Palladium-catalyzed direct C-H arylation of unactivated arenes with aryl Halides

An efficient palladium-catalyzed direct C-H arylation of unactivated arenes has been discovered. This method employs aryl halides as the direct coupling partners with arenes without using any external ligands. This catalysis opens a new methodology for the preparation of symmetrical as well as unsymmetrical biaryls in a user-friendly approach.     

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.     

Arylation of unactivated arenes

Transition metal-catalyzed and metal-free direct arylation of unactivated arenes is described. The transition metal-catalyzed direct arylation of unactivated arenes as a state-of-the-art method towards biaryl synthesis is highlighted in this Perspective.     

Biochemistry of anionic calix[n]arenes

This review treats the biological properties of the various anionic calix[n]arenes, both as soluble forms and in the colloidal state. The complexation of these molecules with amino-acids, peptides and proteins is discussed, as is their interaction with model membranes. The complexations with various Active Pharmaceutical Ingredients as complexes, for tamoxifen as solid state and colloidal structures, are treated in depth. Two sections deal with the direct biological action of the calix[n]arenes and their use as biosensors. A final section deals with the toxicity, in reality the lack of toxicity of the calix[n]arenes.     

Gold-catalyzed direct amination of arenes with azodicarboxylates

Gold(III) chloride catalyzed direct amination of arenes with azodicarboxylates was developed. The new catalytic system was active to a broad range of substrates, and the reaction was carried out under mild conditions. It represents the first catalytic system for the direct amination of electron-deficient arenes with azodicarboxylates to the best of our knowledge. This reaction provides an important approach for the synthesis of heterocyclic compounds in pharmaceutical and chemical industries.     

Amine‐Catalyzed Direct Photoarylation of Unactivated Arenes

Constructing biaryls through direct aromatic C? H functionalization of unactivated arenes has become a popular topic in organic chemistry. Many efficient methods have been developed. In this Communication, a direct arylation of unactivated arenes with a broad range of aryl iodides is reported. This reaction proceeds through a new type of amine‐catalyzed single electron transfer initiated radical coupling procedure to form biaryls in high yields under UV irradiation at room temperature. Only 20 mol% of TMEDA is used as the catalyst. No other additives are required for this transformation, thus avoiding the use of toxic transition metal catalysts, strong bases, or large amounts of other organic additives. This greener protocol provides a new strategy to achieve direct aromatic C? H functionalization and offers a new example of cost‐effective and environmentally benign access to biaryls.     

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.     

Metal- and Reagent-Free Electrochemical Synthesis of Alkyl Arylsulfonates in a Multi-Component Reaction

This work presents the first electrochemical preparation of alkyl arylsulfonates by direct anodic oxidation of electron-rich arenes. The reaction mechanism features a multi-component reaction consisting of electron-rich arenes, an alcohol of choice and excess SO₂ in an acetonitrile-HFIP reaction mixture. In-situ formed monoalkyl sulfites are considered as key intermediates with bifunctional purpose. Firstly, this species functions as nucleophile and secondly, excellent conductivity is provided. Several primary and secondary alcohols and electron-rich arenes are implemented in this reaction to form the alkyl arylsulfonates in yields up to 73 % with exquisite selectivity. Boron-doped diamond electrodes (BDD) are employed in divided cells, separated by a simple commercially available glass frit.     

Direct oxidative coupling of arenes with olefins by Rh-catalyzed C-H activation in air: observation of a strong cooperation of the acid

A [{RhCl(cod)}(2)]/CCl(3) COOH system was developed for the oxidative coupling of non-chelate-assisted arenes with olefins in the presence of catalytic amounts of Cu(OAc)(2) ?H(2) O as a co-oxidant and oxygen as the terminal oxidant. The acid was an indispensable component in this system and played a very important role in the coupling reaction. This catalytic system was applied to the direct oxidative coupling of a series of arenes and olefins and the corresponding products were afforded in high yields with special chemo- and regioselectivity. This reaction provides an atom-efficient route to vinylarenes, which are widely used in various fine chemicals.     

Transition‐Metal‐Catalyzed Direct Arylation of (Hetero)Arenes by C?H Bond Cleavage

The area of transition‐metal‐catalyzed direct arylation through cleavage of C? H bonds has undergone rapid development in recent years, and is becoming an increasingly viable alternative to traditional cross‐coupling reactions with organometallic reagents. In particular, palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners—including electrophilic aryl chlorides and tosylates as well as simple arenes in cross‐dehydrogenative arylations. Furthermore, less expensive copper, iron, and nickel complexes were recently shown to be effective for economically attractive direct arylations.     

Manganese‐Mediated C−H Alkylation of Unbiased Arenes Using Alkylboronic Acids

The alkylation of arenes is an essential synthetic step of interest not only from the academic point of view but also in the bulk chemical industry. Despite its limitations, the Friedel–Crafts reaction is still the method of choice for most of the arene alkylation processes. Thus, the development of new strategies to synthesize alkyl arenes is a highly desirable goal, and herein, we present an alternative method to those conventional reactions. Particularly, a simple protocol for the direct C?H alkylation of unbiased arenes with alkylboronic acids in the presence of Mn(OAc)₃?2H₂O is reported. Primary or secondary unactivated alkylboronic acids served as alkylating agents for the direct functionalization of representative polyaromatic hydrocarbons (PAHs) or benzene. The results are consistent with a free‐radical mechanism.     

O-alkyl resorcarenes: where are we now?

This review describes the current position in the emerging field of direct synthesis of O-alkyl resorcarenes through the use of O-protected precursors. The use of this approach for the selective synthesis of the diastereoisomers of resorc[4]arenes, the synthesis of parent resorcarenes and pyrogalloranes and the preparation of chiral partially alkylated resorc[4]arenes are highlighted. The applications of such molecules, with regard to their role as ligand platforms, for binding of cations, organic electron acceptors and in chiral discrimination are discussed.     

Manganese(III)-mediated direct phosphonylation of arenes

Manganese (III)-promoted direct phosphonylation of mono- and disubstituted arenes with dialkylphosphite afforded regioselective dialkylphosphonates in good yields. The reactions can apply to arenes bearing electron-donating groups and electron-withdrawing groups such as ester and nitrile.     

Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts

A Ru‐catalyzed direct C? H activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future C? H activation development that would allow the remote functionalization of aromatic systems.     

Site-Selective Electrochemical C−H Carboxylation of Arenes with CO2

Herein, a direct, metal-free, and site-selective electrochemical C−H carboxylation of arenes by reductive activation using CO₂ as the economic and abundant carboxylic source was reported. The electrocarboxylation was carried out in an operationally simple manner with high chemo- and regioselectivity, setting the stage for the challenging site-selective C−H carboxylation of unactivated (hetero)arenes. The robust nature of the electrochemical strategy was reflected by a broad scope of substrates with excellent atom economy and unique selectivity. Notably, the direct and selective C−H carboxylation of various challenging arenes worked well in this approach, including electron-deficient naphthalenes, pyridines, simple phenyl derivatives, and substituted quinolines. The method benefits from being externally catalyst-free, metal-free and base-free, which makes it extremely attractive for potential applications.     

A Surprising Substituent Effect Provides a Superior Boronic Acid Catalyst for Mild and Metal‐Free Direct Friedel–Crafts Alkylations and Prenylations of Neutral Arenes

The development of more general and efficient catalytic processes for Friedel–Crafts alkylations is an important objective of interest toward the production of pharmaceuticals and commodity chemicals. Herein, 2,3,4,5‐tetrafluorophenylboronic acid was identified as a potent air‐ and moisture‐tolerant metal‐free catalyst that significantly improves the scope of direct Friedel–Crafts alkylations of a variety of slightly activated and neutral arenes, including polyarenes, with allylic and benzylic alcohols. This method also provides a simple alternative for the direct installation of prenyl units commonly found in naturally occurring arenes. Alkylations with benzylic alcohols occur under exceptionally mild conditions.     

Iodine(III)/AlX3-mediated electrophilic chlorination and bromination of arenes. Dual role of AlX3 (X = Cl,Br) for (PhIO)n depolymerization and as the halogen source

An efficient chlorination and bromination of arenes mediated by in situ-formed PhI(X)OAlX₂ (X = -Cl, -Br), which is proposed as a plausible halogenating species, is described. The proposed dual role displayed by AlX₃, enables the Iodosylbenzene [(PhIO)_n] depolymerization while also acting as the halogen source by transferring the chlorine or bromine atoms to the iodine(III) center. This process allowed the chlorination and bromination of different arenes and heteroarenes under mild and open flask conditions. To the best of our knowledge, this is the first report describing a dual role of aluminum salts applied to the direct C-H chlorination and bromination of arenes.     

Direct Aryl C−H Amination with Primary Amines Using Organic Photoredox Catalysis

The direct catalytic C−H amination of arenes is a powerful synthetic strategy with useful applications in pharmaceuticals, agrochemicals, and materials chemistry. Despite the advances in catalytic C−H functionalization, the use of aliphatic amine coupling partners is limited. Described herein is the construction of C−N bonds, using primary amines, by direct C−H functionalization with an acridinium photoredox catalyst under an aerobic atmosphere. A wide variety of primary amines, including amino acids and more complex amines are competent coupling partners. Various electron‐rich aromatics and heteroaromatics are useful scaffolds in this reaction, as are complex, biologically active arenes. We also describe the ability to functionalize arenes that are not oxidized by an acridinium catalyst, such as benzene and toluene, thus supporting a reactive amine cation radical intermediate.     

The strength of parallel-displaced arene-arene interactions in chloroform

[reaction: see text] Triptycene-derived compounds have been prepared to serve as conformational equilibrium reporters for direct measurements of arene-arene interactions in the parallel-displaced orientation. A series of such compounds bearing arenes with different substituents were synthesized, and the ratios of the syn and anti conformers were determined by variable-temperature NMR spectroscopy. The syn conformer allows attached arenes to interact with each other while the anti conformer does not. The free energies derived from the syn/anti ratios in chloroform range from slightly positive (0.2 kcal/mol) to considerably negative (-0.98 kcal mol) values. The interactions between the arenes bearing electron-donating groups (EDG) are either negligible or slightly repulsive, while the interactions between arenes bearing electron-withdrawing groups (EWG) are attractive. Intermediate free energy values are obtained for those compounds bearing arenes with one EDG and one EWG.     

V@CN催化的芳烃的氧气羟基化反应

制备了V@CN催化剂,并用于氧气条件下芳烃的直接羟基化反应。结果表明,在V@CN催化剂作用下,带有不同吸电子基团(CN, NO2, COOH, CF3和COCH3)的芳烃均可被O2氧化得到相应的酚,产率中等。含有卤素(F, Cl和Br)的芳烃也可在该催化体系作用下转化为相应的酚。