Sulfur-assisted propargyl-allenyl isomerizations and intramolecular cyclization for the synthesis of tricyclic thiophene derivatives

Article abstract of DOI:10.1016/j.tetlet.2010.09.063

A facile and efficient cyclization for the synthesis of tricyclic thiophene derivatives was developed. As a metal-free process, a result of the ready availability of the starting materials and the simple and convenient operation, the type of reaction presented here has potential utility in organic synthesis.

Full text of DOI:10.1016/j.tetlet.2010.09.063

Tetrahedron Letters 51 (2010) 6240–6242
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Sulfur-assisted propargyl–allenyl isomerizations and intramolecular cyclization
for the synthesis of tricyclic thiophene derivatives
Guangyu Xu a, Kaixiong Chen a, Hongwei Zhou b,
⇑
a Chemistry & Chemical Engineering College, Hunan Normal University, Changsha 410081, PR China
b Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310028, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 July 2010
Revised 13 September 2010
Accepted 17 September 2010
Available online 22 September 2010
A facile and efficient cyclization for the synthesis of tricyclic thiophene derivatives was developed. As a
metal-free process, a result of the ready availability of the starting materials and the simple and conve-
nient operation, the type of reaction presented here has potential utility in organic synthesis.
Ó 2010 Elsevier Ltd. All rights reserved.
This Letter is dedicated to the memory of
Professor Xian Huang
1. Introduction
Garratt has reported a bisallene-diradical mechanism6 which
may account for the formation of 2a. To examine the possible
Thiophene-based compounds are of interest to the organic com-
munity over the past decades because of their intrinsic properties
such as drug activity, wide range of photobiological activity, lumi-
nescence, redox activity, and electron transport.1,2 In this regard,
polycyclic S-heterocycles could be useful for various applications
in organic chemistry.3
O
O
O
Ph
Ph
Ph
Et3N
[4 + 2]
S
Ga(OTf)3
Sulfur-assisted propargyl–allenyl isomerization has been a use-
ful and efficient method to thio-allenes, which may be used as an
‘activated olefin’ to achieve cyclization.4 Recently, we reported a sul-
fur-assisted propargyl–allenyl isomerizations intramolecular [4+2]
cycloaddition promoted by triethylamine and Ga(OTf)3 (Scheme 1).5
We found that due to the weak basicity of triethylamine, the
presence of electron-withdrawing group is essential to trigger the
propargyl–allenyl isomerization. It may be reasonably envisioned
that (3-cyclohexenylprop-2-ynyl) (3-p-tolylprop-2-ynyl)sulfane
(1a) could undergo cyclization promoted by the stronger bases.
Stimulated by this proposal, we initiated our study by treating 1a
with various bases. After careful examination, we isolated 4-p-to-
lyl-4,4a,5,6,7,8-hexahydronaphtho[2,3-c]thiophene (2a) in 82%
yield by treatment of 1a with DBU in toluene at 90 °C. The stereo-
chemistry of 2a was established by NOESY experiment which clearly
showed an NOE effect between the Ha and Hb (Scheme 2).
S
S
Scheme 1.
NOE
Hb
Ha
DBU, toluene
S
90 oC, 12h
82%
S
2a
1a
Scheme 2.
This unexpected result and the fact that 2a could be obtained in
good yield without the promotion of Lewis acid attracted us to
hypothesize that the possible pathway might be different from the
[4+2] cycloaddition shown in Scheme 1. For further confirmation,
we conducted a control experiment by treatment of 1a with DBU
and Ga(OTf)3, and no Lewis acid effect was observed (Scheme 3).
0.05 eq. Ga(OTf)3
2a
DBU, toluene
90 oC, 12h
75%
S
1a
⇑
Corresponding author. Fax: +86 571 88920271.
E-mail address: zhouhw@zju.edu.cn (H. Zhou).
Scheme 3.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.09.063

G. Xu et al. / Tetrahedron Letters 51 (2010) 6240–6242
6241
D
DBU, toluene
D
S
methanol-d4
S
S
D
D
1a
(86%)
D
D
S
S
2a
D
D (80%)
Scheme 4.
Table 1
Synthesis of tricyclic thiophene derivativesa
Table 1 (continued)
Entry
Substrate
Time (h)
Product
Yield (%)
Entry
Substrate
Time (h)
Product
Yield (%)
1
12
82
S
S
S
S
1f
2a
1a
2f
7
12
71
2
10
75
S
S
S
S
1b
2g
1g
2b
Cl
Cl
8
15
77
3
12
68
S
S
S
S
2h
1h
Cl
2c
1c
1d
Cl
4
10
73
S
9
16
63
S
S
S
2d
1i
1j
2i
2j
Cl
Cl
5
6
10
16
71
64
10
24
0
S
S
S
S
2e
1e
a
Substrate 1 (0.5 mmol) and DBU (0.6 mmol) in toluene (2 mL) at 90 °C under a
N2 atmosphere.

6242
G. Xu et al. / Tetrahedron Letters 51 (2010) 6240–6242
pathway for our reaction, we treated 1a with DBU in the methanol-
d4/toluene (1:10) and observed that both the protons of the thio-
phene ring were deuterated, demonstrating that the bisallene-
diradical mechanism is more plausible because the monoallene
intermediate and the [4+2] cycloaddition pathway should influ-
ence only one methylene group (Scheme 4).
141.0, 140.8, 137.0, 136.1, 129.1 (double carbon), 128.8 (double
carbon), 120.2, 116.8, 116.4, 50.4, 44.1, 34.8, 33.5, 26.7, 25.9,
21.0; MS (m/z) 280 (M, 60), 281 (M+1, 10); HRMS calcd for
C19H20S: 280.1286. Found: 280.1280.
Acknowledgment
With this result in hand, we examined the scope of the reaction
and obtained tricyclic thiophene derivatives in moderate to good
yields (Table 1).
Financial support was received from the Natural Science Foun-
dation of China (Nos. 20702046, 20972134).
Notably, the (3-cyclohexenylprop-2-ynyl)(hept-2-ynyl)sulfane
(1j) could not offer the expected product (entry 10, Table 1), prob-
ably because the presence of the aryl ring could stabilize the radi-
cal intermediate. Compared to the smooth Diels–Alder cyclization
of 3-(3-(hept-2-ynylthio)prop-1-ynyl)cyclohex-2-enone,5 this re-
sult may give indirectly further proof for the pathway proposed
in Scheme 3.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.09.063.
References and notes
In summary, we have developed a facile and efficient cycliza-
tion for the synthesis of tricyclic thiophene derivatives. As a me-
tal-free process, a result of the ready availability of the starting
materials and the simple and convenient operation, the type of
reaction presented herein has potential utility in organic synthesis.
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To 0.5 mmol of (3-cyclohexenylprop-2-ynyl) (3-p-tolylprop-2-
ynyl)sulfane (1a) was added 0.6 mmol of DBU in 2 mL of toluene
under a N2 atmosphere, followed by heating to 90 °C for 12 h. After
evaporation, chromatography on silica gel (eluent/petroleum
ether) of the reaction mixture afforded the desired product 2a in
a yield of 82%.
Compound 2a: yield: 82%, 115 mg; oil; 1H NMR (400 MHz,
CDCl3) d 7.19–7.14 (m, 4H), 6.84–6.83 (d, J = 2.4 Hz, 1H), 6.33–
6.31 (m, 2H), 3.61–3.58 (d, J = 4.0 Hz, 1H), 2.52–2.45 (m, 1H),
2.48–2.47 (m, 1H), 2.37 (s, 3H), 2.30–2.16 (m, 1H), 1.82–1.78 (m,
2H), 1.38–1.27 (m, 4H); 13C NMR (CDCl3, 100 MHz) d 142.0,
5. Zhou, H.; Zhu, D.; Xie, Y.; Huang, H.; Wang, K. J. Org. Chem. 2010, 75, 2706.
6. Garratt, P. J.; Neoh, S. B. J. Am. Chem. Soc. 1975, 97, 3255.