Regio- and stereoselective iodoarylation of arylacetylenes using molecular iodine promoted by hypervalent iodine

Article abstract of DOI:10.1016/j.tetlet.2009.06.015

Iodoarylation of arylacetylenes with electron-rich arenes using a simple reagent system: I₂ and PhI(OCOPh)₂ proceeded regio- and stereoselectively to give trans adducts, 1,1-diaryl-2-iodoethenes, in good to high yields.

Full text of DOI:10.1016/j.tetlet.2009.06.015

Tetrahedron Letters 50 (2009) 4759–4761
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regio- and stereoselective iodoarylation of arylacetylenes using molecular
iodine promoted by hypervalent iodine
*
Md. Ataur Rahman, Tsugio Kitamura
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi, Saga 840-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Iodoarylation of arylacetylenes with electron-rich arenes using a simple reagent system: I2 and
PhI(OCOPh)2 proceeded regio- and stereoselectively to give trans adducts, 1,1-diaryl-2-iodoethenes, in
good to high yields.
Received 30 April 2009
Revised 3 June 2009
Accepted 5 June 2009
Available online 7 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Catalytic functionalization of aromatic CÀH bonds via forma-
tion of a new carbon–carbon bond between arenes and alkynes
has received significant attention. The process provides a direct
synthesis of various functionalized aromatic compounds bearing
conjugated carbon–carbon double bonds in one step, which is the
useful alternative to Heck-type coupling reactions of aromatic ha-
lides and olefins. To date, various methods for the functionalization
of arenes with alkynes have been developed,1 which are catalyzed
by transition metals or Lewis acids.
Although such metal-catalyzed carbon–carbon bond formation
reactions are excellent and very powerful methods, there are some
limitations, for instance, special caution for handling metal cata-
lysts under inert atmosphere and requirement of activated sub-
strates or strong acidic or severe conditions. These drawbacks of
the transition metal-catalyzed reaction of arenes with alkynes
have directed our attention to develop a more convenient and
new synthetic method for the functionalization of arenes without
using any transition metal catalysts.
Iodine is a unique element which acts as a weak oxidizer at the
same time as a reducing agent. Iodine molecule (I2) shows an elec-
trophilic property, but the reactivity in the addition reaction is low.
In the iodination reaction of arenes with I2, we have found that the
reaction of arenes with I2 proceeds smoothly in the presence of
potassium peroxodisulfate (K2S2O8) as an oxidant to give iodoare-
nes in good yields.2 To explore the use of molecular iodine, we ex-
tended the iodination reaction to iodoarylation of alkynes. It was
assumed that an alkyne would be first activated by iodine and then
would undergo electrophilic substitution with an arene. Iodoaryla-
tion of alkynes itself is a rare reaction. To the best of our knowl-
edge, there are no reports on the iodoarylation of alkynes using
molecular iodine except for an elaborated, expensive iodine source,
bis(pyridine)iodonium(I) tetrafluoroborate (IPy2BF4).3 Here, we re-
port a convenient and very simple reagent system of molecular io-
dine and hypervalent iodine compounds for iodoarylation reaction
of alkynes, providing regio- and stereoselective synthesis of 1,1-
diaryl-2-iodoethenes.
Iodoarylation of alkynes is accompanied by generation of pro-
ton and competes with protonation of alkynes. Actually, the iodo-
arylation of an alkyne with pentamethylbenzene (2a) using an I2/
K2S2O8 reagent system was found to produce a hydroarylation
product as a by-product along with a desired iodoarylation prod-
uct. However, the contamination of the iodoarylation product with
the inseparable by-product caused many difficulties in separation
and purification processes. (Diacetoxyiodo)benzene, PhI(OAc)2, is
a promising reagent which has both functions of oxidizing iodine
and of trapping proton with acetate anion. Thus, we considered
the use of PhI(OAc)2, which is the most commercially available
hypervalent iodine compound and is widely used one in organic
synthesis.
Initial work was concentrated on the efficiency of the iodoary-
lation of p-methylphenylacetylene (1a) with pentamethylbenzene
(2a) in the presence of I2 and PhI(OAc)2 (Scheme 1).
Iodoarylation reaction of 1a (1 mmol) and 2a (1 mmol) was car-
ried out using 1.25 mmol each of I2 and PhI(OAc)2. The results are
given in Table 1. The reaction in 1,2-dichloroethane (DCE) at 45 °C
for 28 h gave pure 1-iodo-2-(pentamethylphenyl)-2-(4-methyl-
phenyl)ethene (3aa), but the yield was low (12%) (entry 1).
Increasing the amount of 2a and PhI(OAc)2, the reaction was con-
I2
PhI(OAc)2
I
+
1a
2a
3aa
* Corresponding author. Tel.: +81 952 28 8550; fax: +81 952 28 8548.
E-mail address: kitamura@cc.saga-u.ac.jp (T. Kitamura).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.015

4760
M. A. Rahman, T. Kitamura / Tetrahedron Letters 50 (2009) 4759–4761
Table 1
Table 3
Iodoarylation reaction of 1a with 2aa
The reaction of alkyne 1 with arenes 2 in the presence of PhI(OCOPh)2
a
Entry 2a
(mmol)
PhI(OAc)2
(mmol)
Solvent Temp
Time
(h)
Yield of 3aab
(%)
Entry
Alkyne 1
ArH 2
Time (h)
Product 3
Yieldb (%)
(°C)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
2a
2b
2c
2d
2e
2a
2b
2c
2d
2e
2a
2b
2c
2d
2e
65
65
67
72
72
65
70
73
76
72
72
72
73
76
76
3aa
3ab
3ac
3ad
3ae
3ba
3bb
3bc
3bd
3be
3ca
3cb
3cc
3cd
3ce
86
75
56
42c
33c
71
61
59
32
24
69
67
56
27
23
1
2
3
4
5
1
5
5
10
10
1.25
DCE
45
60
60
28
48
48
65
65
12
23
52
78
13
3
3
3
3
AcOH
CH3CN
CH3CNc 82
AcOEtc
82
a
Reaction conditions: 1a (1 mmol), 2a, I2 (1.25 mmol), PhI(OAc)2, and a solvent
(2 mL).
b
Isolated yield based on 1a.
4 mL was used.
c
ducted in AcOH or MeCN at 60 °C (entries 2 and 3), indicating that
MeCN gave a better result. Extension of the reaction time and a
higher temperature improved the yield of 3aa to give the best re-
sult (78%) (entry 4). Using the conditions of entry 4, the reaction
in AcOEt instead of MeCN resulted in a low yield (13%) of 3aa (en-
try 5).
a
Reaction conditions: 1 (1 mmol), 2 (10 mmol), I2 (1.25 mmol), PhI(OCOPh)2
(3 mmol), MeCN (6 mL) at 82 °C.
b
Isolated yield based on 1.
A mixture of E- and Z-isomers.
c
We attempted to determine the stereochemistry of iodoarylation
product 3aa by NOE experiments, but only a small enhancement
(3%) of the vinylic proton was observed when the ortho methyl pro-
ton was irradiated. This may be attributed to the deviation of the
pentamethylphenyl ring from the olefinic plane. Then, we estimated
the chemical shift of the vinylic proton according to the literature.4
The calculation of the chemical shift concerning the vinylic proton
of 3aa gives 6.57 ppm for the E isomer and 6.84 ppm for the Z isomer.
Therefore, the observed chemical shift of 6.31 ppm indicates that the
stereochemistry of 3aa is E. This result suggests that the iodoaryla-
tion of arylalkynes proceeds with trans addition.
I2, PhI(OCOPh)2
R
+
Ar
H
MeCN, 82 oC
2
1
1a: R = Me
1b: R = H
1c: R = F
2a: Ar = Me5C6
2b: Ar = 2,4,6-Me3C6H2
2c: Ar = 2,3,5,6-Me4C6H
2d: Ar = 3-Br-2,4,6-Me3C6H
2e: Ar = 2,5-Me2C6H3
Using the conditions of entry 4 as listed in Table 1, we con-
ducted the iodoarylation of 1a with several electron-rich arenes.
The results are given in Table 2. The reaction with mesitylene
(2b), durene (2c), and bromomesitylene (2d) gave the correspond-
ing iodoarylation products 3 in moderate yields (entries 1–3).
In order to increase the reactivity of the hypervalent iodine re-
agent, the derivative of benzoic acid, PhI(OCOPh)2,5 was employed
in the iodoarylation reaction under the same conditions as
PhI(OAc)2. To ourdelight, PhI(OCOPh)2 improvedtheyieldof theiod-
oarylation product to afford 3aa in 86% yield (see, Table 3, entry 1).
Then, we furthermore conducted the iodoarylation reaction using
PhI(OCOPh)2. The outline of the reaction is drawn in Scheme 2 and
the results are given in Table 3. In the reaction of 4-methylphenyl-
acetylene (1a), electron-rich mesitylene (2b) gave the product 3ab
in high yield (entry 2). The reaction of 1a with durene (2c) and 2-bro-
momesitylene (2d) gave 3ac and 3ad in 56 and 42% yields, respec-
tively (entries 3 and 4). The reaction with p-xylene (2e) gave low
yield (entry 5) of iodoarylation product 3ae owing to the formation
of inseparable, polar substances. Similarly, the reactions of phenyl-
R
3aa: R = Me, Ar = Me5C6
3ab: R = Me, Ar = 2,4,6-Me3C6H2
3ac: R = Me, Ar = 2,3,5,6-Me4C6H
3ad: R = Me, Ar = 3-Br-2,4,6-Me3C6H
3ae: R = Me, Ar = 2,5-Me2C6H3
3ba: R = H, Ar = Me5C6
3bb: R = H, Ar = 2,4,6-Me3C6H2
3bc: R = H, Ar = 2,3,5,6-Me4C6H
3bd: R = H, Ar = 3-Br-2,4,6-Me3C6H
3be: R = H, Ar = 2,5-Me2C6H3
3ca: R = F, Ar = Me5C6
3cb: R = F, Ar = 2,4,6-Me3C6H2
3cc: R = F, Ar = 2,3,5,6-Me4C6H
3cd: R = F, Ar = 3-Br-2,4,6-Me3C6H
3ce: R = F, Ar = 2,5-Me2C6H3
I
Ar
3
Scheme 2.
acetylene (1b) and 4-fluorophenylacetylene (1c) also afforded iodo-
arylation products 3 in moderate to high yields.
A reaction path is proposed as shown in Scheme 3. The iodoary-
lation of an arylalkyne is initiated by oxidation of iodine with
PhI(OCOPh)2 giving a hypoiodite, IOCOPh.6 The in situ-generated
IOCOPh adds the arylalkyne to form a cyclic iodonium benzoate,
which undergoes aromatic electrophilic substitution with an elec-
tron-rich arene to afford a final product, accompanying deprotona-
tion with benzoate anion. Although the regioselectivity is derived
from a larger cationic character at the carbon bearing the aryl
group in the cyclic iodonium ion, the stereoselectivity can be ex-
plained by the contribution of the cyclic iodonium ion. Its presence
is an important factor to cause trans addition giving the stereo-
chemically defined product.7
In conclusion, we have demonstrated that arylacetylenes un-
dergo regio- and stereoselective iodoarylation in the presence of
a simple reagent system composed of I2 and PhI(OCOPh)2. Iodine
group is particularly useful for further elaboration by merging
the iodoalkene structures with metal-catalyzed cross-coupling
Table 2
Iodoarylation reaction of 1a with several arenes 2a
I2
PhI(OAc)2
+
Ar
H
I
2
1a
Ar
3
Entry
Arene 2
Temp (°C)
Time (h)
Yieldb (%)
1
2
3
Mesitylene (2b)
Durene (2c)
Bromomesitylene (2d)
82
82
82
65
65
65
62
40
26c
a
Reaction conditions: 1a (1 mmol),
2
(10 mmol), I2 (1.25 mmol), PhI(OAc)2
(3 mmol), and MeCN (4 mL).
b
Isolated yield based on 1a.
A mixture of E- and Z-isomers.
c

M. A. Rahman, T. Kitamura / Tetrahedron Letters 50 (2009) 4759–4761
4761
References and notes
−
PhI
I2
+
PhI(OCOPh)2
Ar1
IOCOPh
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Chem. 2009, 1111; (b) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013; (c) Kitamura,
T.; Fujiwara, Y., In Comprehensive Organometallic Chemistry III; Crabtree, R. H.;
Mingos, D. M. P., Eds.; Elsevier: Oxford, 2007; Vol. 10 (Ojima, I., Ed.), Chap. 10.05,
pp 213–250.; (d) Nevado, C.; Echavarren, A. M. Synthesis 2005, 167; (e) Ritleng,
V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731; (f) Kakiuchi, F.; Chatani, N.
Adv. Synth. Catal. 2003, 345, 1077; (g) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002,
35, 826; (h) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633; (i)
Guari, Y.; Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047; (j) Dyker,
G. Angew. Chem., Int. Ed. 1999, 38, 1698.
I
OCOPh
I
Ar1
Ar2
H
Ar1
Ar2
−
PhCOOH
2. Hossain, Md. D.; Oyamada, J.; Kitamura, T. Synthesis 2008, 690.
3. Barluenga, J.; Rodriguez, M. A.; Gonzalez, J. M.; Campos, P. J. Tetrahedron Lett.
1990, 31, 4207.
Scheme 3.
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5. Stang, P. J.; Boehshar, M.; Wingert, H.; Kitamura, T. J. Am. Chem. Soc. 1988, 110,
3272.
6. (a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic Press: New
York, 1997; (b) Madsen, J.; Viuf, C.; Bols, M. Chem. Eur. J. 2000, 1140.
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Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.06.015.