Amination reactions of aryl halides with nitrogen-containing reagents mediated by palladium/imidazolium salt systems.

Nucleophilic N-heterocyclic carbenes have been conveniently used as catalyst modifiers in amination reactions involving aryl chlorides, aryl bromides, and aryl iodides with various nitrogen-containing substrates. The scope of a coupling process using a Pd(0) or Pd(II) source and an imidazolium salt in the presence of a base, KO(t)Bu or NaOH, was tested using various substrates. The Pd(2)(dba)(3)/IPr.HCl (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) system presents the highest activity with respect to electron-neutral and electron-rich aryl chlorides. The ligand is also effective for the synthesis of benzophenone imines, which can be easily converted to the corresponding primary amines by acid hydrolysis. Less reactive indoles were converted to N-aryl-substituted indoles using as supporting ligand the more donating SIPr.HCl (5, SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene). The Pd(OAc)(2)/SIPr.HCl/NaOH system is efficient for the N-arylation of diverse indoles with aryl bromides. The general protocol developed has been applied successfully to the synthesis of a key intermediate in the synthesis of an important new antibiotic. Mechanistically, palladium-to-ligand ratio studies strongly support an active species bearing one nucleophilic carbene ligand.     

Palladium-catalyzed C–S bond formation by using N-amido imidazolium salts as ligands

N-Amido imidazolium salt was employed as a ligand in the palladium-catalyzed cross-coupling reaction of aryl halides and thiols, and showed good activity in the formation of thioether. The best combination for the coupling with aryl bromides was N-amido imidazolium salt 2 and NaHMDS, and that for the coupling with aryl iodides was N-amido imidazolium salt 1 and KO^tBu. The coupling reactions were conducted in the presence of Pd(OAc)₂ (1 mol %) in DMSO at 80 °C for 12 h.     

Highly efficient carbazolyl-derived phosphine ligands: application to sterically hindered biaryl couplings

A new family of phosphine ligands bearing a bulky carbazolyl scaffold is described. With the combination of ligand 2a and Pd(OAc)(2), difficult tri-ortho-substituted biaryl couplings are accomplished smoothly. In particular, the catalyst loading as low as 0.02 mol% of Pd for non-activated 2,6-disubstituted aryl chloride coupling can be achieved.     

Aryl-aryl coupling reaction using a novel and highly active palladium reagent prepared from Pd(OAc)2, 1,3-bis[diphenylphosphino]propane (DPPP), and Bu3P

A palladium-assisted coupling reaction of aryl triflate with arene was investigated, and a novel Pd reagent prepared from equimolar Pd(OAc)2, 1,3-Bis[diphenylphosphino]propane (DPPP), and Bu3P was developed. This method is useful for intramolecular biaryl coupling reactions, not only between aryl triflate and arene (triflate-amide), but also between aryl halide and arene (halo-amide).     

Efficient imidazolium salts for palladium-catalyzed Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions

The system, Pd(OAc)2/imidazolium salts (L2), was found as an efficient catalyst in the Heck coupling reaction of olefins with aryl halides and Suzuki reactions of various aryl halides with aryl boronic acids under aerobic condition. This catalytic system demonstrates great tolerance to a wide range of groups on all substrates of aryl halides, alkenes and aryl boronic acids.     

Preparation of 2,5-disubstituted oxazoles from N-propargylamides

[reaction: see text] 2,5-Disubstituted oxazoles have been prepared through the reaction of N-propargylamides with aryl iodides in the presence of Pd(2)(dba)(3), tri(2-furyl)phosphine, and NaO(t)()Bu. The reaction appears to proceed through a palladium-catalyzed coupling step followed by the in situ cyclization of the resultant coupling product.     

Indolylbenzimidazole‐based ligands catalyze the coupling of arylboronic acids with aryl halides

A novel class of compounds bearing indole and benzimidazole rings was designed and easily synthesized from 2‐indolecarboxylic acid and o‐phenylenediamine. The catalytic system derived from a 2‐indolylbenzimidazole‐based ligand and Pd(OAc)₂ in situ could lead to complete conversion of aryl bromides at 0.5 mol% Pd loading under mild reaction conditions. In the presence of a catalyst, sterically hindered biaryls were selectively generated in excellent yields by adjusting reaction parameters through the coupling of arylboronic acids with aryl halides. The efficiency of this reaction was demonstrated by its compatibility with various functional groups.     

Ferrocenyl bisoxazoline as an efficient non‐phosphorus ligand for palladium‐catalyzed copper‐free Sonogashira reaction in aqueous solution

Pd(OAc)₂‐catalyzed Sonogashira coupling reactions of alkynes and a variety of aryl halides with 1,3‐bis(5‐ferrocenylisoxazoline‐3‐yl)benzene as an efficient non‐phosphorus ligand under copper‐free conditions are presented. The main advantages over previous methodologies include low catalyst loading (0.2 mol% Pd(OAc)₂ and 0.4 mol% ferrocenyl bisoxazoline ligand are sufficient for these coupling reactions), less problematic reaction medium (water–dimethylformamide) and more convenient operation (no requirement for nitrogen protection).     

An improved catalyst for the asymmetric arylation of ketone enolates

A new catalyst system for the enantioselective alpha-arylation of ketones is reported. This catalyst, prepared from Pd(2)(dba)(3) and a bulky dialkylphosphino-binaphthyl ligand, is able to effect the asymmetric arylation of ketone enolates with aryl bromides utilizing NaO(t)()Bu as base. These new catalysts enjoy much higher reactivity than previous systems; arylation reactions could be effected at room temperature with only 2 mol % of the Pd catalyst. The coupling of alpha-alkyl-alpha'-protected cyclopentanones proceeded in high yield, and the resulting quaternary stereogenic center was installed in up to 94% ee.     

Effective Pd-nanoparticle (PdNP)-catalyzed Negishi coupling involving alkylzinc reagents at room temperature

Pd(OAc)(2) is an efficient catalyst precursor for Negishi coupling in the presence of Bu(4)NBr. Secondary and primary alkylzinc reagents with beta-H and arylzinc reagents all reacted with aryl iodides at temperatures as low as -20 degrees C, giving moderate to good yields. One example of coupling between alkynylzinc reagents and aryl iodides was tested and the yield was good. Preliminary kinetic studies indicated that the process involved PdNPs as the active catalytic species.     

Guanidine/Pd(OAc)2-catalyzed room temperature Suzuki cross-coupling reaction in aqueous media under aerobic conditions

A highly efficient Pd(OAc)2/guanidine aqueous system for the room temperature Suzuki cross-coupling reaction has been developed. The new water-soluble and air-stable catalyst Pd(OAc)2.(1f)2 from Pd(OAc)2 and 1,1,3,3-tetramethyl-2-n-butylguanidine (1f) was synthesized and characterized by X-ray crystallography. In the presence of Pd(OAc)2.(1f)2, coupling of arylboronic acids with a wide range of aryl halides, including aryl iodides, aryl bromides, even activated aryl chlorides, was carried out smoothly in aqueous solvent to afford the cross-coupling products in good to excellent yields and high turnover numbers (TONs) (TONs up to 850,000 for the reaction of 1-iodo-4-nitrobenzene and phenylboronic acid). Furthermore, this mild protocol could tolerate a broad range of functional groups.     

Palladium catalysed aryl enol ether synthesis from vinyl triflates

Vinyl triflates can be efficiently converted into the corresponding aryl enol ethers by treatment with a phenol, NaO(t)Bu and a catalyst generated from Pd2dba3 and 2-(di-(t)Bu-phosphino)biphenyl.     

Palladium/Imidazolium salt as a versatile catalyst for sequential coupling reactions of aryl dihalides to unsymmetrically substituted arenes

A simple method for one-pot sequential Heck/Suzuki coupling reactions of a range of substituted aryl dihalides has been described. The Pd(OAc)₂/imidazolium system catalyzed double coupling reactions proceed without isolation of the intermediates giving unsymmetrically polysubstituted biphenyls in good to excellent yields. Further couplings of the resultant products bearing additional C-Cl bonds with substituted arylboronic acids or amines lead to unsymmetrical terphenyls and aminobiphenyl derivatives.     

在催化体系可回收和无配体条件下溴化四丁基铵中钯催化卤代芳烃与芳基硼酸的Suzuki-Miyaura交叉偶联反应

我们发展一种在催化体系可回收和无配体条件下溴化四丁基铵（TBAB）中钯催化卤代芳烃与芳基硼酸的Suzuki-Miyaura交叉偶联反应方法。我们发现水的量对反应有很大的影响。当水的用量为1 %（质量比）时,反应的结果最好。在3 mol%的醋酸钯和1.5 g的TBAB（含1%的水）,一系列卤代芳烃与芳基硼酸的顺利地发生Suzuki-Miyaura交叉偶联反应,得到中等及良好的产率。而且在溴代芳烃和活泼的氯代芳烃的交叉反应中,Pd(OAc)2/TBAB催化体系可以回收重复使用多次,并且催化活性基本不变。     

Room-temperature Negishi cross-coupling of unactivated alkyl bromides with alkyl organozinc reagents utilizing a Pd/N-heterocyclic carbene catalyst

A high-yielding cross-coupling reaction of unactivated alkyl bromides possessing beta-hydrogens with alkylzinc halides utilizing a Pd/N-heterocyclic carbene (NHC) catalyst at room temperature is described. A variety of Pd sources, Pd2(dba)3, Pd(OAc)2, or PdBr2, with the commercially available ligand precursor 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IPr.HCl) successfully coupled 1-bromo-3-phenylpropane with n-butylzinc bromide in THF/NMP. An investigation of different NHC precursors showed that the bulky 2,6-diisopropylphenyl moiety was necessary to achieve high coupling yields (75-85%). The corresponding ethyl analogue was moderately active (11%). A range of unsymmetrical NHC precursors were prepared and evaluated. The ligand precursor containing one 2,6-diisopropylphenyl and one 2,6-diethylphenyl afforded the coupling product in 47% yield, clearly suggesting a direct relationship between the steric topography created by the flanking N-substituents and catalyst activity. Under optimal conditions, a number of alkyl bromides and alkylzinc halides possessing common functional groups (amide, nitrile, ester, acetal, and alkyne) were effectively coupled (61-92%). It is noteworthy that beta-substituted alkyl bromides and alkylzinc halides successfully underwent cross-coupling. Also, under these conditions alkyl chlorides were unaffected.     

Effect of counterions and central cores of tripodal imidazolium salts on palladium-catalyzed Suzuki-Miyaura cross-coupling reactions

Seven tripodal imidazolium salts were synthesized and used as catalyst precursors in cross-coupling reactions of aryl halides with arylboronic acids. Effect of counterions and central cores of seven tripodal imidazolium salts was investigated. The tripodal imidazolium salt anchored to benzene with anion PF₆⁻ was found most effective with Pd(OAc)₂ for the cross-coupling of aryl bromides with arylboronic acids.     

N‐Heterocyclic carbene/phosphite synergistically assisted Pd/C‐catalyzed Suzuki coupling of aryl chlorides

An N‐heterocyclic carbene and phosphite synergistically enhanced Pd/C catalyst system has been developed for Suzuki coupling of aryl chlorides and aryl boronic acids from commercially available Pd/C with sterically demanding N,N′‐bis(2,6‐diisopropylphenyl)imidazolylidene and trimethylphosphite. A remarkable increase in catalytic activity of Pd/C was observed when used along with 1 equiv. N,N′‐bis(2,6‐diisopropylphenyl)imidazolium chloride and 2 equiv. phosphite with respect to palladium in appropriate solvents that were found to play a crucial role in Pd/C‐NHC‐P(OR)₃‐catalyzed Suzuki coupling. A dramatic ortho‐substitution effect of carbonyl and nitrile groups in aryl chlorides was observed and explained by a modified quasi‐heterogeneous catalysis mechanism. The Pd/C catalyst could be easily recovered from reaction mixtures by simple filtration and only low palladium contamination was detected in the biparyl products. A practical process for the synthesis of 4‐biphenylcarbonitrile has therefore been developed using the N‐heterocyclic carbene/phosphite‐assisted Pd/C‐catalyzed Suzuki coupling. Copyright © 2013 John Wiley & Sons, Ltd.     

Palladium-catalyzed site-selective arylation of symmetric dichlorobenzaldehyde to non-symmetric diaryl benzaldehyde via Suzuki coupling

Arylation of 2,6-dichlorobenzaldehyde by aryl boronic acids via site-selective Suzuki coupling catalyzed by PdCl₂ supported on 4 Å molecular sieves produces 2-aryl-6-chlorobenzaldehyde which on subsequent coupling with a different aryl boronic acid in the presence of Pd(OAc)₂–NHC ligand leads to non-symmetric diaryl benzaldehyde in good overall yield.     

MOF-253 immobilized Pd and Cu as recyclable and efficient green catalysts for Sonogashira reaction

MOF-253·Pd(OAc)₂ and MOF-253·CuI were prepared, characterized, and evaluated firstly as heterogeneous co-catalysts, which showed high catalytic activity in Sonogashira coupling reaction of various substituted (hetero)aryl halides with terminal alkynes at 70–120 °C, and afforded the corresponding products in 45–99% yields with high TON (～2722 for Pd). The best result was achieved with an extremely low Pd (0.036 mol%) and Cu (0.397 mol%) loading. Moreover, the catalysts can be reused at least five times without significantly reducing the activity. Besides, Hg(0) and PVP-poisoning experiments confirmed that the present catalysts were efficient and heterogeneous catalysts in this coupling reaction.     

Palladacycles bearing tridentate CNS-type benzamidinate ligands as catalysts for cross-coupling reactions

Three pendant benzamidines, [Ph-C(=NC(6)H(5))-{NH(E)}] [E = -(CH(2))(2)SMe (1); -(CH(2))(2)S(t)Bu (2); -o-C(6)H(4)SMe (3)], are described. Reactions of 1, 2 or 3 with one molar equivalent of Pd(OAc)(2) in CH(2)Cl(2) give the palladacyclic complexes, [Ph-C{-NH(η(1)-C(6)H(4))}{=N(E)}]Pd(OAc) [E = -(CH(2))(2)SMe (4); -(CH(2))(2)S(t)Bu (5); -o-C(6)H(4)SMe (6)], as mononuclear palladium complexes respectively. A minor product described as 5', {[Ph-C{-N(C(6)H(5))}{-N(CH(2))(2)S(t)Bu}]Pd(OAc)}(2), was isolated as benzamidinate-bridged dinuclear palladium complex upon recrystallizing from Et(2)O/hexane solution. Treatment of 1, 2 or 3 with one molar equivalent of PdCl(2) in the presence of NEt(3) in CH(2)Cl(2) gives the palladacyclic complexes, [Ph-C{-NH(η(1)-C(6)H(4))}{=N(E)}]PdCl [E = -(CH(2))(2)SMe (7); -(CH(2))(2)S(t)Bu (8); -o-C(6)H(4)SMe (9)], as mononuclear palladium complexes respectively. The crystal and molecular structures are reported for compounds 5, 5' and 6-8. The application of these palladacyclic complexes to the Suzuki and Heck coupling reactions was examined.