Ruthenium-catalyzed Direct Arylations Research Articles

Mechanism of Ruthenium-Catalyzed Direct Arylation of C–H Bonds in Aromatic Amides: A Computational Study

Ruthenium-catalyzed arylation of ortho C–H bonds directed by a bidentate 8-aminoquinoline moiety not only is important to construct new biaryl derivates but also merges important research areas. In this study, the density functional theory (DFT) method M11-L was employed to predict the mechanism of this C–H bond arylation reaction. The computational results indicate that the initial step for this reaction is catalyst loading by electrophilic deprotonation to generate a substrate-coordinated Ru(II) intermediate, which is the key compound in the complete catalytic cycle. The catalytic cycle includes electrophilic deprotonation by carbonate, oxidative addition of bromobenzene, reductive elimination to form a new aryl–aryl bond, proton transfer to release the product, and ligand exchange to regenerate the initial Ru(II) intermediate. Theoretical calculations suggest that the oxidative addition of bromobenzene is the rate-determining step of the whole catalytic cycle, and the apparent activation free energy is...

Ruthenium-catalyzed direct arylations with aryl chlorides

Aryl chlorides are readily available at lower cost than the corresponding bromides and iodides, but are much more challenging as substrates in metal-catalyzed cross-couplings.

ChemInform Abstract: Highly Regioselective Ruthenium‐Catalyzed Direct Arylation of Thiazolo[3,2‐b]‐1,2,4‐triazoles with Aryl Iodides and Aryl Bromides via C—H Bond Activation.

Abstract We have developed a convenient ruthenium-catalyzed direct arylation for highly regioselective synthesis of thiazolo[3,2- b ]-1,2,4-triazole derivatives via C–H bond activation. This transformation has provided a new synthetic route to a variety of thiazolo[3,2- b ]-1,2,4-triazoles and afforded desired products in good yields.

Highly regioselective ruthenium-catalyzed direct arylation of thiazolo[3,2-b]-1,2,4-triazoles with aryl iodides and aryl bromides via C–H bond activation

We have developed a convenient ruthenium-catalyzed direct arylation for highly regioselective synthesis of thiazolo[3,2-b]-1,2,4-triazole derivatives via C–H bond activation. This transformation has provided a new synthetic route to a variety of thiazolo[3,2-b]-1,2,4-triazoles and afforded desired products in good yields.

Ruthenium-catalyzed direct arylation of C–H bonds in aromatic amides containing a bidentate directing group: significant electronic effects on arylation

Arylation of ortho C–H bonds is achieved by a ruthenium-catalyzed reaction of aromatic amides having an 8-aminoquinoline moiety with aryl bromides. The reaction shows high functional group compatibility. The reaction proceeds in a highly selective manner at the less hindered C–H bonds of meta-substituted aromatic amides. Significant electronic effects are observed in Hammett plots. Electron-withdrawing groups on the aromatic amides facilitate the reaction. In contrast, both electron-donating groups and electron-withdrawing groups on aryl bromides accelerate the reaction.

ChemInform Abstract: Ruthenium‐Catalyzed C—H Bond Arylations of Arenes Bearing Removable Directing Groups via Six‐Membered Ruthenacycles.

Ruthenium-catalyzed direct arylations of phenols bearing removable directing groups were accomplished through carboxylate assistance via six-membered ruthenacycles as key intermediates.

ChemInform Abstract: Ruthenium‐Catalyzed Direct Arylations Through C—H Bond Cleavages

AbstractReview: 93 refs.

Synthesis of the Biaryl Core of Anacetrapib

Anacetrapib inhibits cholesteryl ester transfer protein (CETP), a plasma glycoprotein that transfers cholesteryl ester from high density ­lipoprotein to low density lipoprotein and very low density lipoprotein, consequently lowering the risk of atherosclerosis. Key steps in the synthesis depicted are (1) a highly regioselective SNAr reaction of 1-bromo-2,4-fluorobenzene (A) with potassium methoxide (rr =17:1) and (2) a multi-kilogram scale ruthenium-catalyzed direct arylation of oxazoline F to construct the biaryl G.

Preparative Scale Synthesis of the Biaryl Core of Anacetrapib via a Ruthenium-Catalyzed Direct Arylation Reaction: Unexpected Effect of Solvent Impurity on the Arylation Reaction

In this report, we disclose our findings regarding the remarkable effect of a low-level impurity found in the solvent used for a ruthenium-catalyzed direct arylation reaction. This discovery allowed for the development of a robust and high-yield arylation protocol that was demonstrated on a multikilogram scale using carboxylate as the cocatalyst. Finally, a practical, scalable, and chromatography-free synthesis of the biaryl core of Anacetrapib is described.

Mechanistic Insight into Direct Arylations with Ruthenium(II) Carboxylate Catalysts

Mechanistic studies revealed ruthenium-catalyzed direct arylations to proceed through reversible C-H bond activation and subsequent rate-limiting oxidative addition with aryl halides, which led to the development of widely applicable well-defined ruthenium(II) carboxylate catalysts.

Ruthenium‐Catalyzed Direct Arylations of N‐Aryl 1,2,3‐Triazoles with Aryl Chlorides as Electrophiles

Ring ring ring: Ruthenium-catalyzed direct arylations of N-aryl 1,2,3-triazoles with chlorides as arylating reagents proceed efficiently with an in situ generated complex derived from phosphane PCy(3) in N-methyl-2-pyrrolidone (NMP) as solvent.

Assisted Ruthenium-Catalyzed C−H Bond Activation: Carboxylic Acids as Cocatalysts for Generally Applicable Direct Arylations in Apolar Solvents

Catalytic amounts of aromatic carboxylic acid MesCO H enabled efficient ruthenium-catalyzed direct arylations in apolar solvents with unparalleled broad scope via a concerted deprotonation-metalation mechanism.