Diaryliodonium Salts Research Articles

Pd-Catalyzed C(sp3)-H Biarylation via Transient Directing Group Strategy.

Here, we describe a highly selective Pd-catalyzed C(sp3)-H biarylation of 2-methylbenzaldehydes using cyclic diaryliodonium salts as arylation reagents. The key strategy is the employment of tert-leucine as a bidentate transient directing group for the proximity-driven metalation to achieve reactivity and selectivity in C-H activation. Various functionalized biaryls bearing both aldehyde and iodine functional groups were prepared successfully, which could be further transformed into a wide range of compounds with potential applications in pharmaceutical chemistry and materials science.

Atroposelective Ring Opening of Cyclic Diaryliodonium Salts Using a Chiral Co Anion and Cu Catalyst

Key words cobalt anion - copper catalysis - atroposelectivity - C–N coupling - aryl iodides

Iridium(III)-Catalyzed Sequential C(2)-Arylation and Intramolecular C-O Bond Formation from Azulenecarboxylic Acids and Diaryliodonium Salts Access to Azulenofuranones.

Described herein is the iridium-catalyzed sequential C(2)-arylation reaction and intramolecular C-O bond formation from azulenecarboxylic acids and diaryliodonium salts, leading to the formation of 3-arylazulenofuranones. The sequential reaction proceeded smoothly through generation of 2-arylazulene-1-carboxylic acids derived from the iridium-catalyzed regioselective C(2)-arylation reaction without the decarboxylation reaction.

Atroposelective Ring Opening of Cyclic Diaryliodonium Salts with Bulky Anilines Controlled by a Chiral Cobalt(III) Anion

AbstractThe present work demonstrates a CuCl and anionic chiral cobalt(III)‐catalyzed enantioselective ring‐opening reaction. The small‐size, ligand‐free copper species enabled the cross‐coupling of iodonium salts with a series of bulky aromatic amines in high ee values. The chiral cobalt(III) anion causes appreciable chemical shift changes of cyclic diaryliodoniums in 1H NMR spectra.

Atroposelective Ring Opening of Cyclic Diaryliodonium Salts with Bulky Anilines Controlled by a Chiral Cobalt(III) Anion.

The present work demonstrates a CuCl and anionic chiral cobalt(III)-catalyzed enantioselective ring-opening reaction. The small-size, ligand-free copper species enabled the cross-coupling of iodonium salts with a series of bulky aromatic amines in high ee values. The chiral cobalt(III) anion causes appreciable chemical shift changes of cyclic diaryliodoniums in 1 H NMR spectra.

Wet carbonate-promoted radical arylation of vinyl pinacolboronates with diaryliodonium salts yields substituted olefins

Since the landmark work of Heck, Negishi and Suzuki on Pd-catalyzed crossing coupling reactions, innovative discovery of new reactions forming C-C bonds and constructing functional olefins via nonmetal catalysts remains an imperative area in organic chemistry. Herein, we report a transition-metal-free arylation method of vinyl pinacolboronates with diaryliodonium salts to form C(sp2)-C(sp2) bond and provide trans-arylvinylboronates. The resulting vinylboronates can further react with the remaining aryl iodides (generated from diaryliodonium salts) via Suzuki coupling to afford functional olefins, offering an efficient use of aryliodonium salts. Computational mechanistic studies suggest radical-pair pathway of the diaryliodonium salts promoted by the multi-functional wet carbonate.

Copper-Catalyzed Selective Arylation of Nitriles with Cyclic Diaryl Iodonium Salts: Direct Access to Structurally Diversified Diarylmethane Amides with Potential Neuroprotective and Anticancer Activities.

A novel, simple, and high-yielding approach for the preparation of diarylmethane amide derivatives has been developed by reacting cyclic diaryl iodonium salts with nitriles using CuCl as a catalyst. The procedure is efficient with high atom economy and a wide substrate range. Importantly, selective arylation of nitriles was obtained without affecting the phenyl amino/hydroxyl groups. Furthermore, two of the diarylmethane amides (3k, 3s) displayed excellent neuroprotective and anticancer activities.

Covalent Functionalization of Carbon Surfaces: Diaryliodonium versus Aryldiazonium Chemistry

Covalently modified carbon surfaces remain central to a number of applications. Surface modification is often achieved using aryldiazonium chemistry, which has become the gold standard for the functionalization of carbon-based surfaces. However, the higher reactivity and thus the lower stability of diazonium precursors at carbon interfaces have prompted a search for alternative chemistries. Diaryliodonium salts have emerged as stable alternatives to the conventional aryldiazonium precursors. In this contribution, we provide a detailed comparison between the two types of chemistries by carrying out electrochemical covalent grafting of graphite substrates using nitrophenyl groups generated from the corresponding aryldiazonium and diaryliodonium salts under identical experimental conditions. The electrochemical process was studied using cyclic voltammetry, whereas the covalently grafted substrates were characterized using a battery of surface analytical techniques spanning multiple length scales. Analysis of the modified substrates using Raman spectroscopy revealed that the efficiency of covalent grafting is higher for iodonium chemistry than that for aryldiazonium chemistry. This observation was further corroborated by detailed morphological characterization of the covalent films using atomic force microscopy and molecular-resolution scanning tunneling microscopy, which revealed higher surface coverage for iodonium modified substrates. The chemical composition of the films was probed using X-ray photoelectron spectroscopy. The detailed and systematic comparison presented here clearly demonstrates that diaryliodonium chemistry presents a robust and reliable alternative to the widely used aryldiazonium chemistry.

Palladium-Catalyzed Site-Selective Benzocylization of Aromatic Acids with o-Fluoro-Substituted Diaryliodonium Salts toward 3,4-Benzocoumarins.

By using 2-fluoro-substituted diaryliodonium salts, a novel benzocylization has been accomplished for the synthesis of 3,4-benzocoumarin derivatives via a cascade of ortho-arylation and defluorination in the presence of palladium catalysts. The reaction exhibits a broad compatibility of readily available aromatic acids with an excellent level of site-selectivity. Mechanistic investigations revealed a unique reactivity of carboxylic acid directed arylation by followed nucleophilic substitution of aromatic fluoride in the present system.

Metal-Free Living Cationic Polymerization Using Diaryliodonium Salts as Organic Lewis Acid Catalysts

A metal-free initiating system for the living cationic polymerization of alkyl vinyl ethers (VEs) and styrene derivatives was developed using diaryliodonium salts as an organic Lewis acid catalyst....

Copper-Catalyzed Asymmetric Intermolecular N-Monoarylation of Unprotected Sulfonamides via Desymmetrization of Diaryliodonium Salts at Room Temperature

A copper-catalyzed asymmetric intermolecular N-monoarylation of weakly nucleophilic sulfonamide by desymmetrization of cyclic diaryliodonium salts has been developed. Chiral copper(II)–diamine ligand complexes catalyzed this intermolecular asymmetric aryl C–N cross-coupling reaction effectively at room temperature to afford a series of N-monoarylsulfonamides in good to excellent yields and enantioselectivities.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

Owing to the pioneering works performed on the metal-catalyzed sp2 C–H arylation of indole and pyrrole by Sanford and Gaunt, N– and C-arylation involving diaryliodonium salts offers an attractive complementary strategy for the late-stage diversification of heteroarenes. The main feature of this expanding methodology is the selective incorporation of structural diversity into complex molecules which usually have several C–H bonds and/or N–H bonds with high tolerance to functional groups and under mild conditions. This review summarizes the main recent achievements reported in transition-metal-catalyzed N– and/or C–H arylation of heteroarenes using acyclic diaryliodonium salts as coupling partners.

Deacetylative Aryl Migration of Diaryliodonium Salts with C(sp2)-N Bond Formation toward ortho-Iodo N-Aryl Sulfonamides.

An unprecedented approach of metal-free C(sp2)-N bond formation via deacetylation/intramolecular aryl migration is demonstrated with novel N-sulfonamide substituted diaryliodonium salts. The reaction provides a variety of ortho-iodo N-aryl sulfonamides. The products were employed in several coupling reactions to afford useful diarylamine scaffolds. Furthermore, the key intermediates of zwitterionic iodoniums in the reaction were isolated and verified by the X-ray crystallographic analysis, which showcased unambiguous mechanistic insight into the reactivity of the reaction cascade.

Synthesis of N‐Carbonyl Acridanes as Highly Potent Inhibitors of Tubulin Polymerization via One‐Pot Copper‐Catalyzed Dual Arylation of Nitriles with Cyclic Diphenyl Iodoniums

AbstractA novel Copper‐catalyzed cascade reaction between six‐membered cyclic diaryliodonium salts and nitriles is reported for the facile access to a variety of N‐carbonyl acridanes in good to excellent yields (up to 82%). The reaction is efficient and atom‐economical with a broad substrate scope (e. g. both aryl / alkyl nitriles and substituted / unsubstituted cyclic diaryliodonium salts compatible in the system). This method is particularly useful for the synthesis of substituted N‐carbonyl acridanes which are present in many pharmaceutically important compounds, but are not easy to obtain in conventional approaches. Furthermore, one of the newly synthesized acridanes displayed high antiproliferative activity against MB‐468 cancer cells (IC50=26 nM, comparable to paclitaxel and colchicine) by inhibiting tubulin polymerization. Together, these findings might grant a rapid access to a novel molecular scaffold with potential anticancer utilities.magnified image

Analysis of Perfluorooctanesulfonate Isomers and Other Perfluorinated Alkyl Acids in Serum by In-Port Arylation Gas Chromatography Negative Chemical Ionization–Mass Spectrometry

Perfluorooctanesulfonate (PFOS) is a common environmental pollutant and has been detected in various environmental media. Several major isomers have been identified, and their profiles provide important signatures from the source of contamination. Gas chromatography has a significant resolving power for the isomers. However, methods for derivatizing sulfonates for a sensitive analysis are limited. In this study, in-port derivatization with diaryl iodonium salts into aryl sulfonates was used. A technical mixture of PFOS was separated on gas chromatography to afford 11 isomers. In electron-capture negative ionization, the PFOS derivatives form specific fragmented anions (sulfinate anions). The derivatization was also applied to other per- or polyfluoroalkyl acids (PFASs; 13 perfluoroalkyl carboxylic acids and 10 sulfonates). Analysis of human serum samples was achieved with as little as 50 μL of sample and indicated the presence of PFOS isomers and PFASs. The detection limits of PFOS isomers were 0.02–0.09 ng mL–¹ with sufficient recoveries (85%–98%), and those for other PFASs ranged from 0.01–1 ng mL–¹ (recoveries, 80%–100%), which are suitable for the analysis of human serum samples.

Lewis Acidity Scale of Diaryliodonium Ions toward Oxygen, Nitrogen, and Halogen Lewis Bases.

Equilibrium constants for the associations of 17 diaryliodonium salts Ar2I+X- with 11 different Lewis bases (halide ions, carboxylates, p-nitrophenolate, amines, and tris(p-anisyl)phosphine) have been investigated by titrations followed by photometric or conductometric methods as well as by isothermal titration calorimetry (ITC) in acetonitrile at 20 °C. The resulting set of equilibrium constants KI covers 6 orders of magnitude and can be expressed by the linear free-energy relationship lg KI = sI LAI + LBI, which characterizes iodonium ions by the Lewis acidity parameter LAI, as well as the iodonium-specific affinities of Lewis bases by the Lewis basicity parameter LBI and the susceptibility sI. Least squares minimization with the definition LAI = 0 for Ph2I+ and sI = 1.00 for the benzoate ion provides Lewis acidities LAI for 17 iodonium ions and Lewis basicities LBI and sI for 10 Lewis bases. The lack of a general correlation between the Lewis basicities LBI (with respect to Ar2I+) and LB (with respect to Ar2CH+) indicates that different factors control the thermodynamics of Lewis adduct formation for iodonium ions and carbenium ions. Analysis of temperature-dependent equilibrium measurements as well as ITC experiments reveal a large entropic contribution to the observed Gibbs reaction energies for the Lewis adduct formations from iodonium ions and Lewis bases originating from solvation effects. The kinetics of the benzoate transfer from the bis(4-dimethylamino)-substituted benzhydryl benzoate Ar2CH-OBz to the phenyl(perfluorophenyl)iodonium ion was found to follow a first-order rate law. The first-order rate constant kobs was not affected by the concentration of Ph(C6F5)I+ indicating that the benzoate release from Ar2CH-OBz proceeds via an unassisted SN1-type mechanism followed by interception of the released benzoate ions by Ph(C6F5)I+ ions.

Enantioselective Synthesis of Axially Chiral Biaryls via Copper-Catalyzed Thiolation of Cyclic Diaryliodonium Salts.

Here, we report a chiral copper(II)-bisoxazoline-catalyzed enantioselective ring opening of cyclic diaryliodonium salts with heteroaryl thiols. The readily available 2-mercaptobenzoxazole and 2-mercaptobenzothiazole derivatives reacted efficiently with cyclic diaryliodonium salts and afforded various axially chiral biaryls bearing iodine and sulfur functional groups in excellent yields and enantioselectivities. The products were further transformed into diverse enantiopure alkyl biaryl sulfides, which can be employed as chiral ligands.

Palladium-Catalyzed Four-Component Carbonylative Cyclization Reaction of Trifluoroacetimidoyl Chlorides, Propargyl Amines, and Diaryliodonium Salts: Access to Trifluoromethyl-Containing Trisubstituted Imidazoles.

A palladium-catalyzed four-component carbonylative cyclization reaction for the expeditious construction of trifluoromethyl-containing trisubstituted imidazoles has been achieved. With readily accessible trifluoroacetimidoyl chlorides, propargyl amines, and diaryliodonium salts as the starting materials, the carbonylative transformation proceeds smoothly under mild conditions to enable the formation of multifunctionalized imidazole molecules in a one-pot, one-step manner. Diaryliodonium salts serve as both oxidants and aryl sources in the reaction.

Harnessing Ionic Interactions and Hydrogen Bonding for Nucleophilic Fluorination.

We review recent works for nucleophilic fluorination of organic compounds in which the Coulombic interactions between ionic species and/or hydrogen bonding affect the outcome of the reaction. SN2 fluorination of aliphatic compounds promoted by ionic liquids is first discussed, focusing on the mechanistic features for reaction using alkali metal fluorides. The influence of the interplay of ionic liquid cation, anion, nucleophile and counter-cation is treated in detail. The role of ionic liquid as bifunctional (both electrophilic and nucleophilic) activator is envisaged. We also review the SNAr fluorination of diaryliodonium salts from the same perspective. Nucleophilic fluorination of guanidine-containing of diaryliodonium salts, which are capable of forming hydrogen bonds with the nucleophile, is exemplified as an excellent case where ionic interactions and hydrogen bonding significantly affect the efficiency of reaction. The origin of experimental observation for the strong dependence of fluorination yields on the positions of -Boc protection is understood in terms of the location of the nucleophile with respect to the reaction center, being either close to far from it. Recent advances in the synthesis of [18F]F-dopa are also cited in relation to SNAr fluorination of diaryliodonium salts. Discussions are made with a focus on tailor-making promoters and solvent engineering based on ionic interactions and hydrogen bonding.

Toward the Robust Synthesis of [18F]F‐DOPA: Quantum Chemical Analysis of SNAr Cold Fluorination of Diaryl Iodonium Salt by 19F−

Quantum chemical analysis is presented for S NAr cold fluorination of diaryliodonium salts by 19F− observed by Wirth et al. [Eur. J. Org. Chem. 2015, 625]. We examine the origin of experimentally obtained low yields (0–5%) of fluorination by calculating and comparing the relative Gibbs free energies of pre‐reaction complexes and the Gibbs free energies of activation for fluorination, bromination, and intramolecular cyclization. Focusing on the counter‐anion in diaryliodonium salt, we propose that S NAr bromination would be the predominant process rather than fluorination, resulting in very small amount of fluorinated product. Discussions are made for possible means of improving the yields in cold fluorination.