One-pot synthesis of diaryliodonium salts from arenes and aryl iodides with Oxone-sulfuric acid

Article abstract of DOI:10.3762/bjoc.14.70

A facile synthesis of diaryliodonium salts utilizing Oxone as versatile and cheap oxidant has been developed. This method shows wide applicability and can be used for the preparation of iodonium salts containing electron-donating or electron-withdrawing groups in good yields. In addition, this procedure can be applied to the preparation of symmetric iodonium salts directly from arenes via a one-pot iodination-oxidation sequence.

Full text of DOI:10.3762/bjoc.14.70

One-pot synthesis of diaryliodonium salts from arenes and
aryl iodides with Oxone–sulfuric acid
Natalia Soldatova1, Pavel Postnikov1, Olga Kukurina1, Viktor V. Zhdankin1,2,
Akira Yoshimura1, Thomas Wirth*3 and Mekhman S. Yusubov*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 849–855.
1The Tomsk Polytechnic University, 634050 Tomsk, Russia,
2Department of Chemistry and Biochemistry, University of Minnesota,
Duluth MN 55812, USA and 3School of Chemistry, Cardiff University,
Park Place, Main Building, Cardiff CF10 3AT, UK
doi:10.3762/bjoc.14.70
Received: 18 February 2018
Accepted: 27 March 2018
Published: 12 April 2018
Email:
Thomas Wirth* - wirth@cf.ac.uk; Mekhman S. Yusubov* -
yusubov@tpu.ru
This article is part of the Thematic Series "Hypervalent iodine chemistry in
organic synthesis".
* Corresponding author
Associate Editor: D. Y.-K. Chen
Keywords:
© 2018 Soldatova et al.; licensee Beilstein-Institut.
License and terms: see end of document.
diaryliodonium salts; iodine; iodonium; oxidation; Oxone
Abstract
A facile synthesis of diaryliodonium salts utilizing Oxone as versatile and cheap oxidant has been developed. This method shows
wide applicability and can be used for the preparation of iodonium salts containing electron-donating or electron-withdrawing
groups in good yields. In addition, this procedure can be applied to the preparation of symmetric iodonium salts directly from
arenes via a one-pot iodination–oxidation sequence.
Introduction
Diaryliodonium salts, which are also known as diaryl-λ3- The development of novel synthetic approaches to diaryliodo-
iodanes, are widely considered to be an important and practi- nium salts based on the use of inexpensive, commercially avail-
cally useful class of hypervalent iodine compounds [1-4]. able oxidants is an important and challenging goal. A vast
Diaryliodonium salts have found broad synthetic application as majority of existing procedures involve the interaction of elec-
electrophilic arylating reagents in reactions with various nucleo- trophilic hypervalent iodine(III) species with suitable arenes
philes including electron-rich carbon-centered species [5-7]. through ligand exchange processes [16-20]. The reactive hyper-
The unique arylating reactivity of diaryliodonium salts has been valent iodine(III) species can be used as stable reagents or can
demonstrated in many metal-catalyzed and also metal-free be generated in situ [21-25]. In particular, Olofsson and
transformations [8-15].
co-workers reported procedures based on the in situ generation
849

Beilstein J. Org. Chem. 2018, 14, 849–855.
of reactive λ3-iodane species directly from arenes, which was a could not be achieved even after 24 h stirring. The addition of
significant achievement in this field [26-29]. However, these aqueous KBr to the reaction mixture resulted in the formation of
now well-established processes involve oxidations using the desired bromide salt 3a in 30% isolated yield. The addition
mCPBA in the presence of strong organic acids [30-35]. There- of KBr is necessary as the high solubility of the diaryliodonium
fore, the development of new, convenient and inexpensive sulfonates does not allow their isolation from the reaction mix-
methods utilizing readily available and easy-to-handle oxidants ture. Dilution of the reaction mixture with dichloromethane did
still remains a highly desirable goal.
not increase the yield of the target product significantly
(Table 1, entry 2). Moreover, we observed the formation of
Previously, we have published the utilization of Oxone® 4-iodobenzenesulfonic acid in both cases, probably due to the
(2KHSO5·KHSO4·K2SO4) as a readily available and effective high concentration of sulfuric acid in the reaction mixture.
oxidant for the preparation of various hypervalent iodine com- Mixing dichloromethane with acetonitrile resulted in an in-
pounds [36-42]. Oxone is used as an efficient oxidant for the creased yield of 3a and a decreased amount of 4-iodobenzene-
direct conversion of substituted 2-iodobenzoic acids to aryl- sulfonic acid (Table 1, entry 3). When the reaction was carried
benziodoxoles [37,38], 2-iodobiphenyl to dibenziodolium com- out in pure acetonitrile, the iodonium salt 3a was formed in
pounds [39], iodoarenes to iodylbenzenes and [bis(trifluoroace- 75% yield (Table 1, entry 4). The addition of 2 equivalents of
toxy)iodo]arenes [40,41], and for the preparation of diaryliodo- Oxone increased the yield to 92% (Table 1, entry 5). Surprising-
nium trifluoroacetates and triflates [42]. Yakura also used ly, a smaller amount of toluene did not affect the yield (Table 1,
Oxone® as an oxidant for the generation of iodine(III) species entry 6). In order to avoid the formation of undesired 4-iodo-
in the oxidation of phenols [43]. In the present work, we report benzenesulfonic acid, the reaction was carried out using smaller
the development of a reliable and convenient procedure for the amounts of acid (Table 1, entries 7 and 8). That reaction
preparation of diaryliodonium bromides using Oxone in the proceeds smoothly with only 7.5 equivalents of sulfuric acid
presence of sulfuric acid.
producing the target compound 3a high yields. However, the
use of 3.75 equivalents of sulfuric acid resulted in a significant-
ly lower yield.
Results and Discussion
After having investigated previously described reaction condi-
tions [37,38], initial optimization studies were performed using With the optimized procedure, the synthetic utility of this
iodobenzene and toluene as reactants for the synthesis of method using various aryliodides and arenes was investigated
diaryliodonium salt 3a (Table 1). A simple mixing of the (Table 2). Iodobenzene (1a) smoothly reacts with arenes con-
starting materials with finely ground Oxone and sulfuric acid taining electron-donating substituents to form the correspond-
leads to the formation of a very viscous and dark reaction mix- ing iodonium salts in high yields. 3-Trifluoromethyliodoben-
ture (Table 1, entry 1). Full conversion of the starting materials zene (1b) exhibited higher reactivity, and iodonium salts have
Table 1: Optimization studies.a
entry
solvent
toluene (equiv)
Oxone (equiv)
H2SO4 (equiv)
yieldb (%)
1
2
3
4
5
6
7
8
–
2.8
2.8
2.8
2.8
2.8
1.2
1.2
1.2
1.3
1.3
1.3
1.3
2
15
30c
40c
60c
75c
92c
88c
86
CH2Cl2
CH2Cl2/MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
15
15
15
15
2
15
2
7.5
3.75
2
53
aReaction conditions: PhI (1 mmol), overnight, rt; bisolated yield; caccording to NMR data product contains up to 10% of (4-tolyl)phenyliodonium
4-iodobenzenesulfonate as an impurity.
850

Beilstein J. Org. Chem. 2018, 14, 849–855.
Table 2: Synthesis of diaryliodonium bromides.a
R1 (1)
R2 (2)
product 3
yieldb (%)
86c
R1 = H (1a)
R2 = Me (2a)
3a
3b
R1 = H (1a)
R1 = H (1a)
R2 = H (2b)
74d,e,f
R2 = 1,4-Me2 (2c)
75
3c
3d
3e
3f
R1 = H (1a)
R2 = 1,3,5-Me3 (2d)
75
R1 = 3-CF3 (1b)
R2 = H (2b)
85e,f
R1 = 3-CF3 (1b)
R2 = Me (2a)
76c
R1 = 3-CF3 (1b)
R2 = 1,4-Me2 (2c)
95
92
3g
3h
R1 = 3-CF3 (1b)
R2 = 1,3,5-Me3 (2d)
851

Beilstein J. Org. Chem. 2018, 14, 849–855.
Table 2: Synthesis of diaryliodonium bromides.a (continued)
R1 = 3-CF3 (1b)
R1 = 4-Br (1c)
R1 = 4-Br (1c)
R2 = Cl (2e)
51g,h
70c
32
3i
3j
R2 = Me (2a)
R2 = 1,4-Me2 (2c)
3k
R1 = 4-Br (1c)
R1 = 4-Br (1c)
R2 = 1,3,5-Me3 (2d)
71
3l
R2 = Cl (2e)
34g,h
3m
R1 = 3,5-(CF3)2 (1d)
R2 = H (2b)
35e,f
3n
R1 = 3,5-(CF3)2 (1d)
R2 = 1,3,5-Me3 (2d)
62
3o
aReaction conditions: 1 (1 mmol), 2 (1.1 mmol), H2SO4 (7.5 mmol), MeCN (2 mL) overnight, rt; bisolated yield; c1.2 mmol of 2a was used; daccording
to NMR data product contains an up to 1.5% of diphenyliodonium 4-iodobenzenesulfonate as impurity; e11.3 mmol of H2SO4 was used; f1.3 mmol of
2b was used; g15 mmol of H2SO4 was used; h1.5 mmol of 2e was used.
been isolated in higher yields. Moreover, iodoarene 1b reacted improve the yields. Subsequently it was shown that the addi-
with the moderately electron-poor chlorobenzene (2e) forming tion of aqueous potassium bromide can be modified and other
iodonium salt 3i in 51% yield. In contrast, 4-bromoiodoben- counter anions can be introduced to prepare different
zene (1c) was less reactive and afforded iodonium salts 3j–m in diaryliodonium salts. This has been demonstrated in the prepa-
lower yields. Similar reactions of 3,5-bis(trifluoromethyl)iodo- ration of diaryliodonium salts using 1-iodo-3-trifluoromethyl-
benzene (1d) with benzene and mesitylene formed the corre- benzene (1b) and mesitylene (2d) as model substrates (Table 3).
sponding iodonium salts 3n and 3o in moderate yields.
The yield of the salts 3h and 3p–s do not depend on
With electron-deficient arenes 2 such as chlorobenzene (2e) and the nature of the anion and its source. Small differences in
benzene, an excess of sulfuric acid and arene was used to yield can be explained by different solubility of salts in aceto-
852

Beilstein J. Org. Chem. 2018, 14, 849–855.
Table 3: Preparation of diaryliodonium salts with different anions.a
NaX / HX
product
yieldb (%)
NaBr
3h
3p
3q
3r
92
82
89
81
80
TsOH
TfOH
NaBF4
NaPF6
3s
aReaction conditions: 1b (1 mmol), 2d (1.1 mmol), Oxone (1 mmol), H2SO4 (7.5 mmol), MeCN (2 mL), NaX or HX (2 mmol) overnight, rt; bisolated
yield.
nitrile/water. Diaryliodonium bromides were isolated in Finally, a one-step procedure for the preparation of symmetric
higher yields because of the low solubility of these products iodonium salts directly from arenes via an in situ iodination was
(Table 3).
developed (Table 4). Arenes 2b–e can be transformed to the
Table 4: Preparation of symmetric iodonium salts via a one-step iodination–oxidation procedure.a
R2 (2)
product 3
yieldb (%)
84c,d
R2 = H (2b)
3b
R2 = 1,4-Me2 (2c)
80
3t
R2 = 1,3,5-Me3 (2d)
77
3u
R2 = Cl (2e)
40e
3v
aReaction conditions: ArH (2.2 mmol), Oxone (2 mmol), H2SO4 (7.5 mmol), MeCN (2 mL) overnight, rt; bisolated yield; caccording to NMR data the
product contains up to 1.5% of diphenyliodonium 4-iodobenzenesulfonate as impurity; d11.3 mmol of H2SO4 and 2.6 mmol of 2b were used;
e15 mmol of H2SO4 and 3.0 mmol of 2e were used.
853

Beilstein J. Org. Chem. 2018, 14, 849–855.
References
symmetric iodonium salts 3b and 3t–v by the reaction with
iodine, Oxone, and sulfuric acid. The attempted synthesis of the
symmetric iodonium salt using toluene as substrate led to a
regioisomeric mixture of products due to the low regioselectivi-
ty of iodination.
1. Yusubov, M. S.; Maskaev, A. V.; Zhdankin, V. V. ARKIVOC 2011, i,
370–409. doi:10.3998/ark.5550190.0012.107
2. Zhdankin, V. V. Hypervalent Iodine Chemistry; Wiley: Chichester,
2014.
3. Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328–3435.
doi:10.1021/acs.chemrev.5b00547
This procedure allowed the synthesis of iodonium salts with
arenes containing electron-donating groups. Unfortunately,
electron-poor arenes exhibited a lower reactivity and bis-(4-
chlorophenyl)iodonium bromide have been isolated in only
40% yield. Nevertheless, the developed procedure is character-
ized by important advantages, such as simplicity, the use of
inexpensive and available reagents, and typically good
yields of iodonium salts. It is a versatile addition to the
methodology toolbox for the preparation of diaryliodonium
salts.
4. Wirth, T., Ed. Hypervalent Iodine Chemistry in Topics in Current
Chemistry; Springer: Berlin, 2016; Vol. 373.
5. Merritt, E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009, 48,
9052–9070. doi:10.1002/anie.200904689
6. Aradi, K.; Tóth, B. L.; Tolnai, G. L.; Novák, Z. Synlett 2016, 27,
1456–1485. doi:10.1055/s-0035-1561369
7. Fañanás-Mastral, M. Synthesis 2017, 49, 1905–1930.
doi:10.1055/s-0036-1589483
8. Gonda, Z.; Novák, Z. Chem. – Eur. J. 2015, 21, 16801–16806.
doi:10.1002/chem.201502995
9. Dey, C.; Lindstedt, E.; Olofsson, B. Org. Lett. 2015, 17, 4554–4557.
doi:10.1021/acs.orglett.5b02270
10.Tinnis, F.; Stridfeldt, E.; Lundberg, H.; Adolfsson, H.; Olofsson, B.
Org. Lett. 2015, 17, 2688–2691. doi:10.1021/acs.orglett.5b01079
11.Cahard, E.; Male, H. P. J.; Tissot, M.; Gaunt, M. J. J. Am. Chem. Soc.
2015, 137, 7986–7989. doi:10.1021/jacs.5b03937
12.Modha, S. G.; Greaney, M. F. J. Am. Chem. Soc. 2015, 137,
1416–1419. doi:10.1021/ja5124754
Conclusion
In conclusion, a new facile protocol for the preparation of
diaryliodonium salts using cheap and readily available Oxone as
an oxidant in the presence of sulfuric acid has been developed.
The procedure allows the synthesis of a wide range of iodo-
nium salts containing electron-donating and electron-
withdrawing substituents. Particularly attractive is the
possibility of the one-pot synthesis of symmetric bis-aryliodo-
nium salts directly from arenes via an iodination–oxidation se-
quence.
13.Beaud, R.; Phipps, R. J.; Gaunt, M. J. J. Am. Chem. Soc. 2016, 138,
13183–13186. doi:10.1021/jacs.6b09334
14.Yin, K.; Zhang, R. Org. Lett. 2017, 19, 1530–1533.
doi:10.1021/acs.orglett.7b00310
15.Seidl, T. L.; Stuart, D. R. J. Org. Chem. 2017, 82, 11765–11771.
doi:10.1021/acs.joc.7b01599
16.Margida, A. J.; Koser, G. F. J. Org. Chem. 1984, 49, 3643–3646.
doi:10.1021/jo00193a039
17.Kitamura, T.; Matsuyuki, J.-i.; Nagata, K.; Furuki, R.; Taniguchi, H.
Synthesis 1992, 945–946. doi:10.1055/s-1992-26272
18.Kitamura, T.; Matsuyuki, J.-i.; Taniguchi, H. Synthesis 1994, 147–148.
doi:10.1055/s-1994-25423
Supporting Information
Supporting Information File 1
Experimental details and NMR spectra.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-70-S1.pdf]
19.Pike, V. W.; Butt, F.; Shah, A.; Widdowson, D. A.
J. Chem. Soc., Perkin Trans. 1 1999, 245–248. doi:10.1039/a809349k
20.Carroll, M. A.; Pike, V. W.; Widdowson, D. A. Tetrahedron Lett. 2000,
41, 5393–5396. doi:10.1016/S0040-4039(00)00861-3
21.Kaźmierczak, P.; Skulski, L. Synthesis 1995, 1027–1032.
doi:10.1055/s-1995-4045
Acknowledgements
22.Kryska, A.; Skulski, L. Molecules 2001, 6, 875–880.
doi:10.3390/61100875
This work was supported by the Russian Foundation for Basic
Research (RFBR-mol_nr 17-33-50111), the Tomsk Polytechnic
University Competitiveness Enhancement Program and the
Royal Society (IE160304). We thank the EPSRC National
Mass Spectrometry Facility, Swansea, for mass spectrometric
data.
23.Hossain, M. D.; Kitamura, T. Tetrahedron 2006, 62, 6955–6960.
doi:10.1016/j.tet.2006.04.073
24.Hossain, M. D.; Ikegami, Y.; Kitamura, T. J. Org. Chem. 2006, 71,
9903–9905. doi:10.1021/jo061889q
25.Dohi, T.; Yamaoka, N.; Itani, I.; Kita, Y. Aust. J. Chem. 2011, 64,
529–535. doi:10.1071/CH11057
26.Bielawski, M.; Zhu, M.; Olofsson, B. Adv. Synth. Catal. 2007, 349,
2610–2618. doi:10.1002/adsc.200700373
ORCID® iDs
Pavel Postnikov - http://orcid.org/0000-0001-9713-1290
Olga Kukurina - http://orcid.org/0000-0001-6017-5628
Viktor V. Zhdankin - http://orcid.org/0000-0002-0315-8861
Akira Yoshimura - http://orcid.org/0000-0002-2577-397X
Thomas Wirth - http://orcid.org/0000-0002-8990-0667
Mekhman S. Yusubov - http://orcid.org/0000-0001-9233-1824
27.Bielawski, M.; Olofsson, B. Chem. Commun. 2007, 2521–2523.
doi:10.1039/b701864a
28.Bielawski, M.; Aili, D.; Olofsson, B. J. Org. Chem. 2008, 73,
4602–4607. doi:10.1021/jo8004974
29.Zhu, M.; Jalalian, N.; Olofsson, B. Synlett 2008, 592–596.
doi:10.1055/s-2008-1032050
854

Beilstein J. Org. Chem. 2018, 14, 849–855.
30.Jalalian, N.; Olofsson, B. Tetrahedron 2010, 66, 5793–5800.
doi:10.1016/j.tet.2010.05.004
31.Seidl, T. L.; Sundalam, S. K.; McCullough, B.; Stuart, D. R.
J. Org. Chem. 2016, 81, 1998–2009. doi:10.1021/acs.joc.5b02833
32.Lindstedt, E.; Reitti, M.; Olofsson, B. J. Org. Chem. 2017, 82,
11909–11914. doi:10.1021/acs.joc.7b01652
33.Carreras, V.; Sandtorv, A. H.; Stuart, D. R. J. Org. Chem. 2017, 82,
1279–1284. doi:10.1021/acs.joc.6b02811
34.Gemoets, H. P. L.; Laudadio, G.; Verstraete, K.; Hessel, V.; Noël, T.
Angew. Chem., Int. Ed. 2017, 56, 7161–7165.
doi:10.1002/anie.201703369
35.Laudadio, G.; Gemoets, H. P. L.; Hessel, V.; Noël, T. J. Org. Chem.
2017, 82, 11735–11741. doi:10.1021/acs.joc.7b01346
36.Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64,
4537–4538. doi:10.1021/jo9824596
37.Yusubov, M. S.; Yusubova, R. Y.; Nemykin, V. N.; Zhdankin, V. V.
J. Org. Chem. 2013, 78, 3767–3773. doi:10.1021/jo400212u
38.Yusubov, M. S.; Soldatova, N. S.; Postnikov, P. S.; Valiev, R. R.;
Svitich, D. Y.; Yusubova, R. Y.; Yoshimura, A.; Wirth, T.;
Zhdankin, V. V. Eur. J. Org. Chem. 2018, 640–647.
doi:10.1002/ejoc.201701595
39.Postnikov, P. S.; Guselnikova, O. A.; Yusubov, M. S.; Yoshimura, A.;
Nemykin, V. N.; Zhdankin, V. V. J. Org. Chem. 2015, 80, 5783–5788.
doi:10.1021/acs.joc.5b00741
40.Zagulyaeva, A. A.; Yusubov, M. S.; Zhdankin, V. V. J. Org. Chem.
2010, 75, 2119–2122. doi:10.1021/jo902733f
41.Soldatova, N.; Postnikov, P.; Troyan, A. A.; Yoshimura, A.;
Yusubov, M. S.; Zhdankin, V. V. Tetrahedron Lett. 2016, 57,
4254–4256. doi:10.1016/j.tetlet.2016.08.038
42.Soldatova, N. S.; Postnikov, P. S.; Kukurina, O. S.; Zhdankin, V. V.;
Yoshimura, A.; Wirth, T.; Yusubov, M. S. ChemistryOpen 2017, 6,
18–20. doi:10.1002/open.201600129
43.Yakura, T.; Omoto, M.; Yamauchi, Y.; Tian, Y.; Ozono, A. Tetrahedron
2010, 66, 5833–5840. doi:10.1016/j.tet.2010.04.124
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(https://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.14.70
855