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.
