Effect of water molecules on the cycloaromatization of non-conjugated aromatic tetraynes

Article abstract of DOI:10.1246/bcsj.79.944

Cycloaromatization of the thienyl tetrayne 1, which was prepared in several steps from bis(trimethylsilyl)butadiyne and 3-bromothiophene-2-carbaldehyde, in benzene (0.33 mM) in the presence of molecular sieves 3A at room temperature gave the indeno[2,1-b]thiophene ring-fused 1H-2-benzopyran derivative 10 and indeno[2,1-b]thiophene derivative 11 in 11 and 40% yields, respectively. In contrast, cycloaromatization of 1 in the presence of water molecules at room temperature gave the indeno[2,1-b]thiophene ring-fused 1H-2-benzopyran derivative 10 and the indene ring-fused indeno[2,1-b]thiophene derivative 12 in 82 and 14% yields, respectively. Cycloaromatization of the phenyl tetrayne 9 in the presence of water molecules at room temperature also resulted in a dramatic change in product yields.

Full text of DOI:10.1246/bcsj.79.944

944 Bull. Chem. Soc. Jpn. Vol. 79, No. 6, 944–949 (2006)
Ó 2006 The Chemical Society of Japan
Effect of Water Molecules on the Cycloaromatization
of Non-Conjugated Aromatic 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
Received January 5, 2006; E-mail: kawano@sanken.osaka-u.ac.jp
Cycloaromatization of the thienyl tetrayne 1, which was prepared in several steps from bis(trimethylsilyl)butadiyne
and 3-bromothiophene-2-carbaldehyde, in benzene (0.33 mM) in the presence of molecular sieves 3A at room temper-
ature gave the indeno[2,1-b]thiophene ring-fused 1H-2-benzopyran derivative 10 and indeno[2,1-b]thiophene derivative
11 in 11 and 40% yields, respectively. In contrast, cycloaromatization of 1 in the presence of water molecules at room
temperature gave the indeno[2,1-b]thiophene ring-fused 1H-2-benzopyran derivative 10 and the indene ring-fused
indeno[2,1-b]thiophene derivative 12 in 82 and 14% yields, respectively. Cycloaromatization of the phenyl tetrayne 9
in the presence of water molecules at room temperature also resulted in a dramatic change in product yields.
The cyclization of conjugated polyyne systems such as ene-
diyne (the Bergman cyclization), enyne–allene (the Saito–
Myers cyclization), and enyne–ketene (the Moore cyclization)
forms arene radicals with DNA-cleaving activity.1 While much
effort and most recent investigations have focused on using
these diradical-forming methods for DNA cleavage,2 Grissom
and Calkins first utilized the Bergman cycloaromatization of
1,2-diethynylbenzene derivatives as a means of generating a
radical for carrying out a subsequent radical ring annulation re-
action to give 3,4-dihydrobenz[e]indenes.3–5 Since then, many
examples have been reported using the resulting carbon dirad-
icals for the construction of multicyclic systems.1 We have
recently reported that aromatic acyclic polyyne derivatives
undergo cycloaromatization under mild conditions to afford
polycyclic aromatic compounds such as fluorenol and semi-
bullvalene skeletons.6–11 In the course of elucidating the reac-
tion mechanism into the cycloaromatization of non-conjugated
aromatic polyyne derivatives, we examined the effects of a va-
riety of factors, including solvent, temperature, and concentra-
tion, on the cycloaromatization. We describe herein the effects
of water molecules on the cycloaromatization of the thienyl
tetrayne 1 and phenyl tetrayne 9, which are among the non-
conjugated aromatic tetraynes.12
in methanol at 0 ꢁC, followed by stannylation by tributyltin
chloride in diisopropylamine at room temperature, gave the
stannane 5, which was used for the next step without purifica-
tion because of its instability. The Stille coupling reaction of
5 with commercially available 3-bromothiophene-2-carbalde-
hyde in the presence of [PdCl2(PPh3)2] in toluene at 80 ꢁC gave
the coupling product 6 in 77% yield. Similarly, the reaction of 5
with commercially available 2-bromobenzaldehyde under sim-
ilar conditions gave the coupling product 7 in 90% yield. The
resulting coupling products 6 and 7 were allowed to react with
a monolithio derivative of BTB in ether at ꢂ78 ꢁC to afford
alcohol derivatives 8 and 9 in 91 and 83% yields, respectively.
Dess–Martin oxidation of 8 in dichloromethane (CH2Cl2) at
0 ꢁC gave the desired product 1 in almost quantitative yield.
This compound was also used for the next step without further
purification due to its instability.
Cycloaromatization of Thienyl Tetraynes. In the first
place, we examined the cycloaromatization of the thienyl tet-
rayne 1. The results are summarized in Table 1. Cycloaroma-
tization of 1 in benzene (0.33 mM) in the presence of molecu-
lar sieves 3A at room temperature gave the indeno[2,1-b]thio-
phene ring-fused 1H-2-benzopyran derivative 10 and indeno-
[2,1-b]thiophene derivative 11 in 11 and 40% yields, respec-
tively (Entry 1). The production of 11 suggests that a radical in-
termediate is involved in the cycloaromatization of 1 under an-
hydrous conditions. In contrast, cycloaromatization of 1 in ben-
zene in the presence of excess H2O (100 equivalents) at room
temperature proceeded smoothly to give the indeno[2,1-b]thio-
phene ring-fused 1H-2-benzopyran derivative 10 and indene
ring-fused indeno[2,1-b]thiophene derivative 12 in 82 and 14%
yields, respectively (Entry 2). When deuterium oxide (D2O)
was used instead of H2O, compounds 10 and 12, both of which
were deuterated at the 7- and 6-positions of each molecular
framework, were obtained in 78 and 21% yields, respectively
(Entry 3). No production of 11 under hydrous conditions
suggests that an ionic intermediate is involved in the cyclo-
aromatization of 1 in the presence of H2O. Similarly, we also
examined the cycloaromatization of 1 under higher concentra-
Results and Discussion
Preparation of Non-Conjugated Thienyl Tetraynes and
Phenyl Tetraynes. Scheme 1 provides an outline for the
preparation of the non-conjugated thienyl tetrayne and phenyl
tetrayne derivatives 1 and 9. Trimethylsilyl-monoprotected
butadiynylstannane 2 was prepared in situ by lithiation of bis-
(trimethylsilyl)butadiyne (BTB),13 followed by stannylation
of the resulting monolithio derivative. The Stille coupling reac-
tion of the stannane 2 with iodide 3, which was prepared in 96%
yield by O-methylation of commercially available 2-iodoben-
zyl alcohol in tetrahydrofuran (THF) at 0 ꢁC,7 in the presence of
dichlorobis(triphenylphosphine)palladium(II) [PdCl2(PPh3)2]
in toluene at 110 ꢁC, afforded the coupling product 4 in 99%
yield. Cleavage of the silyl group of 4 with potassium carbonate
Published on the web June 6, 2006; doi:10.1246/bcsj.79.944

T. Kawano et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 6 (2006)
945
b
a
TMS
TMS
TMS
n-Bu3Sn
TMS
MeO
BTB
2
4
CHO
d
c
n-Bu3Sn
Ar
MeO
MeO
5
CHO
CHO
CHO
S
6:
7:
Ar
O
HO
Ar
TMS
TMS
S
e
f
MeO
MeO
8: thiophene-2,3-diyl
9: 1,2-phenylene
1
Scheme 1. Preparation of non-conjugated aromatic tetrayne derivatives. Reagents and Conditions: (a) (1) MeLi–LiBr, Et2O, rt; (2)
n-Bu3SnCl, rt; (b) 1-iodo-(2-methoxymethyl)benzene (3), [PdCl2(PPh3)2], toluene, 110 ꢁC (99%); (c) (1) K2CO3, MeOH, 0 ꢁC, (2)
n-Bu3SnCl, diisopropylamine, rt; (d) 3-bromothiophene-2-carbaldehyde (for 6), 2-bromobenzaldehyde (for 7), [PdCl2(PPh3)2],
toluene, 80 ꢁC (77% for 6, 90% for 7); (e) MeLi–LiBr, BTB, Et2O, ꢂ78 ꢁC (91% for 8, 83% for 9); (f) (for 8) Dess–Martin period-
inane, CH2Cl2, 0 ꢁC (99%).
Table 1. Cycloaromatization of Thienyl Tetraynes
TMS
TMS
O
O
S
S
OMe
O
O
TMS
H(D)
S
TMS
H(D)
10
11
benzene, rt, 48 h
MeO
O
1
S
OMe
12
Yield/%a)
Entry
Concentration/mM
Conditions
MS 3A
H2O (100 equiv)
D2O (100 equiv)
MS 3A
10
11
12
b)
1
2
3
4
5
6
0.33
0.33
0.33
50
50
50
11
82
78 (90)c)
24
84
40
—
—
17
—
—
—
14
21 (78)
—
12
15 (77)
H2O (100 equiv)
D2O (100 equiv)
83 (96)
1
a) Isolated yield. b) Not detected. c) Deuteration degree determined by H NMR integration in
parenthesis.
tion (50 mM). However, no concentration-dependence for cy-
cloaromatization of 1 under similar conditions was observed
(Entries 4–6).
Cycloaromatization of Phenyl Tetraynes. We next ex-
amined the cycloaromatization of the phenyl tetrayne 9. The
results are summarized in Table 2. Cycloaromatization of 9
in benzene (0.33 mM) in the presence of molecular sieves
3A at room temperature gave the fluorene ring-fused 1H-2-
benzopyran derivatives 13 and 14 in lower yields of 23 and
11%, respectively (Entry 1). In contrast, cycloaromatization of
9 in benzene in the presence of excess H2O (100 equivalents)
at room temperature proceeded smoothly to give 13 and 14 in
73 and 5% yields, respectively (Entry 2). When D2O was used
instead of H2O, compounds 13 and 14, both of which were
deuterated at the 7-position of each molecular framework,
were obtained in 71 and 4% yields, respectively (Entry 3).

946 Bull. Chem. Soc. Jpn. Vol. 79, No. 6 (2006)
Table 2. Cycloaromatization of Phenyl Tetraynes
Effect of Water on the Cycloaromatization
TMS
TMS
HO
TMS
HO
MeO
benzene, rt, 72 h
O
O
MeO
H(D)
H(D)
9
13
14
Yield/%a)
Entry
Concentration/mM
Conditions
MS 3A
H2O (100 equiv)
D2O (100 equiv)
MS 3A
H2O (100 equiv)
D2O (100 equiv)
1
13
14
1
2
3
4
5
6
0.33
0.33
0.33
50
50
50
23
73
71 (90)b)
20
40
11
5
4 (92)
24
54
35 (94)
45 (95)
a) Isolated yield. b) Deuteration degree determined by H NMR integration in parenthesis.
TMS
TMS
O
O
O
TMS
S
S
S
O
OMe
MeO
1
10 (90%)
12 (9%)
benzene (50 mM)
H2O (100 eq.)
rt, 48 h
TMS
TMS
TMS
HO
MeO
HO
O
O
O
13
14 (43%)
13 (50%)
Scheme 2. Cycloaromatization of the thienyl tetrayne 1 in the presence of the fluorene ring-fused 1H-2-benzopyran derivative 13.
In this reaction, no production of a Diels–Alder adduct such as
11 in the cycloaromatization of 1 under hydrous conditions
suggests that ionic species are a key intermediate in the cyclo-
aromatization of 9. Similarly, we also examined the cycloaro-
matization of 9 under higher concentration (50 mM). Increas-
ing the concentrations of the cyclization dramatically changed
the yield of compound 14 up to ca. 50% yield, though no
dependence on concentration for cycloaromatization of 9 un-
der anhydrous conditions was observed (Entries 4–6).
Cycloaromatization of the Thienyl Tetrayne 1 in the
Presence of the Fluorene Ring-Fused 1H-2-Benzopyran
13. To examine the mechanism for the formation of 14 in de-
tail, we investigated the cycloaromatization of the thienyl tet-
rayne 1 in the presence of the fluorene ring-fused 1H-2-benzo-
pyran derivative 13, as shown in Scheme 2. Cycloaromatiza-
tion of 1 in benzene (50 mM) in the presence of an equimolar
amount of 13 and excess H2O (100 equivalent) gave the meth-
ylated fluorene ring-fused 1H-2-benzopyran derivative 14 in
43% yield, as well as 90% yield of the indeno[2,1-b]thiophene
ring-fused 1H-2-benzopyran derivative 10, and 9% yield of the
indene ring-fused indeno[2,1-b]thiophene derivative 12, along
with recovery (50%) of 13. These results indicate that cyclo-
aromatization of 9 under higher concentration (50 mM) in the
presence of H2O consequently takes place in a mode of inter-
molecular reaction, and that compound 14 is obtained by meth-
ylation of the hydroxy functional group of 13.
Plausible Reaction Mechanism for the Cycloaromatiza-
tion. A plausible mechanism for the cycloaromatization of
non-conjugated aromatic tetraynes is illustrated in Scheme 3.
Activation of the non-conjugated tetrayne system is triggered
by cyclization of the position ‘‘a’’ in the initial step, followed
by cyclization of the position ‘‘b’’ to the (ꢀ,ꢀ)-1,2-didehydro-
benzene diradical 16 via the diradical 15. Diels–Alder reaction
of 16 with benzene as a solvent yields the indenothiophene de-
rivative 11. Cyclization of compound 16 can affords the inter-
mediate 17, which is made up of five rings. The intermediate
17 is rapidly protonated at the 7-position by a proton source
such as water molecules. Then, the following demethylation
gives indenothiophene 10 or fluorene ring-fused 1H-2-benzo-
pyran derivative 13. Methylation of 13 yields the methylated
fluorene ring-fused 1H-2-benzopyran derivative 14. Abstrac-
tion of a proton in the pyran ring of 17 after protonation, fol-
lowed by ring-contraction to a five-membered ring from a six-
membered ring produces the fluorene ring-fused indenothio-

T. Kawano et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 6 (2006)
947
TMS
TMS
R'
R
R'
TMS
R'
R
R
b
a
Ar
Ar
OMe
Ar
MeO
15
MeO
16
R, R': =O (For 1)
R: H, R': OH (For 9)
TMS
1
R'
R
12
5
H
O
Ar
7
H
Me
Diels-Alder
Reaction
17
Protonation at the 7-position
Demethylation
TMS
Deprotonation + Ring-contraction
TMS
R'
O
R
S
O
Ar
OMe
10 or 13
12
TMS
Methylation
(for 13)
O
TMS
S
OMe
MeO
11
O
14
S
Ar
,
Scheme 3. A plausible mechanism for the construction of the polycyclic aromatic compounds 10–14.
phene 12. In view of considering the plausible reaction mech-
anism we suggested, no production of Diels–Alder product on
cycloaromatization of the phenyl tetrayne 9 may be because
the intermediate 16 is unstable and chemical equilibrium shifts
to 17 to a great extent. Lower yields of products for cycloaro-
matization of 9 under anhydrous conditions may be also caused
by the instability of 16. No ring-contraction product like com-
pound 12 in the cycloaromatization of 9 was obtained because a
benzylic hydroxy proton that is located at the 12-position of 17
is more acidic than the proton, which is located at the 5-position
of 17. Demethylation would be caused by the hydroxy function-
al group of 17. It can be concluded that water molecules act as
an important factor for the displacement of the equilibrium to
17 and for the stabilization of the intermediate 17.
that water molecules play an important role in the cycloaroma-
tization of non-conjugated aromatic tetraynes. Furthermore,
we have found that cycloaromatization of non-conjugated tet-
raynes in this study takes place in a radical or ionic reaction
mode according to the reaction conditions.
Experimental
General. All reactions were carried out under an argon atmo-
sphere with dry solvents under anhydrous conditions unless other-
wise noted. Solvents and reagents were purified by literature
methods where necessary.14 All melting points were determined
on a Yanagimoto micro melting point apparatus (Yanaco MP-
500D) and are uncorrected. Infrared (IR) spectra were recorded
on a Perkin-Elmer system 2000 FT-IR spectrometer. UV absorp-
tion spectra were obtained using a Hitachi 260-30 spectrophotom-
eter. 1H NMR spectra were recorded on a JEOL JNM-LA400
(400 MHz) spectrometer; chemical shifts (ꢁ) are reported in parts
per million relative to tetramethylsilane (TMS). Splitting patterns
are designated as s, singlet; d, doublet; t, triplet; q, quartet; m,
Conclusion
In conclusion, we have demonstrated that cycloaromatiza-
tion of non-conjugated aromatic tetraynes proceeds smoothly
to give a series of new polycyclic aromatic compounds, and

948 Bull. Chem. Soc. Jpn. Vol. 79, No. 6 (2006)
Effect of Water on the Cycloaromatization
multiplet; br, broad; dsp, double of septets. Mass spectra (MS)
were recorded on a JEOL JMS-600 mass spectrometer. Elemental
analyses were performed by the Materials Analysis Center of the
Institute of Scientific and Industrial Research, Osaka University.
Column chromatography was performed on Merck silica gel 60.
Compound 3 was prepared from commercially available 2-iodo-
benzyl alcohol according to the literature procedure.8
J ¼ 7:8 Hz, 1H), 7.29 (t, J ¼ 7:8 Hz, 1H), 7.26 (d, J ¼ 4:9 Hz,
1H), 4.66 (s, 2H), 3.48 (s, 3H); IR (KBr): 2350, 2200, 1655
cmꢂ1; FABMS (NBA) m=z 281 ½ðM þ HÞꢃþ; Found: C, 72.61;
H, 4.11; S, 11.45%. Calcd for C17H12O2S: C, 72.83; H, 4.31; S,
11.44%.
2-{4-[2-(Methoxymethyl)phenyl]buta-1,3-diynyl}benzalde-
hyde (7). This compound was prepared from the stannane 5 and
2-bromobenzaldehyde according to the method used for the prep-
aration of 6. Colorless needles; yield 90%; mp 53.5–54.0 ꢁC;
1H NMR (400 MHz, CDCl3) ꢁ 10.52 (s, 1H), 7.94–7.92 (m, 1H),
7.66–7.25 (m, 7H), 4.66 (s, 2H), 3.48 (s, 3H); IRþ(KBr): 2210,
1700 cmꢂ1; FABMS (NBA) m=z 298 ½ðM þ HÞꢃ ; Found: C,
83.33; H, 5.04%. Calcd for C19H14O2: C, 83.19; H, 5.14%.
1-(3-{4-[2-(Methoxymethyl)phenyl]buta-1,3-diynyl}thiophen-
2-yl)-5-(trimethylsilyl)penta-2,4-diyn-1-ol (8). To a solution of
bis(trimethylsilyl)butadiyne (1.36 g, 7.00 mmol) in ether (15 mL)
was added dropwise a solution of methyllithium–lithium bromide
complex (1.5 M, 2.33 mL, 3.50 mmol) in ether at room tempera-
ture. After being stirred at the same temperature for 5 h, the result-
ing lithium acetylide was cooled to ꢂ78 ꢁC. The lithium acetylide
was added dropwise to a solution of 6 (470 mg, 1.75 mmol) in dry
ether (15 mL)–THF (5.0 mL), and then the reaction mixture was
stirred at room temperature for 3 h. After treatment with saturated
aqueous ammonium chloride, the reaction mixture was extracted
with ether. The organic layer was washed with H2O and brine,
and then dried over anhydrous MgSO4. After removal of the sol-
vent, the residue was purified by column chromatography (silica
gel, hexane–AcOEt) to give 8 (642 mg, 91%) as a pale yellow
1-Methoxymethyl-2-[4-(trimethylsilyl)buta-1,3-diynyl]ben-
zene (4). To a solution of bis(trimethylsilyl)butadiyne (2.64 g,
13.6 mmol) in ether (15 mL) was added dropwise a solution of
methyllithium–lithium bromide complex (1.5 M, 6.05 mL, 9.08
mmol) in ether at room temperature. After being stirred at the
same temperature for 5 h, tributyltin chloride (2.46 mL, 9.08 mmol)
was added to the resulting reaction mixture at room temperature,
and the reaction mixture was stirred at the same temperature for
2 h. After being concentrated in vacuo, the resulting residue was
diluted with benzene, and then filtered through a pad of Celite.
The filtrate was evaporated to dryness under reduced pressure to
give the trimethylsilyl-monoprotected butadiynylstannane 2. To
a solution of 2 in toluene (40 mL) were added iodide 3 (150 mg,
6.05 mmol), and dichlorobis(triphenylphosphine)palladium(II)
[PdCl2(PPh3)2] (211 mg, 0.303 mmol) at 0 ꢁC. After being stirred
at 110 ꢁC for 2 h, the resulting reaction mixture was cooled to
room temperature, and treated with 10% aqueous potassium fluo-
ride. After being stirred for 0.5 h and filtrated through a pad of
Celite, the resulting mixture was extracted with benzene. The or-
ganic layer was washed with H2O and brine, and then dried over
anhydrous MgSO4. After removal of the solvent, the residue was
purified by column chromatography (silica gel, hexane–AcOEt) to
give 4 (1.47 g, 99%) as a brown oil: 1H NMR (400 MHz, CDCl3) ꢁ
7.48–7.43 (m, 2H), 7.36–7.32 (m, 1H), 7.22 (m, 1H), 4.60 (s, 2H),
3.24 (s, 3H), 0.23 (s, 9H); IR (neat): 2350 cmꢂ1; FABMS (NBA)
m=z 243 ½ðM þ HÞꢃþ; Found: C, 74.22; H, 7.53%. Calcd for
C15H18OSi: C, 74.33; H, 7.49%.
1
oil; H NMR (400 MHz, CDCl3) ꢁ 7.54 (d, J ¼ 7:6 Hz, 1H), 7.49
(d, J ¼ 7:6 Hz, 1H), 7.40 (t, J ¼ 7:6 Hz, 1H), 7.27 (t, J ¼ 7:6 Hz,
1H), 7.26 (d, J ¼ 5:1 Hz, 1H), 7.08 (d, J ¼ 5:1 Hz, 1H), 6.00 (d,
J ¼ 5:4 Hz, 1H), 4.66 (s, 2H), 3.49 (s, 3H), 2.53 (d, J ¼ 5:4 Hz,
1H), 0.20 (s, 9H); IR (neat): 3340, 2350, 2100 cmꢂ1; FABMS
(NBA) m=z 403 ½ðM þ HÞꢃþ; Found: C, 71.40; H, 5.39; S, 7.78%.
Calcd for C24H22O2SSi: C, 71.60; H, 5.51; S, 7.96%.
3-{4-[2-(Methoxymethyl)phenyl]buta-1,3-diynyl}thiophene-
2-carbaldehyde (6). To a solution of 4 (1.00 g, 4.06 mmol) in
methanol (15 mL) was slowly added potassium carbonate (57.0
mg, 0.41 mmol) at 0 ꢁC, and then the resulting reaction mixture
was stirred at the same temperature for 1 h. After being neutralized
by 1 M hydrochloric acid, the mixture was extracted with ether.
The oraganic layer was washed with H2O and brine, and then
dried over anhydrous MgSO4. After removal of the solvent, the
residue was purified by column chromatography (benzene) to give
the de-protected compound. The resulting compound was added to
a mixture of N,N-diisopropylethylamine (8 mL) and tributyltin
chloride (2.20 mL, 8.12 mmol) at 0 ꢁC. After being stirred at the
same temperature for 2 h, the reaction mixture was evaporated
in vacuo. The residue was diluted with benzene, filtrated through
a pad of Celite, and then evaporated to dryness under reduced
pressure to afford the stannane 5. To a solution of 5 and commer-
cially available 3-bromothiophene-2-carbaldehyde in toluene
(30 mL) was added [PdCl2(PPh3)2] (119 mg, 0.169 mmol). After
being heated under reflux for 2 h, the reaction mixture was cooled
to room temperature, and treated with 10% aqueous potassium
fluoride. After being stirred for 0.5 h and filtrated through a pad
of Celite, the resulting mixture was extracted with benzene. The
organic layer was washed with H2O and brine, and then dried over
anhydrous MgSO4. After removal of the solvent, the residue was
purified by column chromatography (silica gel, hexane–AcOEt) to
give 6 (698 mg, 77%) as pale yellow needles; mp 64.5–65.5 ꢁC;
1H NMR (400 MHz, CDCl3) ꢁ 10.17 (s, 1H), 7.70 (d, J ¼ 4:9 Hz,
1H), 7.56 (d, J ¼ 7:8 Hz, 1H), 7.50 (d, J ¼ 7:8 Hz, 1H), 7.42 (t,
1-(2-{4-[2-(Methoxymethyl)phenyl]buta-1,3-diynyl}phenyl)-
5-(trimethylsilyl)penta-2,4-diyn-1-ol (9). This compound was
prepared from the aldehyde 7 according to the method used for
the preparation of 8. Pale yellow oil; yield 83%; 1H NMR (400
MHz, CDCl3) ꢁ 7.69 (d, J ¼ 7:8 Hz, 1H), 7.55 (d, J ¼ 7:8 Hz,
2H), 7.48 (d, J ¼ 7:3 Hz, 1H), 7.44–7.36 (m, 2H), 7.34–7.25 (m,
2H), 5.94 (s, 1H), 4.67 (s, 2H), 3.52 (s, 3H), 2.81 (s, 1H), 0.19
(s, 9H); IR (KBr): 3350, 2220, 2100 cmꢂ1; FABMS (NBA) m=z
397 ½ðM þ HÞꢃþ; Found: C, 78.52; H, 5.89%. Calcd for C26H24-
O2Si: C, 78.75; H, 6.10%.
1-(3-{4-[2-(Methoxymethyl)phenyl]buta-1,3-diynyl}thiophen-
2-yl)-5-(trimethylsilyl)penta-2,4-diyn-1-one (1). To a solution
of 8 (200 mg, 0.497 mmol) in dry CH2Cl2 (80 mL) was added
the Dess–Martin reagent (1.05 g, 2.49 mmol) at 0 ꢁC. After being
stirred at the same temperature for 0.5 h, the reaction mixture was
poured into saturated aqueous sodium hydrogencarbonate, and
then extracted with CH2Cl2. The organic layer was washed with
H2O and brine, and then dried over anhydrous MgSO4. After re-
moval of the solvent, the residue was purified by column chroma-
tography (silica gel, hexane–AcOEt) to give 1 (198 mg, 99%) as a
yellow powder; 1H NMR (400 MHz, CDCl3) ꢁ 7.62 (d, J ¼ 5:1
Hz, 1H), 7.54 (d, J ¼ 7:8 Hz, 1H), 7.49 (d, J ¼ 7:8 Hz, 1H), 7.40
(t, J ¼ 7:8 Hz, 1H), 7.26 (d, J ¼ 5:1 Hz, 1H), 7.24 (t, J ¼ 7:8 Hz,
1H), 4.67 (s, 2H), 3.49 (s, 3H), 0.14 (s, 9H); FABMS (NBA) m=z
401 ½ðM þ HÞꢃþ. This compound was used for the next step with-
out further purification due to its instability.
Cycloaromatization of 1 under Anhydrous Conditions. To

T. Kawano et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 6 (2006)
949
a solution of 1 (100 mg, 0.248 mmol) in dry benzene (750 mL
or 5.0 mL) was added molecular sieves 3A at room temperature.
After being stirred at room temperature for 48 h, the resulting re-
action mixture was filtrated, and then the filtrate was evaporated in
vacuo to give an oily residue. The residue was purified by column
chromatography (silica gel, hexane–AcOEt) to give 10 and 11.
Indeno[2,1-b]thiophene Ring-Fused 1H-2-Benzopyran 10:
Yellow plates; mp 129.4–129.8 ꢁC; 1H NMR (400 MHz, CDCl3)
ꢁ 8.79 (d, J ¼ 7:6 Hz, 1H), 7.71 (d, J ¼ 4:6 Hz, 1H), 7.40–7.30
(m, 2H), 7.20 (d, J ¼ 7:6 Hz, 1H), 7.10 (d, J ¼ 4:6 Hz, 1H), 6.86
of 1 (100 mg, 0.248 mmol) in dry benzene (50 mL) were added
H2O (0.45 mL, 100 equivalent) and 13 (95 mg, 0.248 mmol) at
room temperature. After being stirred at the same temperature
for 48 h, the resulting solution was evaporated in vacuo to give
an oily residue. The residue was purified by column chromatogra-
phy (silica gel, hexane–AcOEt) to give 10 (90%), 12 (9%), and 14
(43%), along with the recovery of 13 (50%).
We thank the Materials Analysis Center of ISIR-Sanken,
Osaka University for assisting us with elemental analysis.
(s, 1H), 5.05 (s, 2H), 0.34 (s, 9H); IR (KBr): 2150, 1700 cmꢂ1
;
FABMS (NBA) m=z 387 ½ðM þ HÞꢃþ; Found: C, 71.20; H, 4.65;
References
S, 8.47%. Calcd for C23H18O2SSi: C, 71.47; H, 4.69; S, 8.30%.
Indeno[2,1-b]thiophene 11:
Yellow powder; mp 74.3–
1
2
K. K. Wang, Chem. Rev. 1996, 96, 207.
For examples, see: a) A. L. Smith, K. C. Nicolaou, J. Med.
75.3 ꢁC; H NMR (400 MHz, CDCl3) ꢁ 7.78 (d, J ¼ 4:9 Hz, 1H),
7.55 (d, J ¼ 7:3 Hz, 1H), 7.44 (t, J ¼ 7:3 Hz, 1H), 7.42 (d, J ¼
4:9 Hz, 1H), 7.36 (t, J ¼ 7:3 Hz, 1H), 7.07 (d, J ¼ 7:3 Hz, 1H),
6.88–6.85 (m, 2H), 6.72–6.67 (m, 2H), 5.28 (t, J ¼ 5:9 Hz, 1H),
4.54 (t, J ¼ 5:9 Hz, 1H), 4.22 (d, J ¼ 12:2 Hz, 1H), 4.13 (d, J ¼
12:2 Hz, 1H), 3.20 (s, 3H), ꢂ0:04 (s, 9H); IR (KBr): 2140,
1700 cmꢂ1; FABMS (NBA) m=z 479 ½ðM þ HÞꢃþ; Found: C,
75.04; H, 5.23; S, 6.77%. Calcd for C30H26O2SSi: C, 75.27; H,
5.47; S, 6.70%.
1
Chem. 1996, 39, 2103. b) K. C. Nicolaou, W.-M. Dai, Angew.
Chem., Int. Ed. Engl. 1991, 30, 1387. c) K. C. Nicolaou, P.
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Kuo, N. S. Finney, J. Am. Chem. Soc. 1989, 111, 8057. f) T. P.
Lackhart, P. B. Comita, R. G. Bergman, J. Am. Chem. Soc.
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J. Org. Chem. 1997, 62, 603.
4
5422.
5
2315.
6
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41, 1447.
8
39, 6923.
Cycloaromatization of 1 in the Presence of Water. To a
solution of 1 (100 mg, 0.248 mmol) in dry benzene (750 mL or
5.0 mL) was added H2O (0.45 mL, 100 equivalents) at room tem-
perature. After being stirred at room temperature for 48 h, the re-
sulting solution was evaporated in vacuo to give an oily residue.
The residue was purified by column chromatography (silica gel,
hexane–AcOEt) to give 10 and 12.
J. W. Grissom, D. Klingberg, D. Huang, B. J. Slattery,
J. W. Grissom, T. L. Calkins, J. Org. Chem. 1993, 58,
J. W. Grissom, T. L. Calkins, Tetrahedron Lett. 1992, 33,
T. Kawano, H. Inai, K. Miyawaki, I. Ueda, Tetrahedron
Indene Ring-Fused Indeno[2,1-b]thiophene 12:
Yellow
plates; mp 202.5–203.0 ꢁC; 1H NMR (400 MHz, CDCl3) ꢁ 8.60
(d, J ¼ 7:1 Hz, 1H), 7.74 (d, J ¼ 4:6 Hz, 1H), 7.60 (d, J ¼ 7:1
Hz, 1H), 7.43 (t, J ¼ 7:1 Hz, 1H), 7.40 (s, 1H), 7.37 (t, J ¼ 7:1
Hz, 1H), 7.13 (d, J ¼ 4:6 Hz, 1H), 5.53 (s, 1H), 3.03 (s, 3H),
0.41 (s, 9H); IR (KBr): 2150, 1700 cmꢂ1; FABMS (NBA) m=z
401 ½ðM þ HÞꢃþ; Found: C, 71.69; H, 4.88; S, 7.88%. Calcd for
C24H20O2SSi: C, 71.96; H, 5.03; S, 8.01%.
K. Miyawaki, T. Kawano, I. Ueda, Tetrahedron Lett. 2000,
K. Miyawaki, T. Kawano, I. Ueda, Tetrahedron Lett. 1998,
9
39, 6491.
T. Kawano, C. Ikemoto, I. Ueda, Tetrahedron Lett. 1998,
Cycloaromatization of Non-Conjugated Phenyl Tetrayne 9.
Compounds 13 and 14 were obtained according to the methods for
the cycloaromatization of 1.
10 K. Miyawaki, R. Suzuki, T. Kawano, I. Ueda, Tetrahedron
Lett. 1997, 38, 3943.
Fluorene Ring-Fused 1H-2-Benzopyran 13: Yellow plates;
mp 63.5–64.0 ꢁC; 1H NMR (400 MHz, CDCl3) ꢁ 8.78–8.76 (m,
1H), 7.70–7.68 (m, 2H), 7.63–7.61 (m, 1H), 7.43–7.41 (m, 2H),
7.30 (s, 1H), 7.23–7.21 (m, 2H), 5.84 (d, J ¼ 3:3 Hz, 1H), 5.05 (d,
J ¼ 12:9 Hz, 1H), 5.04 (d, J ¼ 12:9 Hz, 1H), 3.38 (d, J ¼ 3:4 Hz,
1H), 0.36 (s, 9H); IR (KBr): 3565, 2140 cmꢂ1; FABMS (NBA)
m=z 383 ½ðM þ HÞꢃþ; Found: C, 78.47; H, 5.52%. Calcd for
C25H22O2Si: C, 78.50; H, 5.80%.
11 The thienyl tetrayne 1, which has a carbonyl functional
group, was selected because 1 can cycloaromatize at room temper-
ature, whereas no cycloaromatization of thienyl tetrayne possess-
ing a hydroxy group takes place at room temperature. The phenyl
tetrayne 9, which has a hydroxy functional group, was selected be-
cause 9 can cycloaromatize at room temperature, whereas cyclo-
aromatization of phenyl tetrayne possessing a carbonyl group rap-
idly decomposes at room temperature.
Methylated Fluorene Ring-Fused 1H-2-Benzopyran 14:
Brown oil; 1H NMR (400 MHz, CDCl3) ꢁ 8.91–8.89 (m, 1H),
7.41–7.19 (m, 8H), 5.63 (s, 1H), 5.06 (d, J ¼ 12:7 Hz, 1H), 4.99
(d, J ¼ 12:7 Hz, 1H), 3.27 (s, 3H), 0.33 (s, 9H); IR (KBr): 2210,
1700 cmꢂ1; FABMS (NBA) m=z 397 ½ðM þ HÞꢃþ; Found: C,
78.70; H, 6.35%. Calcd for C26H24O2Si: C, 78.75; H, 6.10%.
Cycloaromatization of 1 in the Presence of 13. To a solution
12 A. B. Holmes, C. L. D. Jenning-White, A. H. Schulthess,
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13 R. C. Larock, L. W. Harrison, J. Am. Chem. Soc. 1984,
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14 Purification of Laboratory Chemicals, ed. by D. D. Perrin,
W. L. Armarego, Pergamon, New York, 1988.