One-pot synthesis of diaryliodonium salts using toluenesulfonic acid: A fast entry to electron-rich diaryliodonium tosylates and triflates

Article abstract of DOI:10.1055/s-2008-1032050

A direct synthesis of symmetric and unsymmetric electron-rich diaryliodonium salts is described. The use of MCPBA and toluenesulfonic acid delivers diaryliodonium tosylates in high yields. An in situ anion exchange has also been developed, giving access to the corresponding triflate salts. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032050

592
LETTER
One-Pot Synthesis of Diaryliodonium Salts Using Toluenesulfonic Acid: A Fast
Entry to Electron-Rich Diaryliodonium Tosylates and Triflates
Synthesis of
E
lectron-R
i
ich
D
n
iaryliodonium
g
T
osylates
a
z
nd
T
riflate
h
s
ao Zhu, Nazli Jalalian, Berit Olofsson*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden
Fax +46(8)154908; E-mail: berit@organ.su.se
Received 3 December 2007
screening with molecular iodine, anisole, MCPBA,10 and
Abstract: A direct synthesis of symmetric and unsymmetric elec-
tron-rich diaryliodonium salts is described. The use of MCPBA and
toluenesulfonic acid delivers diaryliodonium tosylates in high
yields. An in situ anion exchange has also been developed, giving
access to the corresponding triflate salts.
various acids revealed that this indeed was the case
(Table 1, entries 1–5). Although perchloric acid had
shown promising results with other substrates,11 it was too
reactive to allow formation of the di(4-methoxyphenyl)io-
donium salt. Useful yields were obtained with p-toluene-
sulfonic acid (TsOH) and trifluoroacetic acid (TFA), and
the reaction was subsequently optimized with TsOH (en-
tries 6–9).12 The use of elevated temperature delivered
di(4-methoxyphenyl)iodonium tosylate (2a) in 73% yield
within 10 minutes (entry 3). Although the reaction was
considerably slower at room temperature, the yield was
improved to 89% yield (entry 6). The amount of TsOH
was subsequently investigated, and three equivalents were
found sufficient to obtain 2a in high yield (entries 7–9).
Interestingly, the product seems to decompose slowly
upon prolonged heating (cf. entries 7 and 8).
Key words: hypervalent iodine, diaryliodonium salts, oxidations,
arenes, electrophilic aromatic substitution
Hypervalent iodine compounds have recently received
considerable attention as mild, nontoxic and selective re-
agents.1,2 Iodine(III) reagents with two carbon ligands
have similar properties to certain transition-metal com-
plexes, and can be used in C–C bond-forming reactions.2
Diaryl-l3-iodanes, also called diaryliodonium salts, are
the most well-known compounds in this class. Due to their
highly electron-deficient nature and hyperleaving-group
ability, they are versatile arylating agents with a variety of
nucleophiles, e.g. in a-arylation of carbonyl compounds.3
They can be employed in copper- and palladium-cata-
lyzed cross-coupling reactions, allowing milder reaction
conditions than in couplings with aryl halides.4 Further-
more, diaryliodonium salts are used to generate benzynes5
and serve as photo initiators in polymerizations.6
Table 1 Screening of Acids and Optimizationa
I +
X
MCPBA, HX,
CH2Cl2
+
4
2
I2
OMe
MeO
OMe
Entry Acid (equiv) Temp
Time
Anion X Yield (%)b
1
2
3
4
5
6
7
8
9
TfOH (4)
HClO4 (4)
TsOH (4)
TFA (6)
0 °C
r.t.
10 min
30 min
10 min
30 min
1 h
OTf
0c
0c
Synthetic routes to diaryliodonium salts generally require
several reaction steps that often are time-consuming and
moderate-yielding.7,8 In order to make these efficient ary-
lating agents more easily available, we have recently de-
ClO4
OTs
80 °C
60 °C
60 °C
r.t.
73
veloped
a
high-yielding, one-pot synthesis of
O2CCF3
OAc
OTs
64
0
diaryliodonium triflates from arenes and aryl iodides or
molecular iodine (Scheme 1).9 This procedure is quite
general, but fails in the synthesis of symmetric, electron-
rich salts. We thus set out to find suitable conditions for a
one-pot synthesis of electron-rich salts, and herein we
present our preliminary results.
AcOH (6)
TsOH (4)
TsOH (2)
TsOH (2)
TsOH (3)
14 h
89
75
61
87
r.t.
14 h
OTs
80 °C
r.t.
14 h
OTs
MCPBA,
TfOH, CH2Cl2
Ar1I + Ar2H
14 h
OTs
OTf
Ar2
I
or
Ar1
a I2 (1 equiv), anisole (4 equiv) and MCPBA (3 equiv) in CH2Cl2 were
used in all reactions.
I2 + ArH
b Isolated yield.
Scheme 1 Synthesis of diaryliodonium triflates
c Black tar was formed, no product could be isolated.
Acids with higher pKa than TfOH were expected to pro-
mote the reaction with less byproduct formation. A
The optimized conditions were subsequently applied to
various arenes, as depicted in Table 2. Thiophene gave
salt 2b in good yield both at room temperature and at 40 °C
(entries 2 and 3). As expected, the reactivity of alkyl-sub-
stituted arenes was lower, and elevated temperature was
SYNLETT 2008, No. 4, pp 0592–0596
x
x.
x
x.
2
0
0
8
Advanced online publication: 16.01.2008
DOI: 10.1055/s-2008-1032050; Art ID: G40207ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Electron-Rich Diaryliodonium Tosylates and Triflates
593
needed to obtain salts 2d–f (entries 5–8). Toluene gave a cation of diaryliodonium triflates9 could not be employed
regioisomeric mixture of symmetric salt 2f and (2-meth- on salts 2, since the excess TsOH precipitated with the io-
ylphenyl)(4-methylphenyl)iodonium salt 2g in a 2:1 ratio, donium salt upon treatment with diethyl ether. The prod-
resulting from iodination para and ortho to the methyl ucts were thus purified by column chromatography
substituent, respectively (entry 8). All other products were instead.
obtained completely regioselectively.
Diaryliodonium triflates are more easily applicable than
The use of 2,2,2-trifluoroethanol (TFE) has recently been tosylate salts, due to the non-nucleophilic properties of the
reported to enhance the reaction rate of iodine(III) com- triflate anion.4 Thus, we subsequently investigated an in
pounds with arenes.13 Although pure TFE proved ineffi- situ anion exchange of salt 2a to the corresponding triflate
cient in our system, the use of a 1:1 mixture of TFE and salt 3a (Scheme 2). Fortunately, addition of 2.5 equiva-
CH2Cl2 resulted in higher yields than pure CH2Cl2 for lents trifluoromethanesulfonic acid to the reaction mix-
some salts (see entry 7 and Table 3). Our standard purifi- ture after complete conversion to the tosylate salt
Table 2 Application to Various Arenesa
MCPBA,
–OTs
TsOH, CH2Cl2
I
ArH
+
I2
Ar
Ar
1
2
Entry
1
Arene 1
Temp
r.t.
Time
14 h
Product 2
Yield (%)b
OTs
I
PhOMe (1a)
89
2a
MeO
OMe
OTs
I
S
S
2
3
thiophene (1b)
thiophene (1b)
r.t.
14 h
66
68
2b
40 °C
15 min
2b
OTs
I
4
5
mesitylene (1c)
p-xylene (1d)
r.t.
20 h
1 h
59
66
2c
OTs
I
80 °C
2d
OTs
I
6
Pht-Bu (1e)
Pht-Bu (1e)
r.t.
18 h
10
76
t-Bu
t-Bu
2e
7c
80 °C
30 min
2e
OTs
I
2f
8
9
PhMe (1f)
PhH (1g)
80 °C
10 min
49d
OTs
I
2g
OTs
I
80 °C
1 h
0e
2h
a Iodine (1 equiv), arene (4 equiv), MCPBA (3 equiv) and TsOH (3–4 equiv) were used in all reactions.
b Isolated yield of 2.
c TFE was used as co-solvent.
d Regioisomeric mixture (2:1), see text.
e No reaction took place.
Synlett 2008, No. 4, 592–596 © Thieme Stuttgart · New York

594
M. Zhu et al.
LETTER
followed by 1 hour stirring at room temperature resulted Finally, the synthesis of unsymmetrical diaryliodonium
in 3a in 71% yield. This in situ anion exchange should be salts was investigated with TsOH. As expected, the reac-
generally applicable to synthesis of electron-rich diaryl- tion of iodobenzene with electron-rich arenes delivered
iodonium triflates that are unobtainable by the direct tri- the corresponding diaryliodonium tosylates in good yields
fluoromethanesulfonic acid mediated reaction (Scheme 1). (Table 3). Biphenyl- and naphthyl salts cannot be synthe-
Table 3 Syntheses of Unsymmetrical Salts from Aryl Iodides
MCPBA,
TsOH
–OTf
Ar2
–OTs
Ar2
I+
I+
TfOH
Ar1I
+
Ar2H
Ar1
Ar1
r.t., 1 h
4
1
2
3
Entry
1b
ArI 4
ArH 1
Product 2 (3)
Yield (%)a
100 (100)c
OTs
I
PhI (4a)
PhOMe (1a)
2i
OMe
(3i)
OTs
I
S
2d
3d
PhI (4a)
PhI (4a)
thiophene (1b)
biphenyl (1h)
98
2j
OTs
Ph
I
50 (48)c
2k
(3k)
OTs
OTs
4b,d
PhI (4a)
mesitylene (1c)
97
I
2l
I
5b,d
PhI (4a)
PhI (4a)
p-xylene (1d)
Pht-Bu (1e)
79
72
2m
OTs
I
6
2n
t-Bu
OTs
I
7
8
PhI (4a)
PhI (4a)
PhMe (1f)
PhH (1g)
79e
85e
2o
2h
OTs
I
9d
1-iodonaphthalene (4b)
mesitylene (1c)
34
2p
a Isolated yield of 2.
b The arene was added after 1 h.
c Isolated yield of 3 after in situ anion exchange.
d TFE was used as co-solvent.
e NMR yield, 2 could not be separated from TsOH.
TfO–
TsO–
I+
2
I +
2
MCPBA,
TsOH
TfOH
+
I2
40 °C, 15 min
r.t., 1 h
MeO
MeO
MeO
1a
2a
3a 71%
Scheme 2 In situ anion exchange
Synlett 2008, No. 4, 592–596 © Thieme Stuttgart · New York

LETTER
Synthesis of Electron-Rich Diaryliodonium Tosylates and Triflates
595
sized in the TfOH-mediated reaction.9 Biphenyl was suc-
cessfully employed with TsOH to give salt 2k (entry 3).
High yields could be obtained also with less electron-rich
arenes (entries 4–8). Notably, diphenyliodonium tosylate
(2h) could be formed in this reaction, whereas the direct
reaction of iodine and benzene failed (cf. Table 2, entry 9
and Table 3, entry 8).
(d, J = 9.1 Hz, 4 H), 7.52 (d, J = 8.1 Hz, 2 H), 7.01 (d, J = 8.1 Hz, 2
H), 6.79 (d, J = 9.1 Hz, 4 H), 3.76 (s, 6 H), 2.29 (s, 3 H). 13C NMR
(100 MHz, CDCl3): d = 162.1, 142.9, 139.1, 136.8, 128.4, 126.0,
117.3, 140.4, 55.5, 21.2. IR (film): 2920.4, 2841.7, 1572.1, 1488.0,
1255.0, 118.5, 1012.0 cm–1. ESI-HRMS: m/z calcd for C14H14IO2
[M – TsO–]+: 341.0033; found: 341.0031.
Synthesis of (4-Methoxyphenyl)(phenyl)iodonium Tosylate (2i)
from Iodobenzene and Anisole
Electron-rich aryl iodides could also be used, as exempli-
fied by 1-iodo-naphthalene (4b). This aryl iodide deliv-
ered the unsymmetric, electron-rich salt 2p, albeit in
modest yield (entry 9). The reactions were initially run
stepwise, with formation of PhI(OH)OTs (Koser’s salt)14
before addition of the arene in order to avoid side reac-
tions between the oxidant and the arene. Surprisingly, the
true one-pot procedure proved as efficient, and in reac-
tions with 4b no product could be obtained in the stepwise
reaction. All products were obtained completely regiose-
lectively. One equivalent of TsOH was found sufficient to
mediate the reaction when TFE was used as co-solvent,
which simplified the purification substantially as precipi-
tation in diethyl ether could be employed.
MCPBA10 (81%, 53 mg, 0.25 mmol), iodobenzene (25 mL, 0.25
mmol), and anisole (35 mL, 0.25 mmol) were dissolved in CH2Cl2
(0.5 mL) and 2,2,2-trifluoroethanol (0.5 mL). Then, TsOH·H2O (47
mg, 0.25 mmol) was added to the solution and the mixture was
stirred at r.t. for 6 h and the solution was concentrated in vacuo.
Et2O (1 mL) was added and the mixture was stirred at r.t. for 10 min
to precipitate out an off-white solid. The precipitate was filtered off,
washed with Et2O, and dried under vacuum to give salt 2i (113 mg,
100%).
Analytical Data for Dithienyliodonium Tosylate (2b)
1
Mp 134 °C (dec.). H NMR (400 MHz, CDCl3): d = 7.76 (dd,
J = 3.8, 1.1 Hz, 2 H), 7.50 (dd, J = 5.4, 1.1 Hz, 2 H), 7.46 (d-like,
J = 8.0 Hz, 2 H), 7.06 (d-like, J = 8.0 Hz, 2 H), 6.95 (dd, J = 5.4, 3.8
Hz, 2 H), 2.32 (s, 3 H). 13C NMR (100 MHz, CDCl3): d = 141.10,
140.3, 139.6, 135.3, 129.1, 128.7, 126.0, 102.2, 21.3. IR (film):
2975.2, 1659.7, 1381.6, 1214.8, 1187.1, 1048.1 cm–1. ESI-HRMS:
m/z calcd for C8H6IS2 [M – TsO–]+: 292.8950; found: 292.8955.
The in situ anion exchange to the corresponding triflate
salts could be employed also on this reaction, as exempli-
fied by the synthesis of (4-methoxyphenyl)phenyliodoni-
um triflate (3i) and (biphenyl)phenyliodonium triflate
(3k). In both cases the anion exchange took place in near
quantitative yields (entries 1 and 3).
Synthesis of Di(4-methoxyphenyl)iodonium Triflate (3a) by in
Situ Anion Exchange
Iodine (26.1 mg, 0.103 mmol), anisole (45 mL, 0.412 mmol), and
MCPBA10 (81%, 66 mg, 0.309 mmol) were dissolved in 1 mL of
CH2Cl2. Then, TsOH·H2O (78 mg, 0.412 mmol) was added to the
mixture and the solution was stirred at 40 °C for 15 min. At 0 °C
TfOH (23 mL, 0.258 mmol) was added dropwise and the mixture
was stirred at r.t. for 1 h. After the solvents were evaporated in vac-
uo, the residue was submitted to flash chromatography (CH2Cl2–
Et2O = 2:1 → CH2Cl2–MeOH = 25:1) to give 3a as pale green crys-
tals (72 mg, 71%).
The limitations of this reaction are seen with electron-de-
ficient arenes, which give byproducts by incorporation of
the aryl moiety of TsOH rather than reaction with the add-
ed arene (Scheme 3).15
I+
OTs
I
MCPBA,
+
TsOH, 80 °C
F
Acknowledgment
only product
This work was financially supported by the Swedish Research
Council, Wenner-Gren Foundations, and the Trygger Foundation.
Scheme 3 Byproduct formation by reaction with TsOH
To summarize, the use of TsOH in combination with
MCPBA enabled the one-pot synthesis of previously un-
obtainable, electron-rich diaryliodonium salts. Also less
electron-rich salts can be synthesized in good yields. Fur-
thermore, the described in situ anion exchange gives ac-
cess also to the corresponding triflate salts, which are
more useful in certain applications.
References and Notes
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T.; Chen, D.-W.; Kida, M. Tetrahedron Lett. 1997, 38,
6709. (b) Pike, V. W.; Butt, F.; Shah, A.; Widdowson, D. A.
Representative Synthetic Procedures16
Synthesis of Di(4-methoxyphenyl)iodonium Tosylate (2a) from
Iodine and Anisole
Iodine (23.7 mg, 0.093 mmol), MCPBA10 (81%, 50 mg, 0.236
mmol), and anisole (35 mL, 0.325 mmol) were dissolved in CH2Cl2
(2 mL). Then, TsOH·H2O (60 mg, 0.316 mmol) was added to the so-
lution and the mixture was stirred at r.t. for 14 h. The solution was
concentrated in vacuo and the residue was submitted to flash chro-
matography (CH2Cl2–Et2O–MeOH = 100:50:2
→
CH2Cl2–
MeOH = 20:1) to give the desired salt as pale yellow crystals (72
mg, 89%); mp 138–139 °C. 1H NMR (400 MHz, CDCl3): d = 7.85
Synlett 2008, No. 4, 592–596 © Thieme Stuttgart · New York

596
M. Zhu et al.
LETTER
(12) For syntheses of diaryliodonium tosylates, see ref. 7b, 7f
J. Chem. Soc., Perkin Trans. 1 1999, 245. (c) Kitamura, T.;
Matsuyuki, J.; Taniguchi, H. Synthesis 1994, 147.
and: (a) Margida, A. J.; Koser, G. F. J. Org. Chem. 1984, 49,
3643. (b) Zhdankin, V. V.; Maydanovych, O.; Herschbach,
J.; Bruno, J.; Matveeva, E. D.; Zefirov, N. S. Tetrahedron
Lett. 2002, 43, 2359. (c) Carroll, M. A.; Pike, V. W.;
Widdowson, D. A. Tetrahedron Lett. 2000, 41, 5393.
(d) Martin-Santamaria, S.; Carroll, M. A.; Carroll, C. M.;
Carter, C. D.; Rzepa, H. S.; Widdowson, D. A.; Pike, V. W.
Chem. Commun. 2000, 649. (e) Prof. Tsugio Kitamura
presented some unpublished results on the synthesis of these
compounds at the SIS Conference at Chiba University in
November 2007.
(d) Kitamura, T.; Kotani, M.; Fujiwara, Y. Tetrahedron Lett.
1996, 37, 3721. (e) Zhdankin, V. V.; Scheuller, M. C.;
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V. W.; Widdowson, D. A. J. Chem. Soc., Perkin Trans. 1
1997, 2463. (i) Carroll, M. A.; Pike, V. W.; Widdowson, D.
A. Tetrahedron Lett. 2000, 41, 5393.
(8) Shorter reaction routes: (a) Stang, P. J.; Zhdankin, V. V.;
Tykwinski, R. Tetrahedron Lett. 1992, 33, 1419. (b) Stang,
P. J.; Zhdankin, V. V.; Tykwinski, R.; Zefirov, N. S.
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Kasumov, T. M.; Koz’min, A. S.; Sorokin, V. D.; Stang, P.
J.; Zhdankin, V. V. Synthesis 1993, 1209. (d) Beringer, F.
M.; Falk, R. A.; Karniol, M.; Lillien, I.; Masulio, G.;
Mausner, M.; Sommer, E. J. Am. Chem. Soc. 1959, 81, 342.
(e) Iwama, T.; Birman, V. B.; Kozmin, S. A.; Rawal, V. H.
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T. J. Org. Chem. 2006, 71, 9903. (h) Kryska, A.; Skulski, L.
Molecules 2001, 6, 875. (i) Kazmierczak, P.; Skulski, L.
Synthesis 1995, 1027.
(9) (a) Bielawski, M.; Olofsson, B. Chem. Commun. 2007,
2521. (b) Bielawski, M.; Zhu, M.; Olofsson, B. Adv. Synth.
Catal. 2007, 2610.
(10) New, commercially available cans of MCPBA were found to
contain large and variable amounts of H2O. The MCPBA
needs to be dried under vacuum at r.t. for 1 h to obtain
reproducible results.
(13) Dohi, T.; Ito, M.; Morimoto, K.; Minamitsuji, Y.; Takenaga,
N.; Kita, Y. Chem. Commun. 2007, 4152.
(14) Togo, H.; Yamamoto, Y. Synlett 2005, 2486.
(15) The sulfonic acid moiety of TsOH is expected to form
sulfuric acid upon formation of this byproduct. In order to
confirm that, the reaction mixture described in Scheme 3
was diluted with MeOH and a few drops of aq BaCl2 solution
was added. White precipitates were formed, indicating the
presence of SO42–. In a parallel reaction, toluene was used
instead of fluorobenzene, which resulted in no precipitates in
the test with BaCl2. See: Jackson, D. D. J. Am. Chem. Soc.
1901, 23, 799.
(16) The reactions were carried out in sealed tubes to allow for
reaction temperatures above the boiling point of CH2Cl2, and
were run without precaution to avoid moisture or air, i.e.
without inert gas or dried solvent. TfOH (≥99%) was stored
under argon atmosphere. The percentage of active oxidizing
agent in MCPBA was determined by iodometric titration,
see: Vogel, A. I.; Furniss, B. S.; Hannaford, A. J.; Rogers,
V.; Smith, P. W. G.; Tatchell, A. R. Vogel’s Textbook of
Practical Organic Chemistry; Longman: London / New
York, 1978, 1280.
(11) Unpublished results from our laboratory.
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