meta-Allylation of Arenes via Ruthenium-Catalyzed Cross-Dehydrogenative Coupling.

A successful example of oxidative meta-dehydrogenative allylation of arenes with alkenes has been developed using Ru(PPh3)3Cl2 as a catalyst and DTBP as an oxidant. In the allylation process, pyrimidines, pyrazoles, and purines, found widely in nucleosides, were effective auxiliary groups. Gram-scale experiments took place smoothly under optimized conditions. Mechanistic studies indicated that ruthenium-catalyzed meta-dehydrogenative allylation was a free-radical process. The allylation process developed herein provides an efficient and practical strategy to prepare versatile meta-allylated arenes.

m-CAr-H Bond Alkylations and Difluoromethylation of Tertiary Phosphines Using a Ruthenium Catalyst.

m-CAr-H bond functionalization of tertiary phosphines was developed using [Ru(p-cymene)Cl2]2 as a catalyst. Desired product structures were confirmed by single-crystal X-ray diffraction. Mechanistic experiments indicated that m-CAr-H bond functionalization was a radical reaction and that a hexagonal ruthenacycle complex was a crucial intermediate in the process. Therefore, this study provides a novel method for the late-stage meta-position modification of biphenyl monophosphine ligands.

Meta-Dehydrogenative Alkylation of Arenes with Ethers, Ketones, and Esters Catalyzed by Ruthenium.

A meta-dehydrogenative alkylation of arenes with cyclic ethers, ketones, and esters catalyzed by ruthenium is achieved in the presence of a di-tert-butyl peroxide (DTBP) oxidant. Interestingly, when quinoline and isoquinoline are employed as the directing group, or a chain ether as alkylation reagent, the system produces Minisci reaction products. Mechanistic study indicates that meta-dehydrogenative alkylation is a radical process initiated by DTBP with the assistance of a CAr-Ru bond ortho/para-directing effect.

Ruthenium-Catalyzed meta-Selective CAr-H Bond Formylation of Arenes.

The meta-CAr-H bond formylation of arenes has been achieved using CHBr3 as a formyl source in the presence of [Ru(p-cym)(OAc)2] as a catalyst. This method provides efficient access to the preparation of various meta-substituted aromatic compounds, such as alcohols, ethers, amines, nitriles, alkenes, halogens, carboxylic acids, and their derivatives, through transformation of the versatile formyl group. Furthermore, mechanistic studies show that the key active species is a pentagonal ruthenacycle complex.

Ruthenium-catalyzed meta-C-H bond alkylation of aryl 2-pyridyl ketones.

The first example of meta-selective CAr-H bond functionalization of aryl 2-pyridyl ketones has been developed using [Ru(p-cymene)Cl2]2 as the catalyst and alkyl bromide as the coupling reagent. This development provides an efficient strategy for modifying the meta-position of aryl 2-pyridyl ketone skeletons, which are found in various functional molecules.

Rh(III)-Catalyzed Synthesis of 2-Alkylbenzimidazoles from Imidamides and N-Hydroxycarbamates.

An efficient tandem reaction of imidamides and N-hydroxycarbamates has been developed. Valuable 2-alkylbenzimidazoles could be easily obtained in up to 97% yield for more than 20 examples. The products would further streamline the synthesis of molecules, which are essential building blocks in organic synthesis and drug discovery. This protocol features high regioselectivity, efficiency, good tolerance of functional groups, and mild reaction conditions.

Ruthenium-Catalyzed ortho/meta-Selective Dual C-H Bonds Functionalizations of Arenes.

The first example of transition-metal-catalyzed ortho/meta-selective dual C-H functionalizations of arenes in one reaction is described. In this transformation, ortho-C-H chlorination and meta-C-H sulfonation of 2-phenoxypyri(mi)dines were achieved simultaneously under catalysis by [Ru(p-cymene)Cl2]2. The other reactant, namely, an arylsulfonyl chloride, played the role of both a sulfonation and chlorination reagent. More importantly, the arylsulfonyl chloride was also an oxidant in the process. Mechanistic studies indicated that six-membered ruthenacycles were the key intermediate in the reaction.

Construction of Fused Polyheterocycles through Sequential [4 + 2] and [3 + 2] Cycloadditions.

A method for Pd-catalyzed aerobic oxidative reaction of quinazolinones and alkynes has been developed for sequential [4 + 2] and [3 + 2] cycloadditions to assemble a novel fused-polycyclic system containing tetrahydropyridine and dihydrofuran rings. The reaction process involves C-H and N-H bond functionalization for the formation of tetrahydropyridine and an oxygen radical cyclization for the dihydrofuran ring. This atom- and step-economical synthesis is highly efficient and has good substrate tolerance, which provides a new approach for the construction of polycyclic molecules with potential pharmaceutical interest.

Ruthenium-catalyzed meta/ortho-selective C-H alkylation of azoarenes using alkyl bromides.

meta/ortho-Selective CAr-H (di)alkylation reactions of azoarenes have been achieved via [Ru(p-cymene)Cl2]2 catalyzed ortho-metalation using various types of alkyl bromides. Particularly, dual meta-alkylation of azoarene and reduction offer an attractive strategy for the synthesis of meta-alkylanilines, which are difficult to access via traditional aniline functionalization methods.

Access to C4-Functionalized Quinolines via Copper-Catalyzed Tandem Annulation of Alkynyl Imines with Diazo Compounds.

An efficient synthesis of C4-functionalized quinolines through copper-catalyzed tandem annulation of alkynyl imines with diazo compounds is described. This transformation involves an in situ formation of allene and intramolecular electrocyclization, which features high efficiency, mild reaction conditions, easy operation, and broad functional-group tolerance. A wide variety of C4-functionalized quinolines were provided in up to 92% yield for 33 examples.

Copper(II)-catalyzed electrophilic amination of quinoline N-oxides with O-benzoyl hydroxylamines.

Copper acetate-catalyzed C-H bond functionalization amination of quinoline N-oxides was achieved using O-benzoyl hydroxylamine as an electrophilic amination reagent, thereby affording the desired products in moderate to excellent yields. Electrophilic amination can also be performed in good yield on a gram scale.

Copper-catalyzed intermolecular dehydrogenative amidation/amination of quinoline N-oxides with lactams/cyclamines.

C-H, N-H dehydrogenative coupling of quinoline N-oxides with lactams/cyclamines has been achieved in the presence of the Cu(OAc)2 catalyst to give good to excellent yields. This study provides a new strategy for the construction of a 2-aminoquinoline skeleton via direct functionalization of aryl C-H bonds.