Arylation Of Pyridines Research Articles

Meta-Selective Copper-Catalyzed C-H Arylation of Pyridines and Isoquinolines through Dearomatized Intermediates.

C(sp2)-H functionalization offers an efficient strategy for the synthesis of various elaborated N-containing heteroarenes. Along these lines, oxazino pyridines that can be readily prepared from pyridines, have been introduced as powerful substrates in radical- and ionic-mediated meta-C-H functionalization. However, the regioselective meta-C-H arylation of pyridines remains a great challenge. Herein, a copper-catalyzed meta-selective C-H arylation of pyridines and isoquinolines through bench-stable dearomatized intermediates is reported. Electrophilic aryl-Cu(III) species, generated from readily accessible aryl I(III) reagents, enable the efficient meta-arylation of a broad range of pyridines and isoquinolines. The method also allows the meta-selective alkenylation of these heteroarenes using the corresponding alkenyl I(III)-reagents. Late-stage arylation of drug-derived pyridines and larger-scale experiments demonstrate the potential of this synthetic methodology.

Meta‐Selective Copper‐Catalyzed C−H Arylation of Pyridines and Isoquinolines through Dearomatized Intermediates

AbstractC(sp2)−H functionalization offers an efficient strategy for the synthesis of various elaborated N‐containing heteroarenes. Along these lines, oxazino pyridines that can be readily prepared from pyridines, have been introduced as powerful substrates in radical‐ and ionic‐mediated meta‐C−H functionalization. However, the regioselective meta‐C−H arylation of pyridines remains a great challenge. Herein, a copper‐catalyzed meta‐selective C−H arylation of pyridines and isoquinolines through bench‐stable dearomatized intermediates is reported. Electrophilic aryl‐Cu(III) species, generated from readily accessible aryl I(III) reagents, enable the efficient meta‐arylation of a broad range of pyridines and isoquinolines. The method also allows the meta‐selective alkenylation of these heteroarenes using the corresponding alkenyl I(III)‐reagents. Late‐stage arylation of drug‐derived pyridines and larger‐scale experiments demonstrate the potential of this synthetic methodology.

Unified ionic and radical C-4 alkylation and arylation of pyridines.

C-H Functionalization of pyridines is an efficient strategy to access pyridine derivatives occurring in pharmaceuticals, agrochemicals, and materials. Nucleophilic additions to pyridiniums via both ionic and radical species have proven particularly useful. However, these reactions suffer from poor regioselectivity. By identifying an enzyme-mimic pocket-type urea activation reagent, we report a general platform for pyridine C-4 functionalization. Both ionic and radical nucleophiles can be incorporated to achieve the alkylation and arylation. Notably, the highly regioselective C-4 radical arylation is disclosed for the first time. The broad scope of nucleophiles and pyridines renders this platform applicable to the late-stage functionalization of drug-like molecules and the preparation of complex biologically important molecules.

Direct 2-Pyridyl-Alkylation of Benzyne with N-Alkylpyridinium Salts

AbstractA 2-pyridyl-alkylation of benzyne using N-alkylpyridinium salts has been developed under either photochemical or thermal conditions. This metal-free dicarbofunctionalization of benzyne undergoes a de Mayo-type process including cascade dearomative [3+2] cycloaddition and rearomative ring-opening reaction. An electron-deficient N-cyclic alkyl group was necessary. A formal ortho-C–H arylation of pyridine has been achieved.

Synthesis of 2-Arylpyridines and 2-Arylbipyridines via Photoredox-Induced Meerwein Arylation with in Situ Diazotization of Anilines.

We report herein a sustainable method for the preparation of 2-arylpyridines through C-H arylation of pyridines using in situ formed diazonium salts (from commercially available aromatic amines) in the presence of a photoredox catalyst under blue light-emitting diode (LED) irradiation. The reaction is tolerant to a wide range of functional groups (e.g., halogen, nitrile, formyl, acetyl, ester). Applications to the C-H bond arylation of bipyridine ligands is also presented.

ChemInform Abstract: Palladium‐Catalyzed C—H Arylation of Pyridines with Aryl Triflates.

Methods that can directly arylate pyridines have significant potential in synthetic chemistry. Herein, we present palladium-catalyzed C–H arylation of pyridines with aryl triflates that occurs regi...

Palladium-catalyzed C–H Arylation of Pyridines with Aryl Triflates

Methods that can directly arylate pyridines have significant potential in synthetic chemistry. Herein, we present palladium-catalyzed C–H arylation of pyridines with aryl triflates that occurs regi...

ChemInform Abstract: Synthesis of Asymmetrically Substituted Terpyridines by Palladium‐Catalyzed Direct C—H Arylation of Pyridine N‐Oxides.

AbstractThe convenient and scalable synthesis of the title compounds is accomplished in fewer steps compared to known cross‐coupling methods.

ChemInform Abstract: Arylation of Pyridines via Suzuki—Miyaura Cross‐Coupling and Pyridine‐Directed C—H Activation Using a Continuous‐Flow Approach.

AbstractSuzuki—Miyaura coupling and arylation reactions of 2‐phenylpyridine are performed by using continuous flow conditions.

Arylation of Pyridines via Suzuki-Miyaura Cross-Coupling and Pyridine-­Directed C-H Activation Using a Continuous-Flow Approach

Suzuki–Miyaura cross-coupling reactions between heteroaryl bromides and arylboronic acids were performed employing a continuous-flow approach using a simple flow reactor designed in-house. Pd(PPh₃)₄ was used as catalyst, and arylboronic acids containing both electron-withdrawing and electron-donating groups were applied. The coupling process required 23 minutes of residence time to be completed and generally good yields were obtained. Subsequent arylation of 2-phenyl pyridine was carried out via a C–H activation strategy using substituted bromobenzene compounds and a ruthenium(II) catalyst. To the best of our knowledge in this work we present for the first time the possibility of performing intermolecular C–H activation in a continuous-flow system.

ChemInform Abstract: Palladium‐Catalyzed Direct Arylation of Pyridine N‐Oxide with 2‐Bromoacetanilides. Synthesis of Benzisoxazolo[2,3‐a]pyridinium Tetrafluoroborates.

AbstractA short synthesis of title compounds (IV) is achieved by regioselective Pd‐catalyzed direct C—H arylation of pyridine N‐oxide and subsequent cyclization via hydrolysis, diazotation, and intramolecular substitution of dinitrogen.

ChemInform Abstract: Silver‐Catalyzed 2‐Pyridyl Arylation of Pyridine N‐Oxides with Arylboronic Acids at Room Temperature.

ChemInform Abstract: Silver‐Catalyzed 2‐Pyridyl Arylation of Pyridine N‐Oxides with Arylboronic Acids at Room Temperature.

ChemInform Abstract: C—H Arylation of Pyridines: High Regioselectivity as a Consequence of the Electronic Character of C—H Bonds and Heteroarene Ring.

AbstractA new and highly regioselective method for C—H arylation of pyridines and quinolines containing electron‐withdrawing substituents is reported.

C-H arylation of pyridines: high regioselectivity as a consequence of the electronic character of C-H bonds and heteroarene ring.

We report a new catalytic protocol for highly selective C-H arylation of pyridines containing common and synthetically versatile electron-withdrawing substituents (NO(2), CN, F and Cl). The new protocol expands the scope of catalytic azine functionalization as the excellent regioselectivity at the 3- and 4-positions well complements the existing methods for C-H arylation and Ir-catalyzed borylation, as well as classical functionalization of pyridines. Another important feature of the new method is its flexibility to adapt to challenging substrates by a simple modification of the carboxylic acid ligand or the use of silver salts. The regioselectivity can be rationalized on the basis of the key electronic effects (repulsion between the nitrogen lone pair and polarized C-Pd bond at C2-/C6-positions and acidity of the C-H bond) in combination with steric effects (sensitivity to bulky substituents).

ChemInform Abstract: Synthesis of Unsymmetrically Substituted Bipyridines by Palladium‐Catalyzed Direct C—H Arylation of Pyridine N‐Oxides.

AbstractA wide range of substituted pyridine N‐oxides undergoes a direct C—H arylation with 2‐, 3‐ and 4‐halopyridines affording 2,2′‐, 2,3′‐ and 2,4′‐bipyridine N‐oxides with moderate yields.

Synthesis of Unsymmetrically Substituted Bipyridines by Palladium-Catalyzed Direct C−H Arylation of Pyridine N-Oxides

Substituted bipyridines were efficiently prepared by direct coupling between pyridine N-oxides and halopyridines using a palladium catalyst. Pyridine N-oxides with electron-withdrawing substituents gave the best yields. This method allows the convenient preparation of 2,2'-, 2,3'-, and 2,4'-bipyridines which are useful as functionalized ligands for metal complexes or as building blocks for supramolecular architectures.

Cp2Ni-KOt-Bu-BEt3 (or PPh3) Catalyst System for Direct C−H Arylation of Benzene, Naphthalene, and Pyridine

Ni-catalyzed direct C-H arylation of benzene and naphthalene using aryl halides was investigated. For the first time, the arylation was successfully catalyzed by Cp(2)Ni (5 mol %) in the presence of KOt-Bu and BEt(3). This Ni catalyst system was also applied to direct C-H arylation of pyridine, an electron-deficient heteroarene; PPh(3) was used instead of BEt(3) in this case.

Gold(I)-catalyzed direct C–H arylation of pyrazine and pyridine with aryl bromides

An efficient procedure for the direct C–H arylation of electron-poor aromatics such as pyrazine and pyridine with aryl bomides is described. In the presence of catalytic amount of Cy 3PAuCl and with the use of t-BuOK as base, pyrazine undergoes the direct C–H arylation with aryl bromides at 100 °C, and the yields of the arylated products depend on the nature of aryl bromides. In the cases of electron-rich aryl bromides used, the arylated pyrazines can be obtained in good to high yields. For electron-poor aryl bromides, the addition of AgBF 4 is the crucial point to accelerate the coupling reaction to give the arylated products in moderate yields. Pyridine also reacts with electron-rich aryl bromides catalyzed by Cy 3PAuCl to give a mixture of arylated regioisomers in moderate yield. However, in order to realize the direct C–H arylation of pyridine with electron-poor aryl bromides, the addition of silver salt as additive and a milder reaction temperature (60 °C) are required.

Synthesis of 2‐Substituted Pyridines via a Regiospecific Alkylation, Alkynylation, and Arylation of Pyridine N‐Oxides.

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.

Synthesis of 2-Substituted Pyridines via a Regiospecific Alkylation, Alkynylation, and Arylation of Pyridine N-Oxides

[structure: see text]. Sequential addition of Grignard reagents to pyridine N-oxides in THF at room temperature followed by treatment with acetic anhydride at 120 degrees C afforded 2-substituted pyridines in good to high yields. Furthermore, by exchanging acetic anhydride for DMF in the second step, 2-substituted pyridine N-oxides were obtained, as intermediates suitable for addition of a second Grignard reagent for the synthesis of 2,6-disubstituted pyridines.