Copper‐Catalyzed Reaction Cascade of Thiophenol Hydroxylation and S‐Arylation through Disulfide‐Directed C−H Activation

Copper‐catalyzed thiophenol C?H activation is described. Through an initial attempt to conduct C‐arylation with arylboronic acid, a rather surprising sequential C?H activation and S‐arylation was discovered. Mechanistic investigation revealed the disulfide intermediate as the key component in directing C?H oxidation. The overall reaction proceeded under mild conditions with molecular oxygen as the oxidant. Discovery of disulfide as the directing group provides a potential new direction for catalytic C?H functionalization under mild conditions.     

Ligand‐Free Copper‐Catalyzed Arylation of Imidazole and N,N′‐Carbonyldiimidazole,and Microwave‐Assisted Synthesis of N‐Aryl‐1H‐imidazoles

Microwave‐assisted arylation of 1H‐imidazoles and N,N′‐carbonyldiimidazole under ligand‐free copper‐mediated conditions in tetraethyl orthosilicate is reported. Valuable evidence for understanding of the Cu‐catalyzed mechanism of the Ullmann reaction is also presented.     

AgONO‐Assisted Direct CH Arylation of Heteroarenes with Anilines

A novel copper‐catalyzed C?H arylation of heteroarenes with anilines by an in situ diazonium reaction is established by using silver nitrite (AgONO) as an unconventional nitrosating reagent under acid‐free conditions. It provides a complementary approach for the C?H arylation of electron‐rich heteroarenes with aromatic amines affording a variety of heterobiaryls in moderate to good yields.     

Palladium‐Catalyzed γ‐C(sp3)−H Arylation of Thiols by a Detachable Protecting/Directing Group

Reported herein is a palladium‐catalyzed, directed γ‐C(sp³)?H arylation of protected thiols. The key is to utilize Michael acceptors as a dual reagent to install a protecting/directing group on thiols by a thiol‐Michael click reaction, and remove it later under basic conditions. The C?H arylation proceeds with high functional‐group tolerance and the deprotected thiols can be further transformed into other sulfur‐containing compounds. This unique mode of activation could open the door for site‐selective functionalization of thiols or other sulfur‐containing compounds at unactivated positions.     

Late‐Stage Diversification of Peptides by Metal‐Free CH Arylation

The bioorthogonal late‐stage diversification of functionalized oligopeptides was accomplished through a metal‐free, site‐selective C?H arylation of engineered indole derivatives under mild reaction conditions.     

Direct Palladium‐Catalyzed β‐Arylation of Lactams

A direct and catalytic method is reported here for β‐arylation of N‐protected lactams with simple aryl iodides. The transformation is enabled by merging soft enolization of lactams, palladium‐catalyzed desaturation, Ar?X bond activation, and aryl conjugate addition. The reaction is operated under mild reaction conditions, is scalable, and is chemoselective. Application of this method to concise syntheses of pharmaceutically relevant compounds is demonstrated.     

The Photoredox‐Catalyzed Meerwein Addition Reaction: Intermolecular Amino‐Arylation of Alkenes

A variety of amides are efficiently accessible under mild conditions by intermolecular amino‐arylation using a photo Meerwein addition with visible light. The reaction has a broad substrate scope, tolerates a large range of functional groups, and was applied to the synthesis of a 3‐aryl‐3,4‐dihydroisoquinoline.     

Domino N‐/C‐Arylation via In Situ Generation of a Directing Group: Atom‐Efficient Arylation Using Diaryliodonium Salts

Both aryl components of diaryliodonium salts can be used in a domino one‐pot reaction via in situ generation of a directing group. A number of heterocycles undergo N‐arylation which is followed by ruthenium‐catalyzed C‐arylation. Notably the reaction extends well to unsymmetrical diaryliodonium salts with a number of highly selective examples shown.     

Visible‐Light‐Mediated Selective Arylation of Cysteine in Batch and Flow

A mild visible‐light‐mediated strategy for cysteine arylation is presented. The method relies on the use of eosin Y as a metal‐free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation of the required diazonium salts. The batch and flow protocol described herein can be applied to obtain a broad series of arylated cysteine derivatives and arylated cysteine‐containing dipeptides. Moreover, the method was applied to the chemoselective arylation of a model peptide in biocompatible reaction conditions (room temperature, phosphate‐buffered saline (PBS) buffer) within a short reaction time.     

Ligand‐Enabled Catalytic CH Arylation of Aliphatic Amines by a Four‐Membered‐Ring Cyclopalladation Pathway

A palladium‐catalyzed C? H arylation of aliphatic amines with arylboronic esters is described, proceeding through a four‐membered‐ring cyclopalladation pathway. Crucial to the successful outcome of this reaction is the action of an amino‐acid‐derived ligand. A range of hindered secondary amines and arylboronic esters are compatible with this process and the products of the arylation can be advanced to complex polycyclic molecules by sequential C? H activation reactions.     

Thioketone‐Directed Palladium(II)‐Catalyzed C−H Arylation of Ferrocenes with Aryl Boronic Acids

A palladium(II)‐catalyzed thioketone‐chelation‐assisted direct C?H arylation of ferrocenes is described. With thioketone as an efficient directing group, various monoaryl‐ and diaryl‐substituted thiocarbonylferrocenes were obtained by palladium‐catalyzed direct C?H functionalization in high yields under mild and base‐free reaction conditions. Furthermore, the arylated thiocarbonylferrocene could undergo diverse transformations.     

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.     

Polyaniline‐Induced CH Arylation of Arenes with Arenediazonium Salts

A reduced form of polyaniline has been shown to induce direct arylation of an arenediazonium salt with an arene (Gomberg–Bachmann reaction) to give the cross‐coupling product in moderate to good yields under mild conditions. Various arenediazonium salts and arenes, including heteroarenes such as furans, thiophenes, and pyrroles, are employed for the reaction. The most favorable combination of substrates is an electron‐poor arenediazonium salt with an electron‐rich heteroarene. Investigation of the mechanism by reactions with radical scavengers and experiments on kinetic isotope effects indicated the occurrence of a radical chain reaction initiated by one‐electron reduction of an arenediazonium salt by the polyaniline. Only 1 mol % (based on aniline tetramer) of the polyaniline is required for the cross‐coupling reaction to occur. This reaction proceeds under metal‐free conditions and with no need for photonic activation.     

Ligand‐Enabled β‐C–H Arylation of α‐Amino Acids Without Installing Exogenous Directing Groups

Herein we report acid‐directed β‐C(sp³)‐H arylation of α‐amino acids enabled by pyridine‐type ligands. This reaction does not require the installation of an exogenous directing group, is scalable, and enables the preparation of Fmoc‐protected unnatural amino acids in three steps. The pyridine‐type ligands are crucial for the development of this new C(sp³)‐H arylation.     

Dual Photoredox/Nickel‐Catalyzed Three‐Component Carbofunctionalization of Alkenes

The potential of merging photoredox and nickel catalysis to perform multicomponent alkene difunctionalizations under visible‐light irradiation is demonstrated here. Secondary and tertiary alkyl groups, as well as sulfonyl moieties can be added to the terminal position of the double bond with simultaneous arylation of the internal carbon atom in a single step under mild reaction conditions. The process, devoid of stoichiometric additives, benefits from the use of bench‐stable and easy‐to‐handle reagents, is operationally simple, and tolerates a wide variety of functional groups.     

Microwave‐Assisted Palladium‐Catalyzed Direct Arylation of 1,4‐Disubstituted 1,2,3‐Triazoles with Aryl Chlorides

Treatment of 1,4‐disubstituted 1,2,3‐triazoles with aryl chlorides in the presence of potassium carbonate under palladium catalysis and microwave irradiation at 250 °C for 15 min leads to arylation of the triazole at the 5‐position. A variety of functional groups, including ester and hydroxy groups, are compatible. The procedure is suitable for the regioselective preparation of trisubstituted triazoles. Microwave irradiation accelerates the reaction, thus allowing the rapid synthesis of trisubstituted triazoles, which are difficult to synthesize selectively.     

SBA‐15‐functionalized melamine–pyridine group‐supported palladium(0) as an efficient heterogeneous and recyclable nanocatalyst for N‐arylation of indoles through Ullmann‐type coupling reactions

SBA‐15‐functionalized melamine–pyridine group‐supported palladium(0) was found to serve as a heterogeneous and recyclable nanocatalyst for N‐arylation of indoles with aryl iodides under a low catalyst loading (0.3 mol% of Pd) through Ullmann‐type C? N coupling reactions. A variety of aryl iodides could be aminated to provide the N‐arylated products in good to excellent yields without the need of an inert atmosphere. Also, this catalyst was found to be an efficient system for the N‐arylation of other nitrogen‐containing heterocycles with aryl iodides. The heterogeneous palladium catalyst could be recovered by simple filtration of the reaction solution and reused for six cycles without significant loss in its activity. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Cu‐Mediated Selective N‐Arylation of Aminotriazole Acyclonucleosides

Novel N‐aryltriazole nucleosides were synthesized via a Cu‐mediated C? N cross‐coupling reaction, using 3‐aminotriazole acyclonucleosides and various boronic acid reagents. Interestingly, N‐arylation proceeded much more rapidly on the amide group than on the amine group, leading to selective N‐arylation of the amide functionality on nucleosides containing both groups on the triazole nucleobase.     

Noncovalent Substrate‐Directed Enantioselective Heck Reactions: Synthesis of S‐ and P‐Stereogenic Heterocycles

S‐ and P‐Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open‐flask reaction conditions. Several five‐membered aryl‐ sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process.