Suzuki Miyaura Cross-coupling Research Articles

Enzymatic Peptide and Protein Bromination: The BromoTrp Tag.

Bio-orthogonal reactions for modification of proteins and unprotected peptides are of high value in chemical biology. The combination of enzymatic halogenation with transition metal-catalyzed cross-coupling provides a feasible approach for the modification of proteins and unprotected peptides. By a semirational protein engineering approach, variants of the tryptophan 6-halogenase Thal were identified that enable efficient bromination of peptides with a C-terminal tryptophan residue. The substrate scope was explored using di-, tri-, and tetrapeptide arrays, leading to the identification of an optimized peptide tag we named BromoTrp tag. This tag was introduced into three model proteins. Preparative scale post-translational bromination was possible with only a single cultivation and purification step using the brominating E. coli coexpression system Brocoli. Palladium-catalyzed Suzuki-Miyaura cross-coupling of the bromoarene was achieved with Pd nanoparticle catalysts at 37 °C, highlighting the rich potential of this strategy for bio-orthogonal functionalization and conjugation.

Synthesis of Trifluoromethylated Pyrimido[1,2-b]indazole Derivatives through the Cyclocondensation of 3-Aminoindazoles with Ketoester and Their Functionalization via Suzuki-Miyaura Cross-Coupling and SNAr Reactions.

A new series of trifluoromethylated pyrimido[1,2-b]indazol-4(1H)-one derivatives was synthesized with good to excellent yields through a simple condensation of 3-aminoindazole derivatives with ethyl 4,4,4-trifluoro 3-oxobutanoate. The functionalization of the corresponding chlorinated fused tricyclic scaffolds via Suzuki-Miyaura and aromatic nucleophilic substitution reactions led to the synthesis of highly diverse trifluoromethylated pyrimido[1,2-b]indazole derivatives with good yields.

Palladium-catalyzed chemoselective Suzuki–Miyaura cross-coupling reaction of poly(pseudo)halogenated arenes

This paper presents general examples of the palladium-catalyzed chemoselective Suzuki–Miyaura cross-coupling reaction of polyhalogenated aryl triflates with a reactivity order of C–Br > C–Cl > C–OTf. A diverse array of bromo(hetero)aryl triflates was successfully coupled with (hetero)aryl boronic acids, achieving excellent reactivity and chemoselectivity. This was accomplished using a catalyst system composed of Pd(OAc)2 and SelectPhos (L1), with catalyst loadings reducible to as low as 0.02 mol% Pd. The sequential double functionalization of bromochloroaryl triflates was also demonstrated successfully, paving the way for the synthesis of terphenyl derivatives.

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.

Rosa Indica flower petal anthocyanin mediated biogenic synthesis of PdNPs: Catalyst intended for the Suzuki-Miyaura reactions

In the present work, theRosa Indicaflowerpetals anthocyanin extract has been employed as a “green” natural source for the synthesis and topping of noble metal nanoparticles [palladium nanoparticles (PdNPs)]. TheRosa Indicaflowerpetals anthocyanin extract effectively replaces the toxic chemicals and stabilizers. The formed PdNPs were exposed to their structural properties examination by the Ultraviolet–Visible absorption, Energy-dispersive X- ray and Fourier TransformInfrared spectroscopic analysis. The diffractionpattern of the PdNPs@ rose-anthocyanin to the X-ray recognizes their crystalline nature. In addition, the detailed analysis of the X-ray pattern and microscopic images ofFESEM, TEM reveals that formed PdNP@ rose-anthocyanin possesses FCC crystal lattice with average dimensions of the particle ∼ 12 nm. The EDS analysis shows that the PdNPs@ rose-anthocyanin contains ∼ 80 wt% PdNPs. Further, the PdNP@ rose-anthocyanin were efficiently catalyses the Suzuki-Miyaura cross-coupling (CC) reactions between an aryl halide and phenylboronic acid in the presence of K2CO3 as a suitable base. To catalyse the reaction, PdNPs@ rose-anthocyanin works as heterogeneous catalyst in the absence of heating. Moreover, it provides a good to high yield of the corresponding coupled products under aerobic conditions with optimum reaction time in the aqueous medium, particularly at room temperature with a virtuous Turnover number relative to several synthesized PdNPs. Further, the catalyst PdNP@ rose-anthocyanin shows righteous catalytic activity without significant loss in its efficiency up to four reusable cycles.

Pd nanoparticles supported in PDMAEMA-b-PLMA micelles: A superb catalytic platform for Suzuki-Miyaura cross-coupling in water

Pd nanoparticles (NPs) supported by micelles formed with poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (Pd/PDMAEMA-b-PLMA) were prepared and employed as catalyst in the Suzuki-Miyaura cross-coupling reaction of aryl bromides with arylboronic acids in water. Most reactions proceeded with high efficiency at room temperature with only 0.05 mol% Pd loading in the absence of ligands, which afforded the desired functionalized biaryls in 73–98 % yields after 24 h. After reaction, Pd/PDMAEMA-b-PLMA retained in the aqueous phase was easily separated from the insoluble biaryl product and could be further reused two times without significant loss in catalytic efficiency. Characterization of the catalyst disclosed that sub-2 nm Pd NPs were embedded in the hydrophilic corona of polymeric micelles that served as nanoreactors in water.

Magnetically recoverable Pd-SILP-Fe3O4@SiO2 catalyst for the Suzuki–Miyaura cross-coupling

An efficient method for the synthesis of range of biaryl through Suzuki-Miyaura cross-coupling of a variety of aryl boronic acids with aryl halides employing highly water dispersible, magnetically separable, palladium tagged, magnetic nanoparticle supported, ionic liquid phase catalyst (Pd-SILP-Fe3O4@SiO2) in water under aerobic conditions has been developed. This nanocatalyst exhibited high thermal stability, high catalytic efficiency, high turnover frequencies (TOF), compatibility in aqueous systems, easy magnetic recovery, and reusability up to 6th run. The major advantages of this method are mild reaction conditions, easy set-up, easy workup, low Pd loading (0.00084 mol% of Pd), higher yields, and use of water as a green solvent, which makes it both environmentally and economically appealing.

Palladium(II)-immobilized Triptycene based Hypercrosslinked Polymers: An Efficient, Green, and Reusable Heterogenous Catalyst for Suzuki-Miyaura Cross-coupling Reaction.

The Suzuki-Miyaura cross-coupling (SMCC) involves the coupling of organohalides and organoboron molecules in the presence of Pd(II)-based catalysts. Often SMCC reactions employ homogenous catalysts. However, such homogenous SMCC reactions are associated with certain limitations which has motivated design of effective and sustainable Pd(II)-based heterogeneous catalytic systems. Herein, we report a systematic development of a Pd(II)-immobilized and triptycene based ionic hyper crosslinked polymer (Pd@TP-iHCP) and explored its application as a heterogeneous catalyst for SMCC reaction. Pd@TP-iHCP has ample N-heterocyclic carbene (NHC) pendants that anchor Pd(II) centres on the polymeric matrix. Pd@TP-iHCP was characterized satisfactorily using FT-IR, 13 C CP-MAS NMR, BET surface area analysis, SEM, EDX and HRTEM. The performance of Pd@TP-iHCP as a heterogeneous catalyst for SMCC reactions was explored using various combinations of aryl boronic acids and aryl halides. Experimental results show that Pd@TP-iHCP is associated with a moderately high surface area. It is an efficient catalyst for SMCC (in aqueous media) with a modest loading of 0.8 mol % Pd(II)-catalyst since high yields of the expected products were obtained in shorter time intervals. Pd@TP-iHCP also features excellent stability and catalyst recyclability since it could be re-used for several cycles without any significant decrease in catalytic efficiency.

One-pot synthesis of ligand-free highly active Pd catalyst supported on NiFe spinel oxide for Suzuki–Miyaura cross-coupling reaction

This work underscores the development of an easily separable, very simple yet highly active heterogeneous Pd catalyst supported on Ni−Fe spinel oxide containing a low percentage of noble metal Pd (only 1 at.%) enabling the access to an advanced set of catalysts for Suzuki–Miyaura carbon–carbon (C−C) cross-coupling reaction that are not easily accessible with homogeneous catalysts. A series of catalytic experiments have revealed optimum reaction conditions for C−C coupling between aryl bromide and phenyl boronic acid. Among a set of prepared catalysts, NiPdFe-1 (Ni/Pd molar ratio=1:1) is found to be the most active catalyst for the coupling reaction completing in just about 30 min under mild reaction conditions like 100 °C using Na2CO3 as the base in a very common organic solvent, DMF. Interaction between the oxide support and Pd(0) makes the Pd surface more electron-rich which accelerates the rate-determining step of the C−C coupling reaction by faster electron transfer from Pd(0) to the aryl halides. Moreover, the catalyst is essentially heterogeneous, stable, magnetically separable and durable for several cycles without losing its activity. Good to excellent isolated yields have been obtained with a variety of functionalities on both the aryl bromide and phenyl boronic acid with varying electronic properties.

Phenoxythiazoline (FTz)-Cobalt(II) Precatalysts Enable C(sp2 )-C(sp3 ) Bond-Formation for Key Intermediates in the Synthesis of Toll-like Receptor 7/8 Antagonists.

Evaluation of the relative rates of the cobalt-catalyzed C(sp2 )-C(sp3 ) Suzuki-Miyaura cross-coupling between the neopentylglycol ester of 4-fluorophenylboronic acid and N-Boc-4-bromopiperidine established that smaller N-alkyl substituents on the phenoxyimine (FI) supporting ligand accelerated the overall rate of the reaction. This trend inspired the design of optimal cobalt catalysts with phenoxyoxazoline (FOx) and phenoxythiazoline (FTz) ligands. An air-stable cobalt(II) precatalyst, (FTz)CoBr(py)3 was synthesized and applied to the cross-coupling of an indole-5-boronic ester nucleophile with a piperidine-4-bromide electrophile that is relevant to the synthesis of reported toll-like receptor (TLR) 7/8 antagonist molecules including afimetoran. Addition of excess KOMe⋅B(Oi Pr)3 improved catalyst lifetime due to attenuation of alkoxide basicity that otherwise resulted in demetallation of the FI chelate. A first-order dependence on the cobalt precatalyst and a saturation regime in nucleophile were observed, supporting turnover-limiting transmetalation and the origin of the observed trends in N-imine substitution.

Copper-Catalyzed Regiodivergent Borylation of Fluorinated Alkynes and Palladium-Catalyzed Regiospecific Suzuki–Miyaura Cross-Coupling

AbstractAlkenylboranes are key intermediates in modern organic synthesis, and they are usually obtained by the borylation of alkynes. We report herein highly regio- and stereoselective syntheses of α,Z- and β,Z-trifluoromethylated alkenylboranes by copper-catalyzed borylation reactions. Further functionalizations by palladium-catalyzed Suzuki–Miyaura cross-couplings have been developed and, interestingly, a marked difference in reactivity between the α- and β-borylated isomers has been identified.

Regio- and chemoselective synthesis of polyaryl flavones by combination of C-O/C-H activation and Suzuki-Miyaura cross coupling reactions

The first regioselective ruthenium-catalyzed arylation of flavone-derived compounds is reported. Exploring the molecular structure-reactivity different 5-,5,8-, 5,7-, 5,6- and 5,7,8-aryl substituted flavones were prepared through Ru-, Ni- and Pd-catalyzed coupling reactions with aryl boronic species under regio- and chemoselective approach in moderate to excellent yields. The obtained derivatives were thoroughly characterized by spectroscopic techniques, such as 1H NMR, 13C NMR and HRMS data. The convenient availability of starting natural product chrysin confers facility to the employed reactions which products may find application in pharmaceutical and material science areas.

Mechanochemical Synthesis of PdO2 Nanoparticles Immobilized over Silica Gel for Catalytic Suzuki-Miyaura Cross-Coupling Reactions Leading to the C-3 Modification of 1H-Indazole with Phenylboronic Acids.

The C-3 modification of 1H-indazole has produced active pharmaceuticals for the treatment of cancer and HIV. But, so far, this transformation has seemed less available, due to the lack of efficient C-C bond formation at the less reactive C-3 position. In this work, a series of silica gel-supported PdO2 nanoparticles of 25-66 nm size were prepared by ball milling silica gel with divalent palladium precursors, and then employed as catalysts for the Suzuki-Miyaura cross-coupling of 1H-indazole derivative with phenylboronic acid. All the synthesized catalysts showed much higher cross-coupling yields than their palladium precursors, and could also be reused three times without losing high activity and selectivity in a toluene/water/ethanol mixed solvent. Although the palladium precursors showed an order of activity of PdCl2(dppf, 1,1'-bis(diphenylphosphino)ferrocene) > PdCl2(dtbpf, 1,1'-bis(di-tert-butylphosphino)ferrocene) > Pd(OAc, acetate)2, the synthesized catalysts showed an order of C1 (from Pd(OAc)2) > C3 (from PdCl2(dtbpf)) > C2 (from PdCl2(dppf)), which conformed to the orders of BET (Brunauer-Emmett-Teller) surface areas and acidities of these catalysts. Notably, the most inexpensive Pd(OAc)2 can be used as a palladium precursor for the synthesis of the best catalyst through simple ball milling. This work provides a highly active and inexpensive series of catalysts for C-3 modification of 1H-indazole, which are significant for the large-scale production of 1H-indazole-based pharmaceuticals.

Pd "Kills Two Birds with One Stone" for the Synthesis of Catalyst: Dual Active Sites of Pd Triggers the Kinetics of O2 Electrocatalysis.

Noble metal-based catalyst, despite their exorbitant cost, are the only successful catalyst for bifunctional oxygen electrocatalysis owing to their capability to drive forward the reaction rate kinetically. Therefore, it is desirable to diminish the noble metal loading without any compromise in the catalyst performance. In this study, the aim to achieve two goals with one action via a single-step route to have ultra-low loading of Pd in the catalyst. The Pd is used as a catalyst for C─C bond formation followed by complexation reactions or vice versa, in conventional Suzuki-Miyaura cross-coupling (SMCC) reaction, which yields a Pd-based porous organic polymer. Interestingly, it is found that dispersed Pd nanocluster (PdNC ) is present together with Pd single atom doped into nanocarbon (Pd-NC) matrix in the catalyst (PdNC /Pd-NC800 ) that obtained after pyrolysis of the porous polymer. The catalyst exhibits remarkable bifunctional activity and durability towards oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Further, it is studied that the in situ attenuated total reflection infrared (ATR-IR) spectroscopy at different electrochemical potentials during ORR and OER to observe the reaction intermediates. The homemade zinc-air battery with the catalyst displayed great performance, establishing the significance of PdNC /Pd-NC800 as a bifunctional oxygen electrocatalyst.

Fabrication of boronic acid-functionalized covalent organic framework for the selective adsorption of cis-diol-containing compounds

In this work, we report a post-synthetic modification strategy to synthesize a boronic acid-functionalized porphyrin-based covalent organic framework (denoted as BA-COF) via the Suzuki-Miyaura cross-coupling reaction. Interestingly, BA-COF exhibits excellent selectivity in adsorbing cis-diol-containing compounds (CDC). The selective adsorption mechanism was addressed in detail, which is probably due to the boronate affinity from boronic acid group, hydrophilic interaction from the nitrogen-rich framework as well as “host–guest” interaction from the unique “trap” structure of porphyrin-based COF. The characterized results demonstrated its uniform morphology, large specific surface area, and excellent thermal stability. The adsorption kinetics demonstrated that the adenosine adsorption onto BA-COF conformed to the pseudo-second-order kinetic model and belonged to chemisorption. Based on the fitting of adsorption isotherms and thermodynamic analysis, the adenosine adsorption onto BA-COF was monomolecular layer adsorption and was a spontaneous endothermic reaction. Moreover, the reuse performance of BA-COF was investigated through consecutive adsorption–desorption cycle experiments. This work also demonstrates the potential of BA-COF for effective and selective adsorption of CDC in real sample.

CO2-Triggered Hierarchical-Pore UiO-66-Based Pickering Emulsions for Efficient and Recyclable Suzuki-Miyaura Cross-Coupling in Biphasic Systems.

Hierarchical-pore metal-organic frameworks (H-MOFs) are considered to be emerging stabilizers for Pickering emulsion formation because of their hierarchically arranged pores, tailorable structures, and ultrahigh surface areas. However, stimulus-triggered Pickering emulsions built by H-MOFs have been seldom presented to date despite their great significance in diverse applications. Herein, by grafting Pd(OAc)2 on the hierarchical-pore zirconium MOF UiO-66, namely, H-UiO-66, with the aid of 1-alkyl-3-methylimidazolium 2-cyanopyrrolide salts ([CnMIM][2-CN-Pyr], n = 4, 6, and 8), a series of Pd(OAc)2-[CnMIM][2-CN-Pyr]@H-UiO-66 have been developed and utilized as emulsifiers for constructing CO2-switching Pickering emulsions. It was found that Pd(OAc)2-[CnMIM][2-CN-Pyr]@H-UiO-66 was able to stabilize the n-hexane-water mixture to form a Pickering emulsion even at an amount of 0.5 wt %. Upon alternate addition of CO2 and N2 at normal pressure, Pickering emulsions could be smartly converted between demulsification and re-emulsification. Through combining varieties of spectroscopic techniques, the mechanism of the switchable phase transformation lay in the acid-base reaction of ionic liquids with CO2 on H-UiO-66 and the creation of more hydrophilic salts, which reduced the wettability of the emulsifier and destabilized the emulsion. As an example of application, the stimulus-triggered Pickering emulsion was employed as a palladium-catalyzed Suzuki-Miyaura cross-coupling microreactor to achieve the combination of chemical reactions, isolation of products, and recovery of catalysts.

Carbonyl-Supported Coordination in Imidazolates: A Platform for Designing Porous Nickel-Based ZIFs as Heterogeneous Catalysts.

Zeolitic imidazolate frameworks (ZIFs) are a subclass of metal-organic framework that have attracted considerable attention as potential functional materials due to their high chemical stability and ease of synthesis. ZIFs are usually composed of zinc ions coordinated with imidazole linkers, with some other transition metals, such as Cu(II) and Co(II), also showing potential as ZIF-forming cations. Despite the importance of nickel in catalysis, no Ni-based ZIF with permanent porosity is yet reported. It is found that the presence and arrangement of the carbonyl functional groups on the imidazole linker play a crucial role in completing the preferred octahedral coordination of nickel, revealing a promising platform for the rational design of Ni-based ZIFs for a wide range of catalytic applications. Herein, the synthesis of the first Ni-based ZIFs is reported and their high potential as heterogeneous catalysts for Suzuki-Miyaura cross-coupling C─C bond forming reactions is demonstrated.

Nickel complexes bearing N,N,N-tridentate quinolinyl anilido-imine ligands: Synthesis, characterization and catalysis in Suzuki-Miyaura cross-coupling reaction

Four nickel complexes incorporating N,N,N-quinolinyl anilido-imine ligands based on ortho-C6H4F(CH = NAr) and 8-aminoquinoline, Ni[{2-[ArN = C(H)]C6H4}N(8-C9H6N)]Br (Ar = 2,6-iPr2C6H3 (1a), 2,4,6-(CH3)3C6H2 (1b), 4-BrC6H4 (1c)) and Ni[{2-[ArN = C(H)]C6H4}N(8-C9H6N)]2 (Ar = 4-ClC6H4 (1d)) were synthesized and structurally characterized by HR-MS, IR, NMR spectroscopy and X-ray crystallography. These nickel(II) complexes were used in Suzuki-Miyaura coupling and exhibited moderate to excellent catalytic activity with a low catalyst loading of 2.0 mol%.

Photocatalytic Free Radical-Controlled Synthesis of High-Performance Single-Atom Catalysts.

Single-atom catalysts (SACs) have emerged as crucial players in catalysis research, prompting extensive investigation and application. The precise control of metal atom nucleation and growth has garnered significant attention. In this study, we present a straightforward approach for preparing SACs utilizing a photocatalytic radical control strategy. Notably, we demonstrate for the first time that radicals generated during the photochemical process effectively hinder the aggregation of individual atoms. By leveraging the cooperative anchoring of nitrogen atoms and crystal lattice oxygen on the support, we successfully stabilize the single atom. Our Pd1 /TiO2 catalysts exhibit remarkable catalytic activity and stability in the Suzuki-Miyaura cross-coupling reaction, which was 43 times higher than Pd/C. Furthermore, we successfully depose Pd atoms onto various substrates, including TiO2 , CeO2 , and WO3 . The photocatalytic radical control strategy can be extended to other single-atom catalysts, such as Ir, Pt, Rh, and Ru, underscoring its broad applicability.

Photoactive mesoporous magnetic nanocomposite of TiO2-Pd for a clean and sustainble Suzuki-Miyaura cross-coupling reaction via blue-LED and Mott-Schottky effect

Intelligently designed effective photocatalysts and their surface manufacturing are essential to generating chemical energy from solar energy in photocatalytic organic reactions. In this paper, we have synthesized a robust photocatalyst for CC coupling reaction under visible light irradiation. The designed structure including Fe3O4@SiO2/TiO2 decorated with l-Histidine/Pd, showed significant photocatalytic activity in a CC coupling reaction. The main advantages of this heterogeneous photocatalyzed CC cross-coupling reaction are its environment friendly, high yield of products, stability, durability, recyclability, and simple and facile synthesis approach.