Regioselective synthesis of 1,3,5-substituted benzenes via the InCl 3/2-iodophenol-catalyzed cyclotrimerization of alkynes

Article abstract of DOI:10.1021/jo201010d

A novel indium(III)-catalyzed cyclotrimerization of alkynes in the presence of 2-iodophenol gave 1,3,5-substituted benzenes in excellent yields with complete regioselectivity. The reaction condition is tolerant to air, and atom economical, in accordance with the concept of modern green chemistry. This method provides a rapid and efficient access to 1,3,5-substituted benzenes.

Full text of DOI:10.1021/jo201010d

NOTE
pubs.acs.org/joc
Regioselective Synthesis of 1,3,5-Substituted Benzenes via the
InCl3/2-Iodophenol-Catalyzed Cyclotrimerization of Alkynes
Yan-li Xu, Ying-ming Pan,* Qiang Wu, Heng-shan Wang,* and Pei-zhen Liu
Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China),
School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, People’s Republic of China
S Supporting Information
b
ABSTRACT: A novel indium(III)-catalyzed cyclotrimerization of alkynes in the
presence of 2-iodophenol gave 1,3,5-substituted benzenes in excellent yields with
complete regioselectivity. The reaction condition is tolerant to air, and atom
economical, in accordance with the concept of modern green chemistry. This
method provides a rapid and efficient access to 1,3,5-substituted benzenes.
he importance of the chemistry of the carbonÀcarbon triple
Table 1. Screening of Additives for the Synthesis of 1,3,5-
Substituted Benzenea
T
bond has been well recognized since this functional group
has shown to be one of the main building blocks of organic and
material chemistry.1 The transition-metal-catalyzed cyclotrimer-
ization of alkynes continues attract considerable attention by
virtue of its intrinsic atom economy and convergent nature,
as well as the importance of substituted benzenes as synthetic
intermediates.2 Since it was first discovered by Reppe and co-
workers,3 complexes of many transition metals involving palla-
dium, ruthenium, cobalt, nickel, rhodium, or other transition
metals have been developed as effective catalysts or precursors
for the transformation.4 However, a mixture of 1,3,5- and 1,2,4-
trisubstituted benzenes is obtained in general. This drawback
limits the application of transition-metal-based methods. There-
fore, a cheaper, more general and efficient catalyst with a high
regioselectivity has been in great demand. Herein, we describe
the highly regioselective synthesis of 1,3,5-trisubstituted ben-
zenes via the InCl3-catalyzed5 trimerization of alkynes.6
Initially, phenylacetylene (1a) (0.9 mmol) was treated with
2-iodophenol (0.3 mmol) in the presence of 10 mol % of InCl3 in
chlorobenzene at reflux for 24 h, and the desired 1,3,5-triphenyl
benzene (2a) was isolated in 91% yield (Table 1, entry 1).7 In an
attempt to better understand the structureÀactivity relationship
of an additive, we decided to screen the indium(III)-catalyzed
cyclotrimerization using a variety of phenol, thiophenol, aniline,
and nitrobenzene derivatives.8 As a result, we found that the use
of different monohydroxyl- and/or monoiodo-based additives
in combination with InCl3 afforded the cyclotrimerization
product 1,3,5-triphenylbenzene (Table 1, entries 1À8). When
additives with no hydroxyl or iodo substituents were used, such
as 2-aminobenzenethiol and 1,2-diaminobenzene, the reaction
failed to afford the desired products (Table 1, entries 10 and 11).
Surprisingly, 1,2-benzenediol did not work as an additive in
this cyclotrimerization (Table 1, entry 9). Control experiments
confirmed that in the absence of either 2-iodophenol or InCl3 the
reaction led to recovery of starting materials,9 which illustrated
the necessity of both phenol and iodo derivatives and indium-
(III) catalyst in this transformation.
entry
additive
yieldb (%)
1
2
2-iodophenol
91
10
8
phenol
3
2-chlorophenol
2-aminophenol
4-tert-butylphenol
4-nitrophenol
4
30
65
5
5
6
7
2-iodobenzenamine
1-iodo-3-nitrobenzene
1,2-benzenediol
2-aminobenzenethiol
1,2-diaminobenzene
50
8
8
9
0
10
0
11
0
a Reaction conditions: all reactions were carried out in sealed tubes
using 1a (0.9 mmol), additive (0.3 mmol), and InCl3 (10 mol %) in PhCl
(2 mL) at reflux 24 h. b Isolated yield of pure product based on
phenylacetylene 1a.
As 2-iodophenol proved to be the most effective additive,
further experiments were focused on its use with other metal
cations. A variety of Lewis acid catalysts and solvents were
screened using phenylacetylene (1a, 0.9 mmol, Table 2) as a
model substrate. First, Fe(OTf)3 exhibited activity similar to that
of InCl3, affording the cyclized product 2a in 85% yield (Table 2,
entry 2), while FeCl3 (anhydrous) failed to afford the desired
product (Table 2, entry 3). Zn(II) catalysts afforded the
Received: June 3, 2011
Published: September 14, 2011
r
2011 American Chemical Society
8472
dx.doi.org/10.1021/jo201010d J. Org. Chem. 2011, 76, 8472–8476
|

The Journal of Organic Chemistry
NOTE
Table 2. Optimization of Formation of Substituted Benzenea
smoothly affording the desired product 2b in 88% yield (Table 3,
entry 2). However, diphenylethyne did not form the benzene
derivative 2c under the same conditions (Table 3, entry 3). The
terminal aryl alkyne 1d possessing an electron-donating group at
the aryl ring (R1 = 4-MeOC6H4) reacted smoothly and afforded
the desired product 2d in 96% yield (Table 3, entry 4). Sub-
strates 1e and 1f possessing electron-withdrawing groups (R1 =
4-FC6H4, 4-BrC6H4) at the aryl ring were also successfully
employed in the cyclotrimerization and gave the benzene
derivatives 2e and 2f in 41% and 60% yields, respectively
(Table 3, entries 5 and 6). Remarkably, electron-rich terminal
alkynes provided the desired products in higher yields than
electron-poor terminal alkynes did. Moreover, the cyclotri-
merizations of alkynes 1gÀj (R1 = 4-MeC6H4, 4-EtC6H4,
4-nPrC6H4, and 3-MeC6H4) also proceeded smoothly to afford
benzene derivative 2gÀj in excellent yields with complete
regioselectivity (Table 3, entries 7À10). However, the cyclotri-
merizations 1k did not form the desired benzene derivative 2k
(Table 3, entry 11), presumably due to the steric effect of the
substituent in the ortho-position of 1k.11 Additionally, alkynes
bearing a heterocyclic aromatic substituent such as 2-ethy-
nylthiophene 1l were found to afford the desired product 2l in
60% yield (Table 3, entry 12). The terminal alkyl alkynes 1m and
1n in the presence of InCl3/2-iodophenol also underwent a
smooth cyclotrimerization to give the products 2m and 2n in
90% and 95% yields, respectively (Table 3, entries 13 and 14).
However, 3,3-dimethyl-1-butyne and cyclopropylacetylene failed
to afford the desired products and led to recovery of starting
materials (Table 3, entries 16 and 17). In addition, the reaction
of 5-chloropentyne under the same conditions resulted in the
formation of a complex mixture of unidentified compounds
(Table 3, entry 15). These results indicated the limitations of
the InCl3/2-iodophenol catalytic system.
entry
catalyst
InCl3
solvent
PhCl
yieldb (%)
1
2
91
85
0
Fe(OTf)3
FeCl3
PhCl
3
PhCl
4
ZnCl2
PhCl
10
15
70
60
50
10
0
5
Zn(OTf)2
Cu(OTf)2
Bi(OTf)3
AgOTf
Sc(OTf)3
CuCl
PhCl
6
PhCl
7
PhCl
8
PhCl
9
PhCl
10
11
12
13
14
15
16
17
18
PhCl
BiCl3
PhCl
0
InCl3
PhCH3
CH3NO2
DCE
40
10
5
InCl3
InCl3
InCl3
THF
0
InCl3
CH3COCH3
CH3CN
DCM
0
InCl3
0
InCl3
0
a Reaction conditions: all reactions were carried out in sealed tubes using
1a (0.9 mmol), 2-iodophenol (0.3 mmol), and catalyst (10 mol %) in
solvent (2 mL) at reflux 24 h. b Isolated yield of pure product based on
phenylacetylene 1a.
cycloadduct 2a in 10À15% yields (Table 2, entries 4 and 5). The
trimerization of alkyne 1a using Cu(OTf)2, Bi(OTf)3, AgOTf,
and Sc(OTf)3 produced 2a in 70%, 60%, 50%, and 10% yields,
respectively (Table 2, entries 6À9). CuCl- and BiCl3-catalyzed
trimerization of 1a failed (Table 2, entries 10 and 11). InCl3 was
found to be the most effective catalyst to promote the cyclo-
trimerization efficiently. In addition, it was found that the solvent
played a crucial role in this reaction (Table 2, entries 1 and
12À18). The InCl3/2-iodophenol-catalyzed cyclotrimerization
of 1a was performed using several solvents at refluxing tempera-
ture. Chlorobenzene was found to be the most suitable solvent
to afford the product 2a in 91% yield (Table 2, entry 1). When
the reaction was carried out in toluene, the yield of product 2a
dramatically decreased to 40% (Table 2, entry 12). The reaction
in nitromethane or 1,2-dichloroethane yielded only 10 and 5% of
2a, respectively (Table 2, entries 13 and 14). In other solvents,
such as THF, CH3COCH3, CH3CN, and DCM, starting material
1a was recovered (Table 2, entries 15À18). The above investiga-
tions revealed that the InCl3/2-iodophenol/chlorobenzene sys-
tem is the best combination for promoting the cyclotrimerization
of alkyne 1a.
We proposed a possible mechanism of the indium(III)
chloride catalyzed cyclotrimerization of alkynes, shown in
Scheme 1. Our hypothesis is that the cis-addition of alkynes
and InCl3 may form cis-chloroindium intermediate 3, followed by
consecutive cis-addition of alkynes, and the chloroindiumation
intermediate may give the new chloroindiumation intermediate 5
which then undergoes cyclization to generate intermediate 6.12
Upon the assistance of 2-iodophenol, the reaction affords
benzene derivatives and regenerates the active InCl3 quickly
(Scheme 1).13 When R1 = alkyl, p-BrPh, p-MeOPh, or p-MePh,
R2 = H, and R1 = alkyl, R2 = alkyl, there is less steric hindrance
in 5 during the ring-closure process, and the products of the
cyclotrimerization are symmetrical benzene derivatives. When
R1 = Ph, R2 = Ph, and R1 = alkyl (tert-Butyl and cyclopropyl) or
o-MeOPh, R2 = H, 5 is more sterically hindered, and no desired
product was obtained.
In summary, we have developed a novel cyclotrimerization of
alkynes catalyzed by InCl3 in conjunction with 2-iodophenol
to give a variety of 1,3,5-trisubstituted benzenes in excellent
yields with complete regioselectivity. This operationally simple
method gives a rapid access to the 1,3,5-trisubstituted benzenes.
Air-tolerant and atom-economical characteristics of the method
accord with the concept of modern green chemistry and will be
appealing for industries.
With these optimal conditions in hand, we examined the
scope of this cyclotrimerization reaction. The alkyl- and aryl-
substituted alkynes gave the corresponding symmetrical product
2 in complete regioselectivities (Table 3).10 Initially, we carried
out the cyclotrimerization of 1-phenyl-2-trimethylsilylacetylene
under prolonged reaction time (72 h); however, the product 2a
obtained was only in 15% yield instead of tris(trimetylsilyl)-
triphenylbenzene (2ab) (Table 3, entry 1). 2-Butyne reacted
’ EXPERIMENTAL SECTION
A general experimental procedure for the reaction of alkynes (1)
catalyzed by InCl3/2-iodophenol is described below: The reaction
8473
dx.doi.org/10.1021/jo201010d |J. Org. Chem. 2011, 76, 8472–8476

The Journal of Organic Chemistry
NOTE
Table 3. Synthesis of Substituted Benzenes 2 Catalyzed by InCl3/2-Iodophenola
a Reaction conditions: all reactions were carried out in sealed tubes using 1a (0.9 mmol), 2-iodophenol (0.3 mmol), and InCl3 (10 mol %) in
chlorobenzene (2 mL) at reflux 24 h. b Yield of the isolated product after flash chromatography. c Reaction time is 72 h.
mixture of alkyne 1 (0.9 mmol), 2-iodophenol (0.3 mmol), chloroben-
zene (2.0 mL), and indium trichloride (0.09 mmol) in a 10 mL sealed
tube was stirred at reflux and monitored periodically by TLC. Upon
completion, chlorobenzene was removed under reduced pressure using
an aspirator, and then the residue was purified by flash chromatography
(hexane/ethyl acetate) on silica gel to afford the 1,3,5-trisubstituted
benzenes.
1,3,5-Triphenylbenzene (2a). This product was purified via flash
column chromatography with hexane, yielding 91% as a white solid: mp
172À174 °C (lit.14 mp 170À172 °C); 1H NMR (500 MHz, CDCl3) δ
7.39À7.42 (m, 3H), 7.49À7.51 (m, 6H), 7.72À7.73 (m, 6H), 7.81
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 125.2, 127.4, 127.5, 128.8,
141.2, 142.4; MS [M + H+] 307.
a white solid: mp 142À143 °C (lit.16 mp 140À142 °C); 1H NMR (500
MHz, CDCl3) δ 3.88 (s, 9H), 7.02 (d, J = 8.6 Hz, 6H), 7.63 (d, J = 8.6
Hz, 6H), 7.67 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 55.4,
114.3,123.8, 128.3, 133.9, 141.8, 159.3; MS: [M + H+] 397.
1,3,5-Tris(4-fluorophenyl)benzene (2e). Purified via flash
column chromatography with hexane, yielding 41% as a yellow solid:
mp 238À239 °C (lit.14 mp 238À240 °C); 1H NMR (500 MHz, CDCl3)
δ 7.67 (s, 3H), 7.63À7.65 (m, 6H), 7.15À7.19 (m, 6H); 13C NMR
(125 MHz, CDCl3) δ 163.7, 141.6, 137.1, 128.9, 124.9, 115.8; MS
[M + H+] 361.
1,3,5-Tris(4-bromophenyl)benzene (2f). Purified via flash
column chromatography with hexane, yielding 60% as a yellow solid:
mp 261À263 °C (lit.14 mp 260À261 °C); 1H NMR (500 MHz, CDCl3)
δ 7.48 (d, J = 8.4 Hz, 6H), 7.61 (d, J = 8.4 Hz, 6H), 7.86 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 120.3, 124.9, 129.1, 132.3, 133.8, 141.7;
MS [M + H+] 544.
Hexamethylbenzene (2b). This product was purified via flash
column chromatography with hexane, yielding 88% as a white solid:
mp 162À164 °C (lit.15 mp 162À163 °C); 1H NMR (500 MHz, CDCl3)
δ 2.24 (s, 18H); 13C NMR (125 MHz, CDCl3) δ 132.0, 16.8; MS
[M + H+] 163.
1,3,5-Tris(4-methylphenyl)benzene (2g). Purified via flash
column chromatography with 1% ethyl acetate/hexane, yielding 88%
1
1,3,5-Tris(4-methoxyphenyl)benzene (2d). Purified via flash
column chromatography with 10% ethyl acetate/hexane, yielding 96% as
as a pale yellow solid: mp 175À176 °C (lit.15 mp 177À178 °C); H
NMR (500 MHz, CDCl3) δ 2.42 (s, 9H), 7.29 (d, J = 7.8 Hz, 6H), 7.60
8474
dx.doi.org/10.1021/jo201010d |J. Org. Chem. 2011, 76, 8472–8476

The Journal of Organic Chemistry
NOTE
Scheme 1. Proposed Mechanism
(500 MHz, CDCl3) δ 1.36 (d, J = 7.0 Hz, 18H), 2.96À3.00 (m, 3H),
7.01 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 24.1, 34.3, 122.1, 148.7;
MS [M + H+] 205. Anal. Calcd for C153H24: C, 88.16; H, 11.84. Found:
C, 88.32; H, 11.58.
’ ASSOCIATED CONTENT
S
Supporting Information. Spectra data for all products.
b
This material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: panym2004@yahoo.com.cn; wang_hengshan@yahoo.
com.cn.
’ ACKNOWLEDGMENT
This study was supported by 973 projects (2011CB512005),
National Natural Science Foundation of China (20762001), the
projects of Key Laboratory for the Chemistry and Molecular
Engineering of Medicinal Resources (Guangxi Normal Uni-
versity), Ministry of Education of China (CMEMR2011-15),
Guangxi Natural Science Foundation of China (2011GXNSF-
D018010 and 2010GXNSFF013001), and Guangxi’s Medicine
Talented Persons Small Highland Foundation (0808).
(d, J = 8.0 Hz, 6H), 7.73 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 21.1.
124.6, 127.2, 129.5, 137.3, 138.4, 142.2; MS: [M + H+] 349.
1,3,5-Tris(4-ethylphenyl)benzene (2h). Purified via flash col-
umn chromatography with 1% ethyl acetate/hexane, yielding 84% as a
pale yellow solid: mp 111À113 °C (lit.17 mp 112À114 °C); 1H NMR
(500 MHz, CDCl3) δ 1.31 (t, J = 7.6 Hz, 9H), 2.74 (q, J = 7.6 Hz, 6H),
7.33 (d, J = 7.8 Hz, 6H), 7.63 (d, J = 7.9 Hz, 6H), 7.76 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 15.6, 28.5, 124.6, 127.3, 128.3, 138.7, 142.2, 143.6;
MS [M + H+] 391.
’ REFERENCES
(1) Acetylene Chemistry: Chemistry, Biology, and Material Science;
Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; Wiley-VCH:
Weinheim, 2005.
(2) For selected examples, see: (a) Joosten, A.; Soueidan, M.;
Denhez, C.; Harakat, D.; Helion, F.; Namy, J.; Vasse, J.; Szymoniak, J.
Organometallics 2008, 27, 4152. (b) Morohashi, N.; Yokomakura, K.;
Hattori, T.; Miyano, S. Tetrahedron Lett. 2006, 47, 1157. (c) Ladipo,
F. T.; Sarveswaran, V.; Kingston, J. V.; Huyck, R. A.; Bylikin, S. Y.; Carr,
S. D.; Watts, R.; Parkin, S. J. Organomet. Chem. 2004, 689, 502. (d) Zhu,
Z.; Wang, C.; Xiang, X.; Pi, C.; Zhou, X. Chem. Commun. 2006, 19, 2066.
(e) Bu, X.; Zhang, Z.; Zhou, X. Organometallics 2010, 29, 3530.
(3) Reppe, W.; Schichting, O.; Klager, K.; Toepel, T. Justus Liebigs
Ann. Chem. 1948, 560, 1.
1,3,5-Tris(4-propylphenyl)benzene (2i). Purified via flash col-
umn chromatography with 1% ethyl acetate/hexane, yielding 90% as
1
a pale yellow solid: mp 142À143 °C; H NMR (500 MHz, CDCl3)
δ 1.00 (t, J = 7.3 Hz, 9H), 1.76À1.66 (m, 6H), 2.69À2.64 (m, 6H), 7.30
(d, J = 8.0 Hz, 6H), 7.63 (d, J = 8.1 Hz, 6H), 7.76 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 13.9, 24.6, 37.7, 124.6, 127.2, 128.9, 138.6, 142.0,
142.1; MS [M + H+] 433. Anal. Calcd for C33H36: C, 91.61; H, 8.39.
Found: C,91.84; H, 8.24.
(4) For selected examples, see: (a) Takeda, A.; Ohno, A.; Kadota, I.;
Gevorgyan, V.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119, 4547. (b) Li,
J.; Jiang, H.; Chen, M. J. Org. Chem. 2001, 66, 3627. (c) Cheng, J.; Wei,
G.; Huang, S.; Zhao, J.; Jiang, H. J. Mol. Catal. A: Chem. 2007, 263, 169.
(d) Lombardo, M.; Pasi, F.; Trombini, C.; Seddon, K. R.; Pitner, W. R.
Green Chem. 2007, 9, 321. (e) Yong, L.; Butensch€on, H. Chem. Commun.
2002, 2852. (f) Saino, N.; Amemiya, F.; Tanabe, E.; Kase, K.; Okamoto,
S. Org. Lett. 2006, 8, 1439. (g) Hilt, G.; Vogler, T.; Hess, W.; Galbiati, F.
Chem. Commun. 2005, 1474. (h) Kakeya, M.; Fujihara, T.; Kasaya, T.;
Nagasawa, A. Organometallics 2006, 25, 4131. (i) Tagliatesta, P.; Floris,
B.; Galloni, P.; Leoni, A.; D’Arcangelo, G. Inorg. Chem. 2003, 42, 7701.
(j) Yoshida, K.; Morimoto, I.; Mitsudo, K.; Tanaka, H. Chem. Lett. 2007,
36, 998. (k) Tanaka, K.; Toyoda, K.; Wada, A.; Shirasaki, K.; Hirano, M.
Chem.ÀEur. J. 2005, 11, 1145. (l) Johnson, E. S.; Balaich, G. J.; Fanwick,
P. E.; Rothwell, I. P. J. Am. Chem. Soc. 1997, 119, 11086.
1,3,5-Tris(3-methylphenyl)benzene (2j). Purified via flash
column chromatography with 1% ethyl acetate/hexane, yielding 85%
as a white solid: mp 117À118 °C (lit.18 mp 116.8À118.1 °C); 1H NMR
(500 MHz, CDCl3) δ 2.46 (s, 9H), 7.22 (d, J = 7.5 Hz, 3H), 7.38 (t, J =
7.6 Hz, 3H), 7.51 (d, J = 7.6 Hz, 6H), 7.76 (s, 3H); 13CNMR (125 MHz,
CDCl3) δ 21.5, 124.5, 125.1, 128.2, 128.3, 128.7, 138.4, 141.3, 142.4;
MS [M + H+] 349.
1,3,5-Tris(2-thienyl)benzene (2l). Purified via flash column
chromatography with hexane, yielding 60% as a pale yellow solid: mp
157À158 °C (lit.19 mp 156À158 °C); 1H NMR (500 MHz, CDCl3) δ
7.13 (dd, J = 5.0, 3.6 Hz, 3H), 7.32À7.36 (m, 3H), 7.42 (dd, J = 3.5,
1.0 Hz, 3H), 7.75 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 122.8, 123.9,
125.4, 128.1, 135.7, 143.6; MS [M + H+] 325.
1,3,5-Triethylbenzene (2m). Purified via flash column chroma-
tography with hexane, yielding 90% as yellow oil: 1H NMR (500 MHz,
CDCl3) δ 1.34 (t, J = 7.6 Hz, 9H), 2.71 (q, J = 7.6 Hz, 6H), 6.96 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 15.6, 28.9, 124.8, 144.2; MS [M + H+]
163. Anal. Calcd for C12H18: C, 88.82; H, 11.18. Found: C, 88.59;
H, 11.41.
(5) Recent reviews for InCl3-based reactions: (a) Ranu, B. C. Eur. J.
Org. Chem. 2000, 2347. (b) Fringuelli, F.; Piermatti, O.; Pizzo, F.;
Vaccaro, L. Curr. Org. Chem. 2003, 7, 1661. (c) Babu, G.; Perumal, P. T.
Aldrichim. Acta 2000, 33, 16. (d) Babu, S. A. Synlett 2002, 531. (e) Baba,
A.; Yasuda, M.; Nishimoto, Y.; Saito, T.; Onishi, Y. Pure Appl. Chem.
2008, 80, 845.
1,3,5-Triisopropylbenzene (2n). Purified via flash column chro-
(6) Cyclotrimerization of acetophenone-type substrates also pro-
vides 1,3,5-trisubstituted benzenes. For selected examples, see: (a) Dash,
1
matography with hexane, yielding 95% as pale yellow oil: H NMR
8475
dx.doi.org/10.1021/jo201010d |J. Org. Chem. 2011, 76, 8472–8476

The Journal of Organic Chemistry
NOTE
B. P.; Satapathy, R.; Gaillard, E. R.; Maguire, J. A.; Hosmane, N. S. J. Am.
Chem. Soc. 2010, 132, 6578. (b) Periasamy, M.; Jayakumar, K. N.;
Bharathi, P. J. Org. Chem. 2005, 70, 5420. (c) Cao, X.-Y.; Liu, X.-H.;
Zhou, X.-H.; Zhang, Y.; Jiang, Y.; Cao, Y.; Cui, Y.-X.; Pei, J. J. Org. Chem.
2004, 69, 6050. (d) Zhao, Y.; Li, J.; Li, C.; Yin, K.; Ye, D.; Jia, X. Green
Chem. 2010, 12, 1370.
(7) No other isomers (e.g., 1,2,4-trisubstituted benzene) have been
detected by 500 MHz 1H NMR analysis.
(8) For selected example, see: (a) Sashuk, V.; Ignatowska, J.; Grela,
K. J. Org. Chem. 2004, 69, 7748. (b) Grela, K.; Ignatowska, J. Org. Lett.
2002, 4, 3747.
(9) Product 2a was not detected in the absence of 2-iodophenol even
when a stoichiometric amount of InCl3 was used.
(10) A mixture of 1,3,5- and 1,2,4-trisubstituted benzenes was
obtained by the previously reported methods. See: (a) Cadierno, V.;
Garcia-Garrido, S. E.; Gimeno, J. J. Am. Chem. Soc. 2006, 128, 15094. (b)
Goswami, A.; Ito, T.; Okamoto, S. Adv. Synth. Catal. 2007, 349, 2368.
(11) Cicero has also reported that 1-ethynyl-2,6-dimethoxybenzene
failed to afford the product 1,3,5-tri(2,6-dimethoxyphenyl)benzene
and/or 1,2,4-tri(2,6-dimethoxyphenyl)benzene in the presence of vana-
dium phthalocyanine. See: Cicero, D.; Lembo, A.; Leoni, A.; Tagliatesta,
P. New J. Chem. 2009, 33, 2162.
(12) 2-Iodophenol may play the assisting role in stabilizing the
intermediates (3, 4, and 5) and keeping their geometry favorable for the
addition with compound 1.
(13) Li, J.; Jiang, H.; Chen, M. J. Org. Chem. 2001, 66, 3627.
(14) Kumar, A.; Dixit, M.; Singh, S. P.; Raghunandan, R.; Maulik,
P. R.; Goel, A. Tetrahedron Lett. 2009, 50, 4335.
(15) Breschi, C.; Piparo, L.; Pertici, P.; Caporusso, A. M.; Vitulli, G.
J. Organomet. Chem. 2000, 607, 57.
(16) Kothe, G.; Zimmermann, H. Tetrahedron 1973, 29, 2305.
(17) Lyle, R. E.; DeWitt, E. J.; Nichols, N. M.; Cleland, W. J. Am.
Chem. Soc. 1953, 75, 5959.
(18) Ono, F.; Ishikura, Y.; Tada, Y.; Endo, M.; Sato, T. Synlett 2008,
15, 2365.
(19) Pelter, A.; Jenkins, I.; Jones, D. E. Tetrahedron 1997, 53, 10357.
8476
dx.doi.org/10.1021/jo201010d |J. Org. Chem. 2011, 76, 8472–8476