Highly efficient iodine-catalyzed hydroarylation of arenes with styrenes

Article abstract of DOI:10.1016/j.tetlet.2007.07.178

Iodine mediates the hydroarylation of styrenes with arenes and heteroarenes to afford 1,1-diarylalkanes in good to high yields. Details regarding the substrate scope and selectivity of this hydroarylation reaction are discussed.

Full text of DOI:10.1016/j.tetlet.2007.07.178

Tetrahedron Letters 48 (2007) 6881–6885
Highly efficient iodine-catalyzed hydroarylation
of arenes with styrenes
Cheng-Ming Chu, Wan-Ju Huang, Ju-Tsung Liu and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
Received 25 June 2007; revised 24 July 2007; accepted 26 July 2007
Available online 31 July 2007
Abstract—Iodine mediates the hydroarylation of styrenes with arenes and heteroarenes to afford 1,1-diarylalkanes in good to high
yields. Details regarding the substrate scope and selectivity of this hydroarylation reaction are discussed.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Arenes and heteroarenes have important functionaliza-
tion due to their essential role in chemical industry as
well as in the pharmaceuticals, agrochemicals, and fine
and bulk chemical industries. In general, Friedel–Crafts
reaction of aromatic and heteroaromatic compound is
one of the fundamental reactions for forming carbon–
carbon bond. Recently, there has been considerable
interest in developing C–H transformations of arenes
and heteroarenes using various transition-metal and
acid catalysts.1 The addition of olefins to acetophenones
(Murai reaction)2 and aromatic imines,3 the addition of
olefins to arenes4,5 and heterocyclic compounds,6 the
addition of aromatics to alkynes7 or alcohols,8 and the
cyclization of arene–alkyne substrates9 are elegant
examples of this. Such reactions manifest significant
drawbacks, for instance, the extreme reaction conditions
of high temperature and strong acidic, poor regioselec-
tivity, and a large amount of salt byproducts in essen-
tially. Therefore, the development of new synthetic
methods for hydroarylation of alkenes would be signif-
icant and the ongoing task is organic synthesis.
Recently, several papers have been reported about the
Friedel–Crafts hydroarylation of alkenes with electron-
rich aromatic and heteroaromatic compounds, which
were catalyzed by FeCl3, Bi(OTf)3, BiCl3, and
Sm(OTf)3.10 In recent years, molecular iodine (I2) has
attracted more attention because of their diverse appli-
cability as catalysts in organic synthesis.11 As part of
our continuous interest in employment of iodine as an
alternative, most simple, less expensive, and less toxic
reagent,11o–u herein we report a highly efficient Friedel–
Crafts hydroarylation of alkenes with arenes or hetero-
arenes under solvent-free condition.
Interest in the direct addition of arenes to styrenes and
by the fact that iodine is a highly efficient and mild cat-
alyst for oxidation to aromatic,12 we decided to inspect
the iodine catalyzed hydroarylation of styrene (Eq. 1).
R2
(Het)Ar R2
R3
H
R3
3 - 20 mol%
cat. I2
+
(Het)Ar-H
R1
R1
n
n
ð1Þ
In general, styrene 1a and anisole 2a were used as a rep-
resentative. Initially, endeavors were mainly focused on
the efficiency of the iodide catalyzed reaction (entries
1–5 of Table 1). Several reactions were conducted at this
stage by using 1 equiv of 1a and 2 equiv of anisole 2a
under solvent-free conditions. Only a slight conversion
of 1a to 3aa was observed in the presence of 3 mol %
of hydriodic acid, suggesting that the different cation
such as Li+, Na+, K+, or Cu+ or proton or the anion
such as iodide Iꢀ catalyzed reaction is not favorable for
hydroarylation. The parallel of the catalytic activity of
the iodine was also observed in iodine monochloride
(ICl)-catalyzed reactions. However, inferior results
obtained (entries 6 and 7) are probably due to the high
reactivity nature of ICl and this property makes
ICl to decompose to the hydrogen chloride and hydrogen
iodide rapidly in the presence of trace of moisture
and also induces the rapid exothermic decomposition
Keywords: Friedel–Crafts reaction; Iodine; Heteroarenes; Hydroaryla-
tion; Styrene.
*
Corresponding author. Tel.: +886
2 29350749; fax: +886 2
29324249; e-mail: cheyaocf@ntnu.edu.tw
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.178

6882
C.-M. Chu et al. / Tetrahedron Letters 48 (2007) 6881–6885
Table 1. Reaction of anisole 2a with styrene 1a in the presence of
various iodide catalyst
and the polymerization of styrene to occur in the reac-
tion. The best result was observed when the reaction
was carried out in the presence 3 mol % of iodine to
quantitatively afford the corresponding product 3aa after
4 h (entry 8).13,14 Finally, no catalytic effect was observed
when the molecular bromine was used under the same
conditions (entry 9).
3 mol% cat.
+
4 h
OMe
OMe
1a
2a
3aa
Entry Catalysta Temperature Conversionb 3aac Sel.d
(ꢁC)
(%)
(%)
The substrate scope of the reaction under the optimized
conditions was investigated, and we first explored the
extent of the iodine-catalyzed hydroarylation by chang-
ing the arene components and all the experimental re-
sults were summarized in Table 2. The reaction was
amenable to a wide variety of arenes for the hydroaryla-
tion. When different arenes and heteroarenes were em-
ployed, regioisomeric products resulted from both
para- and ortho-attack of the electrophile. Remarkably,
to our great satisfaction, under iodine catalysis, even
ortho-xylene and thiophene possessing less reactivity re-
acted smoothly and cleanly in good yield (entries 9 and
10), although slightly higher catalyst loads (20 mol %) or
longer reaction times were required. However, electron-
rich groups as strong as aniline were ineffective in this
Friedel–Crafts hydroarylation.
1
2
3
4
5
6
7
8
9
LiI
NaI
CuI
KI
80
80
80
80
80
80
80
80
80
3
2
1
—
—
—
—
4
20
51
98
—
2
HI
10
39
72
100
3
5.3:1
4.0:1
4.1:1
5.7:1
ICl
ICle
I2
Br2
a Reaction condition: 3 mmol of styrene 1a, 6 mmol of anisole 2a,
3 mol % of catalyst, under solvent free condition at 80 ꢁC.
b GC conversion of styrene.
c GC yields of product 3aa.
d 4-/2-substituted isomer were determined by 1H NMR of the crude
reaction.
e 10 mol % of catalyst.
Table 2. Reaction of styrene with various arenes in the presence of iodinea
I2 (mol%)
+
(Het)ArH
Ar(Het)
heat
1a
2
3
Entry
1
Het(Ar)H (equiv)
I2 (mol %)
3
T (ꢁC)/time (h)
Product 3
Yieldb (%)/sel.c
98/5.7:1
1.5
80/3
3aa
OMe
OMe
2
3
4
3
80/2
3ab
94/2.2:1
OH
OH
2.5
10
100/12
3acd
63/11.6:1
SMe
SMe
4
5
1.5
2
3
3
80/4
80/4
3ad
3ae
98/99:1
88/2.2:1
OMe
MeO
OMe
OMe
OH
HO
MeO
OMe
6
2
3
80/4
3af
95/—
OMe
MeO
O
O
I
O
7
8
2
5
5
5
80/7
80/5
3ag
75/24:1
70/99:1
O
I
3ah
OMe
OMe

C.-M. Chu et al. / Tetrahedron Letters 48 (2007) 6881–6885
6883
Table 2 (continued)
Entry
Het(Ar)H (equiv)
I2 (mol %)
T (ꢁC)/time (h)
Product 3
Yieldb (%)/sel.c
72/3.5:1
S
9
5
5
100/16
3ai
S
10
6
20
130/2
3ajd
58/9.2:1
a Reaction condition: 3 mmol of styrene under solvent free conditions.
b GC yields.
c Major and minor isomer were determined by 1H NMR of the crude reaction.
d The side product is 1,3-diphenylbut-1-ene.
Table 3. Reaction of various styrene derivatives with anisole in the presence of iodinea
R2
R2
R3
R3
+
I2 (mol%)
R1
R1
OMe
heat
OMe
3
1
2a
Entry
1d
Vinylarene
I2 (mol %)
T (ꢁC)/time (h)
Product 3
Yieldb (%)/sel.c
98/99:1
5
5
80/4
3ba
3ca
OMe
2
135/24
76/4.0:1
OMe
OMe
3
4
5
5
3
5
80/4
80/4
80/8
3da
3ea
3fa
98/8.3:1
99/99:1
97/2.0:1
OMe
OMe
Br
Br
Br
Br
6
5
5
3
80/8
80/4
80/3
3ga
98/2.5:1
98/6.2:1
OMe
OMe
7d
3ha
Br
F
Br
F
8
3ia
98/2.6:1
OMe
(continued on next page)

6884
C.-M. Chu et al. / Tetrahedron Letters 48 (2007) 6881–6885
Table 3 (continued)
Entry
Vinylarene
I2 (mol %)
5
T (ꢁC)/time (h)
Product 3
Yieldb (%)/sel.c
75/4.3:1
9
70/3
3ja
OMe
10
11
3
6
70/2
80/4
3ka
53/6.0:1
62/8.8:1
OMe
3la
Me
NC
Me
NC
OMe
12
13
10
10
120/24
120/36
3ma
94/1.5:1
95/99:1
OMe
3na
OMe
a Reaction condition: 2 mmol of styrene, 2 equiv of anisole in the presence of different amount of I2 under solvent free condition.
b GC yields.
c Major and minor isomer were determined by 1H NMR of the crude reaction.
d 1.5 equiv of anisole.
We continued to elucidate the scope of the new method-
ology, this time in terms of differently substituted sty-
rene derivatives in the reaction with anisole. This
method demonstrated good compatibility with various
functional substituted in phenyl group of styrene,
including alkyl groups, cyano, and halides (Table 3). It
was found that different halo-substituted styrenes
reacted well in the hydroarylation, and the diarylalkane
products were obtained in 97–98% yield (entries 5–8).
The electron-releasing groups generally increased poly-
mer reaction of these substrates and as such lower yields
of the corresponding products were obtained. For exam-
ple, styrene bearing one methyl group on the benzene
nucleus was converted to diarylalkane 3la in 62% iso-
lated yield in the presence of 6 mol % of iodine (entry
11). However, 4-cyanostyrene containing an electron-
withdrawing group was obtained in 94% yield in the
presence of 10 mol % of iodine after 24 h (entry 12).
Additionally, the a-substituted styrene derivatives could
be converted to the corresponding products containing
higher para-substituted selectivity in 95–99% yields as
a greater than 99:1 mixture (entries 1, 4, and 13). The
use of indene and dihydronaphthalene as substrates in
the reaction can generate aryl-dihydroindene and
tetrahydronaphthalene derivatives, which are the impor-
tant intermediates in the preparation of different
products such as agrochemicals and fungicides, and use-
ful compounds such as nafenopin, a peroxisome
proliferators.10b
and styrene substrates of diverse structural features pro-
viding good to excellent yields of the diarylalkane prod-
ucts. In contrast, iodine was shown to be cheap and easy
to handle in opposition to transition-metal catalyst.
Acknowledgment
Financial support of this work by the National
Science Council of the Republic of China and National
Taiwan Normal University (96TOP001) is gratefully
acknowledged.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2007.
07.178.
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Iodine demonstrated consistent performance with arene

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