Palladium-catalyzed Suzuki Reaction Research Articles

The Suzuki Reaction in Aqueous Media Promoted by P, N Ligands

The synthesis and structure of palladium complexes of trisubstituted PTA derivatives, PTAR3, are described. Water-soluble phosphine ligands 1,3,5-triaza-7-phosphaadmantane (PTA), tris(aminomethyl)phosphine trihydrobromide, tri(aminomethyl) phosphine, 3,7-dimethyl-1,5,7-triaza-3-phosphabicyclo[3,3,1]nonane (RO-PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA), lithium 1,3,5-triaza-7-phosphaadamantane-6-carboxylate (PTA-CO2Li), 2,4,6-triphenyl-1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane, and 2,4,6-triphenyl-1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane were used as ligands for palladium catalyzed Suzuki reactions in aqueous media. RO-PTA in combination with palladium acetate or palladium chloride was the most active catalyst for Suzuki cross coupling of aryl bromides and phenylboronic acid at 80 °C in 1:1 water:acetonitrile. The activity of Pd(II) complexes of RO-PTA is comparable to PPh2(m-C6H4SO3Na) (TPPMS) and P(m-C6H4SO3Na)3 (TPPTS) and less active than tri(4,6-dimethyl-3-sulfonatophenyl)phosphine trisodium salt (TXPTS). Activated, deactivated, and sterically hindered aryl bromides were examined, with yields ranging from 50% to 90% in 6 h with 5% palladium precatalyst loading. X-ray crystal structures of (RO-PTA)PdCl2, (PTAR3)2PdCl2 (R = Ph, p-tert-butylC6H5), and PTAR3 (R = p-tert-butylC6H5) are reported.

Low-Bandgap Benzodifuranone-Based Polymers

π-Conjugated monomers and polymers containing benzodifuranone units in the main chain were prepared. Polymers were obtained using palladium-catalyzed Suzuki and Stille polycondensation reactions of dibromo-substituted benzodifuranone derivatives with either dihexylfluorene diboronester or bis(trimethylstannyl)thiophene. The optical and electronic properties were investigated using UV/vis absorption spectroscopy and cyclic voltammetry. It was found that the polymers show very broad absorption bands with a high extinction coefficient up to 32 500 L mol–1 cm–1. The polymers also show reversible redox behavior, giving small HOMO–LUMO gaps up to 1.30 eV with strong donor–acceptor character.

A simple and efficient protocol for a palladium-catalyzed ligand-free Suzuki reaction at room temperature in aqueous DMF

A convenient, effective and mild protocol has been developed for the palladium-catalyzed ligand-free Suzuki reaction of aryl bromides with arylboronic acids in aqueous N,N-dimethylformamide (DMF) in the presence of K2CO3 and a catalytic amount of PdCl2 in air at room temperature. It is noteworthy that the volume ratio of water–DMF and base play important roles in the reaction, and various functional groups are tolerated under the optimized conditions. Furthermore, this protocol could be extended to the cross-couplings of nitrogen-based heteroaryl halides with arylboronic acids in moderate to excellent yields.

Oxygen-promoted PdCl2-catalyzed ligand-free Suzuki reaction in aqueous media

A simple and efficient protocol has been developed for the PdCl(2)-catalyzed ligand-free and aerobic Suzuki reaction of aryl bromides or nitrogen-based heteroaryl bromides with arylboronic acids in good to excellent yields in aqueous ethanol. A systematic investigation on the effect of different atmospheres on the reactivity of the palladium-catalyzed Suzuki reaction has been carried out, the results show that an aerobic atmosphere demonstrates a positive effect on the reactivity of the Suzuki reaction in an aqueous media and a negative effect in a pure organic solvent, which exhibits that the water plays a crucial role for the function of the atmosphere on the palladium-catalyzed ligand-free Suzuki reaction.

ChemInform Abstract: Synthesis of Unnatural Amino Acids via Suzuki Cross-Coupling of Enantiopure Vinyloxazolidine Derivatives.

(R and S )-α-Amino alcohols and α-amino acids, including 4-methoxyhomophenylalanine, with a variety of unnatural side chains have been synthesized via palladium-catalyzed cross-coupling Suzuki reactions. The key building blocks 1 and 2, synthesized from the common achiral precursor 2-butene-1,4-diol, were made enantiopure utilizing a Pseudomonas cepacia lipase-catalyzed kinetic resolution. The optimal conditions for the Suzuki cross-coupling and the subsequent oxidations of the resultant α-amino alcohols are described.

A simple procedure for the covalent grafting of triphenylphosphine ligands on silica: application in the palladium catalyzed Suzuki reaction

An organic-inorganic hybrid material derived from covalently grafting a palladium complex of the type (L)(2)PdCl(2) (L = Si(OMe)(3) functionalized PPh(3)) on silica was synthesized, characterized and sucessfully applied as a catalyst for the Suzuki reaction.

β-Phase formation in poly(9,9-di-n-octylfluorene) by incorporating an ambipolar unit containing phenothiazine and 4-(dicyanomethylene)-2-methyl-6-[p-(dimethylamino)styryl]-4H-pyran

Novel fluorene-based blue-light-emitting copolymers (F8Rs) in the β-phase are designed and synthesized using the palladium-catalyzed Suzuki reaction. The β-phase can be generated by introducing an ambipolar unit, that contains 10-n-hexylphenothiazine (PTZ) and 4-(dicyanomethylene)-2-methyl-6-[p-(dimethylamino)styryl]-4H-pyran (DCM) (as the donor and acceptor moieties, respectively) on a polyfluorene backbone. By comparing the absorption (peak at 437 ± 1 nm), photoluminescence (PL) (peak at 441 ± 1 nm), and X-ray diffraction (XRD) (peak centered around 2θ = 7.0°) characteristics of the resulting polymers (F8Rs) with those of the polyfluorene homopolymer (PFO), we found that fluorene-based copolymers with ambipolar moieties, such as PTZ and DCM, can prompt the formation of the β-phase after spin-coating without gelling in a poor solvent, exposure to tetrahydrofuran vapor, cooling to liquid-N2 temperature, and reheating. The PL and electroluminescence (EL) efficiencies of the copolymer F8R5 are higher than those of PFO (by factors of two and 15, respectively). The EL spectrum of the copolymer showed almost pure blue emission, with CIE (Commission Internationale de l′Eclairage) coordinates of x = 0.17 and y = 0.10.

Sodium 2-(2-pyridin-3-ylethylamino)ethyl sulfonate: an efficient ligand and base for palladium-catalyzed Suzuki reaction in aqueous media

PdCl 2, N-donor ligand and base mediated Suzuki coupling reaction of aryl halides and arylboronic acid in water are described. The corresponding Suzuki products were obtained in good to excellent yields.

Synthesis and screening of small molecule inhibitors of anthrax edema factor

The synthesis and development of a novel class of molecules that inhibit anthrax edema factor, an adenylyl cyclase, is reported. These molecules are derived from the initial discovery that histidine and imidazole adducts of the prostaglandin PGE 2 reduce the net secretory response of cholera toxin-challenged mice and act directly on the action of anthrax edema factor, a calmodulin-dependent adenylyl cyclase. The simple enones examined in this letter were prepared by palladium-catalyzed Suzuki reaction.

A New Class of Iridium Complexes Suitable for Stepwise Incorporation into Linear Assemblies: Synthesis, Electrochemistry, and Luminescence

A new family of cationic iridium(III) complexes is reported that contain two cyclometalating terdentate ligands. The complex [Ir(N--C--N-dpyx)(N--N--C-phbpy)]+ (1) contains one N--C--N-coordinating ligand, cyclometalating through the central phenyl ring, and one N--N--C-coordinated ligand, cyclometalated at the peripheral phenyl ring [dpyxH = 1,3-di(2-pyridyl)-4,6-dimethylbenzene; phbpyH = 6-phenyl-2,2'-bipyridine]. This binding mode dictates a mutually cis arrangement of the cyclometalated carbon atoms: the complexes are thus bis-terdentate analogues of the well-known [Ir(N--C-ppy)2(N--N-bpy)]+ family of complexes, which similarly contain a cis-C2N4 coordination environment. The dpyx ligand can be brominated regioselectively at the carbon atom para to the metal under mild conditions. Starting from a modified complex, [Ir(N--C--N-dpyx)(N--N--C-mtbpy-phi-Br)]+ (2), which incorporates a pendent bromophenyl group, a sequential cross-coupling-bromination-cross-coupling strategy can be applied for the stepwise introduction of aryl groups into the ligands, using in situ palladium-catalyzed Suzuki reactions with arylboronic acids [mtbpyH-phi-Br = 4-(p-bromophenyl)-6-(m-tolyl)bipyridine]. Dimetallic complexes 6 and 7 have similarly been prepared by a palladium-catalyzed reaction of complex 2 with 1,4-benzenediboronic acid and 4,4'-biphenyldiboronic acid, respectively. All five monometallic complexes and both dimetallic systems are luminescent in solution, emitting around 630 nm in MeCN at 298 K, with quantum yields in the range of 0.02-0.06, superior to [Ir(ppy)2(bpy)]+. The luminescence, electrochemistry, and singlet-oxygen-sensitizing abilities of the new family of complexes are discussed in the context of the tris-bidentate analogues and related bis-terdentate compounds that contain a trans arrangement of cyclometalated carbon atoms.

Synthesis and biological evaluation of novel oxophenylarcyriaflavins as potential anticancer agents

We report the synthesis and biological evaluation of new oxophenylarcyriaflavins designed as potential anticancer agents. An efficient synthesis involving palladium-catalyzed Suzuki and Stille reactions is presented, without any indolic protective group. The central ring closure of the scaffold was performed through an electrophilic reaction on the position C-2 of the indole ring. The use of indole and 5-benzyloxyindole, along with substituted phenyl rings, generated three different scaffolds, which were successively exploited to modulate the structure. The cytotoxicity of the newly designed compounds on four cancer cell lines and activities against three kinases (CDK1, CDK5 and GSK3) were evaluated. Several compounds showed a marked cytotoxicity with IC(50) values in the sub-micromolar range, and induced important cell cycle perturbations, with a G2/M arrest. Some compounds revealed DNA binding properties and were found to inhibit topoisomerase-mediated DNA relaxation of supercoiled DNA, but these properties are not mandatory for a cytotoxic action. A novel lead compound () has been identified and warrants further investigations.

Preparation of monodentate phosphinite ligands: their applications in palladium catalyzed Suzuki reactions

Two phosphinites 2,6-OMe, 4-Me, 1-OPR 2C 6H 2 ( 5a: R=Ph; 5b: R= t Bu) were prepared in good yields. Two methoxy groups are placed on the 2,6 positions of the phosphinites deliberately thereby to avoid a plausible orthometallation process while coordinating toward palladium metal. Further reaction of 5a with PdCl 2 in the ratio of 2:1 and 1:1 gave 5a ligated palladium complexes {( 5a)PdCl(μ-Cl)} 2 7a and {( 5a) 2PdCl 2} 8a, respectively. As revealed from their crystal structures, the former is a dimeric complex with anticipated molecular arrangement; nevertheless, the latter is a monomeric complex with unexpected, energetically unfavorable cis form. By contrast, only dimeric form was observed from the reaction of 5b with PdCl 2. It is believed that the bulky substituents, t Bu, on 5b prevent the formation of a monomeric complex in cis form. Fair to good efficiencies were observed for the Suzuki–Miyaura cross-coupling reactions employed in situ-prepared 5/Pd(OAc) 2 as the catalytic precursor.

PEG-Supported Dipyridyl Ligand for Palladium-Catalyzed Suzuki and Suzuki-Type Reactions in PEG and Aqueous Media

An air- and water-stable PEG-supported bidentate nitrogen ligand is prepared and its applications in the palladium-catalyzed Suzuki reaction of aryl halides with arylboronic acids in PEG and Suzuki-type reaction of aryl halides with sodium tetraphenylborate in aqueous media are reported. The homogeneous catalyst system is environmentally friendly and offers the advantages of high activity, reusability and easy separation.

Preparation of a palladium dimer with a cobalt-containing bulky phosphine ligand: Its application in palladium catalyzed Suzuki reactions

A palladium dimer with a cobalt-containing phosphine ligand, {(μ-PPh 2CH 2PPh 2)Co 2(CO) 4(μ,η-( tBu) 2PC CC 6H 4-κC 1)Pd(μ-Cl)} 2 ( 3), was prepared from the reaction of its monomer precursor, (μ-PPh 2CH 2PPh 2)Co 2(CO) 4(μ,η-( tBu) 2PC CC 6H 4-κC 1)Pd(μ-OAc) ( 2), with LiCl. The crystal structure of 3, determined by X-ray diffraction methods, revealed a doubly chloride-bridged palladium dimeric conformation. Suzuki coupling reactions of bromobenzene with phenylboronic acid were carried out catalytically using these two novel palladium complexes 2 and 3 as catalyst precursors. Factors such as the molar ratio of substrate/catalyst, reaction temperature, base and solvent that might affect the catalytic efficiencies were investigated. As a general rule, the performance is much better by employing 3 than 2 as the catalyst precursor.

Biphenyl-Based Phosphine Ligands

(A) Buchwald and co-workers have used biphenyl ligands 1 and 2 for palladium-catalyzed Suzuki reactions of arylhalides at room temperature. 2b

Polymer-Incarcerated Palladium-Catalyzed Suzuki and Heck Reactions

A polymer-incarcerated (PI) palla­dium catalyst was practically prepared from Pd(NO3)2 and a polystyrene-based copolymer 1 with NaOAc under reducing conditions. Thus, when a solution of 1 with those reagents was heated for three hours, a polymer-supported palladium was successfully formed, which was coacervated with hexane and crosslinked to give PI Pd. In the presence of 5 mol% Pd of PI Pd catalyst, the Mizorogi-Heck reaction of PhI with ethyl acrylate and K2CO3 in NMP was performed to afford ethyl cinnamate in 94% yield. The Suzuki-Miyaura couplings of aryl bromides or 4-acetyl chlorobenzene with arylboronic acids (1.5 equiv) were also examined to give biphenyl derivatives in 95% quantitative yields (8 examples). The PI Pd catalyst was recyclable two times for these reactions.

Improved Synthesis of Monohalogenated Cavitands and Their Use in the Synthesis of Further Functionalized Cavitands

A new procedure for the synthesis of monohalogenated cavitands was established, which is at least one step shorter and far more atom-efficient than previously published pathways. These monohalogenated cavitands were demonstrated to be versatile synthons for the synthesis of further functionalized derivatives through cyanation, carboxylation, and a series of palladium-catalyzed Suzuki reactions.

Synthesis of 3-iodoindoles by the Pd/Cu-catalyzed coupling of N,N-dialkyl-2-iodoanilines and terminal acetylenes, followed by electrophilic cyclization.

[reaction: see text] 3-Iodoindoles have been prepared in excellent yields by coupling terminal acetylenes with N,N-dialkyl-o-iodoanilines in the presence of a Pd/Cu catalyst, followed by an electrophilic cyclization of the resulting N,N-dialkyl-o-(1-alkynyl)anilines using I2 in CH2Cl2. Aryl-, vinylic-, alkyl-, and silyl-substituted terminal acetylenes undergo this process to produce excellent yields of 3-iodoindoles. The reactivity of the carbon-nitrogen bond cleavage during cyclization follows the following order: Me > n-Bu, Me > Ph, and cyclohexyl > Me. Subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting 3-iodoindoles proceed smoothly in good yields.

Syntheses of 2‐(Pentafluorophenyl)thiophene Derivatives via the Palladium‐Catalyzed Suzuki Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Microwave‐Assisted Multistep Synthesis of Functionalized 4‐Arylquinolin‐2(1H)‐ones Using Palladium‐Catalyzed Cross‐Coupling Chemistry.

AbstractFor Abstract see ChemInform Abstract in Full Text.