Palladium-catalyzed direct 5-arylation of formyl- or acetyl-halothiophene derivatives

Pd(OAc)₂ was found to catalyze the direct arylation of some functionalized halothiophene derivatives allowing the synthesis in only one step of polyfunctionalized arylated thiophenes. In the presence of 2-acetyl-3-chlorothiophene, 2-acetyl-4-chlorothiophene, 2-acetyl-3-bromothiophene diethylacetal or 2-(4-bromothiophen-2-yl)-[1,3]dioxolane, and a variety of aryl bromides, the 5-arylation products were obtained in moderate to high yields employing only 0.5 mol% catalyst. On the other hand, the use of 2-formyl-3-chlorothiophene, 2-acetyl-3-bromothiophene or 2-formyl-3-bromothiophene gave disappointing results.     

Palladium-catalyzed direct oxidative vinylation of thiophenes and furans under weakly basic conditions

The palladium-catalyzed oxidative coupling of thiophenes and furans with alkenes proceeds in the presence of copper and lithium salts as oxidant and additive, respectively, under weakly basic or almost neutral conditions to afford the corresponding vinylated heteroarenes. Under such conditions, diphenyl(hydroxy)methyl and acetal functions on the heteroarene substrates are tolerable. The former function on a thiophene ring can be substituted by palladium-catalyzed arylation via C-C bond cleavage after the vinylation to produce 2-aryl-5-vinylthiophenes.     

Palladium-catalysed direct arylations of heteroaromatics using more eco-compatible solvents pentan-1-ol or 3-methylbutan-1-ol

The palladium-catalysed direct coupling of aryl halides with heteroaromatics in greener solvents than DMF or DMAc, which are often employed for such couplings, would be a considerable advantage for both industrial application and sustainable development. We observed that a range of aryl bromides undergoe coupling via C-H bond activation/functionalisation reaction of thiazoles or imidazoles in moderate to good yields using pentan-1-ol or 3-methylbutan-1-ol as the solvents. Pentan-1-ol and 3-methylbutan-1-ol are less toxic than DMF or DMAc, moreover they are bioresources as they can be obtained by fermentation. Therefore, these reaction conditions are certainly more eco-compatible than those generally employed for such couplings.     

Palladium-catalysed direct 3- or 4-arylation of thiophene derivatives using aryl bromides

The palladium-catalysed direct 3- or 4-arylation of 2,5-disubstituted thiophenes using aryl bromides gives a simple access to a variety of 3- or 4-arylthiophene derivatives. Moderate to good yields of 3-arylated thiophenes were obtained using 2,5-dimethylthiophene. In the presence of unsymmetrically disubstituted, 2-acetyl-5-methylthiophene, a regioselective arylation on carbon 4 of thiophene was observed. This reaction provides only HX associated to the base as by-product and reduces the number of steps to prepare these compounds.     

Direct arylation of oxazole and benzoxazole with aryl or heteroaryl halides using a palladium-diphosphine catalyst

Through the use of PdCl(dppb)(C₃H₅) as a catalyst, a range of aryl bromides and chlorides undergoes coupling via C-H bond activation/functionalization reaction with oxazole or benzoxazole in good yields. This air-stable catalyst can be used at low loadings with several substrates. Surprisingly, better results in terms of substrate/catalyst ratio were obtained in several cases using electron-excessive aryl bromides than with the electron-deficient ones. This seems to be mainly due to the relatively low thermal stability of some of the 2-arylbenzoxazoles formed with electron-deficient aryl halides. With these substrates, in order to obtain higher yields of product, the reactions had to be performed at a lower temperature (100-120 °C) using a larger amount of catalyst. On the other hand, in the presence of the most stable products, the reactions were performed at 150 °C using as little as 0.2 mol% catalyst. Arylation of benzoxazole with heteroaryl bromides also gave the coupling products in moderate to high yields using 0.2-5 mol% catalyst. With this catalyst, electron-deficient aryl chloride such as 4-chlorobenzonitrile, 4-chloroacetophenone or 2-chloronitrobenzene have also been used successfully.     

Palladium-catalyzed cross-coupling of trimethoxysilylbenzene with aryl bromides and chlorides using phosphite ligands

Phosphites were employed as ligands in palladium-catalyzed Hiyama coupling reactions. The optimized reaction conditions were equimolar amounts (5 mol % each) of Pd(acac)₂ and phosphite 1 in p-xylene at 80 °C with TBAF as an additive. This catalyst system exhibited high activities in the reactions with trimethoxysilylbenzene and aryl bromides that have electron-donating or electron-withdrawing groups. In the case of aryl chlorides, substrates possessing electron-withdrawing groups gave the coupled products in high yields.     

Microwave-assisted Pd(OH)2-catalyzed direct C−H arylation of free-(NH2) adenines with aryl halides

A direct C−H arylation of free-(NH₂) adenines using Pd(OH)₂/C (Pearlman’s catalyst) and stoichiometric amount of copper iodide under ligandless microwave activation is described. This new protocol proved to be highly effective to synthesize a variety of 8-aryladenine derivatives 3 without prior protection of the amino substituent. The arylation reaction takes place rapidly within few minutes and allows the coupling to proceed regioselectively at the 8-position with a wide range of aryl halides including aryl iodides, bromides and the less reactive aryl chlorides.     

Palladium(0) nanoparticles-catalyzed ligand-free direct arylation of benzothiazole via C-H bond functionalization

Palladium nanoparticles, generated in situ efficiently catalyzes direct 2-C-H arylation of benzothiazole without requirement of any ligand. A wide range of substituted aryl and heteroaryl iodides participate in this reaction producing a series of 2-aryl/heteroaryl-benzothiazoles in high yields.     

Palladium(0) nanoparticle-catalyzed sp C-H activation: a convenient route to alkyl-aryl ketones by direct acylation of aryl bromides and iodides with aldehydes

Palladium(0) nanoparticles efficiently catalyze aliphatic aldehyde C-H functionalization by aryl halides to produce alkyl-aryl ketones in good yields. A wide range of substituted aryl and hetero-aryl bromides/iodides and open-chain aldehydes of varied chain length participated in this reaction.     

Palladium(II)-catalyzed arylation of unactivated C(sp3)-H bonds by using 2,1,3-benzoselenadiazole-4-amine as directing ligand

A modified bidentate directing ligand derived from 2,1,3-benzoselenadiazole (BSeD) was designed and synthesized. It exhibited high regioselectivity in the catalytic activation of unactivated C(sp³)-H bonds with aryl iodides in the presence of palladium catalyst in yields up to 94%.     

Palladium-catalyzed alkenation of thiophenes and furans by regioselective C-H bond functionalization

A palladium-catalyzed direct alkenation of thiophenes and furans has been developed in the presence of AgOAc and pyridine. A variety of olefinic substrates such as acrylates, acrylamides, and acrylonitrile can perform the direct oxidative coupling reactions with various thiophenes and furans to give the mono-alkenylated products in good yields. In most cases, the (E)-isomers were isolated as the major products.     

Palladium-catalyzed synthesis of indole fused coumarins via cross-dehydrogenative coupling

The present method describes a palladium-catalyzed cross-dehydrogenative coupling reaction of coumarin and aniline for the synthesis of indole fused coumarin derivatives. The one-pot method is operationally simple and molecular oxygen is used as sole oxidant. The target compounds are obtained in good yields from commercially available precursors.     

C-H activations on a 1H-1,4-benzodiazepin-2(3H)-one template

Air stable benzodiazepine containing palladacycles were synthesized by a C-H activation reaction and studied by mass spectrometry and X-ray crystallography. Catalytic C-H functionalizations of 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one with diphenyliodonium hexafluorophosphate led to a mixture, which included the starting material and the expected product 1-methyl-5-(2′-biphenyl)-1H-1,4-benzodiazepin-2(3H)-one.     

Palladium-catalyzed site-selective hydrogen isotope exchange (HIE) reaction of arylsulfonamides using amino acid auxiliary

Hydrogen isotope exchange (HIE) is a versatile method for the introduction of deuterium to organic compounds. Herein, regioselective deuteration of sulfonamides is achieved by palladium-Catalyzed HIE reaction. By using amino acid as weakly coordination-directing auxiliary, a variety of sulfonamides are efficiently deuterated at the ortho-position. Placing competing directing groups on the aromatic ring does not affect the site-selectivity.     

Palladium-catalyzed functionalization of indoles with 2-acetoxymethyl substituted electron-deficient alkenes

A new functionalization of indoles via palladium-catalyzed reaction of indoles and 2-acetoxymethyl substituted electron-deficient alkenes is reported. The reaction was carried out under neutral condition and no isomerization of the carbon-carbon double bond was observed.     

Sonogashira cross-coupling reactions of aryl chlorides with alkynes catalysed by a tetraphosphine-palladium catalyst

A range of aryl chlorides undergoes cross-couplings with alkynes in good yields in the presence of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst. A variety of aryl chlorides such as chloroacetophenone, chlorobenzonitrile, chloronitrobenzene, chloroanisole or chlorotoluene have been used successfully. The reaction also tolerates several alkynes such as phenylacetylene, dec-1-yne, ethynylcyclohexene or alk-1-ynols. Furthermore, this catalyst can be used at low loading with some substrates.     

Palladium-catalyzed intramolecular vinylarylation of alkene: Access to spirocyclic scaffold

A Pd(0)-catalyzed cascade reaction of (Z)-1-iodo-1,6-diene bearing a N-heteroaryl ring, including indole, pyrrole as well as imidazole, is reported. The reaction proceeds via Heck-type carbopalladation, which is followed by C-H activation of the attached N-hetero ring, thus delivering 6,5-spirocycles in moderate to good yields. Furthermore, the preliminary attempt at asymmetric version was also conducted.     

Palladium-catalyzed carbonylative coupling of benzyl chlorides with aryl boronic acids in aqueous media

A novel chemoselective protocol for the carbonylative Suzuki coupling of benzyl chlorides with aryl boronic acids at low pressure of carbon monoxide has been developed. Applying a commercially available palladium acetate/PCy₃ catalyst system in the presence of potassium phosphate as the base and water as the solvent the coupling reactions proceeded smoothly. To demonstrate the general applicability 12 different α-arylated acetophenones have been synthesized in moderate to good yields (41-78%) under mild conditions.     

Alkenyl bromides: useful coupling partners for the palladium-catalysed coupling with heteroaromatics via a C-H bond activation

Alkenyl bromides were found to be useful reactants for the palladium-catalysed direct C-H activation/functionalisation reaction of heteroaromatics such as benzoxazole or benzothiazole. Moderate to good yields of coupling products were obtained using both α- and β-substituted alkenyl bromides or even the trisubstituted alkenyl bromide 2-bromo-3-methylbut-2-ene. This reaction is environmentally attractive as it provides only HX associated to the base as a by-product.     

Selective cis-addition of C-H bonds of pyrroles and thiophenes to alkynes catalyzed by a dinuclear palladium complex

Pyrroles and thiophenes reacted with alkynes in the presence of dinuclear palladium complexes with high stereoselectivity (cis-addition) in almost all cases. While regioselectivity in the reaction with pyrroles depended on substituents on the nitrogen atom and alkynes, all reactions of thiophenes afforded 2-alkenylthiophenes.