Facile synthesis of diiodinated dihydronaphthalenes and naphthalenes via iodine mediated electrophilic cyclization

Article abstract of DOI:10.1039/c0cc05442a

A facile, efficient, and general synthetic method for a wide range of 2,3-diiodinated 1,4-dihydrothiophenes and naphthalenes has been developed via the electrophilic iodocyclization of various aryl propargyl alcohols. The resulting product 2p can be used

Full text of DOI:10.1039/c0cc05442a

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2011, 47, 4013–4015
www.rsc.org/chemcomm
COMMUNICATION
Facile synthesis of diiodinated dihydronaphthalenes and naphthalenes via
iodine mediated electrophilic cyclizationw
Fan Yang,a Tienan Jin,*ab Ming Baoc and Yoshinori Yamamoto*ab
Received 8th December 2010, Accepted 7th February 2011
DOI: 10.1039/c0cc05442a
A facile, efficient, and general synthetic method for a wide range
of 2,3-diiodinated 1,4-dihydrothiophenes and naphthalenes has
been developed via the electrophilic iodocyclization of various
aryl propargyl alcohols. The resulting product 2p can be used for
the synthesis of a rubrene intermediate.
ð1Þ
First we investigated the effect of solvents on the iodine-
Electrophilic iodocyclization of alkyne or allene bound
mediated electrophilic cyclization of 1a for the formation of
substrates is one of the most powerful methods for the
the 2,3-diiodo-1,4-dihydrothiophene 2a as shown in Table 1.
efficient synthesis of a variety of functionalized carbo-
cycles and heterocycles under mild conditions.1–7
The use of CH2Cl2 and CHCl3 led to good yields of 2a
(B80%), while the use of CH3CN resulted in moderate yield
of 1a (entries 1–3). It was found that CH3NO2 was the best
Furthermore, the corresponding iodine-containing products
can be readily converted to structurally interesting and
solvent, giving 2a in 88% isolated yield (entry 4). The decrease
elaborated compounds through transition metal-catalyzed
of the amount of I2 (2 equiv.) gave a slightly lower yield of 2a
transformations. Kruglov reported in 1937 an interesting
(entry 5). The use of MeOH and THF as solvents resulted in
iodocyclization of acetylene glycols, which produced
decomposition of 1a (entries 6 and 7).
3,4-diiododihydrofuran derivatives, however, since then the
protocol has never been investigated widely.6a Quite recently,
cyclization of various aryl propargyl alcohols were summaried
The scope and limitations of iodine mediated electrophilic
Liang and co-workers have successfully extended this
chemistry to the construction of various oxygen-containing
dihalogenated heterocycles.6b,c In the continuation of our
interest in iodocyclization chemistry,7 and in the development
of efficient synthetic methods of naphthalene derivatives,8
we envisioned that if one of the hydroxyl groups in
acetylene glycols is replaced with a suitable aromatic group,
2,3-diiododihydronaphthalene derivatives might be produced
via a Friedel–Craft type cyclization. This proved to be the case.
Herein, we report a facile and efficient synthetic methodology
in Table 2. The reactions of substrates 1b–e bearing an
electron-donating and an electron-withdrawing aromatic
group (R2) at the propargyl alcoholic carbon produced the
corresponding dihydronaphthalenes 2b–e in good to high yields
(entries 1–4). Remarkably, the presence of a double bond in
substrate 1f was also tolerated; the desired dihydronaphthalene 2f
was obtained in 88% yield (entry 5). Not only naphthyl
substituent (1g), but also heterocycles, such as thienyl (1h)
Table 1 Optimization of reaction conditions for the formation of 2aa
for
a variety of 2,3-diiodinated dihydronaphthalenes 2
and naphthalenes 3 by the electrophilic iodocyclization of
various substituted aryl propargyl alcohols 1 (eqn (1)). The
resulting dihydronaphthalenes 2 and naphthalene derivatives 3
are potentially useful as precursors for p-electronic organic
materials.
Entry
Solvent
Time/h
Yieldb (%)
1
2
3
4
5
6
7
CH2Cl2
CHCl3
1
1
3
3
3
5
5
81
80
68
CH3CN
CH3NO2
CH3NO2
MeOH
THF
a Department of Chemistry, Graduate School of Science,
Tohoku University, Sendai 980-8548, Japan.
91 (88)
89c
0d
E-mail: tjin@m.tohoku.ac.jp, yoshi@m.tohoku.ac.jp;
Fax: +81 22-795-6784; Tel: +81 22-795-6581
b WPI-AIMR (WPI-Advanced Institute for Materials Research),
Tohoku University, Sendai 980-8577, Japan
0d
a
Reaction conditions: 1a (0.2 mmol), I2 (0.6 mmol), anhydrous
solvents (0.1 M), room temperature. b 1H NMR yield was determined
by using CH2Br2 as an internal standard. Isolated yield is shown in
c State Key Laboratory of Fine Chemicals, Dalian University of
Technology, Dalian 116012, China
c
d
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c0cc05442a
parenthesis. 2 equiv. of I2 was used. 1a was decomposed.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 4013–4015 4013

View Article Online
Table 2 Electrophilic iodocyclization of various aryl propargyl alcohols for the formation of 2a
Entry
Substrates
1
Products
2
Yieldb (%)
1
2
3
4
5
6
7
8
R2 = 4-Me–C6H4
R2 = 2-Me–C6H4
R2 = 4-Cl–C6H4
1b
1c
1d
1e
1f
1g
1h
1i
2b
2c
2d
2e
2f
2g
2h
2i
90
95
85
52
88
98
81
84
R2 = 4-CO2Me–C6H4
R2 = (E)-CH|CHC6H5
R2 = 1-naphthyl
R2 = 2-thienyl
R2 = 2-(1-tosyl)pyrroyl
9
R1 = 2-Me–C6H4
R1 = 4-MeO–C6H4
R1 = 3-MeO–C6H4
R1 = 4-Cl–C6H4
1j
1k
1l
2j
2k
2l:2l0
2m
84
87
82
61
10
11
12
1m
13
R1–Ar = 1-naphthyl
1n
2n
93
14
15
R3 = Me
R3 = Ph
1o
1p
dr = 2.3 : 1.0
dr = 6 : 1
2o
2p
75
77
a
b
Reaction conditions: 1 (0.2 mmol), I2 (0.6 mmol) in CH3NO2 (0.1 M) at room temperature for 2–5 hours. Isolated yield.
and tosyl-protected pyrroyl (1i) groups, at R2 afforded the
desired products in high yields (entries 6–8). Subsequently,
we examined the effect of substituent at R1. Similarly, the
substrates 1j–l having electron-donating groups at R1 underwent
the cyclization smoothly to give the product in high yields,
while 1m bearing an electron-withdrawing group afforded 2m
in moderate yield (entries 9–12). However, in the case of
3-methoxy-substituted substrate 1l, the reaction gave a 10 : 1
mixture of regioisomers (entry 11). When R1–Ar was a
naphthyl group, the reaction proceeded well to give the
dihydrophenanthrene derivative 2n in high yield (entry 13).
The reactions also worked well with the substrates 1o and 1p
having a methyl or a phenyl group at R3, furnishing the
expected tetrasubstituted dihydronaphthalenes 2o and 2p,
respectively, as a mixture of two diastereomers (entries 14
and 15). It is noteworthy that when an alkyl substituted
substrate 1q having a b-proton to the propargyl alcohol, such
as cyclohexyl group, was employed, the reaction gave the
b-proton eliminated substrate 4q as a sole product (eqn (2)).
iodocyclization smoothly to afford the corresponding
3-bromo-2-iodo-dihydronaphthalene 2b0 in good yield as a
single regioisomer, which was further oxidized with DDQ to
produce the naphthalene derivative 3b0 quantitatively
(eqn (3)).
ð3Þ
Based on these observations, a plausible iodocyclization
mechanism is proposed as shown in Scheme 1. Presumably,
initial activation of the propagyl hydroxyl group of 1a with a
Lewis acidic iodine9 leads to the propargyl carbocation
intermediate A or allene cation B10 along with an unstable
hypoiodous acid (HOI) and an iodine anion. Attack of the
iodine anion onto the g-position of A or the cation in B affords
iodoallene C which reacts with hypoiodous acid to form an
ð2Þ
We further tested this iodocyclization with IBr as an
electrophile instead of iodine. Fortunately, in the presence
of two equivalents of IBr, 1b underwent the electrophilic
Scheme 1 A proposed mechanism.
c
4014 Chem. Commun., 2011, 47, 4013–4015
This journal is The Royal Society of Chemistry 2011

View Article Online
iodonium intermediate D.11 Subsequent intramolecular Friedel–
Craft type reaction of the aromatic ring with the activated
allene5f followed by deprotonation produces 2a and H2O.
Interestingly, when alkoxy groups, such as methoxy or
ethoxy, were substituted at the propargylic position, the
reaction proceeded under an elevated temperature (50 1C),
giving the naphthalene derivative 3a as a major product along
with the formation of dihydrofuran 5a6 as a minor product
(eqn (4)). However, in the case of the isopropyl group at R,4
the reaction produced 5a as a major product.
(b) A. K. Verma, T. Aggarwal, V. Rustagi and R. C. Larock,
Chem. Commun., 2010, 46, 4064; (c) S. Mehta, J. P. Waldo and
R. C. Larock, J. Org. Chem., 2009, 74, 1141; (d) S. A. Worlikar,
T. Kesharwani, T. Yao and R. C. Larock, J. Org. Chem., 2007, 72,
1347; (e) S. P. Bew, G. M. M. EL-Taeb, D. V. Knight and
W.-F. Tan, Eur. J. Org. Chem., 2007, 5759; (f) J. Barluenga,
H. Va
Soc., 2003, 125, 9028.
3 For selected recent examples of the synthesis of N-heterocycles,
see: (a) J. Barluenga, M. Trincado, E. Rubio and J. M. Gonzalez,
zquez-Villa, A. Ballesteros and J. M. Ganzalez, J. Am. Chem.
´ ´
´
Angew. Chem., Int. Ed., 2003, 42, 2406; (b) D. Yue and
R. C. Larock, Org. Lett., 2004, 6, 1037; (c) M. Amjad and
D. W. Knight, Tetrahedron Lett., 2004, 45, 539; (d) X. Zhang,
M. A. Campo, T. Yao and R. C. Larock, Org. Lett., 2005, 7, 763;
(e) Q. Huang, J. A. Hunter and R. C. Larock, J. Org. Chem., 2002,
67, 3437.
4 For selected recent examples of the synthesis of S-heterocycles, see:
(a) X. F. Ren, M. I. Konaklieva, H. Shi, S. Dickey, D. V. Lim,
J. Gonzalez and E. Turos, J. Org. Chem., 1998, 63, 8898;
(b) B. L. Flynn, G. P. Flynn, E. Hamel and M. K. Jung, Bioorg.
Med. Chem. Lett., 2001, 11, 2341; (c) X. F. Ren, E. Turos,
C. H. Lake and M. R. Churchill, J. Org. Chem., 1995, 60, 6468;
(d) X. F. Ren, M. I. L. Konaklieva, M. Krajkowski, T. S. Janik,
E. Turos, C. H. Lake and M. R. Churchill, J. Org. Chem., 1995, 60,
6484; (e) K. O. Hessian and B. L. Flynn, Org. Lett., 2003, 5, 4377.
5 For selected recent examples of the synthesis of carbocycles, see:
(a) J. Barluenga, J. H. Vazquez-Villa, A. Ballesteros and
ð4Þ
Rubrene has been studied widely as an organo-electronic
material in the research of field effect transistor, luminescence,
and others.12 We have successfully applied the present method
for the synthesis of rubrene intermediate 6p. The iodocyclization
product 2p was converted to the diiodonaphthalene 3p under
DDQ oxidation, which was treated with n-BuLi and diphenyl
isobenzofuran, giving the corresponding oxo-bridged adduct
6p in 83% yield (eqn (5)).
J. M. Gonzalez, Org. Lett., 2003, 5, 4121; (b) X. Zhang,
´
S. Sarkar and R. C. Larock, J. Org. Chem., 2006, 71, 236;
(c) J. Barluenga, J. H. Vazquez-Villa, I. Merino, A. Ballersteros
and J. M. Gonzalez, Chem.–Eur. J., 2006, 12, 5790; (d) H. P. Bi,
´
L.-N. Guo, X.-H. Duan, F. R. Gou, S.-H. Huang, X.-Y. Liu and
Y.-M. Liang, Org. Lett., 2007, 9, 397; (e) Z. A. Khan and T. Wirth,
Org. Lett., 2009, 11, 229; (f) J. Barluenga, E. Campos-Gomez,
A. Minatti, D. Rodriguez and J. M. Gonzalez, Chem.–Eur. J.,
2009, 15, 8946.
6 (a) A. A. Kruglov, Zh. Obshch. Khim., 1937, 7, 2605; (b) K.-G. Ji,
H.-T. Zhu, F. Yang, X.-Z. Shu, S.-C. Zhao, X.-Y. Liu, A. Shaukat
and Y.-M. Liang, Chem.–Eur. J., 2010, 16, 6151; (c) K.-G. Ji,
H.-T. Zhu, F. Yang, A. Shaukat, X.-F. Xia, Y.-F. Yang, X.-Y. Liu
and Y.-M. Liang, J. Org. Chem., 2010, 75, 5670.
7 (a) D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil and
Y. Yamamoto, Angew. Chem., Int. Ed., 2007, 46, 4764;
(b) D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil, Z. Huo
and Y. Yamamoto, J. Am. Chem. Soc., 2008, 130, 15720;
(c) Z. Huo, H. Tomeba and Y. Yamamoto, Tetrahedron Lett.,
2008, 49, 5531; (d) Z. Huo, I. D. Gridnev and Y. Yamamoto,
J. Org. Chem., 2010, 75, 1266.
ð5Þ
In conclusion, we have developed an efficient and general
iodine-mediated electrophilic cyclization for the synthesis of
2,3-diiodo-dihydronaphthalenes from aryl propargyl alcohols.
The reaction most probably proceeds through the in situ
formation of an allene intermediate under Lewis acidic
conditions, followed by the Friedel–Craft type reaction. In
addition, we found that in the case of alkoxy substituent
propargy alcohols, the reaction produced 2,3-diiodonaphthalenes.
Furthermore, we have demonstrated that the resulting product
can be applicable for the synthesis of an organo-electronic
material. Further extension of the present methodology to the
construction of heterocycles and application to the synthesis of
useful optoelectronic materials are in progress.
8 (a) N. Asao, K. Takahashi, S. Lee, T. Kasahara and
Y. Yamamoto, J. Am. Chem. Soc., 2002, 124, 12650;
(b) N. Asao, T. Nogami, S. Lee and Y. Yamamoto, J. Am. Chem.
Soc., 2003, 125, 10921; (c) N. Asao, H. Aikawa and Y. Yamamoto,
J. Am. Chem. Soc., 2004, 126, 7458.
9 K. Rossen, R. A. Reamer, R. P. Volante and P. J. Reider, Tetrahedron
Lett., 1996, 37, 6843.
10 For the Lewis acidic iodine-catalyzed C- and O-nucleophilic
substitution reactions of propargyl alcohols, see: (a) P. Srihari,
D. C. Bhunia, P. Sreedhar, S. S. Mandal, J. S. S. Reddy and
J. S. Yadav, Tetrahedron Lett., 2007, 48, 8120; (b) J. S. Yadav,
B. V. S. Reddy, N. Thrimurtulu, N. M. Reddy and A. R. Prasad,
Tetrahedron Lett., 2008, 49, 2031.
Notes and references
11 (a) T. Ishikawa, S. Manabe, T. Aikawa, T. Kudo and S. Saito, Org.
Lett., 2004, 6, 2361; (b) L.-F. Yao and M. Shi, Org. Lett., 2007, 9,
5187; (c) L.-F. Yao and M. Shi, Chem.–Eur. J., 2009, 15, 3875;
(d) K. Komeyama, N. Saigo, M. Miyagi and K. Takaki, Angew.
Chem., Int. Ed., 2009, 48, 9875.
1 For reviews, see: (a) R. C. Larock, in Acetylene Chemistry.
Chemistry, Biology, and Material Science, ed. F. Diederich,
P. J. Stang and R. R. Tykwinski, Wiley-VCH, New York, 2005,
ch. 2, pp. 51–99; (b) Y. Yamamoto, I. D. Gridnev, N. T. Patil and
T. Jin, Chem. Commun., 2009, 5075.
12 (a) J. A. Dodge, J. D. Bain and A. R. Chamberlin, J. Org. Chem.,
1990, 55, 4190; (b) J. Lu, D. M. Ho, N. J. Vogelaar, C. M. Kraml
and R. A. Pascal, Jr., J. Am. Chem. Soc., 2004, 126, 1168.
2 For selected recent examples of the synthesis of O-heterocycles,
see: (a) R. Mancuso, S. Mehta, B. Gabriele, G. Salerno,
W. S. Jenks and R. C. Larock, J. Org. Chem., 2010, 75, 897;
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 4013–4015 4015