2-ol) ligand scaffold, which is a rare example of a high-oxidation species, as demonstrated by structural, spectroscopic and theoretical data. Electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements revealed that the CoIV center of the mononuclear complex in the solid state resides in the high spin state (sextet, S=5/2). The complex can effectively catalyze water oxidation via a single-site water nucleophilic attack pathway with an overpotential of only 360 mV in a phosphate buffer with a pH of 6. The key intermediate toward water oxidation was speculated based on theoretical calculations and was identified by in situ spectroelectrochemical experiments. The results are important regarding the accessibility of high-oxidation state metal species in synthetic models for achieving robust and reactive oxidation catalysis.

Mechanistic investigation of zwitterionic MOF-catalyzed enyne annulation using UNLPF-14-MnIII as catalyst

Hybrid quantum mechanics/molecular mechanics calculations were performed to elucidate how [MnIIIporphyrin]+X−-based metal-organic frameworks (MOFs) catalyze the [2 + 1] cycloisomerization of enynes and why zwitterionic MOFs exhibit strong activity in Lewis acid catalysis. The calculations showed that zwitterionic MOFs have a “pure cationic active center” leading to a concerted nucleophilic attack pathway with lower barriers. In contrast, metals with coordinating anions have reduced electrophilicity, resulting in a stepwise radical-type pathway with much higher barriers. Further calculations showed the nature of catalysis was strongly depended on the charge on the anion ligand. A good linear relationship between the NPA charge and barrier was found, and verified by 73 anions with small derivations, which presents a universal adaptive character for various coordinated anions.

Switching the O–O bond-formation mechanism by controlling water activity

Switching the O–O bond-formation mechanism by controlling water activity

Oxygen Atom Transfer as an Alternative Pathway for Oxygen-Oxygen Bond Formation.

Fundamental understanding of catalytic mechanisms of water oxidation is a prerequisite for the design and development of efficient and rugged water oxidation catalysts. In this work, a detailed mechanistic study of the water oxidation mechanism of the [RuII(npm)(4-pic)2(H2O)]2+ (npm = 4-t-butyl-2,6-di(1',8'-naphthyrid-2'-yl)-pyridine, pic = 4-picoline) complex, [RuII-OH2]2+, reveals oxygen atom transfer from highly reactive ruthenium oxo intermediates to noncoordinating nitrogen atoms of the ligand as a novel route for oxygen evolution via storage of oxidizing equivalents as N-oxide groups on the ligand framework. Theoretical calculations show that the initial complex, [RuII-OH2]2+, is transformed to a di-N-oxide [RuII-OH2,(-NO)2]2+ complex upon oxidation via facile OAT steps from RuV=O species and that [RuV=O,(-NO)2]3+ represents the most likely reactive species for the critical O-O bond formation. Furthermore, a new stepwise mechanism for oxygen evolution is introduced, which proceeds via coupling of Ru-O and N-O moieties producing a peroxide intermediate, [RuV-OO-N,(-NO)]3+, and can compete with the water nucleophilic attack pathway for the oxygen evolution reaction. In this mechanism, a water molecule is oxidatively activated to an "oxygen atom" which is "stored" at a noncoordinating pyridine. Oxidative activation of a second water molecule, facilitated by coordination expansion of the intermediate N-oxide, generates the second oxygen atom required to produce a dioxygen molecule.

Metal‐Free Oxidative B−N Coupling of nido‐Carborane with N‐Heterocycles

A general method for the oxidative substitution of nido-carborane (7,8-C2 B9 H12 - ) with N-heterocycles has been developed by using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant. This metal-free B-N coupling strategy, in both inter- and intramolecular fashions, gave rise to a wide array of charge-compensated, boron-substituted nido-carboranes in high yields (up to 97 %) with excellent functional-group tolerance under mild reaction conditions. The reaction mechanism was investigated by density-functional theory (DFT) calculations. A successive single-electron transfer (SET), B-H hydrogen-atom transfer (HAT), and nucleophilic attack pathway is proposed. This method provides a new approach to nitrogen-containing carboranes with potential applications in medicine and materials.

Metal‐Free Oxidative B−N Coupling of nido‐Carborane with N‐Heterocycles

AbstractA general method for the oxidative substitution of nido‐carborane (7,8‐C2B9H12−) with N‐heterocycles has been developed by using 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ) as an oxidant. This metal‐free B−N coupling strategy, in both inter‐ and intramolecular fashions, gave rise to a wide array of charge‐compensated, boron‐substituted nido‐carboranes in high yields (up to 97 %) with excellent functional‐group tolerance under mild reaction conditions. The reaction mechanism was investigated by density‐functional theory (DFT) calculations. A successive single‐electron transfer (SET), B−H hydrogen‐atom transfer (HAT), and nucleophilic attack pathway is proposed. This method provides a new approach to nitrogen‐containing carboranes with potential applications in medicine and materials.

Lability and Basicity of Bipyridine-Carboxylate-Phosphonate Ligand Accelerate Single-Site Water Oxidation by Ruthenium-Based Molecular Catalysts.

A critical step in creating an artificial photosynthesis system for energy storage is designing catalysts that can thrive in an assembled device. Single-site catalysts have an advantage over bimolecular catalysts because they remain effective when immobilized. Hybrid water oxidation catalysts described here, combining the features of single-site bis-phosphonate catalysts and fast bimolecular bis-carboxylate catalysts, have reached turnover frequencies over 100 s-1, faster than both related catalysts under identical conditions. The new [(bpHc)Ru(L)2] (bpH2cH = 2,2'-bipyridine-6-phosphonic acid-6'-carboxylic acid, L = 4-picoline or isoquinoline) catalysts proceed through a single-site water nucleophilic attack pathway. The pendant phosphonate base mediates O-O bond formation via intramolecular atom-proton transfer with a calculated barrier of only 9.1 kcal/mol. Additionally, the labile carboxylate group allows water to bind early in the catalytic cycle, allowing intramolecular proton-coupled electron transfer to lower the potentials for oxidation steps and catalysis. That a single-site catalyst can be this fast lends credence to the possibility that the oxygen evolving complex adopts a similar mechanism.

The Ru-tpc Water Oxidation Catalyst and Beyond: Water Nucleophilic Attack Pathway versus Radical Coupling Pathway

Many Ru water oxidation catalysts have been documented in the literature. However, only a few can catalyze the O–O bond formation via the radical coupling pathway, while most go through the water nucleophilic attack pathway. Understanding the electronic effect on the reaction pathway is of importance in design of active water oxidation catalysts. The Ru-bda (bda = 2,2′-bipyridine-6,6′-dicarboxylate) catalyst is one example that catalyzes the O–O bond formation via the radical coupling pathway. Herein, we manipulate the equatorial backbone ligand, change the doubly charged bda2– ligand to a singly charged tpc– (2,2′:6′,2″-terpyridine-6-carboxylate) ligand, and study the structure–activity relationship. Surprisingly, kinetics measurements revealed that the resulting Ru-tpc catalyst catalyzes water oxidation via the water nucleophilic attack pathway, which is different from the Ru-bda catalyst. The O–O bond formation Gibbs free energy of activation (ΔG⧧) at T = 298.15 K was 20.2 ± 1.7 kcal mol–1. The electro...

A nickel (II) PY5 complex as an electrocatalyst for water oxidation

A Ni-PY5 [PY5=2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine)] complex has been found to act as an electrocatalyst for oxidizing water to dioxygen in aqueous phosphate buffer solutions. The rate of water oxidation catalyzed by the Ni-PY5 is remarkably enhanced by the proton acceptor base HPO42−, with rate constant of 1820M−1s−1. Controlled potential bulk electrolysis with Ni-PY5 at pH 10.8 under an applied potential of 1.5V vs. normal hydrogen electrode (NHE) resulted in dioxygen formation with a high faradaic efficiency over 90%. A detailed mechanistic study identifies the water nucleophilic attack pathway for water oxidation catalysis.

Design of a dinuclear ruthenium based catalyst with a rigid xanthene bridge for catalytic water oxidation

A new dinuclear ruthenium complex 1 (L1[Ru(bda)2(picoline)]2) based on Ru–bda (H2bda=2,2′-bipyridine-6,6′-dicarboxylic acid) and dipyridyl xanthene (L1=4,5-dipyridyl-2,7-di-tert-butyl-9,9-dimethyl xanthene) ligand was synthesized to probe the catalytic oxidation of water. An oxygen evolution experiment displays a low catalytic water oxidation activity with a first-order reaction kinetic mechanism. The result indicates that the OO bond formation of the dinuclear catalyst 1 follows a water nucleophilic attack pathway rather than a radical coupling pathway. The most plausible interpretation is that the steric hindrance effects of the L1 and bda ligands lead to a disadvantage in forming the face-to-face configuration of the two active sites in a one dimer molecule.