An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C−H Bond Activations

C−H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site‐selectivity have limited its use for graphene segment synthesis. A Pd‐catal‐ yzed one‐step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2‐ or 4‐fold C−H arylation of unactivated benzene derivatives. A Pd₂(dibenzylideneacetone)₃ catalytic system, using cyclic diaryliodonium salts as π‐extending agents, leads to site‐selective inter‐ and intramolecular tandem arylation sequences. Moreover, N ‐substituted triphenylenes are applied to a field‐effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.     

C‐2 Selective Arylation of Indoles with Heterogeneous Nanopalladium and Diaryliodonium Salts

A simple and efficient method to prepare synthetically useful 2‐arylindoles is presented, using a heterogeneous Pd catalyst and diaryliodonium salts in water under mild conditions. A remarkably low leaching of metal catalyst was observed under the applied conditions. The developed protocol is highly C‐2 selective and tolerates structural variations both in the indole and in the diaryliodonium salt. Arylations of both N?H indoles and N‐protected indoles with ortho‐substituted, electron‐rich, electron‐deficient, or halogenated diaryliodonium salts were achieved to give the desired products in high to excellent isolated yields within 6 to 15 h at room temperature or 40 °C.     

Study of Ground State Interactions of Enantiopure Chiral Quaternary Ammonium Salts and Amides,Nitroalkanes, Nitroalkenes,Esters, Heterocycles,Ketones and Fluoroamides

Chiral phase-transfer catalysis provides high level of enantiocontrol, however no experimental data showed the interaction of catalysts and substrates. ¹H NMR titration was carried out on Cinchona and Maruoka ammonium bromides vs. nitro, carbonyl, heterocycles, and N−F containing compounds. It was found that neutral organic species and quaternary ammonium salts interacted via an ensemble of catalyst ⁺N−C−H and (sp²)C−H, specific for each substrate studied. The correspondent BArF salts interacted with carbonyls via a diverse set of ⁺N−C−H and (sp²)C−H compared to bromides. This data suggests that BArF ammonium salts may display a different enantioselectivity profile. Although not providing quantitative data for the affinity constants, the data reported proofs that chiral ammonium salts coordinate with substrates, prior to transition state, through specific C−H positions in their structures, providing a new rational to rationalize the origin of enantioselectivity in their catalyses.     

Transition-Metal-Free Aryl–Aryl Cross-Coupling: C−H Arylation of 2-Naphthols with Diaryliodonium Salts

Transition-metal-free regioselecitive C−H arylation of 2-naphthols with diaryliodonium salts has been developed. The reaction proceeds under very simple experimental conditions and affords a range of products with various substitution patterns. The method allows for the incorporation of electron-deficient aryls, which complements well currently existing metal-free aryl–aryl cross-couplings of phenols that have been so far restricted to the introduction of electron-rich aryl moieties. The mechanism of the reaction was studied by means of DFT calculations, demonstrating that the C−C bond formation occurs via a dearomatization of 2-naphthol substrate, followed by a subsequent rearomatization by tautomerization. The computations show that the use of a low polarity solvent and an insoluble inorganic base is key to securing the high selectivity of the C−C coupling over a competing C−O arylation pathway, by preventing the incipient deprotonation of 2-naphthol.     

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.     

Palladium-Catalyzed C8-Arylation of Naphthalenes through C−H Activation: A Combined Experimental and Computational Study

Herein, a direct C8-arylation reaction of 1-amidonaphthalenes is described. By using diaryliodonium salts as arylating agents, the palladium-catalyzed C−H activation reaction showed perfect C8 regioselectivity and a wide functional group tolerance. In most cases, the desired polyaromatic compounds were isolated in good to excellent yields. To explain the observed regioselectivity, DFT calculations were performed and highlighted the crucial role of the amide directing group. Finally, the utility of this method is showcased by the synthesis of benzanthrone derivatives.     

Synthesis of Cyclic and Acyclic ortho-Aryloxy Diaryliodonium Salts for Chemoselective Functionalizations

Two regioselective, high-yielding one-pot routes to oxygen-bridged cyclic diaryliodonium salts and ortho-aryloxy-substituted acyclic diaryliodonium salts are presented. Starting from easily available ortho-iodo diaryl ethers, complete selectivity in formation of either the cyclic or acyclic product could be achieved by varying the reaction conditions. The complimentary reactivities of these novel ortho-oxygenated iodonium salts were demonstrated through a series of chemoselective arylations under metal-catalyzed and metal-free conditions, to deliver a range of novel, ortho-functionalized diaryl ether derivatives.     

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.     

Synthesis of Complex Diarylamines through a Ring-Opening Difunctionalization Strategy**

The diarylation and skeletal diversification of unstrained cyclic amines was exploited to expand and modify the favorable properties of this important substrate class with pivotal roles in drug discovery. Cyclic amines were employed in the synthesis of a novel class of amino-substituted diaryliodonium salts, which were converted to highly functionalized diarylamines through an atom-efficient one-pot N-arylation/ring opening reaction with external nucleophiles. The reaction proceeds through in situ formation of a diarylammonium intermediate that undergoes a nucleophilic ring opening by cleavage of the strong C−N bond. A wide variety of diarylamines was obtained through introduction of two different aryl groups of varied electronics, and the retained iodo-substituent enables downfield diversifications of the products. More than 20 nucleophiles, including amines, phenols, carboxylic acids, thiols and halides, were alkylated with high functional group tolerance, and the strategy proved efficient also in in late-stage functionalization of natural products and pharmaceuticals.     

A Modular Flow Design for the meta-Selective C−H Arylation of Anilines

Described herein is an effective and practical modular flow design for the meta-selective C−H arylation of anilines. The design consists of four continuous-flow modules (i.e., diaryliodonium salt synthesis, meta-selective C−H arylation, inline copper extraction, and aniline deprotection) which can be operated either individually or consecutively to provide direct access to meta-arylated anilines. With a total residence time of 1 hour, the desired product could be obtained in high yield and excellent purity without the need for column chromatography, and the residual copper content meets the standards for parenterally administered pharmaceutical substances.     

Iron‐catalyzed carbon–sulfur bond formation: Atom‐economic construction of thioethers with diaryliodonium salts

Diaryliodonium salts are characterized by poor atom economy with the formation of one equivalent of an iodoarene as waste. We have developed an atom‐economic iron‐catalyzed protocol for the synthesis of a variety of thioethers with diaryliodonium salts. Not only cyclic diaryliodonium salts but also linear diaryliodonium salts were found to perform well in the reactions.     

Metal‐Free Arylation of Oxygen Nucleophiles with Diaryliodonium Salts

Phenols and carboxylic acids are efficiently arylated with diaryliodonium salts. The reaction conditions are mild, metal free, and avoid the use of halogenated solvents, additives, and excess reagents. The products are obtained in good‐to‐excellent yields after short reaction times. Steric hindrance is very well tolerated, both in the nucleophile and diaryliodonium salt. The scope includes ortho‐ and halo‐substituted products, which are difficult to obtain by metal‐catalyzed protocols. Many functional groups are tolerated, including carbonyl groups, heteroatoms, and alkenes. Unsymmetric salts can be chemoselectively utilized to obtain products with hitherto unreported levels of steric congestion. The arylation has been extended to sulfonic acids, which can be converted to sulfonate esters by two different approaches. With recent advances in efficient synthetic procedures for diaryliodonium salts the reagents are now inexpensive and readily available. The iodoarene byproduct formed from the iodonium reagent can be recovered quantitatively and used to regenerate the diaryliodonium salt, which improves the atom economy.     

A Modular Flow Design for the meta‐Selective C−H Arylation of Anilines

Described herein is an effective and practical modular flow design for the meta ‐selective C−H arylation of anilines. The design consists of four continuous‐flow modules (i.e., diaryliodonium salt synthesis, meta ‐selective C−H arylation, inline copper extraction, and aniline deprotection) which can be operated either individually or consecutively to provide direct access to meta ‐arylated anilines. With a total residence time of 1 hour, the desired product could be obtained in high yield and excellent purity without the need for column chromatography, and the residual copper content meets the standards for parenterally administered pharmaceutical substances.     

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.     

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.     

Redox cationic polymerization: The diaryliodonium salt/ascorbate redox couple

Strong Brønsted acids are produced on reduction of diaryliodonium salts containing anions of the type BF₄^?, AsF₆^?, PF₆^?, SbF₆^? by ascorbic acid and its derivatives in the presence of catalytic amounts of copper salts. The cationic polymerizations of cyclohexene oxide, tetrahydrofuran, and s-trioxane were studied using the diaryliodonium salt/ascorbate redox couple.     

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.     

One‐pot Annulation for Biaryl‐fused Monocarba‐closo‐dodecaborate through Aromatic B−H Bond Disconnection

We have developed a one‐pot annulation reaction of monocarba‐closo‐dodecaborate with cyclic diaryliodonium salts to afford biaryl‐fused derivatives. Aryl functionalities are introduced at both the 1‐carbon and unreactive ortho‐boron vertices of the “σ‐aromatic” carborane cage without the need for pre‐functionalization. DFT calculations revealed that the palladium‐catalyzed C?B bond‐formation step in this process proceeds through a concerted metalation–deprotonation (CMD)‐type pathway for the B?H bond disconnection on the aromatic cage, though such bonds are generally regarded as hydridic.     

Copper-catalyzed direct N-arylation of N-arylsulfonamides using diaryliodonium salts in water

An efficient copper-catalyzed N-arylation of N-arylsulfonamides with diaryliodonium salts is reported. The reaction employs diaryliodonium salts and N-arylsulfonamides in water at room temperature, giving the products in moderate to excellent yields.     

Determination of Diaryliodonium Species by Reverse Iodometric Titration with Ascorbic Acid

Diaryliodonium salts are used in organic chemistry, materials science and pharmaceutical chemistry. For the quantitative analysis of diaryliodonium salts, only instrumentally demanding techniques requiring highly skilled operators are available. Surprisingly, no titration method taking advantage of the oxidising ability of diaryliodonium is available in the literature. In the present work, a titration method for the determination of diaryliodonium salts is presented. It is based on the reaction of diaryliodonium species with ascorbic acid, whose excess is subsequently determined by means of iodometric potentiometric titration. Application of the protocol to various diaryliodonium salts revealed the scope and limitations of the method.