Expeditious synthesis of papilionaceous molecules containing oligobenzofurans

Article abstract of DOI:10.1055/s-0031-1290066

An efficient synthetic route to construct particular papilionaceous molecules containing oligobenzofurans is described. The key steps involved composing the backbone of the molecules by the Sonogashira cross-coupling reaction, followed by closing the benz

Full text of DOI:10.1055/s-0031-1290066

PAPER
439
Expeditious Synthesis of Papilionaceous Molecules Containing
Oligobenzofurans
Papilionaceous
Molecul
e
es Containi
n
ng Oligoben
-
z
ofuransYu Chai, Er-Qun Yang, Yu-Long Zhang, An-Le Xie, Xiao-Ping Cao*
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University,
Lanzhou, 730000, P. R. of China
Fax +86(931)8912582; E-mail: caoxp@lzu.edu.cn
Received 30 August 2011; revised 28 October 2011
not lead the reaction to completion. Therefore, the simul-
taneous complete construction of oligobenzofuran ring
systems in one molecule is not straightforward. Herein,
we describe our recent efforts to explore a general syn-
Abstract: An efficient synthetic route to construct particular papil-
ionaceous molecules containing oligobenzofurans is described. The
key steps involved composing the backbone of the molecules by the
Sonogashira cross-coupling reaction, followed by closing the ben-
zofuran ring under alkaline conditions, and further aromatic cy- thetic approach for the construction of papilionaceous
clization of a multi-benzofuranyl precursor using ferric chloride as
the oxidative reagent. Basic optical studies (UV-Vis, fluorescence,
and fluorescence quantum yield) have been carried out on the syn-
the Sonogashira cross-coupling reaction, sodium hydrox-
thesized molecules.
molecules 1–3 and symmetric three-fold substituted pre-
cursor 4 (Figure 1) containing benzofurans by employing
ide-promoted ring closing, and further oxidative cycliza-
tion using ferric chloride as the key steps. The
corresponding studies of their optical properties by UV-
Key words: expeditious synthesis, papilionaceous molecule, oli-
gobenzofurans, ferric chloride, oxidative aromatic cyclization
Vis and fluorescence spectroscopy are also presented.
Benzofurans have attracted considerable attention not
O
O
only because of their biological activity and presence in a
variety of significant natural products,1 but also because
they represent important versatile building blocks in or-
ganic chemistry2 and have suitable properties in particular
photoelectric fields.3 Consequently, extensive research on
these types of compounds has triggered much interest
among organic chemists4 and numerous synthetic strate-
gies have been reported for their construction.5 In general,
the standard approach to construct the benzofuran ring
system involved palladium-catalyzed intramolecular cy-
clization. More specifically, one reaction was through the
Claisen rearrangement6 of an allyl aryl ether, followed
O
O
O
O
1
O
O
2
by palladium-catalyzed
intramolecular
oxidative
cyclization5b–d of the corresponding 2-allylphenol. Anoth-
er approach was via palladium-catalyzed heteroannula-
tion of 2-halophenols with terminal or internal alkynes.7
Other methods to construct this benzofuran ring system
also exist.8 These benzofuran compounds usually exhibit-
ed some unique properties, which made them promising
materials in a wide variety of photoelectric fields, and not
surprisingly the number of new products appearing each
year has increased. However, reports available for the
synthesis of dibenzofurans or higher congeners are limit-
ed when compared with the methods available for the syn-
thesis of monobenzofuran, especially for those molecules
containing multi-benzofuranyl groups. Due to more reac-
tion sites, the introduction of multi-benzofuranyl precur-
sors into an aromatic ring may render the neighboring
reaction sites susceptible to reaction inertness, and does
O
O
O
O
3
HO
O
O
OH
O
OH
SYNTHESIS 2012, 44, 439–445
x
x
.x
x
.2
0
1
1
Advanced online publication: 16.01.2012
DOI: 10.1055/s-0031-1290066; Art ID: H85011SS
© Georg Thieme Verlag Stuttgart · New York
4
Figure 1 Structures of molecules 1–4

440
W.-Y. Chai et al.
PAPER
In our synthetic route, arylacetylene 9, a building block
for the construction of the skeleton of the target mole-
cules, was prepared in advance. To combat the probable
insolubility of the target molecules, a tertiary butyl group
was introduced into the backbone. The preparation of
compound 9 began with commercially available 4-tert-
butylphenol (5) (Scheme 1). Thus, the reaction of com-
pound 5 with potassium iodide, hydrogen peroxide (30%),
and concentrated sulfuric acid in methanol9 at room tem-
perature provided compound 6 in 60% yield on a 50 g
scale. The phenolic hydroxy group of compound 6 was
then protected as the acetate by reacting with acetic anhy-
dride in pyridine to afford 7 in 95% yield. Subsequently,
acetate 7 was subjected to a Sonogashira cross-coupling
reaction with (trimethylsilyl)acetylene in the presence
O
O
O
O
O
O
O
O
10, 91%
I
I
I
I
of bis(triphenylphosphine)palladium(II)
chloride
[PdCl2(PPh3)2], CuI, and triethylamine at 40 °C under an
argon atmosphere to provide the desired alkyne 8 in 93%
yield. Next, removal of the trimethylsilyl group with tetra-
n-butylammonium fluoride (TBAF) and acetic acid at
room temperature finished the synthesis of arylacetylene
9 in 92% yield.
12
PdCl2(PPh3)2
9
CuI, Et3N, 40 °C
Br
Br
Br
Br
OH
OH
OAc
Br
I
I
Br
KI, H2O2
Ac2O
13
H2SO4
MeOH, r.t.
60%
Py, r.t.
95%
5
6
7
O
O
O
O
O
OAc
TMS
O
H
TMS
O
O
PdCl2(PPh3)2, CuI, Et3N
40 °C, 93%
O
O
O
O
8
OAc
H
11, 74%
TBAF, AcOH, r.t.
92%
Scheme 2 Synthesis of intermediates 10 and 11
With two important intermediates 10 and 11 in hand, we
started to accomplish the synthesis of compound 1 and in-
vestigated the method to oxidatively close the benzofuran
ring (Scheme 3). First, four-fold substituted alkyne 10 and
sodium hydroxide (NaOH) was dissolved in a mixture of
dichloromethane and methanol (1:1 v/v) at room temper-
ature, resulting in the removal of the acetyl groups. The
reaction was then subjected to a solution of NaOH in
methanol with refluxing to provide the desired four-fold
benzofuran 1 in 49% yield via the two continuous pro-
cesses. However, when subjecting the six-fold substituted
alkyne 11 to the same process, the symmetric 1,3,5-cy-
clized compound 4 was obtained in 77% yield instead of
the fully cyclized compound. From the single-crystal
analysis of the six-fold substituted alkyne 11 (Figure 2),
the precursor of 4, we believe that the simultaneous gen-
9
Scheme 1 Synthesis of the arylacetylene 9
The two key intermediates, four-fold or six-fold substitut-
ed alkynes 10 and 11, were prepared smoothly using the
palladium-catalyzed Sonogashira cross-coupling reaction
(Scheme 2). Here, the cross-coupling reaction of 1,2,4,5-
tetraiodobenzene (12)10 or the commercially available
perbromobenzene (13) with arylacetylene 9 in the pres-
ence of PdCl2(PPh3)2, CuI, and triethylamine at 40 °C un-
der an argon atmosphere provided the desired alkyne 10 in
91% yield or the alkyne 11 in 74% yield.
Synthesis 2012, 44, 439–445
© Thieme Stuttgart · New York

PAPER
Papilionaceous Molecules Containing Oligobenzofurans
441
10
11
1) NaOH, CH2Cl2, MeOH, r.t.
2) NaOH, MeOH, reflux
HO
O
O
O
O
O
O
OH
1, 49%
O
OH
FeCl3 (8 equiv), MeNO2
3 min, 50%
hν, 95%, or
FeCl3 (6 equiv), MeNO2
3 min, 90%
4, 77%
O
O
O
O
O
O
FeCl3 (3 equiv)
MeNO2
3 min, 90%
O
O
2
3
Scheme 3 Synthesis of 1, 2, 3, and 4
eration of the six benzofuran rings dramatically increased
the difficulty of the reaction due to the tremendous steric
hindrance of the C3 centrosymmetric nonplanar skeleton
in compound 11. However, the formation of the 1,3,5-cy-
clized compound 4 was relatively easier.
Therefore, after a series of unsuccessful attempts, the fo-
cus was diverted to the optical properties of 4 and these
properties were compared with the synthetic four- or six-
fold substituted alkynes 10 and 11, and other papiliona-
ceous benzofurans 1–3. Thus, a series of conditions were
investigated for the oxidative aromatic cyclization of the
multi-benzofuran rings in compound 1 (Table 1). In our
initial attempts, 2,3-dichloro-5,6-dicyano-1,4-benzo-
quinone (DDQ, Table 1, entry 1)11 was chosen as an oxi-
dant to afford the oligobenzofuran 3. Unfortunately, the
substrate 1 decomposed within 10 minutes. Then, we used
copper(II) chloride or copper(I) bromide as Lewis acids
with n-BuLi12 to accomplish the aromatic cyclization of 1
(entry 2), but no traces of compound 3 was observed even
after reacting overnight. Surprisingly, one-fold aromatic
cyclized oligobenzofuran 2 was unexpectedly obtained
under both visible or UV light conditions. The reaction
was accomplished within 20 minutes in 95% yield (based
on recovered starting material). However, there is some
problem in this reaction because the cyclization occurred
in one-fold only, and the reaction mixture could not be
separated by column chromatography. Perhaps, the reac-
tion time is an important factor. However, some unknown
Figure 2 X-ray crystallographic structure of compound 11
precipitates emerged after prolonged reaction time (en-
tries 3 and 4). Then, one-fold oligobenzofuran 2 was se-
lected as a substrate to get the desired two-fold
oligobenzofuran 3. Thus, according to the preceding pro-
© Thieme Stuttgart · New York
Synthesis 2012, 44, 439–445

442
W.-Y. Chai et al.
PAPER
cedure, all treatments of substrate 2 with DDQ, CuCl2,and was formed, then another radical was generated, and in-
CuBr failed to produce compound 3 (entries 1, 2, and 4). tramolecular cyclization occurred rapidly, which avoided
After an extensive literature search13 and also on the basis the intermolecular cross-coupling reaction. Hence, the
of our previous experience,14 the anhydrous ferric chlo- concentration of FeCl3 is the more important factor, the
ride was expected to be a good reagent to facilitate the bigger concentration resulted in the intermolecular cross-
multi-fold aromatic cyclization by controlling the equiva- coupling reaction among the multi-benzofuran radicals
lents of FeCl3 used in the reaction. Therefore, the Scholl while the smaller one was unable to produce fresh radicals
reaction was employed. The experiments were all carried to generate the second oligobenzofuran. Therefore, after
out at 0 °C in nitromethane (1 mL) (entries 5–11). The ini- the first aromatic cyclization in substrate 1, the resulting
tial attempt at the cyclization of compound 1 was started one-fold oligobenzofuran 2 was treated with FeCl3 again,
with 24 equivalents of FeCl3 in less than 3 minutes, how- and the two-fold oligobenzofuran 3 was obtained in high-
ever, the substrate 1 decomposed rapidly (entry 5). This er yield from substrate 1 directly.
result indicated that the equivalents of FeCl3 used were
All synthesized compounds were characterized by 1H and
too large for the reaction, even up to the extent of 12
13C NMR, DPET spectroscopy, mass spectrometry, and
equivalents. Hence, several other equivalents of FeCl3
1
exact mass measurement. H NMR spectra proved to be
were screened to test this assumption. Experimental re-
very useful in the characterization of the various analo-
sults showed that use of 6 or 8 equivalents of FeCl3 was
gous products. Hence, the chemical shifts and integration
data gleaned from H NMR spectra were very helpful in
determining the formation of oligobenzofuran ring
(Figure 3). After a series of comparisons, it was found that
the number of the muilt-benzofuran protons (d = 6.77
ppm) was four in substrate 1, remained two in one-fold
oligobenzofuran 2, and disappeared in two-fold oligoben-
zofuran 3. Besides, the signals of aryl and tertiary butyl
remarkably different. Compound 1 reacted with FeCl3 (6
equiv) for 3 minutes to give oligobenzofuran 2 in 90%
yield (entry 6), but the two-fold oligobenzofuran 3 was
only obtained with FeCl3 (8 equiv) in 50% yield (entry 8).
The Rf values of both compounds were uniform in TLC
plates. Therefore, the equivalent of FeCl3 was crucial for
the preparation of target compound. Interestingly, sub-
strate 1 reacted with FeCl3 (7 equiv) to provide oligoben-
1
groups were shifted to the lower field in oligobenzofuran.
zofuran 2 in 63% yield (entry 7), and the oligobenzofuran
3 with FeCl3 (9 equiv) in 10% yield (entry 9). Besides, the
reaction time was prolonged to 15 minutes using 6 equiv-
alents of FeCl3. This gave a mixture of 2 and 3 in 90%
yield (1:1, determined by 1H NMR spectroscopy), but the
yield decreased to 75% after keeping overnight (entry 10).
It was surprising that the half-cyclized 2 reacted with 3
equivalents of FeCl3 to provide oligobenzofuran 3 suc-
cessfully in 90% yield (entry 11). This result suggested
that the Scholl reaction may work better for partially
closed substrate.15 In our case, when the first two benzo-
furan radicals were generated in substrate 1 with appropri-
ate concentration of FeCl3, the one-fold oligobenzofuran
Similarly, 13C NMR spectroscopy showed the presence of
12 × CH3, 18 × CH, and 24 × C in substrate 1, 12 × CH3,
16 × CH, and 26 × C in one-fold oligobenzofuran 2,
12 × CH3, 14 × CH, and 28 × C in two-fold oligobenzofu-
ran 3, respectively. According to high-resolution mass
spectral data, compounds 1, 2, and 3 show m/z [M + Na]+
with successive decrease of two hydrogens (see Support-
ing Information).
At present, with papilionaceous oligobenzofurans 1–3,
four- or six-fold substituted alkyne 10 or 11, and 1,3,5-cy-
clized compound 4 in hand, the corresponding basic opti-
cal properties were observed (Table 2).
Table 1 Attempts to Synthesize Compound 3
Entry
Substrate
Conditions
Time (min)
Results
1
2
1 (or 2)
DDQ11
10
decomposition
no reaction
2, 95% (brsm)
precipitate
decomposition
2, 90%
12
1 (or 2)
n-BuLi, CuCl212 (or n-BuLi, CuBr, O2
)
overnight
3
1
20
hn (visible light or UV)
hn (visible light or UV)
4
1 (or 2)
>20
5
1
1
1
1
1
1
2
FeCl3 (24 equiv or 12 equiv), MeNO2 (1 mL)13,14
FeCl3 (6 equiv), MeNO2 (1 mL)
FeCl3 (7 equiv), MeNO2 (1 mL)
FeCl3 (8 equiv), MeNO2 (1 mL)
FeCl3 (9 equiv), MeNO2 (1 mL)
FeCl3 (6 equiv), MeNO2 (1 mL)
FeCl3 (3 equiv), MeNO2 (1 mL)
3
6
3
7
3
2, 63%
8
3
3, 50%
9
3
3, 10%
10
11
15 (or overnight)
3
2 and 3 (1:1), 90% (or 75%)
3, 90%
Synthesis 2012, 44, 439–445
© Thieme Stuttgart · New York

PAPER
Papilionaceous Molecules Containing Oligobenzofurans
443
estingly, the band position in the UV-Vis spectrum of
oligobenzofuran 2 was blue-shifted 33 nm when com-
pared with oligobenzofuran 3, but only 6 nm compared to
compound 1. Similarly compound 2 showed blue-shift by
41 nm and 24 nm, respectively, in fluorescence spectrum
compared to 1 and 3. This observation suggested that the
symmetrical extent of the molecular structure represented
a significant feature that influenced their spectroscopic
properties. For the fluorescence quantum yield in solu-
tion, the increases of conjugation brought about an obvi-
ous increase, that is, 1 < 2 < 3, but the quantum yield for
alkyne 10 was higher than compound 1. We speculated
that the structure of alkyne 10 could be regarded as an oli-
go(phenylene ethynylene)s (OPEs) core, which was in ac-
cordance with our earlier studies.16 Similarly, alkyne 11
could also be treated as a OPE core, which should have a
higher quantum yield than the corresponding benzofuran
4. However, because of the nonplanar structure and the
contorted backbone of alkyne 11 (Figure 2), the quantum
yield of it was almost the same as the corresponding ben-
zofuran 4. Taken together, the oligobenzofurans 1 and 3
possess the planar structures, while compound 2 has the
nonplanar one. Moreover, oligobenzofuran 3 has the most
perfect plane structure and conjugation, which was proved
by UV-Vis, fluorescence spectroscopy, and the fluores-
cence quantum yield itself.
Figure 3 1H NMR spectra of 1, 2, and 3
In conclusion, we have synthesized novel papilionaceous
molecules containing multi- or oligo-benzofurans 1, 2, 3,
and 4 under alkaline conditions and further expeditious ar-
omatic cyclization of a multi-benzofuranyl precursor us-
ing ferric chloride as an important oxidative reagent using
suitable concentration. This method facilitated the
straightforward and rapid construction of oligobenzofuran
systems for further studies by examining their structures,
physical, and chemical properties. Moreover, basic opti-
cal studies (UV-Vis, fluorescence, and fluorescence quan-
tum yield in solution) have been carried out.
Table 2 Spectroscopic Properties of 1–3, 10, 4, and 11
Optical property
labsa (nm)
1
2
3
10
4
11
325
461
22
319
437
50
352
478
67
322
396
40
359
449
22
353
448
22
lemb (nm)
F (%)c
a Only the largest absorption maxima are listed.
b Wavelength of emission maximum when excited at the absorption
maximum.
All reactions that required anhydrous conditions were carried by
standard procedures under an argon atmosphere. Commercially
available reagents were used as received. The solvents were dried
by distillation over the appropriate drying reagents. Petroleum ether
(PE) used for column chromatography had a bp range of 60–90 °C.
Reactions were monitored by TLC on silica gel plates. Column
chromatography was generally performed on silica gel (200–300
mesh). Melting points were determined by use of a Reichert Micro-
scope apparatus and are uncorrected. 1H, 13C NMR, and DEPT 135
were recorded on a Mercury Plus-400 spectrometer or a Mercury
Plus-600 spectrometer. The chemical shifts (d) are reported in ppm
relative to TMS (d = 0.00 ppm) for 1H NMR (standard abbreviations
were used to denote signal multiplicity) and CHCl3 (d = 77.0 ppm)
for 13C NMR measurements. Coupling constants (J) are in Hz.
High-resolution mass spectral data (HRMS) were obtained on
APEX II FT-MS (ESI) or APEX-QE-FTMS (MALDI) mass spec-
c Quantum yield using a sample concentration of 10–6 M in CH2Cl2.
The band positions in the UV-Vis spectra of 1 or 3 are red-
shifted relative to alkyne 10. Moreover, oligobenzofuran
3 gave rise to the largest increase and red-shifted 30 nm
with respect to the alkyne 10. This phenomenon is also
observed in compound 4 and alkyne 11. But oligobenzo-
furan 2 was a special case, with a band position little lower
than compound 1 because of its nonplanar structure skel-
eton. Similarly, the band positions of the fluorescence
spectra for the oligobenzofuran 1 or 3 also showed succes-
sive increases than alkyne 10, the biggest red shift of 82
nm being observed for compound 3. A higher red shift
was also observed in compound 4 and alkyne 11. Similar- trometers. IR spectra were recorded on a Nicolet NEXUS 670 FT-
IR spectrometer. UV-Vis spectra were recorded on a T6 spectro-
photometer using quartz cells with a path length of 1.0 cm. Fluores-
ly, the nonplanar compound 2 showed band positions a lit-
tle lower than compound 1. The data definitely indicated
that the preferable conjugated molecules such as com-
pounds 3 and 4 had better spectroscopic properties. Inter-
cence spectra were recorded on
a Perkin-Elmer LS-55
spectrophotometer. Fluorescence quantum yields were determined
using a sample concentration of 10–6 M in CH2Cl2.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 439–445

444
W.-Y. Chai et al.
PAPER
4-tert-Butyl-2-ethynylphenyl Acetate (9)14
(1 mL), and extracted with CH2Cl2 (3 × 10 mL). The combined or-
ganic layers were dried (MgSO4) and concentrated under reduced
pressure. The residue was dissolved in MeOH (10 mL) and treated
with NaOH (34 mg, 0.85 mmol). The reaction mixture was stirred
at reflux overnight (monitored by TLC, eluent: PE–CH2Cl2, 5:1),
quenched with aq 1 M HCl (1 mL), and extracted with CH2Cl2
(3 × 10 mL). The combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. Flash column chromatogra-
phy of the residue on silica gel (PE–CH2Cl2, 3:1) gave 1 (52 mg,
49%) as a pale-yellow solid; mp 252–253 °C.
To a stirred solution of 8 (0.16 g, 0.56 mmol) in THF (5 mL) was
added AcOH (0.064 mL) and TBAF (0.26 g, 0.82 mmol). The reac-
tion mixture was stirred for 1 h at r.t., quenched with sat. aq NH4Cl
(2 mL), and extracted with CH2Cl2 (3 × 10 mL). The combined or-
ganic layers were dried (MgSO4) and concentrated under reduced
pressure. Flash column chromatography of the residue on silica gel
(PE–EtOAc, 30:1) afforded 9 (0.11 g, 92%) as a colorless solid; mp
61–62 °C.
IR (KBr): 3284, 2964, 2220 (C≡C), 1763, 1493, 1368, 1206, 1183,
1123, 1011, 893, 842 cm–1.
IR (KBr): 2960, 2863, 1737, 1458, 1369, 1261, 1163, 877, 812 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.32 (s, 9 H, 3 × CH3), 2.34 (s, 3
H, COCH3), 3.24 (s, 1 H, ≡CH), 7.02 (d, J = 8.8 Hz, 1 H, ArH), 7.39
(dd, J = 8.8, 2.4 Hz, 1 H, ArH), 7.56 (d, J = 2.4 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.9 (CH3), 31.2 (CH3), 34.5 (C),
79.2 (C, ≡CH), 81.2 (C, ≡C), 115.4 (C), 121.7 (CH), 127.3 (CH),
130.6 (CH), 148.8 (C), 149.8 (C), 169.1 (C).
1H NMR (400 MHz, CDCl3): d = 1.44 (s, 36 H, 12 × CH3), 6.77 (s,
4 H, 4 × H-3¢), 7.43 (dd, J = 8.8, 2.0 Hz, 4 H, ArH), 7.48 (d, J = 8.8
Hz, 4 H, ArH), 7.61 (d, J = 1.2 Hz, 4 H, ArH), 8.33 (s, 2 H, ArH-
3,6).
13C NMR (100 MHz, CDCl3): d = 31.8 (CH3), 34.7 (C), 106.4 (CH,
C-3¢), 110.7 (CH), 117.4 (CH), 122.8 (CH), 128.6 (C), 129.2 (C),
131.1 (CH), 146.0 (C), 153.0 (C), 154.0 (C).
HRMS (ESI): m/z [M + NH4]+ calcd for C14H20NO2: 234.1489;
found: 234.1484.
HRMS (MALDI): m/z [M + Na]+ calcd for C54H54O4 + Na:
789.3914; found: 789.3918.
1,2,4,5-[Tetrakis(2-acetyloxy-5-tert-butyl)phenylethynyl]ben-
zene (10)
6,7-Bis(5-tert-butylbenzo[b]furan-2-yl)bis(5-tert-butylben-
zo[b]furan-2-yl)[2,3-a:3¢,2¢-c]naphthalene (2)
Method A: Compound 1 (20 mg, 0.026 mmol) was dissolved in
CH2Cl2 (10 mL), and then exposed to UV light for 20 min. The mix-
ture was then concentrated under reduced pressure. Flash column
chromatography on silica gel (PE–CH2Cl2, 10:1) gave 2 (19 mg,
95% brsm) as a pale-yellow solid; mp 236–237 °C.
To a stirred solution of 12 (0.27 g, 0.46 mmol) and Et3N (10 mL) in
THF (5 mL) was added PdCl2(PPh3)2 (35 mg, 0.05 mmol), CuI (20
mg, 0.10 mmol), and 9 (0.60 g, 2.78 mmol). The reaction mixture
was stirred under argon at 40 °C for 48 h. Et2O (10 mL) and aq 0.1
N HCl (2 mL) were added. The organic layer was separated, washed
with H2O (10 mL), dried (MgSO4), and concentrated under reduced
pressure. Flash column chromatography of the residue on silica gel
(PE–EtOAc, 10:1) afforded 10 (0.39 g, 91%) as a pale-yellow solid;
mp 135–136 °C.
Method B: To a stirred solution of 1 (20 mg, 0.026 mmol) in CH2Cl2
(20 mL) was added a solution of FeCl3 (26 mg, 0.16 mmol) in anhyd
MeNO2 (1 mL) dropwise under argon at 0 °C. Stirring was contin-
ued at this temperature for 3 min, and the reaction mixture was
quenched with MeOH (1 mL). The solvent was removed under re-
duced pressure. Flash chromatography of the residue on silica gel
(PE–CH2Cl2, 3:1) afforded 2 (18 mg, 90%) as a pale-yellow solid;
mp 236–237 °C.
IR (KBr): 2962, 2870, 2212 (C≡C), 1769, 1450, 1367, 1194, 1122,
1010, 898, 838 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.29 (s, 36 H, 12 × CH3), 2.26 (s,
12 H, 4 × COCH3), 7.04 (d, J = 8.8 Hz, 4 H, ArH), 7.39 (dd, J = 8.8,
2.4 Hz, 4 H, ArH), 7.66 (d, J = 2.4 Hz, 4 H, ArH), 7.71 (s, 2 H, ArH-
3,6).
13C NMR (100 MHz, CDCl3): d = 20.7 (CH3), 31.1 (CH3), 34.4 (C),
90.9 (C, ≡C), 91.1 (C, ≡C), 116.0 (C), 121.7 (CH), 125.0 (C), 127.3
(CH), 130.3 (CH), 135.2 (CH), 148.8 (C), 149.2 (C), 169.0 (C).
IR (KBr): 2958, 2867, 1741, 1471, 1363, 1253, 1203, 1121, 1067,
871, 811 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.43 (s, 18 H, 6 × CH3), 1.59 (s,
18 H, 6 × CH3), 6.77 (s, 2 H, 2 × H-3¢), 7.42 (d, J = 8.8 Hz, 2 H,
ArH), 7.51 (d, J = 8.8 Hz, 2 H, ArH), 7.60 (s, 2 H, ArH), 7.64 (d,
J = 8.8 Hz, 2 H, ArH), 7.73 (d, J = 8.8 Hz, 2 H, ArH), 8.62 (s, 2 H,
ArH-4¢¢), 8.97 (s, 2 H, ArH).
HRMS (ESI): m/z [M + H]+ calcd for C62H63O8: 935.4517; found:
935.4519.
Hexakis[(2-acetyloxy-5-tert-butyl)phenylethynyl]benzene (11)
According to the preceding procedure for the preparation of alkyne
10, perbromobenzene (13; 0.08 g, 0.15 mmol) and alkyne 9 (0.26 g,
1.20 mmol) provided compound 11 (0.15 g, 74%) as a pale-yellow
solid; mp 174–175 °C.
13C NMR (100 MHz, CDCl3): d = 31.9 (CH3), 32.0 (CH3), 34.8 (C),
35.0 (C), 106.2 (CH, C-3¢), 110.7 (CH), 111.5 (CH), 115.6 (C),
117.5 (CH), 118.8 (CH), 119.4 (C), 122.6 (CH), 123.3 (CH), 124.3
(C), 124.7 (CH), 127.3 (C), 128.9 (C), 146.0 (C), 146.2 (C), 149.0
(C), 153.1 (C), 154.6 (C), 155.0 (C).
IR (KBr): 2961, 2871, 2207 (C≡C), 1762, 1491, 1364, 1186, 1120,
HRMS (MALDI): m/z [M + Na]+ calcd for C54H52O4 + Na:
787.3758; found: 787.3752.
1008, 893, 829 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.26 (s, 54 H, 18 × CH3), 1.99 (s,
18 H, 6 × COCH3), 7.03 (d, J = 8.8 Hz, 6 H, ArH), 7.41 (dd, J = 8.8,
2.4 Hz, 6 H, ArH), 7.71 (d, J = 2.4 Hz, 6 H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.5 (CH3), 31.1 (CH3), 34.4 (C),
90.4 (C, ≡C), 95.4 (C, ≡C), 116.3 (C), 121.9 (CH), 127.4 (CH),
127.5 (C), 131.0 (CH), 148.7 (C), 149.4 (C), 169.3 (C).
Tetrakis(5-tert-butylbenzo[b]furan-2-yl)[2,3-a:3¢,2¢-c:2¢¢,3¢¢-
f:3¢¢¢,2¢¢¢-h]anthracene (3)
Method A: To a stirred solution of 1 (20 mg, 0.026 mmol) in CH2Cl2
(20 mL) was added a solution of FeCl3 (34 mg, 0.21 mmol) in anhyd
MeNO2 (1 mL) dropwise under argon at 0 °C. Stirring was contin-
ued at this temperature for 3 min, and the reaction mixture was
quenched with MeOH (1 mL). The solvent was removed under re-
duced pressure. Flash chromatography of the residue on silica gel
(PE–CH2Cl2, 3:1) afforded 3 (10 mg, 50%) as a pale-yellow solid;
mp >380 °C.
HRMS (ESI): m/z [M + H]+ calcd for C90H91O12: 1363.6505; found:
1363.6501.
1,2,4,5-Tetrakis(5-tert-butylbenzo[b]furan-2-yl)benzene (1)
To a stirred solution of 10 (0.13 g, 0.14 mmol) in CH2Cl2 and
MeOH (1:1 v/v) was added NaOH (34 mg, 0.85 mmol). The reac-
tion mixture was stirred at r.t. overnight, quenched with aq 1 M HCl
Method B: To a stirred solution of 2 (20 mg, 0.026 mmol) in CH2Cl2
(20 mL) was added a solution of FeCl3 (13 mg, 0.08 mmol) in anhyd
Synthesis 2012, 44, 439–445
© Thieme Stuttgart · New York

PAPER
Papilionaceous Molecules Containing Oligobenzofurans
445
MeNO2 (1 mL) dropwise under argon at 0 °C. Stirring was contin-
ued at this temperature for 3 min. Purification according to method
A afforded 3 (18 mg, 90%).
Katritzky, A. R.; Boulton, A. J., Eds.; Academic Press: New
York, 1975, 337. (d) Nicolaou, K. C.; Pfefferkorn, J. A.;
Roecker, A. J.; Cao, G. Q.; Barluenga, S.; Mitchell, H. J.
J. Am. Chem. Soc. 2000, 122, 9939.
IR (KBr): 2959, 2924, 2854, 1463, 1370, 1261, 1157, 1069, 810
cm–1.
1H NMR (400 MHz, CDCl3): d = 1.61 (s, 36 H, 12 × CH3), 7.68 (d,
J = 8.8 Hz, 4 H, ArH), 7.79 (d, J = 8.8 Hz, 4 H, ArH), 8.69 (s, 4 H,
ArH-4), 9.06 (s, 2 H, ArH).
13C NMR (150 MHz, CDCl3): d = 32.1 (CH3), 35.1(C), 111.4 (CH),
115.2 (C), 118.8 (CH), 119.3 (C), 123.5 (CH), 124.3 (CH), 128.8
(C), 146.3 (C), 149.1 (C), 153.6 (C).
(2) (a) Bird, C. W. In Progress in Heterocyclic Chemistry, Vol.
5; Suschitzky, H.; Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1993, 129. (b) Ono, M.; Kawashima, H.; Nonaka,
A.; Kawai, T.; Haratake, M.; Mori, H.; Kung, M. P.; Kung,
H. F.; Saji, H.; Nakayama, M. J. Med. Chem. 2006, 49,
2725. (c) Chambers, J. J.; Kurrasch-Orbaugh, D. M.; Parker,
M. A.; Nichols, D. E. J. Med. Chem. 2001, 44, 1003.
(3) Saadeh, H.; Goodson, T. III; Yu, L. Macromolecules 1997,
30, 4608.
(4) (a) Hou, X. L.; Cheung, H. Y.; Hon, T. Y.; Kwan, P. L.; Lo,
T. H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998, 54,
1955. (b) Duan, X.-H.; Liu, X.-Y.; Guo, L.-N.; Liao, M.-C.;
Liu, W.-M.; Liang, Y.-M. J. Org. Chem. 2005, 70, 6980.
(c) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc.
2004, 126, 11164.
(5) (a) Zhang, H.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem.
Int. Ed. 2004, 43, 6144. (b) Hosokawa, T.; Maeda, K.;
Koga, K.; Moritani, I. Tetrahedron Lett. 1973, 14, 739.
(c) Hosokawa, T.; Ohkata, H.; Moritani, I. Bull. Chem. Soc.
Jpn. 1975, 48, 1533. (d) Hosokawa, T.; Murahashi, S.-I.
Acc. Chem. Res. 1990, 23, 49.
(6) Castro, A. M. M. Chem. Rev. 2004, 104, 2939.
(7) (a) Arcadi, A.; Cacchi, S.; Rosario, M. D.; Fabrizi, G.;
Marinelli, F. J. Org. Chem. 1996, 61, 9280. (b) Katritzky,
A. R.; Fali, C. N.; Li, J. J. Org. Chem. 1997, 62, 8205.
(c) Larock, R. C.; Yum, E. K.; Doty, M. J.; Sham, K. K. C.
J. Org. Chem. 1995, 60, 3270. (d) Bishop, B. C.; Cottrell, I.
F.; Hands, D. Synthesis 1997, 1315. (e) Inoue, M.; Carson,
M. W.; Frontier, A. J.; Danishefsky, S. J. J. Am. Chem. Soc.
2001, 123, 1878.
(8) (a) Hughes, C. C.; Trauner, D. Angew. Chem. Int. Ed. 2002,
41, 1569. (b) Wang, Q.; Huang, Q.; Chen, B.; Lu, J.; Wang,
H.; She, X.; Pan, X. Angew. Chem. Int. Ed. 2006, 45, 3651.
(9) Iskra, J.; Stavber, S.; Zupan, M. Synthesis 2004, 1869.
(10) Mattern, D. L. J. Org. Chem. 1984, 49, 3051.
(11) Zhai, L.; Shukla, R.; Rathore, R. Org. Lett. 2009, 11, 3474.
(12) (a) Iyoda, M. Adv. Synth. Catal. 2009, 351, 984.
(b) Ohmae, T.; Nishinaga, T.; Wu, M.; Iyoda, M. J. Am.
Chem. Soc. 2010, 132, 1066. (c) Miyake, Y.; Wu, M.;
Rahman, M. J.; Kuwatani, Y.; Iyoda, M. J. Org. Chem. 2006,
71, 6110.
(13) (a) Rempala, P.; Kroulík, J.; King, B. T. J. Org. Chem. 2006,
71, 5067. (b) Wu, J.; Pisula, W.; Müllen, K. Chem. Rev.
2007, 107, 718. (c) King, P. T.; Kroulík, J.; Robertson, C.
R.; Rempala, P.; Hilton, C. L.; Korinek, J. D.; Gortari, L. M.
J. Org. Chem. 2007, 72, 2279. (d) Zhou, Y.; Liu, W.-J.;
Zhang, W.; Cao, X.-Y.; Zhou, Q.-F.; Ma, Y.; Pei, J. J. Org.
Chem. 2006, 71, 6822.
HRMS (MALDI): m/z [M + Na]+ calcd for C54H50O4 + Na:
785.3601; found: 785.3603.
{1,3,5-Tris(5-tert-butylbenzo[b]furan-2-yl)-2,4,6-tris[(5-tert-bu-
tyl-2-hydroxy)phenylethynyl]}benzene (4)
According to the preceding procedure for the preparation of benzo-
furan 1, alkyne 11 (0.10 g, 0.07 mmol) provided compound 4 (0.06
g, 77%) as a pale-yellow solid; mp 221–222 °C.
IR (KBr): 3330, 2955, 2929, 2867, 1948 (C≡C), 1778, 1461, 1365,
1217, 1168, 1101, 1007, 893, 873, 804 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.11 (s, 27 H, 9 × CH3), 1.43 (s,
27 H, 9 × CH3), 5.46 (s, 3 H, OH), 6.73 (d, J = 8.8 Hz, 3 H, ArH),
6.78 (d, J = 2.4 Hz, 3 H, ArH-3¢), 7.18 (dd, J = 8.8, 2.4 Hz, 3 H,
ArH), 7.38 (s, 3 H, ArH), 7.48 (dd, J = 8.8, 2.0 Hz, 3 H, ArH), 7.60
(d, J = 8.8 Hz, 3 H, ArH), 7.72 (d, J = 2.0, Hz, 3 H, ArH).
13C NMR (100 MHz, CDCl3): d = 31.3 (CH3), 31.8 (CH3), 33.9 (C),
34.8 (C), 92.8 (C, ≡C), 94.1 (C, ≡C), 108.2 (C), 109.4 (CH), 110.9
(CH), 114.4 (CH), 117.5 (CH), 123.7 (CH), 124.9 (C), 127.7 (C),
128.5 (CH, overlapping signals), 134.5 (C), 142.9 (C), 146.4 (C),
152.3 (C), 153.2 (C), 155.0 (C).
HRMS (ESI): m/z [M + H]+ calcd for C78H79O6: 1111.5871; found:
1111.5873.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
The authors are grateful to the National Basic Research Program of
China (973 Program, Grant No. 2010CB833200), the National Na-
tural Science Foundation of China (Grant Nos. 20972060 and
21061160494), the Specialized Research Fund for the Doctoral Pro-
gram of Higher Education (Grant No. 20090211110007), and the
111 Project for continued financial support.
References
(14) Wang, T.; Li, Z.-Y.; Xie, A.-L.; Yao, X.-J.; Cao, X.-P.;
Kuck, D. J. Org. Chem. 2011, 76, 3231.
(15) Feng, X.; Wu, J.; Enkelmann, V.; Müllen, K. Org. Lett.
2006, 8, 1145.
(16) Shi, Z.-F.; Wang, L.-J.; Wang, H.; Cao, X.-P.; Zhang, H.-L.
Org. Lett. 2007, 9, 595.
(1) (a) Zeni, G.; Larock, R. C. Chem. Rev. 2004, 104, 2285.
(b) Keay, B. A. Comprehensive Heterocyclic Chemistry II,
Vol. 2; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Pergamon: Oxford, 1996, 395. (c) Cagniant, P.; Cagniant,
D. In Advances in Heterocyclic Chemistry, Vol. 18;
© Thieme Stuttgart · New York
Synthesis 2012, 44, 439–445