Development of new recyclable reagents and catalytic systems based on hypervalent iodine compounds

Article abstract of DOI:10.1016/j.mencom.2010.06.001

Recent advances in the development of polymer-supported iodine(V) oxidants, recyclable monomeric hypervalent iodine(III) reagents and catalytic systems based on hypervalent iodine compounds are discussed. These efficient and environmentally friendly reagents and catalysts are particularly useful for oxidative transformations of alcohols to carbonyl compounds and for oxidations at the benzylic position.

Full text of DOI:10.1016/j.mencom.2010.06.001

Mendeleev
Communications
Focus Article, Mendeleev Commun., 2010, 20, 185–191
Development of new recyclable reagents and catalytic
systems based on hypervalent iodine compounds
Mekhman S. Yusubova,b and Viktor V. Zhdankin*c
a Siberian State Medical University, 634050 Tomsk, Russian Federation
b Tomsk Polytechnic University, 634050 Tomsk, Russian Federation
c Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth,
MN 55812, USA. Fax: +1 218 726 7394; e-mail: vzhdanki@d.umn.edu
DOI: 10.1016/j.mencom.2010.06.001
Recent advances in the development of polymer-supported iodine(V) oxidants, recyclable monomeric hypervalent iodine(III)
reagents and catalytic systems based on hypervalent iodine compounds are discussed. These efficient and environmentally
friendly reagents and catalysts are particularly useful for oxidative transformations of alcohols to carbonyl compounds and for
oxidations at the benzylic position.
During the past decade, the chemistry of hypervalent iodine
O
O
O
O
O
O
O
O
compounds has attracted a significant research interest.1–13
Hypervalent iodine reagents are used extensively in organic
synthesis as efficient oxidizing reagents whose chemical properties
are similar to those of mercury(II), thallium(III), lead(IV) and
chromium(VI) derivatives but without the toxicity and environ-
mental problems of these heavy metal congeners. Among hyper-
valent iodine compounds, pentavalent iodine derivatives (λ5-iodanes)
are especially important as efficient oxidants.1–4 In particular,
heterocyclic λ5-iodane, 1-hydroxy-1-oxo-1H-1λ5-benzo[d][1,2]-
iodoxol-3-one 1, known under the name of its tautomeric
form of 2-iodoxybenzoic acid (IBX), has received widespread
application in organic synthesis as an efficient and mild oxidant
that can be used for selective oxidation of primary and secondary
alcohols and for other important oxidations.1–4 However, the
explosive character and low solubility of IBX in common organic
solvents restrict the practical application of this reagent. The
low solubility and unfavorable physical and chemical properties
of IBX 1 arise from strong intermolecular secondary bonding
observed for this compound in a solid state.14,15
OH
I
I
I
I
O
O
O
N
R2
O
R1
NHR
OR
1 (IBX)
2 (IBX-amides) 3 (IBX-esters)
4 (NIPA)
O
O
O
I
O
O
O
O
O
O
I
I
I
O
O
Ts
O
R
S
S
N
R
O
NHR
OR
5
6
7
8
Earlier, we have developed a series of stable and soluble IBX
analogues: IBX-amides 2,16 IBX-esters 3,17,18 N-(2-iodylphenyl)-
acylamides (NIPA) 4,19 2-iodylphenyl ethers 5,20 2-iodyl-
benzenesulfonamides 6,21 2-iodylbenzenesulfonate esters 722
and N-(2-iodylphenyl)tosylamides 8.23 According to X-ray data,
Viktor V. Zhdankin (right) received his M.S. (1978), Ph.D. (1981), and Doctor of
Chemical Sciences (1986) degrees at M. V. Lomonosov Moscow State University in the
research laboratories of Professor N. S. Zefirov. He moved to the University of Utah in
1990, where he worked for three years as instructor of organic chemistry and senior
research associate with Professor P. J. Stang. In 1993, he joined the faculty of the
University of Minnesota Duluth, where he is currently a professor of chemistry. He
published over 220 scientific papers, edited several books and co-authored the Handbook
of Heterocyclic Chemistry (3rd edn., 2010) with Professors A. R. Katritzky, C. A. Ramsden
and J. A. Joule. His main research interests are in the fields of synthetic and mechanistic
organic chemistry of hypervalent main-group elements (iodine, xenon, selenium, sulfur and phosphorus) and organofluorine chemistry.
Professor Zhdankin is a member of the Editorial Board of Mendeleev Communications and a scientific editor of ARKIVOC.
Mekhman S. Yusubov (left) received his M.S. (1985), Ph.D. (1991), and Doctor of Chemical Sciences (1998) degrees at Tomsk
Polytechnic University in the laboratory of Professor V. D. Filimonov. He is a head of Chemistry Department at Siberian State
Medical University and a professor at Tomsk Polytechnic University. Since 1994, he has been involved in intense international
collaborative research programs with leading research laboratories in South Korea, Germany and the United Kingdom. In 2004, he
started a joint research in the area of recyclable hypervalent iodine reagents with Professor V. V. Zhdankin in University of
Minnesota Duluth. His main research interests are in the fields of chemistry of natural products and hypervalent iodine reagents.
Professor Yusubov has published over 100 scientific papers.
– 185 –
© 2010 Mendeleev Communications. All rights reserved.

Focus Article, Mendeleev Commun., 2010, 20, 185–191
a pseudocyclic moiety due to the intramolecular nonbonding
an amide function, the carbamoylbutanoic acid moiety was
chosen as a linker. Commercially available 2-iodoaniline 14
was reacted with glutaric anhydride to give acid 15, which was
subsequently coupled to aminomethylpolystyrene with 1-hydroxy-
1H-benzotriazole/diisopropylcarbodiimide (HOBt/DIC) to give
resin 16. To block any possible free amino groups, the resin
was subsequently treated with an excess of acetic anhydride and
pyridine (Scheme 1). The loading of resin 16 was determined
by elemental analysis and corresponded to 82% conversion.
Oxidation of resin 16 to NIPA resin 17 was initially performed
with 3,3-dimethyldioxirane, as it was described for a solution-
phase synthesis.19 The obtained resin was characterized by IR
spectroscopy and elemental analysis. Oxidizing activity of
NIPA resin 17 was measured by GC analysis with an excess
of benzyl alcohol as a test substrate and was found to be
0.31 mmol g–1 with respect to IO2 groups. Much higher loading
levels (0.7–0.8 mmol g–1) have been reached by the oxidation
of resin 16 using an equimolar mixture of tetrabutylammonium
Oxone® [2Bu4NHSO5·Bu4NHSO4·(Bu4N)2SO4] with methane-
sulfonic acid. To avoid the supplementary preparation of tetra-
butylammonium Oxone®, we have performed the oxidation
of polymer 16 in the CH2Cl2–H2O biphasic system using
Oxone® (2KHSO5·KHSO4·K2SO4), Bu4NHSO4 and MeSO3H
(Scheme 1). Overall, our synthesis of NIPA resin 17 employs
commercially available aminomethylated polystyrene; it includes
three simple steps and affords the resin with good loading of
0.70–0.80 mmol g–1. Combined with straightforward synthesis
and cheap starting materials, NIPA resin 17 represents a good
alternative to previously reported IBX resins 9–13.29–31
iodine-oxygen interaction with ortho-substituent is a key struc-
tural feature present in these compounds.15–23 The presence of
ortho-coordination in compounds 2–8 leads to partial disrup-
tion of the polymeric network, and consequently enhances
their solubility and reactivity. Among these pseudocyclic IBX
analogues, readily available, non-explosive and thermally stable
hypervalent iodine reagents 2–5 have proved to be particu-
larly useful, selective oxidizing reagents towards alcohols and
sulfides.16–20,24
Despite their useful reactivity, enhanced stability, and environ-
mentally benign nature, reagents 2–5 are not perfect with respect
to the Green Chemistry principles.25 According to a basic
principle of Green Chemistry, catalytic or recyclable reagents
are superior to stoichiometric reagents. Here, we survey our
recent research efforts on the development of recyclable oxidants
and catalytic systems based on hypervalent iodine compounds.
Polymer-supported iodine(V) oxidants
Polymer-supported reagents have found broad application in
organic synthesis since the development of the solid-phase and
combinatorial high throughput synthesis techniques. Attach-
ment of a chemical reagent to an insoluble polymer matrix
enables easy reaction work-up by simple filtration, automated
parallel synthesis and fast reaction optimization.26–28 A number
of polymer-supported hypervalent iodine(III) reagents have also
been reported.2–5
The presence of a functional group in the ortho-position of
pseudocyclic iodylarenes 2–5 provides a convenient opportunity
of linking a hypervalent iodine(V) reagent to the polymeric
backbone. Shortly after our preparation of IBX-amides 216 and
IBX-esters 3,17 Lee and co-workers have reported the synthesis
of polymer-supported IBX-amides 9, 10 and IBX-ester 11 starting
from commercially available hydroxy or amino polystyrene in
two steps.29 Oxidant resins 9–11 were prepared with loadings
of 0.65–1.08 mmol g–1, and they were evaluated with a series of
alcohol substrates. Polymer supported IBX-amide 10 exhibited
particularly fast and efficient oxidative activities toward alcohols
under mild reaction conditions.29 IBX-amide resin 10 is also
an efficient oxidant for the oxidative bromination of activated
aromatic compounds using tetraethylammonium bromide.30
Linclau and co-workers reported an improved synthesis of solid-
supported IBX-amide resins 12 and 13 using inexpensive and
commercially available 2-iodobenzoyl chloride and Merrifield
resin.31 Oxidation of alcohols to the corresponding carbonyl
compounds can be accomplished using 1.2 equiv. of resins 12
and 13. Recycling of the resin is also possible with a minimal
loss of activity after two reoxidations.31
O
OH
I
I
NH2
NH
O
i
89%
14
15
H
N
O
I
NH
O
ii, iii
82%
NH2
1.57 mmol g–1
4.0 mmol g–1
16
H
N
O
O
O
I
NH
O
iv
0.7–0.8 mmol g–1
17
H
N
H
Scheme 1 Preparation of NIPA resin. Reagents and conditions: i, glutaric
anhydride (1.1 equiv.), PhMe, reflux, 3 h; ii, 15 (1 equiv.), HOBt (1.1 equiv.),
DIC (1.0 equiv), DMF, 105 °C, 8 h, then room temperature, 8 h; iii, Ac2O
(2.0 equiv.), pyridine (2.0 equiv.), 80 °C, 3 h; iv, Oxone® (10 equiv.), MsOH
(10 equiv.), Bu4NHSO4 (5 equiv.), CH2Cl2–H2O, room temperature, 36 h.
N
O
O
O
O
I
O
I
O
O
9
10
Carbonyl compounds are important intermediates for the
preparation of a wide variety of organic substances. Hence, there
is an ensuing interest in developing new mild and selective
methods for the oxidation of alcohols, especially using solid-
supported reagents.33,34 Hypervalent iodine based oxidants do not
rely on heavy metal salts or additional co-oxidants, thus meeting
scalable, economical and environmentally friendly requirements
put forth by the contemporary chemical industry. In this context,
NIPA resin 17 appears to be an apt reagent, since its synthesis,
in contrast to IBX resins,29–31 does not contain multiple labor-
intensive and time-consuming steps. Based on solution-phase
H
O
O
N
n
O
O
I
O
I
O
O
11
12 n = 1
13 n = 3
In the context of these findings, we considered the develop-
ment of a polymer-supported N-(2-iodylphenyl)acylamide reagent
(NIPA resin).32 In order to furnish a pseudo benziodoxazine
scaffold and to assure proper immobilization to the resin through
– 186 –

Focus Article, Mendeleev Commun., 2010, 20, 185–191
Table 1 Oxidations of alcohols with NIPA resin 17.
Conver-
Conver-
Entry
1
Alcohol
Product
Entry
11
Alcohol
Product
sion (%)a
sion (%)a
OH
O
OH
OH
O
O
> 99
> 99
OH
O
2
3
> 99
> 99
12
13
> 99b
MeO
MeO
OH
O
94b,c
O
OH
NO2
NO2
O
OH
OH
O
4
98
14
61
OH
O
O
OH
H
O
5
6
> 99
> 99
15
16
> 99
H
O
96
OH
6
6
OH
OH
O
7
8
> 99
> 99
17
18
85d
OH
O
MeS
MeS
> 99
O
OH
(89%)e
OH
OH
O
7
7
S
S
O
N
N
> 99
9
> 99
> 99
19
20
O
O
OH
OH
(86%)e
S
S
OH
OH
O
10
90f
N
N
OH
aAll oxidations were carried out with 1.0 equiv. of NIPA resin 17 in dry dichloroethane at reflux (85 °C) for 60 min, unless otherwise noted. The resin was
removed by filtration and washed with dry dichloroethane. The resulting filtrates were analyzed by GC-MS. For product isolation, combined filtrates from
several resin washings were passed through small pad of silica gel, silica gel washed with DCE, and the combined DCE fractions were evaporated to yield
the respective carbonyl compound, pure by 1H NMR. bOxidation was performed for 30 min. c(Z)-isomer (6%) was detected. dOxidation was carried out with
0.5 equiv. of NIPA resin 17. 4-(Methylsulfinyl)benzaldehyde (7%) and [4-(methylthio)phenyl]methanol (8%) were detected. eIsolated yields. fOxidation was
carried out with 2.0 equiv. of NIPA resin 17 in dry DCE at 60 °C for 180 min.
NIPA chemistry, no acidic additives (in contrast to IBX-amide
resins)29–31 are required to effect fast conversion to the corre-
sponding alcohol.
these linkers was achieved through easy steps with excellent
yields. Thus, the reaction of commercially available 2-iodo-
phenol 18 with ethyl 4-bromobutanoate gave ester 19, which
was afterwards saponified to afford acid 20. Acid 20 was
subsequently coupled to aminomethylated polystyrene with
HOBt/DIC to yield resin 22 (Scheme 2). To block any possible
free amino groups, the resin was treated with an excess of
acetic anhydride and pyridine.
Since 2-iodophenol can be easily attached to the halo-
methylated polymers through a simple nucleophilic substitu-
tion, we have also investigated Merrifield resin as a solid support.
This resin is cheaper than aminomethylated polystyrene and is
more stable to the typical acidic oxidation conditions that have
previously been used for the oxidation of known polymer-
supported reagents. Although direct attachment of 2-iodophenol
18 to Merrifield resin was unsuccessful, readily available alcohol
21 was successfully coupled to the Merrifield resin via an ether
link to yield polymer 23 (Scheme 2).
We tested NIPA resin 17 with a variety of alcohol substrates:
benzylic, allylic, primary and secondary alcohols, a diol and a
thioalcohol (Table 1).32 Most alcohols were oxidized to the
respective aldehyde or ketone products in excellent purities and
yields. Interestingly, oxidation of cis-cyclohexane-1,2-diol yielded
only the respective hydroxycyclohexanone and, in contrast to
IBX amides, no C–C bond cleavage was observed. The poly-
meric material, resulting from the reduction of NIPA resin 17
with alcohols, can be collected and reoxidized according to the
procedure described above (Scheme 1). A moderate decline in
oxidative activity was observed after multiple recovery steps,
putatively due to iodine loss in the course of resin reoxidation
under acidic conditions.
At the next step, we have investigated the preparation of
polymer-supported 2-iodylphenol ethers 5, which are readily
available and stable IBX analogues having a pseudocyclic four-
membered ring motif.20 To create a 2-iodylphenol ether scaffold
and to ensure proper immobilization to resin through amide
and ether bonds, 4-hydroxybutanoic acid and 1,4-butanediol
moieties, respectively, were chosen as linkers.35 Preparation of
The loadings of resins 22 and 23 were determined by
elemental analysis and corresponded to 89 and 70% conver-
sions, respectively. Oxidation of polymers 22 and 23 was initially
performed with 3,3-dimethyldioxirane (Scheme 2, method A),
as described for the solution phase synthesis of monomeric
– 187 –

Focus Article, Mendeleev Commun., 2010, 20, 185–191
presence of a sulfide group. The reduced polymeric materials
I
I
O
formed in the reactions of resins 24 and 25 with alcohols can be
collected and reoxidized according to the procedure described
above (Scheme 2). A slow decline in oxidative activity was
observed after multiple recovery steps, possibly, due to iodine
loss in the course of resin reoxidation.35
In summary, a series of polymer-supported hypervalent
iodine(V) oxidants based on ortho-substituted iodylarenes linked
to a polystyrene backbone has been developed. These new
recyclable reagents have the advantage of easy reaction work-up
by simple filtration, and they can find practical applications in
the solid-phase and combinatorial high throughput synthesis
techniques.
OH
O
Br(CH2)3COOEt
OEt
3
K2CO3, DMF,
60 °C, 12 h, 96%
18
19
LiOH,
THF–H2O,
98%
I
I
O
O
O
BH3·Me2S
THF, 93%
OH
OH
3
3
21
20
i, NaH, DMF,
0 °C, 15 min
i, HOBt, DIC,
DMF, 105 °C,
8 h, then room
temperature, 8 h
ii, Ac2O, Py,
80 °C, 4 h
Recyclable monomeric hypervalent iodine(III) reagents
Despite the utility of the polymer-supported reagents, they still
have several drawbacks. These reagents require a multistep pre-
paration, they are insoluble and, therefore, have lower reactivity
compared to the corresponding monomeric analogues. Moreover,
the repeated use of these polymers leads to significant degrada-
tion due to the benzylic oxidation of the polystyrene chain. The
other previously reported approaches to recyclable hypervalent
iodide reagents involve complex molecular species,36,37 which
require multistep syntheses, or employ fluorous alkyl iodides
and fluorous solvents for separation of products.38
In the last few years, much effort has been devoted to the
development of simple, nonpolymeric, recyclable iodanes, which
show reactivities similar to those of the original hypervalent
iodine(III) reagents. We have found that 3-iodosylbenzoic acid
27 (Scheme 3) is an excellent oxidizing reagent whose reduced
form, 3-iodobenzoic acid 26, can be removed at the end of the
reaction by treatment with an anion-exchange resin or by
addition of NaHCO3, and it can be easily recycled.39 Likewise,
3-(dichloroiodo)benzoic acid is an excellent chlorinating reagent
that can be similarly recycled via 3-iodobenzoic acid.40 In
contrast to the previously reported protocols,36–38 hypervalent
iodine reagents derived from 3-iodobenzoic acid are inexpensive
and readily available compounds that can be easily recovered
from the reaction mixture. Recently, we have reported the
preparation and X-ray crystal structure of two new recyclable
nonpolymeric hypervalent iodine reagents derived from 3-iodo-
benzoic acid, namely, 3-[bis(trifluoroacetoxy)iodo]benzoic acid
28 and 3-[hydroxy(tosyloxy)iodo]benzoic acid 29.41 Com-
pounds 28 and 29 were conveniently prepared in high yield by
treatment of 3-iodosylbenzoic acid 27 with trifluoroacetic acid
or p-toluenesulfonic acid, respectively (Scheme 3).
Cl
NH2
ii,
,
KI, room temperature,
3 days
I
I
O
O
O
O
N
3
3
H
23
22
Method A or B
Method A or B
O
O
O
O
O
I
I
O
O
O
N
3
3
H
25
24
A: loading 0.81 mmol g–1
B: loading 0.55 mmol g–1
A: loading 1.23 mmol g–1
B: loading 0.86 mmol g–1
O
O
Method A:
, acetone, room temperature
Method B: Oxone®, NaHCO3, H2O, acetone, CH2Cl2,
room temperature, 3 days
Scheme 2 Synthesis of polymer-supported 2-iodylphenol ethers 24 and 25.
2-iodylphenol ethers 3.20 Resins 24 and 25 were characterized by
IR spectroscopy and elemental analysis. The oxidizing activity
of reagents 24 and 25 was measured by GC-MS analysis using
an excess of 4-methoxybenzyl alcohol as the test substrate under
reflux in 1,2-dichloroethane for 3 h. Based on these measure-
ments, the loadings of resins 24 and 25 were found to be 1.23
and 0.81 mmol g–1, respectively, on a IO2 group basis. Since
the dioxirane oxidation was effective but not very practical
(3,3-dimethyldioxirane is unstable and not readily available),
we have tested the in situ generated dioxirane as the oxidizing
agent. The modified protocol (Scheme 2, method B) consists
of treatment of resins 22 and 23 with Oxone®, NaHCO3, and
acetone at room temperature and affords resins 24 and 25
with only slightly lower loading levels (0.74–0.86 mmol g–1 for
polymer 24 and 0.50–0.55 mmol g–1 for polymer 25). We have
used this practical procedure (method B) for the preparation of
numerous batches of resins 24 and 25 in gram quantities.
AcOOH,
AcOH, 12 h
80%
HO2C
I
HO2C
IO
26
27
CF3CO2H
reflux, 1 h
TsOH·H2O
83% MeCN, room
temperature, 1 h
92%
The oxidative properties of resins 24 and 25 were evaluated
by the reactions with benzylic, allylic, primary and secondary
alcohols. With all tested alcohols, a 100% conversion to the
respective carbonyl products has been reached in 0.5–3 h at
room temperature, which is indicative of a higher oxidative
reactivity of reagents 24 and 25 compared to NIPA resin 17.
Although both reagents gave corresponding carbonyl compounds
with high conversion and purity, resin 24 performed these
oxidations faster in most cases. Both reagents showed good
selectivity towards the oxidation of a hydroxy group in the
HO2C
I(OCOCF3)2
HO2C
I(OH)OTs
28
29
Scheme 3 Preparation of 3-iodosylbenzoic acid 27 and its derivatives 28
and 29.
Products 28 and 29 were isolated as white, stable, micro-
crystalline compounds and analyzed by NMR spectroscopy,
elemental analysis, and X-ray crystallography.41 The structural
features and reactivity patterns of compounds 28 and 29 are similar
– 188 –

Focus Article, Mendeleev Commun., 2010, 20, 185–191
to those of [bis(trifluoroacetoxy)iodo]benzene PhI(OCOCF3)2
Ishihara et al.58 have developed an optimized procedure for the
catalytic oxidation of alcohols by using 2-iodylbenzenesulfonic
acid63 as an extremely active catalyst and Oxone® as a terminal
oxidant (Scheme 5). However, the synthetic value of the iodine(V)-
based catalytic cycle is limited by the reoxidation step of iodine(I)
or iodine(III) to iodine(V) species, which proceeds relatively
slowly even at temperatures above 70 °C.58–62
and [hydroxy(tosyloxy)iodo]benzene PhI(OH)OTs, which belong
to the most important and widely used hypervalent iodine
reagents.1–5 The oxidative properties of reagents 28 and 29
were evaluated in the most typical reactions previously reported
for PhI(OCOCF3)2 and PhI(OH)OTs, such as the oxidation of
sulfides,36 the oxidative iodination of arenes,42 the α-tosyl-
oxylation of ketones36 and the Hofmann-type rearrangement36
(Scheme 4). The products of these reactions (Scheme 4) were
conveniently separated from the by-product, 3-iodobenzoic
acid 26, by simple treatment with ion-exchange resin IRA-900.
3-Iodobenzoic acid 26 can be easily regenerated from IRA-900
resin by treatment with aqueous HCl, and it can be reoxidized
to reagent 27 without additional purification.39 An alternative
procedure for product separation involves basic aqueous work-up
followed by acidification with HCl.40
2KHSO5·KHSO4·K2SO4
(Oxone®), 70 °C, MeCN–H2O,
several hours
ArI
or
ArIO
Carbonyl
compounds
3KHSO4·K2SO4
ArIO2
Alcohols
Ar = 2-HOOCC6H4 or 2-HO3SC6H4
Scheme 5 Iodine(V)-catalyzed oxidations using Oxone®.58–60
O
Based on our studies of RuCl3-catalyzed disproportionation
of iodine(III) species to iodobenzene and iodylbenzene,64,65
we have developed an extremely mild and efficient tandem
catalytic system for the oxidation of alcohols and hydrocarbons
via a RuIII-catalyzed reoxidation of ArIO to ArIO2 using Oxone®
as a stoichiometric oxidant.66 Taking into account that the RuIII-
catalyzed oxidation of alcohols usually occurs only at tem-
peratures above 80 °C, while iodylarenes are effective oxidants
at room temperature,2–4 we investigated the oxidation of alcohols
using the PhI/RuCl3 tandem catalytic system. The reaction
was optimized using 1-phenylethanol as a model substrate. As
expected, in the absence of PhI and in the presence of RuCl3
(0.16 mol%), or in the presence of PhI without RuCl3 the oxida-
tion of 1-phenylethanol at room temperature proceeds very
slowly. The combined application of PhI and RuCl3 results in
the almost instantaneous oxidation of 1-phenylethanol to aceto-
phenone with a 100% conversion reached in less than 20 min.
Alcohols 30 are smoothly oxidized under these reaction condi-
tions to afford respective oxidation products 31 in excellent
isolated yields at room temperature (Scheme 6).
28, MeCN–H2O, 5:1,
room temperature, 20 min
S
S
86%
I
I
28, I2, MeCN,
50% aq. H2SO4 (0.05 ml),
room temperature, 60 min
89%
O
O
29, MeCN,
OTs
reflux, 60 min
94%
O
29, MeCN, room
NH2
temperature, 60 min
NH2
93%
O2N
O2N
Scheme 4 Representative reactions of reagents 28 and 29.
PhI (5 mol%), Oxone®
RuCl3 (0.16 mol%)
OH
R2
O
In summary, we have reported the preparation, X-ray structural
characterization, and reactivity of 3-[bis(trifluoroacetoxy)iodo]-
benzoic acid 28 and 3-[hydroxy(tosyloxy)iodo]benzoic acid 29,
new recyclable iodine(III) reagents derived from 3-iodosyl-
benzoic acid. Compounds 28 and 29 have a reactivity pattern
similar to the most common non-recyclable hypervalent iodine
reagents, PhI(OCOCF3)2 and PhI(OH)OTs; however, their reduced
form, 3-iodobenzoic acid 26, can be easily recovered from
reaction mixture and reused. In contrast to the polymer-sup-
ported recyclable reagents, compounds 28 and 29 are soluble
in organic solvents, and they can be recovered from reaction
mixtures without any loss of activity.
R1
R1
R2
MeCN–H2O (1:1, v/v),
room temperature
30
31
Scheme 6 PhI/RuCl3-cocatalyzed oxidation of alcohols.66
Selective oxidation of activated and unactivated C–H bonds
is of particular interest for organic chemists. The pentavalent
iodine reagent, IBX 1, has been demonstrated to be a reagent of
choice for the oxidation of benzylic C–H bonds.67,68 Recently,
the oxidation of benzylic C–H bonds has been performed under
catalytic conditions by the in situ formed IBX using Oxone® as
a terminal oxidant at 70–80 °C for 8–48 h.62 We investigated
the oxidation of C–H bonds using the PhI/RuCl3 tandem catalytic
system. The reaction was optimized using ethylbenzene as a
model substrate. As expected, in the absence of PhI and in the
presence of RuCl3 or in the presence of PhI and in the absence
of RuCl3 the oxidation of ethylbenzene at room temperature
does not occur or proceeds very slowly. The combined applica-
tion of PhI and RuCl3 results in up to 80% conversion of ethyl-
benzene to acetophenone. The optimized reaction conditions
require the addition of 4.2 mole-equiv. of Oxone® in small portions
over 11 h and the use of 10 mol% PhI (Table 2, entry 1).
Catalytic application of hypervalent iodine reagents
The catalytic use of hypervalent iodine reagents is one of the
most impressive recent developments in organoiodine chem-
istry.5,8–10 Numerous examples of catalytic utilization of the
iodine(III) species have been reported.43–57 In particular, the
iodine(I)/iodine(III) catalytic cycle based on the in situ oxida-
tion of ArI using peracids has been utilized for the α-functional-
ization of carbonyl compounds,43–46 the oxidative cleavage of
alkenes and alkynes,47 the TEMPO-mediated oxidation of benzylic
alcohols,48 and various intramolecular cyclizations.49–57 Like-
wise, the iodine(V) based catalytic cycles employing Oxone®
as a stoichiometric oxidant have been used for the oxidation of
alcohols,58–60 the oxidation of p-alkoxyphenols to quinones61
and the oxidation of benzylic C–H bonds.62 For example,
The results of the oxidation of hydrocarbons under catalytic
conditions are summarized in Table 2. In general, moderate to
high yields of aromatic ketones are obtained in these oxidations
under very mild reaction conditions (entries 1–8). Compared to
the high-temperature IBX/Oxone® procedure,62 our protocol is
– 189 –

Focus Article, Mendeleev Commun., 2010, 20, 185–191
Table 2 PhI/RuCl3-cocatalyzed oxidation of hydrocarbons.a
Oxone®
RuIII
PhIO2
PhIO
Ar
Ar
O
Yield
(%)b
Entry
1
Substrate
Time/h
12
Product
O
RuV
O
80c
80
Ph
Ph
Ph
O
Scheme 7 PhI/RuCl3 tandem catalytic system for the oxidation of organic
substrates with Oxone®.66
2
3
26
3
Ph
to PhIO2 using Oxone as a stoichiometric oxidant. Due to the
mild reaction conditions, our protocol is highly selective, and it
generally does not afford products of C–C bond cleavage.
O
77
23
Et
Et
O
Conclusions
A survey of current literature demonstrates that hypervalent
iodine compounds attract significant interest as efficient and
environmentally friendly oxidizing reagents, which can be used
instead of the toxic derivatives of mercury(II), thallium(III),
lead(IV), chromium(VI) and other heavy metals.1–13 Our contri-
bution to this area of research consists in the development of
new hypervalent iodine reagents,16–23,73–92 some of which have
already found practical application in organic synthesis. The
recent discovery of recyclable reagents and catalytic systems
based on the iodine redox chemistry has initiated a major surge
of research activity and added a new dimension to the field of
hypervalent iodine chemistry. Taking into account the import-
ance of Green Chemistry principles,25 it can be anticipated that
the current trend toward the synthetic application of recyclable
reagents and catalytic systems based on hypervalent iodine
chemistry will continue in the future. We hope that our recent
studies described here will provide an added stimulus for the
further development of the chemistry of hypervalent iodine
compounds.
But
But
4
5
6
1
O
69
72
O
6
7
20
20
O
O
38
O
8
9
1
8
95
This work was supported by the Government of the Russian
Federation (cooperative research programme on hypervalent
iodine chemistry FCP 2010-1.5-000-010-044) and the US National
Science Foundation (research grant no. CHE-1009038).
1.5
OH
aAll reactions were performed at room temperature in MeCN–H2O (1:1, v/v)
using 1.0 mmol of a hydrocarbon, 2–6 mmol of Oxone®, 0.16 mol% of
RuCl3 and 5 mol% of PhI unless otherwise noted. bYields of isolated
products are shown; unreacted hydrocarbons were also present in all entries.
c10 mol% of PhI was used.
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Received: 11th May 2010; Com. 10/3523
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