High-yielding one-pot synthesis of diaryliodonium triflates from arenes and iodine or aryl iodides

Article abstract of DOI:10.1039/b701864a

Unsymmetric and symmetric diaryliodonium triflates are synthesized from both electron-deficient and electron-rich substrates in a fast, high yielding, and operationally simple protocol employing arenes and aryl iodides or iodine. The Royal Society of Chem

Full text of DOI:10.1039/b701864a

View Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
High-yielding one-pot synthesis of diaryliodonium triflates from arenes
and iodine or aryl iodides{
Marcin Bielawski and Berit Olofsson*
Received (in Cambridge, UK) 6th February 2007, Accepted 27th February 2007
First published as an Advance Article on the web 20th March 2007
DOI: 10.1039/b701864a
commercially available oxidant in the presence of an arene and a
suitable acid, the anion of which would end up in the iodonium
salt (eqn. 1).
Unsymmetric and symmetric diaryliodonium triflates are
synthesized from both electron-deficient and electron-rich
substrates in a fast, high yielding, and operationally simple
protocol employing arenes and aryl iodides or iodine.
ð1Þ
mCPBA has recently been reported to oxidize iodobenzene to
(diacyloxyiodo)benzene,16 which encouraged us to investigate
whether this oxidant could be employed also in the direct synthesis
of iodonium salts. Suitable reaction conditions for the reaction of
iodobenzene (1a) and benzene (2a) with mCPBA in organic
solvents were thus screened. Boron trifluoride and trifluorometha-
nesulfonic acid were deemed interesting acids, as they could give
rise to iodonium salts with tetrafluoroborate and triflate anions,
respectively, without a subsequent anion exchange step. Initial
attempts to combine mCPBA with boron trifluoride etherate in
dichloromethane at room temperature were encouraging, as a
diphenyliodonium salt was formed in moderate yield. Due to
problems with purification and anion identification, the use of
triflic acid instead of BF3?OEt2 was next investigated.
Hypervalent iodine compounds have recently received consider-
able attention as mild, non-toxic and selective reagents in organic
synthesis.1,2 Iodine(III) reagents with two heteroatom ligands, e.g.
(diacetoxyiodo)benzene and iodosylbenzene, are successfully
employed in oxidations of alcohols, alkenes and a-oxidations of
carbonyl compounds.3 The properties of iodine(III) reagents with
two carbon ligands resemble those of metals such as Hg, Pb and
Pd, allowing for reaction pathways similar to metal-catalyzed
reactions while avoiding the drawbacks of cost, toxicity and
threshold values in pharmaceutical products.2 Diaryliodonium
salts are the most studied compounds in this class; they are
versatile electrophiles in a-arylation of carbonyl compounds4,5 and
metal-catalyzed cross-couplings,6 and are frequently employed as
photoinitiators in polymerizations.7
Gratifyingly, the treatment of iodobenzene with mCPBA,17
TfOH and excess benzene in dichloromethane at room tempera-
ture resulted in a clean reaction to give iodonium triflate 3a in 82%
isolated yield (Table 1, entry 1). The reaction time could be
considerably reduced by increasing the temperature, delivering 3a
in 89% yield after 1 h at 40 uC (entry 3) or in 85% yield after only
10 min at 80 uC (entry 4). In this fast and operationally simple one-
pot reaction, 3a is formed directly from commercially available
substrates and can be isolated with a suitable anion in high yield
after a simple workup.
Synthetic routes to diaryliodonium salts typically involve 2–3
steps, with initial oxidation of an aryl iodide to iodine(III) followed
by ligand exchange with an arene to obtain the diaryliodonium
salt.8 Preformed inorganic iodine(III) reagents, such as iodosyl
fluorosulfate, have been employed to shorten the route.9 These
reagents are, however, not commercially available. Reported
reactions with oxidation and ligand exchange in the same pot
suffer from narrow substrate scope10,11 or long reaction times,11
need excess reagents12 or employ toxic chromium reagents.13 In
many cases a subsequent anion exchange step is necessary, as the
anion influences both the solubility and reactivity of the iodonium
salt. Non-nucleophilic anions, such as triflate or tetrafluoroborate,
have proven superior to halide anions in many applications.6,14
The lack of general and efficient methods for the synthesis of
diaryliodonium salts is cumbersome, and clearly limits their scope
as environmentally benign reagents in organic chemistry.15 The
development of an operationally simple protocol with broad
substrate scope would greatly facilitate the application of these
efficient, non-toxic arylation agents. Herein we present our
preliminary results on a fast, high-yielding, one-pot synthesis of
the title compounds.
To determine the generality of this novel one-pot reaction, it was
applied to the synthesis of various diaryliodonium salts 3 from
aryl iodides 1 and arenes 2 (Table 2). Most previous protocols
have been restricted to the synthesis of either electron-rich or
Table 1 Temperature influence on the synthesis of 3aa
Entry 2a (equiv.) TfOH (equiv.) T (uC) Time
Yield (%)b
An atom efficient and simple one-pot synthesis of diaryliodo-
nium salts would involve treatment of an aryl iodide with a
1
2
3
4
a
5
2
2
1.1
2
3
3
3
rt
rt
40
80
21 h
21 h
1 h
82
89
89
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm
University, SE-106 91 Stockholm, Sweden. E-mail: berit@organ.su.se;
Fax: +46-8-154908; Tel: +46-8-162204
{ Electronic supplementary information (ESI) available: Synthetic proce-
dures, analytical data and NMR spectra for salts 3. See DOI: 10.1039/
b701864a
10 min 85
Reaction conditions: 1a (0.23 mmol), 2a and mCPBA (0.25 mmol)
were dissolved in CH2Cl2 (2 mL), TfOH was added at rt and the
reaction was stirred at the indicated temperature for the indicated
time in a sealed tube. Isolated yield.
b
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 2521–2523 | 2521

View Online
stannane,18 which further illuminates the efficiency and environ-
Table 2 Synthesis of substituted diaryliodonium salts 3a
mental friendliness of our procedure.
Unsymmetrical salt 3c could also be formed by the reaction of
4-iodotoluene (1b) with benzene, as shown in entry 6. Aryl iodide
1b was also employed to form the symmetrically substituted bis(4-
methylphenyl)iodonium salt 3f (entry 7). The reason for the
moderate yield of 3f is unclear, as 2-iodotoluene (1c) delivered salts
3g and 3h in high yields upon reaction with benzene and toluene,
respectively (entries 8, 9).
Yield
(%)c
Entry 1 (Ar1I)
2 (Ar2H)
Salt 3b
1d
2
1a (PhI)
1a (PhI)
2a (PhH)
2b (PhI)
3a
85
85
Generally, the synthesis of electron-rich salts was easier from
iodobenzene and a substituted arene than from the ‘‘reverse’’
reaction of a substituted aryl iodide with benzene (compare entries
3 and 6). 4-Iodoanisole and 2-iodothiophene both participated in
the reaction with benzene, but unidentified byproducts were
formed.
3
4
1a (PhI)
1a (PhI)
2c (PhMe)
85
87
2d (PhOMe)
Electron-deficient iodonium salts were, on the other hand, best
made from the corresponding electron-deficient aryl iodide with
benzene as the arene. This is exemplified by the reaction of iodo-4-
nitrobenzene (1d) with benzene, which delivered salt 3i in 85% yield
(entry 10). The reverse reaction with iodobenzene and nitroben-
zene was sluggish and gave salt 3b as a byproduct, the result of
competing reaction pathways of 1a between oxidation and reaction
with the formed iodine(III) intermediate.
5
1a (PhI)
2e (thiophene)
82
6d
7
1b (4-MePhI) 2a (PhH)
1b (4-MePhI) 2c (PhMe)
3c
71
52
The generality of the developed protocol is especially evident
from the successful reaction of 2-chloro-5-iodopyridine (1e) with
benzene or anisole to give salts 3j and 3k, respectively (entries 11,
12). Iodonium salts containing this aryl moiety have recently been
used in an efficient total synthesis of (2)-epibatidine.4 Pyridyl
iodonium salts have previously been inaccessible by acidic routes,
and salt 3j was formerly obtained by a basic, atom-inefficient two-
step procedure19 in moderate yield, which was still inadequate for
the preparation of salt 3k.20 The formation of iodonium salts 3
from substituted arenes 2 was in all cases highly regioselective,
yielding salts 3b–d,f,h,k with complete para-selectivity. Likewise,
the reaction of 1a with thiophene (2e) afforded only 2-substituted
3e.
8
1c (2-MePhI)
1c (2-MePhI)
2a (PhH)
85
9
2c (PhMe)
87
85
10
1d (4-NO2PhI) 2a (PhH)
11d
12d
a
1e (2-chloro-5- 2a (PhH)
iodopyridine)
60
53
Having succeeded in the direct synthesis of diaryliodonium salts
from aryl iodides, we looked into possible extensions of this
reaction. As aryl iodides are readily available but often expensive,
we argued that it might be possible to form the aryl iodide in situ.21
Hence, the reaction of benzene (2a) and iodine with mCPBA and
TfOH was studied, and indeed delivered iodonium salt 3a in high
yield in only 10 min at 80 uC or 22 hours at room temperature
(Table 3, entries 1, 2).
1e (2-chloro-5- 2d (PhOMe)
iodopyridine)
Reaction conditions:
1
(1.0 equiv.),
2
(1.1 equiv.), mCPBA
(1.1 equiv.) and TfOH (2.0 equiv.) in CH2Cl2, see Table 1 and ESI
for details. Formed with complete regioselectivity. Isolated yield.
3.0 equiv. of TfOH were used.
b
c
d
This efficient synthesis of diaryliodonium salts was subsequently
applied to other arenes. Toluene (2c) yielded a mixture of salts 3h
and 3f with 3 : 1 regioselectivity favouring ortho-iodination
(entry 3). The regioselectivity was higher at lower conversions, and
pure 3h was obtained after one hour at 0 uC (entry 4).
Chlorobenzene (2f) gave symmetric salt 3l with complete para-
selectivity (entry 5). Even highly functionalized, deactivated arene
2g participated in the reaction to give salt 3m (entry 6). As this one-
pot reaction involves several consecutive steps and many possible
sources of byproducts, it is surprising that salts 3 are easily isolated
in moderate to good yields.
electron-deficient iodonium salts, as the reactivity of the arenes
varies dramatically with the electronic properties.8 Aryl iodides 1
and arenes 2 were thus selected to investigate the formation of
both electron-rich and electron-deficient salts, including heteroaryl
salts.
The use of iodobenzene both as aryl iodide (1a) and arene (2b)
yielded 4-iodophenyl(phenyl)iodonium triflate (3b) as a single
regioisomer (entry 2). Likewise, the reaction of 1a with toluene (2c)
was smooth, and unsymmetrical salt 3c could be isolated in good
yield (entry 3). The electron-rich arenes anisole (2d) and thiophene
(2e) were, as expected, very reactive under the standard conditions.
By decreasing the temperature to 278 uC, salts 3d and 3e could be
obtained in excellent yields (entries 4, 5). Heteroaryl salt 3e has
previously been synthesized in several steps via the corresponding
In conclusion, a facile, direct synthesis of diaryliodonium
triflates from the corresponding aryl iodide and arene has been
realized. The method is fast, high yielding, operationally simple
and has a large substrate scope. Electron-rich salts are conveniently
2522 | Chem. Commun., 2007, 2521–2523
This journal is ß The Royal Society of Chemistry 2007

View Online
F. M. Beringer, W. J. Daniel, S. A. Galton and G. Rubin, J. Org.
Chem., 1966, 31, 4315–4318.
Table 3 Direct synthesis of salts 3 from arenes and iodinea
6 D. Kalyani, N. R. Deprez, L. V. Desai and M. S. Sanford, J. Am.
Chem. Soc., 2005, 127, 7330–7331; N. R. Deprez, D. Kalyani, A. Krause
and M. S. Sanford, J. Am. Chem. Soc., 2006, 128, 4972–4973.
7 Y. Toba, J. Photopolym. Sci. Technol., 2003, 16, 115–118; A. Varvoglis,
The Organic Chemistry of Polycoordinated Iodine, Wiley–VCH Verlag,
Weinheim, 1992.
T
Yield
(%)c
Entry 2 (ArH)
(uC) Time
Salt 3b
8 M. Ochiai, M. Toyonari, T. Nagaoka, D.-W. Chen and M. Kida,
Tetrahedron Lett., 1997, 38, 6709–6712; M. A. Carroll, V. W. Pike and
D. A. Widdowson, Tetrahedron Lett., 2000, 41, 5393–5396; A. Shah,
V. W. Pike and D. A. Widdowson, J. Chem. Soc., Perkin Trans. 1, 1997,
2463–2465; T. Kitamura, M. Kotani and Y. Fujiwara, Tetrahedron
Lett., 1996, 37, 3721–3722; T. Kitamura, J. Matsuyuki and
H. Taniguchi, Synthesis, 1994, 147–148; V. V. Zhdankin,
M. C. Scheuller and P. J. Stang, Tetrahedron Lett., 1993, 34,
6853–6856; G. F. Koser, R. H. Wettach and C. S. Smith, J. Org.
Chem., 1980, 45, 1543–1544.
9 N. S. Zefirov, T. M. Kasumov, A. S. Koz’min, V. D. Sorokin, P. J. Stang
and V. V. Zhdankin, Synthesis, 1993, 1209–1210; P. J. Stang,
V. V. Zhdankin and R. Tykwinski, Tetrahedron Lett., 1992, 33,
1419–1422; P. J. Stang, V. V. Zhdankin, R. Tykwinski and N. S. Zefirov,
Tetrahedron Lett., 1991, 32, 7497–7498.
1
2
3
4
5
2a (PhH)
2a (PhH)
2c (PhMe)
2c (PhMe)
2f (PhCl)
80
rt
rt
0
10 min 3a
78
81
52
31
57
22 h
2 h
1 h
21 h
3a
3h : 3f ratio 3 : 1
3h
rt
6
2g (4-nitro- rt
m-xylene)
19 h
24
10 T. Iwama, V. B. Birman, S. A. Kozmin and V. H. Rawal, Org. Lett.,
1999, 1, 673–676.
a
Reaction conditions: I2 (1.0 equiv.),
(4 equiv.) and TfOH (4 equiv.) in CH2Cl2, see ESI for details.
Formed with complete regioselectivity apart from entry 3.
Isolated yield.
2 (4–10 equiv.), mCPBA
11 M. D. Hossain and T. Kitamura, Tetrahedron, 2006, 62, 6955–6960;
M. D. Hossain and T. Kitamura, J. Org. Chem., 2006, 71, 9903–9905.
12 A. Kryska and L. Skulski, Molecules, 2001, 6, 875–880.
13 P. Kazmierczak and L. Skulski, Synthesis, 1995, 1027–1032.
14 P. Kazmierczak and L. Skulski, Bull. Chem. Soc. Jpn., 1997, 70,
219–224.
15 E.g. Sanford and coworkers needed four different methods to produce
the iodonium salts used in their novel arylation protocol, see ref. 6.
16 T. Dohi, A. Maruyama, M. Yoshimura, K. Morimoto, H. Tohma and
Y. Kita, Angew. Chem., Int. Ed., 2005, 44, 6193–6196; M. Ochiai,
Y. Takeuchi, T. Katayama, T. Sueda and K. Miyamoto, J. Am. Chem.
Soc., 2005, 127, 12244–12245; Y. Yamamoto and H. Togo, Synlett,
2006, 798–800.
b
c
synthesized from iodobenzene and the corresponding arene, and
electron-deficient salts are formed by the reaction of a substituted
aryl iodide with benzene. The protocol can be extended to the
synthesis of iodonium salts directly from iodine and arenes,
conveniently circumventing the need for aryl iodides. A thorough
investigation of the scope and limitations of these reactions is
underway, and will be reported separately.
17 Commercial mCPBA was used without drying. The exact amount of
oxidant was determined by titration, see ESI.
18 D. Bykowski, R. McDonald, R. J. Hinkle and R. R. Tykwinski, J. Org.
Chem., 2002, 67, 2798–2804.
This work was financially supported by the Department of
Organic Chemistry at Stockholm University.
19 N. S. Pirguliyev, V. K. Brel, N. G. Akhmedov and N. S. Zefirov,
Synthesis, 2000, 81–83.
20 For the synthesis and use of 3j, see B. Olofsson and V. K. Aggarwal,
Proc. 2nd Int. Conf. on Hypervalent Iodine, 2006, 47–50. The attempts to
synthesize salt 3k are unpublished.
Notes and references
1 T. Wirth, Angew. Chem., Int. Ed., 2005, 44, 3656–3665.
2 P. J. Stang, J. Org. Chem., 2003, 68, 2997–3008.
3 A. Varvoglis, Tetrahedron, 1997, 53, 1179–1255; V. V. Zhdankin and
P. J. Stang, Chem. Rev., 2002, 102, 2523–2584.
4 V. K. Aggarwal and B. Olofsson, Angew. Chem., Int. Ed., 2005, 44,
5516–5519.
5 P. Gao and P. S. Portoghese, J. Org. Chem., 1995, 60, 2276–2278;
J. H. Ryan and P. J. Stang, Tetrahedron Lett., 1997, 38, 5061–5064;
21 The oxidation of iodine and arenes to aryl iodides or (diacetoxyiodo)-
benzene is known; see M. D. Hossain and T. Kitamura, Tetrahedron
Lett., 2006, 47, 7889–7891 and references therein. After the completion
of this work Kitamura reported a procedure for the direct synthesis of
diaryliodonium salts from iodine, requiring heating at 40 uC for 72 h
and a sequential anion exchange step (12 h), see ref. 11.
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 2521–2523 | 2523