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

Abstract

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.

1. Introduction

Compounds of polyvalent iodine, commonly known as hypervalent iodine reagents, have found wide application in modern organic synthesis as reagents and catalysts. Many features of hypervalent iodine chemistry are similar to the transition metals chemistry, and further exploration of these similarities has led to the creation of new reagents and important synthetic methodologies.¹ In contrast to heavy transition metals, iodine is an environmentally friendly and a relatively inexpensive element (according to the U.S. Geological Survey bulk average price of iodine in the United States from 2017 to 2023 was between $19 and $61 per kilogram, see https://www.statista.com/statistics/1001991/average-price-iodine-us/). Many “metal-free” synthetic applications of hypervalent iodine chemistry are based on the unique oxidizing properties and commercial availability of polyvalent iodine compounds. Compounds of hypervalent iodine are widely utilized in synthetically important oxidations, halogenations, aminations, and many other oxidative transformations of organic substrates. Iodonium salts are important arylating reagents, and iodonium ylides and imides are excellent carbene and nitrene precursors. Particularly important are derivatives of benziodoxoles, such as trifluoromethylbenziodoxoles, alkynylbenziodoxoles, alkenylbenziodoxoles, and azidobenziodoxoles, which are used as group transfer reagents under metal-free conditions, or under transition metal catalysis, or using photocatalysts under photoirradiation conditions. It is important to emphasize that in many cases the reactions of hypervalent iodine compounds are unique and cannot be performed by using any other common, non-iodine-based reagent.

The important role of polyvalent iodine in modern chemistry is confirmed by a large number of recently published books and reviews covering several hot areas of hypervalent iodine chemistry. Just in the last 6 years, between 2016 and 2023, three books²⁻⁴ and over a hundred major reviews covering different areas of hypervalent iodine chemistry have been published.⁵⁻¹³¹ Several newly developed synthetic methodologies are based on the similarities between chemistry of hypervalent iodine and the chemistry of transition metals. In particular, hypervalent iodine(III) reagents and catalysts can effectively promote numerous coupling reactions, leading to the formation of new carbon–carbon and carbon–element bonds.¹³² The use of hypervalent iodine(III) compounds for the creation of new carbon–carbon bonds was summarized in several reviews.^74,79,80,133 Numerous recent reviews were dedicated to the reactions of hypervalent iodine compounds, resulting in the formation of new carbon–nitrogen bonds.^{8,15,44,55,75,81−85,134} Construction of C–O,¹³⁵ C–S, and C–Se bonds mediated by hypervalent iodine reagents under metal-free conditions was also reviewed.¹³⁶ Development of enantioselective catalytic systems based on the unique redox and photoredox properties of iodine(III) has been an important direction in the field of hypervalent iodine chemistry summarized in numerous specialized reviews.^{12,26,28,40,41,43,45,53,65,93−95,137,138}

Application of hypervalent iodine reagents in organic synthesis has been an active area of research.¹³⁹ Numerous recent reviews were dedicated to applications of hypervalent iodine in the following reactions: functionalization of alkenes,^117,118,140 direct C–H bond functionalization,^10,66,141 chlorinations and fluorinations,^{30,69,72,86,87,142−145} phenolic dearomatization reactions,^{47,56,63,121,122,146} rearrangements promoted by hypervalent iodine,^{25,67,123,147,148} synthesis of spiroheterocycles,¹¹⁹ applications of hypervalent iodine(III) reagents in organophosphorus chemistry,¹²⁴ reactions of hypervalent iodine with boronic compounds,¹⁴⁹ reactions of hypervalent iodine with enol and ynol surrogates,¹⁵⁰ hypervalent iodine compounds in transition metal chemistry,^21,125 copper-catalyzed hypervalent iodine-mediated functionalization of unactivated compounds,¹⁵¹ palladium-catalyzed organic reactions involving hypervalent iodine reagents,¹⁵² organocatalytic group transfer from hypervalent iodine species,¹²⁰ glycosylation reactions,^153,154 functionalization of carbohydrates,¹³¹ tandem reactions that allow for incorporating the aryl motif into the products through a subsequent one-pot nucleophilic addition or catalytic coupling reaction,¹⁵⁵ and late-stage peptide and protein functionalization.²² Iodine(III) compounds are commonly utilized for the preparation of various heterocycles via oxidative formation of C–C, C–O, C–N, C–S, N–O, N–N, or N–S bonds.^{24,48,50,62,68,70,73,88−91,116,156−158} Hypervalent iodine reagents are broadly used in total synthesis of natural products.^{11,42,58,61,92,159}

Numerous reviews have summarized recent synthetic applications of different classes of polyvalent iodine compounds. In particular, aryliodonium salts are important arylating reagents^{6,32,60,96−101,160−167} and precursors for Positron Emission Tomography.^102,168 Iodonium ylides are used as carbene precursors and also as reagents for radiofluorination.^103,104,169 (Diacetoxyiodo)benzene is an important reagent with various synthetic applications.¹⁷⁰ Numerous recent reviews were dedicated to the application of group-transfer benziodoxole-based reagents.^{7,105−107,109,171} Trifluoromethylbenziodoxoles are important trifluoromethylating reagents.^27,108 Azidobenziodoxoles are exceptionally effective reagents for direct azidation of C–H bonds.^5,19,111 Ethynylbenziodoxoles and vinylbenziodoxoles are useful alkynylating and alkenylating reagents.^{13,110,130,172} Weiss’ reagent, [PhI(Pyr)₂]²⁺ 2TfO^–, is a synthetically useful oxidizing reagent.¹⁷³ Radical and photochemical reactions of benziodoxole derivatives is a hot area of modern hypervalent iodine chemistry.^{14,112,113,174} Applications of in situ generated hypervalent iodine reagents in organic synthesis have recently been reviewed.¹⁷⁵

Synthetic applications of several new classes of hypervalent iodine compounds have recently been reviewed, such as pseudocyclic hypervalent iodine reagents,¹¹⁴ benziodoxole sulfonates,^51,78 water-soluble hypervalent iodine reagents and their reactions in aqueous medium,^115,176,177 and recyclable hypervalent iodine reagents.²⁰

New methods for generating derivatives of polyvalent iodine using green chemistry methods were recently reviewed. The anodic oxidation of aryl iodides provides an efficient approach to hypervalent iodine derivatives. Electrochemically generated hypervalent iodine species have been utilized as in-cell or ex-cell mediators for valuable fluorinations and oxidative transformations.^{36,37,126,178−181} Another environmentally sustainable procedure, the aerobic preparation of hypervalent iodine reagents, is based on the oxidation of iodoarenes by the reactive intermediates generated during autoxidation of aldehydes.¹²⁷

Iodonium salts have found some industrial application as initiators of polymerization.^46,128,129 Hypervalent organic polyiodides are used in disinfectants, polarizing films, dye-sensitized solar cells, and precursors to low-density graphitic films.¹⁸² It can be expected that the interest in industrial applications of hypervalent iodine compounds will grow in the future.

The present review provides an update of our 2016 comprehensive review.¹⁸³ The review is limited to synthetic applications of iodine(III) reagents excluding the chemistry of iodine(V). Recent publications in the area of iodine(V) chemistry are mainly represented by numerous papers on routine oxidations of alcohol groups in complex molecules by Dess-Martin periodinate or 2-iodoxybenzoic acid, which is a traditional and well-reviewed area of organic synthesis.^29,31,57,184 Our present review covers literature on organoiodine(III) compounds published mainly in the last 5–7 years, through spring 2024.

2. Structure and Reactivity of Hypervalent Iodine(III) Compounds

Because of the large size of the iodine atom, the bonding in compounds of polyvalent iodine is different from the light main-group elements. Computational studies indicate that the typical light p-block elements double bonds formed by the interatomic π-bonding do not exist in the derivatives of polyvalent iodine.¹⁸⁵ Structure and reactivity of polyvalent iodine compounds is usually explained by the presence of a hypervalent bond, a linear, three-center-four-electron bond L—I—L formed by the overlap of the 5p orbital on iodine atom with the orbitals on the ligands L. Hypervalent bond is highly polarized, longer, and weaker compared to a regular covalent bond, resulting in special structural features and reactivity typical of the derivatives of polyvalent iodine. Reactions of hypervalent iodine compounds are commonly discussed in terms of oxidative addition, ligand exchange, reductive elimination, and ligand coupling, which are typical of the transition metal chemistry.¹⁻³ General aspects of structure and reactivity of hypervalent iodine compounds have been discussed in our 2016 review.¹⁸³ In summary, the iodine(III) organic derivatives ArIX₂ have trigonal bipyramidal geometry with electronegative ligands X in the axial positions, and the aryl substituent and two unshared electronic pairs occupying the equatorial positions. Iodonium salts R₂IX with inclusion of a weakly bonded anionic part X of the molecule have a similar distorted trigonal bipyramidal structure. The hypervalent I–X bond length in iodine(III) compounds is longer than an average I–X covalent bond length in compounds of monovalent iodine. Bond angles R–I–R in iodonium salts and iodonium ylides, as well as bond angles R–I–N in iodonium imides, are close to 90°.

Several structural studies of hypervalent iodine compounds were recently published. Dutton and co-workers have reported numerous studies on structural verification of several common hypervalent iodine reagents.^186−190 In particular, the structure of Stang’s reagent, PhI(CN)OTf, was confirmed by X-ray crystallography and determined to be best described as an ion-pair in organic solution.¹⁸⁶ The structure of a complex of PhICl₂ with pyridine was established by X-ray, NMR, and theoretical studies.¹⁸⁸ Reinvestigation of the structure of PhI(OTf)₂ has demonstrated the actual identity of the reagent being used was PhI(OTf)(OAc).¹⁹¹ While PhI(OTf)₂ is unstable, the para-nitro-substituted derivative, 4-O₂NC₆H₄I(OTf)₂, was isolated as a stable compound and characterized by X-ray diffraction.¹⁸⁹ The previously proposed molecule of PhIBr₂ was demonstrated to be a mixture of PhI and Br₂ on the basis of spectroscopical and computational studies.¹⁹⁰ Waser and co-workers have reviewed X-ray and NMR structural data of ethynylbenziodoxolones (EBXs) reagents and their analogues.¹⁹²

Reactivity of hypervalent iodine compounds in radical reactions under photochemical conditions was summarized in recent reviews.^14,40 Numerous recent publications were dedicated to the effects of halogen bonding and Lewis acidity on structure and reactivity of hypervalent iodine compounds.^34,193−200

Theoretical studies of the mechanisms of catalytic and stoichiometric iodine-mediated reactions have been discussed in numerous recent publications.^{193,201−220}

3. Acyclic Iodine(III) Compounds as Reagents

3.1. Iodine(III) Compounds with Halide Ligands

3.1.1. (Difluoroiodo)arenes

The chemistry and synthetic applications of hypervalent iodine fluorides have been extensively reviewed previously^221−224 and summarized in numerous recent reviews.^{30,69,72,86,87} Two general methods are known for the synthesis of (difluoroiodo)arenes. The first method involves the fluorination of an iodoarene by a fluorinating reagent or a combination of a common oxidant with a fluoride source. The second method is based on the ligand exchange between a hypervalent iodine compound and a fluoride source. These two approaches have been summarized in numerous previous publications.^225−228 In the following text, several recently published synthetic procedures for converting iodoarenes to the corresponding (difluoroiodo)arenes are described. Gilmour’s group²²⁸ has published an improved procedure for the synthesis of (difluoroiodo)arenes that was originally reported by Shreeve’s group in 2005.^228,229 In the improved procedure, para-iodotoluene is mixed with Selectfluor and CsF as an additional fluoride source to give para-(difluoroiodo)toluene in 62% yield. Using Et₃N·HF instead of CsF improved the yield up to 92% yield; however, Et₃N·HF is a potentially hazardous reagent. Monitoring this reaction by NMR indicated poor conversion after 48 h for iodoarenes with a strong electron-withdrawing groups such as nitro- and trifluoromethyl group, while the conversion was good for iodoarene with electron-donating groups. Murphy’s group reported a large scale procedure for the preparation of para-(difluoroiodo)toluene up to 50 mmol.²²⁶ This procedure involves three steps to prepare para-(difluoroiodo)toluene starting from 4-iodotoluene in 64–72% yield without purification of intermediate products in the first and second steps. Togni’s group developed direct synthesis of (difluoroiodo)arenes from iodoarenes with various electron-withdrawing groups in the ortho-position.²²⁷ It has been noted that the ortho-substituent provides a minor improvement of hydrolytic stability of the obtained (difluoroiodo)arenes and it plays an important role during the reaction with TCICA (trichloroisicyanuric acid) and KF, inhibiting further oxidation of iodine(III) to iodine(V). The reaction of iodoarene 1 and TCICA with KF as the fluoride source affords the corresponding products 2 in good yields (Scheme 1). The authors suggest that the introduction of an electron-withdrawing group at the ortho-position suppresses overoxidation of the produced iodine(III) product to an iodine(V) compound. This methodology provides a mild and efficient approach to electron-deficient (difluoroiodo)arenes and complements the methods of Shreeve’s group²²⁹ and Gilmour’s group²²⁸ which utilize Selectfluor to synthesize electron-rich (difluoroiodo)arenes.

Scheme 1. Preparation of (Difluoroiodo)arenes 2 with Ortho Substitution.

In 2022, Zhang and co-workers reported a one-step synthesis of (difluoroiodo)arenes using silver difluoride (AgF₂) as fluorinating reagent.²²⁵ The reaction of iodoarene 3 with AgF₂ is carried out by stirring at room temperature for 1 h to give (difluoroiodo)arenes 4 in good yileds (Scheme 2). In the reaction of 2,4,6-trimethyliodobenzene, slight heating was necessary to give the respective product in 82% yield. A moderately unstable product 4 with methoxy group in the para-position was obtained in 79% yield.

Scheme 2. Preparation of (Difluoroiodo)arenes 4 Using AgF₂.

(Difluoroiodo)arenes can participate in ligand exchange reactions to produce the corresponding products.^230−232 Dutton and co-workers used the ligand exchange reaction between p-NO₂C₆H₄IF₂5 and TMSOTf to synthesize p-NO₂C₆H₄IF(OTf) 6 (Scheme 3), the structure of which was characterized by X-ray crystallography.²³⁰ Previously, the formation of PhIF(OTf) in situ from iodobenzene and xenon fluorotriflate −78 °C was proposed by Stang, Zefirov, and co-workers without any structural proof based on the formation of iodonium salts in the reactions with alkynes.²³³ Dutton and co-workers have found that the presence of the nitro group stabilizes compound 6 by preventing degradation via an electrophilic aromatic substitution pathway observed in previous studies of ArI(OTf)₂ species.¹⁸⁹ The authors also found that compound 6 reacts with anisole and toluene to give the corresponding diaryiodonium triflates, but it does not react with bromobenzene.

Scheme 3. Preparation of p-NO₂C₆H₄IF(OTf) 6.

Bolm and co-workers have reported that p-TolIF₂ reacts with NH-sulfoximines, leading to the formation of unstable ligand exchange species as confirmed by ¹H NMR, ¹⁹F NMR, and ESI-MS.²³² These species were utilized in situ in subsequent reactions with alkenes. The reaction of p-TolIF₂7 with various NH-sulfoximines 8 and styrenes 9 under Blue-LED with Ru photoredox catalyst gave the corresponding fluoro sulfoximination products 10 in moderate to good yields (Scheme 4). The same authors also reported that when the active species generated by ligand exchange between p-TolIF₂7 and NH-sulfoximine 8 were stirred in dichloromethane or dibromomethane under Blue-LED without Ru photoredox catalyst conditions, the corresponding chlorinated or brominated products instead of the fluorinated products 10 were formed.²³¹ A radical mechanism was proposed for these reactions because the products were not formed under dark conditions or in the presence of the radical scavenger such as TEMPO or BHT.

Scheme 4. Fluoro Sulfoximidations of Styrenes 9.

As a useful fluorination reagent, p-TolIF₂7 has been used in direct mono- and difluorination reactions of various substrates.^87,183 As a recent example, Balz-Scheimann fluorination of aromatic diazonium salts with p-TolIF₂7 in the presence of BF₃·Et₂O has been reported by Hu and co-workers.²³⁴ Murphy’s group developed a denitrogenative hydrogen-fluorination of benzaldehyde hydrazine derivatives with electron-withdrawing group.²³⁵ The same research group has demonstrated that the reaction of p-TolIF₂7 with diaryl- or dialkyl phosphine oxides 11 leads to the corresponding phosphate fluorides 12 (Scheme 5),²³⁶ and the reaction with some substrates yields phosphinic acid as a by-product. In the reaction with diethylphosphite, the desired product was obtained in only 34% yield. Although some products 12 are unstable, they can be effectively converted to stable phosphinate esters by treatment with ethanol and isolated. The authors proposed a reaction mechanism involving initial nucleophilic addition of phosphine 13 to the electrophilic iodane 7, forming phosphonium adduct 14. Subsequent nucleophilic attack by fluoride anion on the phosphonium atom in adduct 14 gives intermediate 15, whose deprotonation affords the final phosphoric fluoride 12 (Scheme 6).

Scheme 5. Preparation of Phosphate Fluorides 12.

Scheme 6. Proposed Reaction Mechanism of Fluorination of Phosphine Oxide 11.

Monofluorination reactions using ArIF₂ in situ, in which a fluoride source is added to iodosylbenzene, DIB, or PIFA to form ArIF₂ in the reaction system, are also known.^237,238 Xu and Tang reported that the reaction of alkylsilanes 16 with iodosylbenzene 17 using two fluoride sources, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone hydrofluoride (DMPU·HF) and CsF, gave the corresponding alkyl fluorides 18 (Scheme 7).²³⁸ Using this procedure, a variety of primary alkylsilanes 16 bearing electron-donating or electron-withdrawing substituents in aromatic ring and not-aryl-substituted alkylsilanes 16 were converted to products 18 in good yields. In the reactions of secondary alkylsilanes no products 18 were observed, and the major by-products were alkenes and ketones. The reaction could be carried out on the gram scale. For the mechanism, the results of a radical clock reaction and the addition of TEMPO indicate that radical species are involved. In the presence of CsF and DMPU·HF, PhIF₂ is generated from alkylsilane and PhIO with organopentafluorosilicate as the by-product.

Scheme 7. Fluorination Reaction of Alkylsilanes 16.

Substrates bearing diazo or benzaldehyde hydrazone moiety react with p-TolIF₂7, producing products of difluorination.^239−241 For example, Murphy and co-workers demonstrated that the reaction of benzaldehyde hydrazone 19 with p-TolIF₂7 and a catalytic amount of TiF₃ yields the corresponding gem-difluorides 20 in moderate yields (Scheme 8).²³⁹ In the reaction without TiF₃, the monofluoride is the main product due to insufficient activation of 7. In this reaction, starting compounds 19 react with reagent 7 to form diazo species as the reaction intermediate, which was confirmed by ¹H NMR.

Scheme 8. gem-Difluorination Reaction of Hydrazones 19.

It has been reported that the reaction of aryl-substituted allenes 21 with p-TolIF₂7 in the presence of a catalytic amount of BF₃ yields α-(difluoromethyl)styrenes 22 via 1,2-aryl group shift (Scheme 9).²⁴² The reactions of para-substituted substrates 21 work best, while the yields of ortho- and meta-substituted derivatives are generally lower. The reaction also proceeds well with allene compounds having an alkyl substituent at the α-position, resulting in the desired products in moderate yields. Futhermore, the reaction was confirmed to proceed under similar conditions for 1-naphthyl and 2-naphthylallenes. To identify which double bond of the allene is involved in this reaction, the authors tested the allene compound with deuterated terminal hydrogens and found that this reaction produced α-difluoromethylstyrene with deuterated hydrogens at the β-position. This result confirmed that no terminal double bond was involved in this reaction. When exocyclic allenes are used as substrates, the ring expansion reaction proceeds and the cyclic products are obtained in moderate yields.²⁴³

Scheme 9. Preparation of α-(Difluoromethyl)styrenes 22.

The synthesis of difluorinated compounds from styrenes via 1,2-phenyl group shift reaction using (difluoroiodo)benzene generated by adding a fluoride source to DIB or PhIO was also reported.²⁴⁴ For example, Wang and co-workers reported that the reaction of aryl-substituted alkenyl N-methyliminodiacetyl (MIDA) boronates 23 with DIB 24 and HF·Py gave β-difluorinated alkylborons 25 in low to good yields (Scheme 10).²⁴⁵ When 1,1-disubstituted alkenyl MIDA boronates were used as substrates, α-difluorinated alkylborons were successfully obtained. The authors prepared a deuterated substrate and based on the analysis of products found that 1,2-aryl shift occurs during the reaction. The proposed reaction mechanism starts from the interaction between the double bond of the substrate 23 and (difluoroiodo)benzene generated from PIDA and Py·HF, leading to regioselective vicinal fluoroiodination intermediate 27 via species 26 (Scheme 11). The observed regioselectivity is explained by the ability of the aryl group to stabilize the developing benzylic carbocation. At the next step, departure of the PhI leaving group affords phenonium ion species 28. Finally, the regioselective fluoride attack results in the ring-opening of 28 forming final products 25.

Scheme 10. Synthesis of β-Difluorinated Alkylborons 25 from Styrenes 23.

Scheme 11. Proposed Mechanism of Formation of Products 25 from Styrenes 23.

Difluorination reactions with alkynes using (difluoroiodo)arene generated in the reaction system were reported by Li’s group.²⁴⁶ They reported that the reaction of aryl alkynylcyclopropanes 29 with pentafluoro(diacetoxyiodo)benzene 30 and an excess amount of HF·Py gave the ring-expanded difluoroalkylidene cyclobutane compounds 31 with (E)-stereoselectivity (Scheme 12). The reaction proceeded efficiently with electron-poor phenyl-substituted alkynylcyclopropanes as substrates but was complicated for the electron-rich aryl-substituted and alkyl-substituted alkynylcyclopropanes, presumably because of the competing oxidation of the substrate under reaction conditions. The proposed mechanism of this reaction involves the initial ligand exchange of compound 30 with HF·Py giving activated iodoarene difluoride 32, which then interacts with the triple bond of substrates 29 to form π-complex 33. At the next step, the regio- and stereoselective fluoride attack on π-complex 33 affords intermediate 34, which undergoes a Wagner–Meerwein-type rearrangement to form cyclobutyl cation 35. Finally, the trapping of this cation by second fluoride leads to stereoselective formation of products 31 (Scheme 13).

Scheme 12. Preparation of Difluorinated Alkylidenecyclobutanes 31.

Scheme 13. Proposed Mechanism of Formation of Difluorinated Alkylidenecyclobutanes 31.

Variuos (difluoroiodo)arenes, ArIF₂, can be generated from the corresponding iodoarenes in situ and further reacted with organic substrates using electrochemical or chemical oxidation in the presence of fluoride anions.^247,248

The McDonald group found that iron(II) complex 36 bearing tris(2-pyridylmethyl)amine react with (difluoroiodo)benzene 37 at room temperature in acetonitrile to form μ-fluorido-diiron(III) complex 38 (Scheme 14).²⁴⁹ The structure of the obtained compound, which is bridged by fluorine atoms, was determined by X-ray structural analysis. Furthermore, the addition of Lewis acid Sc(OTf)₃ to compound 38 resulted in the formation of a monomeric product 39. The same group also found that the reaction of iron(II) complex with tris(2-benzimidazoylmethyl)amine and (difluoroiodo)benzene formed the analogous μ-fluorido-diiron(III) complex.²⁵⁰

Scheme 14. Synthesis of μ-Fluorido-Diiron(III) Complex 38 and Monomeric Product 39.

Liu and co-workers have reported the palladium-catalyzed oxidative fluorocarbonylation of unactivated alkenes 40 using 2,5-(CH₃)₂C₆H₃IF₂41 (Scheme 15).²⁵¹ The reaction is applicable to a variety of alkenes 40, and the addition of MeOH and TMSCHN₂ during the reaction yields the corresponding β-fluoro carboxylic esters 42. When H₂O or amine were used instead of MeOH and TMSCHN₂, β-fluoro carboxylic acids and amides were obtained.

Scheme 15. Fluorocarbonylation of Unactivated Alkenes 40.

Additional recent examples of synthetic applications of (difluoroiodo)arenes include the following works: fluorination of cis-1,4-polyisoprene,²⁵²para-selective benzylation of aryl iodides by the in situ preparation of ArIF₂,²⁴⁷ oxidative fluoroarylation of benzylidenecyclopropanes by in situ generated ArIF₂,²⁵³ and hypervalent iodine-mediated gem-difluorination of vinyl halides by in situ generated ArIF₂.²⁵⁴

3.1.2. (Dichloroiodo)arenes

From an historical point of view, (dichloroiodo)benzene is one of the first reported hypervalent iodine compounds that has been intensively used as a convenient chlorinating reagent for over a century.^221−224 The chemistry and synthetic applications of hypervalent iodine chlorides have recently been reviewed.^30,86 Numerous synthetic approaches have been developed to (dichloroiodo)arenes, which are the oldest known hypervalent iodine compounds with many practical applications.²⁵⁵ The classic general approach to (dichloroiodo)arenes is based on reactions of iodoarenes with chlorine gas or chlorine-derived oxidants.²⁵⁶ Alternatively, (dichloroiodo)arenes can be prepared by ligand exchange reactions of other hypervalent iodine reagents with sources of chloride anion.²⁵⁷ Ligand exchange reactions of (dichloroiodo)arenes leading to other hypervalent iodine reagents are also known.^230,258 In recent years, numerous oxidations or oxidative chlorination reactions of various organic or organometallic substrates with (dichloroiodo)arenes have been reported. Computational studies of several chlorination reactions have also been performed.^211,259

Electrophilic or radical addition or substitution reactions are the most typical reactions of (dichloroiodo)arenes. Chlorinations by substitution reactions have been reported for a variety of aromatic and aliphatic substrates.^{236,260−269} Ibrahim and Adamo reported that the reaction of β-sulfidocarbonyl compounds 43 with a (dichloroiodo)benzene 44 at room temperature for a few minutes afforded the corresponding β-aryl-β-chlorocarbonyl compounds 45 in moderate to good yields (Scheme 16).²⁶⁰ This reaction is also applied to alkylphenyl sulfides as substrates. When (S)-β-sulfidocarbonyl compounds are used as substrates in this reaction, (R)-β-aryl-β-chlorocarbonyl compounds are obtained with high stereoselectivity. Based on this result, the authors suggest that the reaction mechanism starts from the oxidation of sulfur with (dichloroiodo)benzene, followed by an S_N2-like reaction with the chloride anion to afford product 45.

Scheme 16. Reaction of β-Sulfidocarbonyl Compounds 43 with (Dichloroiodo)benzene 44.

Dutton and co-workers reported aromatic chlorination reactions of (dichloroiodo)benzene with arenes in the presence of additives.^{188,270−272} They have found that the addition of pyridine as an additive to (dichloroiodo)benzene 44 gives the corresponding tetracoordinated hypervalent iodine compound 46 (Scheme 17), the structure of which was characterized by X-ray structural analysis.¹⁸⁸ The N–I distance is 2.750 Å, which is longer than the covalent distance of a typical N–I bond. Likewise, when tetrabutylammonium chloride is used as an additive instead of pyridine, similar tetracoordinated hypervalent iodine compounds can be obtained.²⁷¹ This group has also investigated the mechanism of this reaction using NMR and computational chemistry.

Scheme 17. Preparation of Tetracoordinated Hypervalent Iodine Compound 46.

Reactions using (dichloroiodo)arenes to add chlorine to organic substrates have also been reported. Liu and co-workers reported that the reaction of substituted aromatic isonitrile 47 with (dichloroiodo)benzene 44 in acetonitrile proceeded as gem-dichlorination, yielding the corresponding carbonimide dichlorides 48 in moderate to good yields (Scheme 18).²⁷³ In contrast, the reaction with aliphatic isonitrile did not yield the product of gem-dichlorination. The potential synthetic value of carbonimide dichlorides 48 is that these compounds can be used as synthetic intermediates for 2,2,3,3-tetrachloroaziridine, propyl formimidate, and benzophenone imine. The reaction begins with the hypervalent iodine center of 44 attacking the nucleophilic carbon atom of isonitrile 47 to form intermediate 49. Subsequently, intermolecular nucleophilic substitution results in the formation of a C–Cl bond to produce intermediate 50. Then, intermediate 50 undergoes reductive elimination from the iodine center to give the dichlorination product 48 (Scheme 19).

Scheme 18. gem-Dichlorination of Aromatic Isonitriles 47 Using 44.

Scheme 19. Proposed Mechanism of gem-Dichlorination Reaction of Aromatic Isonitriles 47.

Chlorocyclization reactions have also been reported.^259,274,275 Du and co-workers have reported that the reaction of methyl o-alkynylbenzoate 51 with (dichloroiodo)benzene 44 proceeds with the formation of carbon–oxygen and carbon-chlorine bonds to produce the corresponding 4-chloroisocoumarins 52 (Scheme 20).²⁷⁵ The reaction proceeds even when ethyl or tert-butyl groups are used instead of methyl groups in the ester moiety of the substrate, and especially when benzyl esters are used; benzyl chloride is obtained as a byproduct, which is an important product in predicting the reaction mechanism. The proposed reaction mechanism of this chlorolactonization reaction starts from the initial coordination of PhICl₂44 with the alkyne triple bond to give intermediate 53. This is followed by a concerted process involving nucleophilic attack of the carbonyl oxygen atom on the triple bond and the triple bond on the hypervalent iodine center of PhICl₂44, affording cyclic oxonium ion 54. At the next step, chloride anion nucleophilically attacks the methyl carbon center in 54, leading to intermediate 55. Finally, reductive elimination of iodobenzene in 55 gives the chlorination product 52 (Scheme 21). A similar chlorocyclization reaction using methyl o-styrylbenzoate or methyl o-styrylbenzamide has also been reported. In this chlorolactonization reaction, the corresponding 3,4-dihydroisocoumarins or 3,4-dihydroisocoumarin-1-imines were efficiently obtained.²⁷⁴

Scheme 20. Reaction of Methyl o-Alkynylbenzoates 51 with Reagent 44.

Scheme 21. Proposed Mechanism of Chlorolactonization of Methyl o-Alkynylbenzoates 51.

It has been reported that (dichloroiodo)benzene reacts with disulfides or diselenides, forming highly reactive sulfenyl chlorides or selenenyl chlorides.^276−282 The generated active species can then react with various substrates, leading to the corresponding sulfur or selenium products. For example, Du and co-workers reported that sulfenyl chloride or selenenenyl chloride species, generated in situ by the addition of dichloroiodobenzene 44 to a disulfide or diselenide, react with alkynone (Z)-o-methyl oximes 56, providing the corresponding organoselanyl- or organosulfanyl-isoxazoles 57 (Scheme 22).²⁷⁹ The authors attempted to isolate the active species, selenyl chloride, and performed NMR measurements. They have also found that the isolated selenyl chloride species can be used to obtain products 57, confirming that it is the key intermediate in this reaction. It has also been reported that when methyl o-alkynylbenzoate was used as a substrate under similar reaction conditions, 4-sulfenyl- or 4-selenyl-substituted isocoumarin products could be effectively obtained.²⁷⁷ Du and Zhao reported a method for generating organosulfenyl chloride species from sulfoxide and (dichloroiodo)benzene 44 and cyclization reactions using this species.²⁸³

Scheme 22. Oxidative Cyclization Reaction of Alkynone (Z)-o-Methyl Oximes 56.

Chlorosulfurization reactions as well as intramolecular oxidative cyclization reactions could also be performed using reactive sulfenyl chloride species generated from disulfide compounds and (dichloroiodo)benzene 44.²⁷⁸ The reaction of a disulfide compound and (dichloroiodo)benzene 44 with p-toluenesulfonyl difluorodiazoethane 58 gives the corresponding products of chlorosulfurization 59 (Scheme 23). The reaction with diselenides instead of disulfides yields the corresponding selenium products. Instead of difluorodiazoethanes 58, diazo compounds with perfluoroalkyl groups, α-diazophosphonates, α-diazoesters, or α-diazoketones can also be used to obtain the corresponding products in good yield.

Scheme 23. gem-Chlorosulfurization of p-Toluenesulfonyl Difluorodiazoethane 58.

Du and co-workers reported that the reaction of KSeCN with (dichloroiodo)benzene 44 and conjugated enamine compounds 60 allows synthesis of 2-amino-1,3-selenazole compounds 61 (Scheme 24).²⁸⁴ It was suggested that selenocyanogen (SeCN)₂ is initially generated from (dichloroiodo)benzene and KSeCN in this reaction. The generated (SeCN)₂ reacts with conjugated enamine compounds to give final products 61. Another possible reaction intermediate is chloroselenocyanate, ClSeCN. However, a control reaction of ClSeCN with conjugated enamine 60 gives product 61 only in low yield, confirming that ClSeCN is not a likely intermediate in this reaction.

Scheme 24. Preparation of 2-Amino-1,3-selenazoles 61.

The same group has also reported the reaction of chlorothiocyanate ClSCN generated from (dichloroiodo)benzene and NH₄SCN.^285,286 The reaction of o-alkenylbenzoic acids 62 with NH₄SCN and (dichloroiodo)benzene 44 gave the corresponding cyanated isobenzofuranones 63 (Scheme 25).²⁸⁵ The proposed mechanism of this reaction involves consecutive generation of the reactive electrophilic species (SCN)₂64 and Cl-SCN 65 from PhICl₂44 and NH₄SCN. Next, electrophilic addition of Cl-SCN 65 to the double bond of 62 produces thiiranium ion 66, which is highly reactive toward nucleophilic ring opening. The carbonyl oxygen of the carboxylic acid moiety would attack the more substituted position via the S_N1 mechanism to afford intermediate 67. Final deprotonation of this intermediate B gives final product 63 (Scheme 26). When KSeCN was used instead of NH₄SCN, the corresponding selenocyanated isobenzofuranones were obtained via chloroselenocyanate, ClSeCN, as active species. Similar to the reactions of KSeCN and NH₄SCN, a reaction of tetramethylammonium trifluoromethylselenate, NH₄SeCF₃, with (dichloroiodo)benzene to generate CF₃SeSeCF₃ species has also been reported.²⁸⁷

Scheme 25. Preparation of Thiocyanated Isobenzofuranones 63.

Scheme 26. Proposed Mechanism of Formation of Thiocyanated Isobenzofuranones 63.

(Dichloro)iodobenzene can also be used in the hydrogen atom abstraction (HAT) reactions. Hu and Yin reported that when 4-methylquinoline 68 and an aliphatic alcohol 69 were reacted with dichloroiodobenzene under LED irradiation, an α-heteroarylation reaction of the aliphatic alcohol occurred and the corresponding secondary alcohols 70 were obtained (Scheme 27).²⁸⁸ In the presence of radical scavengers such as TEMPO, butylated hydroxytoluene (BHT), or 1,1-diphenylethylene the reaction did not yield products 70, indicating that radicals were involved in this reaction. The authors suggest that the radical species generated in this system participate in selective hydrogen atom abstraction from alcohols.

Scheme 27. Reaction of 4-Methylquinoline 68 and Alcohols 69 with Reagent 44 under Blue-LED.

(Dichloroiodo)arenes have been used as oxidants of various transition metal complexes. Numerous recent works have reported reactions of (dichloroiodo)arenes with compounds of Fe,^289,290 Ni,^291−293 Cu,²⁹⁴ Y,²⁹⁵ Zr,²⁹⁵ Ru,²⁹⁶ Rh,^297,298 Pd,^299−302 Os,³⁰³ Ir,^304−306 Pt,^307−317 and Au.^318−333 The oxidized organometallic compounds were analyzed by X-ray structural analysis, NMR, UV–vis, luminescence, EPR instrumentation, and DFT computational chemistry to investigate their structure and properties. For example, Gabbai and co-workers reported that the reaction of platinum complex 71 with (dichloroiodo)benzene 44 gave chlorinated complex 72 (Scheme 28).³¹⁰ In the presence of dimethylsulfide, complex 72 undergoes a clean photolysis that affords products 71 and 73 (Scheme 29), which is a unique example of a germanium-centered light-induced reduction resulting in the ipso-chlorination of a phenylgermanium species.

Scheme 28. Preparation of Complex 72 using Reagent 44.

Scheme 29. Photolysis of Complex 72.

Osakada and Tsuchida et al. have reported that the reaction of gold complexes 74 with (dichloroiodo)benzene 44 yields a mixture of thianthrene 75 and its dimer 76 in moderate yields (Scheme 30).³²¹ The authors propose that the reaction pathway leading to these two products are derived from two independent mechanisms. One mechanism is the oxidation of the thiantrenyl ligand to form a radical cation intermediate, while the other oxidation reaction is thought to occur at the two Au centers.³³⁴

Scheme 30. Reaction of Gold Complexes 74 with Reagent 44.

3.2. Iodine(III) Compounds with Oxygen Ligands

3.2.1. [Bis(acyloxy)iodo]arenes

[Bis(acyloxy)iodo]arenes represent an important class of hypervalent iodine compounds with many practical applications summarized in numerous previous review articles.^{10,147,335−337} According to CAS SciFinder, over 2,500 research papers on various synthetic uses of just (diacetoxyiodo)benzene, PhI(OAc)₂, were published between 2016 and 2024; however, most of these applications deal with routine oxidative transformations of various organic substrates, which were summarized in earlier reviews. This section mainly covers novel applications of [bis(acyloxy)iodo]arenes in synthetically useful reactions.

Several general synthetic approaches to [bis(acyloxy)iodo]arenes have been developed. The classical general approach to (diacetoxyiodo)arenes is based on the reaction of an oxidant with an iodoarene in acetic acid solution. Older procedures involve the use of potentially explosive concentrated hydrogen peroxide as the oxidant, while recently developed methods utilize the less explosive oxidants.^338−341 Structures of several recently synthesized (diacetoxyiodo)arenes have been characterized by X-ray analysis.^339,342,343 In addition to structural characterization, a computational study of the oxidizing capacity of various (diacetoxyiodo)arenes has also been reported.²⁰⁶ Synthesis of several other [bis(acyloxy)iodo]arenes by ligand exchange reactions of (diacetoxyiodo)arenes with different carboxylic acids and study of their solubility in organic solvents has been recently published.³⁴⁴

(Diacetoxyiodo)arenes are efficient oxidants for a variety of organic substrates. A useful feature of these compounds is that they can be easily converted to different hypervalent iodine reagents during the reaction in the presence of appropriate additives. (Diacetoxyiodo)benzene (DIB) 24 is an efficient reagent that can oxidize phenolic compounds to quinone derivatives resulting from subsequent intra-^345−355 and intermolecular cyclization or addition reactions.^356−367 Such dearomatization reactions can produce quinone products from phenols or anilines.^368−377 The cyclization reactions on nitrogen have been reported for dearomatization of aniline compounds in the absence of external nucleophiles. For example, Mal and co-workers reported that the reaction of sulfonamide derivatives 77 with DIB 24 results in the replacement of a tert-butyl group with a new carbon–nitrogen bond to give carbazole products 78 (Scheme 31).³⁷⁸ This reaction proceeds successfully for substrates with different substituents on the aromatic ring and various sulfonamide groups. The same group has also reported a cyclization reaction on the sulfur atom of thiophenol instead of the nitrogen atom using DIB 24 as the oxidant.³⁷⁹ Other reactions of anilines using DIB have been reported, such as the synthesis of azo compounds by aniline coupling.^380,381

Scheme 31. Preparation of Carbazole Compounds 78 from Anilines 77.

Oxidation of aldoximes with DIB 24 generates the corresponding nitrile oxides, which react with alkenes or alkynes to give the corresponding heterocyclic compounds.^382−385 The in situ generated nitrile oxides can also be trapped by the reaction with acetic acid, leading to the formation of N-acetylamides.³⁸⁶ For example, the reaction of α-MIDA borylaldoximes 79 with DIB 24 in the presence of acetic acid yields the corresponding N-acetoxyamides 80 in good yields (Scheme 32). The resulting N-acetoxyamides 80 can be further converted to boron-containing hydroxylamines by appropriate treatment. Oxidation of ketoximes with DIB 24 has also been reported.^387,388

Scheme 32. Preparation of N-Acetoxyamides 80 from Aldoximes 79.

Various reactions of amines with DIB 24 resulting in the oxidation of nitrogen atom have been reported.^389−408 For example, Murai and co-workers reported an oxidative rearrangement reaction of amines promoted by DIB.³⁹² In this reaction, secondary amines 81 react with DIB in trifluoroethanol solution and are subsequently treated with a reducing agent to obtain rearrangement products 82 in moderate to high yields (Scheme 33). The proposed reaction mechanism includes the in situ generation of N–I(III) intermediate 83 which further undergoes 1,2-carbon-to-nitrogen migration, leading to iminium species 84. These species are reduced by NaCNBH₃ to afford final products 82 (Scheme 34). The same group has also reported the oxidative rearrangement reactions using primary amines.³⁹⁴

Scheme 33. Oxidative Rearrangement of Secondary Amines 81.

Scheme 34. Proposed Mechanism for the Formation of 82.

Preparation of nitrile compounds by oxidative cleavage of amines by DIB has been reported. The reaction of 5-aminopyrazoles 85 with DIB 24 gives the corresponding 1,2-diaza-1,3-dienes 86 (Scheme 35).^401,405 The authors believe that radical intermediates are not involved in this reaction because in the presence of radical scavengers such as TEMPO and BHT the reaction affords products 86 in unchanged yields. Bao and Sun reported a similar oxidative cleavage of the amine moiety of 2-aminobenzothiazole upon treatment with DIB, leading to a conjugated nitrile intermediate which could be trapped by a [4 + 2] cycloaddition reaction with alkenes.⁴⁰⁸ The reaction of 2-aminobenzothiazoles 87 with DIB 24 in the presence of alkenes 88 yields dihydro-1,4-benzothiazines 89 (Scheme 36). The key intermediate in this reaction appears to be the conjugated cyano compound 90 formed by the oxidative cleavage of 2-aminobenzothiazole with DIB.

Scheme 35. DIB-Mediated Oxidative Cleavage Reaction of 5-Aminopyrazoles 85.

Scheme 36. DIB-Mediated Oxidative Ring-Expansion Reaction of 2-Aminobenzothiazoles 87.

Luo and He have reported that a denitrogenation reaction occurs when a hydrazone is treated with DIB.⁴⁰⁹ The reaction of N-arylsulfonylhydrazones 91 with DIB 24 under basic conditions yields denitrogenated vinylsulfone products 92 (Scheme 37). Since this reaction does not yield products 92 in the presence of TEMPO, the authors suggest that the reaction mechanism involves radicals.

Scheme 37. Denitrogenation of N-Arylsulfonylhydrazones 91 Using DIB 24.

Several Hofmann rearrangement reactions of cyclic imides^410,411 or amides^412−414 with hypervalent iodine reagents were previously reported. More recently, the Patureau group reported that the reaction of benzotriazole in the presence of DIB with N-methoxyamide as a substrate leads to a nitrogen–nitrogen coupling reaction.⁴¹⁵ In this reaction, DIB 24 and N-methoxy amide 93 are added to the benzotriazole 94 to obtain the nitrogen–nitrogen cross-coupling compound 95 (Scheme 38). Aromatic and aliphatic N-methoxyamides 93 can be used in this reaction. In this reaction, if N-methoxyamide and DIB were reacted for 16 h and then benzotriazole was added, products 95 were not formed. In contrast, when benzotriazole and DIB were reacted for 16 h and then N-methoxyamide 93 was added, the desired product 95 was obtained. The authors suggested that the amide substrates decompose in the presence of DIB, while benzotriazole is stable under these conditions.

Scheme 38. Cross-Coupling Reaction of N-Methoxyamide 93 and Benzotriazole 94.

Reactions of alkoxy amides with long alkyl chains with alkynes or alkenes instead of methoxy groups have also been reported.^416,417 When DIB 24 is reacted with alkoxyamides 96 with an alkyne moiety, an intramolecular cyclization reaction proceeds in 1 min to give the corresponding cycloheptatriene-fused lactams 97 (Scheme 39).⁴¹⁷ A similar cyclization occurs when alkenes are used instead of alkynes. The authors have used DFT calculations to explain the reaction mechanism.

Scheme 39. Preparation of Cycloheptatriene-Fused Lactam 97.

DIB has been used as an effective reagent in the oxidation reactions of urea derivatives. Jeffrey and co-workers reported that a [2 + 3] cycloaddition reaction proceeds when DIB 24 is added to a mixture of N,N-dibenzyloxyurea 98 and an indole 99, yielding the corresponding imidazoloindole products 100 (Scheme 40).⁴¹⁸ The reaction mechanism includes initial formation of a diazaoxyallylic cationic species 101 by the oxidation of N,N-dibenzyloxyurea 98 with DIB 24, which then reacts with indole 99 to produce a zwitterionic intermediate 102, followed by an intramolecular cyclization reaction to form final product 100 (Scheme 41). Romo and co-workers have reported a similar [2 + 3] cycloaddition reaction with indole of a compound with a guanidine skeleton instead of urea.⁴¹⁹

Scheme 40. Cycloaddition Reaction of Indoles 99.

Scheme 41. Proposed Mechanism for Cycloaddition Reaction of Compounds 98 and 99 Using Reagent 24.

It is known that DIB is an effective oxidant not only for nitrogen compounds but also for sulfur compounds.^420−423 The oxidation of organic sulfides to sulfoxides using DIB has been well-documented.¹⁸³ On the other hand, the reactions in which sulfur compounds react with nitrogen compounds in the presence of DIB to form various products with a sulfur–nitrogen bond have also been reported recently.^424−428 For example, Willis and co-workers reported that the reaction of sulfinamidines 103 with DIB 24 and amines 104 yielded sulfonimidamide products 105 with new S–N bonds (Scheme 42).⁴²⁵ The reaction proceeds efficiently with sulfinamidines bearing various functional groups and with a variety of amines. This chemistry is suitable for the preparation of several known sulfondiimidamide-derived medicinal agents. The same group has also reported a similar reaction utilizing sulfinamides instead of sulfinamidines. resulting in the corresponding sulfonimidamide products.⁴²⁸

Scheme 42. Preparation of Sulfonimidamides 105.

Recently, Lu’s group reported the synthesis of sulfinimidate esters from sulfenamides.⁴²⁹ In this reaction, the addition of sulfonamide 106 and alcohol 107 to DIB 24 efficiently produced sulfinimidate ester 108 (Scheme 43). A variety of alcohols can be used in this reaction; even when the alcohols derived from natural products (e.g., the hair growth stimulator RU58841 and the estrogen receptor modulator (SERM) ospemifene) are used, the corresponding products 108 are obtained in moderate yields.

Scheme 43. Preparation of Sulfinimidate Esters 108.

It was reported recently that the reaction of allyl compounds with DIB, amine, and a catalytic amount of a selenium reagent leads to a metal-free C–H amination of the allylic position.^430−432 For example, a vinylsilane 109, a sulfonamide 110, and a catalytic amount of selenium reagent 111 react with DIB to form compound 112 with the aminated allylic position (Scheme 44).⁴³⁰ This reaction also proceeds efficiently when a pinacol boronic acid derivative is used instead of the vinylsilane. The proposed mechanism of this reaction involves initial generation of a reactive selenium bis(imide) species 113, which undergoes a sequential ene reaction to yield intermediate 114, followed by a [2,3]-sigmatropic rearrangement affording aminated product 115. Final product 112 is formed from intermediate 115, while the selenium catalyst is regenerated from DIB 24 and amine 110 to form selenium bis(imide) species 113 (Scheme 45). The same group has also recently reported that selective C–H amination reactions can also occur for allyl compounds without silyl or boron group substituents.⁴³²

Scheme 44. Allylic C–H Amination of 109.

Scheme 45. Proposed Mechanism of Product 112 Formation.

DIB and its derivatives are useful reagents for intramolecular cyclization reactions, and numerous cyclization reactions leading to various ring structures have been reported in recent years.^{417,433−449} Cuny and co-workers reported an oxidative cyclization of protected acrylamides 116 using DIB 24 in acetic acid to give oxazolidine-2,4-dione derivatives 117 in good yields (Scheme 46).⁴⁴² The suggested reaction mechansim includes initial coordination of DIB 24 with the double bond of acrylamides 116 via intermediate 118 (Scheme 47) followed by cyclization via elimination of isobutylene to form intermediate 119. Finally, nucleophilic substitution of the hypervalent iodine leaving group in 119 with an acetate anion affords final product 117.

Scheme 46. Preparation of 5,5-Disubstituted Oxazolidine-2,4-dione 117.

Scheme 47. Proposed Mechanism for the Conversion of Compound 116 to Product 117.

Activation of DIB by the addition of Brønsted acid or Lewis acid has been well-documented; however, the structure of the activated species was not reliably confirmed. In 2016, Shafir and co-workers were the first to report the X-ray structure of PhI(OAc)OTf produced by the ligand exchange reaction between DIB and TMSOTf.⁴⁵⁰ This reagent was further converted by dimerization to the Zefirov’s reagent [PhIOIPh](OTf)₂, the structure of which was also revealed for the first time by X-ray analysis. Furthermore, when BF₃ was added to DIB instead of TMSOTf, the structure of the activated PhI(OAc)₂-BF₃ complex was also confirmed by X-ray analysis, and the reactivity of this complex was experimentally investigated along with NMR studies and DFT calculations. In recent years, a number of sigmatropic rearrangement reactions of unsaturated compounds promoted by DIB-BF₃ or DIB-TMSOTf have been reported.^450−458 Several examples of such reactions of DIB with various unsaturated compounds are shown in Scheme 48. In these reactions, DIB 24 reacts with substrates 120, 123, 126, 129, and 132 to form the corresponding intermediates 121, 124, 127, 130, and 133, which then undergo intramolecular sigmatropic reactions to yield final products 122, 125, 128, 131, and 134. These reactions can also be carried out using ArI(OAc)₂ with various substituents in the Ar ring. On the other hand, it has been reported that, under similar reaction conditions, when benzylsilane or benzylborate compounds are used instead of allylsilanes 123, the insertion reaction proceeds to the para-position instead of the ortho-position.^459,460

Scheme 48. Sigmatropic Rearrangement Reactions Using DIB 24.

Wengryniuk and co-workers reported the sigmatropic reaction using PIFA and its derivatives instead of DIB.⁴⁶¹ In this reaction, the addition of pyridine and TMSOTf to 2-cyclohexen-1-one 135 followed by the addition of PIFA 136 leads to the rearrangement product 137 (Scheme 49). The reaction proceeds efficiently even when PIFA with various functional groups is used in this reaction. The proposed mechanism of this reaction involves the formation of β-pyridinium silyl enol ether 138 from pyridine and TMSOTf followed by ligand exchange reaction with PIFA 136 to form an intermediate 139, which is then converted to final product 137 via a [3,3]-sigmatropic reaction (Scheme 50).

Scheme 49. Sigmatropic Rearrangement Reaction Using PIFA 136.

Scheme 50. Proposed Mechanism α-Arylation of Ketone 135.

Yorimitsu and co-workers reported a sigmatropic reaction using naphthol derivatives. In this reaction, 2-(diacetoxyiodo)naphthalene 140 reacts with 2-naphthols 141 in acetic acid to afford the corresponding binaphthyl derivatives 142 in moderate yield (Scheme 51).⁴⁶² The proposed mechanism of this reaction includes the initial ligand exchange of reagent 140 and 2-naphthol 141 to form intermediate 143, sigmatropic reaction of which yields product 142. The authors have also found that products 142 can be converted to π-extended furan compounds upon heating under basic conditions.

Scheme 51. Preparation of Binaphthyl Compounds 142.

Szpilman’s group reported the umpolung Morita-Baylis-Hillman (MBH) reaction of α,β-unsaturated compounds using DIB.⁴⁶³ The reaction of compounds 144 with DIB 24 using pyridinium p-toluenesulfonate (PPTS) as a nucleophile, followed by treatment with triethylamine, yields the α-tosylated products 145 in moderate yield (Scheme 52). On the other hand, when acetic acid is used as a nucleophile, an acetoxylation occurs at the α-position, and the initial acetoxylated product is then converted to a 1,2-diketone by passing through a basic column. The proposed mechanism of this reaction includes the initial addition of pyridine and DIB 24 to unsaturated compound 144, producing an electrophilic enolonium intermediate 146, followed by the reaction with tosylate anion to form adduct 147, which is further converted to final product 145 by triethylamine (Scheme 53). The intermediate adduct 146 was detected by NMR. Maulide and co-workers reported the use of DIB and silyl enol ether as the starting material to generate enolonium intermediates, followed by the introduction of an Ar group at the α-position via 1,2-rearrangement of the Ar group.⁴⁶⁴

Scheme 52. α-Tosyloxylation of α,β-Unsaturated Compounds 144.

Scheme 53. Proposed Mechanism of α-Tosyloxylation Reaction of Compounds 144.

Various reactions resulting in a regioselective introduction of a substituent at the C5 position of 8-aminoquinolinamides 148 using DIB or other (diacyloxyiodo)iodobenzene reagents have been reported.^465−469 Typical examples of such reactions leading to the corresponding products of insertion 149–152 in moderate yields are shown below (Scheme 54). It was suggested that the mechanism of these reactions involves initial SET interaction of an iodine(III) reagent with 8-aminoquinolinamides 148. Similar insertion reactions using metal reagents have also been reported.^470,471 Other heterocyclic substrates such as imidazopyridines^472−482 and quinoxalinones^483,484 have been used for the analogous regioselective insertion reactions at the C3 position.

Scheme 54. Functionalization of 8-Aminoquinolinamides 148 Using (Diacyloxyiodo)benzene Reagents.

A common methodology involves combining DIB with various additives to generate new active species, which then react with the substrate.^485−508 In particular, it has been reported that the addition of halide anion sources to PhI(OAc)₂ results in the formation of hypervalent iodine halide species PhI(OAc)X or PhIX₂ which are further used for halogenation of various substrates in situ. These species can be used for halogenations of substrates with sp² carbon,^{485,488,489,491,494,507,508}sp carbon,^499,500,506 and sp³ carbon atoms.⁴⁹² It has been reported that halogenation-cyclization reactions of alkenes can be used for the synthesis of various cyclic products.^{486,493,497,498,501} For example, Bolm and co-workers have developed a method for halocyclizations of S-alkenylsulfoximines. Treatment of unsaturated NH-sulfoximines 153 with a combination of DIB 24 and potassium iodide leads to the formation of S-oxides of dihydro isothiazoles 154 (n = 1) or tetrahydro-1,2-thiazines 154 (n = 1) in good yields with high diastereoselectivities and regioselectivities (Scheme 55).

Scheme 55. Halocyclization of Sulfoximimes 153 Using DIB/KI Combination.

This methodology has also been used for halogenation at the nitrogen atom. The generated nitrogen-halogen bond is relatively unstable and quickly breaks by a radical pathway, resulting in inter-^509,510 or intramolecular amination reactions.^511−520 Some representative examples of intramolecular amination reactions are shown below (Scheme 56). These amination reactions can proceed at the sp² or the sp³ carbon atom. It has also been reported that this reaction can be carried out efficiently under photochemical conditions such as visible light and LEDs. DIB and halogen additives can react with various amides, e.g., 155, 157, 159, 161, and 163, to obtain the corresponding cyclization products 156, 158, 160, 162, and 164 in low to high yields. Proposed mechanism of these reactions generally includes homolytic cleavage of the initially formed halogen-nitrogen bond to form a nitrogen radical, which then undergoes an intramolecular HAT followed by the cyclization reaction.

Scheme 56. Cyclizations of Amino Derivatives Using DIB 24 with an Additive.

The Nagib group reported various amination reactions utilizing imidate derivatives prepared from nitriles and alcohols.^521−525 In these reactions, DIB and NaI are added to imidates to form oxazoline products in the mixture, which are then treated with HCl to obtain the desired β C–H amination products (Scheme 57).⁵²¹ The authors found that imidates derived from various alcohols can be used as substrates in this reaction. The same group has also reported that a similar reaction proceeds using a catalytic amount of I₂ instead of a stoichiometric amount of NaI.⁵²³ They have also found that the reactions using stoichiometric amounts of CsI yield oxazole products in moderate to high yields.⁵²⁴ In these reactions, an N–I intermediate 168 is formed from imidate 167, DIB 24, and an iodine additive, followed by homolytic cleavage of the N–I bond to give nitrogen radical species 169 which then undergoes an intramolecular 1,5-HAT reaction, leading to the carbon radical species 170 and the final amination products (Scheme 58). In addition, the authors have also performed a Hammett plot study using 2-arylethanol imidates for the HAT reaction, and the negative slope of the Hammett equation indicated that the reaction proceeded faster for the electron-donating group than for the electron-withdrawing group.⁵²³ This result suggests that the electron-donating group at the para-position stabilizes this transition state, while the electron-withdrawing group has the opposite effect.

Scheme 57. β C–H Amination of Imidate 165.

Scheme 58. Generation of Carbon Radicals 170 via HAT Reaction.

In 1998–2005, Kirschning and co-workers reported the preparation and synthetic application of several polymer-supported halogenate(I) complexes by the DIB-promoted oxidation of polystyrene-bound halides.^223,224 Recently, these reagents were used for the generation of polymer-supported azides which were utilized as reagents in photochemical azidation reactions.^526−528

A reaction utilizing a carboxylic acid as the additive has also been reported. In this reaction, the ligand exchange between DIB and carboxylic acid produces iodine(III) species with a new acyloxy group ligand, which reacts with the substrate as a reagent to perform the desired reaction.^529−533 The objective of this exchange reaction is not to introduce a new acyloxy group to the substrate, but to add a specific alkyl radical to the reaction substrate, which is generated by decarboxylation of the corresponding acyloxy group under reaction conditions. For example, when DIB 24, alkenes 171, and difluoroacetic acid 172 reacted under blue LED irradiation, hydrodifluoromethylated products 173 were obtained (Scheme 59). In this reaction, the iodine(III) reagent produced from DIB and difluoroacetic acid is decarboxylated during the reaction under blue LED irradiation to form difluoromethyl radicals, which further react with alkenes to give the desired product.⁵²⁹ The reaction solvent, THF, is used as a hydrogen atom source for the target product (Scheme 59). An example of a similar reaction producing alkyl radicals using sodium alkylsulfinate as an additive has been reported.^534−537

Scheme 59. Hydrodifluoromethylation of Alkenes 171.

The other examples of reagent combinations DIB/additive leading to various reactive species in the reaction mixture include the following: DIB/NaN₃,^538,539 DIB/K(Na)SCN,^540−542 and DIB/CF₃(HCF₂)SO₂Na.^534,535

Phenyliodine bis(trifluoroacetate) (PIFA) is a reagent with a generally similar DIB reactivity. Like DIB, this reagent is used as an efficient oxidant for various organic substrates. For example, the oxidation of phenols using PIFA has been reported in numerous publications.^{346,363,543−546} Treatment of a phenolic compound 174 with PIFA 136 affords bicyclo[3.2.1]octane derivative 175 in 72% yield (Scheme 60).⁵⁴³ This reaction involves an intramolecular [5 + 2] cyclization of the initial product of dearomatization of phenol 174 with PIFA 136, leading to final product 175. The introduction of substituents with electronic and steric effects at the 4- and 5-positions of the substrate yielded the desired products in moderate yields. It has also been reported that the yield of product 175 is slightly lower when DIB is used instead of PIFA in this reaction.

Scheme 60. PIFA-Mediated Cascade Reaction of Phenolic Compound 174.

The use of PIFA for cyclization reactions of various substrates has been reported.^547−556 Shibata’s group reported that the reaction of amino compounds 176 with PIFA and a catalytic amount of I₂ under photoirradiation affords cyclization products 177 in moderate to high yields (Scheme 61).⁵⁵² It was demonstrated that PIFA under photoirradiation conditions was the only effective reagent in this cyclization. When DIB was used instead of PIFA, only trace amounts of product 177 were obtained, and that the desired product was not obtained at all without light. The authors suggest that the generated from PIFA and I₂ trifluoroacetyl hypoiodite IOCOCF₃ represents the active species in this reaction.

Scheme 61. PIFA- and I₂-Meditated Cyclization of Amines 176.

PIFA can be used as an intermolecular coupling reagent.^557−564 The dimerization of substrates by oxidative dearomatization with PIFA was reported by Hajra and co-workers.⁵⁶⁴ The reaction of 2H-indazole 178 as a substrate with PIFA afforded N-1-indazolyl indazolones 179 in moderate to high yields (Scheme 62). The authors suggest that the trifluoromethyl acetate ligand of PIFA serves as the oxygen source in product 179. They also believe that this reaction proceeds by SET mechanism.

Scheme 62. PIFA-Meditated Oxidative Dimerization of 2H-Indazole 178.

In addition to these reactions, numerous oxidations with PIFA have been reported in the previously published review articles.^565,566

DIB, PIFA, and other [bis(acyloxy)iodo]arenes are commonly used as oxidizing reagents in the presence of various transition metal caatalysts.^{125,152,567,568} In the past few years, numerous oxidations catalyzed by compounds of transition metals such as palladium,^569−595 copper,^{470,596−602} silver,^603,604 gold,^605−610 nickel,^611−613 cobalt,^614,615 manganese,^616−619 rhodium,^620,621 platinum^466,622,623 vanadium,⁶²⁴ rhenium,⁶²⁵ ruthenium,⁶²⁶ and iron^627−629 have been reported. Beccalli and co-workers reported palladium-catalyzed enantioselective and regioselective oxidative cycloaddition reactions of alkenol compounds.⁵⁸⁸ In this reaction, the addition of iodine(III) reagent and palladium catalyst to alkenol 180 in the presence of a catalytic amount of pyridinyl oxazoline ligand 181 gives the corresponding six-membered ring product 182 enantioselectively (Scheme 63). The addition of the ligand is important in this reaction. In the absence of ligand, product 182 is obtained in a low yield in a complex mixture of by-products.

Scheme 63. Palladium-Catalyzed Cyclization of Alkenols 180.

The palladium(II)-catalyzed reactions of DIB or PIFA with the same substrate but leading to different products were reported by Broggini and Poli.⁵⁷⁸ For example, the reaction of N-tosylglycine N′-crotyl-N′-benzylamide 183 with DIB and catalytic amounts of Pd(OAc)₂ gave 5-vinylpiperazinone 184 in 50% yield (Scheme 64). The same substrate reacts with PIFA under the same conditions to afford 2-vinylimidazolidinone 185 in 78% yield. The authors have used this difference in reactivity with DIB and PIFA to synthesize several new products.

Scheme 64. Palladium-Catalyzed Cyclizations of Benzylamide 183.

Gao and Song reported that the reaction of bicyclic epoxides with DIB in the presence of a copper catalyst leads to rearranged products.⁶⁰¹ The reaction of 1,3-azasilinyl-4-epoxides 186 with DIB and CuI yielded ring-restructured aldehydes 187 (Scheme 65). Additional experiments have demonstrated that this reaction is specific for silicon compounds. According to ¹³C NMR and ESI-MS measurements, this reaction in the presence of ¹⁸O-water yielded products with Si–¹⁸O bond, which confirms that the oxygen atom in the aldehyde product was oxygen from epoxide. Based on the control experiments, the authors suggest that the in situ generated Cu(II) intermediates are possible active species in this catalytic reaction.

Scheme 65. Ring Rearrangement of 1,3-Azasilinyl-4-Epoxides 186.

Copper-catalyzed C–H amination reactions were reported by Cai and Xia.⁶⁰² In the reaction of 2H-indazole 188 and indazol-3(2H)-one 189 with DIB 24 and a catalytic amount of copper(II) triflate, product 190 aminated at the C3 position of 2H-indazole was obtained (Scheme 66). In the presence of a radical scavenger such as BHT, an adduct of indazol-3(2H)-one 189 and BHT was isolated, implying that radicals derived from indazol-3(2H)-one were involved in the reaction. The role of DIB in this reaction is in the reoxidation of Cu(I) to Cu(II) active species.

Scheme 66. Copper-Catalyzed Coupling Reaction Between 188 and 189.

Nevado’s group reported a successful synthesis of an Au(III) complex from Au(I) compound using the oxidizing power of DIB.⁶¹⁰ The reaction of DIB with polyfluoroaryl gold(I) compounds 191 gave trans-diacetoaryl gold(III) complexes 192 in moderate to high yields (Scheme 67). Reaction of these gold(III) complexes 192 with excess amounts of TMSCN led to ligand exchange reactions, yielding a mixture of trans- and cis-type gold(III) complexes 193 with cyano ligand. The authors have also performed a reductive elimination reaction of the trans-gold(III) complex by heating in 1,4-dioxane solution to afford the corresponding polyfluorinated benzonitriles in high yield.

Scheme 67. Preparation of Gold(III) Complexes from 191 Using DIB 24.

Photocatalytic reactions of DIB have also been reported.^10,630−635 The proposed mechanism of these reactions involves the initial interaction of a photocatalyst with light to generate excited chemical species. The excited species are then oxidized by an iodine(III) reagent to form active species. The active species reacts with the substrate and returns to the original catalytic species to initiate the next cycle. For example, it has been reported that DIB 24 and quinoxaline-2(1H)-one 194 react under 24 W LED irradiation in the presence of a photocatalyst to yield product 195 with a methyl group introduced at the C3 position of quinoxaline-2(1H)-one (Scheme 68).⁶³² DIB serves as the source of the methyl group in this reaction, and when a different carboxylic acid is added, a product with an alkyl group of the carboxylic acid introduced instead of a methyl group is obtained. Products 195 were not obtained in the presence of TEMPO, which indicated that radical species were involved in the reaction mechanism.

Scheme 68. Photocatalyst-Mediated Decarboxylative Methylation of 194.

3.2.2. Iodosylarenes

Iodosylbenzene and other iodosylarenes have been widely used as effective oxidizing reagents for over a century.^221−224 Iodosylarenes in general have a polymeric structure and are insoluble in common organic solvents.^116,183 In the presence of a polar protic solvent such as an alcohol, iodosylbenzene dissolves, forming new hypervalent iodine species with an alkoxy group as a ligand. The structure of some of these alkoxy-substituted species was confirmed by X-ray analysis;⁶³⁶ however, these compounds are unstable and quickly revert back to iodosylbenzene. Mckenzie and co-workers reported the crystal structure of iodosylbenzene using a combination of various analytical instruments and crystallographic approaches.⁶³⁷ Based on the structural analysis, the authors consider that not only the intermolecular interactions of O–I···O–I but also the C–H···π interactions between adjacent phenyl groups contribute to the insolubility of PhIO. Some iodosylbenzene derivatives can dissolve in common organic solvents due to the presence of additional intramolecular interactions.⁶³⁸ The soluble iodosyl compounds have a basic oxygen atom and can form complexes with acidic alcohol such as HFIP; the structure of such a complex was characterized by NMR and X-ray crystallography.⁶³⁹ Iodosyl compounds with pseudocyclic structure that form the complex with TFA have also been reported.⁶⁴⁰ Recently, it has been reported that iodosyl compounds form complexes with various metals, and their structures have been further investigated by X-ray crystallography.^{639,641−647} A common synthesis of iodosylbenzene involves the treatment of (diacetoxyiodo)arenes with a base. In a recently reported method, iodosylarenes are conveniently prepared by the reaction of iodoarenes with sodium hypochlorite under CO₂ conditions.⁶⁴⁸

Iodosylarenes, similar to (diacetoxyiodo)arenes, can be used as efficient oxidizing reagents. Oxidations of phenols,^649,650 anilines,^651−653 alcohols and enolates^654−657 have been recently reported. For example, Gu and co-workers reported that the reaction of 9H-fluorene-9-ols 196 with iodosylbenzene 17 gave the corresponding oxo-spiro compounds 197 (Scheme 69).⁶⁵⁶ The resulting compounds could be converted to biphenyl products by acid treatment. The authors suggested that a phenolic compound 198 is initially formed from the starting material 196 and PhIO 17, which is further converted to final product 197 by oxidative dearomatization.

Scheme 69. Preparation of Oxo-Spiro Compounds 197 from 196 Using PhIO 17.

Stockman and co-workers reported synthesis of sulfonimidates from sulfinamides using PhIO as an oxidant.⁶⁵⁸ Sulfinamides 198 react with PhIO in an alcohol solution to form alkoxy-substituted sulfonimidates 199 in moderate to high yields (Scheme 70). Weakly nucleophilic alcohols and unsaturated alcohols can be used in this reaction. The resulting products 199 can be converted to sulfoximines by reaction with Grignard reagents.

Scheme 70. Synthesis of Sulfonimidates 199 from Sulfinamides 198 and PhIO in the Presence of Alcohols.

Iodosylarenes are commonly utilized as an oxidant in the construction of heterocyclic molecules. It is especially useful for intramolecular cyclizations of various unsaturated precursors.^659−666 It has been reported that the reaction of N-cyclohexenylamide 200 with iodosylarene and BF₃ yields monofluorinated five-membered fused oxazolines 201 and 202 (Scheme 71).⁶⁶¹ In this reaction, BF₃ not only activates the ArIO but also serves as a fluorine source. The position of fluorine introduction depends on the substituents in the substrate. When substituent R² = H at the 4-position of the cyclohexenyl moiety in substrate 200, fluorine is introduced into the ring of product 201, and when substituent R² ≠ H, fluorine is introduced outside the ring of the product 202. In such regioselective fluorination reactions, the stability of the intermediate carbocation is believed to be important. When acetonitrile was used as the reaction solvent, the Ritter-type reaction proceeded and the acetamide group was inserted instead of fluorine, indicating that carbocation was formed during reaction.

Scheme 71. Preparation of Monofluorinated Five-Membered Ring-Fused Oxazolines.

Iodosyl compounds are useful reagents not only for intramolecular reactions but also for intermolecular reactions. For example, the reaction of 1,3-dicarbonyl compounds in the presence of carboxylic acids leads to α-acyloxylated products.⁶⁶⁷ Recently, Dong and co-workers reported that the reaction of a 1,3-dicarbonyl compound, β-oxoamide, with a cyclic amidine gave a polysubstituted imidazolidin-2-one.⁶⁶⁸ Chmielewski and Li have reported the insertion reaction of amines into conjugated macrocycles using PhIO.⁶⁶⁹ When the nickel-centered macrocycle 203 was treated with amine 204 and an excess amount of PhIO 17, 10-azacorroles 205 were obtained (Scheme 72). Structures of several products 205 were established by X-ray analysis.

Scheme 72. Synthesis of 10-Azacorroles 205.

Iodosyl compound can be converted to new hypervalent iodine active species in the presence of appropriate additives. For example, in alcohol solutions, alkoxy-substituted hypervalent iodine species are generated.^670,671 Du and Zhao reported a lactonization reaction promoted by these iodine(III) species.⁶⁷¹ When 2-(1-phenylvinyl)benzoic acid 206 is reacted with PhIO in alcohol as a solvent under heating, the corresponding lactones 207 are obtained (Scheme 73). In this reaction, the generated dialkoxyiodine(III) species react with the alkene moiety of the starting material, followed by 1,2-migration of the aryl group and alkoxylation, leading to final products. The reactions utilizing iodine(III) species generated in the presence of such additives as diselenide,^672,673 iodine source,^215,674 AlX₃ (X = NO₃, Cl, Br),^675−678 carboxylic acid,⁶⁷⁹ and fluoride source^{238,244,680−685} have been reported.

Scheme 73. Lactonization Reaction of 206 with PhIO in Alcohol Solutions.

Reactions of PhIO in the presence of metal compounds such as Mn,^686−692 Cu,⁶⁹³ Fe,⁶⁹⁴ Ru,⁶⁹⁵ and Co⁶⁹⁶ as catalysts have been reported. For example, Feng and Liu reported the asymmetric epoxidation of alkenes using Co catalysts with chiral ligand.⁶⁹⁶ When cyclic trisubstituted alkenes 208 react with PhIO 17 and Co catalysts in the presence of chiral ligand 209, the corresponding epoxy products 210 are obtained with high enantioselectivity (Scheme 74). The reaction also proceeds with acyclic alkenes. The authors have detected the generation of intermediate Co–O species from PhIO and Co catalyst during this reaction by ESI mass spectrometry and have investigated the enantioselectivity by DFT calculations.

Scheme 74. Asymetric Epoxidation of Alkenes 208.

3.3. Iodine(III) Compounds with Nitrogen Ligands

3.3.1. [(Diamido)iodo]arenes

[(Diamido)iodo]arenes are efficient reagents for introducing amido group into various organic substrates.⁸² These compounds are generally prepared by a ligand exchange reaction between (diacetoxyiodo)arenes and a trimethylsilyl-substituted amide or imide. Several (diamidoiodo)arenes have been investigated by X-ray structural analysis.⁶⁹⁷ Compounds with bis(trifluoromethanesulfonyl)imide group as a ligand were also synthesized, but their structures were not reliably confirmed in earlier works.⁶⁹⁸ Recently, Dutton and co-workers have reported X-ray structure of para-nitro-substituted (diamidoiodo)arene 212, which was prepared by the reaction (difluoroiodo)arene 211 with TMSNTf₂ in CDCl₃ (Scheme 75).^187,212 The X-ray structure revealed that the I–N bond distance of this compound is longer than other previously reported I–N bonds. The authors have shown that compound 212 has better oxidizing power than 4-NO₂C₆H₄I(OTf)₂. For example, 3-methylcyclohexene is oxidized to toluene by 4-NO₂C₆H₄I(NTf₂)₂ but not by 4-NO₂C₆H₄I(OTf)₂. The high oxidation potential of 4-NO₂C₆H₄I(NTf₂)₂ is also confirmed by calculations using the B3LYP/6-311+G(d,p) method.

Scheme 75. Synthesis of 4-NO₂C₆H₄I(NTf₂)₂212.

Muñiz and co-workers reported that the reaction of indole compounds 213 with PhI(NTs₂)₂ gave products 214 aminated at the 2-position of the indole (Scheme 76).⁶⁹⁹ When PhI(NMs₂)₂ or PhI(NTsMs)₂ is used instead of PhI(NTs₂)₂, the corresponding products 214 are also obtained in good yields.

Scheme 76. Amination of Indole Compounds 213.

A saccharin analogue of PhI[N(SO₂R)₂]₂ has been prepared and investigated.⁶⁹⁷ It has been demonstrated that this reagent can react with indole derivatives 215 in the presence of a catalytic amount of I₂ under light irradiation to produce compound 216 with saccharin moiety introduced at the 2-position of the indole (Scheme 77). This iodine(III) reagent serves as an oxidant and a nitrogen source in this reaction. Under similar reaction conditions, it can be used for regioselective introduction of saccharin moiety into various other heterocyclic compounds.

Scheme 77. Selective C–H Amidation of Indole 215.

3.3.2. [Acyloxy(amido)iodo]arenes

[Acyloxy(amido)iodo]arenes can be generally synthesized by adding an equal amount of a trimethylsilyl-substituted amide or imide to (diacetoxyiodo)arene. The structure of these compounds was confirmed by X-ray crystallography.^82,700 [Acyloxy(amido)iodo]arene can be further converted to [(diamido)iodo]arene by adding a second equivalent of trimethylsilyl-substituted amide. [Acyloxy(amido)iodo]arenes are useful as the amidation reagents similar to [(diamido)iodo]arenes. For example, it has been reported that the reaction of alkoxyalkynes 217 with PhI(OAc)NTs₂ under heating efficiently affords NTs₂-substituted 2,5-dihydrofuran 218 (Scheme 78).⁷⁰¹ The proposed reaction mechanism involves the reaction of PhI(OAc)NTs₂ with alkyne 217 to form intermediate alkynyliodine(III) species 219. Subsequent Michael addition of the NTs₂ anion generates alkylidene carbene 220, which is further converted to final product 218 by intramolecular 1,5-C–H insertion (Scheme 79).

Scheme 78. Preparation of NTs₂-Substituted 2,5-Dihydrofuran 218.

Scheme 79. Proposed Reaction Mechanism for the Synthesis of 218 from 217.

PhI(OAc)N(SO₂R)₂ reagents can be be generated and utilized in situ.⁷⁰² For example, the reaction of aromatic alkynes 221 with DIB 24 and dibenzenesulfonimides provides the corresponding ynamides 222 in moderate yields (Scheme 80).⁷⁰³ In this reaction, alkylidene carbene is also generated as a key intermediate, but because aryl-substituted alkynes are used, the common 1,2-rearrangement occurs, leading to alkynes 222.

Scheme 80. Preparation of (PhSO₂)₂N-Substituted Alkynes 222 from Alkynes 221.

An example of the formation and use of the PhI(OAc)NTs₂ reagent in situ has been reported for the cyclization of N-allylamides.⁷⁰⁴ The reaction of DIB 24 and bis-tosylimide with N-allylamides 223 gives the corresponding oxazolines 224 (Scheme 81). Under similar conditions, the reaction of N-allylthioamides afforded thiazolines. In these reactions, the generated PhI(OAc)NTs₂ species activate the alkene moiety, initializing the cyclization.

Scheme 81. Oxidative Cyclization of N-Allylamides 223.

3.3.3. Iodonium Imides

Iodonium sulfonimides, PhI = NSO₂R, can be generally synthesized from DIB and sulfonamides under basic conditions and are known to be insoluble in common organic solvents due to the polymeric structure.⁸⁵ It has been demonstrated that the introduction of a coordinating substituent in the ortho-position of the phenyl ring improves the solubility and stability of iodonium imides and improves their reactivity. The most common synthetic application of these reagents is the transfer of the imino group to the substrate, but it is also known that they can be used as oxidants.⁷⁰⁵ Typical imino group transfer reactions are represented by the oxidative iminination of various transition metal compounds, such as complexes of Cu,⁷⁰⁶ Fe,^707−709 and Ag.⁷¹⁰ For example, Campbell and co-workers reported that the addition of PhINTs to a Ag(I) complex 225 gave an Ag(II) complex 226 (Scheme 82), whose structure was determined by X-ray crystallography.⁷¹⁰ In a similar reaction of Ag(I) complex 225 with an excess amount of PhINSO₂Ph, the corresponding Ag(II) complexes containing N(SO₂Ph)₂ were obtained in high yields and confirmed by X-ray analysis. Furthermore, the authors have confirmed by NMR that a Ag(III) complex can be generated in the system from an excess amount of iminiodane with Ag(I) complex, and they suggested that this is the active species in the silver-catalyzed aziridination of alkenes by PhINTs.

Scheme 82. Preparation of Ag(II) Complex 226.

Typical metal-catalyzed reactions of iminoiodanes include aziridination of alkenes, C–H amination, and transamination toward heteroatoms.⁸⁵ In recent years, aziridination reactions utilizing various metal catalysts have been reported.^711−715 There have also been numerous reports on the methodologies based on generating iodonium imide species in situ to perform these reactions.^716−723 In addition to aziridination of olefins, aminocyclopropanation reactions of allenes are also known. Pérez and co-workers reported that the reaction of allenes 227, alcohols, and iminiodanes in the presence of silver catalysts gave the corresponding aminocyclopropanated compounds 228 in moderate yields (Scheme 83).⁷¹³ The structures of the products have been determined by X-ray crystallography. The authors have also reported that, under similar conditions, the reaction without the alcohol yields azetidine when the substrate is an aromatic allene, while the reaction with an aliphatic allene yields methylene aziridine.

Scheme 83. Synthesis of Aminocyclopropanes 228 from Allenes 227.

Several examples of C–H amination reactions using iodonium imides with various metal catalysts have been investigated, and stereoselective and regioselective aminations have been reported.^724−728 For example, White and co-workers reported a benzyl position selective C–H amination reaction utilizing Mn catalyst.⁷²⁶ The reaction of aromatic compounds 229 proceeds in the presence of Mn catalyst and iodine(III) reagent to give the corresponding C–H amination products 230 (Scheme 84). This reaction can also be used for C–H amination of compounds with various natural product skeletones. A characteristic feature of the selectivity of this amination is that when the substrate has an electron-rich benzyl position and an electron-deficient benzyl position, the electron-rich benzyl position is selectively aminated, and in amination reactions to secondary and tertiary benzyl positions, amination proceeds in a secondary position regioselectively. According to the results of deuterium experiments, the authors suggest that the rate-limiting step in this reaction is the C–H bond cleavage step. Recently, in addition to these C–H amination reactions, Pérez’s group has also reported Si–H amination reactions of silane compounds.⁷²⁹

Scheme 84. Selective Benzylic C–H Amination of 229.

Transimination reactions have been investigated previously, and a variety of new methods have been reported very recently.^730−732 Numerous reports on the imination reactions of sulfur atom using the in situ generated iodonium imide species from NH₂CO₂NH₄,^733−739 (NH₄)₂CO₃,^740,741 and NH₃^742,743 have recently been published. The generated PhI = NH species could exist for only a short time but has been successfully detected by HRMS. For example, Bull and Luisi reported that the reaction of a tertiary amine compound 231 with PhIO 17, NH₂CONH₄, and TsOH efficiently produced a quaternary ammonium product 232 in which the NH₂ group from NH₂CONH₄ was attached to the nitrogen atom of the amine (Scheme 85).⁷³⁸ The reaction is chemoselective and proceeds nitrogen-atom-selectively even if the substrate contains an oxygen atom or double bond. The authors believe that this reaction involves intermediate formation of PhI = NH species in the reaction system.

Scheme 85. Preparation of Hydrazinium Tosylate Salts 232.

Reactions utilizing iminoiodane without the use of metal catalysts are known, and C–H amination and trans-imination reactions have been reported.^744−748 Saito and co-workers reported the cycloaddition reaction using iminoiodanes without metal catalysts.⁷⁴⁹ This reaction was performed by adding C₆F₅INTs to an alkyne 233 in the presence of BF₃ in nitrile solvent to give the corresponding imidazole 234 (Scheme 86).⁷⁴⁹ The authors synthesized a highly electrophilic iminoiodane, C₆F₅INTs, and found that this reagent has enhanced reactivity in this reaction.

Scheme 86. [2 + 2 + 1] Cycloaddition Reaction Using C₆F₅INTs.

Reactions using iminoiodanes under light irradiation conditions^750−754 or with photocatalysts⁷⁵⁵ have recently been reported. For example, Kobayashi and Takemoto reported the amination of various substrates by activation of iminoiodanes under photoirradiation.^750,751,754N-Acyliminoiodanes and N-sulfonyliminoiodanes were used as the iodine reagents in the reaction. The N-acyliminoiodanes were previously reported to be unstable compounds,⁷⁵⁶ but the authors found that they could be stabilized by introducing a coordinating substituent at the ortho-position, and their structures were confirmed by X-ray crystallography. In the reaction with N-acyliminoiodane, mesitylene 235 reacted with the iodine(III) reagent 236 (n = 1) under photoirradiation at 365 nm to give the corresponding N-acylated compound 237 (n = 1) in 77% yield (Scheme 87).⁷⁵¹ This reaction also proceeded with iodine reagents bearing perfluoroalkyl groups of different chain lengths to give the respective products in moderate yields. The reaction proceeds efficiently with anisoles and heteroarenes, including some bioactive compounds as substrates, while reactions with toluene, bromobenzene, and chlorobenzene did not afford the products 237.

Scheme 87. Photoinduced C–H Amination of Mesitylene 235 Using Reagent 236.

3.4. μ-Oxo-iodine(III) Compounds

Numerous representatives of μ-oxo-iodine(III) compounds, which are formed by bridging two hypervalent iodine moieties with oxygen atoms, have been synthesized and structurally investigated.¹⁸³ In general, these compounds are more electrophilic and more reactive than their monomeric analogues because of the presence of the bridging oxygen.^757,758 The general method of their synthesis consists of adding water to a monomeric hypervalent iodine reagent under stirring.⁷⁵⁹ Since 2016, several new iodine(III) compounds with μ-oxo structure have been synthesized, and their structures have been determined by X-ray crystallography.^{258,343,760,761} Recently, Powers and co-workers have found that crystallization of equal amounts of iodine(III) compounds 238 and 239 from a TFE-MeCN mixture yielded yellow crystals of μ-oxo-iodine(III) compound 240 with a tetrameric structure confirmed by X-ray crystallography (Scheme 88).⁷⁶¹ This structure is formed by the elimination of water from dimer 241, which is initially formed by condensation of 238 and 239. The formation of 241 was confirmed by mass spectrometric analysis.

Scheme 88. Steps in the Formation of Tetrameric Molecule 240.

Deng’s group has successfully synthesized μ-oxo-iodine(III) compounds with a nitrooxy group as a ligand, and their structures have been confirmed by X-ray.²⁵⁸ Two methods for synthesizing these compounds have been reported: (1) the reaction of DIB with nitric acid and (2) the reaction of silver nitrate with ArICl₂; both methods yielded the corresponding μ-oxo-iodine(III) compounds in moderate to high yields. The authors have also investigated the reactivity of these compounds and reported that cyclopropyl trimethylsilyl ether 242 reacts with reagent 243 in the presence of a zinc catalyst to afford β-substituted ketones 244 in which the carbon–carbon bond in the original cyclopropane ring was cleaved (Scheme 89). When TEMPO is added as an additive, the yield of the target product is low and the product due to the combination of the substrate and TEMPO is formed. From these results, the authors suggest that the radical species may be involved in this reaction. They also evaluated the reaction mechanism by computational methods. In the reaction using β-ketoesters and β-keto amides as substrates, the corresponding α-nitrooxylated compounds were efficiently obtained.

Scheme 89. Nitrooxylation of Cyclopropyl Trimethylsilyl Ether 242.

3.5. Iodine(III) Compounds with Sulfonyloxy Ligands

3.5.1. [Hydroxy(sulfonyloxy)iodo]arenes

[Hydroxy(sulfonyloxy)iodo]arenes can be easily synthesized by ligand exchange reactions from [bis(acyloxy)iodo]arenes such as DIB and the corresponding sulfonic acid, most commonly, p-toluenesulfonic acid.^24,762 These reagents are not only efficient oxidants for various substrates^763−768 but also useful sulfoxyloxylating agents.^769−771 Furthermore, a difunctionalization reaction of iodination-sulfoxyloxylation has recently been reported.⁷⁷² The reaction of 2H-indazole 245 and [hydroxyl(tosyloxy)iodo]benzene (HTIB) 246 in acetic acid solvent under heating affords the corresponding disubstituted 2H-indazole compound 247, which is C-4-sulfonyloxylated and C-7-iodinated (Scheme 90). This reaction proceeds with very high regioselectivity, producing products 247 in generally high yields. Similar reactions of iodine(III) reagents with various other sulfonyloxy groups produce respective products in moderate to high yields.

Scheme 90. Difunctionalization of 2H-Indazole 245.

Intramolecular cyclization reactions of HTIB leading to the formation of carbon-heteroatom^773−776 and carbon–carbon bonds^777,778 have been reported. For example, Das and co-workers reported that the reaction of exocyclic β-enaminones 248 with HTIB 246 in the presence of AgSbF₆ leads to the formation of the corresponding carbazolones 249 via intramolecular carbon–carbon bond formation (Scheme 91).⁷⁷⁶ In the reaction of an exocyclic β-enaminone with 2-aminopyridine as a substituent, an intramolecular carbon-heteroatom bond formation occurs to yield the corresponding imidazo[1,2-a]pyridine. The authors suggest that the rate-limiting step in this reaction is not the aromatic C–H bond cleavage because the deuterium labeling experiments did not reveal any significant kinetic isotope effects. The presence of AgSbF₆ is important because the generated iodonium salt 250 with the hexafluoroantimonate counterion acts as a photoinitiator and initiates a free radical reaction via the radical-cation pathway.

Scheme 91. Synthesis of Carbazolones 249 from Exocyclic β-Enaminone 250.

Szpilman’s group has reported the reaction of various substrates with enolonium species generated from mixing silyl enol ethers with HTIB reagents.^779−782 For example, silyl enol ether 251 reacts with HTIB 246 in the presence of BF₃·Et₂O to form enolonium species 252, and then an aromatic compound 253 was added to the reaction to give the corresponding α-arylated ketone 254 (Scheme 92).⁷⁸¹ When one more molecule of silyl enol ether was added instead of the aromatic compound, the corresponding 1,4-diketone was obtained. The authors confirmed the presence of enolonium species formed in this reaction by NMR studies.⁷⁸² The same group also reported that the reaction of vinyl azide as the starting material instead of silyl enol ether with HTIB leads to the formation of an analogue of the enolonium species, the azide-enolonium species, which reacts with a nucleophile to give the corresponding α-keto compound.⁷⁸³

Scheme 92. α-Arylation of Ketones 254 via Enolonium Species 252.

3.5.2. [Cyano(trifluoromethylsulfonyloxy)iodo]arenes

[Cyano(trifluoromethylsulfonyloxy)iodo]benzene, PhI(CN)OTf, can be conveniently synthesized by reacting iodosylbenzene or DIB with TMSOTf and TMSCN at low temperature.^51,784 This reagent was originally reported more than 30 years ago, but its structure was not reliably established. Recently, Dutton and co-workers have revealed its X-ray structure.¹⁸⁶ In particular, the authors found that the I–O bond distance in PhI(CN)OTf is longer than that of the known partially ionic PhI(OAc)OTf. In addition, ¹⁹F NMR studies indicated that the triflate signal in this compound is close to the signal of triflate anion, suggesting that PhI(CN)OTf is an ionic compound.

ArI(CN)OTf reagents are commonly used in the synthesis of various iodonium salts.^785,786 For example, Hinkle and Pike have reported the cyclization reaction of propargylic alcohols 255 with ArI(CN)OTf, leading to the corresponding naphthyl(aryl)iodonium thiflates 256 in low to good yields (Scheme 93).⁷⁸⁶ The authors found from X-ray structural analysis that the hydroxyl group of the fragment R in product 256 is coordinated to the iodine center.

Scheme 93. Cyclization of Propargylic Alcohols 255 to Naphthyl(aryl)iodonium Triflates 256.

[Cyano(trifluoromethylsulfonyloxy)iodo]arenes can also be used as cyano-trifluorosulfonyloxylating reagents.⁷⁸⁷ Studer’s group has reported that the reaction of alkynes 257 with 3,5-(CF₃)₂C₆H₃I(CN)OTf in the presence of iron catalyst can regioselectively afford cyano-triflated products 258 in low to good yields (Scheme 94). These reactions are synthetically useful because they can convert disubstituted alkynes to tetrasubstituted alkenes in one step, and the OTf moiety of the obtained products can be further converted by appropriate treatment.

Scheme 94. Cyanotriflation of Alkynes 257.

3.5.3. [Bis(sulfonyloxy)iodo]arenes

The existence of [bis(sulfonyloxy)iodo]arenes was suggested long ago; however, their structures were not confirmed because of the high reactivity and low stability of these compounds.^187,191 In particular, the generation of PhI(OTf)₂ in situ has been utilized in many papers, but no identification data was provided.^453,788 Recently, Dutton and co-workers have reported the first successful preparation of p-NO₂C₆H₄I(OTf)₂259 from p-NO₂C₆H₄IF₂5 and 2 equiv of TMSOTf (Scheme 95), and its structure was established by X-ray crystallography.¹⁸⁹ The length of the I–O bond was found to be shorter than that of the reported I-OTf of PhI(OAc)OTf. The authors also found that p-NO₂C₆H₄I(OTf)₂259 peaks at a downfield compared to PhI(OAc)(OTf) in the fluorine NMR, suggesting that the I–O bond of p-NO₂C₆H₄I(OTf)₂259 is more associative than that of PhI(OAc)(OTf). The compound was highly unstable and decomposed at room temperature, but not under a nitrogen atmosphere at 150 K.

Scheme 95. Preparation of p-NO₂C₆H₄I(OTf)₂259.

The same authors have found that the reaction of compound 259 with triphenylmethane 260 yields diaryliodonium triflate 261 in 75% yield (Scheme 96).⁷⁸⁹ The control reaction using PhI(OAc)(OTf) instead of 259 did not proceed, indicating the higher reactivity of p-NO₂C₆H₄I(OTf)₂259. According to NMR studies, the reaction of compound 259 with cycloheptatriene yields tropylium triflate and the reaction with adamantane gives adamantyl triflate. Furthermore, the reaction of 259 with 1-fluoroadamantane affords p-NO₂C₆H₄I(F)(OTf). From this result, the authors also suggested that compound 259 can act as a Lewis acid.

Scheme 96. Reaction of Triphenylmethane 260 with p-NO₂C₆H₄I(OTf)₂259.

3.6. Iodine(III) Compounds with Carbon Ligands

3.6.1. Iodine(III) Compounds with Trifluoromethyl Ligand

Acyclic hypervalent iodine compounds with trifluoromethyl groups as ligands are usually unstable at room temperature. The formation of [PhICF₃]⁺-species in solution was confirmed by mass spectrometry,⁷⁹⁰ and X-ray structures of pseudocyclic trifluoromethyl-substituted iodanes were previously reported.⁷⁹¹ More recently, in 2018, Wang and co-workers reported the preparation of PhI(CF₃)Cl in high yields by adding TMSCF₃ to PIFA and treating with NaCl.⁷⁹² X-ray structural data indicated a significant ionic character of the I–Cl bond in this compound. This compound can work as a CF₃-introducing reagent for various organic substrates.^793−800 For example, PhI(CF₃)Cl 262 reacts with aromatic isocyanides 263, forming trifluoromethylation and cyclization products 264 in good yields (Scheme 97).⁸⁰⁰

Scheme 97. Trifluoromethylation-Cyclization of Isocyanides 263 with PhI(CF₃)Cl 262.

It has been reported that this reagent can transfer CF₃ to a carbon atom as well as to a nitrogen atom. For example, the reaction of PhI(CF₃)Cl 262 with nitriles 265 and a nitrogen nucleophile leads to N-trifluoromethylation and amination of the nitrile to give the corresponding amidine products 266 (Scheme 98).⁷⁹⁴N-Heterocycles as well as cyclic and acyclic amines can be used as nitrogen-based nucleophiles in this reaction. Other than nitrogen nucleophiles, alcohols and thiols can also be used as nucleophiles; in this case, the corresponding imidate and thioimidate products are obtained. It was suggested that these reactions involve initial interaction of nitrile 265 with the iodine reagent to form N-CF₃ nitrilium ions 267, followed by the reaction of a nucleophile to convert it to the final product. It has been recently reported that when methylene isocyanides are used as nucleophiles, the trifluoromethylation of the nitrile is followed by a cyclization reaction to yield the corresponding N-CF₃ imidazoles.⁷⁹³

Scheme 98. Synthesis of N-Trifluoromethyl Amidines 266 from Nitriles Using PhICF₃Cl 262.

PhI(CF₃)Cl can also be used for the addition of trifluoromethyl groups to alkynes and alkenes. For example, it has been reported that the reaction with alkynes 268 with PhI(CF₃)Cl 262 in the presence of NaH leads to the formation of alkenes 269 with syn addition of hydrogen and a trifluoromethyl group (Scheme 99).⁷⁹⁵ In the presence of TEMPO this reaction did not yield alkenes 269, which suggests that radicals are involved in the mechanism. Deuterium experiment indicated that the hydrogen atom for the conversion of alkynes to alkenes comes from DMF as the reaction solvent.

Scheme 99. Hydrotrifluoromethylation of Ynamides 268.

Reactions utilizing perfluoroalkyl-substituted iodanes have also been reported. For example, Studer and co-workers reported that perfluoropropyl-substituted hypervalent iodine reagent 271 reacts with aromatic alkyne 270 in the presence of a copper catalyst to give alkene 272 as a result of anti-addition (Scheme 100).⁸⁰¹ A similar reaction can also be efficiently performed with iodine reagents having perfluorohexyl or perfluorooctyl group as a ligand. The authors sugested that this reaction proceeds via initial generation of perfluoroalkyl radical from the iodine reagent and copper catalyst.

Scheme 100. Regio- and Stereoselective Perfluoropropylation of Alkyne 270.

3.6.2. Iodine(III) Compounds with Diazomethyl Ligand

Hypervalent iodine compounds with a diazomethyl group as the ligand were originally synthesized nearly 30 years ago, and their structure was investigated by X-ray.⁸⁰² These compounds can be used as reagents for transfer of the diazomethyl group to various substrates.⁸⁰³ For example, Singh and co-workers reported that the reaction of carbohydrazides 273 with reagent 274 under basic conditions yields diazirine compounds 275 (Scheme 101).⁸⁰⁴ Aromatic and aliphatic carbohydrazides can be used as substrates in this reaction. The reaction also proceeds with iodine reagents having ester moieties with various substituents. The authors suggested that the nitrogen atom of the carbohydrazide 273 initially reacts with reagent 274 to yield intermediate product 276 in which the diazomethyl group is transferred to the nitrogen atom, followed by intramolecular cyclization and oxidation to give the final product 275. In addition to this reaction, transfer reactions of the diazomethyl group to nitrogen atom with various substituents have also been reported.^805,806 Furthermore, transfer reactions to sulfur^807−809 and phosphorus atoms⁸⁰⁸ are also known.

Scheme 101. Diazirination of Carbohydrazides 273.

The transfer reaction of the diazomethyl group to the carbon atom has also been reported. Suero and co-workers reported that reactions of silyl enol ethers 277 with reagent 274 under basic conditions afford β-diazocarbonyl compounds 278 (Scheme 102).⁸¹⁰ They found that the reaction proceeds even when natural products and pharmaceuticals were used as substrates. The obtained β-diazocarbonyl compounds undergo stereoselective intramolecular cyclization using a rhodium catalyst to selectively afford 1,3-C–H-inserted cyclized compounds.

Scheme 102. α-Diazomethylation of Silyl Enol Ethers 277.

Li and co-workers have also reported the reaction of aromatic tertiary amines 279 with reagent 274 to introduce the diazomethyl group at the ortho-position of the nitrogen (Scheme 103).⁸¹¹ The resulting products 280 can be converted to the corresponding indole compounds using a rhodium catalyst. The authors suggest that the diazomethyl radical species are generated in this reaction via the formation of an EDA complex between the amine and the iodine reagent. A method for generating diazomethyl radical species with a photocatalyst and iodine(III) reagent under LED irradiation is known, and reactions using these conditions have been reported.⁸¹²

Scheme 103. ortho-Diazomethylation of Aromatic Tertiary Amines 277.

3.6.3. Iodonium Ylides

Iodonium ylides are carbon analogues of iodonium imides with the carbon atom bonded to the iodine atom.^104,198 Electron-withdrawing groups such as carbonyl and sulfonyl are usually used as the stabilizing substituents. Iodonium ylides can be synthesized by reacting DIB with a diketone or disulfonyl compound under basic conditions. Recently, Yoshino and Matsunaga reported a procedure in which aryl tin or germanium compounds are reacted with I(CO₂CF₃)₃ to generate PIFA species in the reaction system, followed by the addition of a Meldrum’s acid derivative to produce the corresponding ylide.⁸¹³ The same group also reported the synthesis of ylides using iodine triacetate.⁸¹⁴ Structures of several new ylides were investigated by X-ray diffraction studies.^815−818 The negatively charged carbon ligands in ylides in general have low nucleophilicity; however, they may act as nucleophiles toward highly electrophilic substrates.⁸¹⁹ Numerous reactions involving the carbon ligand of iodonium ylide have been well investigated, including cyclopropanation,^820−824 spirocyclization,^825−827 and ylide transfer reactions.^828,829 In recent years, heterocyclic ring annulation reactions utilizing iodonium ylides and various substrates have been reported. For example, Gao and Li reported a [3 + 3] cyclization reaction using iodonium ylide 281 and enaminone 282 in the presence of rhodium and silver catalyst, resulting in the corresponding isocoumarin products 283 (Scheme 104).⁸³⁰ Interestingly, this reaction does not proceed with acyclic iodonium ylides. The authors have suggested that the transition state in this reaction involves a C–H cleavage based on deuteration experiments. Similar reactions leading to isocoumarins have been reported by other groups.^831−833 Hung and Yu reported that when ruthenium catalyst was used instead of rhodium catalyst in a similar reaction, a [3 + 2] cyclization occurs to afford the corresponding 3a,7a-dihydroxyhexahydro-4H-indol-4-one.⁸³⁴ Heterocyclic ring annulation reactions utilizing various substrates and iodonium ylides and resulting in [3 + 3],^835−839 [3 + 2],^840−845 [4 + 1],⁸⁴⁶ and [4 + 2]^{835,847−855} cyclizations have also been reported.

Scheme 104. [3 + 3] Annulation of Enaminones 282 Using Iodonium Ylide 281.

While most of these reactions require transition metal catalysts, several publications report heterocyclic synthesis using single electron transfer methodology that does not require transition metal catalysts.^856−858 For example, it has been reported that the reaction of acyclic aromatic tertiary amines 284 with iodonium ylide 285 in the presence of visible light irradiation proceeds as the [4 + 1] cyclization to give the corresponding indoline derivatives 286 (Scheme 105).⁸⁵⁶ It is also known that when cyclic aromatic tertiary amine compounds were used, N-phenylpyrrolidines could be obtained. In these reactions, the addition of TEMPO does not yield the desired product, while the addition of CCl₄ yields a chlorinated compound derived from CCl₄, indicating that radicals are involved in the reaction. The authors hypothesize that EDA complexes are formed with iodine(III) and amine reagents in the early stages of the reaction, and these complexes induce single-electron transfer under visible light. As well as cyclization reactions, such reactions using single-electron transfer reactions have also been used in three-component condensation reactions.^859,860

Scheme 105. Cyclization of Aromatic Tertiary Amines 284 Using Iodonium Ylide 285.

The insertion of iodonium ylide carbon ligands into C–H bonds has been investigated previously,¹⁰⁴ and several new reports have been published recently.^861−864 Jiang and Liu reported that the reaction of a pyridine compounds 287 with an inactive C(sp³)–H bond with a cyclic iodonium ylide 288 in the presence of rhodium and silver catalysts gives products 289 in which the ligand of the iodonium ylide is inserted into the C(sp³)–H bond (Scheme 106).⁸⁶² The obtained products could be further converted into various derivatives under appropriate conditions. The authors found that the reaction of 2-(tert-butyl)pyridine with rhodium and silver catalysts in the absence of iodonium ylide produced a cyclic pyridine-rhodium complex compound 290. The reaction of the obtained complex 290 with iodonium ylide 288 gave the desired product, implying that the pyridine-rhodium complex is an important key intermediate in the reaction.

Scheme 106. Unactivated C(sp³)–H Bond Insertion Reaction of Pyridines 287.

Several reactions based on the generation and utilization of iodonium ylides in situ have been reported.^865−868 Ylide species can be generated by reacting an aliphatic monovalent iodine compound with a diazo compound. Tambar’s group has reported sigmatropic rearrangement reactions using this approach. Addition of tert-butyl α-diazo ester 291 to aryl-substituted allylic iodides 292 in the presence of copper catalysts leads to a [2,3]-sigmatropic rearrangement affording the corresponding terminal alkene products 293 with high regioselectivity (Scheme 107). This reaction proceeds efficiently even with polysubstituted allyl iodides.

Scheme 107. Copper-Catalyzed [2,3]-Sigmatropic Rearrangement.

The reactions of iodonium ylides resulting in nucleophilic substitution of the iodonium moiety in an aromatic ring have been reported. In particular, iodonium ylides are commonly used to introduce fluorine-18 radiolabeling into unactivated aromatic rings.^102,869,870 In recent years, numerous syntheses of iodonium ylides with various substituents in the aromatic ring followed by fluorine-18 radiolabeling on the aromatic ring have been reported.^871−880 For example, Li and Cai reported the synthesis and radiofluorination reaction of iodonium ylide 294 to give fluorinated product 295 with a radiolabeled ortho-position (Scheme 108). Reaction with iodonium ylide having an alkoxy group in the para-position also yields compounds with ¹⁸F in the para-position. Product 295 can be used as a radioactive tracer suitable for medical imaging of 11β -HSD1 in the primate brain. Several similar reactions leading to the functionalization of the aromatic ring of iodonium ylides have been reported.^881−883

Scheme 108. Radiofluorination of Iodonium Ylide 294.

3.6.4. Iodonium Salts

Iodonium salts are generally defined as hypervalent iodine(III) compounds with two carbon ligands, and their chemistry has been summarized in numerous review articles.^{32,54,60,88,165,884,885} The most typical reactions of iodonium salts result in a transfer of the carbon ligand to various nucleophilic organic substrates. Recent examples of the reactions of iodonium salts bearing alkynyl, alkenyl, alkyl, and aryl groups as the ligands are discussed in this section.

Alkynyliodonium salts can be conveniently synthesized by ligand exchange reactions between alkynyltin compounds and hypervalent iodine(III) reagents.⁸⁸⁶ Reactions of alkynyliodonium salts with various nucleophiles lead to a transfer of the alkynyl ligand yielding the corresponding substituted alkynes.^887−890 The C–H bond insertion reactions using alkynyliodonium salts are also known.⁸⁹¹ For example, Kalek and co-workers reported that the reaction of aldehydes 296 with alkynyliodonium salts 297 in the presence of an NHC catalyst yields ynones 298 in which the C–H bond of the aldehyde is replaced by the alkynyl group (Scheme 109). Based on ¹³C-labeling experiments and DFT calculations, the authors suggest that the alkynyl group insertion into the C–H bond of the aldehyde proceeds by direct substitution of iodine via a Breslow intermediate that occurs at the α-acetylenic carbon.

Scheme 109. NHC-Catalyzed Synthesis of Ynones 298 from Alkynyliodonium Salts and Aldehydes.

Recent studies have demonstrated that alkynyliodonium salts can be used for the generation of diatomic carbon (C₂). Miyamoto and Uchiyama reported that upon treatment of alkynyliodonium salt 299 with TBAF in the presence of 9,10-dihydroanthracene 300, C₂ is generated and trapped to form anthracene 301 and acetylene 302 (Scheme 110).⁸⁹² They also reported that nanocarbons such as graphite, carbon nanotubes, and C₆₀ can be produced by reacting alkynyliodonium salt 299 with a source of fluoride anion. The mechanism of C₂ formation has been investigated by computational chemistry.^893−895 Recently, a reaction utilizing this mehod of C₂ generation was reported by Saito’s group.⁸⁹⁶ They reported that the reaction of alkynyl iodonium triflate 303 with N-(acyloxy)sulfonamide 304 under basic conditions gave the corresponding N-(acyloxy)-N-alkynylamide 305 (Scheme 111). The authors have also found that, in the presence of TEMPO or galvinoxyl, product 305 is not formed, which supports the reaction mechanism involving C₂ reactive species.

Scheme 110. C₂ Generation and Trapping Reaction in the Presence of 9,10-Dihydroanthracene 300.

Scheme 111. Reaction of Alkynyliodonium Salt 303 with N-(Acyloxy)sulfonamides 304.

Vinyliodonium salts are useful reagents for vinyl group transfer. Recently, a convenient synthesis of vinyliodonium salts by reactions of alkynes with iodine(III) reagents such as DIB or PhIO has been reported.^681,788,897 The preparation of vinyliodonium salts from alkynyliodonium salts by addition reaction has also been reported.^898,899 Vinyliodonium salts can transfer the vinyl group from iodine to carbon atoms⁹⁰⁰ and various heteroatoms.^{785,901−906} It has also been reported that these salts can be used for the transfer reactions to radioactive atoms.^907,908 Gao and co-workers reported the vinyl group transfer reaction to oxygen atoms of arylhydroxylamines.⁹⁰² The reaction of arylhydroxylamines 306 with vinyliodonium salt 307 under basic conditions and in the presence of a copper catalyst affords the corresponding indoles 308 (Scheme 112). The authors suggest that the reaction proceeds by the vinylation to oxygen atoms of arylhydroxylamines to give O-vinyl-N-arylhydroxylamines 309, followed by several steps involving [3,3]-sigmatropic rearrangements leading to final product. The resulting compounds 308 can be converted to other indole derivatives by appropriate treatment. In addition to the vinyl group transfer reactions to various atoms, vinyl group insertion reactions into C–H bonds have also been reported.^909−913

Scheme 112. Synthesis of Indoles 308 from Arylhydroxylamines 306 and Vinyliodonium Salt 307.

It has been reported that vinyliodonium salts can be used for cyclization reactions as well as the addition of vinyl groups to substrates. For example, Stirling and Novák reported an efficient two-step synthesis of vinyliodonium salts from vinyl iodides and the aziridination reaction using them.⁹¹⁴ In this reaction, reagent 310 and an amine 311 are combined under basic conditions to give the corresponding aziridine 312 (Scheme 113). The authors have also proposed the reaction mechanism. The suggested mechanism involves initial nucleophilic addition of amine to the β carbon of the vinyl moiety, followed by cyclization to the aziridine ring.

Scheme 113. Aziridination of Amines 311 Using Vinyliodonium Salt 310.

Several representatives of alkyliodonium salts stabilized by electron-withdrawing substituents on the alkyl group were previously known, and several new such compounds have been synthesized and investigated recently.⁸⁸⁵ Various reactions of alkyliodonium salts have been studied, including the transfer of alkyl groups to various heteroatoms^915−917 and the insertion of alkyl groups into C–H bonds.^918−921 For example, Stirling and Novák reported the synthesis of a new alkyliodonium compound 313 from 3-chloro-1,1,1,2-tetrafluoro-2-iodopropane via a dyotropic rearrangement. and its structure was established by X-ray crystallography.⁹²² The authors have also found that the reaction of compound 313 with anilines 314 under basic conditions gave the corresponding alkylanilines 315 (Scheme 114). In addition to anilines, the authors have also reported N-alkylation reactions of heterocyclic compounds and C-alkylation reactions of indoles.

Scheme 114. N-Alkylations of Anilines 314 Using Alkyliodonium Salt 313.

Diaryliodonium salts represent one of the most common classes of hypervalent iodine compounds with many practical uses. A broad variety of symmetric, nonsymmetric, and heterocyclic diaryliodonium compounds have been synthesized and utilized as reagents in organic synthesis.^{32,54,60,98,884,923−925} Diaryliodinium salts with various functional groups have been recently synthesized using two main approaches: (1) the reaction of aromatic compounds with hypervalent iodine(III) reagents or (2) the in situ oxidation of aryl iodides in the presence of aromatic compounds.^926−940 Various counteranions have been introduced in the structure of diaryliodinium salts.^{196,941−944} Structures of numerous new diaryliodinium salts have been established by X-ray crystallography. The reactivity of these compounds as Lewis acids depending on the substituents in the aromatic ring has been investigated.^945,946 Diaryliodonium salts are widely used as reagents for the arylation of nucleophilic carbon^947−958 or heteroatoms^959−973 in various substrates. The reactions of diaryliodonium salts with the corresponding nucleophiles are often used for the introduction of a radioactive label into an aromatic ring, such as the introduction of radioactive fluorine,^974−979 bromine,⁹⁸⁰ and carbon.⁹⁸¹

Several rearrangement reactions resulting in the transfer of an aryl group in diaryliodonium species to a heteroatom at the ortho-position of the second aryl substituent have recently been reported.^982−985 Olofsson and co-workers have reported that heating of a diaryliodonium salts 316 bearing a cyclic amino group in the ortho-position, followed by the addition of piperidine as a nucleophile under basic conditions, affords the corresponding anilines 317 (Scheme 115).⁹⁸⁴ The initial product of this reaction, quaternary ammonium salt 318 resulting from the rearrangement of iodonium salt 316, can be isolated. Ammonium salts 318 can be efficiently converted to the final aniline products by adding piperidine or other nitrogen, halogen, and oxygen nucleophiles.

Scheme 115. Synthesis of Anilines 317 from Diaryiodonium Salts 316.

Diaryliodonium salts are commonly used as benzyne or aryne precursors.¹⁰⁰ Recently, numerous examples of such reactions have been reported.^{166,923,986−992} Kitamura and his group have reported the synthesis and reactions of diaryliodonium salt that can consequently generate benzyne species at the 1- and 4-positions.⁹⁸⁶ For example, the reaction of [2,5-bis(trimethylsilyl)-4-(trifloxy)phenyl](phenyl)iodonium triflate 319 in the presence of CsF with 2,5-dimethylfuran as a first arynophile and tetraphenylcyclopentadienone as a second arynophile leads to a double cycloaddition reaction to give the corresponding product 320 in high yield (Scheme 116). The same group has also succeeded in synthesizing diaryliodonium salt, which can generate benzyne species at both the 1- and 3-positions, and reported the double cycloaddition reaction using this salt.

Scheme 116. 1,4-Double Cycloaddition of Diaryliodonium Triflate 318.

4. Cyclic Iodine(III) Compounds as Reagents

Cyclic hypervalent iodine compounds in general have higher thermal stability and modified reactivity compared to their acyclic analogues. The high thermal stability and lower reactivity of these compounds is explained by the link between apical and equatorial ligands at the iodine center, which restricts pseudorotation and reductive elimination of the iodoarene fragment.^993,994 The vast majority of practically important cyclic hypervalent iodine reagents are based on the heterocyclic systems of benziodoxole or benziodazole. In recent years, various iodine-substituted benziodoxole derivatives have been prepared and utilized as reagents for transfer of the substituent on hypervalent iodine to organic substrate. The chemistry and synthetic applications of benziodoxoles and other hypervalent iodine heterocycles have been summarized in numerous recent reviews.^{5,7,19,106,107}

4.1. Cyclic Iodine(III) Compounds with Halide Ligands

4.1.1. Fluorobenziodoxoles and Fluorobenziodazoles

Cyclic hypervalent iodine compounds with fluorine atoms as ligands belong to a relatively new class of iodine reagents originally synthesized about 10 years ago.⁴⁹ A new synthesis of fluorobenziodoxoles from the corresponding aryl iodides and AgF₂ was recently reported.²²⁵ Fluorobenziodoxoles are useful fluorinating reagents, similar to acyclic difluoroiodoarenes. In particular, numerous examples of fluorocyclizations of olefinic substrates using fluorobenziodoxoles have been reported.^995−1006 Li and Lu have found that the reaction of fluorobenziodoxole 322 with an unsaturated carbamate 321 leads to an intramolecular fluorocyclization yielding fluorinated oxazolidin-2-ones 323 (Scheme 117).¹⁰⁰³ The addition of TEMPO to the reaction reduces the yield of the products 323, and the addition of BHT yields a BHT-substituted products, which suggest that radical species are involved in the reaction mechanism. Fluorobenziodoxole with a radioactive fluorine ligand can also be used in this reaction to introduce radioactive fluorine atom into the product.

Scheme 117. Intramolecular Fluorination of Carbamates 321 Using Fluorobenziodoxole 322.

When a diazocarbonyl compound, instead of an olefin, is used as a substrate in the reaction with a hypervalent iodine reagent in the presence of an oxygen nucleophile, an intermolecular oxyfluorination reaction proceeds, yielding the corresponding fluorinated product.^1007−1009 It has also been reported that, in the reaction of diazonium salts with a catalytic amount of iodine reagent and catalytic amount of BF₃·Et₂O, Baltz-Schemann reaction proceeds efficiently and the corresponding aromatic fluorinated compounds are obtained.²³⁴ Several other fluorination reactions of hypervalent iodine fluorides have been reported.^1010,1011 For example, Zhang and co-workers reported that the reaction of cyclopropane derivative 324 with fluorobenziodazole 325 in the presence of BF₃·Et₂O leads to a ring-expanding fluorination reaction, resulting in the corresponding six-membered cyclic products 326 (Scheme 118).¹⁰¹⁰ The authors suggested that the active iodine species in this reaction is the complex of the iodine reagent and BF₃, which was observed by NMR and mass spectrometry. The reaction mechanism was proposed using DFT calculations.

Scheme 118. Ring Expansion Fluorination of Cyclopropanes 324 Using Reagent 325.

Several reactions of fluorobenziodoxoles resulting in addition–elimination of fluorine have been reported.^{999,1012,1013} For example, Gulder and co-workers reported a reaction in which the addition of fluorobenziodoxole 322 in the presence of a nucleophile to 2-pyridyl ketones 327 leads to α-functionalized pyridyl ketone 328 (Scheme 119).¹⁰¹³ In this reaction, the α-position of the pyridyl ketone is first fluorinated, followed by a substitution reaction with a nucleophile to obtain the final product. In the absence of a nucleophile, the reaction yields the product of α-fluorination of the pyridyl ketone. The presence of the nitrogen atom in position 2 of the pyridyl ketone is essential; the product cannot be obtained by using a ketone substrate with a benzene ring instead of a pyridine ring or an isomer with a different position of nitrogen of the pyridine ring.

Scheme 119. α-Functionalization of 2-Pyridyl Ketones 327.

4.1.2. Chlorobenziodoxoles and Chlorobenziodazoles

Chlorobenziodoxoles, cyclic iodine(III) derivatives with a chlorine atom ligand, are important chlorinating reagents for various organic substrates.⁴⁹ Several new chlorination reactions using chlorobenziodoxoles have been reported recently.^1014−1018 Murphy and co-workers reported that the reaction of aromatic allenes 329 with chlorobenziodoxole 330 yields products of dichlorination of the terminal double bond 331 with predominant (Z)-selectivity (Scheme 120). In the reaction of an aromatic allene with an alkyl group R¹ at the α-position of the allene, a mixture of dichlorinated and monochlorinated products is formed. A similar reaction of an allene with (dichloroiodo)benzene is not selective, leading to several isomers of dichlorinated products.

Scheme 120. Dichlorination of Aromatic Allenes 329 Using Chlorobenziodoxole 330.

Chlorobenziodoxoles can also be used as selective oxidants of organic substrates.^1019−1022 For example, the reaction of alkynes 332 with chlorobenziodoxole 333 and sodium sulfonates 334 efficiently yields 1,2-disulfonylethenes 335 with high (E)-selectivity (Scheme 121).¹⁰²⁰ The authors believe that radicals are involved in this reaction because in the presence of TEMPO product 335 is not formed. They also assume that the initial products of ligand exchange between chlorobenziodoxole with sodium arylsulfinates are the active species in this reaction, as confirmed by ESI-MS spectrometry.¹⁰²¹

Scheme 121. Disulfonation of Terminal Alkynes 332.

Du and co-workers have found that the reaction of chlorobenziodazole 336 with silver cyanate in water and chloroform as cosolvents formed μ-oxo compound 337 (Scheme 122).¹⁰²³ The authors have also reported that, in the absence of water, compound 338 with isocyanate ligand was obtained. Both structures were determined by X-ray crystallography.

Scheme 122. Ligand Exchange Reactions of Chlorobenziodazole 336.

4.2. Cyclic Iodine(III) Compounds with Oxygen Ligands

4.2.1. Alkoxybenziodoxoles

The acyclic hypervalent iodine compounds with alkoxy group ligands are relatively unstable and difficult to handle, whereas the cyclic derivatives, alkoxybenziodoxoles, are stable compounds. Alkoxybenziodoxoles can be prepared by a ligand exchange reaction of hydroxy- or acetoxybenziodoxoles with the corresponding alcohol,¹⁰²⁴ and their structure has been established by X-ray analysis.^636,1025 Recently, these compounds have been used as the reagents for C–H oxidation reactions.^{213,1024,1026−1029} For example, Chen and co-workers reported that sulfides 339 react with methoxybenziodoxole 340 in the presence of a photocatalyst under LED irradiation to form 2-iodobenzoic esters 341 via C–H acyloxylation reaction (Scheme 123).¹⁰²⁶ This reaction proceeds efficiently not only with aryl- and alkyl-substituted substrates 339 but also with sulfur compounds with amino acid fragments as substituents. The C–H bond cleavage is the rate-determining step in this reaction, as confirmed by the reaction of deuterium-substituted substrate. The reaction most likely has a radical mechanism as supported by the experiments in the presence of TEMPO or BHT.

Scheme 123. C–H Acyloxylation of Sulfides 339.

Wallentin and co-workers prepared numerous alkoxybenziodoxoles by ligand exchange reactions between various alcohols and acetoxybenziodoxole, and reported C–H oxidation with these reagents.¹⁰²⁴ When these alkoxybenziodoxoles 342 were treated with blue LED irradiation in the presence of a photocatalyst, an intramolecular cyclization reaction proceeded, resulting in the chromane products 343 (Scheme 124). In this reaction, the photocatalytic one-electron reduction of compound 342 generates the corresponding alkoxy radicals, followed by radical cyclization to yield the final products 343 along with 2-iodobenzoic acid as a by-product. This radical cyclization proceeds by competitive 1,5- and 1,6-addition reactions, resulting in the formation of two structural isomers.

Scheme 124. Photocatalyst-Induced Intramolecular Cyclization of 342.

A C–H alkylation reaction of heteroaromatic rings using in situ generated alkoxybenziodoxole has been reported.¹⁰³⁰ In this reaction, cyclic acetoxybenziodoxole 344 reacts with various alcohols 345 and 4-chloroquinoline 346 in the presence of a photocatalyst and under irradiation with compact fluorescent lamps to form products 347 in which the 2-position of the quinoline ring is alkylated (Scheme 125). The reaction is also applicable to the substrates derived from natural products. The authors were able to isolate the initially formed alkoxybenziodoxole and demonstrated that it can be directly used in this reaction.

Scheme 125. Photocatalyst Mediated C–H Alkylation of 4-Chloroquinoline 346.

4.2.2. Acyloxybenziodoxoles

Acyloxybenziodoxoles are usually prepared by ligand exchange reactions between hydroxybenziodoxoles or acetoxybenziodoxoles and carboxylic acids, and the structures of several acyloxybenziodoxoles have been determined by X-ray crystallography.^1030,1031 Preparation of numerous acyloxybenziodoxoles using various carboxylic acids has been reported.^1031−1043 Acyloxybenziodoxoles can be formed in situ in the reaction system by ligand exchange reactions and used for the generation of acyloxy radicals via radical cleavage of the I–OCOR bond under reaction conditions. Further decarboxylation of the acyloxy radicals can produce alkyl radicals. The radical species generated in this process then undergoes various inter- and intramolecular reactions. As an example of the intermolecular reaction, Cramail and Landais reported that acetoxybenziodoxole 344 reacts with oxamic acid 348 and alcohol 349 under blue LED irradiation in the presence of a photocatalyst, leading to a decarboxylation reaction of oxamic acid and forming urethane products 350 (Scheme 126).¹⁰³⁷ It was reported that the addition of amines instead of alcohols yields the corresponding ureas. The proposed mechanism of this reaction involves initial formation of the carbamoyl radicals followed by their reaction with alcohols or amines to give final products. This mechanism was confirmed by additional experiments with TEMPO additives. The same group reported that when 4-methylquinoline 351 was used instead of alcohol in this reaction, products 352 with a carbamoyl group introduced at the 2-position were obtained.¹⁰³⁶ Other than 4-methylquinoline heterocycles can be used in this reaction to give the corresponding products regioselectively and in high yield. Recently, the same group has reported an example of a similar reaction using Os(bptpy)₂(PF₆)₂ instead of 4-CzIPN as a photocatalyst under near-infrared light irradiation.¹⁰³⁴

Scheme 126. Radical Reactions of Oxamic Acid 348 Using Acetoxybenziodoxole 344.

Several intra-^1044,1045 and intermolecular reactions^1046−1048 have been reported using one-electron transfer process between excited photocatalyst and acetoxybenziodoxole. An intramolecular cyclization occurs in the reaction of acetoxybenziodoxole 344 with cyclic alcohols 353 bearing an anilide moiety in the presence of [Ru(bpy)₃Cl₂·6H₂O] as a photocatalyst under blue LED irradiation and leading to the medium-sized ring lactams 354 (Scheme 127).¹⁰⁴⁵ This reaction also proceeds with heterocycle-substituted alcohols as substrates, resulting in the corresponding lactam products. Additional experiments in the presence of TEMPO suggested that this reaction proceeds via amidyl radicals. As an example of an intermolecular reaction utilizing a similar combination of a photocatalyst and acetoxybenziodoxole, a reaction of primary alkylborates 355 with TsCN 356 leading to cyanoalkanes 357 was reported (Scheme 128).¹⁰⁴⁸ It was also reported that the reaction of alkylborates with pyridine-N-oxides instead of TsCN yields alkylated pyridine-N-oxides.¹⁰⁴⁶

Scheme 127. Intramolecular Cyclization of Cyclic Alcohols 353.

Scheme 128. Cyanation of Alkyltrifluoroborates 355.

Acyloxybenziodoxoles and their derivatives have also been used as coupling reagents for various substrates.^1049−1051

4.3. Cyclic Iodine(III) Compounds with Nitrogen Ligands

4.3.1. Azidobenziodoxoles and Derivatives

Preparation, structure, and reactivity of azidobenziodoxoles were originally reported about 30 years ago.^1052,1053 The chemistry of these compounds was recently summarized in several specialized reviews.^7,19,111 These compounds have been used as efficient reagents for transfer of the azido groups to various organic substrates.^7,107 Some azidobenziodoxoles have low thermal stability and can be sensitive to friction and shock. To improve the stability of these reagents, substituents can be introduced into the aromatic ring,¹⁰⁵⁴ or the iodoxole ring can be modified with various functional groups.¹⁰⁵⁵ The stability of azidobenziodoxoles has also been investigated by computational analysis.^207,1056 Typical reactions of azidobenziodoxoles include the following: azide addition to unsaturated compounds,^1057−1068 azidation of C–H bonds,^1069−1082 and application as HAT reagents utilizing the generated azido radical species.^1083−1085 Waser and co-workers reported that reactions of alkenes 358 and alkynyl borates 359 with azidobenziodazole 360 under blue light irradiation in the presence of a photocatalyst yield products 361 in which the azido and the alkynyl groups are regioselectively bonded to the alkene (Scheme 129).¹⁰⁵⁷ Proposed mechanism of this reaction includes initial generation of azido radicals by interation of the photocatalyst excited by blue light reacting with the iodine reagent, followed by regioselective addition to the olefin. When diphenyl phosphate is used in place of the alkyne, the corresponding product is obtained in moderate yield. The authors also noted that the azide moiety of the obtained compound can be efficiently converted to an amine by reduction.

Scheme 129. Azido-Alkynylation of Alkenes 359.

Azidobenziodoxoles can also be used in intramolecular azidation-cyclization reactions. For example, Cao and Deng reported that the reaction of tryptamines 362 with azidobenziodoxolone 363 in the presence of a copper catalyst and a catalytic amount of a chiral ligand leads to a dearomatic asymmetric azidation-cyclization reaction to afford the corresponding tricyclic products 364 with high enantioselectively (Scheme 130).¹⁰⁶⁶ The authors believe that azide-Cu intermediates are initially formed from the iodine reagent and copper catalyst, and further reaction proceeds via radical addition of active azido radicals generated from these intermediates to tryptophan. Addition of various radical scavengers to the reaction suppressed the formation of products 364, confirming the involvement of radical species in the reaction mechanism.

Scheme 130. Dearomatic Azidation-Cyclization of Triptamines 362.

Selective azidation of the alkyl group attached to the 2-position of the indole ring using azidobenziodoxoles has been reported. For example, the reaction of indole derivatives 365 with azidobenziodoxole 363 in the presence of a copper(I) catalyst provides products 366 that are selectively azidated in the alkyl group (Scheme 131).¹⁰⁸² A similar azidation occurs with tetrahydrocarbazole as a substrate.

Scheme 131. Selective C–H Azidation of Indoles 365.

The azido radical species produced from azidobenziodoxole can also be used in hydrogen abstraction reactions of various substrates. For example, Chen and Wang reported that the reaction of compound 367 containing a tertiary alkyl group as a substrate with azidobenziodoxole 363 in a chloroform-water mixture under visible light irradiation yields product 368 in which the tertiary C–H is chlorinated (Scheme 132).¹⁰⁸⁵ This reaction proceeds even when secondary alkyl groups are used as substrates, but the selectivity is slightly reduced. Bromoform can be used instead of chloroform to obtain the corresponding brominated compounds. In this reaction, light irradiation generates active azido radicals, which selectively abstract hydrogen from the substrate, producing carbon radical species, followed by chlorine or bromine abstraction from chloroform or bromoform to give final products.

Scheme 132. Selective C–H Chlorination of Tertiary Alkyl Compounds 367.

4.3.2. Amido-, Amino-, and Iminobenziodoxoles

Numerous cyclic hypervalent iodine compounds with the amino, amido, or similar nitrogen functional groups as ligands have been synthesized, and their structures have been established by X-ray crystallography.^{697,1086−1091} Many of these compounds can be used as efficient nitrogen functional group transfer reagents to various substrates.⁷ For example, Bolm and co-workers reported that the reaction of styrenes 369 with 1-sulfoximidoyl-1,2-benziodoxoles 370 under blue LED irradiation in the presence of Eosin Y as a photocatalyst efficiently gave the bifunctionalized products 371 (Scheme 133).¹⁰⁹² The authors suggest that the hydrogen bonding ability of the phenolic hydroxyl and carboxyl moieties of the photocatalyst Eosin Y influences the intermediates involved in this reaction as well as the stereochemistry of the products. Hydrogen bonding is important in this reaction, and the reactions in the presence of Ru- or Ir-based photocatalysts do not show any significant diastereoselectivity.

Scheme 133. Bifunctionalization of Styrenes 369 Using 1-Sulfoximidoyl-1,2-benziodoxoles 370.

Kiyokawa and Minakata reported several reactions using benziodoxoles with (diarylmethylene)amino groups as ligands.^{1090,1093,1094} For example, in the reaction of styrenes 372 and carboxylic acids 373 with reagents 374 under basic conditions with blue LED irradiation, a bifunctional addition proceeds to give products 375 (Scheme 134).¹⁰⁹³ This reaction proceeds via initial formation of diphenyl iminyl radical and ortho-iodobenzoyloxy radical generated from the iodine(III) reagent by blue LED irradiation.

Scheme 134. Alkylamination of Styrenes 372.

A reaction involving the combination of a benziodoxole and imido compounds to generate an I–N bonded iodine(III) reagent in situ has been reported. Xue and Chen’s group reported that the reaction of dimethylbenziodoxole 376 with cyclic alcohols 377 and imides 378 in the presence of a copper catalyst, a photocatalyst, and catalytic amounts of ligands under blue LED irradiation gave the corresponding imidoketones 379 (Scheme 135).¹⁰⁸⁶ The authors detected the intermediate alkoxy iodine(III) active species in this reaction formed from dimethylbenziodoxole and alcohols and the iodine(III) species with I–N bonds from dimethylbenziodoxole and amino compounds by ¹H NMR. The structure of one of the iodine(III) compounds with an I–N bond has been determined by X-ray crystallography. This reaction is applicable to bioactive molecules with complex skeletons such as cholesterol derivatives and Celecoxib as substrates to obtain the corresponding products. The authors have also investigated the mechanism of this reaction by DET calculations as well as UV–vis and fluorescence quenching experiments.

Scheme 135. Preparation of Aminoketones 379 from Cyclic Alcohols 376 with Imides 378.

Cyclic hypervalent iodine reagents with amino ligands are useful reagents for transfer of the amino group to organic substrates.⁷ For example, Liu and Chen reported that the carbazole-substituted benziodoxole 380 reacts with thiophenes 381 in the presence of a copper catalyst, resulting in a regioselective C–H insertion of the carbazole group forming products 382 (Scheme 136).¹⁰⁸⁹ The C–H amination reactions of anilines using aminobenziodoxoles with cyclic amino group ligands,¹⁰⁸⁸ and α-amination to β-ketoesters using aminobenziodoxoles with acyclic aliphatic amine ligands have also been reported.¹⁰⁸⁷

Scheme 136. C–H Insertion Amination Reaction of Thiophenes 381.

4.4. Cyclic Iodine(III) Compounds with Carbon Atom

4.4.1. Trifluoromethylbenziodoxoles and Derivatives

Trifluoromethylbenziodoxoles and their analogues are cyclic iodine(III) compounds with a trifluoromethyl group as a ligand, which are useful trifluoromethylation reagents that can transfer the trifluoromethyl group to various heteroatoms, unsaturated bonds, and C–H bonds.^27,1095,1096 Various trifluoromethyl-substituted cyclic iodine(III) compounds were synthesized, and their structures were investigated by X-ray crystallography.^1097−1101 Trifluoromethylbenziodoxoles or their analogues are commonly used as the reagents for transferring trifluoromethyl group to heteroatoms such as oxygen,^1102−1104 nitrogen,¹¹⁰⁵ and sulfur^1106−1108 atoms. For example, Togni’s group reported the trifluoromethylation of alcohols using a cyclic iodine(III) reagent derived from 2-iodosufoximine.¹¹⁰⁴ When alcohols 383 were treated with reagent 384 in the presence of Zn(NTf₂)₂, the trifluoromethylation reaction proceeds to form the corresponding trifluoromethyl ether 385 (Scheme 137). When 1-trifluoromethyl-1,2-bendiodoxol-3(1H)-one is used in this reaction instead of 384, the reaction does not proceed, suggesting that electron-withdrawing properties of the sulfoximine fragment in reagent 384 is important. If a mixture of primary and secondary alcohols is used in intermolecular competitive reaction, the trifluoromethylation proceeds in favor of the primary alcohol, and in the reactions of substrates with primary and secondary alcohol moieties in the same molecule, the trifluoromethylation of the primary alcohol occurs.

Scheme 137. Trifluoromethylation of Alcohols Using Cyclic Iodine(III) Reagent 384.

Reactions of some unsaturated substrates with trifluoromethylbenziodoxoles proceed as cyclization-trifluoromethylation, resulting in various cyclic compounds.^1109−1125 Likewise, the reactions of substrates bearing an isocyanate group lead to the products of cyclization (Scheme 138).^{1110,1118,1121,1123} Wang and Li reported that the reaction of aromatic isocyanate compounds 386 with 1-trifluoromethyl-1,2-benziodoxole-3(1H)-one 387 gave trifluoromethylated quinolines 388.¹¹¹⁸ Studer’s group found that the reaction of biaryl isocyano compounds 389 with reagent 387 under electrochemical reaction conditions produced quinoline products 390.¹¹²¹ The reaction of α-benzylated tosylmethylisocyanides 391 yields the corresponding 1-trifluoromethylated isoquinoline derivatives 392.¹¹²³ Furthermore, it has been reported that the reaction of o-isocyanodiphenylamines 393 as substrates provides trifluoromethylated dibenzodiazepine derivatives 394.¹¹¹⁰ In these reactions, trifluoromethyl radical species are generated from the iodine(III) reagent under reaction conditions, which further react with the isocyanate to generate imidoyl radical species, followed by intramolecular cyclization to produce the final products.

Scheme 138. Cyclotrifluoromethylation of Isocyanate Substrates Using 387.

Bifunctionalization reactions of unsaturated compounds with reagent 387 or its analogues in the presence of nucleophilic substrates have been reported. Various reactions proceed by the addition of trifluoromethyl radicals generated from reagent 387 to unsaturated bonds, and the radical species containing nitrogen,^1126−1129 oxygen,^{1008,1130−1132} or carbon^1133−1144 atoms have been utilized as the second radical species for the bifunctionalization reactions of unsaturated bonds. Bifunctionalization reactions of styrene using trifluoromethylbenziodoxoles have been reported (Scheme 139). For example, the reaction of arylhydrazines 395 with reagent 387 and styrene 396 under blue LED irradiation in the presence of rose bengal as a photocatalyst proceeds as aminotrifluoromethylation of styrene, resulting in the efficient formation of the corresponding amines 397.¹¹²⁹ The addition of radical scavengers to this reaction decreased the yield of products 297. The reaction progress stops when blue LED irradiation is stopped, which suggests that the reaction probably does not have a radical chain propagation mechanism. Reactions involving 1,2-oxytrifluoromethylation of styrene have also been reported. The reaction of N-hydroxyphthalimide 398 and styrene 396 with iodine reagent 399 in the presence of vanadium catalyst results in enantioselective 1,2-oxytrifluoromethylation to give the corresponding bifunctionalized product 400.¹¹³¹ The reaction proceeds enantioselectively for styrenes with various substituents. The enantioselectivity of this reaction has been analyzed by computational methods. Li and Han have also reported that the reaction of styrene 396 with aromatic aldehydes 401 in the presence of an NHC catalyst results in acylfluoroalkylation of styrene to give the corresponding products 402.¹¹³⁸ The reaction proceeds with various aliphatic alkenes as well as styrenes with various substituents. Even indoles and complex biologically active compounds can be used in place of styrene in this reaction.

Scheme 139. Bifunctionalization of Styrene 396.

The bifunctionalization reactions are also possible for alkyne derivatives.^1145−1147 For example, Liu and co-workers reported that reactions of aryl-substituted alkynes 403 with TMSCN and benziodoxole 399 in the presence of a copper catalyst lead to regioselective bifunctionalization, yielding the corresponding alkene derivatives with atroposelectivity (Scheme 140).¹¹⁴⁵ A similar reaction proceeds when TMSN₃ is used instead of TMSCN to give the corresponding azides. The authors suggest that this reaction has a radical mechanism since adding CBr₄ to the reaction competitively yields a bromine adduct, and using a radical clock substrate with a cyclopropyl group opens the ring to give the corresponding allene product. The selectivity of the reaction is also explained by DFT calculations.

Scheme 140. Bifunctionalization of Alkynes 403.

The cyclic iodine(III) reagents with trifluoromethyl ligand can also be used for the trifluoromethyl group insertion into C–H bonds of various substrates.^1148−1150 For example, MacMillan and co-workers reported that the reaction of pyrrolidine 405 with trifluoromethylbenziodoxole 387 under Kessi lamp irradiation in the presence of decatungstate and a copper catalyst led to regioselective trifluoromethylation to C–H, resulting in 3-(trifluoromethyl)pyrrolidine 406 in 66% yield (Scheme 141).¹¹⁵⁰ The reaction proceeds regioselectively for various aliphatic amines and benzylic position selectively for benzylic substrates. The authors have confirmed the presence of “Cu-CF₃” species in various control experiments and suggest that this species may potentially be a catalytic intermediate in the reaction.

Scheme 141. C–H Trifluoromethylation of Pyrrolidine 405.

Trifluoromethylation reactions at the C(sp²)–H bonds have also been reported.^1151−1160 For example, it was reported that aniline compounds 407 react with trifluoromethylbenziodoxole 387 in the presence of a catalytic amount of Ni(OH)₂ to give products 408 with trifluoromethyl group in the aromatic ring (Scheme 142).¹¹⁵⁴ This reaction proceeds efficiently with various substituted anilines. Khaskin and co-workers reported that the reaction of 1,3,5-trimethoxybenzene 409 with C₂F₅-substituted benziodoxole 410 in the presence of nickel catalyst gave fluoroalkylated product 411 in 86% yield.¹¹⁵⁷ This reaction efficiently proceeds with electron-rich aromatic compounds; however, a decrease in yield is observed for electron-deficient aromatic substrates. In the reactions of C₃F₇-substituted benziodoxole as the reagent, the analogous fluoroalkylated product was obtained in similar yields.

Scheme 142. C–H Perfluoroalkylation of Aromatic Compounds 407 and 409.

4.4.2. Cyanobenziodoxoles

Cyclic iodine compounds with a cyano group as a ligand are used as reagents that can introduce a cyano group into various organic substrates.^7,106 In contrast with the cyclic iodine reagents, the acyclic hypervalent iodine compounds are not effective cyano group transfer reagents. Reactions utilizing cyclic iodine reagents bearing a cyano group can be used to convert the N–H bond to a N–CN bond,^1161,1162 and the acidic C–H bond to a C–CN bond.^1163,1164 Feng and Liu reported that the reaction of the β-ketoester 1-indanone derivatives 412 with cyanobenziodoxole 413 in the presence of a chiral catalyst results in enantioselective α-cyanation to afford the corresponding products 414 (Scheme 143).¹¹⁶⁴ A similar enantioselective cyanation reaction proceeds with β-ketoamide compounds as the substrates. The reaction does not provide products of cyanation with acyclic β-ketoester or nonaromatic cyclic β-ketoester as the substrates.

Scheme 143. Asymmetric α-Cyanation of β-Keto Esters 412.

Reactions of carboxylic acids or their derivatives with cyanobenziodoxole 413 proceed as a decarboxylation-cyanation process.^1165−1168 For example, Waser and co-workers reported that the reactions of an aliphatic carboxylic acids 415 with cyanobenziodoxole 413 under blue LED irradiation in the presence of a photocatalyst proceeds to a cyanation reaction via decarboxylation, efficiently yielding the corresponding cyano products 416 (Scheme 144).¹¹⁶⁸ This reaction does not work effectively with the acyclic hypervalent iodine reagents. The authors suggested that this reaction mechanism involves radicals since the reaction in the presence of TEMPO produces less product, while the reaction with a substrate having a cyclopropylmethyl group produces ring-opened products.

Scheme 144. Decarboxylative Cyanation of Carboxylic Acids 415.

The TMS group can be substituted by the cyano group using cyclic hypervalent iodine reagents. Yuan and co-workers reported that α-silylated tertiary aliphatic amines 417 react with cyanobenziodoxole under blue LED irradiation to give the corresponding cyano compounds (Scheme 145).¹¹⁶² The authors propose the formation of an EDA (electron donor–acceptor) complex between the iodine and the amine as a key intermediate in this reaction. The presence of the EDA complex was confirmed by UV–vis spectroscopy. The 1:1 ratio of iodine(III)/amine in this complex was found by the Job’s method.

Scheme 145. Desilylative Cyanation of Amines 417.

4.4.3. Cyclic Diaryliodonium Salts

The chemistry and synthetic applications of cyclic aryliodonium salts were summarized in a comprehensive review.¹⁶¹ Very recently, a number of various polycyclic diaryliodonium compounds have been synthesized and investigated.^101,161,1169 Similar to the acyclic diaryliodonium salts, these compounds have a relatively high stability. The iodonium atom in cyclic diaryliodonium salts can be substituted with various nucleophiles, forming new heterocyclic or carbocyclic rings, which has been utilized in the synthesis of the corresponding heterocyclic,^1170−1177 triphenylene,^1178−1182 and spirocyclic compounds.^1183,1184 Cyclic diaryliodonium salts can also react with various nucleophiles to give the ring-opening products.^1185−1190 Tan and Xu reported that the reaction of cyclic diaryliodonium salt 419 with tellurium powder in the presence of 2-picoline as a base gives dibenzotellurophene 420 in high yield (Scheme 146).¹¹⁷² Cyclic diaryliodonium salts with various substituents can be used as substrates in this reaction. The authors have also found that tritellurasumanene can be synthesized from the corresponding cyclic diaryliodonium salt by using this methodology.

Scheme 146. Synthesis of Dibenzotellurophene 420.

Rohde and Hong reported that the reaction of cyclic diaryliodonium salt 419 with unactivated heterocycles 421 under basic conditions yields the corresponding polycyclic heteroarenes 421 (Scheme 147).¹¹⁸² In this reaction, the corresponding products could be efficiently obtained using substituted cyclic diaryliodonium salts and benzene instead of heterocycles 421. Addition of TEMPO resulted in lower yields of the product, and the TEMPO adduct was detected by ESI-MS, leading the authors to suggest that radicals are involved in the reaction. In a competitive reaction involving a heteroaromatic compound mixed with its deuterated analogue, the kinetic isotope effect is close to 1, indicating that the deprotonation of the C–H of the heteroaromatic ring is not a rate- determining step.

Scheme 147. Preparation of Polycyclic N-Heteroarenes 422.

As an example of ring-opening reactions of cyclic diaryliodonium compounds 423, Wu and Liao reported that the reaction with amines 424 in the presence of a catalytic amount of palladium and a ligand under a carbon monoxide atmosphere leads to the enantioselective double carbonylation, yielding the corresponding ketoamides 425 (Scheme 148).¹¹⁸⁵ In the reaction using aromatic amines instead of aliphatic amines, the monocarbonylation reaction proceeds and the corresponding amides are selectively produced. The authors evaluated the mechanism of these reactions by DET calculations. Active palladium(IV) species generated by the action of iodonium salt were detected by HRMS and ³¹P NMR.

Scheme 148. Palladium-Catalyzed Enantioselective Double Carbonylation.

Similar to their acyclic analogues, cyclic diaryliodonium salts can produce benzyne species under basic conditions, which has been utilized in several recent works.^1191,1192 Zhang and Wu reported that the reaction of cyclic iodonium salt 419 with phenolic compounds 426 in the presence of cesium carbonate as a base lead to a meta-selective o-arylation reaction, resulting in the efficient formation of the corresponding diaryl ethers 427 (Scheme 149).¹¹⁹¹ The same research group has also reported a reaction using tetrabutylammonium halide instead of a phenol compound as a nucleophile, in which a meta-selective halogenation also proceeds, resulting in the corresponding dihalobiaryl products.¹¹⁹² In the presence of furan instead of phenol or halide, the corresponding cycloadduct was obtained, supporting the generation of benzyne intermediates in this reaction.

Scheme 149. meta-Selective O-Arylation of Cyclic Iodonium Salt 419.

4.4.4. Alkynyl- and Alkenylbenziodoxoles

The chemistry and synthetic applications of alkynyl- and vinylbenziodoxoles were summarized in recent comprehensive reviews.^13,130,172 Cyclic hypervalent iodine derivatives with alkynyl ligands can be synthesized by ligand exchange reactions of the approporiate cyclic hypervalent iodine reagents with silylated or boronated alkynes. Recently, numerous new alkynyl derivatives of benziodoxole or benziodazole have been synthesized and structurally investigated by X-ray crystallography.^1193−1198 These cyclic alkynyl iodine(III) derivatives have been used in a number of reactions as useful reagents for transfer of the alkynyl group to a variety of substrates.^{106,1199,1200} In particular, these reagents can be used for alkynylation of unsaturated substrates such as alkenes^1201−1205 and alkynes.^1206,1207 Chen and Liu reported that the reaction of aliphatic alkenes 428 with alkynylbenziodoxoles 429 under a carbon monoxide atmosphere in the presence of a catalytic amount of palladium proceeds as alkynylcarbonylation to form the corresponding esters 430 (Scheme 150).¹²⁰⁵ The resulting compounds can be converted to a variety of heterocyclic products by appropriate treatment. The same group also reported that hydrogen-alkynation of alkenes can be achieved by a related reaction using (n-hex)₃SiH as the hydrogen source instead of carbon monoxide.¹²⁰¹

Scheme 150. Alkynylcarbonylation of Alkenes 428.

Reaction of diazo compounds 431 with alkynylbenziodoxoles 432 under blue light irradiation proceeds as oxy-alkynylation, yielding propargylic esters 433 (Scheme 151).¹²⁰⁸ The authors assume that radicals are not involved in the mechanism of this reaction since the addition of TEMPO or BHT does not decrease the product yield. They suggested that this reaction may involve singlet carbenes generated from diazo compounds under blue LED conditions. It is also known that the oxy-alkynylation of diazo compounds to the corresponding propargylic esters can be achieved by the reaction with alkynylbenziodoxoles in the presence of a copper catalyst.^1209,1210 Alcohols or amines can be introduced in this reaction instead of 2-iodobenzoic acid.^1211,1212

Scheme 151. Synthesis of Propargylic Esters 433 from Diazo Compounds 431.

Alkynylbenziodoxoles have been used as alkynylating reagents toward heteroatoms as well as various C–H bonds.^1213−1221 Furthermore, alkynylation-decarboxylation reactions of carboxylic acids in the presence of photocatalysts have been reported.^{1165,1222−1225} These reactions have been summarized in recent review articles.^13,130 Recently, Tada and Ito have synthesized cyclic iodine(III) reagents with diyne ligands.¹²²⁶ They reported that the reaction of reagent 434 with amines 435 in the presence of a copper catalyst and a ligand gave the corresponding diynamides 436 (Scheme 152). The resulting diynamide product can be further converted to ynamides via CuAAC (copper-catalyzed azide–alkyne cycloaddition) by appropriate treatment.

Scheme 152. Preparation of Diynamides 436 from Amines 435 Using Reagent 434.

It has been reported that cyclic alkynyl iodine(III) compounds can be converted to cyclic alkenyl iodine(III) compounds by reaction with various nucleophiles.^{172,1227−1235} For example, Waser and co-workers reported that the reaction of alkynylbenziodoxoles 437 with sulfonamides 438 under basic conditions proceeds stereoselectively, resulting in Z-alkenylbenziodoxoles 439 (Scheme 153).¹²³³ Phenolic compounds can also be used as nucleophiles in this reaction. The role of the base is to prevent the formation of the ynamide, which is a thermodynamically favorable by-product. In general, cyclic alkenyl iodine(III) compounds can be synthesized by two approaches: (1) by the in situ reaction of 2-iodobenzoic acids with an oxidant and then reacting with an alkene or alkyne followed by base treatment,^1236,1237 or (2) by reacting the cyclic iodine(III) reagents with alkynes.^1238−1241

Scheme 153. Synthesis of Alkenylbenziodoxoles 439 from Alkynylbenziodoxoles 437.

Alkenylbenziodoxoles are used as reagents that can transfer alkenyl groups to various substrates.^1242−1248 For example, Olofsson and co-workers reported that the reaction of alkenylbenziodoxoles 440 with thiols 441 proceeds stereoselectively under basic conditions to give E-alkenylthioethers 442 (Scheme 154).¹²⁴⁶ Mercaptothiazoles can also be used as nucleophiles in this reaction.

Scheme 154. Alkenylation of Thiols 441 Using Alkenylbenziodoxoles 440.

5. Pseudocyclic Hypervalent Iodine(III) Reagents

Hypervalent iodine compounds with appropriate substituents in the ortho-position of the aromatic ring have a pseudocyclic structure due to the intramolecular noncovalent interaction between iodine and the neighboring group. The presence of additional intramolecular coordination at the iodine(III) center leads to a significant improvement of solubility and stability, as well as to modified reactivity of a hypervalent iodine reagent.¹²⁴⁹ Synthetic applications of pseudocyclic hypervalent iodine compounds were summarized in a comprehensive review.¹¹⁴ The coordinating group in the ortho-position of pseudocyclic hypervalent iodine compounds can contain oxygen atoms,^{639,640,750,751,991,1250−1255} such as carbonyl, ether, and hydroxyl groups, or nitrogen-containing functional groups.^1256−1258 Two general methods for the synthesis of common pseudocyclic hypervalent iodine(III) reagents are known. The first method is to add acid to a cyclic hypervalent iodine(III) compound in order to open the ring and create a coordinating functional group. The second method is by the oxidation of iodoarenes with coordinating functional groups in the ortho-position. The structure of numerous pseudocyclic hypervalent iodine compounds has been confirmed by X-ray crystallography.^{640,750,991,1250,1252−1258} For example, the addition of TfOH to hydroxybenziodoxoles 443, followed by the addition of alkynes 444, efficiently synthesizes the corresponding pseudocyclic β-trifluorosulfonyloxy alkenyliodonium salts 445 (Scheme 155).¹²⁵⁰ These products can also be obtained by adding Tf₂O instead of TfOH.¹²⁵⁹ The structure of compounds 445 was determined by X-ray crystallography. The obtained pseudocyclic compounds 445 react with sodium azide in the presence of crown ether by the addition-elimination mechanism with retention of configuration, resulting in the alkenylbenziodoxoles with an azide group at the β-position.

Scheme 155. Preparation of Pseudocyclic Alkenyliodonium Triflates 445.

Wirth and co-workers reported the synthesis of pseudocyclic hypervalent iodine compounds 447 by the oxidation of iodoarenes 446 with a heteroaryl carbonyl group at the ortho-position of the iodine atom (Scheme 156).¹²⁵⁵ The structure of these compounds was confirmed by X-ray crystallography. The authors have demostrated that compounds 447 can be used as oxidants for various substrates. Compared to the analogous noncyclic iodine(III) reagent, [hydroxy(tosyloxy)iodo]benzene (HTIB), compounds 447 were generally more reactive in these reactions. In contrast, catalytic reactions using iodoarenes 446 as organocatalysts did not proceed efficiently.

Scheme 156. Synthesis of Pseudocyclic Iodine(III) Compounds 447.

Nachtsheim and co-workers prepared pseudocyclic iodonium compound 449 by oxidation of iodobenzene 448 with 1H-pyrazole ring substituents at both ortho-positions (Scheme 157).¹²⁵⁸ The authors have also synthesized pseudocyclic compounds from iodoarenes with ortho-substituents other than pyrazole N-heterocycles, such as triazoles, benzimidazoles, and benzoxazoles. Compound 449 was found to perform as a useful oxidant for a variety of substrates. Interestingly, structure 449 resembles a pincer complex typical of transition metal complexes.

Scheme 157. Synthesis of Pseudocyclic Iodine(III) Compound 449 with 1H-Pyrazole Rings.

Suero and co-workers found that reactions of alkynes 450 with pseudocyclic iodine reagents 451 acting as a carbyne source in the presence of rhodium catalyst produce cyclopropenium salts 452 (Scheme 158).¹²⁶⁰ This reaction can be performd only by using pseudocyclic iodine reagents; the analogous reactions with cyclic or noncyclic iodine(III) reagents do not give products 452. The authors suggest that this reaction mechanism involves initial formation of rhodium-carbynoid species, which reacts with an alkyne to yield final products. The resulting cyclopropenium salts 452 can be further reacted with appropriate nucleophiles to obtain the corresponding cyclopropenes as a single regioisomer.

Scheme 158. Preparation of Cyclopropenium Salts 452 from Alkynes 450.

Pseudocyclic diaryliodonium compounds with a boronic acid group at the ortho-position of the iodine atom are unique reagents for generating aryne species under aqueous conditions, which can further react with various substrates to yield the corresponding products.^100,991 Very recently, it was reported that the reaction of a pseudocyclic diaryliodonium compound 453 with sulfur compounds 454 under aqueous conditions at room temperature yields the corresponding sulfonium salts 455 in high yield (Scheme 159).¹²⁶¹ Using sulfoxides instead of sulfides as substrates in this reaction leads to ortho-hydroxysulfonium compounds.

Scheme 159. Synthesis of Arylsulfonium Triflates 455 from Sulfides 454.

6. Catalytic Cycles Based on Iodine(III) Species

Catalytic application of hypervalent iodine species is a hot topic in modern synthetic organic chemistry. An excellent book “Iodine Catalysis in Organic Synthesis” edited by Ishihara and Muñiz was published in 2022.⁴ Several recent reviews on this topic were also published.^{28,29,118,1262,1263} This section will provide an update on important development in this area published after 2021. Various catalytic reactions employing hypervalent iodine species generated from catalytic amounts of iodoarenes and stoichiometric oxidants have been reported since 2005.^1264,1265 Numerous new iodoarenes were designed and utilized as organocatalysts under different reaction conditions. It should be noted that most of these reactions require a relatively large amount of iodoarene, up to 20–30%, which makes them different from the truly catalytic reactions of transition metals. mCPBA, Selectfluor, and Oxone are most commonly used as terminal oxidants to generate hypervalent iodine species from iodoarenes in these reactions.²⁸ In recent years, reactions using oxygen as the terminal oxidant^{127,1266,1267} and electrochemical reactions have also been developed.^1268−1271 Gilmor and co-workers have reported the reaction of different iodoarenes with Selectfluor as the oxidant to generate the corresponding aryliodofluoronium species utilized in various catalytic fluorination reactions.^1272−1276 For example, enynes 456 react with Selectfluor (F-TEDA-BF₄), and amine·HF in the presence of catalytic amounts of 4-iodotoluene to yield products of difluorination of the double bond (Scheme 160).¹²⁷² The resulting products 457 can be further converted to a variety of compounds by appropriate treatment. The authors propose that the initially generated hypervalent iodine(III) species in this system react with the double bond followed by alkynyl group rearrangement to give final products 457. The same group also reported a difluorination reaction that utilizes an alkyl group shift instead of an alkynyl shift.¹²⁷⁷

Scheme 160. Catalytic Difluorination of Enynes 456.

Saito’s group reported the cycloisomerization-arylation of propargylic amides using F-TEDA-PF₆, an analogue of Selectfluor, as a terminal oxidant with catalytic amounts of iodoarene in the presence of arenes.¹²⁷⁸ The reaction of propargylamides 458 with electron-rich arenes 459 and the oxidant F-TEDA-PF₆ in the presence of catalytic iodoarene and DMSO affords oxazole compounds 460 (Scheme 161). The authors suggest a role for DMSO in the generation of sulfinyl fluoride active species (MeSOF) from DMSO and F-TEDA-PF₆ and confirmed the presence of these species by ¹H NMR. The same group has also reported the reaction using Bn₂SO instead of DMSO and confirmed the presence of BnSOF active species by NMR.¹²⁷⁹ More recently, the authors have succeeded in developing a catalytic system combining TFDA-PF₆ with Bn₂SO and NsCl, which was utilized in the synthesis of furans from 2-propargyl-1,3-dicarbonyl compounds.¹²⁸⁰

Scheme 161. Cycloisomerization-Arylation of N-Propargyl Amides 458.

König and co-workers reported catalytic reactions utilizing the generation of the corresponding (diacyloxyiodo)arenes from iodoarenes and carboxylic acids and Selectfluor.^1281,1282 For example, carboxylic acids 461 under light irradiation in the presence of catalytic amounts of iodobenzene and stoichiometric Selectfluor in the presence of water and BF₃ experience a Ritter-type reaction involving decarboxylation and resulting in the corresponding amides 462 (Scheme 162).¹²⁸¹ Benzyl carboxylic acids and aliphatic carboxylic acids with primary, secondary, or tertiary carbon atoms can be used as substrates in this reaction. The authors assume that (diacyloxyiodo)arene is initially generated in the reaction system, which is then photolyzed to cleave the acyloxy groups and undergo decarboxylation to generate radical species, followed by conversion to cationic species, and finally trapping by nitrile to form final amide. The same authors have also reported a Ritter-type amination of benzylic compounds using radical species generated from (diacyloxyiodo)arene under similar reaction conditions.¹²⁸²

Scheme 162. Decarboxylative Amination of Carboxylic Acids 461.

mCPBA and iodoarenes are a classic and the most common combination for generation of hypervalent iodine species in the reaction system.^28,1283 For example, when a catalytic amount of iodoarene and mCPBA as a terminal oxidant are added to phenylpropanamides 463, an intramolecular cyclization reaction proceeds, resulting in oxyindole compounds 464 (Scheme 163).¹²⁸⁴ This reaction in the presence of a chiral iodoarene yields the corresponding products with moderate enantioselectivity. The intramolecular cyclization in this reaction proceeds preferentially at the C–N bond rather than the C–O bond. On the other hand, when a substituent is introduced into the aromatic ring of the phenylpropanamide substrate, a competitive reaction involving the C–O and C–N bonds occurs, yielding two products.

Scheme 163. Hypervalent Iodine-Mediated Intramolecular Cyclization of 463.

Jiang and co-workers reported enantioselective cycloamino fluorination of cinnamylbenzamide using BF₃ as a fluorine source.¹²⁸⁵ The reaction using cinnamylbenzamides 465, chiral iodoarene, mCPBA, and BF₃ yields the 6-membered ring products 466, while with the use of benzamides 467, the corresponding seven-membered ring products 468 are obtained (Scheme 164). The authors demonstrated that the reaction is substrate-specific, as the desired product is not produced when the length of the alkyl group is extended or when the aromatic ring is removed from the substrate. In the reactions using Py–HF or Et₃N–HF instead of BF₃, and in the reactions using PhIF₂, no desired product was obtained, which suggests that BF₃ is not only a fluorine source but is also an activator of the hypervalent iodine species produced in the reaction system. The authors have also investigated mechanisms of these reactions using computational methods.

Scheme 164. Catalytic Intramolecular Cyclofluorination of Benzamides 465 and 467.

Zhang and co-workers have demonstrated that the reaction of various aryl carbonyl compounds 469 with chiral iodoarenes in the presence of mCPBA and TsOH proceeds as enantioselective tosyloxylation, yielding the corresponding α-tosyloxy compounds 470 (Scheme 165).¹²⁸⁶ The iodoarene used in this reaction is designed to introduce two sterically demanding BINOL functional groups around the iodine, thereby immobilizing the reaction field and preventing free rotation of the substituent. This catalytic design can also be used for intramolecular cyclization reactions. When 5-oxo-5-arylpentanoic acids are used as a substrate in the presence of TFA, the reaction proceeds enantioselectively as a lactonization reaction to afford the corresponding lactones. Wirth group has also reported the synthesis of chiral iodotriptycenes and their use for catalytic enantioselective α-tosyloxylation of propiophenone.¹²⁸⁷

Scheme 165. Catalytic α-Tosyloxylation of Ketones 469.

As an example of a recent catalytic reaction using Oxone as an oxidant, Saito and co-workers reported the α-amidation of diketone compounds with iminoiodane species.¹²⁸⁸ This reaction was performed by the addition of TfNH₂ and Oxone to 1,3-dicarbonyl compounds 471 in the presence of iodoarene, giving α-amide products 472 in moderate yield (Scheme 166). This catalytic reaction does not proceed with 1,3-carbonyl compounds bearing sterically bulky substituents. The authors have also succeeded in generating PhINTf from PhIO and TfNH₂ and using it to obtain the desired products.

Scheme 166. α-Amidation of 1,3-Dicarbonyl Compounds 471.

De Vos and co-workers reported on the diacetoxylation of alkenes using an electrocatalytic method without the use of organic oxidants.¹²⁶⁸ The reaction takes place under Pt anode and Ni cathode conditions, and the reaction of alkenes 473, catalytic amounts of iodobenzene with BF₃, acetic acid, and acetic anhydride gives the corresponding diacetoxy compounds 474 (Scheme 167). This reaction proceeds even when a carbon rod anode is used instead of the platinum anode. These reaction conditions can also be used for acetoxylactonization. In the reaction of an alkene with a cyclopropyl ring as a substrate, the products of the ring opening were obtained. The authors suggested that a one-electron oxidation mechanism was involved in this reaction.

Scheme 167. Electrocatalytic Diacetoxylation of Alkenes 473.

8. Conclusion

The literature summarized in this review reflects an increasing current interest in synthetic applications of hypervalent iodine(III) reagents. Just in 8 years after publication of our 2016 review, numerous new synthetic methodologies based on hypervalent iodine chemistry have been developed and increasingly employed in organic chemistry. Hypervalent iodine reagents are commercially available and environmentally safe compounds with diverse synthetic applications.

Thousands of new research papers dedicated to various uses of hypervalent iodine compounds are published every year. Most of these papers deal with the classic, commercially available reagents, such as (diacetoxyiodo)benzene, (dichloroiodo)benzene, iodosylbenzene, 1-hydroxybenziodoxole, and various iodonium salts. At the same time, the newly deleloped cyclic reagents, including azido-, alkynyl-, and alkenylbenziodoxoles, are attracting significant research activity as the efficient group transfer reagents. Numerous new synthetic methodologies based on hypervalent iodine reagents have been developed recently. Most notably, catalytic and photocatalytic reactions of these compounds are gaining significant interest. Synthetic utilization of new hypervalent iodine reagents and catalytic systems, and the discovery of enantioselective reactions based on chiral hypervalent iodine reagents and catalysts has become an important direction in the field of modern hypervalent iodine chemistry.

Hypervalent iodine reagents and synthetic methodologies involving hypervalent iodine species represent an essential tool of modern organic synthesis. Many synthetic applications of hypervalent iodine compounds are unique and cannot be achieved by using any alternative methods. We anticipate that the development of new reagents and synthetic methodologies based on hypervalent iodine chemistry will continue to be an active area of research in the future.

Biographies

Akira Yoshimura was born in Osaka (Japan) and completed his M.S. degree in 2007 and Ph.D. in 2010, both from Tokushima University, under the supervision of Professor Masahito Ochiai. During 2010–2015 he carried his postdoctoral research with Professor Viktor V. Zhdankin at the University of Minnesota Duluth. In 2016–2017 he worked as a Visiting Assistant Professor in Southern Methodist University (Dallas, USA). Since 2022 he is an Associate Professor at the Aomori University in Japan. His research interests are in the fields of synthetic and mechanistic organic chemistry of hypervalent iodine and bromine and heterocyclic chemistry.

Viktor V. Zhdankin received his M.S. (1978), Ph.D. (1981), and Doctor of Chemical Sciences (1986) degrees from Moscow State University. He moved to the University of Utah in 1990, where he worked for 3 years as an Instructor of organic chemistry and Senior Research Associate with Professor Peter J. Stang. In 1993, he joined the faculty of the University of Minnesota Duluth, where he is currently a Professor of Chemistry. His main research interests are in the areas of synthetic and mechanistic organic chemistry of hypervalent main-group elements and organofluorine chemistry.

Author Contributions

CRediT: Akira Yoshimura writing - original draft; Viktor V Zhdankin project administration.

The authors declare no competing financial interest.