Oxidative Addition Step Research Articles

Hydrogenation Studies of Iridium Pyridine Diimine Complexes with O- and S-Donor Ligands (Hydroxido, Methoxido and Thiolato)

For square-planar late transition metal pyridine, diimine (Rh, Ir) complexes with hydro-xido, methoxido, and thiolato ligands. We could previously establish sizable metal-O- and S π-bonding interactions. Herein, we report the hydrogenation studies of iridium hydroxido and methoxido complexes, which quantitatively lead to the trihydride compound and water/methanol. The iridium trihydride displays a highly fluctional structure with scrambling hydrogen atoms, which can be described as a dihydrogen hydride system based on NMR and DFT investigations. This contrasts the iridium sulfur compounds, which are not reacting with dihydrogen. According to DFT and LNO-CCSD(T) calculations, hydrogenation of the methoxido complex proceeds by a two-step mechanism, i.e., an oxidative addition step of H2 to an Ir(III) dihydride intermediate with consecutive reductive O-H elimination of methanol. Based on PNO-CCSD(T) calculations, the reactivity difference between the O- and S-donors can be traced to the stronger H-O bonds in the water/methanol products compared to the S-H bonds in the sulphur congeners, which serves as a driving force for hydrogenation.

DFT Investigation on Palladium-Catalyzed [2 + 2 + 1] Spiroannulation between Aryl Halides and Alkynes: Mechanism, Base Additive Role, and Solvent and Ligand Effects.

Transition metal-catalyzed spiroannulations are practical strategies for constructing spirocyclic skeletons of pharmaceutical and biological significance, yet the microscopic mechanism still lacks in-depth explorations. Here, the palladium-catalyzed [2 + 2 + 1] spiroannulation between aryl halides and alkynes was studied by employing the density functional theory (DFT) method. Based on comprehensive explorations on a couple of possible reaction pathways, it is found that the reaction probably experiences C-I oxidative addition, alkyne migration insertion, Cs2CO3-assisted aryl C-H activation, C-Br bond oxidative addition, C-C coupling, arene dearomatization and reductive elimination in sequence and leads to the formation of the spiro[4,5]decane pentacyclic product (P) ultimately. Among these, the C-Br bond oxidative addition step acts as the rate-determining step (RDS) of the whole reaction, featuring a practical free energy barrier of 32.4 kcal·mol-1 at 130 °C. Computationally predicted kinetics such as half-life transferred from the RDS step's barrier on the optimal reaction pathway (1.2 × 101 h) coincides well with corresponding experimental results (91% yield of the spiro[4,5]decane pentacyclic product P after reacting 10 h at 130 °C). In addition, theoretical predictions regarding the solvent/ligand effects and base additive role in the reaction, rationalized by distortion-interaction/natural population/noncovalent interaction analyses, are also in good agreement with experimental data and trend. This good agreement between experiment and theory makes sense for new designations and further experimental improvements of such Pd-catalyzed transformations.

Hydroxy Group-Enabled Regio- and Stereoselective Hydroalkylation of Alkynyl Cyclobutanol via Palladium-Catalyzed C-C Bond Activation of Cyclopropanol: A One-Step Access to Vinyl Cyclobutanols.

The regio-/stereoselective synthesis of vinyl cyclobutanols from alkynyl cyclobutanols is demonstrated. Here, selective C-C bond activation of the cyclopropyl alcohol ring has been achieved in the presence of the cyclobutanol ring. The KIE experiments indicated the noninvolvement of the O-H oxidative addition step in the rate-determining step. Further, the applicability of these vinyl cyclobutanols for the synthesis of 1,4-diketones and 1,6-diketone is demonstrated.

Unlocking Enantioselectivity: Synergy of 2-Pyridone and Chiral Amino Acids in Pd-Catalyzed β-C(sp3)-H Transformations.

Enantioselective C(sp3)-H activation has garnered significant attention in synthetic and computational chemistry. Chiral transient directing groups (TDGs) hold promise for enabling Pd(II)-catalyzed enantioselective C(sp3)-H functionalization. Despite the interest in this strategy, it presents a challenge because the stereogenic center on the chiral TDG is frequently distant from the C-H bond, leading to a mixture of functionalized products. Our computational study on Pd(II)-catalyzed enantioselective β-C(sp3)-H arylation of aliphatic ketone with chiral amino acids provides a sustainable route to synthesizing complex chiral molecular scaffolds. The cooperative action of 2-pyridone derivatives and chiral amino acids is crucial in promoting the enantio-discriminating C-H activation, oxidative addition, and reductive elimination steps. Using 5-nitro-2-pyridone as the optimal external ligand demonstrates its ability to achieve the highest level of enantioselection. In contrast, the modeled 3,5-di((trifluoromethyl)sulfonyl)-2-pyridone ligand facilitates the most straightforward C-H activation. This study underscores the pivotal role of the alkyl substituent at the α-position of the amino acid (TDG) in altering enantioselectivity.

Rationalization of a Streptavidin Based Enantioselective Artificial Suzukiase: An Integrative Computational Approach.

An Artificial Metalloenzyme (ArM) built employing the streptavidin-biotin technology has been used for the enantioselective synthesis of binaphthyls by means of asymmetric Suzuki-Miyaura cross-coupling reactions. Despite its success, it remains a challenge to understand how the length of the biotin cofactors or the introduction of mutations to streptavidin leads the preferential synthesis of one atropisomer over the other. In this study, we apply an integrated computational modeling approach, including DFT calculations, protein-ligand dockings and molecular dynamics to rationalize the impact of mutations and length of the biotion cofactor on the enantioselectivities of the biaryl product. The results unravel that the enantiomeric differences found experimentally can be rationalized by the disposition of the first intermediate, coming from the oxidative addition step, and the entrance of the second substrate. The work also showcases the difficulties facing to control the enantioselection when engineering ArM to catalyze enantioselective Suzuki-Miyaura couplings and how the combination of DFT calculations, molecular dockings and MD simulations can be used to rationalize artificial metalloenzymes.

Consolidation of the Oxidant-Free Au(I)/Au(III) Catalysis Enabled by the Hemilabile Ligand Strategy.

In this minireview we survey the challenges and strategies in gold redox catalysis. Gold's reluctance to oxidative addition reactions due to its high redox potential limits its applicability. Initial attempts to overcome this problem focused on the use of sacrificial external oxidants in stoichiometric amounts to bring Au(I) compounds to Au(III) reactive species. Recently, innovative approaches focused on employing hemilabile ligands, which are capable of coordinating to Au(I) and stabilizing square-planar Au(III) intermediates, thus facilitating oxidative addition steps and enabling oxidant-free catalysis. Notable examples include the use of the (P^N) bidendate MeDalphos ligand to achieve various cross-coupling reactions via oxidative addition Au(I)/Au(III). Importantly, hemilabile ligand-enabled catalysis allows merging oxidative addition with π-activation, such as oxy- and aminoarylation of alkenols and alkenamines using organohalides, expanding gold's versatility in C-C and C-heteroatom bond formations and unprecedented cyclizations. Moreover, recent advancements in enantioselective catalysis using chiral hemilabile (P^N) ligands are also surveyed. Strikingly, versatile bidentate (C^N) hemilabile ligands as competitors of MeDalphos have appeared recently, by designing scaffolds where phosphine groups are substituted by N-heterocyclic or mesoionic carbenes. Overall, these approaches highlight the evolving landscape of gold redox catalysis and its tremendous potential in a broad scope of transformations.

Consolidation of the Oxidant‐Free Au(I)/Au(III) Catalysis Enabled by the Hemilabile Ligand Strategy

AbstractIn this minireview we survey the challenges and strategies in gold redox catalysis. Gold's reluctance to oxidative addition reactions due to its high redox potential limits its applicability. Initial attempts to overcome this problem focused on the use of sacrificial external oxidants in stoichiometric amounts to bring Au(I) compounds to Au(III) reactive species. Recently, innovative approaches focused on employing hemilabile ligands, which are capable of coordinating to Au(I) and stabilizing square‐planar Au(III) intermediates, thus facilitating oxidative addition steps and enabling oxidant‐free catalysis. Notable examples include the use of the (P^N) bidendate MeDalphos ligand to achieve various cross‐coupling reactions via oxidative addition Au(I)/Au(III). Importantly, hemilabile ligand‐enabled catalysis allows merging oxidative addition with π‐activation, such as oxy‐ and aminoarylation of alkenols and alkenamines using organohalides, expanding gold‘s versatility in C−C and C‐heteroatom bond formations and unprecedented cyclizations. Moreover, recent advancements in enantioselective catalysis using chiral hemilabile (P^N) ligands are also surveyed. Strikingly, versatile bidentate (C^N) hemilabile ligands as competitors of MeDalphos have appeared recently, by designing scaffolds where phosphine groups are substituted by N‐heterocyclic or mesoionic carbenes. Overall, these approaches highlight the evolving landscape of gold redox catalysis and its tremendous potential in a broad scope of transformations.

Dual Photoredox and Nickel Catalysis in Regioselective Diacylation: Exploring the Versatility of Nickel Oxidation States in Allene Activation.

We present a nickel-catalyzed regioselective radical diacylation of allenes with ketoacids to produce 1,4-dione products by dual photoredox and nickel catalysis. This integrated approach merges redox-active oxidative addition and reductive elimination steps with migratory insertion. The acyl radical generated in the photoredox cycle sequentially adds to Ni(I) and Ni(II) intermediates following a Ni(I)-Ni(II)-Ni(II)-Ni(III)-Ni(I) catalytic cycle. This methodology, supported by DFT calculations, demonstrates the potential of nickel catalysis in the creation of complex molecular architectures.

One-step Mo-doped praseodymium oxide construction of oxygen vacancies for efficient photothermal co-catalytic Suzuki coupling reaction

The photothermal synergistic catalytic Suzuki coupling reaction is a sustainable approach to generate biphenyl compounds using clean and renewable solar energy. The one-step Mo doping engineering resulted in more oxygen vacancies and surface free electrons on the PrxOy surface of hollow porous nanotube morphology. Subsequently, energy-efficient and environmentally friendly catalysts (PdO/PrxOy−Moz) with higher catalytic activity were successfully prepared by deposition precipitation method. The concave and convex surfaces of the carriers could better capture visible light. Mo doping greatly extends the visible absorption range of PrxOy. More OVs defects in the PrxOy−Moz carrier inhibit the complexation of photogenerated electron-hole pairs and induce the transfer of free and photogenerated electrons to Pd. The electron-rich Pd accelerated the oxidative addition step of aryl halides to aryl phenylboronic acids, which greatly improved the catalytic performance of PdO/PrxOy−Moz in the photothermal co-catalytic Suzuki coupling reaction.

Mechanistic study on the side arm effect in a palladium/Xu-Phos-catalyzed enantioselective alkoxyalkenylation of γ-hydroxyalkenes

Recently, the asymmetric bifunctionalization of alkenes has received much attention. However, the development of enantioselective alkoxyalkenylation has posed a considerable challenge and has lagged largely behind. Herein, we report a new palladium-catalyzed enantioselective alkoxyalkenylation reaction, using a range of primary, secondary, and tertiary γ-hydroxy-alkenes with alkenyl halides. By employing newly identified Xu-Phos (Xu8 and Xu9) with a suitable side-arm adjacent to the PCy2 motif, a series of allyl-substituted tetrahydrofurans were obtained in good yields with up to 95% ee. Besides (E)-alkenyl halides, (Z)-alkenyl halide was also examined and provided the corresponding (Z)-product as a single diastereomer, supporting a stereospecific oxidative addition and reductive elimination step. Moreover, deuterium labeling and VCD experiments were employed to determine a cis-oxypalladation mechanism. DFT calculations helped us gain deeper insight into the side-arm effect on the chiral ligand. Finally, the practicability of this method is further demonstrated through a gram-scale synthesis and versatile transformations of the products.

Advancing Gold Redox Catalysis: Mechanistic Insights, Nucleophilicity-Guided Transmetalation, and Predictive Frameworks for the Oxidation of Aryl Gold(I) Complexes.

Gold redox catalysis, often facilitated by hypervalent iodine(III) reagents, offers unique reactivity but its progress is mainly hindered by an incomplete mechanistic understanding. In this study, we investigated the reaction between the gold(I) complexes [(aryl)Au(PR3 )] and the hypervalent iodine(III) reagent PhICl2 , both experimentally and computationally and provided an explanation for the formation of divergent products as the ligands bonded to the gold(I) center change. We tackled this essential question by uncovering an intriguing transmetalation mechanism that takes place between gold(I) and gold(III) complexes. We found that the ease of transmetalation is governed by the nucleophilicity of the gold(I) complex, [(aryl)Au(PR3 )], with greater nucleophilicity leading to a lower activation energy barrier. Remarkably, transmetalation is mainly controlled by a single orbital - the gold dx 2 -y 2 orbital. This orbital also has a profound influence on the reactivity of the oxidative addition step. In this way, the fundamental mechanistic basis of divergent outcomes in reactions of aryl gold(I) complexes with PhICl2 was established and these observations are reconciled from first principles. The theoretical model developed in this study provides a conceptual framework for anticipating the outcomes of reactions involving [(aryl)Au(PR3 )] with PhICl2 , thereby establishing a solid foundation for further advancements in this field.

Experimental and computational study of the catalytic activity of Pd and PdCu nanoparticle catalysts and clusters supported on reduced graphene oxide and graphene acid for the suzuki cross-coupling reaction

The catalytic activity of Pd and PdCu nanoparticle catalysts and clusters supported on reduced graphene oxide (RGO) and graphene acid (GA) toward the Suzuki cross-coupling reaction between bromobenzene and phenylboronic acid is investigated experimentally and computationally. The experimental results indicate that the bimetallic PdCu nanoparticle catalysts supported on RGO or GA outperform the supported Pd catalysts and that the PdCu/RGO catalyst exhibits superior activity, reaching a full conversion to the biphenyl product in only 15 min under ambient conditions. The experimental results show that both the Pd and PdCu catalysts have higher activities when supported on RGO than when supported on GA. The computational results using density functional theory show that the RGO provides relatively better support for the C-C coupling reaction than GA. Investigations based on the charge analysis have further revealed that the RGO is a better charge donor and acceptor than GA, facilitating both the reaction's oxidative addition and reductive elimination steps by reducing the respective barrier heights. Doping a Cu atom near the Pd reaction site is shown to enhance this effect further. The relative reactivity trends of RGO- and GA-supported Pd and PdCu clusters obtained from the DFT calculations show exact agreement with the experimental results.

Trimethylsilyl Chloride Aids in Solubilization of Oxidative Addition Intermediates from Zinc Metal.

Trimethylsilyl chloride (TMSCl) is commonly used to "activate" metal(0) powders toward oxidative addition of organohalides, but knowledge of its mechanism remains limited by the inability to characterize chemical intermediates under reaction conditions. Here, fluorescence lifetime imaging microscopy (FLIM) overcomes these prior limitations and shows that TMSCl aids in solubilization of the organozinc intermediate from zinc(0) metal after oxidative addition, a previously unknown mechanistic role. This mechanistic role is in contrast to previously known roles for TMSCl before the oxidative addition step. To achieve this understanding, FLIM, a tool traditionally used in biology, is developed to characterize intermediates during a chemical reaction-thus revealing mechanistic steps that are unobservable without fluorescence lifetime data. These findings impact organometallic reagent synthesis and catalysis by providing a previously uncharacterized mechanistic role for a widely used activating agent, an understanding of which is suitable for revising activation models and for developing strategies to activate currently unreactive metals.

Trimethylsilyl Chloride Aids in Solubilization of Oxidative Addition Intermediates from Zinc Metal

AbstractTrimethylsilyl chloride (TMSCl) is commonly used to “activate” metal(0) powders toward oxidative addition of organohalides, but knowledge of its mechanism remains limited by the inability to characterize chemical intermediates under reaction conditions. Here, fluorescence lifetime imaging microscopy (FLIM) overcomes these prior limitations and shows that TMSCl aids in solubilization of the organozinc intermediate from zinc(0) metal after oxidative addition, a previously unknown mechanistic role. This mechanistic role is in contrast to previously known roles for TMSCl before the oxidative addition step. To achieve this understanding, FLIM, a tool traditionally used in biology, is developed to characterize intermediates during a chemical reaction—thus revealing mechanistic steps that are unobservable without fluorescence lifetime data. These findings impact organometallic reagent synthesis and catalysis by providing a previously uncharacterized mechanistic role for a widely used activating agent, an understanding of which is suitable for revising activation models and for developing strategies to activate currently unreactive metals.

Palladium/Norbornene‐Catalyzed Direct Vicinal Di‐Carbo‐Functionalization of Indoles: Reaction Development and Mechanistic Study

AbstractMethods that can simultaneously install multiple different functional groups to heteroarenes via C−H functionalizations are valuable for complex molecule synthesis, which, however, remain challenging to realize. Here we report the development of vicinal di‐carbo‐functionalization of indoles in a site‐ and regioselective manner, enabled by the palladium/norbornene (Pd/NBE) cooperative catalysis. The reaction is initiated by the Pd(II)‐mediated C3‐metalation and specifically promoted by the C1‐substituted NBEs. The mild, scalable, and robust reaction conditions allow for a good substrate scope and excellent functional group tolerance. The resulting C2‐arylated C3‐alkenylated indoles can be converted to diverse synthetically useful scaffolds. The combined experimental and computational mechanistic study reveals the unique role of the C1‐substituted NBE in accelerating the turnover‐limiting oxidative addition step.

Palladium/Norbornene-Catalyzed Direct Vicinal Di-Carbo-Functionalization of Indoles: Reaction Development and Mechanistic Study.

Methods that can simultaneously install multiple different functional groups to heteroarenes via C-H functionalizations are valuable for complex molecule synthesis, which, however, remain challenging to realize. Here we report the development of vicinal di-carbo-functionalization of indoles in a site- and regioselective manner, enabled by the palladium/norbornene (Pd/NBE) cooperative catalysis. The reaction is initiated by the Pd(II)-mediated C3-metalation and specifically promoted by the C1-substituted NBEs. The mild, scalable, and robust reaction conditions allow for a good substrate scope and excellent functional group tolerance. The resulting C2-arylated C3-alkenylated indoles can be converted to diverse synthetically useful scaffolds. The combined experimental and computational mechanistic study reveals the unique role of the C1-substituted NBE in accelerating the turnover-limiting oxidative addition step.

Engineering the Coordination Environment of Single‐Rh‐Site with N and S Atoms for Efficient Methanol Carbonylation

The local coordination environment of central active sites plays a critical role in tuning the catalytic properties of heterogeneous single‐metal‐site catalysts (HSMSCs). However, carbon supports with inert surface properties provide weak interaction with the active sites, which hamper the effective modulation of the coordination structure of HSMSCs. Herein, this work shows that introducing N and S atoms into carbon support can modify the coordination environment of single‐Rh‐site and effectively improves the catalytic activity for the methanol carbonylation reaction. The synthesized Rh/AC‐NS with single‐Rh‐site exhibits a high methanol conversion of 88% and a stable acetyl production rate of 2812 h−1, in contrast with 1285 h−1 of Rh/AC without N‐ and S‐ functional groups, and meanwhile remarkably higher than those of Rh/AC‐N and Rh/AC‐S with only N‐ or S‐ functional group under the same mild reaction conditions. As revealed by the experimental result and density functional theory (DFT) calculations, the special combination of N‐ and S‐ functional groups offers favorable coordination configuration and also beneficial electronic structure for facilitated CH3I oxidative addition and CO insertion steps of single‐Rh‐site. This work offers new opportunities for rationally tuning the coordination structure of HSMSCs for heterogeneous catalysis.

Template-OrientedPolyaniline-Supported Palladium Nanoclusters for Reductive Homocoupling of Furfural Derivatives.

Developing well-defined structures and desired properties for porous organic polymer (POP) supported catalysts by controlling their composition, size, and morphology is of great significance. Herein, we report a preparation of polyaniline (PANI) supported Pd nanoparticles (NPs) with controllable of the structure and morphology. The protocol involves the introduction of MnO2 with different crystal structures (α, β, γ, δ, ε) serving as both reaction templates and oxidants. MnO2 selectively oxidizes the aniline to polyaniline with diverse regular distribution of benzene and quinone, thus leading to the Pd/PANI catalyst growth mode which prominently impacts the charge transfer between Pd and PANI, as well as the dispersion of metal NPs. In particular, Pd/ε-PANI greatly improves the turnover frequency (TOF), up to 88.3 h-1,in the reductive coupling of the furfural derivatives to potential bio-based plasticizers. Systematic characterizations reveal the unique oxidation state of the support in the Pd/ε-PANI catalyst and coordination mode of Pd that drives the formation of highly dispersed Pd nanoclusters. Density functional theory (DFT) calculations show the more electron rich Pd/PANI catalyst has the lower energy barrier in the oxidative addition step, which favors the C-C coupling reaction.

Template‐Oriented Polyaniline‐Supported Palladium Nanoclusters for Reductive Homocoupling of Furfural Derivatives

AbstractDeveloping well‐defined structures and desired properties for porous organic polymer (POP) supported catalysts by controlling their composition, size, and morphology is of great significance. Herein, we report a preparation of polyaniline (PANI) supported Pd nanoparticles (NPs) with controllable structure and morphology. The protocol involves the introduction of MnO2 with different crystal structures (α, β, γ, δ, ϵ) serving as both the reaction template and the oxidant. The different forms of MnO2 each convert aniline to a PANI that contains a unique regular distribution of benzene and quinone. This leads to the Pd/PANI catalysts with different charge transfer properties between Pd and PANI, as well as different dispersions of the metal NPs. In this case, the Pd/ϵ‐PANI catalyst greatly improves the turnover frequency (TOF; to 88.3 h−1), in the reductive coupling of furfural derivatives to potential bio‐based plasticizers. Systematic characterizations reveal the unique oxidation state of the support in the Pd/ϵ‐PANI catalyst and coordination mode of Pd that drives the formation of highly dispersed Pd nanoclusters. Density functional theory (DFT) calculations show the more electron rich Pd/PANI catalyst has the lower energy barrier in the oxidative addition step, which favors the C−C coupling reaction.

Understanding Formation and Roles of NiII Aryl Amido and NiIII Aryl Amido Intermediates in Ni-Catalyzed Electrochemical Aryl Amination Reactions.

Ni-catalyzed electrochemical aryl amination (e-amination) is an attractive, emerging approach to building C-N bonds. Here, we report in-depth experimental and computational studies that examined the mechanism of Ni-catalyzed e-amination reactions. Key NiII-amine dibromide and NiII aryl amido intermediates were chemically synthesized and characterized. The combination of experiments and DFT calculations suggest (1) there is coordination of an amine to the NiII catalyst before the cathodic reduction and oxidative addition steps, (2) a stable NiII aryl amido intermediate is produced from the cathodic half-reaction, a critical step in controlling the selectivity between cross-coupling and undesired homo-coupling reaction pathways, (3) the diazabicycloundecene additive shifts the aryl halide oxidative addition mechanism from a NiI-based pathway to a Ni0-based pathway, and (4) redox-active bromide in the supporting electrolyte functions as a redox mediator to promote the oxidation of the stable NiII aryl amido intermediate to a NiIII aryl amido intermediate. Subsequently, the NiIII aryl amido intermediate undergoes facile reductive elimination to provide a C-N cross-coupling product at room temperature. Overall, our results provide new fundamental understandings about this e-amination reaction and guidance for further development of other Ni-catalyzed electrosynthetic reactions such as C-C and C-O cross-couplings.