Organometallic Intermediates Research Articles

Unexpected E-to-Z Isomerizations during the Negishi-Type Homocoupling of E-Iodoalkenes.

The direct insertion of Zn into olefin-halide bonds is a challenge. When (E)-alkenyl iodides were treated with a very large excess of Zn nanoparticles, in the presence of Pd(PPh3)4, the dimerization was observed but, unexpectedly, yielding mainly Z,E-1,3-dienes. This apparently contrathermodynamic E-to-Z isomerization of organometallic intermediates is predicted to be general and is explained with the aid of DFT [principally M06/6-311+G(d,p)], MP2, and CCSD(T) calculations.

Direct Visualization of Organometallic Intermediates on Cu(111) with Bond-Resolving Non-Contact Atomic Force Microscopy

Direct Visualization of Organometallic Intermediates on Cu(111) with Bond-Resolving Non-Contact Atomic Force Microscopy

An alcove at the acetyl-CoA synthase nickel active site is required for productive substrate CO binding and anaerobic carbon fixation

One of the seven natural CO2 fixation pathways, the anaerobic Wood-Ljungdahl pathway (WLP) is unique in generating CO as a metabolic intermediate, operating through organometallic intermediates, and in conserving (versus utilizing) net ATP. The key enzyme in the WLP is acetyl-CoA synthase (ACS), which uses an active site [2Ni-4Fe-4S] cluster (A-cluster), a CO tunnel, and an organometallic (Ni-CO, Ni-methyl, and Ni-acetyl) reaction sequence to generate acetyl-CoA. Here, we reveal that an alcove, which interfaces the tunnel and the A-cluster, is essential for CO2 fixation and autotrophic growth by the WLP. Invitro spectroscopy, kinetics, binding, and invivo growth experiments reveal that a Phe229A substitution at one wall of the alcove decreases CO affinity thirty-fold and abolishes autotrophic growth; however, a F229W substitution enhances CO binding 80-fold. Our results indicate that the structure of the alcove is exquisitely tuned to concentrate CO near the A-cluster; protect ACS from CO loss during catalysis, provide a haven for inhibitory CO, and stabilize the tetrahedral coordination at the Nip site where CO binds. The directing, concentrating, and protective effects of the alcove explain the inability of F209A to grow autotrophically. The alcove also could help explain current controversies over whether ACS binds CO and methyl through a random or ordered mechanism. Our work redefines what we historically refer to as the metallocenter "active site". The alcove is so crucial for enzymatic function that we propose it is part of the active site. The community should now look for such alcoves in all "gas handling" metalloenzymes.

Regioselective Palladium-Catalyzed Chain-Growth Allylic Amination Polymerization of Vinyl Aziridines.

Organometallic-mediated chain growth polymerization of readily accessible chemical building blocks is responsible for important commercial and technological advances in polymer science, but the incorporation of heteroatoms into the polymer backbone through these mechanisms remains a challenge. Transition metal π-allyl complexes are well-developed organometallic intermediates for carbon-heteroatom bond formation in small-molecule catalysis yet remain underexplored in polymer science. Here, we developed a regioselective palladium-phosphoramidite-catalyzed chain-growth allylic amination polymerization of vinyl aziridines for the synthesis of novel nitrogen-rich polymers via ambiphilic π-allyl complexes. The polymerization accessed a linear microstructure with four carbons between each nitrogen, which is challenging to achieve through other chain-growth polymerization approaches. The highly regioselective allylic amination polymerization demonstrated the characteristics of a controlled polymerization and was able to achieve molar masses exceeding 20 kg mol-1 with low dispersities (D̵ < 1.3). The identification of the polymer structure and well-defined chain ends were supported by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and chain extension experiments demonstrate opportunities for building more complex materials from this method. A Hammett study was performed to understand the role of the catalyst and monomer structure on regioselectivity, and the data supported a mechanism wherein regioselectivity was primarily controlled by the ligand-metal complex. Postpolymerization desulfonylation provided access to a novel polyamine that demonstrated broad anticancer activity in vitro, which highlights the benefits of unlocking novel polyamine microstructures through regioselective chain-growth allylic amination polymerization.

Predicting Organometallic Intermediates in the Surface-Assisted Ullmann Coupling of Chrysene Isomers.

On-surface polymerization of functional organic molecules has been recently recognized as a promising route to persistent low-dimensional structures with tailorable properties. In this contribution, using the coarse-grained Monte Carlo simulation method, we study the initial stage of the Ullmann coupling of doubly halogenated chrysene isomers adsorbed on a catalytically active (111) crystalline surface. To that end, we focus on the formation of labile metal-organic precursor structures preceding the covalent bonding of chrysene monomers. Four monomeric chrysene units with differently distributed halogen substituents were probed in the simulations, and the resulting precursor structures were compared and quantified. Moreover, the effect of (pro)chirality of chrysene tectons on the structure formation was elucidated by running separate simulations in enantiopure and racemic systems. The calculations showed that suitable manipulation of the halogen substitution pattern allows for the creation of diverse precursor architectures, ranging from straight and winded chains to cyclic oligomers with enantiopure, racemic, and nonracemic composition. The obtained findings can be helpful in developing synthetic strategies for covalent polymers with predefined architecture and functionality.

Two-Dimensional Nonbenzenoid Heteroacene Crystals Synthesized via In-Situ Embedding of Ladder Bipyrazinylenes on Au(111).

Precisely introducing topological defects is an important strategy in nanographene crystal engineering because defects can tune π-electronic structures and control molecular assemblies. The synergistic control of the synthesis and assembly of nanographenes by embedding the topological defects to afford two-dimensional (2D) crystals on surfaces is still a great challenge. By in-situ embedding ladder bipyrazinylene (LBPy) into acene, the narrowest nanographene with zigzag edges, we have achieved the precise preparation of 2D nonbenzenoid heteroacene crystals on Au(111). Through intramolecular electrocyclization of o-diisocyanides and Au adatom-directed [2+2] cycloaddition, the nonbenzenoid heteroacene products are produced with high chemoselectivity, and lead to the molecular 2D assembly via LBPy-derived interlocking hydrogen bonds. Using bond-resolved scanning tunneling microscopy, we determined the atomic structures of the nonbenzenoid heteroacene product and diverse organometallic intermediates. The tunneling spectroscopy measurements revealed the electronic structure of the nonbenzenoid heteroacene, which is supported by density functional theory (DFT) calculations. The observed distinct organometallic intermediates during progression annealing combined with DFT calculations demonstrated that LBPy formation proceeds via electrocyclization of o-diisocyanides, trapping of heteroarynes by Au adatoms, and stepwise elimination of Au adatoms.

Reactivities of Photoredox Generated Nickel‐Nucleophilic Reactive Organometallic Species

AbstractDual photoredox catalysis has revolutionized the field of cross‐coupling reactions, enabling the discovery of numerous highly efficient reactions. This breakthrough is attributed to the exceptional combination of nickel catalysis with photoredox catalysis. Nickel exhibits both oxidative addition and reductive elimination processes, and a wide range of oxidation states (ranging from I to IV) accessible within a single catalytic cycle. Furthermore, nickel complexes are capable of catalyzing various processes through radical mechanisms. The latest feature has proven to be incredibly potent in facilitating the formation of new C−C and C−X bonds (X=H, O, S, N). The powerful combination of photoredox and nickel catalysis reveals an expansive domain of unexplored possibilities. It offers unparalleled opportunities for improving reactions and exploring innovative pathways. Under photoredox conditions, it is possible to form nucleophilic reactive organometallic intermediates, useful in reaction with electrophiles. We have devoted a research program towards the rediscovery and use of organometallic reagents, introduced by Corey, Hegedus, and Semmelack many years ago. The results unveiled the extraordinary capabilities of photoredox catalysis, enabling the creation and efficient utilization of potent nucleophilic organometallic reagents under mild conditions, free from the need for strong bases or stoichiometric metal reductants.

Palladium and copper co-catalyzed chloro-arylation of gem-difluorostyrenes - use of a nitrite additive to suppress β-F elimination.

The installation of fluorine and fluorinated functional groups in organic molecules perturbs the physicochemical properties of those molecules and enables the development of new therapeutics, agrichemicals, biological probes and materials. However, current synthetic methodologies cannot access some fluorinated functional groups and fluorinated scaffolds. One such group, the gem-difluorobenzyl motif, might be convergently synthesized by reacting a nucleophilic aryl precursor and an electrophilic gem-difluoroalkene. Previous attempts have relied on forming unstable anionic or organometallic intermediates that rapidly decompose through a β-F elimination process to deliver monofluorovinyl products. In contrast, we report a fluorine-retentive palladium and copper co-catalyzed chloro-arylation of gem-difluorostyrenes that takes advantage of a nitrite (NO2 -) additive to avoid the favorable β-F elimination pathway that forms monofluorinated products, instead delivering difluorinated products.

Recent advances in organic molecule reactions on metal surfaces.

Chemical reactions of organic molecules on metal surfaces have been intensively investigated in the past decades, where metals play the role of catalysts in many cases. In this review, first, we summarize recent works on spatial molecules, small H2O, O2, CO, CO2 molecules, and the molecules carrying silicon groups as the new trends of molecular candidates for on-surface chemistry applications. Then, we introduce spectroscopy and DFT study advances in on-surface reactions. Especially, in situ spectroscopy technologies, such as electron spectroscopy, force spectroscopy, X-ray photoemission spectroscopy, STM-induced luminescence, tip-enhanced Raman spectroscopy, temperature-programmed desorption spectroscopy, and infrared reflection adsorption spectroscopy, are important to confirm the occurrence of organic reactions and analyze the products. To understand the underlying mechanism, the DFT study provides detailed information about reaction pathways, conformational evolution, and organometallic intermediates. Usually, STM/nc-AFM topological images, in situ spectroscopy data, and DFT studies are combined to describe the mechanism behind on-surface organic reactions.

Chelation-Assisted Iron-Catalyzed C-H Activations: Scope and Mechanism.

ConspectusTo improve the resource economy of molecular syntheses, researchers have developed strategies to directly activate otherwise inert C-H bonds, thus avoiding cumbersome and costly substrate prefunctionalizations. During the past two decades, remarkable progress in coordination chemistry has set the stage for developing increasingly viable metal catalysts for C-H activations. Despite remarkable advances, C-H activations are largely dominated by precious 4d and 5d transition metal catalysts based primarily on palladium, ruthenium, iridium, and rhodium, thus decreasing the inherent sustainable nature of the C-H activation approach. Therefore, advancing catalytic reactions based on Earth-abundant and less toxic 3d transition metals, especially nontoxic and inexpensive iron, represents a desirable and attractive alternative. While research had previously focused on 8-aminoquinoline directing groups in C-H activations, we have devised easily accessible, tunable, and clickable triazoles, which feature widespread applications in bioactive compounds and drugs, among others, as peptide isosteres. Thus, in contrast to other directing groups, the triazole group is a highly desirable structural motif and functions as a bioisostere in medicine and biology, where it is exploited to mimic amide bonds.This Account summarizes the evolution of chelation-assisted iron-catalyzed C-H activations via C-H, C-H/N-H, and C-H/N-H/C-C bond cleavages, with a topical focus on the most recent contributions of our team. Thus, the triazole-enabled iron catalysis has surfaced as a transformative platform for a large variety of C-H transformations, including arylations, alkylations, alkenylations, allylations, annulations, and alkynylations, achieved through C-H activations with organometallic reagents, organohalides, alkynes, alkenes, allenes, and bicyclopropylidenes among others. Consequently, we developed widely applicable methods for the versatile preparation of decorated arenes and heteroarenes, providing access to benzamides, isoquinolones, pyrrolones, pyridones, phenones, indoles, and isoindolinones, among others. Most of these reactions employed 1,2-dichloroisobutane (DCIB) as an oxidant. Notably, chemical-oxidant-free strategies were also developed, with the major breakthroughs being the use of internal oxidants in oxidative annulations, the use of resource-economic electrocatalysis, and the development of well-defined iron(0)-mediated catalysis. In addition, a highly enantioselective inner-sphere C-H alkylation of (aza)indoles was developed by designing novel remotely decorated N-heterocyclic carbene ligands with dispersion energy donors. In addition, detailed mechanistic experiments including kinetic analyses, intermediate isolation, Mößbauer spectroscopy, and computation provided strong support for the mode of catalysis operation, enabling unprecedented C-H activations. Thereby, low-valent iron catalysts paved the way toward weakly coordinating ketones and enantioselective iron-catalyzed C-H activations through organometallic intermediates.

Organometallic intermediates in Böttger test for glucose in urine

The reaction mechanism in organometallic chemistry is not always correctly understood or it is missing. In this communication the reaction route in the Böttger test for glucose is provided. The reagent can be bismuth subnitrate or bismuth meta-hydroxide (also called hydrated oxide of bismuth), since in alkaline medium (sodium carbonate) the nitrate ion is displaced by hydroxyl. The basic medium is essential in order to activate the glucose molecule. The reaction goes through a series of organometallic intermediates in a redox process. Finally, elemental bismuth separation occurs via one electron transfer in a bimolecular reaction. The white insoluble solid formed in situ blackens since it is covered by metallic bismuth.

Visualizing the Hierarchical Evolution of Aryl-Metal Bonding in Organometallic Nanostructures on Ag(111).

On-surface dehalogenative coupling reactions are promising for constructing nanostructures with diverse properties and functionalities. Extensive efforts have been devoted to single aryl-halogen (C-X) substituents and substitutions at various functionalization sites (typically including meta- and para-substitutions) to generate aryl-aryl single bonds. Moreover, multiple C-X substituents at the ortho-site and the peri- and bay-regions have been applied to create a variety of ring scaffolds. However, for multiple C-X substituents, the hierarchy of aryl-metal bond formation and dissociation remains elusive. Herein, by combining scanning tunneling microscopy imaging and density functional theory calculations, we have visualized and demonstrated the hierarchical evolution of aryl-metal bonding in organometallic intermediates involved in a dehalogenative coupling reaction on Ag(111), using a molecular precursor with both para-substitution and potential bay-region substitution. Our results elucidate how metal atoms are progressively embedded into and removed from organometallic intermediates, enhancing the understanding of on-surface dehalogenative coupling reactions for the controlled construction of the desired nanostructures.

Continuous Flow Generation of Highly Reactive Organometallic Intermediates: A Recent Update

Continuous Flow Generation of Highly Reactive Organometallic Intermediates: A Recent Update

The Chemistry of Hager’s Test for Brucine

The purpose of the article is clear up what is happening in the test tube during the Hager’s test for brucine, that is, throughout the interaction of brucine with manganese dioxide in acidic medium. The paper is a Theoretical Organic Chemistry Study based on the chemical deportment of reagent and substrate, in accordance with the reaction medium. A series of reactions occur during the test: electrophilic attack to double bond, acidolysis of organometallic intermediates, oxidation of secondary alcohol to ketone, acid catalysed hydration, reaction of enol, epoxide formation, ring opening, selective reaction of diol, and ring cleavage of seven-member ring. A yellowish-red to blood-red colour is observed after filtering residual black manganese dioxide. This is due to halochromism, present in acidic medium, since there are no chromogenic groupings.

Visible light harvesting alkyne hydrosilylation mediated by pincer platinum complexes

In this manuscript we assess the catalytic properties of pincer platinum complexes in alkyne hydrosilylation either under photo or thermal conditions. The visible light-induced hydrosilylation proved to be more efficient. It can be performed at room temperature and required lower catalyst loadings than that operating under thermal conditions. The platinum complexes play a dual role in photohydrosilylation as serve as a photosensitizer and a catalyst enabling species in bond breaking/forming transformations. In addition, alkyne hydrosilylation is achieved with moderate regio- and stereoselectivity but is enhanced under photocatalytic conditions and in the case of terminal alkynes we have observed the formation of β(Z) products not observable under thermal conditions. Such differences in selectivity constitute an example of stereodivergent catalysis dictated under photochemical or thermal conditions. The selectivity differences are ascribed to a distinctive reaction mechanism for the light- vs thermally-induced process that involve radical or organometallic intermediates, respectively.

The mechanism of the oxidation of narceine by means of selenous acid -sulphuric acid

The chemistry of selenous acid was misunderstood for many years, being explained by electron back donation. In this communication we disclose the reaction mechanism of the interaction of narceine with selenous acid in sulphuric acid. Narceine is a complex molecule that displays a carboxylic acid, a tertiary amine, a ketone, three methoxy groups and a benzodioxole; so, it was necessary select the principal reaction site. Although a methoxy group can be demethylated with the employed reagent since codeine gives the same violet colour obtained with morphine. The chemical deportment of the methylenedioxy ring in the presence of methoxy groups needed revision. It was found that the five-member ring is cleaved preferentially. Thus, a sustained reaction mechanism could be advanced. The reactive species is protonated selenous acid, which reacts with an oxygen of the cyclic group, water being eliminated. The oxonium ion is neutralized by ring opening in a concerted mechanism involving water reaction at the methylene. An organometallic intermediate is obtained, a selenite, and a hemiacetal. Finally, protonation of the selenium-oxygen double bond produces an acidolysis via a synchronous mechanism involving five electron shifts. This way selenium (II) hydroxide, an ortho-quinone and formaldehyde are obtained.

Hydride-Free Hydrogenation: Unraveling the Mechanism of Electrocatalytic Alkyne Semihydrogenation by Nickel-Bipyridine Complexes.

Hydrogenation reactions of carbon-carbon unsaturated bonds are central in synthetic chemistry. Efficient catalysis of these reactions classically recourses to heterogeneous or homogeneous transition-metal species. Whether thermal or electrochemical, C-C multiple bond catalytic hydrogenations commonly involve metal hydrides as key intermediates. Here, we report that the electrocatalytic alkyne semihydrogenation by molecular Ni bipyridine complexes proceeds without the mediation of a hydride intermediate. Through a combined experimental and theoretical investigation, we disclose a mechanism that primarily involves a nickelacyclopropene resting state upon alkyne binding to a low-valent Ni(0) species. A following sequence of protonation and electron transfer steps via Ni(II) and Ni(I) vinyl intermediates then leads to olefin release in an overall ECEC-type pattern as the most favored pathway. Our results also evidence that pathways involving hydride intermediates are strongly disfavored, which in turn promotes high semihydrogenation selectivity by avoiding competing hydrogen evolution. While bypassing catalytically competent hydrides, this type of mechanism still retains inner-metal-sphere characteristics with the formation of organometallic intermediates, often essential to control regio- or stereoselectivity. We think that this approach to electrocatalytic reductions of unsaturated organic groups can open new paradigms for hydrogenation or hydroelementation reactions.

Characterization of Methyl- and Acetyl-Ni Intermediates in Acetyl CoA Synthase Formed during Anaerobic CO2 and CO Fixation.

The Wood-Ljungdahl Pathway is a unique biological mechanism of carbon dioxide and carbon monoxide fixation proposed to operate through nickel-based organometallic intermediates. The most unusual steps in this metabolic cycle involve a complex of two distinct nickel-iron-sulfur proteins: CO dehydrogenase and acetyl-CoA synthase (CODH/ACS). Here, we describe the nickel-methyl and nickel-acetyl intermediates in ACS completing the characterization of all its proposed organometallic intermediates. A single nickel site (Nip) within the A cluster of ACS undergoes major geometric and redox changes as it transits the planar Nip, tetrahedral Nip-CO and planar Nip-Me and Nip-Ac intermediates. We propose that the Nip intermediates equilibrate among different redox states, driven by an electrochemical-chemical (EC) coupling process, and that geometric changes in the A-cluster linked to large protein conformational changes control entry of CO and the methyl group.

Bringing a Mechanistic Lens to the Development of New Transfer Hydroarylation Isodesmic Reactions for the Synthesis of Amides, Thioamides, Amidines, Alkenes and Ketones from Carboxylic Acids via Extrusion and Insertion Elementary Steps

AbstractThe wide availability, ease of handling and structural and functional diversity make carboxylic acids prized building blocks in organic synthesis. The past two decades has seen an explosion of interest in the development of new modes of reactivity of carboxylic acids and their derivatives. Of these, metal‐mediated decarboxylation reactions are attractive as they produce organometallic intermediates that can subsequently be used in C−X (where X=C, N, S etc) bond coupling reactions. Here the results of mechanistic studies integrating both gas‐ and condensed‐phase work are described for development of new extrusion‐insertion (ExIn) classes of reactions for the synthesis of amides, thioamides, amidines, alkenes and ketones from arylcarboxylic acids and suitable (hetero)cumulenes.

Metal Identity Effects in the Pincer Complex-Catalyzed Dehydrogenative Coupling of Formamides with Alcohols to Form Carbamates

This manuscript describes the impact of metal (ruthenium versus iron versus manganese) on the PNP pincer complex-catalyzed dehydrogenative coupling of formamides with alcohols to yield carbamates. Studies are conducted to compare the structure and reactivity of key organometallic intermediates as a function of metal. These reveal that all three pincer catalysts undergo fast reaction with isocyanates (the initial organic products of formamide dehydrogenation) to form off-cycle metallacyclic species. However, the structures and reactivities of these intermediates vary as a function of metal. The N-bound isomer of the metallacycle is formed with Fe (literature) and Ru (this work), while both O-bound (kinetic) and N-bound (thermodynamic) metallacycles are observed with Mn (this work). At 100 °C, the O-bound Mn cycloadduct reacts rapidly with cyclohexanol to release the pincer catalyst along with the corresponding carbamate. In contrast, all three of the N-bound metallacycles show dramatically lower reactivity toward catalyst regeneration under analogous conditions. The reactivity of the pincer complexes toward formamide dehydrogenation also varies as a function of metal, with Ru and Fe ≫ Mn at 100 °C. Overall, the Mn pincer complex is an effective catalyst for the conversion of a variety of formamides and alcohols to carbamates at 150 °C with catalyst loadings as low as 1 mol %. The catalyst performance and substrate scope are comparable to those of the Fe analogue.