Hypervalent Iodine Compounds Research Articles

Merging the Reactivity of (Pseudo)cyclic Hypervalent Iodine Reagents and Carbenes or Carbenoids

AbstractIn this short review, we present applications merging the reactivity of cyclic hypervalent iodine reagents with carbenes and carbenoids developed in the period 2014–2024. The use of more stable cyclic hypervalent iodine reagents has led to major advances in this area. The combination of iodine(III) chemistry with carbenes or carbenoids enables new disconnections that are not possible using classical reactivity. Both the use of hypervalent iodine compounds as partners in reactions with metal carbenes and as reagents combining the reactivity of iodine(III) and carbenes in a single molecule to give carbyne equivalents are discussed in this review.1 Introduction2 Transfer of Fluorinated Groups (F, CF3)3 Oxy- and Aminoalkyn(en)ylation3.1 Oxy- and Aminoalkynylation with Acceptor-Substituted Diazo Compounds3.2 Oxyalkenylation with Acceptor-Substituted Diazo Compounds3.3 Oxyalkynylation with Acceptor-Acceptor-Substituted Diazo Compounds4 Carbyne Equivalents4.1 Diazo-Based Reagents4.2 Sulfur Ylide Based Reagents5 Conclusion

Oxidative Remote Aryl Rearrangement of N-Cinnamyl-N-alkoxybenzyl Sulfonamides Using Hypervalent Iodine(III).

An oxidative remote aryl rearrangement of N-cinnamyl-N-alkoxybenzyl sulfonamides with a hypervalent iodine(III) compound was developed to furnish 5,6-disubstituted 1,3-oxazinanes in high yields. This reaction proceeded through the dearomatization of the alkoxybenzene ring on the benzyl group, which acts as a good aryl donor, inducing the regioselective installation of the aryl group and the oxygen atom via cascade transformation. An enantioselective oxidative remote aryl rearrangement using C2-symmetrical chiral iodoarene gave enantioenriched products with high enantioselectivity.

Recent Applications of Sulfonium Salts in Synthesis and Catalysis.

The use of sulfonium salts in organic synthesis has experienced a dramatic increase during the last years that can arguably be attributed to three main factors; the development of more direct and efficient synthetic methods that make easily available sulfonium reagents of a wide structural variety, their intrinsic thermal stability, which facilitates their structural modification, handling and purification even on large scale, and the recognition that their reactivity resembles that of hypervalent iodine compounds and therefore, they can be used as replacement of such reagents for most of their uses. This renewed interest has led to the improvement of already existing reactions, as well as to the discovery of unprecedented transformations; in particular, by the implementation of photocatalytic protocols. This review aims to summarize the most recent advancements on the area focusing on the work published during and after 2020. The scope of the methods developed will be highlighted and their limitations critically evaluated.

Recent Progress in Synthetic Applications of Hypervalent Iodine(III) Reagents.

Hypervalent iodine(III) compounds have found wide application in modern organic chemistry as environmentally friendly reagents and catalysts. Hypervalent iodine reagents are commonly used in synthetically important halogenations, oxidations, aminations, heterocyclizations, and various oxidative functionalizations of organic substrates. Iodonium salts are important arylating reagents, while iodonium ylides and imides are excellent carbene and nitrene precursors. Various derivatives of benziodoxoles, such as azidobenziodoxoles, trifluoromethylbenziodoxoles, alkynylbenziodoxoles, and alkenylbenziodoxoles have found wide application as group transfer reagents in the presence of transition metal catalysts, under metal-free conditions, or using photocatalysts under photoirradiation conditions. Development of hypervalent iodine catalytic systems and discovery of highly enantioselective reactions using chiral hypervalent iodine compounds represent a particularly important recent achievement in the field of hypervalent iodine chemistry. Chemical transformations promoted by hypervalent iodine in many cases are unique and cannot be performed by using any other common, non-iodine-based reagent. This review covers literature published mainly in the last 7-8 years, between 2016 and 2024.

Visible-Light-Mediated Ring-Opening Geminal Dibromination of Alkenes via Alkoxy Radicals Enabled by Electron Donor-Acceptor Complex.

An electron donor-acceptor complex was utilized to generate alkoxy radicals from alcohols under mild conditions using visible light. This approach was combined with a hydroxybromination process to achieve the deconstructive functionalization of alkenes, leading to the production of geminal dibromides. Mechanistic investigations indicated the intermediacy of hypervalent iodine (III) compounds.

Advancing carbohydrate functionality: The role of hypervalent iodine

Hypervalent iodine reagents have undergone significant development and widespread application in the functionalization of carbohydrates. This is primarily attributed to their exceptional properties, including mildness, ease of handling, high selectivity, environmental friendliness, and stability. This review aims to emphasize the utilization of hypervalent iodine compounds in the functionalization of carbohydrates. The present article covers various aspects, including glycal functionalization, C–H or N–H insertion reactions, O-arylations, C-2 deoxy-2-iodo glycoconjugates, iminosugars, and C3-oxo-glycals, achieved through the use of hypervalent iodine reagents/catalysts. Additionally, it explores hypervalent iodine-mediated bioactive 1,3,5-trioxocane synthesis followed by rare sugars synthesis.

Hypervalent Sulfur Derivatives as Sulfenylating Reagents: Visible-Light-Mediated Direct Thiolation of Activated C(sp2)-H Bonds with Dihalosulfuranes.

In contrast to hypervalent iodine compounds, the chemistry of their sulfur analogues has been considerably less explored. Herein, we report the direct C-H bond thiolation of electron-rich heterocycles, arenes, and 1,3-dicarbonyls by dichlorosulfuranes under mild conditions. Mechanistic studies and density functional theory calculations suggest the radical chain mechanism of the disclosed transformation. The key to success is attributed to a strikingly low S-Cl bond dissociation energy, which enables the generation of radical species upon exposure to daylight.

Hypervalent Iodine Compounds in Carbohydrate Chemistry: Glycosylation, Functionalization and Oxidation.

This mini review article provides an overview on the use of hypervalent iodine compounds (HICs) in carbohydrate synthesis, focusing on their chemistry and recent applications. HICs are similar to transition metals in their reactivity but have the added benefit of being environmentally benign, and are therefore commonly used as selective oxidants and eco-friendly reagents in organic synthesis. Herein, we summarize various synthetic uses of hypervalent iodine reagents in reactions such as glycosylation, oxidations, functionalization, and C-C bond-forming reactions. The goal of this review is to illustrate the advantages and versatility of using HICs as an environmentally sustainable alternative to heavy metals in carbohydrate chemistry.

Phenyliodine bis(trifluoroacetate) as a sustainable reagent: exploring its significance in organic synthesis.

Iodine-containing molecules, especially hypervalent iodine compounds, have gained significant attention in organic synthesis. They are valuable and sustainable reagents, leading to a remarkable surge in their use for chemical transformations. One such hypervalent iodine compound, phenyliodine bis(trifluoroacetate)/bis(trifluoroacetoxy)iodobenzene, commonly referred to as PIFA, has emerged as a prominent candidate due to its attributes of facile manipulation, moderate reactivity, low toxicity, and ready availability. PIFA presents an auspicious prospect as a substitute for costly organometallic catalysts and environmentally hazardous oxidants containing heavy metals. PIFA exhibits remarkable catalytic activity, facilitating an array of consequential organic reactions, including sulfenylation, alkylarylation, oxidative coupling, cascade reactions, amination, amidation, ring-rearrangement, carboxylation, and numerous others. Over the past decade, the application of PIFA in synthetic chemistry has witnessed substantial growth, necessitating an updated exploration of this field. In this discourse, we present a concise overview of PIFA's applications as a 'green' reagent in the domain of synthetic organic chemistry. A primary objective of this article is to bring to the forefront the scientific community's awareness of the merits associated with adopting PIFA as an environmentally conscientious alternative to heavy metals.

A decade of lessons in the activation of ArIL2 species.

Hypervalent iodine(iii) compounds of the general structure ArIL2 are widely used as oxidizing agents for a variety of applications across both organic and inorganic chemistry. Considerable work has been done on the activation of these compounds by tuning the ligands at the iodine centre. This perspective summarises the work of our and other groups on rectification of historically misidentified iodine(iii) reagents of this class, and the syntheses of activated species. Recent advances focusing on increasing the oxidative capacity of I(iii) moieties using Lewis and Brønsted acids and Lewis bases as well as the activation of halogens with I(iii) are discussed.

A Low-Cost, Safe and Anion-Flexible Method for the Electrosynthesis of Diaryl Iodonium Salts

Hypervalent iodine compounds have been studied extensively in the past. They are considered to be non-toxic and mild oxidants which represent useful alternatives to toxic heavy-metal based reagents.[1] Hypervalent iodine(III) and iodine(V) species such as (diacetoxy)iodobenzene (PIDA) and the Dess-Martin periodinane are commercially available and routinely employed in oxidation reactions.[2] For synthesis of both iodine(III) and iodine(V) species, electrochemical approaches have been developed.[3] The electrochemistry of diaryl iodonium salts (see Figure, compound 3), however, is much less explored. Such compounds are typically employed as versatile arylation reagents.[4] Their conventional synthesis starts from a iodoarene that undergoes a reaction with a chemical oxidizer, followed by subsequent treatment with aryl-boron, aryl-silicon or aryl-tin reagents to yield the diaryl iodonium salt.[4] A more practical approach that does not require activated arenes is based on the use of meta-chloroperbenzoic acid (mCPBA) in presence of a strong acid (e.g. triflic acid) for oxidative C-I coupling.[5] Using electric current as an oxidizer constitutes a further advancement for synthesis of diaryl iodonium salts. In a recent example, the electrolytic transformation of iodoarenes has been carried out in a HFIP-MeCN solvent mixture using excess triflic acid as the supporting electrolyte and anion source, rendering aryliodonium triflates in medium to high yields.[6] However, the dependence on the hazardous and costly HFIP and triflic acid still represents a major limitation. In this work, the development of a cheaper, greener, and acid-free synthesis of diaryl iodonium salts is presented.[7] The method uses MeCN as the sole solvent as well as lithium salts as supporting electrolyte/anion source. Since many lithium salts with weakly coordinating anions are commercially available and well soluble in MeCN, the approach provides flexibility regarding the choice of the anion.[1] a) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016, 116, 3328-3435; b) B. Olofsson, I. Marek, Z. Rappoport, PATAI's Chemistry of Functional Groups, John Wiley & Sons, 2018.[2] a) C. H. Willgerodt, J. Prakt. Chem. 1886, 33, 154-160; b) D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155-4156.[3] a) R. Francke, Curr. Opin. Electrochem. 2019, 15, 83-88; b) R. Francke, Curr. Opin. Electrochem. 2021, 28 [4] E. A. Merritt, B. Olofsson, Angew. Chem. Int. Ed. 2009, 48, 9052-9070.[5] M. Bielawski, M. Zhu, B. Olofsson, Adv. Synth. Catal. 2007, 349, 2610-2618.[6] M. Elsherbini, W. J. Moran, Org. Biomol. Chem. 2021, 19, 4706-4711.[7] A. Scherkus, B. H. Müller, R. Francke, 2023; manuscript in preparation. Figure 1

(Invited) Electrochemical Synthesis of Chelation-Stabilized Organo-Λ 3-Bromanes

The chemistry of hypervalent halogen species has made enormous progress over the last few decades, and hypervalent iodine(III) compounds have become common reagents in nowadays organic synthesis. The related isoelectronic hypervalent bromine(III) species feature superior reactivity to the I(III) counterparts due to the higher oxidizing ability, stronger electrophilicity and better leaving group ability (nucleofugality) of the bromanyl moiety. However, the hypervalent bromine chemistry appears to be significantly less developed than that of the iodine(III) compounds. This notable imbalance appears to be due to the relatively low stability and high oxidizing power of bromine(III) reagents, resulting in reactivity that is difficult to control. Furthermore, there is a clear shortage of simple method for the synthesis of bromine (III) species, but known methods often require handling of the highly toxic and corrosive BrF3 precursor. In this context, we have proposed the electrochemical generation of chelation-stabilized hypervalent bromine(III) compounds as a possible solution to the above problems. This presentation will give an overview of our current progress in this field.

X-ray photoemission and absorption spectroscopy of a hypervalent iodine compound, 2-iodosobenzoic acid

To apply a hypervalent iodine compound, 2-iodosobenzoic acid (IBA), to a protecting group of X-ray activated caged compounds, X-ray photoemission and absorption spectroscopy of IBA were performed. The photoemission spectrum of IBA in the valence band region included a component originating from the π*-like orbitals of I-C and I-O. Such characteristic electronic structures may cause the reactivities of IBA. The linear absorption coefficients of the peaks in the iodine K-edge energy region were 38.8, 40.0, and 39.41 cm−1 at around 33.18, 33.23, and 33.32 keV, respectively. Those contribute to discussing reactions of IBA induced by the iodine K-shell excitations quantitatively.

Electrophilic Alkynylation and Alkenylation Using Alkynyl Hypervalent Iodine Compounds

Electrophilic Alkynylation and Alkenylation Using Alkynyl Hypervalent Iodine Compounds

Stabilization of sp-Hybridized Nitrogen Cation by Lewis Acid-Base Complex Formation with Intramolecular Iodine.

Here we show that the sp-hybridized nitrogen cation is strongly stabilized by a peri-iodine substituent in the tetralone system. The cation is captured by anionic species such as CF3 CO2 - , affording hypervalent iodine(III) compounds with a short nitrogen-iodine (N-I) bond, in which the cation serves as a Lewis acid. Notably, the O-I bond of the O-trifluoroacetate or O-acetate is intrinsically weaker than the N-I bond due to its more ionic character and is further weakened by protonation in trifluoroacetic acid. As a result, the oxygen ligand can dissociate in the presence of a Brønsted acid, affording a I+ cation intermediate that retains the N-I bond. We isolated the cation as the tetrafluoroborate, and characterized it experimentally by 1 H NMR spectroscopy and X-ray structure analysis, and theoretically by means of DFT calculation. The results suggest that the N-I bonded cation is intrinsically stable, and is weakly coordinated with water and the BF4 counter anion or trifluoroacetate anion. This cation can be employed as a reagent for α-oxidation of ketones.

A machine learning approach for predicting the reactivity power of hypervalent iodine compounds

The knowledge of chemical reactivity of substrates is a prerequisite to accurately design a chemical reaction; however, it has been a challenging task due to the slow trial-and-error experimental approaches and the high computational cost associated with in silico investigations. Artificial intelligence techniques could serve as an alternative to efficiently determine the relative reactivity of chemical entities. In the context of this research, we propose an artificial neural network model to predict the bond dissociation energies of hypervalent iodine reagents. An open-source cheminformatics package, namely, Mordred, was employed for calculating various 1D, 2D and topological descriptors. The approach utilizes a dataset of more than 1000 hypervalent iodine reagents, and the bond dissociation energies can be predicted with a remarkable accuracy, as suggested by an R2 score of 0.97 and a mean absolute error of 1.96 kcal/mol. Owing to the low cost and high efficiency, this machine learning approach can provide an alternative to the theoretical/experimental approaches to rationally design a chemical reaction and without having to go through the hassle of high-throughput experimentation to reach the desired reaction outcome. In an effort to make the model interpretable, a feature importance algorithm was applied, which identified descriptors contributing most to the development of the model. Features describing electronegativity and polarizability are some of the important contributors to the model’s training.

Decomposition characteristics of a hypervalent iodine compound, 2-iodosobenzoic acid, exposed to monochromatic X-rays around the iodine L3-edge energy region

In clinical settings, the development of novel X-ray-activated caged compounds has been described as a key factor in both therapeutic and diagnostic applications to halt the action of specific medication, i.e., reactivation by external X-ray irradiation causing site-selective bond breakages, during delivery to target organs. In this work, we focused on a hypervalent iodine compound, namely 2-iodosobenzoic acid (IBA), as a candidate for the protecting group of X-ray-activated caged compounds, and investigated the decomposition reactions of IBA induced by X-ray irradiations around the iodine L3-edge energy region. Our results showed that X-irradiations induced bond breakages around the hypervalent iodine atom, and the associated decomposition rate was dependent on the irradiated X-ray photon energy. Particularly, X-ray absorption spectral changes and desorbed molecular fragments confirmed a significant molecular decomposition induced by one of the iodine L-shell excitations. Our findings suggest that the hypervalent iodine compound could be a very promising candidate for the design of novel X-ray-activated caged compounds.

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control.

Halogen bonding is commonly found with iodine-containing molecules, and it arises when Lewis bases interact with iodine's σ-holes. Halogen bonding and σ-holes have been encountered in numerous monovalent and hypervalent iodine-containing compounds, and in 2022 σ-holes were computationally confirmed and quantified in the iodonium ylide subset of hypervalent iodine compounds. In light of this new discovery, this article provides an overview of the reactions of iodonium ylides in which halogen bonding has been invoked. Herein, we summarize key discoveries and mechanistic proposals from the early iodonium ylide literature that invoked halogen bonding-type mechanisms, as well as recent reports of reactions between iodonium ylides and Lewis basic nucleophiles in which halogen bonding has been specifically invoked. The reactions discussed herein are organized to enable the reader to build an understanding of how halogen bonding might impact yield and chemoselectivity outcomes in reactions of iodonium ylides. Areas of focus include nucleophile σ-hole selectivity, and how ylide structural modifications and intramolecular halogen bonding (e.g., the ortho-effect) can improve ylide stability or solubility, and alter reaction outcomes.

Cover Feature: Reactivity of Hypervalent Iodine(III) Reagents Bearing Transferable N‐Based Groups (Eur. J. Org. Chem. 25/2023)

The Cover Feature illustrates the potential and versatility of hypervalent iodine(III) compounds as the root of several methodologies that enable the introduction of nitrogen-based functional groups. The use of hypervalent iodine(III) compounds translates into a robust alternative to established synthetic methodologies. This review focuses on the latest results in the electrophilic transfer of nitrogen-containing functional groups. More information can be found in the Review by M. M. B. Marques et al.

Reactivity of Hypervalent Iodine(III) Reagents Bearing Transferable N‐Based Groups

AbstractHypervalent iodine reagents have the ability of inverting the polarity of functional groups bound to iodine, a reactivity known as umpolung. This reactivity makes hypervalent iodine compounds highly attractive for the creation of electrophilic synthons of known nucleophiles, resulting in novel synthetic disconnections and the formation of new Nu(nucleophile)−N bond.Electrophilic sources of nitrogen‐based groups have been known for many decades and are of great synthetic importance. Traditionally, these reagents are limited to few examples. With the use of hypervalent iodine, the transfer of a wide diversity of nitrogen sources became a possibility. This review compiles the latest reported examples of hypervalent iodine reagents capable of electrophilic transfer of nitrogen‐based groups. It showcases the preparation of such reagents, their synthetic utility, and reaction mechanisms involving these group transfer reagents.