Synthesis of indenothiophenone derivatives by cycloaromatization of non-conjugated thienyl tetraynes

Article abstract of DOI:10.1016/j.tetlet.2005.01.005

Non-conjugated thienyl tetrayne derivatives 1-3 are prepared as novel building block for the construction of indenothiophenone derivatives. Oxidation of 1-3, followed by cycloaromatization of the corresponding ketone derivatives 13-15 proceeds smoothly to afford indenothiophenone derivatives 16-21 in good yields.

Full text of DOI:10.1016/j.tetlet.2005.01.005

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1233–1236
Synthesis of indenothiophenone derivatives by
cycloaromatization of non-conjugated thienyl tetraynes
Tomikazu Kawano,* Hiroki Inai, Kazuhiro Miyawaki and Ikuo Ueda
The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Received 15 December 2004; revised 27 December 2004; accepted 5 January 2005
Available online 18 January 2005
Abstract—Non-conjugated thienyl tetrayne derivatives 1–3 are prepared as novel building block for the construction of indenothio-
phenone derivatives. Oxidation of 1–3, followed by cycloaromatization of the corresponding ketone derivatives 13–15 proceeds
smoothly to afford indenothiophenone derivatives 16–21 in good yields.
Ó 2005 Elsevier Ltd. All rights reserved.
Indenothiophene derivatives have received considerable
attention in the field of organometallic chemistry be-
cause their transition metal complexes have been found
to be promising catalysts for olefin polymerization.1,2
The synthesis of indenothiophene derivatives are
achieved in good yields by Wolff–Kishner reduction of
indenothiophenone derivatives. Therefore, development
of new synthetic methods for the preparation of indeno-
thiophenone derivatives would lead us to novel indeno-
thiophene and its transition metal complexes. However,
far less attention has been devoted to their synthesis in
the literature to date.3–7 Recently, we reported that aro-
matic acyclic polyyne derivatives underwent cycloaro-
matization under mild conditions to afford polycyclic
aromatic compounds such as fluorenol and semibullva-
lene skeletons.8–11 In this study, new non-conjugated thi-
enyl tetrayne derivatives 1–3 were designed. These
compounds would be expected to the formation of indeno-
thiophenone skeletons by their oxidation and the fol-
lowing cycloaromatization. We herein describe the syn-
thesis of 1–3 and their cycloaromatization to
indenothiophenone skeletons (Fig. 1).
Stille coupling reaction was selected as a key step for the
synthesis of 1–3.12,13 Scheme 1 shows an outline for
preparation of 1–3. Trimethylsilyl-monoprotected buta-
diynylstannane (TRIBS) was prepared in situ by lithia-
tion of bis(trimethylsilyl)butadiyne (BTB),14 followed by
stannylation of the resulting monolithio derivative. Buta-
diynylthiophene derivative 4 was prepared in 89% yield
by the Stille coupling reaction of TRIBS with commer-
cially available 3-bromothiophene in the presence of
1:
2:
Ar =
Ar =
S
O
HO
TMS
Ar
Me
S
S
N
Boc
Ar =
Indenothiophenone skeleton
3:
MeO
Figure 1.
Keywords: Cycloaromatization; Tetrayne; Indene; Thiophene.
*
Corresponding author. Tel.: +81 6 6879 8472; fax: +81 6 6879 8474; e-mail: kawano@sanken.osaka-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.005

1234
T. Kawano et al. / Tetrahedron Letters 46 (2005) 1233–1236
a
TMS
TMS
n-Bu3Sn
TMS
BTB
TRIBS
S
Br
or
c
b
n-Bu3Sn
Ar
TMS
Ar
I
7 (from 4)
8 (from 5)
9 (from 6)
Ar =
4:
Me
S
N
or
I
Boc
6:
Ar =
5:
Ar =
Me
MeO
MeO
N
Boc
HO
O
CHO
Br
CHO
TMS
Ar
TMS
Ar
e
d
f
S
S
S
S
Ar
10 (from 7)
11 (from 8)
12 (from 9)
1 (from 10)
2 (from 11)
3 (from 12)
13 (from 1)
14 (from 2)
15 (from 3)
Scheme 1. Preparation of compounds 1–3. Reagents and conditions: (a) (1) MeLi–LiBr, ether, rt; (2) n-Bu3SnCl, rt; (b) 3-bromothiophene (for 4) or
2-(N-tert-butoxycarbonyl-N-methyl)aminomethyl)-1-iodobenzene (for 5) or 2-(methoxymethyl)-1-iodobenzene (for 6), TRIBS, PdCl2(PPh3)2,
toluene, 110 °C; (c) (1) K2CO3, MeOH, 0 °C, (2) n-Bu3SnCl, diisopropylamine, rt; (d) stannanes 7–9, PdCl2(PPh3)2, toluene, 80 °C; (e) MeLi–LiBr,
BTB, ether, À78 °C; (f) Dess–Martin periodinane, CH2Cl2, 0 °C.
dichlorobis(triphenylphosphine)palladium(II), [PdCl2-
(PPh3)2], in toluene at 110 °C. Similarly, butadiynylbenz-
ene derivatives 5 and 6 were prepared in 97% and 99%
yields, respectively, by the Stille coupling reaction of
TRIBS with the corresponding iodobenzene derivatives,
which was prepared according to the literature proce-
dure,15 under the same condition. Cleavage of the silyl
group of 4–6 with potassium carbonate in methanol at
0 °C, followed by stannylation by tri-n-butyltin chloride
in diisopropylamine at room temperature gave stann-
anes 7–9, which were used for the next step without puri-
fication because of their instability. The reaction of
stannanes 7–9 with 3-bromothiophene-2-carbaldehyde
in the presence of PdCl2(PPh3)2 in toluene at 80 °C gave
coupling products 10–12 in 84%, 93% and 77% yields,
respectively. The resulting coupling products 10–12 were
allowed to react with monolithio derivative of BTB in
ether at À78 °C to afford desired products 1–3 in 90%,
91% and 83% yields, respectively.16 Dess–Martin oxida-
tion of 1–3 in dichloromethane at 0 °C gave the corre-
sponding ketone derivatives 13–15 in quantitative
yields. These compounds were also used for the next
step without further purification due to their instability.
and 19 in 82% and 13% yields, respectively. According
to their 1H NMR spectra, compound 18 has been found
to possess two substituents of a methyl group at the 7-
position and a Boc group at the 6-position. On the other
hand, compound 19 has been found to possess a methyl
group at the 6-position. Cycloaromatization of 15 under
the same condition afforded desired products 20 and 21
in 11% and 40% yields, respectively. In contrast to the
cycloaromatization of ketone derivatives 13–15, it is
noteworthy that no desired products were obtained
when a solution of the corresponding alcohol derivatives
1–3 in dry benzene under the same conditions, and that
cycloaromatization of compounds 1–3 at 80 °C gave the
corresponding cyclic alcohol derivatives in 8%, 9% and
6% yields, respectively. The reason why the reactivity
of alcohol derivatives 1–3 were low compared to ketone
derivatives might be that ketone derivatives have conju-
gated ene–yne skeleton, though alcohol derivatives have
non-conjugated one, and then facile overlapping of orbi-
tals in the triple bonds of different substituents easily
makes possible cycloaromatization of ketone
derivatives.
Although we do not have sufficient evidence to discuss
this reaction mechanism in this study, a proposed mech-
anism for the formation of indenothiophenone deriva-
tives in this study is illustrated in Scheme 3.17–22
When a solution of 13 in dry benzene was vigorously
stirred at room temperature under argon atmosphere,
its cycloaromatization proceeded smoothly, after purifi-
cation by silica gel column chromatography (eluent:
hexane–ethyl acetate), to afford indenothiophenone
derivative 16 in 90% yield (Scheme 2). In the presence
of anthracene (20 equiv), the cycloaromatization of 13
led to a Diels–Alder adduct 17 in 88% yield. On the
other hand, cycloaromatization of 14 in dry benzene at
room temperature under argon atmosphere gave iso-
quinoline ring-fused indenothiophenone derivatives 18
At the first step, ketone derivative gives outer-ring
diradical A, which is generated by intramolecular annu-
lation between two butadiynyl functions of ketone
derivatives. The diradical A undergoes further cycliza-
tion to afford an indenothiophenone diradical interme-
diate B. In the case of the cycloaromatization of
compound 13, reaction of B with benzene, which is the

T. Kawano et al. / Tetrahedron Letters 46 (2005) 1233–1236
1235
TMS
O
TMS
O
S
S
benzene (0.33 mM), rt
S
S
13
16 (90%)
TMS
O
S
S
benzene (0.33 mM), rt
17 (88%)
TMS
TMS
O
TMS
O
O
S
benzene (0.33 mM), rt
Me
S
S
N
N
N
Boc
Me Boc
Me
14
18 (82%)
19 (13%)
TMS
TMS
O
TMS
O
O
S
benzene (0.33 mM), rt
S
S
OMe
O
MeO
15
20 (11%)
21 (40%)
Scheme 2. Cycloaromatization to indenothiophenone derivatives.
O
TMS
Indenothiphenone derivatives
S
Ar
TMS
TMS
O
O
Ar
Ar
S
S
A
B
Scheme 3. A proposed mechanism for the construction of indenothiophenone derivatives.
solvent in this reaction, gives product 16. In the presence
of diradical trapping reagent such as anthracene, inter-
mediate B reacts with the reagent to yield desired prod-
uct 17. In the case of the cycloaromatization of
compound 14, intermediate B reacts with nitrogen atom
in substituent of benzene ring to yield multicyclic ring
product 18 associated with migration of methyl group,
along with 19, which is associated with liberation of a

1236
T. Kawano et al. / Tetrahedron Letters 46 (2005) 1233–1236
J = 2.9 Hz), 7.30 (dd, 1H, J = 2.9, 5.1 Hz), 7.25 (d, 1H,
J = 5.1 Hz), 7.18 (d, 1H, J = 5.1 Hz), 7.06 (d, 1H, J =
5.1 Hz), 5.98 (d, 1H, J = 5.4Hz), 2.52 (d, 1H, J = 5.4Hz),
0.20 (s, 9H) ppm. IR (neat) m 3400, 2140, 2100 cmÀ1. Anal.
Calcd for C20H16OS2Si: C, 65.89; H, 4.42; S, 17.59.
Found: C, 65.99; H, 4.64; S, 17.66. FABMS (NBA) m/z
387 [M+Na]+. Compound 2: brown powder, mp 56.7–
58.5 °C, 1H NMR (400 MHz, CDCl3) d 7.54(d, 1H,
J = 7.6 Hz), 7.37 (t, 1H, J = 7.6 Hz), 7.32–7.20 (m, 3H),
7.07 (d, 1H, J = 5.4Hz), 6.00 (d, 1H, J = 5.4Hz), 4.64(s,
2H) 2.91–2.84(m, 3H), 2.72 (s, 1H), 1.50–1.4(m, 9H),
Boc group as carbon dioxide and isobutene. In the case
of compound 15, low yield of compounds 20 and 21
might be due to fast decomposition of intermediate B.
Further studies on the effect of the aromatic moiety
and substituents on the reactivity of the tetraynes will
be reported in detail elsewhere.
In conclusion, we have demonstrated a novel synthetic
method for the preparation of indenothiophenone deriva-
tives by cycloaromatization of non-conjugated thienyl
tetraynes. Further studies on the mechanism of the reac-
tion in this study, and application to other hetero ring-
fused indene derivatives are now in progress.
0.20 (s, 9H) ppm. IR (neat) m 3340, 2220, 2100, 1660 cmÀ1
.
Anal. Calcd for C29H31NO3SSi: C, 69.42; H, 6.22; N, 2.79;
S, 6.39. Found: C, 69.15; H, 6.01; N, 2.65; S, 6.56.
FABMS (NBA) m/z 524[M+Na] +. Compound 3: pale
yellow oil; 1H NMR (400 MHz, CDCl3) d 7.54(d, 1H,
J = 7.6 Hz), 7.49 (d, 1H, J = 7.6 Hz), 7.40 (t, 1H, J =
7.6 Hz), 7.27 (t, 1H, J = 7.6 Hz), 7.26 (d, 1H, J = 5.1 Hz),
7.08 (d, 1H, J = 5.1 Hz), 6.00 (d, 1H, J = 5.4Hz), 4.66 (s,
2H), 3.49 (s, 3H), 2.53 (d, 1H, J = 5.4Hz), 0.20 (s, 9H); IR
Acknowledgments
We thank the Materials Analysis Center of ISIR-San-
ken, Osaka University for assisting us with elemental
analysis.
(neat): 3340, 2350, 2100 cmÀ1
;
Anal. Calcd for
C24H22O2SSi: C, 71.60; H, 5.51; S, 7.96. Found: C,
71.40; H, 5.39; S, 7.78. FABMS (NBA) m/z 402
[(M+H)]+. Calcd for Compound 16: yellow powder, mp
206.0–207.0 °C, 1H NMR (400 MHz, CDCl3) d 7.77 (d,
1H, J = 4.6 Hz), 7.41 (d, 1H, J = 4.6 Hz), 7.40 (d, 1H,
J = 4.9 Hz), 7.25 (s, 1H), 7.11 (d, 1H, J = 4.9 Hz), 6.89–
6.86 (m, 2H), 6.77–6.74(m, 2H), 5.27 (t, 1H, J = 5.9 Hz),
4.94 (t, 1H, J = 5.9 Hz), 0.12 (s, 9H) ppm. IR (neat) m
2150, 1700 cmÀ1. Anal. Calcd for C26H20OS2Si: C, 70.87;
H, 4.57; S, 14.45. Found: C, 70.62; H, 4.49; S, 14.82.
FABMS (NBA) m/z 441 [M+H]+. Compound 18: red
powder, mp 194.5–195.0 °C, 1H NMR (400 MHz, CDCl3)
d 8.67 (d, 1H, J = 7.3 Hz), 7.67 (d, 1H, J = 4.9 Hz), 7.35–
7.30 (m, 2H), 7.20 (d, 1H, J = 7.3 Hz), 7.14(d, 1H,
J = 4.9 Hz), 4.07 (s, 2H) 2.73 (s, 3H), 1.66 (s, 9H), 0.31 (s,
9H) ppm. IR (neat) m 2160, 1720, 1710 cmÀ1. Anal. Calcd
for C29H29NO3SSi: C, 69.70; H, 5.85; N, 2.80; S, 6.42.
Found: C, 69.93; H, 5.89; N, 2.66; S, 6.46. FABMS (NBA)
m/z 500 [M+H]+. Compound 20: yellow plates; mp 129.4–
129.8 °C; 1H NMR (400 MHz, CDCl3) d 8.79 (d, 1H,
J = 7.6 Hz), 7.71 (d, 1H, J = 4.6 Hz), 7.40–7.30 (m, 2H),
7.20 (d, 1H, J = 7.6 Hz), 7.10 (d, 1H, J = 4.6 Hz), 6.86 (s,
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1
1: brown oil, H NMR (400 MHz, CDCl3) d 7.62 (d, 1H,