Palladium-catalyzed Direct Arylation Research Articles

Palladium-Catalyzed Direct (Hetero)arylation of Ethyl Oxazole-4-carboxylate: An Efficient Access to (Hetero)aryloxazoles

A straightforward route toward 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics followed by a two-step hydrolysis/decarboxylation sequence was described. The method was applied here to a neat synthesis of two 2,5-di(hetero)aryloxazole natural products, balsoxin and texaline.

Analysis of the Concerted Metalation-Deprotonation Mechanism in Palladium-Catalyzed Direct Arylation Across a Broad Range of Aromatic Substrates

The concerted metalation-deprotonation mechanism predicts relative reactivity and regioselectivity for a diverse set of arenes spanning the entire spectrum of known palladium-catalyzed direct arylation coupling partners. An analysis following an active strain model provides a more complete portrayal of the important arene/catalyst parameters leading to a successful coupling. The breadth of arenes whose reactivity can be predicted by the CMD mechanism indicates that it may be far more widespread than previously imagined.

Palladium‐Catalyzed Direct Arylations of 1,2,3‐Triazoles with Aryl Chlorides using Conventional Heating

AbstractGenerally applicable, palladium‐catalyzed direct arylations of 1,2,3‐triazoles with aryl chlorides were accomplished through conventional heating at reaction temperatures of 105–120 °C. Thereby, intra‐ and intermolecular CH bond functionalizations were achieved with a variety of differently substituted chlorides as electrophiles, bearing numerous valuable functional groups.

C-H-Activated ortho-Arylation of Anilides and Their Cyclization to Phenanthridines

An efficient synthesis of 2-aryl- and 2,6-diarylanilides is reported utilizing a palladium-catalyzed direct arylation of N-acyl anilines with various aryl iodides. A steric component is evident in this interesting reaction since ortho-substituted aryl iodides failed. Deacylation using NaOH (3 examples, 85-99% yields) led to the corresponding anilines while trifluoroacetic anhydride afforded phenanthridines. The reaction was run also in one pot, without the need to isolate the intermediate coupling products. In general, the substrate scope was well studied.

Synthesis of Alkylated Benzo[2,1-b:3,4-b′]dithiophenes by Annulative Coupling and Their Direct Arylation under Palladium Catalysis

Abstract The annulative coupling of 3,3′-diiodo-2,2′-bithiophene with internal alkynes efficiently proceeds in the presence of a palladium catalyst to afford the corresponding benzo[2,1-b:3,4-b′]dithiophene derivatives. The dithiophenes also undergo palladium-catalyzed direct arylation with aryl bromides at the 2- and 7-positions selectively.

Microwave-Assisted, Palladium-Catalyzed Intramolecular Direct Arylation for the Synthesis of Novel Fused Heterocycles

An efficient synthesis of novel fused heterocycles has been established via microwave-assisted palladium-catalyzed intramolecular direct arylation. The acyclic aryl bromides are readily available from microwave-assisted one-pot annulation of N-(2-bromobenzyl)-2-aminophenols and ethyl 2-bromoalkanoates. The intramolecular direct arylation is then performed in the presence of palladium(II) acetate and dppf (10 mol% each) in toluene using potassium carbonate (2 equiv) as the base under microwave heating (150 °C, 1 h) to afford the products in 43-99% yields. Steric effect is observed for Ar-Ar bond formation, giving a substantial amount of the debromination byproduct.

Intramolecular Palladium-Catalyzed Direct Arylation of Alkenyl Triflates

A catalyst generated from Pd(OAc)2 and dppp is effective for the direct intramolecular arylation of alkenyl triflates. Conjugated alkene-arene-containing carbocycles are produced in good yield. The process tolerates a variety of aryl substituents as well a simple heteroaryl groups. Electron-deficient aryl rings deliver faster reactions.

Palladium-Catalyzed Anilide ortho-Arylation and Subsequent One-Pot Cyclization to Phenanthridines

The palladium-catalyzed direct arylation of anilides possessing several N-acyl substituents has been demonstrated. Removal of the acyl group by base hydrolysis allows a short and efficient synthesis of 2-aryl or 2,6-diarylanilines. The method is functional group tolerant and allows the presence of chloride and bromide substituents on both the anilide and aryl iodide coupling components. The arylation products can be converted to phenanthridines by the reaction with trifluoroacetic anhydride.

Regioselective Palladium‐Catalyzed Arylation and Heteroarylation of Imidazo[1,2‐a]pyridines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Palladium-Catalyzed Direct Arylation of Furans via C−H Functionalization at Low Catalyst Loadings

A system combining the tetraphosphine cis,cis,cis-1,2,3,4-tetrakis((diphenylphosphino)methyl)cyclopentane (Tedicyp) and [Pd(C3H5)Cl]2 was found to promote the direct arylation of furans via C−H functionalization in good yields using very low catalyst loadings.

Regioselective Palladium-Catalyzed Arylation and Heteroarylation of ­Imidazo[1,2-a]pyridines

Palladium-catalyzed direct arylation and heteroarylation of imidazo[1,2-a]pyridines at the 3-position are described. The optimization of the reaction in conventional heating and the adaptation under microwaves irradiation is reported. The compatibility of the synthesis with the presence of bromo or chloro substituents in the 6-position was investigated.

Catalytic Direct Arylation with Aryl Chlorides, Bromides, and Iodides: Intramolecular Studies Leading to New Intermolecular Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Palladium-catalyzed direct arylation of simple arenes in synthesis of biaryl molecules

Significant progress has been made in the direct arylation of simple arenes. A number of catalyst systems have been developed which enable the intramolecular direct arylation of aryl chlorides, bromides and iodides in high yield as well as conditions capable of achieving intermolecular direct arylation with simple arenes. This account describes recent progress by our group and others in the development of these reactions.

Catalytic Direct Arylation with Aryl Chlorides, Bromides, and Iodides: Intramolecular Studies Leading to New Intermolecular Reactions

A catalyst for the intramolecular direct arylation of a broad range of simple and heterocyclic arenes with aryl iodides, bromides, and chlorides has been developed. These reactions occur in excellent yield and are highly selective. Studies with aryl iodides substrates revealed that catalyst poisoning occurs due to the accumulation of iodide in the reaction media. This can be overcome by the addition of silver salts which also permits these reactions to occur at lower temperature. The utility of the methodology is illustrated by a rapid synthesis of a carbazole natural product and by the synthesis of sterically encumbered tetra-ortho-substituted biaryls via ring-opening reactions of the direct arylation products. Mechanistic investigations have provided insight into the catalyst's mode of action and show the presence of a kinetically significant C-H bond cleavage in palladium-catalyzed direct arylation of simple arenes. Knowledge garnered from these studies has led to the development of new intermolecular arylation reactions with previously inaccessible arenes, opening the door for the development of other new direct arylation processes.

Regioselective Synthesis of 1,5-Diaryl-1H-imidazoles by Palladium-Catalyzed Direct Arylation of 1-Aryl-1H-imidazoles

[reaction: see text] A variety of 1,5-diaryl-1H-imidazoles have been regioselectively synthesized by direct coupling of 1-aryl-1H-imidazoles with aryl iodides or bromides in DMF in the presence of CsF as the base and a catalyst precursor consisting of a mixture of Pd(OAc)2 and AsPh3. The data obtained in this synthetic study support a reaction mechanism involving an electrophilic attack of an arylpalladium(II) halide species onto the imidazole ring. Interestingly, some imidazole derivatives synthesized in this study have been found to exhibit significant cytotoxic activity against human tumor cell lines.

Palladium-catalyzed direct arylation of thiazoles with aryl bromides

Thiazole, 2-phenyl or -alkyl substituted one and benzothiazole are efficiently arylated with aryl bromides at the 2- and/or 5-position(s) in the presence of Pd(OAc) 2 and a bulky phosphine ligand using Cs 2CO 3 as base. 2-Phenyl-5-thiazolecarboxanilide undergoes successive diarylation at the 4- and 5-positions accompanied by decarbamoylation.