Silver Ion Promoted,PdII‐Catalyzed Arylation of Arenes with a Free Amine as Directing Group in Aqueous Medium

Palladium(II)‐catalyzed arylation of arenes with aryl boronic acids and a free amine as directing group in aqueous medium has been developed. High reactivity and chemoselectivity for the formation of carbon–carbon bonds were achieved by the use of soluble silver salts. The addition of water is crucial to improve the arylation yield.     

Base‐Promoted Coupling of Carbon Dioxide,Amines, and Diaryliodonium Salts: A Phosgene‐ and Metal‐Free Route to O‐Aryl Carbamates

A phosgene‐ and metal‐free synthesis of O‐aryl carbamates is realized through a three‐component coupling of carbon dioxide, amines and diaryliodonium salts. The reaction only requires a base as the promoter, providing access to a diverse array of O‐aryl carbamates in moderate to high yields with excellent chemoselectivity.     

Metal-free synthesis of aryl esters from carboxylic acids and diaryliodonium salts

An efficient arylation of carboxylic acids with diaryliodonium salts has been developed, giving aryl esters in high yields within short reaction times for both aromatic and aliphatic substrates. The transition-metal-free conditions are compatible with a range of functional groups, and good chemoselectivity is observed with unsymmetric diaryliodonium salts. Furthermore, steric hindrance in the ortho positions is well tolerated both in the carboxylic acid and in the diaryliodonium salt, yielding aryl esters that cannot be obtained via other esterification protocols.     

Transition‐Metal‐Free N‐Arylation of Pyrazoles with Diaryliodonium Salts

A new synthetic method was developed for the N‐arylation of pyrazoles using diaryliodonium salts. The transformation does not require any transition‐metal catalyst and provides the desired N‐arylpyrazoles rapidly under mild reaction condition in the presence of aqueous ammonia solution as a mild base without the use of inert atmosphere. The chemoselectivity of unsymmetric diaryliodonium salts was also explored with large number of examples.     

Transition‐Metal‐Free α‐Arylation of Enolizable Aryl Ketones and Mechanistic Evidence for a Radical Process

The α‐arylation of enolizable aryl ketones can be carried out with aryl halides under transition‐metal‐free conditions using KOtBu in DMF. The α‐aryl ketones thus obtained can be used for step‐ and cost‐economic syntheses of fused heterocycles and Tamoxifen. Mechanistic studies demonstrate the synergetic role of base and solvent for the initiation of the radical process.     

A Metal‐free Approach to 3‐Aryl‐3‐hydroxy‐2‐oxindoles by Treatment of 3‐Acyloxy‐2‐oxindoles with Diaryliodonium Salts

A mild, metal‐free approach has been realized for the facile construction of highly valuable 3‐(hetero)aryl‐3‐hydroxy‐2‐oxindoles. Direct arylations of 3‐acyloxy‐2‐oxindoles with diaryliodonium salts as arylation reagents are implemented in the presence of K₂CO₃ at room temperature without using an organometallic promoter to deliver an array of 3‐(hetero)aryl‐3‐hydroxy‐2‐oxindoles in good yields.     

Transition‐Metal‐Free Formal Sonogashira Coupling and α‐Carbonyl Arylation Reactions

Transition‐metal‐free formal Sonogashira coupling and α‐carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (S_NAr) of β‐carbonyl sulfones to electron‐deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α‐aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two‐step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α‐carbonyl arylated products from a range of electron‐deficient aryl fluorides with a variety of functional groups and aryl‐, heteroaryl‐, alkyl‐, and alkoxy‐substituted sulfone nucleophiles. These transition‐metal‐free reactions complement the metal‐catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions.     

Thermally Induced Carbohydroxylation of Styrenes with Aryldiazonium Salts

The radical carbohydroxylation of styrenes with aryldiazonium salts has been achieved under mild thermal conditions. A broad range of aryldiazonium salts was tolerated, and the reaction principle based on a radical–polar crossover mechanism could be extended to carboetherification as well as to a two‐step, metal‐free variant of the Meerwein arylation leading to stilbenes.     

Microwave‐Promoted Palladium(II)‐Catalyzed C?P Bond Formation by Using Arylboronic Acids or Aryltrifluoroborates

The first Pd^II‐catalyzed P arylation has been performed by using palladium acetate, the rigid bidentate ligand dmphen (dmphen=2,9‐dimethyl‐1,10‐phenanthroline), and without the addition of base or acid. Couplings of arylboronic acids or aryl trifluoroborates with H‐phosphonate dialkyl esters were conducted in 30 min with controlled microwave (MW) heating under non‐inert conditions. Aryl phosphites were also synthesized at room temperature with atmospheric air as the sole reoxidant. The arylated phosphonates were isolated in 44–90 % yields. The excellent chemoselectivity of the method was illustrated in the synthesis of a Mycobacterium tuberculosis glutamine synthetase (MTB‐GS) inhibitor. Online ESIMS was used to detect cationic palladium species in ongoing reactions directly, and a catalytic cycle has been proposed based on these results.     

O‐Arylation of Carboxylic Acids using (Phenyl)[2‐(trimethylsilyl)phenyl]iodonium Triflate as a Precursor of Arynes

Using (phenyl)[2‐(trimethylsilyl)phenyl]iodonium triflate as a precursor of arynes, Larock's method for O‐arylation of carboxylic acids and arynes was developed. A variety of acids including simple aliphatic carboxylic acids, aromatic carboxylic acids, allenoic acids, and p‐toluenesulfonic acid under mild reaction conditions could generate the aryl esters.     

Room‐Temperature Arylation of Thiols: Breakthrough with Aryl Chlorides

The formation of aryl C−S bonds is an important chemical transformation because aryl sulfides are valuable building blocks for the synthesis of biologically and pharmaceutically active molecules and organic materials. Aryl sulfides have traditionally been synthesized through the transition‐metal‐catalyzed cross‐coupling of aryl halides with thiols. However, the aryl halides used are usually bromides and iodides; readily available, low‐cost aryl chlorides often not reactive enough. Furthermore, the deactivation of transition‐metal catalysts by thiols has forced chemists to use high catalyst loadings, specially designed ligands, high temperatures, and/or strong bases, thus leading to high costs and the incompatibility of some functional groups. Herein, we describe a simple and efficient visible‐light photoredox arylation of thiols with aryl halides at room temperature. More importantly, various aryl chlorides are also effective arylation reagents under the present conditions.     

Base‐Mediated O‐Arylation of Alcohols and Phenols by Triarylsulfonium Triflates

A mild and efficient protocol for O‐arylation of alcohols and phenols (ROH) by triarylsulfonium triflates was developed under transition‐metal‐free conditions. Various alcohols, including primary, secondary and tertiary, and phenols bearing either electron‐donating or electron‐withdrawing groups on the aryl rings were smoothly converted to form the corresponding aromatic ethers in moderate to excellent yields. The reactions were conducted at 50 or 80 °C for 24 h in the presence of a certain base and showed good functional group tolerance. The base‐mediated arylation with asymmetric triarylsulfonium salts could selectively transfer the aryl groups of sulfoniums to ROH, depending on their inherent electronic nature. The mechanistic studies revealed that the reaction might proceed through the nucleophilic attack of the in situ formed alkoxy or phenoxy anions at the aromatic carbon atoms of the C?S bonds of triarylsulfonium cations to furnish the target products.     

Ligand‐Free,Cu‐ and Fe‐Catalyzed Selective Ring‐Opening Arylations of Benzoxazoles with Aryl Iodides

Cu‐ or Fe‐based catalyst systems have been reported to selectively catalyze the N,N‐diarylation or N‐monoarylation of benzoxazoles ring‐opening with aryl iodides in the absence of additional added ligand in polyethylene glycol under an inert atmosphere. Two types of coupling products (triphenylamines and diphenylamines) have been examined and the reaction routes can be simply controlled by changing the metal salts (Cu or Fe) as catalyst. A range of substrates have been investigated for the diverse reactions, and the corresponding arylation products were achieved in good to high yields. This selective, low‐cost, and environmentally friendly protocol displays great potential for replacing existing methodologies as well as extending the synthetic applications of benzoxazoles.     

Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts

A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.     

Direct Arylation of N‐Heteroarenes with Aryldiazonium Salts by Photoredox Catalysis in Water

A highly effective visible light‐promoted “radical‐type” coupling of N‐heteroarenes with aryldiazonium salts in water has been developed. The reaction proceeds at room temperature with [Ru(bpy)₃]Cl₂ ? 6 H₂O as a photosensitizer and a commercial household light bulb as a light source. Pyridine and a variety of substituted pyridines are effective substrates under these reaction conditions, and only monosubstituted products are formed with different regioselectivities. Using aqueous formic acid as solvent, an array of xanthenes, thiazole, pyrazine, and pyridazine are compatible with this new arylation approach. The broad substrate scope, mild reaction conditions, and use of water as reaction solvent make this procedure a practical and environmentally friendly method for the synthesis of compounds containing aryl‐heteroaryl motifs.     

Room‐Temperature,Ligand‐ and Base‐Free Heck Reactions of Aryl Diazonium Salts at Low Palladium Loading: Sustainable Preparation of Substituted Stilbene Derivatives

The Pd(OAc)₂‐catalyzed Heck reaction of aryl diazonium salts with 2‐arylacrylates led to cis‐stilbenes with good to excellent stereoselectivity. The environmentally friendly protocol developed in this work features low palladium loading in technical‐grade methanol at room temperature under base‐, additive‐, and ligand‐free conditions. The same protocol applied to simple Heck coupling of aryl diazonium salts with methyl acrylate allows astonishingly low palladium loading, down to 0.005 mol %. The stereoselectivity experimentally observed for the synthesis of cis‐stilbenes has been rationalized by DFT calculations. Moreover, the role of methanol in promoting the reaction has been clarified by a computational study.     

Through‐Space 1,4‐Palladium Migration and 1,2‐Aryl Shift: Direct Access to Dibenzo[a,c]carbazoles through a Triple CH Functionalization Cascade

A palladium‐catalyzed expeditious synthesis of dibenzofused carbazoles from readily available 2‐arylindoles and diaryliodonium salts is reported. Interestingly, after the electrophilic C3 palladation of indole, an unexpected “through‐space” 1,4‐palladium migration to the 2‐aryl moiety, by remote C?H bond activation followed by C?H arylation with diaryliodonium salt, and an unprecedented 1,2‐aryl shift take place. Finally, an intramolecular cross‐dehydrogenative coupling (CDC) at the C2 position affords dibenzo[a,c]carbazoles in high yields. Remarkably, the present migratory annulation occurs through three C?H bond activation one C?C bond cleavage, and the simultaneous construction of three new C?C bonds in a single operation.     

Regiospecific N‐Arylation of Aliphatic Amines under Mild and Metal‐Free Reaction Conditions

A transition metal‐free N‐arylation of primary and secondary amines with diaryliodonium salts is presented. Both acyclic and cyclic amines are well tolerated, providing a large set of N‐alkyl anilines. The methodology is unprecedented among metal‐free methods in terms of amine scope, the ability to transfer both electron‐withdrawing and electron‐donating aryl groups, and efficient use of resources, as excess substrate or reagents are not required.     

Domino‐Heck Reactions of Carba‐ and Oxabicyclic,Unsaturated Dicarboximides: Synthesis of Aryl‐Substituted,Bridged Perhydroisoindole Derivatives

The C? C coupling of the two bicyclic, unsaturated dicarboximides 5 and 6 with aryl and heteroaryl halides gave, under reductive Heck conditions, the C‐aryl‐N‐phenyl‐substituted oxabicyclic imides 7a – c and 8a – c (Scheme 3). Domino‐Heck C? C coupling reactions of 5, 6 , and 1b with aryl or heteroaryl iodides and phenyl‐ or (trimethylsilyl)acetylene also proved feasible giving 8, 9 , and 10a – c , respectively (Scheme 4). Reduction of 1b with LiAlH₄ (→ 11 ) followed by Heck arylation and reduction of 5 with NaBH₄ (→ 13 ) followed by Heck arylation open a new access to the bridged perhydroisoindole derivatives 12a , b and 14a , b with prospective pharmaceutical activity (Schemes 5 and 6).     

Palladium(0)‐Catalyzed Intermolecular Arylative Dearomatization of β‐Naphthols

The first Pd⁰‐catalyzed intermolecular arylative dearomatization of β‐naphthols with aryl halides is described. It was found that Q‐Phos could facilitate the palladium‐catalyzed cross‐coupling‐type dearomatization of β‐naphthols, while avoiding O‐arylation, to construct 2‐naphthalenones in excellent yields and with high chemoselectivity.