Diaryliodonium Salts Research Articles

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.

Electrophilic aryl spiroannulation induced by diaryliodonium salts: efficient synthesis of [5,5]-spiro lactone-lactam scaffolds from α-cyanocarboxylates

Spirocyclic architectures represent one of the privileged three-dimensional scaffolds in pharmaceutical chemistry and drug discovery, while the new-skeletal synthesis of spiromolecules from simple starting materials remains a challenging task. Here, we report a first diaryliodonium salts mediated electrophilic aryl spiroannulation reaction from simple substrates α-cyanocarboxylate. With this strategy, a broad spectrum of new [5,5] spiro-fused skeletons could be efficiently constructed in one step via Cu-catalyzed cascaded N-arylation-acylation and etheral skeleton rearrangement reaction. The key point of this transformation was the intramolecular electrophilic cyclization due to the nucleophilicity of O-atom and electrophilicity of α-C induced by diaryliodonium salts. With this protocol, the more challenging activation of ether bonds was achieved via diaryliodonium salts-mediated. This method has the major advantages of a broad substrate scope and excellent functional group compatibility. Further synthesis elaboration was performed using substrate with steric hindrance to showcase the versatility of this methodology.

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions.

Diaryliodonium(III) salts are versatile reagents that exhibit a range of reactions, both in the presence and absence of metal catalysts. In this study, we developed efficient synthetic methods for the preparation of aryl(TMP)iodonium(III) carboxylates, by reaction of (diacetoxyiodo)arenes or iodosoarenes with 1,3,5-trimethoxybenzene in the presence of a diverse range of organocarboxylic acids. These reactions were conducted under mild conditions using the trimethoxyphenyl (TMP) group as an auxiliary, without the need for additives, excess reagents, or counterion exchange in further steps. These protocols are compatible with a wide range of substituents on (hetero)aryl iodine(III) compounds, including electron-rich, electron-poor, sterically congested, and acid-labile groups, as well as a broad range of aliphatic and aromatic carboxylic acids for the synthesis of diverse aryl(TMP)iodonium(III) carboxylates in high yields. This method allows for the hybridization of complex bioactive and fluorescent-labeled carboxylic acids with diaryliodonium(III) salts.

Efficient access to triphenylene derivatives via carbamate-directed bay-region selective arylation of biphenol derivatives and Scholl cyclization

A novel method for carbamate-directed meta-C-H bond arylation of biphenyl derivatives employing diaryliodonium salts as the arylation agents was explored. Consequently, the Scholl reaction was utilized to cyclize the product, yielding 21 varieties of multifunctional triphenylene derivatives. The maximum yield achieved through this two-step process was 94 %, offering an efficient synthesis route for the production of multi-substituted triphenylene derivatives.

BF3 ⋅ OEt2 and Visible Light‐Controlled [3,3]‐ or [1,3]‐Rearrangement of Quinazolinone N−O Aryl Moieties

AbstractWe described a base‐promoted O‐arylation of N3‐hydroxyl quinazolinones with diaryliodonium salts and sequential BF3 ⋅ OEt2 and visible light‐controlled [3,3]‐ or [1,3]‐rearrangements of quinazolinone N−O aryl moieties to prepare a variety of 2‐(quinazolin‐4‐yloxy)phenols and atropisomeric 3‐(2‐hydroxyphenyl)quinazolin‐4‐ones in 44%‐75% yields and 28%‐70% yields, respectively. Mechanistic studies showed that HBF4 generated in situ from BF3 ⋅ Et2O and water served as the catalyst in this process and aryloxyquinazolinium salts are vital intermediates promoting the [3,3]‐ or [1,3]‐rearrangements. The N−O aryl moieties of aryloxyquinazolinium salts were found to undergo solely [3,3]‐rearrangement with heating whereas [1,3]‐rearrangement occurred via a radical process under irradiation of visible light. This method highlights the formation of aryloxyquinazolinium salts based on the use of BF3 ⋅ OEt2 and visible light to prompt [1,3]‐rearrangement generating atropisomeric quinazolinones.

Transition Metal and Photocatalyst Free Arylation via Photoexcitable Electron Donor Acceptor Complexes:Mediation and Catalysis

AbstractVisible‐light‐activated organic reactions unlock novel avenues for complex molecular transformations, impossible under standard “thermal” conditions, which makes them powerful tools in the arsenal of synthetic chemistry. However, transition metal‐based or organic photoredox catalysts are often used to ensure productive absorption of visible light, which might be not desirable to medicinal chemistry and industry due to toxicity, low sustainability, and high cost of most photocatalysts. A more environmentally and economically benign approach is based on the formation of transient electron donor‐acceptor (EDA) complexes between two reagents or a reagent and an additive, that readily absorb visible light, acting as internal photosensitizers. Within the EDA complex‐based arylation strategies, chemical transformations are mediated by noncovalent interaction between two molecules, namely between electron‐poor aryl halides or their synthetic equivalents and electron‐rich nucleophilic reagents or additives. Moreover, besides stoichiometric EDA complexes between two molecules, EDA complex based organocatalysis can be achieved in certain cases through regeneration of the donor molecules in the course of the reaction. Photoexcitation of the EDA complexes induces a single electron transfer (SET) process to generate aryl radical species for the arylation step. This Review will focus on the state‐of‐the‐art EDA complex‐based arylation strategies utilizing aryl halides, aryldiazonium, diaryliodonium, arylsulfonium and arylphosphonium salts as reactants, published mainly in the last five years.

Transition‐Metal‐Free Allylic Defluorination Cross‐Electrophile Coupling Employing Rongalite

Comprehensive SummaryThe conversion of CF3‐alkenes to gem‐difluoroalkenes using reductive cross‐coupling strategy has received much attention in recent years, however, the use of green and readily available reducing salt to mediate these reactions remains to be explored. In this work, a concise construction of gem‐difluoroalkenes, which requires neither a catalyst nor a metal reducing agent, was established. Rongalite, a safe and inexpensive industrial product, was employed as both a radical initiator and reductant. This procedure was compatible with both linear and cyclic diaryliodonium salts, enabling a wide variety of substrates (>70 examples). The utility of this approach was demonstrated through gram‐scale synthesis and efficient late‐stage functionalizations of anti‐inflammatory drugs.

Copper-Catalyzed Chemoselective O-Arylation of Oxindoles: Access to Cyclic Aryl Carboxyimidates.

We have developed a highly efficient base- and additive-free chemoselective CuO-catalyzed strategy for the O-arylation of 2-oxindoles to synthesize 2-phenoxy-3H-indole and 2-phenoxy-1H-indole derivatives in the presence of diaryl iodonium salts. This method offers a variety of O-arylated oxindoles in good to excellent yields under relatively milder reaction conditions. Furthermore, this methodology was extended for the O-arylation of 2-pyridinone and isoindoline-1-one derivatives as well.

Cu-Catalyzed Halogenation of Diaryliodonium Salts Containing Ortho-sidearm

A simple and efficient halogenation pathway has been delivered with various diaryliodonium salts, containing an ortho alcoholic sidearm, and CuCl or CuBr to produce chloroarenes and bromoarenes in para position only without any ortho aromatic isomer. The reaction conditions include temperature (60 oC), solvent (DMF) and reaction time (2 hours) were optimized in order to obtain high yields of products. All products were isolated and characterized via 1H-NMR and 13C-NMR. With further investigation, these methods could be the main entrance to prepare herbicides, insecticides and bactericides containing haloarenes in their structures.

Gas‐phase Smiles rearrangement of ortho‐nitro‐substituted diaryliodonium cations and their mechanistic insights

RationaleDiaryliodonium salts are useful electrophilic reagents in organic chemistry, finding extensive applications in arylations and photo‐induced polymerizations. However, comprehensive mechanistic investigations, particularly concerning the mass spectrometric behaviors of diaryliodonium salts, are relatively scarce in the literature.MethodsDiaryliodonium salts could be readily ionized using electrospray ionization mass spectrometry (ESI‐MS) to give [Ar1‐I+‐Ar2], and high‐resolution ESI‐tandem mass spectrometry (MS/MS) experiments were conducted to investigate their gas‐phase chemical reactions.ResultsInvestigations on ESI‐MS/MS of [Ar1‐I+‐Ar2] revealed two major fragmentation patterns: (1) reductive elimination resulting in the diaryl coupling product ion [Ar1‐Ar2]+• by the loss of I; (2) generation of aryl cations [Ar1]+ or [Ar2]+ through cleavage of the C–I bonds. We revealed that the introduction of NO2 into Ar2 of [Ar1‐I+‐Ar2] could lead to an unexpected fragmentation ion [Ar1O]+ in MS/MS, arising from an O‐atom transfer process from NO2 to Ar1. Particularly, when NO2 was ortho‐positioned to the iodine in Ar2, the [Ar1O]+ sometimes exhibited dominant behavior.ConclusionsComprehensive ESI‐MS/MS studies and theoretical calculations provided strong support for the O‐atom transfer mechanistic pathway: [Ar1‐I+‐(o‐NO2‐Ar2)] initially underwent a Smiles rearrangement to the intermediate [Ar1‐O‐(o‐NO‐Ar2I)]+, which subsequently dissociated to [Ar1O]+ or [o‐NO‐Ar2I]+•. Herein, we proposed an unexpected “ortho effect” in the gas‐phase fragmentation reaction of [Ar1‐I+‐(o‐NO2‐Ar2)], in which the crucial determinant factor for the aryl migration was identified as the Smiles rearrangement reaction.

Push–pull biphenyl–based iodonium salts: Highly sensitive one-component photoinitiators for photopolymerization under UV–visible LEDs

Diaryliodonium salts play an important role as highly efficient photoinitiators in the field of photopolymerizations. They can rapidly photodecompose to produce free radicals and super acids; thus, can initiate highly efficient photocuring of acrylic and epoxy monomers and resins. However, the absorption of commercialized diphenyliodonium salts is poorly matched with popular LED light sources, and the participation of sensitizers is usually required to achieve efficient photoexcitation. Here, we synthesized five new phenyl biphenyl iodonium salts with different electron-pushing and electron-withdrawing substituents, e.g., methoxy and CN, at the biphenyl substituent. Our results demonstrate that all synthesized iodonium salts have strong absorption in the range (λmax = 258–352 nm; εmax = 21,300–29,900 M−1 cm−1). The photochemistry of these synthesized iodonium salt is strongly influenced by substituents on the biphenyl ring. All iodonium salts can undergo rapid photolysis under light excitation, with higher quantum yield of photoacid generation reaching 0.25 and can quickly initiate cationic photopolymerization of epoxy monomers. Furthermore, free radicals are generated during photolysis, which can successfully trigger free radical polymerization. These iodonium salts with good absorbance in the UVA band demonstrate their potential as excellent photoinitiators under 365–405 nm LED excitation.

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts.

N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have tested this method with a wide range of amides and iodonium triflates, proving its versatility with numerous substrates. Beyond carbazoles, we also produced a variety of other N-heterocycles, such as acridines, phenoxazines, or phenazines, showcasing the robustness of our technique. In a broader sense, this new method creates two C-N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste.

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins.

Cyclic annulation involving diaryliodonium salts is an efficient tool for the construction of two or more chemical bonds in a one-pot process. Ortho-functionalized diaryliodonium salts have showcased distinct reactivity in the exploration of benzocyclization or arylocyclization. With this strategy of ortho-ester-substituted diaryliodonium salts, herein, we utilized a copper catalyst to activate the C-I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents.

Exogenous photocatalyst-free aryl radical generation from diaryliodonium salts and use in metal-catalyzed C-H arylation.

We demonstrate (1) detectable halogen bonding is not critical for enabling light-driven radical generation from diaryliodonium salts and (2) radicals generated by this route can be captured by transition-metals for C-H arylation reactions. These results are the first step toward developing new metal-catalyzed aryl radical couplings without exogenous photocatalysts.

Sequential regioselective arylation of pyrazolones with diaryliodonium salts.

The introduction of aromatic substituents into organic compounds significantly alters their physical and chemical characteristics. Yet, achieving precise control over the site-selectivity of arylation continues to pose a considerable challenge. We present here a controllable method for the site-selective mono-, di-, and triarylation of pyrazolone with diaryliodonium salts. The method showcases robustness, flexibility, and excellent compatibility with a broad range of functional groups. It enables control over both the site of arylation and the number of aryl additions. Specifically, three of the four substitutable positions in pyrazolone can be selectively arylated, effectively producing four products under controlled conditions. Additionally, the method supports one-pot sequential arylation, leading to an array of products with diverse aromatic substituents. Control experiments revealed the specific conditions of each reaction step.

Synthesis of phosphate stabilised iodanes and their application in intramolecular aryl migrations.

A diverse set of hydroxy-benzo[e]iodadioxaphosphinine oxides and derived diaryl iodonium salts are prepared and two examples are characterized by X-ray crystallography, featuring an out-of-plane geometry of the hypervalent bond for both compound classes. Treatment of the phosphate-stabilized diaryliodonium salts with Ca(OH)2 results in an efficient base-induced intramolecular aryl migration under aqueous conditions, yielding iodo-substituted diaryl ethers with yields up to 94%. Our findings highlight the synthetic potential of this previously underexplored compound class in organic transformations.

Novel electron donor-acceptor (EDA) complex promoted arylation of 2-oxo-2H-chromene-3-carbonitriles under visible light irradiation.

An efficient and operationally simple photochemical method has been demonstrated under transition metal-free, photocatalyst-free, and oxidant-free conditions. In recent times, diaryliodonium salts have become one of the most popular arylating sources under photoinduced conditions. Herein, we developed a visible light induced arylation of heterocycles using an EDA complex that is formed in situ from 2,6-lutidine and diaryliodonium triflate. Under light irradiation, the EDA complex generates the aryl radical that undergoes addition with 2-oxo-2H-chromene-3-carbonitriles via an SET process. This method serves as an effective tool to access biologically active and pharmaceutically relevant coumarin scaffolds.

Selective S-arylation of thiols with o-OTf-substituted diaryliodonium salts toward diarylsulfides.

In contrast to the previously reported intramolecular aryl migration, we present the selective sulfenylation of ortho-trifluoromethanesulfonate (OTf) substituted diaryliodonium salts with thiols. As such, diarylsulfides bearing vicinal OTf groups were synthesized in good yields. The unique reactivity of the vicinal OTf group and the sulfur atom in arylsulfides offers further transformations.