Ascorbic Acid as an Initiator for the Direct C?H Arylation of (Hetero)arenes with Anilines Nitrosated In Situ

Ascorbic acid (vitamin C) has been used as a radical initiator in a metal‐free direct C H arylation of (hetero)arenes. Starting from an aniline, the corresponding arenediazonium ion is generated in situ and immediately reduced by vitamin C to an aryl radical that undergoes a homolytic aromatic substitution with a (hetero)arene. Notably, neither heating nor irradiation is required. This procedure is mild, operationally simple, and constitutes a greener approach to arylation.     

Light‐Induced CH Arylation of (Hetero)arenes by In Situ Generated Diazo Anhydrides

Diazo anhydrides (Ar?N?N?O?N?N?Ar) have been known since 1896 but have rarely been used in synthesis. This communication describes the development of a photochemical catalyst‐free C?H arylation methodology for the preparation of bi(hetero)aryls by the one‐pot reaction of anilines with tert‐butyl nitrite and (hetero)arenes under neutral conditions. The key step in this procedure is the in situ formation and subsequent photochemical (>300 nm) homolytic cleavage of a transient diazo anhydride intermediate. The generated aryl radical then efficiently reacts with a (hetero)arene to form the desired bi(hetero)aryls producing only nitrogen, water, and tert‐butanol as byproducts. The scope of the reaction for several substituted anilines and (hetero)arenes was investigated. A continuous‐flow protocol increasing selectivity and safety has been developed enabling the experimentally straightforward preparation of a variety of substituted bi(hetero)aryls within 45 min of reaction time.     

Cobalt-catalyzed direct arylation and benzylation by ch/co cleavage with sulfamates, carbamates, and phosphates

Inexpensive cobalt catalysts enable the first direct arylation and benzylation of (hetero)arenes with aryl carbamates, sulfamates, and phosphates with ample scope. The non-radical C?H/C?O arylation reaction even proved viable at ambient temperature.     

Developments in Direct C?H Arylation of (Hetero)Arenes under Microwave Irradiation

This minireview describes the progress made in the development of direct C? H arylation approaches through the application of focused microwave irradiation. The synergistic combination of microwave‐assisted techniques with the rapidly evolving domain of C? H arylation has opened new vistas in the efficient synthesis of a diverse array of biologically important (hetero)arenes.     

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.     

C−H Bond Arylation of Pyrazoles at the β-Position: General Conditions and Computational Elucidation for a High Regioselectivity

Direct arylation of most five-membered ring heterocycles are generally easily accessible and strongly favored at the α-position using classical palladium-catalysis. Conversely, regioselective functionalization of such heterocycles at the concurrent β-position remains currently very challenging. Herein, we report general conditions for regioselective direct arylation at the β-position of pyrazoles, while C−H α-position is free. By using aryl bromides as the aryl source and a judicious choice of solvent, the arylation reaction of variously N-substituted pyrazoles simply proceeds via β-C−H bond functionalization. The β-regioselectivity is promoted by a ligand-free palladium catalyst and a simple base without oxidant or further additive, and tolerates a variety of substituents on the bromoarene. DFT calculations revealed that a protic solvent such as 2-ethoxyethan-1-ol significantly enhances the acidity of the proton at β-position of the pyrazoles and thus favors this direct β-C−H bond arylation. This selective pyrazoles β-C−H bond arylation was successfully applied for the straightforward building of π-extended poly(hetero)aromatic structures via further Pd-catalyzed combined α-C−H intermolecular and intramolecular C−H bond arylation in an overall highly atom-economical process.     

NADH coenzyme model compound as photocatalyst for the direct arylation of (hetero)arenes

9,10-Dihydro-10-methylacridine (AcrH₂), a NADH coenzyme model compound, as an organo-photoredox catalyst is demonstrated for the cross-coupling of aryl diazonium salts with (hetero)arenes. Under mild and operationally simple conditions, this new photocatalytic protocol has been applied to arylation of a wide variety of (hetero)arenes and tolerates various functional groups.     

Nickel‐Catalyzed N‐Arylation of Primary Amides and Lactams with Activated (Hetero)aryl Electrophiles

The first nickel‐catalyzed N‐arylation of amides with (hetero)aryl (pseudo)halides is reported, enabled by use of the air‐stable pre‐catalyst (PAd‐DalPhos)Ni(o‐tolyl)Cl ( C1 ). A range of structurally diverse primary amides and lactams were cross‐coupled successfully with activated (hetero)aryl chloride, bromide, triflate, tosylate, mesylate, and sulfamate electrophiles.     

Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C−H Arylation/Ring‐Transformation Strategy

We have described a C?H arylation/ring‐transformation strategy for the synthesis of triarylpyridines, which form the core structure of thiopeptide antibiotics. This synthetic method readily gave 2,3,6‐triarylpyridines in a regioselective manner by a two‐phase approach: C?H arylation (a nickel‐catalyzed decarbonylative Suzuki–Miyaura cross‐coupling and decarbonylative C?H coupling for the synthesis of 2,4‐diaryloxazoles) and ring transformation ([4+2] cycloaddition of 2,4‐diaryloxazoles with (hetero)arylacrylic acids). To showcase these methods, we have accomplished the formal synthesis of thiopeptide antibiotics GE2270 s and amythiamicins.     

咔唑桥连NCN齿形钯配合物催化的唑类C-H键直接芳基化反应

基于咔唑的强给电子能力合成了一种对空气稳定的齿形钯配合物催化剂(C1~C6).这种钯催化剂可高效催化唑类和溴代芳烃的直接芳基化反应,在空气条件下,碳酸钾为碱,无需其他添加剂,即取得了较好的催化活性与底物普适性.在相对温和的条件和催化剂用量为0.5mol%时,即可实现噻唑与溴代芳烃直接芳基化反应顺利进行.值得一提的是,这是目前以KOAc为碱的反应体系中,反应活性最高的催化体系.     

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.     

Pd‐Catalyzed Decarboxylative Cross‐Coupling of 2‐Carboxyazine N‐Oxides with Various (Hetero)aryl Halides

Decarboxylative cross‐coupling reactions of substituted 2‐carboxyazine N‐oxides, with a variety of (hetero)aryl halides, by bimetallic Pd⁰/Cu^I and Pd⁰/Ag^I catalysis are reported. Two possible pathways, a conventional bimetallic‐catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C?H arylation sequence have been considered. These methods provide the first general decarboxylative arylation methodology for the 2‐carboxyazine series.     

Origins of regioselectivity in radical arylation of aniline: A computational study

The radical arylation of the para‐substituted anilines under three different conditions (A: arylhydrazines as the radical precursors and MnO₂ as the oxidant in acetonitrile; B: arylhydrazine hydrochlorides as the radical precursors and O₂ as the oxidant in aqueous sodium hydroxide solution; C: arenediazonium salts as the radical precursors and TiCl₃ as the reductant in aqueous hydrochloric acid solution) has been theoretically studied and the origins of the ortho/meta regioselectivity have been explored. The arylation process is suggested to contain three steps: radical generation, radical addition, and rearomatization. Calculations show that the arylation of the neutral anilines is kinetically controlled under conditions A and B, and the regioselectivity is determined by the radical addition. As a directing group, ? NH₂ plays an important role in these cases with the assistance of Mn(OH)₂ (the reduced product of MnO₂ under condition A) and Na⁺ (condition B). As for the arylation of the protonated anilines under condition C, the regioselectivity is affected by the substituents in the para‐position of anilines. Electron‐donating groups support meta‐addition and the selectivity is decided by the radical addition. Conversely, electron‐withdrawing groups favor ortho‐addition, and in this situation the arylation process is thermodynamically controlled and the regioselectivity is determined by the radical addition and rearomatization. © 2015 Wiley Periodicals, Inc.     

Consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles with propynal diethylacetal as a three-carbon building block

A novel consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles via room temperature Sonogashira arylation of propynal diethylacetal used as a propargyl aldehyde synthetic equivalent has been disclosed. The final acetal cleavage-cyclocondensation with hydrazine hydrochloride at 80 °C rapidly furnishes the title compounds in a one-pot fashion.     

Palladium‐Catalyzed Carbonylative α‐Arylation to β‐Ketonitriles

A carbonylative α‐arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting β‐ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient ¹³C‐labelling of the generated carbonyl moiety.     

Palladium(II)‐N‐Heterocyclic Carbene Complexes: Efficient Catalysts for the Direct C‐H Bond Arylation of Furans with Aryl Halides

This paper contains the synthesis and characterization of the seven new benzimidazolium salts and their corresponding new palladium(II)‐NHC complexes with the general formula [PdX₂(NHC)₂], (NHC = N‐heterocyclic carbene, X = Cl or Br), and also their catalytic activity in direct C‐H bond arylation of 2‐substituted furan derivatives with aryl bromides and aryl chlorides. Under the optimal conditions, these palladium(II)‐NHC complexes showed the good catalytic performance for the direct C‐H bond arylation of 2‐substituted furans with (hetero)aryl bromides, and with readily available and inexpensive aryl chlorides. The C‐H bond arylation regioselectively produced C5‐arylated furans by using 1 mol% of the palladium(II)‐NHC catalysts in moderate to high yields.     

Regioselective Ruthenium‐Catalyzed Carbonylative Direct Arylation of Five‐Membered and Condensed Heterocycles

A ruthenium‐catalyzed carbonylative C?H bond arylation process for the three‐component synthesis of complex aryl–(hetero)aryl ketones in an aqueous solution has been developed. By exploiting the ortho‐activating effect of nitrogen‐containing directing groups, a regioselective, successive twofold C(sp²)?C(sp²) bond formation has been achieved. This straightforward catalytic process provides access to versatile products prevalent in multiple bioactive compounds and supplies a valuable functional group for subsequent transformations.     

Application of direct (hetero)arylation in constructing conjugated small molecules and polymers for organic optoelectronic devices

Direct (hetero)arylation, as a sustainable, atom-economic and environmentally benign synthetic protocol compared to conventional coupling techniques, has been extensively applied to the sustainable preparation of π-conjugated materials for organic optoelectronic devices. In this review, we will highlight recent advances made in direct arylation for conjugated small molecules and polymers toward high performance organic optoelectronic devices. Some important insights in direct arylation for synthesizing organic optoelectronic materials are given, together with the challenges and outlook in this significant and hot research field.     

Iridium(III)‐Catalyzed Intermolecular C(sp3)−H Insertion Reaction of Quinoid Carbene: A Radical Mechanism

Described herein is an Ir^III/porphyrin‐catalyzed intermolecular C(sp³)?H insertion reaction of a quinoid carbene (QC). The reaction was designed by harnessing the hydrogen‐atom transfer (HAT) reactivity of a metal‐QC species with aliphatic substrates followed by a radical rebound process to afford C?H arylation products. This methodology is efficient for the arylation of activated hydrocarbons such as 1,4‐cyclohexadienes (down to 40 min reaction time, up to 99 % yield, up to 1.0 g scale). It features unique regioselectivity, which is mainly governed by steric effects, as the insertion into primary C?H bonds is favored over secondary and/or tertiary C?H bonds in the substituted cyclohexene substrates. Mechanistic studies revealed a radical mechanism for the reaction.     

Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C?H Activation and Orthogonal Reactivity

(Pinacolato)boryl ortho‐silyl(hetero)aryl triflates are presented as a new class of building blocks for arylation. They demonstrate unique versatility by delivering boronate or (hetero)aryne reactivity chemoselectively in a broad range of transformations. This approach enables the unprecedented postfunctionalization of fluoride‐activated (hetero)aryne precursors, for example, as substrates in transition‐metal catalysis, and offers valuable new possibilities for aryl boronate postfunctionalization without the use of specialized protecting groups.