Diaryliodonium Salts Research Articles

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

Diaryliodonium salts have become widely recognized as arylating agents in the last two decades. Both, symmetrical and unsymmetrical forms of these salts serve as effective electrophilic arylating reagents in various organic syntheses. The use of diaryliodoniums in C–C and carbon–heteroatom bond formations, particularly under metal-free conditions, has further enhanced the popularity of these reagents. In this review, we concentrate on various arylation reactions involving carbon and other heteroatoms, encompassing rearrangement reactions in the absence of any metal catalyst, and summarize advancements made in the last five years.

Metal-Free Synthesis of Benzisoxazolones Utilizing ortho-Ester and ortho-Cyano-Functionalized Diaryliodonium Salts with Protected Hydroxylamines.

Herein, we report the development of metal-free one/two-pot procedures for the synthesis of benzo[c]isoxazol-3(1H)-one (benzisoxazolone) heterocycles by designing diaryliodonium salts featuring ortho-ester or nitrile functional groups. These react smoothly with protected hydroxylamines under mild conditions to produce N-arylhydroxylamine intermediates, which readily cyclize to give benzisoxazolone derivatives under acidic conditions. This metal-free process maintains the weak N-O bond, tolerates a wide range of diaryliodonium salts and protected hydroxylamines with diverse functional/protecting groups, thereby overcoming the challenges associated with previous transformations. The protocol expands the reaction scope and broadens the chemical space of the fused isoxazolone backbones to include unprecedented five-membered heteroaryl-fused isoxazolones in high yields. This method is also applicable to gram-scale synthesis, and the resulting benzisoxazolones can be effectively derivatized at the N-position to afford valuable compounds.

Ru(II)‐Catalyzed Ortho C−H Arylation of Heterocyclic Biaryls

Ru(II)‐Pheox complexes are known catalysts for carbene insertion reactions. Herein we teach them a new trick: how to perform ortho C−H arylation processes! Our operationally simple protocol tolerates structurally diverse directing groups and both aryl iodides and diaryliodonium salts as group transfers.

Discovery of tetrazole thioethers: An efficient, environmentally friendly and metal-free S-arylation using diaryliodonium salts

An efficient, environmentally friendly, and metal-free method for the synthesis of functionalized tetrazole thioethers via the S-arylation of tetrazole-5-thiones using diaryliodonium salts as aryl transfer reagents has been developed. This novel methodology provides rapid access to tetrazole thioether derivatives under facile conditions. Our study underscores the chemoselectivity of unsymmetrical diaryliodonium salts, emphasizing their preference for the transfer of sterically hindered and electron-deficient aryl groups. Notably, the synthesized compound 3h exhibits antitumor activity against A2789 (ovarian cancer) and MDA-MB-231 (breast cancer) tumor cells. In silico studies predict these compounds to possess good drug-likeness and low toxicity risk. These findings highlight the potential of functionalized tetrazole thioethers as antiproliferative agents and pave the way for further development and optimization in future investigations.

Selective Preparation of Pyrrolo[2,3‐c]tetrahydroquinolines and Indolo[3,2‐c]tetrahydroquinolines through N‐Arylation/Cycloaddition/Rearrangement Annulation Reactions of Alkynyl‐Tethered Oximes with Diaryliodonium Salts

We describe a selective preparation of a variety of functionalized pyrrolo[2,3‐c]tetrahydroquinolines and indolo[3,2‐c]tetrahydroquinolines in 40‐82% and 40‐80% yields from alkynyl‐tethered oximes with diaryliodonium triflates, respectively. The one‐pot reaction underwent N‐arylation, intramolecular [3+2] cycloaddition, selective [1.3] or [3,3]‐rearrangement of N‐O bond in total three steps. Experimental studies revealed that EtOAc solvent and copper(II)‐catalyst played crucial roles on the formation of these two tetrahydroquinoline scaffolds. Moreover, these two tetrahydroquinoline scaffolds could be converted into various tetrahydroquinoline building blocks by further transformations.

Arylation of Secondary Phosphines with Diaryliodonium Salts under Metal‐Free and Non‐Photochemical Conditions

A new, efficient, as well as metal‐ and irradiation‐free approach for the direct arylation of secondary phosphines has been developed. The reaction employs diaryliodonium salts as electrophilic aryl‐transfer reagents, effecting the P–Ar bond‐formation in a single step, under mild conditions, using t‐BuOK as a base and DMSO as a solvent, at room temperature. The protocol furnishes expedient access to diverse unsymmetrical triarylphosphines and, upon a one‐pot oxidation, the corresponding triarylphosphine oxides. Experimental and computational studies support the inner sphere aryl‐transfer mechanism through a reductive coupling at the hypervalent iodine center. The calculations also point to a key role played by potassium ions, providing extra stabilization to the P–C bond‐forming transition state by binding the reactants via cation‐π interactions.

Pd-Catalyzed Dual C-H Activation/Cyclization: Convergent and Divergent Synthesis of 1-Azahelicenes.

Herein, we report a convergent synthesis of 1-azahelicenes using easily available quinoline derivatives and cyclic diaryliodonium salts as starting materials. This reaction undergoes a palladium-catalyzed dual C-H activation/cyclization process to give facile access to a wide range of 1-aza[5]helicenes and 1-aza[6]helicenes with abundant functional groups (including F, Cl, Br, I, CF3, SeR, SR, and heteroaryl) in moderate to excellent yields, thereby providing new opportunities to fine-tune the properties of the helicene backbone. In addition, the obtained products could be further transformed into helicene-based Lewis base catalysts and redox switch materials easily. Notably, one selected 1-azahelicene shined bright yellow light by aggregation. These features enlarge the chemical space of 1-azahelicenes and inspire further utilization in other areas of research.

Low-Cost, Safe, and Anion-Flexible Method for the Electrosynthesis of Diaryliodonium Salts.

An electrochemical approach toward the synthesis of diaryliodonium salts based on anodic C-I coupling between aryl iodides and arenes is presented. In contrast to previous protocols, our method requires no chemical oxidants, strong acids, or fluorinated solvents. A further advantage is that by use of the appropriate supporting electrolyte, the counterion of choice can be introduced, which is time- and cost-saving as compared to postsynthesis ion exchange. This "anion-flexibility" is particularly interesting when considering the pronounced effect of the counterion on the reactivity of diaryliodonium species in aryl transfer reactions. The scope of our method comprises 24 examples with isolated yields of up to 99%. Scalability was demonstrated by the synthesis on a gram scale. Furthermore, it was shown that the diaryliodonium-containing post-electrolysis solution can be used without further workup as a reactive medium for O-arylation reactions. Finally, a series of para-substituted diaryliodonium compounds was studied using linear sweep voltammetry on a microelectrode and analyzed with respect to the influence of the electronic structure on the redox behavior.

Triphenylphosphine Oxide: A Versatile Covalent Functionality for Carbon Nanotubes.

Broadening the scope of functionalities that can be covalently bound to single-walled carbon nanotubes (SWCNTs) is crucial for enhancing the versatility of this promising nanomaterial class in applied settings. Here we report the covalent linkage of triphenylphosphine oxide [Ph3P(O)] to SWCNTs, a hitherto overlooked surface functionality. We detail the synthesis and structural characterization of a new family of phosphine oxide-functionalized diaryliodonium salts that can facilitate direct Ph3P(O) transfer and afford novel SWCNTs with tunable Ph3P(O) content (SWCNT-P). The molecularly-distributed and robust nature of the covalent Ph3P(O) attachment in SWCNT-P was supported by a combination of characterization methods including Raman, infrared, UV/Vis-NIR and X-ray photoelectron spectroscopies coupled with thermogravimetric analysis. Electron microscopy further revealed the effectiveness of the Ph3P(O) moiety for de-bundling SWCNTs to yield SWCNT-P with superior dispersibility and processability. Finally, electrochemical studies established that SWCNT-P is sensitive to the presence of Li+, Na+ and K+ wherein the Gutmann-Beckett Lewis acidity parameters of the ions were quantitatively transduced by Ph3P(O) to electrochemical responses. This work hence presents a synthetic, structural, spectroscopic and electrochemical foundation for a new phosphorus-enriched responsive nanomaterial platform featuring the Ph3P(O) functionality.

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt.

Diaryliodonium(III) salts have been established as powerful halogen-bond donors in recent years. Herein, a new structural motif for this compound class was developed: iodoloisoxazolium salts, bearing a cyclic five-membered iodolium core fused with an isoxazole ring. A derivative of this class was synthesized and investigated in the solid state by X-ray crystallography. Finally, the potential as halogen-bonding activator was benchmarked in solution in the gold-catalyzed cyclization of a propargyl amide.

Synthesis of Diaryl Ethers via Hypervalent Iodine-Mediated C-H Functionalization.

A hypervalent iodine-reagent-based C-H functionalization strategy was utilized to synthesize diaryl ethers. This method directly transforms various arenes into their corresponding diaryliodonium salts, followed by a C-O coupling reaction to produce structurally diverse diaryl ethers. The efficacy of this approach in the late-stage structural modifications of complex molecules was demonstrated.

Borate-mediated aryl polyfluoroalkoxylation under transition-metal-free conditions.

We describe the transition-metal-free coupling for polyfluoroalkoxy arenes using polyfluoroalkoxy borates, which serve as counterions to diaryliodonium salts and transferring mediators of polyfluoroalkoxy groups. This strategy demonstrates high functional group compatibility owing to the low nucleophilicity of the borate mediator, thus offering a practical approach for synthesizing diverse polyfluoroalkoxy arenes.

Basicity‐Controlled Reactivity of meta‐OTf‐Substituted Diaryliodonium Salts for Direct Arylation or Diels‐Alder Cycloaddition of Pyrrole Derivatives

AbstractIn this study, we explored the reactivity of meta‐trifluoromethanesulfonate (OTf) substituted diaryliodonium salts under alkaline conditions. Two distinct pathways with direct arylation of pyrrole derivatives and Diels‐Alder cycloaddition via aryne intermediates, have been found upon the relative alkalinity strength of potassium carbonates or hydroxides. This approach offers a straightforward and efficient route to synthesize heterocyclic aromatics under mild reaction conditions with tolerance of various functional groups.

Transition-Metal-Free C-Diarylations to Reach All-Carbon Quaternary Centers.

Herein, we disclose a convenient protocol for the α-diarylation of carbon nucleophiles to yield heavily functionalized quaternary products. Diaryliodonium salts are utilized to transfer both aryl groups under transition-metal-free conditions, which enables an atom-efficient and high-yielding method with broad functional group tolerance. The methodology is amenable to a wide variety of carbon nucleophiles and can be utilized in late-stage functionalization of complex arenes. Furthermore, it is compatible with a new class of zwitterionic iodonium reagents, which gives access to phenols with an ortho-quaternary center. The diarylated products bear an ortho-iodo substituent that can be utilized in further transformations, including the formation of novel, functionalized six-membered cyclic iodonium salts.

A Modular Dual-Catalytic Aryl-Chlorination of Alkenes.

Alkyl chlorides are a class of versatile building blocks widely used to generate C(sp3)-rich scaffolds through transformation such as nucleophilic substitution, radical addition reactions and metal-catalyzed cross-coupling processes. Despite their utility in the synthesis of high-value functional molecules, distinct methods for the preparation of alkyl chlorides are underrepresented. Here, we report a visible-light-mediated dual catalysis strategy for the modular synthesis of highly functionalized and structurally diverse arylated chloroalkanes via the coupling of diaryliodonium salts, alkenes and potassium chloride. A distinctive aspect of this transformation is a ligand-design-driven approach for the development of a copper(II)-based atom-transfer catalyst that enables the aryl-chlorination of electron-poor alkenes, complementing its iron(III)-based counterpart that accommodates non-activated aliphatic alkenes and styrene derivatives. The complementarity of the two dual catalytic systems allows the efficient aryl-chlorination of alkenes bearing different stereo-electronic properties and a broad range of functional groups, maximizing the structural diversity of the 1-aryl, 2-chloroalkane products.

A Modular Dual‐Catalytic Aryl‐Chlorination of Alkenes

AbstractAlkyl chlorides are a class of versatile building blocks widely used to generate C(sp3)‐rich scaffolds through transformation such as nucleophilic substitution, radical addition reactions and metal‐catalyzed cross‐coupling processes. Despite their utility in the synthesis of high‐value functional molecules, distinct methods for the preparation of alkyl chlorides are underrepresented. Here, we report a visible‐light‐mediated dual catalysis strategy for the modular synthesis of highly functionalized and structurally diverse arylated chloroalkanes via the coupling of diaryliodonium salts, alkenes and potassium chloride. A distinctive aspect of this transformation is a ligand‐design‐driven approach for the development of a copper(II)‐based atom‐transfer catalyst that enables the aryl‐chlorination of electron‐poor alkenes, complementing its iron(III)‐based counterpart that accommodates non‐activated aliphatic alkenes and styrene derivatives. The complementarity of the two dual catalytic systems allows the efficient aryl‐chlorination of alkenes bearing different stereo‐electronic properties and a broad range of functional groups, maximizing the structural diversity of the 1‐aryl, 2‐chloroalkane products.

Synthesis of Heterocyclic Sulfonium Triflates by Cu-Catalyzed Selective Sarylation with Aryl(mesityl)iodonium Salts

Background: An efficient method for synthesizing cyclic arylsulfonium salts has been developed by selective aryl transfer to the sulfur atom from aryl(mesityl)iodonium triflates, a recyclable series of diaryliodonium salts. Methods: The utilization of sulfonium salts as valuable intermediates is well-established, as they exhibit high reactivity under conditions of heating or UV irradiation. However, their synthesis typically involves the reaction of diarysulfoxide with acid anhydride, which requires the oxidation of sulfur(II) to sulfoxide(IV) and thus limits the scope of synthesis. Hence, in this study, we employed recyclable mesityliodonium(III) salts and copper catalysis. Results: The method was used to synthesize cyclic arylsulfonium salts without the need for preoxidation of the sulfur atom, resulting in a facile and high-yield synthesis. Conclusion: The desired cyclic arylsulfonium salts were synthesized through selective transfer of the aryl group from mesityliodonium salts, demonstrating the effectiveness of the new approach.

Arylation of Diethyl Acetamidomalonate with Diaryliodonium Salts En Route to α-Arylglycines.

Diethyl acetamidomalonate (DEAM) has been widely used for the synthesis of α-amino acids via C-alkylation under basic conditions followed by hydrolysis/decarboxylation. In contrast, the C-arylation of this reagent remains undeveloped. Herein, we report a novel strategy for the synthesis of racemic α-arylglycines based on the selective arylation of DEAM with diaryliodonium salts under mild, transition metal-free conditions. The reaction features good functional group tolerance and easy scalability and is applicable to the chemoselective C-H-modification of arenes including approved drugs, thus enabling a straightforward approach to complex α-arylglycines that would be challenging to make otherwise.

Application of Cyclic Diaryliodonium Salts in the Synthesis of Axially Chiral Natural Product Analogues.

The application of cyclic diaryliodonium salts in the synthesis of bioactive natural product analogues was demonstrated. Axially chiral biaryls were obtained via the enantioselective ring opening of cyclic diaryliodonium salts. Regioselective borylation was key in accessing both enantiomers of a biphenol key intermediate in eight steps overall. 8,8″-Amino biflavones were synthesized, their bioactivity profiled, and the eutomer identified. The structure-activity relationship was probed.

Synthesis of Versatile Aryliodine Synthons by Aryliodonium Rearrangement Reactions

AbstractThe excellent reactivity of diaryliodonium salts has primarily been attributed to the efficient departure of the iodoarene unit, facilitating a variety of arylation reactions. However, one equivalent of iodoarene as a side‐product is a chemical waste in these reactions, which was criticized by chemists for hindering its popularity. Recently, the development of synthetic methodology that preserve the aryl iodine moiety received increasing attention. Oxidative rearrangement reactions involving aryliodonium reagents have significantly addressed the atom‐economic issue, thereby broadening the reaction scope. The resulting intricate aryliodine products are viewed as valuable synthons for the synthesis of natural products, pharmaceutical intermediates and other fine chemicals.