Benziodoxole Triflate as a Versatile Reagent for Iodo(III)cyclization of Alkynes

The utility of benziodoxole triflate, derived from α,α‐bis(trifluoromethyl)‐2‐iodobenzyl alcohol, as a versatile reagent for iodo(III)cyclization via electrophilic activation of alkyne, is reported herein. The reagent promotes cyclization of alkynes tethered to a variety of nucleophilic moieties, affording benziodoxole‐appended (hetero)arenes such as benzofurans, benzothiophenes, isocoumarins, indoles, and polyaromatics under mild conditions. This unprecedented class of (hetero)aryl‐I^III compounds proved easy to purify, stable, and amenable to various synthetic transformations.     

Synthesis of Sulfoximidoyl‐Containing Hypervalent Iodine(III) Reagents and Their Use in Transition‐Metal‐Free Sulfoximidations of Alkynes

Well‐defined hypervalent iodine(III) reagents incorporating transferable sulfoximidoyl groups were obtained through ligand exchange reactions of methoxy(tosyloxy)iodobenzene (MTIB) with NH sulfoximines in good to excellent yields. The solid‐state structure of a representative product was characterized by X‐ray crystallography. Utilizing these reagents in synthesis provides a new, transition‐metal‐free approach towards N‐alkynylated sulfoximines.     

Indole Synthesis through Sequential Electrophilic N−H and C−H Bond Activation Using Iodine(III) Reactivity

An intramolecular approach towards the regioselective construction of 2,3‐diarylated indoles is reported. The reaction follows an intramolecular electrophilic N?H and C?H bond functionalization between the aniline and acetylene. This methodology employs the concept of a traceless tether to provide access to the free 2,3‐diarylated indole products comprising a total of 18 examples. Hypervalent iodine reagents were identified as suitable promoters and four different protocols are provided, including stoichiometric and catalytic transformations.     

Reactivity of Hydroxy‐ and Aquo(hydroxy)‐λ3‐iodane–Crown Ether Complexes

We have designed a series of hydroxy(aryl)‐λ³‐iodane–[18]crown‐6 complexes, prepared from the corresponding iodosylbenzene derivatives and superacids in the presence of [18]crown‐6, and have investigated their reactivities in aqueous media. These activated iodosylbenzene monomers are all non‐hygroscopic shelf‐storable reagents, but they maintain high oxidizing ability in water. The complexes are effective for the oxidation of phenols, sulfides, olefins, silyl enol ethers, and alkyl(trifluoro)borates under mild conditions. Furthermore, hydroxy‐λ³‐iodane–[18]crown‐6 complexes serve as efficient progenitors for the synthesis of diaryl‐, vinyl‐, and alkynyl‐λ³‐iodanes in water. Other less polar organic solvents, such as methanol, acetonitrile, and dichloromethane, are also usable in some cases.     

Hypervalent‐Iodine(III)‐Mediated Oxidative Methodology for the Synthesis of Fused Triazoles

The organic chemistry of hypervalent organoiodine compounds has been an area of unprecedented development. This surge in interest in the use of hypervalent iodine compounds has mainly been owing to their highly selective oxidizing properties, environmentally benign character and commercial availability. Hypervalent iodine reagents have also been used as an alternative to toxic heavy metals, owing to their low toxicity and ease of handling. Hypervalent organoiodine(III) reagents are versatile oxidants that have been successfully employed to extend the scope of selective oxidative transformations of complex organic molecules in synthetic chemistry. This Focus Review concerns the tandem in situ generation and 1,5‐electrocyclization of N‐heteroaryl nitrilimines into fused triazoles. We describe the importance of recently developed hypervalent‐organoiodine(III)‐catalyzed oxidative cyclization reactions, building towards the conclusion that hypervalent iodine chemistry is a promising frontier for oxidative cyclization, in particular of hydrazones, for the synthesis of fused triazoles.     

Highly Efficient Method for Synthesis of Benzoquinones Using Hypervalent Iodine(III) Reagent and Sodium Bisulfate

A rapid, one-step, novel approach for the conversion of benzamides into benzoquinones using (diacetoxyiodo)benzene(III) and sodium bisulfate has been developed in aqueous acetonitrile at room temperature. The developed protocol is applicable to several types of substituted benzamide derivatives to get the corresponding benzoquinone products. The developed methodology offers mild reaction condition, short reaction time, and moderate to excellent yields. This is one of the most simple and environmentally benign protocols for synthesis of benzamide derivatives.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Mechanistic Insights on the Iodine(III)‐Mediated α‐Oxidation of Ketones

The synthesis of α‐substituted carbonyl compounds is of great importance due to their ubiquity in both natural and man‐made biologically active compounds. The field of hypervalent iodine chemistry has been a great contributor to access these molecules. For example, the α‐oxidation of carbonyl compounds has been one of the most investigated iodine(III)‐mediated stereoselective transformations. Yet, it is also the transformation that has met the most challenge in terms of achieving high stereoselectivities. The different mechanistic pathways of the iodine(III)‐mediated α‐tosyloxylation of ketones have been investigated. The calculations suggest an unprecedented iodine(III)‐promoted enolization process. Indications that iodonium intermediates could serve as proficient Lewis acids are reported. This concept could have broad impact and foster new developments in the field of hypervalent iodine chemistry.     

Intramolecular Aryl Migration of Diaryliodonium Salts: Access to ortho‐Iodo Diaryl Ethers

By using vicinal trifluoromethanesulfonate‐substituted diaryliodonium salts, a novel approach was developed for the synthesis of ortho‐iodo diaryl ethers by intramolecular aryl migration. The reaction conditions are mild with a broad substrate scope. Mechanistic insight suggests a sulfonyl‐directed nucleophilic aromatic substitution pathway. Additionally, the product ortho‐iodo diaryl ethers serve as versatile synthons as demonstrated with several coupling reactions. Furthermore, a useful thyroxine analogue of the 3‐iodo‐l ‐thyronine (3‐T₁) derivative was synthesized by this aryl migration procedure.     

X-Ray and NMR Structural Data of Ethynylbenziodoxolones (EBXs) Reagents and Their Analogues

First synthesized in 1991, EthynylBenziodoXolones (EBXs) – cyclic hypervalent iodine reagents derived from 2-iodobenzoic acid – are now among the most versatile electrophilic alkynylation reagents. Due to their cyclic structure, these reagents exhibit enhanced stability compared to previously used alkynyl iodonium salts. Over the last decade, both the iodoheterocycle and the arene ring have been extensively modified to fine-tune the reactivity of the reagents, resulting in new analogues such as Ethynylbenziodoxoles (EBxs) or N-heterocyclic reagents. In this article, we have for the first time compiled the structural data available for EBXs and their analogues, focusing especially on X-Ray and NMR data. For selected compounds, molecular electrostatic potentials (MEP) have also been calculated. When considering the tight relationship between structure and reactivity in hypervalent iodine reagents, the collected data is expected to be highly useful for further developments in the field.     

Sunlight‐Driven Decarboxylative Alkynylation of α‐Keto Acids with Bromoacetylenes by Hypervalent Iodine Reagent Catalysis: A Facile Approach to Ynones

A novel and practical decarboxylative alkynylation of α‐keto acids with bromoacetylenes is catalyzed by hypervalent iodine(III) reagents when irradiation by sunlight at room temperature. The product ynones are generated in good yields. Experiments show that results obtained with blue light (λ=450–455 nm) are comparable to those obtained when using sunlight. Mechanistic studies demonstrate that the sunlight‐driven decarboxylation undergoes a radical process.     

Potassium N‐Iodo p‐Toluenesulfonamide (TsNIK,Iodamine‐T): A New Reagent for the Oxidation of Hydrazones to Diazo Compounds

A new reagent for the oxidation of hydrazones to diazo compounds is described. N‐Iodo p‐toluenesulfonamide (TsNIK, iodamine‐T) allows the preparation of α‐diazoesters, α‐diazoamides, α‐diazoketones and α‐diazophosphonates in good yield and in high purity after a simple extractive work‐up. α‐Diazoesters were also obtained in high yield from the corresponding ketones through a one‐pot process of hydrazone formation/oxidation.     

Fluorocyclisation of Oximes to Isoxazolines Through I(I)/I(III) Catalysis

A regioselective fluorocyclisation of β,γ-unsaturated oximes through I(I)/I(III) catalysis is disclosed to generate 5-fluoromethylated isoxazolines. The transformation leverages p-iodotoluene as an inexpensive catalyst, Selectfluor® as the terminal oxidant and an amine⋅HF complex (1 : 7.5) as both the fluoride and Brønsted acid source. The λ³-iodane p-TolIF₂, which is generated in situ, engages the pendant alkene of the substrate to facilitate a cyclisation/fluorination sequence. A range of 5-fluoromethyl isoxazolines can be generated using this method, including aliphatic and aromatic systems (up to 56 % yield). Single crystal X-ray analysis of a representative example reveals a conformation that is consistent with the stereoelectronic gauche effect between the exocyclic C(sp³)−F bond and the C(sp³)−O of the isoxazoline (ϕ_OCCF=−62.0°).     

Sterically Congested 2,6‐Disubstituted Anilines from Direct C−N Bond Formation at an Iodine(III) Center

2,6‐Disubstituted anilines are readily prepared from the direct reaction between amides and diaryliodonium salts. As demonstrated for 24 different examples, the reaction is of unusually broad scope with respect to the sterically congested arene and the nitrogen source, occurs without the requirement for any additional promoter, and proceeds through a direct reductive elimination at the iodine(III) center. The efficiency of the coupling procedure is further demonstrated within the short synthesis of a chemerin binding inhibitor.     

Highly Efficient Method for Synthesis of Bis(Indolyl)Methanes Catalyzed by FeCl3−based Ionic Liquid

A simple and highly efficient green protocol for synthesis of bis(indolyl)methanes was carried out by the reaction of indole with aldehydes and ketones in the presence of FeCl_3?based ionic liquid. These liquids serve as efficient media as well as Lewis acid catalysts.     

Me3Si−SiMe2[oCON(iPr)2−C6H4]: An Unsymmetrical Disilane Reagent for Regio‐ and Stereoselective Bis‐Silylation of Alkynes

The air‐stable unsymmetrical disilane Me₃Si?SiMe₂[oCON(iPr)₂C₆H₄] has been developed for bis‐silylation of alkynes. This reagent tolerates a range of functional groups, providing Z‐vinyl disilanes in high yields. It is proposed that the phenyl‐ring‐tethered amide group directs oxidative addition of Pd⁰ into the Si?Si bond, which might facilitate formation of a six‐membered Pd cycle, generating products with good to excellent regioselectivity.