Ligand Coupling Research Articles

A green protocol for the base, ligand, and phase transfer catalyst free coupling of terminal acetylenes in water

A green protocol for the base, ligand, and phase transfer catalyst free coupling of terminal acetylenes in water

Non-Classical Molecular Activation by Phosphines and N-Heterocyclic Carbenes and Its Application to Catalytic Reactions

Abstract This Award Account reports our recent studies concerning the catalytic transformations that involve a non-classical mode of molecular activation by tertiary phosphines and N-heterocyclic carbenes (NHCs). Regarding organophosphine catalysis, we successfully designed reactions based on a P(III)/P(V) redox couple. A catalytic protocol for generating pentacoordinate P(V) species was devised by the reaction of tertiary phosphines, acyl fluorides and alkynoates. The ability of the thus generated fluorophosphoranes to participate in ligand coupling and ligand metathesis with organosilicon nucleophiles enables synthetic transformations that are otherwise unattainable, including the intermolecular carbofluorination of alkynes and the hydroalkenylation of enol ethers. Regarding nucleophilic NHC catalysis, the use of imidazolium-based NHCs can generate deoxy-Breslow intermediates that are sufficiently nucleophilic to promote the aromatic substitution of aryl halides, aryl ethers and anilides. The protocol can also be used for the nucleophilic activation of styrene derivatives, allowing for the generation of a series of ylide intermediates that can serve as non-stabilized vinyl anion equivalents. These results demonstrate that synthetic transformations involving non-stabilized carbanions can be conducted under catalytic conditions without the use of strong organometallic nucleophiles.

Enantioselective inorganic nanomaterials with near-infrared circular-polarized-activated photothermal response

Chiral inorganic semiconductor materials have great potential in chiral catalysis, biomedicine and chiroptical devices. However, the narrow chiroptical response and weak chiroptical intensity limit their development. Herein, chiral CuS (D-/L-CuS) were prepared by a facile ligand exchange method using alanine (Ala) and penicillamine (Pen), respectively. The properties and stereostructures of chiral ligands resulted in enantioselectivity and chiroptical activity from ultraviolet to near-infrared (NIR) of chiral CuS. And the maximum of asymmetry factor |g| was up to 1.02 × 10-2, which is far higher than those of most chiral ligand-modified inorganic semiconductor nanomaterials. The NIR chiroptical activity facilitated photothermal performance, which could be tuned by circularly polarized light (CPL). D-CuS showed higher photothermal efficiency under right CPL radiation, while L-CuS showed higher photothermal efficiency under left CPL radiation. L-Pen-CuS exhibited the highest photothermal conversion efficiency of 22.18% under left CPL radiation. Moreover, the underlying mechanism of chirality in CuS was revealed for the first time. The coupling of amino acid ligands and CuS through Coulomb interactions allowed chiral transfer, and the orbital hybridization of chiral ligand orbitals with CuS molecular orbitals transferred chiral information. This work will further promote the understanding of induced chirality in inorganic semiconductor materials and the application of chiroptical-active inorganic semiconductor materials.

On the Selectivity in the Synthesis of 3-Fluoropiperidines Using BF3-Activated Hypervalent Iodine Reagents.

Fluorinated piperidines find wide applications, most notably in the development of novel therapies and agrochemicals. Cyclization of alkenyl N-tosylamides promoted by BF3-activated aryliodine(III) carboxylates is an attractive strategy to construct 3-fluoropiperidines, but it suffers from selectivity issues arising from competitive oxoaminations and the inability to easily modulate the reactions diastereoselectivity. Herein, we report an itemized optimization of the reaction conditions carried out on both cyclic and acyclic substrates and outline the origins of substrate- and reagent-based stereo-, regio-, and chemoselectivity. Extensive mechanistic studies encompassing multinuclear NMR spectroscopy, deuterium labeling, rearrangements on stereodefined substrates, and careful structural analyses (NMR and X-ray) of the reaction products are performed. This revealed the processes and interactions crucial for achieving controlled preparation of 3-fluoropiperidines using I(III) chemistry and has provided an advanced understanding of the reaction mechanism. In brief, we propose that BF3-coordinated I(III) reagents attack C═C to produce the corresponding iodiranium(III) ion, which then undergoes diastereodetermining 5-exo-cyclization. Transiently formed pyrrolidines with an exocyclic σ-alkyl-I(III) moiety can further undergo aziridinium ion formation or reductive ligand coupling processes, which dictate not only the final product's ring size but also the chemoselectivity. Importantly, the selectivity of the reaction depends on the nature of the ligand bound to I(III) and the presence of electrolytes such as TBABF4. Reported findings will facilitate the usage of ArI(III)-dicarboxylates in the reliable construction of fluorinated azaheterocycles.

Theoretical Grounding and Formation of Experimental Approaches to Hyaluronidase Structure Consolidation due to Its Computational Interactions with Shortchain Glycosaminoglycan Ligands

The computational study of 3D model hyaluronidase interaction with shortchain glycosaminoglycan ligands demonstrated the diversity and significance of their reaction on enzyme structure. It has been realized due to electrostatic noncovalent interactions (without specific coupling with active site) inducing the perceptible conformational alterations of biocatalyst molecule. As a result of this the inactivation and stabilization of enzyme globule are observed, change of inhibition of biocatalyst by heparin. The binding of chondroitin trimers (on centers cn6, cn3, cn1) to hyaluronidase molecular surface increased the enzyme stability, binding of chondroitin sulfate trimers (on centers cs2, cs4, cs7, cs8 or cs1, cs2, cs4, cs7, cs8) decreased the inhibition of enzyme by tetramer heparin. It should be noted the importance of ligand binding for regulation of enzyme functioning and existence of multiform and multicomponent microenvironment of enzyme. The sequence of preferable coupling of ligands with hyaluronidase is elicited in our study and with its help was evaluate reality of experimental selective modification of enzyme (possibly no covalently or covalently, for instance, with chondroitin sulfate trimers on centers cs7, cs1, cs5) for experimental obtaining of stabilized enzyme forms of medical destination. The perspective approaches for this aim may be the no covalent reaction on hyaluronidase by chondroitin or chondroitin sulfate trimers as well covalent modification of biocatalyst by chondroitin sulfate trimers.

Charge Injection and Energy Transfer of Surface-Engineered InP/ZnSe/ZnS Quantum Dots.

Surface passivation is a critical aspect of preventing surface oxidation and improving the emission properties of nanocrystal quantum dots (QDs). Recent studies have demonstrated the critical role of surface ligands in determining the performance of QD-based light-emitting diodes (QD-LEDs). Herein, the underlying mechanism by which the capping ligands of InP/ZnSe/ZnS QDs influence the brightness and lifetime of the QD-LEDs is investigated. The electrochemical results demonstrate that highly luminescent InP/ZnSe/ZnS QDs exhibit modulated charge injection depending on the length of the surface ligand chains: short alkyl chains on the ligands are favorable for charge transport to the QDs. In addition, the correlation between the spectroscopic and XRD analyses suggests that the length of the ligand chain tunes the ligand-ligand coupling strength, thereby controlling the inter-QD energy transfer dynamics. The present findings shed new light on the crucial role of surface ligands for InP/ZnSe/ZnS QD-LED applications.

The Role of Water Content of Deep Eutectic Solvent Ethaline in the Anodic Process of Gold Electrode.

Traditional coupling of ligands for gold wet etching makes large-scale applications problematic. Deep eutectic solvents (DESs) are a new class of environment-friendly solvents, which could possibly overcome the shortcomings. In this work, the effect of water content on the Au anodic process in DES ethaline was investigated by combining linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS). Meanwhile, we employed atomic force microscopy (AFM) to image the evolution of the surface morphology of the Au electrode during its dissolution and passivation process. The obtained AFM data help to explain the observations about the effect of water content on the Au anodic process from the microscopic perspective. High water contents make the occurrence of anodic dissolution of gold at higher potential, but enhances the rate of the electron transfer and gold dissolution. AFM results reveal the occurrence of massive exfoliation, which confirms that the gold dissolution reaction is more violent in ethaline with higher water contents. In addition, AFM results illustrate that the passive film and its average roughness could be tailored by changing the water content of ethaline.

Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions and hydrogen bonds enhancing enzyme–ligand coupling. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.

Ligand Coupling and Decoupling Modulates Stem Cell Fate

AbstractIn natural microenvironment, various proteins containing adhesive ligands in fibrous and non‐fibrous structures dynamically couple and decouple to regulate stem cell fate. Herein, materials presenting movably couplable ligands are developed by grafting liganded gold nanoparticles (AuNPs) to a substrate followed by flexibly grafting liganded movable linear nanomaterials (MLNs) to the substrate via a long bendable linker, thereby creating a space between the MLNs and the AuNPs in the decoupled state. Magnetic control of the MLNs decreases this space via the bending of the linker to couple the MLNs to the AuNPs. Remote control of ligand coupling stimulates integrin recruitment to the coupled ligands, thereby non‐toxically facilitating the focal adhesion, mechanosensing, and potential differentiation of stem cells, which is suppressed by ligand decoupling. Versatile tuning of size, aspect ratio, distributions, and ligands of the MLNs can help to decipher dynamic ligand‐coupling‐dependent stem cell fate to advance regenerative therapies.

Phosphinoquinoline supported CoII, NiII, and FeII complexes: divergent behaviour upon reduction.

The reduction of [CoLBr2], a CoII complex supported by a diisopropylphosphinoquinoline (L) ligand, induced a ligand coupling giving access to a (PNNP) supported CoII complex which was isolated in 70% yield. This complex was formed using a minimum of 2 equivalents of a reductant (either Mn or KC8). The fate of [CoLBr2] in the presence of 1 equivalent of a reductant was more difficult to study; nevertheless, a CoI complex was characterised in the solid state. In order to determine whether this ligand coupling could occur with other 3d metals, L supported FeII and NiII complexes were synthesised. While no compound could be identified upon reduction of [FeLBr2], both [NiLBr2] and [NiL2Br](Br) led to the reduction at the metal center allowing the isolation of an original Ni0 trimer in a satisfactory yield. This study shows the different behaviours of these 3d metal complexes in the presence of a reductant.

Phosphine-Catalyzed Z-Selective Carbofluorination of Alkynoates Bearing an N-Heteroarene Unit

AbstractWe report herein on the phosphine-catalyzed Z-selective carbofluorination of alkynoates bearing an N-heteroarene unit, by using acyl fluorides as bifunctional reagents. This reaction proceeds through a pentacoordinate fluorophosphorane(V) intermediate, resulting in the formation of a C–F bond by a ligand coupling process. The Z-selectivity is attributed to the thermodynamic stabilization of a Z-isomer by orbital interactions between lone pair electrons of an N-heteroarene and the π* orbital of a carbonyl group.

Alkyne Coupling and Cyclization on Metal Cluster Complexes. Additions and Couplings of Dimethyl acetylenedicarboxylate to Ru6(μ6-C)(CO)14(μ3-η4-C4H4)

Reactions of the hexaruthenium cluster complex Ru6(μ6-C)(CO)14(μ3−η4−C4H4), 2 with dimethyl acetylenedicarboxylate (DMAD) at 25 °C yielded five new compounds: Ru6(μ5-C)(CO)16(μ−η4−C4H4), 3; Ru6(μ6-C)(CO)14[η6-1,2-C6H4(CO2Me)2], 4; Ru6(μ5-C)(CO)14(μ−η4−C4H4)[μ3−C2(CO2Me)2], 5; Ru6(μ5-C)(CO)14(μ−η4−C4H4)[μ3−C2(CO2Me)2], 6 and Ru6(μ6-C)(CO)14[μ3−η6−1,2−C6H4(CO2Me)2], 7. Compounds 4 and 7 are isomers that contain the six-membered arene, dimethyl phthalate, 1,2−C6H4(CO2Me)2, as a ligand. Compound 3 was formed as a side product in low yield (6%) by the simple addition of CO to 2. The addition of CO to 2 causes the cluster to open to that of a spiked, square pyramid. Direct reaction of CO to 2 provided 3 in a good yield (72%). A DMAD ligand was added to the cluster of 2 as a simple triply-bridging ligand to form open Ru6 clusters in compounds 5 and 6. Addition of DMAD to 3 yielded the DMAD derivative Ru6(μ5-C)(CO)15(μ−η4−C4H4)[μ−C2(CO2Me)2], 8 which contains a DMAD ligand bridging a basal edge of an opened spiked-square pyramidal Ru6 cluster. Compound 5 was thermally converted to the new complex Ru6(μ5-C)(CO)14[μ4−η6−CHCHCHCC(CO2Me)C(CO2Me)](μ-H), 9 that contains a bridging CHCHCHCC(CO2Me)C(CO2Me) ligand formed by a coupling of the DMAD ligand to the bridging C4H4 ligand in 5 accompanied by a cleavage of one CH bond and formation of a bridging hydrido ligand. Decarbonylation of 3 with Me3NO yielded the NMe3 derivative Ru6(μ5-C)(CO)15(μ−η4−C4H4)(NMe3), 10 in which the NMe3 ligand is coordinated to the spiked metal atom on the square-pyramidal Ru5 cluster. Treatment of 4 and 7 with CO at 25 °C induced elimination of the 1,2−C6H4(CO2Me)2 ligand to yield free dimethyl phthalate, 11 and formation of the known parent carbonyl complex Ru6(μ6-C)(CO)17. All of the new cluster compounds were characterized by single-crystal X-ray diffraction analyses.

Recent Progress in C(sp2)–C(sp2) Bond Formation Using Ligand Coupling on Sulfur(IV)

AbstractLigand coupling on sulfur, as an alternative to transition-metal-catalyzed cross-coupling reactions, is a useful method for connecting sp2 carbons. Although pioneered more than 50 years ago, its synthetic utility has been overlooked until recently. This short review summarizes progress in C(sp2)–C(sp2) bond formation using ligand coupling on sulfur and discusses control of selectivity, expansion of the scope, and applications of the reaction.1 Introduction2 Cross-Coupling of Heteroaryl Reagents3 Phenothiazinium-Mediated C(sp2)–C(sp2) Cross-Coupling4 C(sp2)–C(sp2) Bond Formation Mediated by Sulfuranes Generated from Arynes and Sulfoxides5 S-Alkenylbenzothiophenium-Mediated Alkenyl-Alkenyl Coupling6 Conclusion

Explaining Regiodivergent Vinylations with Vinylbenziodoxolones**

AbstractVinylbenziodoxolones have recently been identified as efficient hypervalent iodine(III) reagents for electrophilic vinylations under transition metal‐free conditions. Their unique reactivity allows synthesis of either internal or terminal alkenes, depending on the nucleophile class. This paper constitutes the first mechanistic investigation of VBX vinylations, and makes use of NMR studies, deuterium labelling and computations to rationalize the observed regio‐ and stereochemical outcome. Internal alkene formation in S‐vinylation was found to proceed through the ligand coupling mechanism typical of diaryliodonium salts, whereas terminal alkene formation in P‐vinylations took place via a phosphinous acid‐coordinated VBX complex, which underwent concerted deprotonation and Michael‐type addition. Subsequent base‐assisted protonation and E2 elimination delivered the terminal alkene. The findings can be used to predict the regioselectivity in vinylations of other nucleophile classes.

Explaining Regiodivergent Vinylations with Vinylbenziodoxolones.

Vinylbenziodoxolones have recently been identified as efficient hypervalent iodine(III) reagents for electrophilic vinylations under transition metal‐free conditions. Their unique reactivity allows synthesis of either internal or terminal alkenes, depending on the nucleophile class. This paper constitutes the first mechanistic investigation of VBX vinylations, and makes use of NMR studies, deuterium labelling and computations to rationalize the observed regio‐ and stereochemical outcome. Internal alkene formation in S‐vinylation was found to proceed through the ligand coupling mechanism typical of diaryliodonium salts, whereas terminal alkene formation in P‐vinylations took place via a phosphinous acid‐coordinated VBX complex, which underwent concerted deprotonation and Michael‐type addition. Subsequent base‐assisted protonation and E2 elimination delivered the terminal alkene. The findings can be used to predict the regioselectivity in vinylations of other nucleophile classes.

Transformations of Main-Group Organometallics Induced by Transition Metals

AbstractThe oxidative dehydrometallation of silyl or boron enolates is induced by palladium(II) catalyst to result in the versatile introduction of α,β-unsaturated carbon–carbon double bonds via palladium enolates. Selective oxidative cross- and homo-coupling reactions of silyl or boron enolates induced by vanadium(V) oxidant provide a selective synthetic method for accessing 1,4-dicarbonyl compounds in a nucleo­phile-nucleophile coupling mode. The ligand coupling reaction of main-group organometallic compounds induced by vanadium(V) oxi­dant provides a unique method for intramolecular carbon–carbon bond formation of nucleophiles. The last two reactions are a complementary strategy for the nucleophile-electrophile coupling reaction. The dehydrometallation and coupling reactions probably proceed through two- and one-electron oxidation processes, respectively.1 Introduction2 Palladium-Catalyzed Dehydrometallation3 Homo- and Cross-Coupling of Main-Group Organometallic Compounds4 Oxidative Ligand Coupling of Main-Group Organometallic Compounds5 Conclusion

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Intermediates, state transitions, and ligand coupling in the dynamic mechanism of the hEAAT3 glutamate transporter

The most abundant excitatory neurotransmitter in the brain, L-Glu, is involved in a variety of neuronal signaling processes. This explains the keen interest in the excitatory amino acid transporter (EAAT) family and its role in the regulation of intra- and extra-cellular Glu concentrations. The human EAAT3 protein (hEAAT3) operates by an elevator mechanism to transfer the substrate from an outward-facing state (OFS) to an inward-facing state (IFS) from which the Glu can be released into the cell.

Vacuum vapor migration strategy for atom–nanoparticle composite catalysts boosting bifunctional oxygen catalysis and rechargeable Zn–air batteries

A “vacuum vapor migration strategy” is employed to successfully prepare a novel CoNi–N–C catalyst containing uniformly dispersed CoNi alloy nanoparticles as a conceptually solid–ligand coupling with atomic Co–Nx–C active sites.

Mechanism of H+ dissociation–induced O–O bond formation via intramolecular coupling of vicinal hydroxo ligands on low-valent Ru(III) centers

The understanding of O-O bond formation is of great importance for revealing the mechanism of water oxidation in photosynthesis and for developing efficient catalysts for water oxidation in artificial photosynthesis. The chemical oxidation of the RuII2(OH)(OH2) core with the vicinal OH and OH2 ligands was spectroscopically and theoretically investigated to provide a mechanistic insight into the O-O bond formation in the core. We demonstrate O-O bond formation at the low-valent RuIII2(OH) core with the vicinal OH ligands to form the RuII2(μ-OOH) core with a μ-OOH bridge. The O-O bond formation is induced by deprotonation of one of the OH ligands of RuIII2(OH)2 via intramolecular coupling of the OH and deprotonated O- ligands, conjugated with two-electron transfer from two RuIII centers to their ligands. The intersystem crossing between singlet and triple states of RuII2(μ-OOH) is easily switched by exchange of H+ between the μ-OOH bridge and the auxiliary backbone ligand.