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Hypervalent Iodine Compounds

Weaker and longer than covalent linkages, hypervalent bonds are the result of a linear three-center, four-electron (3c-4e) electronic distribution (hypervalent model). Hypervalent iodine reagents are useful synthetic tools due to their low toxicity, ready availability, and ease of handling.

Specific hypervalent iodine reagents: Dess-Martin Periodinane, Hydroxy(tosyloxy)iodobenzene, Iodosobenzene diacetate, Iodosobenzene bis(trifluoroacetate), Iodosylbenzene, 2-Iodoxybenzoic Acid, Iodobenzene Dichloride

Recent Literature

[dibmim][BF4] can be used for the oxidation of alcohols to carbonyl compounds. This oxidizing agent offers a high degree of selectivity for the oxidation of primary alcohols to carbonyl compounds without oxidation to carboxylic acids in ionic liquids. [dibmim][BF4] can be reused after oxidation with peracetic acid.
W. Qian, E. Jin, W. Bao, Y. Zhang, Angew. Chem. Int. Ed., 2005, 44, 952-955.

A highly efficient 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) catalyzed reaction using recyclable 1-chloro-1,2-benziodoxol-3(1H)-one as the terminal oxidant allows the conversion of various alcohols to their corresponding carbonyl compounds in high to excellent yields at room temperature in ethyl acetate, which is an environmentally friendly organic solvent.
X.-Q. Li, C. Zhang, Synthesis, 2009, 1163-1169.

2-Iodoxybenzenesulfonic acid, which can be generated in situ from 2-iodobenzenesulfonic acid sodium salt, is a much more active catalyst than modified IBXs for the oxidation of alcohols with Oxone. Highly efficient and selective methods for the oxidation of alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones were established.
M. Uyanik, M. Akakura, K. Ishihara, J. Am. Chem. Soc., 2009, 131, 251-262.

In the presence of nucleophiles (alcohols or amines), ion-supported (di­acetoxyiodo)benzene promoted sp3 C-H oxidation of nitromethyl aryl ketones to provide the corresponding α-keto esters and amides in good yields. The reaction is ecofriendly and offers mild conditions, short reaction times, and a recyclable reagent.
X. Jang, B. Gan, J. Liu, Y. Xie, Synlett, 2016, 27, 2737-2741.

Oxidative cleavage of various olefins to the corresponding ketones/carboxylic acids occurs with catalytic amounts of 3,4,5,6-tetramethyl-2-iodobenzoic acid (TetMe-IA) and oxone as terminal oxidant in acetonitrile-water mixture at rt. The reaction mechanism involves dihydroxylation of the olefin with oxone, oxidative cleavage by TetMe-IBX, and oxidation of the aldehyde functionality to the corresponding acid with oxone.
J. N. Moorthy, K. N. Parida, J. Org. Chem., 2014, 79, 11431-11439.

Hypervalent iodine reagents promote a facile and efficient transformation of primary amides to secondary amides. The hypervalent iodine reagent mediates a Hofmann-type rearrangement to an isocyanate intermediate, which is subsequently trapped by an in situ generated carboxylic acid from the hypervalent iodine reagent to provide the corresponding secondary amides.
X. Wang, P. Yang, B. Hu, Q. Zhang, D. Li, J. Org. Chem., 2021, 86, 2820-2826.

Stable, microcrystalline 2-iodylphenol ethers were prepared by the dimethyldioxirane oxidation of the corresponding 2-iodophenol ethers. 2-Iodylphenol ethers can selectively oxidize sulfides to sulfoxides and alcohols to the respective aldehydes or ketones.
A. Y. Koposov, R. R. Karimov, I. M. Geraskin, V. N. Nemykin, V. V. Zhdankin, J. Org. Chem., 2006, 71, 8452-8458.

A mild, efficient and environmentally friendly oxidation of sulfides to sulfoxides with a recyclable ion-supported hypervalent iodine reagent tolerates hydroxyl, nitrile, methoxy, carbon-carbon double bonds, and ester functionalities. Aliphatic and aromatic sulfides are selectively oxidized to the corresponding sulfoxides at room temperature in excellent yields without over-oxidation.
W. Qian, L. Pei, Synlett, 2006, 709-712.

The reactivity of iodoarene amide catalysts in the α-oxytosylation of propiophenone is influenced by steric and electronic properties. A very reactive meta-substituted benzamide catalyst was employed in the α-oxytosylation of a series of substituted propiophenones to provide α-tosyloxy ketones in excellent isolated yield.
T. R. Lex, M. I. Swasy, D. C. Whitehead, J. Org. Chem., 2015, 80, 12234-12243.

Various ketones could be reacted into α-tosyloxy ketones in the presence of MCPBA, PTSA•H2O, catalytic amounts of iodine and tert-butylbenzene in a mixture of acetonitrile and 2,2,2-trifluoroethanol. In the reaction, 4-tert-butyl-1-iodobenzene is formed at first and then converted into the α-tosyloxylation reagent 4-tert-butyl-1-[(hydroxy)(tosyloxy)iodo]benzene by the reaction with MCPBA and PTSA•H2O.
A. Tanaka, K. Moriyama, H. Togo, Synlett, 2011, 1853-1854.

Various α-tosyloxyketones were efficiently prepared in high yields from the reaction of ketones with m-chloroperbenzoic acid and p-toluenesulfonic acid in the presence of a catalytic amount of iodobenzene.
Y. Yamamoto, H. Togo, Synlett, 2006, 798-800.

α-Acetoxylation of ketones catalyzed by iodobenzene using acetic anhydride and 30% aqueous hydrogen peroxide as the oxidant is an effective and economical method for the preparation of α-acetoxy ketones in good yields.
J. Sheng, Y. Li, M. Tang, B. Gao, G. Huang, Synthesis, 2007, 1165-1168.

Oxidation of alkyl aryl ketones in the presence of Oxone, trifluoroacetic anhydride and a catalytic amount of iodobenzene affords α-hydroxyalkyl aryl ketones in good yield. This method provides an effective and economical entry for the α-hydroxylation of ketones.
C. Chen, X. Feng, G. Zhang, Q. Zhao, G. Huang, Synthesis, 2008, 3205-3208.

A new and reliable method for the direct construction of biologically important aryl lactones and phthalides from carboxylic and benzoic acids is based on selective benzylic C-H abstraction in the presence of hypervalent iodine(III) reagents and KBr.
T. Dohi, N. Takenaga, A. Goto, A. Maruyama, Y. Kita, Org. Lett., 2007, 9, 3129-3132.

[4-Iodo-3-(isopropylcarbamoyl)phenoxy]acetic acid is a highly reactive and easily separable catalyst for the oxidative cleavage of tetrahydrofuran-2-methanols to γ-lactones in the presence of Oxone as the terminal oxidant.The catalyst and product were easily separated by only liquid-liquid separation without chromatography.
T. Yakura, T. Fujiwara, H. Nishi, Y. Nishimura, H. Nambu, Synlett, 2018, 29, 2316-2320.

A boryl-directed intermolecular C-H amination of allyl N-methyliminodiacetyl boronates (B(MIDA)s) and propargylic B(MIDA)s provide α-amino boronates with an exceptionally high level of site-selectivity. A wide variety of highly functionalized secondary and tertiary α-amino boronates are formed in very good yields under mild reaction conditions.
Y. Liu, Z.-H. Chen, Y. Li, J. Qian, Q. Li, H. Wang, J. Am. Chem. Soc., 2022, 144, 14380-14387.

Bis(pyridine) iodonium tetrafluoroborate (Barluenga’s reagent) promotes the rearrangement of propargylic alcohol derivatives under mild conditions to provide β-unsubstituted, β-monosubstituted, and β,β-disubstituted α-iodoenones in high yields. β-Substituted α-iodoenones are obtained with excellent (Z)-selectivity.
T. Suárez-Rodríguez, Á. L. Suárez-Sobrino, A. Ballesteros, J. Org. Chem., 2018, 83, 12575-12583.

A formal enone-α-H to F substitution provides 2-fluoroenones in a single step from ubiquitous enones in good yield. The reaction is applicable to a wide range of aromatic and alkenyl enones and is carried out at room temperature using HF-pyridine complex as the fluoride source. The reaction takes place through a rare umpolung Morita-Baylis-Hillman-type mechanism.
S. Maity, A. M. Szpilman, Org. Lett., 2023, 25, 1218-1222.

A visible-light-induced oxidation of alcohols generates alkoxyl radicals mediated by iodine(III) reagents under mild reaction conditions. The β-fragmentation of alkoxyl radicals enables selective C(sp3)-C(sp3) bond cleavage and alkynylation/alkenylation reactions with various strained cycloalkanols and linear alcohols.
K. Jia, F. Zhang, H. Huang, Y. Chen, J. Am. Chem. Soc., 2016, 138, 1514-1517.

2-Nitrocyclopropanes bearing ketones, amides, esters, and carboxylic acids in the 1 position may be accessed as single diastereoisomers from the corresponding unsaturated carbonyl compounds and nitromethane as source of the nitro-methylene component at room temperature under mild conditions. The products may be converted into, e.g., cyclopropyl-amino acids in a single step.
A. Ghosh, Y. B. Lipisa, N. Fridman, A. M. Szpilman, J. Org. Chem., 2023, 88, 1977-1987.

The water-soluble μ-oxo-bridged hypervalent iodine trifluoroacetate reagent [(PhI(OCOCF3)]2O enables aqueous oxidations of phenolic substrates to dearomatized quinones in excellent yields in most cases compared to conventional phenyliodine(III) diacetate and bis(trifluoroacetate).
T. Dohi, T. Nakae, N. Takenaga, T. Uchiyama, K.-i. Fukushima, H. Fujioka, Y. Kita, Synthesis, 2012, 44, 1183-1189.

A copper-catalyzed amidation of arylboronic acids with nitriles provides an efficient and complementary methodology for the synthesis of a broad range of N-arylamides.
H. Huang, Z.-T. Jiang, Y. Wu, C.-Y. Gan, J.-M. Li, S.-K. Xiang, C. Feng, B.-Q. Wang, W.-T. Yang, Synlett, 2016, 27, 951-955.

The use of PhINTs as a reagent enables a mild Hofmann rearrangement of aromatic and aliphatic carboxamides. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols.
A. Yoshimura, M. W. Luedtke, V. V. Zhdankin, J. Org. Chem., 2012, 77, 2087-2091.

Alkylcarboxamides can be converted to the respective alkylcarbamates by Hofmann rearrangement using hypervalent iodine species generated in situ from PhI and Oxone in methanol. In addition, substituted benzamides can be converted to the respective quinone derivatives by treatment with Oxone and iodobenzene in aqueous acetonitrile.
A. A. Zagulyaeva, C. T. Banek, M. S. Yusubov, V. V. Zhdankin, Org. Lett., 2010, 12, 4644-4647.

Hofmann rearrangement of carboxamides to carbamates using Oxone as an oxidant can be efficiently catalyzed by iodobenzene via hypervalent iodine species generated in situ in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in aqueous methanol solutions. Under these conditions, Hofmann rearrangement of various carboxamides affords corresponding carbamates in high yields.
A. Yoshimura, K. R. Middleton, M. W. Luedtke, C. Zhu, V. V. Zhdankin, J. Org. Chem., 2012, 77, 11399-11404.

Dinuclear iodine(III) reagents with a defined structure enable an intermolecular diamination of alkenes. These highly reactive hypervalent iodine(III) compounds are accessible through protolytic aminolysis events, which generate defined imido-iodine(III) groups.
C. Röben, J. A. Souto, E. C. Escudero-Adán, K. Muńiz, Org. Lett., 2013, 15, 1008-1011.

Dehydrosulfurization using a hypervalent iodine(III) reagent enables a simple and efficient preparation of symmetrical and unsymmetrical carbodiimides from the corresponding thioureas. The oxidation afforded carbodiimides in excellent yields and high selectivity. A possible mechanism for the transformation is proposed.
C. Zhu, D. Xu, Y. Wei, Synthesis, 2011, 711-714.

A hypervalent iodine mediated reaction between carboxylic acids and N,N-dimethylformamide occurs under mild conditions at room temperature to provide O-aroyl-N,N-dimethylhydroxylamines in good yields, which are important electrophilic amination reagents. The process shows good functional group compatibility and air and moisture tolerance.
C. Zhang, Q. Yue, Z. Xiao, X. Wang, Q. Zhang, D. Li, Synthesis, 2017, 49, 4303-4308.

Iodobenzene can be used as a recyclable catalyst in combination with m-chloroperbenzoic acid as the terminal oxidant for an efficient and regioselective monobromination of electron-rich aromatic compounds. The bromination of electron-rich aromatic compounds with lithium bromide was fast in tetrahydrofuran at room temperature, providing regioselective monobrominated products in good yields.
Z. Zhou, X. He, Synthesis, 2011, 207-209.

A catalytic, vicinal difluorination of olefins displays broad functional group tolerance, using inexpensive p-iodotoluene as the catalyst. Preliminary efforts toward the development of an enantioselective variant are reported.
I. G. Molnár, R. Gilmour, J. Am. Chem. Soc., 2016, 138, 5004-5007.

Poly{[4-(hydroxy)(tosyloxy)iodo]styrene} was efficient in the halotosyloxylation reaction of alkynes with iodine or NBS or NCS. The polymer reagent could be regenerated and reused.
J.-M. Chen, X. Huang, Synthesis, 2004, 1557-1558.

A Rh(II)-catalyzed oxidative coupling of aldehydes and sulfonamides provides N-sulfonylcarboxamides in one step. Various sulfonamides were found to react with aromatic and aliphatic aldehydes to afford the desired products in very good yields.
J. Chan, K. D. Baucom, J. A. Murry, J. Am. Chem. Soc., 2007, 129, 14106-14107.

The direct fluorination reaction of acetophenone derivatives, acetonaphthones, benzyl phenyl ketone, propiophenone, butyrophenone, 1-indanone, and phenacyl chloride using iodosylarenes and TEAˇ5HF gives the corresponding α-fluoroketone derivatives in good yields under mild conditions except for use of a HF reagent.
T. Kitamura, K. Muta, K. Muta, J. Org. Chem., 2014, 79, 5842-5846.

A desulfurizing difluorination reaction of benzyl sulfides having an electron-withdrawing group such as an ester, a ketone, a nitrile, or an amide in the presence of IF5 gave gem-difluoro compounds in good yield.
T. Fukuhara, S. Hara, Synlett, 2009, 198-200.

Organoiodine(I/III) chemistry enables a metal-free, catalytic enantioselective intermolecular oxyamination of aryl- and alkyl-substituted alkenes with N-(fluorosulfonyl)carbamate as a bifunctional N,O-nucleophile with high enantioselectivity and electronically controlled regioselectivity. The oxyaminated products can be easily deprotected in one step to reveal free amino alcohols in high yields.
C. Wata, T. Hashimoto, J. Am. Chem. Soc., 2021, 143, 1745-1751.

An oxidative cyclization of β-substituted β,γ-unsaturated carboxylic acids using a hypervalent iodine reagent provides 4-substituted furan-2-ones. The use of the highly electrophilic PhI(OTf)2, which is in situ prepared from PhI(OAc)2 and Me3SiOTf, is crucial. Depending on the substitution pattern at the α-position of the substrates, furan-2(5H)-ones or furan-2(3H)-ones are produced.
K. Kiyokawa, K. Takemoto, S. Yahata, T. Kojima, S. Minakata, Synthesis, 2017, 49, 2907-2912.

A hypervalent iodine species, which is formed in situ in the presence of oxone as terminal oxidant, catalyzes the oxidation of aldoximes to generate nitrile oxides. A subsequent reaction with alkenes gives the corresponding isoxazolines in good yields, whereas the reaction with alkynes gives the corresponding isoxazoles in moderate yields.
A. Yoshimura, K. R. Middleton, A. D. Todora, B. J. Kastern, S. R. Koski, A. V. Maskaev, V. V. Zhdankin, Org. Lett., 2013, 15, 4010-4013.

In a convenient one-pot, three-step procedure for the synthesis of isoxazolines starting from aldehydes, the aldehydes are first transformed with hydroxylamine sulfate into aldoximes, which are then oxidized to nitrile oxides by an in situ generated hypervalent iodine compound. Finally, a 1,3-dipolar cycloaddition between the nitrile oxides and alkenes provides isoxazolines in good yields.
L. Han, B. Zhang, C. Xiang, J. Yan, Synthesis, 2014, 46, 503-509.

A chiral triazole-substituted iodoarene catalyzes an enantioselective oxidative cyclization of N-allyl carboxamides to provide highly enantioenriched oxazolines and oxazines. Quaternary stereocenters can be constructed and, besides N-allyl amides, the corresponding thioamides and imideamides are well tolerated as substrates.
A. H. Abazid, T.-N. Hollwedel, B. J. Nachtsheim, Org. Lett., 2021, 23, 5076-5080.

A cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions enables the preparation of five-, six-, and seven-membered rings with a range of substitutions. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible.
A. Alhalib, S. Kamouka, W. J. Moran, Org. Lett., 2015, 17, 1453-1456.

The auto-oxidation of isobutyraldehyde in the presence of molecular oxygen generates acyloxy radicals, which in situ afford a hypervalent iodine compound with p-anisolyl iodide. A hypervalent iodine mediated reaction of N'-arylidene acetohydrazides provides substituted 1,3,4-oxadiazoles in good yields in parallel.
J. Chauhan, M. K. Ravva, S. Sen, Org. Lett., 2019, 21, 6562-6565.

An oxidative desulfurization approach enables the construction of oxadiazole and thiadiazole heterocycles in the presence of iodobenzene and Oxone. The use of iodobenzene and the inexpensive readily available oxidant Oxone makes the reaction system simple and versatile for desulfurization.
K. N. Patel, N. C. Jadhav, P. B. Jagadhane, V. N. Telvekar, Synlett, 2012, 23, 1970-1972.

(Phenyliodonio)sulfamate (PISA) is a readily accessible and bench-stable water-soluble hypervalent iodine(III) reagent, that enables the synthesis of various indoles via C-H amination of 2-alkenylanilines involving an aryl migration/intramolecular cyclization cascade with excellent regioselectivity.
H.-D. Xia, Y.-D. Zhang, Y.-H. Wang, C. Zhang, Org. Lett., 2018, 20, 4052-4056.

Sulfonamidyl (hetero)arenes can be synthesized by a C(sp2)-H amidation with bench-stable amidyl-iminophenylacetic acids in the presence of a hypervalent iodine reagent. The hypervalent iodine reagent covalently activates the iminophenylacetic acid for the facile sulfonamidyl radical generation under mild photocatalytic oxidative conditions.
Y. Pan, Z. Liu, P. Zou, Y. Chen, Y. Chen, Org. Lett., 2022, 24, 6681-6685.

A hypervalent iodine(III)-mediated intramolecular decarboxylative Heck-type reaction of 2-vinyl-phenyl oxamic acids provides various 2-quinolinones with excellent chemoselectivity at room temperature via a unique ring-strain-enabled radical decarboxylation mechanism. This protocol features metal-free reaction conditions and operational simplicity.
H. Fan, P. Pan, Y. Zhang, W. Wang, Org. Lett., 2018, 20, 7929-7932.

Hypervalent Iodine Chemistry