Coupling Of Halides Research Articles

Interfacial Tuning of Electrocatalytic Ag Surfaces for Fragment-Based Electrophile Coupling.

Construction of C‒C bonds in medicinal chemistry frequently draws on the reductive coupling of organic halides with ketones or aldehydes. Catalytic C(sp3)‒C(sp3) bond formation, however, is constrained by the competitive side reactivity of radical intermediates following sp3 organic halide activation. Here, an alternative paradigm deploys catalytic Ag surfaces for reductive fragment-based electrophile coupling compatible with sp3 organic halides. We use in-situ spectroscopy, electrochemical analyses, and simulation to uncover the catalytic interfacial structure and guide reaction development. Specifically, Mg(OAc)2 outcompetes the interaction between Ag and the aldehyde, thereby tuning the Ag surface for selective product formation. Data are consistent with an increased population of Mg-bound aldehyde facilitating the addition of a carbon-centered radical (product of Ag-electrocatalyzed organic halide reduction) to the carbonyl. Electron transfer from Ag to the resultant alkoxy radical yields the desired alcohol. Molecular interfacial tuning at reusable catalytic electrodes will accelerate development of sustainable organic synthetic methods.

Radical coupling of aryl halides to arenes facilitated by Ni(COD)(DQ) and other nickel sources.

The air-stable complex Ni(COD)(DQ) (COD = 1,5-cyclooctadiene, DQ = duroquinone) promotes the coupling of aryl halides to arenes in the presence of KOtBu. This complex has recently been shown to perform coupling reactions based on organonickel intermediates, but in this case the coupling reactions proceed via aryl radicals as shown by our newly developed assay for aryl radicals. Coupling with this nickel source is more efficient than with Ni(COD)2, Ni(PPh3)4 and Ni(acac)2, all of which we also show to operate through aryl radical pathways.

Light-Promoted, Nickel-Catalyzed C–N Coupling of (Hetero)aryl Halides with Benzophenone Hydrazone for the Synthesis of Nitrogen-Containing Heterocycles

A highly effective C-N coupling reaction of (hetero)aryl halides with benzophenone hydrazone is reported. Catalyzed by a Ni(II)–aryl halide complex under UV irradiation (390–395 nm) in the presence of a...

Nickel-catalyzed cross-coupling aminations via high-throughput mechanochemistry enabled by resonant acoustic mixing

Resonant Acoustic Mixing (RAM) allows High Throughput Experimentation (HTE) using commercially available 96-well plates as exemplified by the nickel catalyzed C–N cross coupling of aryl halides with different amine and anilines.

Computational analysis of R-X oxidative addition to Pd nanoparticles.

Oxidative addition (OA) is a necessary step in mechanisms of widely used synthetic methodologies such as the Heck reaction, cross-coupling reactions, and the Buchwald-Hartwig amination. This study pioneers the exploration of OA of aryl halide to palladium nanoparticles (NPs), a process previously unaddressed in contrast to the activity of well-studied Pd(0) complexes. Employing DFT modeling and semi-empirical metadynamics simulations, the oxidative addition of phenyl bromide to Pd nanoparticles was investigated in detail. Energy profiles of oxidative addition to Pd NPs were analyzed and compared to those involving Pd(0) complexes forming under both ligand-stabilized (phosphines) and ligandless (amine base) conditions. Metadynamics simulations highlighted the edges of the (1 1 1) facets of Pd NPs as the key element of oxidative addition activity. We demonstrate that OA to Pd NPs is not only kinetically facile at ambient temperatures but also thermodynamically favorable. This finding accentuates the necessity of incorporating OA to Pd NPs in future investigations, thus providing a more realistic view of the involved catalytic mechanisms. These results enhance the understanding of aryl halide (cross-)coupling reactions, reinforcing the concept of a catalytic "cocktail". This concept posits dynamic interconversions between diverse active and inactive centers, collectively affecting the outcome of the reaction. High activity of Pd NPs in direct C-X activation paves the way for novel approaches in catalysis, potentially enhancing the field and offering new catalytic pathways to consider.

A General Copper Catalytic System for Suzuki-Miyaura Cross-Coupling of Unactivated Secondary and Primary Alkyl Halides with Arylborons.

Suzuki-Miyaura cross-couplings (SMC) are powerful tools for the construction of carbon-carbon bonds. However, the couplings of sp3-hybridized alkyl halides with arylborons often encounter several problematic issues such as sluggish oxidation addition of alkyl halides and competitive β-hydride elimination side pathways of metal-alkyl species. In precedent reports, copper is mainly utilized for the coupling of sp2-aryl halides, and the cross-couplings with unactivated alkyl halides are far less reported. Herein, we demonstrate that a high-efficiency copper system enabled the coupling of arylborons with various unactivated secondary and primary alkyl halides including bromides, iodides, and even robust chlorides. The present system features broad scope, excellent functionality tolerance, scalability, and practicality. Moreover, the current system could be applied for the late-stage functionalization of complex molecules in moderate to high efficiency.

Pd-SILP-Fe3O4@SiO2: An efficient supported ionic liquid phase catalyst for the Mizoroki-Heck coupling

An efficient method for the Mizoroki-Heck coupling of aryl halides with alkenes employing already reported palladium tagged, magnetic nanoparticle supported, ionic liquid phase catalyst (Pd-SILP-Fe3O4@SiO2) in water under aerobic conditions has been developed. Various di-substituted alkenes were synthesized with excellent yields using a highly water dispersible Pd-SILP-Fe3O4@SiO2 catalyst. This nanocatalyst displayed high thermal stability, compatibility in aqueous systems, high catalytic efficiency, high turnover frequencies (TOF), easy magnetic recovery, and reusability up to 6th run. The main advantages of the protocol are its robustness, mild reaction conditions, easy set-up, easy workup, low Pd loading (0.001 mol% of Pd), higher yields, and use of water as a green solvent, which makes it both environmentally and economically appealing.

Green Synthesis of CuO Nanoparticles Using Agaricus bisporus Extract as a Highly Efficient Catalyst for the Suzuki Cross-Coupling Reaction.

Copper oxide nanoparticles (CuONPs) were synthesized using a rapid, eco-friendly, cost-effective, efficient, and biological method employing aqueous Agaricus bisporus extract as a capping and reducing agent. The formation of CuONPs was checked by UV-vis spectroscopy and was characterized by X-ray diffraction analysis (XRD), dynamic light scattering spectroscopy (DLS), transmission electron microscopy (TEM), and surface area and porosimetry analyzer. The characterization results showed that the synthesized nanoparticles had a spherical-like appearance and a crystal structure with 40-100 nm particle size. The green synthesized CuONPs were found to be an excellent and sustainable heterogeneous catalyst (TOF up to 29700 h-1 ) for the Suzuki C-C coupling of aryl halides with phenylboronic acid in a very short reaction time (10 minutes). Moreover, the easily recovered catalyst can be reused five times with just a negligible reduction in catalytic behavior.

Adenine based Bio UiO‐66 with Pd(II) as a novel catalyst for green Suzuki cross‐coupling in aqueous media

The novel developed heterogeneous catalyst Ad/Pd‐UiO‐66 has been synthesized by hydrothermal technique. The prepared catalyst was identified by some analytical techniques such as Fourier transform‐infrared spectroscopy (FT‐IR), high‐resolution transmission electron microscopy (HR‐TEM), X‐ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X‐ray diffraction (XRD), and field emission scanning electron microscopy (FE‐SEM). The Ad/Pd‐UiO‐66 was used as catalyst in the Suzuki C–C coupling in the green aqueous media. This catalyst showed excellent efficiency for the C–C coupling of aryl halides with phenylboronic acid and 4‐methyl phenylboronic acid. The best results was recorded for coupling of iodobenzene with phenylboronic acid (95% conversion in 30 min). Furthermore, the stability and recyclability of the catalyst under optimized conditions were investigated. The catalyst was recovered and reused up to 5 times with no significant decrease in activity.

Zinc-induced one-pot coupling of alkyl halides and alcohols to access CD3-labeled alkyl sulfides

Zinc-induced one-pot coupling of alkyl halides and alcohols to access CD3-labeled alkyl sulfides

Metallaphotoredox‐Catalyzed Three‐Component Couplings for Practical Synthesis of Ureas and Carbamates†

Comprehensive SummaryUreas are widely used in drugs, materials and catalysts because of their diamide structure, which can form strong hydrogen bonds. Therefore, it is of great scientific significance to develop efficient and green methods for the synthesis of urea compounds, especially unsymmetrical ureas. Here, we have disclosed novel and highly efficient three‐component coupling reactions of organic halides, sodium cyanate and amines enabled by nickel/photoredox dual catalysis for the preparation of unsymmetrical ureas. The reaction features simple and safe operations, broad substrate scopes, and product diversities. It allows the facile synthesis of N‐aryl/vinyl ureas from readily available, user‐friendly feedstocks under mild conditions (27 examples, 36%—98% yields). In addition, this method is further derived to alcohols as nucleophiles to synthesize a series of carbamates (15 examples, 40%—95% yields). The mechanism experiment shows that the isocyanate produced by the coupling of halide and sodium cyanate may be the key intermediate in this reaction.

C–O Coupling of Aryl Halides with Phenols by a Copper Catalyst Immobilized on Fe3O4 Nanoparticles

C–O Coupling of Aryl Halides with Phenols by a Copper Catalyst Immobilized on Fe3O4 Nanoparticles

Photocatalyzed Aminomethylation of Alkyl Halides Enabled by Sterically Hindered N-Substituents.

The catalytic C(sp3 )-C(sp3 ) coupling of alkyl halides and tertiary amines offers a promising tool for the rapid decoration of amine skeletons. However, this approach has not been well established, partially due to the challenges in precisely distinguishing and controlling the reactivity of amine-coupling partners and their product homologues. Herein, we developed a metal-free photocatalytic system for the aminomethylation of alkyl halides through radical-involved C(sp3 )-C(sp3 ) bond formation, allowing for the synthesis of sterically congested tertiary amines that are of interest in organic synthesis but not easily prepared by other methods. Mechanistic studies disclosed that sterically hindered N-substituents are key to activate the amine coupling partners by tuning their redox potentials to drive the reaction forward.

Photocatalyzed Aminomethylation of Alkyl Halides Enabled by Sterically Hindered N‐Substituents

AbstractThe catalytic C(sp3)−C(sp3) coupling of alkyl halides and tertiary amines offers a promising tool for the rapid decoration of amine skeletons. However, this approach has not been well established, partially due to the challenges in precisely distinguishing and controlling the reactivity of amine‐coupling partners and their product homologues. Herein, we developed a metal‐free photocatalytic system for the aminomethylation of alkyl halides through radical‐involved C(sp3)−C(sp3) bond formation, allowing for the synthesis of sterically congested tertiary amines that are of interest in organic synthesis but not easily prepared by other methods. Mechanistic studies disclosed that sterically hindered N‐substituents are key to activate the amine coupling partners by tuning their redox potentials to drive the reaction forward.

Electrochemical NiH‐Catalyzed C(sp3)−C(sp3) Coupling of Alkyl Halides and Alkyl Alkenes

AbstractHerein, an electrochemically driven NiH‐catalyzed reductive coupling of alkyl halides and alkyl alkenes for the construction of Csp3−Csp3 bonds is firstly reported. Notably, alkyl halides serve dual function as coupling substrates and as hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature of this reaction is realized by introducing an intramolecular coordinating group to the substrate, where the product can be easily adjusted to give the desired branched products. The method proceeds under mild conditions, exhibits a broad substrate scope, and affords moderate to excellent yields with over 70 examples, including late‐stage modification of natural products and drug derivatives. Mechanistic insights offer evidence for an electrochemically driven coupling process. The sp3‐carbon‐halogen bonds can be activated through single electron transfer (SET) by the nickel catalyst in its low valence state, generated by cathodic reduction, and the generation of NiH species from alkyl halides is pivotal to this transformation.

Electrochemical NiH-Catalyzed C(sp3)-C(sp3) Coupling of Alkyl Halides and Alkyl Alkenes.

Herein, an electrochemically driven NiH-catalyzed reductive coupling of alkyl halides and alkyl alkenes for the construction of Csp3-Csp3 bonds is firstly reported. Notably, alkyl halides serve dual function as coupling substrates and as hydrogen sources to generate NiH species under electrochemical conditions. The tunable nature of this reaction is realized by introducing an intramolecular coordinating group to the substrate, where the product can be easily adjusted to give the desired branched product. The method proceeds under mild conditions, exhibits a broad substrate scope, and affords moderate to excellent yields with over 70 examples, including late-stage modification of natural products and drug derivatives. Mechanistic insights offer evidence for an electrochemically driven coupling process. The sp3-carbon-halogen bonds can be activated through single electron transfer (SET) by the nickel catalyst in its low valence state, generated by cathodic reduction, and the generation of NiH species from alkyl halides is pivotal to this transformation.

Effective Activation of Strong C−Cl Bonds for Highly Selective Photosynthesis of Bibenzyl via Homo‐Coupling

AbstractCarbon‐carbon (C−C) coupling of organic halides has been successfully achieved in homogeneous catalysis, while the limitation, e.g., the dependence on rare noble metals, complexity of the metal‐ligand catalylst and the poor catalyst stability and recyclability, needs to be tackled for a green process. The past few years have witnessed heterogeneous photocatalysis as a green and novel method for organic synthesis processes. However, the study on C−C coupling of chloride substrates is rare due to the extremely high bond energy of C−Cl bond (327 kJ mol−1). Here, we report a robust heterogeneous photocatalyst (Cu/ZnO) to drive the homo‐coupling of benzyl chloride with high efficiency, which achieves an unprecedented high selectivity of bibenzyl (93 %) and yield rate of 92 % at room temperature. Moreover, this photocatalytic process has been validated for C−C coupling of 10 benzylic chlorides all with high yields. In addition, the excellent stability has been observed for 8 cycles of reactions. With detailed characterization and DFT calculation, the high selectivity is attributed to the enhanced adsorption of reactants, stabilization of intermediates (benzyl radicals) for the selective coupling by the Cu loading and the moderate oxidation ability of the ZnO support, besides the promoted charge separation and transfer by Cu species.

Effective Activation of Strong C-Cl Bonds for Highly Selective Photosynthesis of Bibenzyl via Homo-Coupling.

Carbon-carbon (C-C) coupling of organic halides has been successfully achieved in homogeneous catalysis, while the limitation, e.g., the dependence on rare noble metals, complexity of the metal-ligand catalylst and the poor catalyst stability and recyclability, needs to be tackled for a green process. The past few years have witnessed heterogeneous photocatalysis as a green and novel method for organic synthesis processes. However, the study on C-C coupling of chloride substrates is rare due to the extremely high bond energy of C-Cl bond (327 kJ mol-1 ). Here, we report a robust heterogeneous photocatalyst (Cu/ZnO) to drive the homo-coupling of benzyl chloride with high efficiency, which achieves an unprecedented high selectivity of bibenzyl (93 %) and yield rate of 92 % at room temperature. Moreover, this photocatalytic process has been validated for C-C coupling of 10 benzylic chlorides all with high yields. In addition, the excellent stability has been observed for 8 cycles of reactions. With detailed characterization and DFT calculation, the high selectivity is attributed to the enhanced adsorption of reactants, stabilization of intermediates (benzyl radicals) for the selective coupling by the Cu loading and the moderate oxidation ability of the ZnO support, besides the promoted charge separation and transfer by Cu species.

Coupling of alkynes and aryl halides with nickel-catalyzed Sonogashira reactions

Coupling of alkynes and aryl halides with nickel-catalyzed Sonogashira reactions

N,N'-Diaryldihydrophenazines as Visible-Light Photocatalysts for Anilines' Arylation Using a Dual Photoredox/Ni(II) Cross-Coupling Strategy.

It has been shown that cheap and easily available N,N'-diaryldihydrophenazines can successfully replace Ir(III)- and Ru(II)-based photocatalysts in the dual photoredox/Ni(II) C-N coupling of aryl halides with a wide range of anilines (32 examples). The efficient, operationally simple approach to diarylamines has been elaborated, which is amenable to scaling up via a flow apparatus.