An expedient synthesis of bis-fused benzofuran and a two-directional ring- closing metathesis for the synthesis of bisbenzoxepines and bisbenzoxocines

Article abstract of DOI:10.1055/s-0028-1083339

Synthesis of bis-fused benzofuran derivatives by the implementation of palladium-mediated intramolecular cyclization is described. To our knowledge, this is the first report of the synthesis of bis-fused benzofuran by this protocol. Bisbenzoxepine and bis

Full text of DOI:10.1055/s-0028-1083339

674
PAPER
An Expedient Synthesis of Bis-Fused Benzofuran and a Two-Directional Ring-
Closing Metathesis for the Synthesis of Bisbenzoxepines and Bisbenzoxocines
S
ynthesis of Bis-F
r
used Ben
i
zofura
s
ns hna C. Majumdar,* Buddhadeb Chattopadhyay, Santanu Chakravorty
Department of Chemistry, University of Kalyani, Kalyani, West Bengal 741235, India
Fax +91(33)25828282; E-mail: kcm_ku@yahoo.co.in
Received 25 September 2008; revised 27 October 2008
doubly fused benzofuran ring systems by the implementa-
Abstract: Synthesis of bis-fused benzofuran derivatives by the im-
plementation of palladium-mediated intramolecular cyclization is
described. To our knowledge, this is the first report of the synthesis
of bis-fused benzofuran by this protocol. Bisbenzoxepine and bis-
tion of palladium-mediated intramolecular cyclization
from the starting materials having two hydroxy and two
allylic moieties. Therefore, the aforesaid findings prompt-
benzoxocine derivatives were also synthesized by the application of ed us to undertake the palladium-mediated C–O bond
two-directional ring-closing metathesis.
forming reactions leading to the doubly fused benzofuran
ring systems.
Key words: palladium catalyst, Grubbs catalyst, intramolecular cy-
clization, two-directional ring-closing metathesis, 5-exo-trig, ben-
zofuran, oxepine, oxocine
The precursors 3a–e for our present investigation were
prepared in 80–95% yields by the Claisen rearrangement
of the diallylated derivatives 2a–e in refluxing 1,2-dichlo-
robenzene (DCB) for 8–10 hours. The diallylated deriva-
tives 2a–e in turn were prepared in good to excellent
yields by refluxing the dihydroxy derivatives 1a–e in ace-
tone with allyl bromides in the presence of anhydrous po-
tassium carbonate and a small amount of sodium iodide
for 12–24 hours (Scheme 1).
As a part of our continuing study concerning the carbon–
carbon bond-forming reactions utilizing the palladium-
mediated intramolecular cyclization strategy, we have
reported1,2 variously functionalized medium-sized hetero-
cycles with a possible evaluation of the potentially bioac-
tive moieties. We have also developed1,2 an important
synthetic methodology for the construction of medium-
sized heterocyclic compounds from the unactivated allyl-
ic system via the C–H activation method by the applica-
tion of intramolecular Heck reaction sequence. Most
recently, we have reported3 the first example of [1,3] aryl-
oxy shift along with a cycloisomerization process by the
implementation of palladium-mediated intramolecular
cyclization. Moreover, we have also described4 very re-
cently the first example of eight-membered sulfur hetero-
cycles from a sulfone ester-tether precursor by the
palladium-mediated intramolecular Heck reaction. In this
article, we wish to present the first example of doubly
fused [5,6,5] and [5,6,6,5] heterocyclic compounds from
the allylhydroxy precursors via the palladium-mediated
intramolecular cyclization.
OH
OH
O
(i)
(ii)
1a
3a
OH
2a
O
OH
HO
(ii)
(i)
OH
O
O
HO
OH
(i)
1b
3b
2b
(ii)
O
O
O
HO
OH
(i)
HO
OH
1c
2c
3c
OH
It is well known that benzofurans represent a very impor-
tant class of heterocyclic compounds. The benzofuran
moiety is present in many biologically active compounds,
displaying a wide range of pharmacological activities, in-
cluding anti-HIV, anticancer, and antimicrobial activity.5–7
The importance of benzofurans justify the continuous en-
deavors directed towards the development of new, selec-
tive and efficient synthesis of these heterocycles.
Particularly, during the last years, a number of synthetic
approaches to benzofurans by heteroannulation of alicy-
clic precursors have appeared in literature.8–11 Moreover,
to our knowledge, there is no report on the construction of
OH
OH
(ii)
OH
O
1d
2d
3d
OH
O
OH
(i)
(ii)
HO
HO
O
1e
2e
3e
Scheme 1 Reagents and conditions: (i) allyl bromide, acetone,
K2CO3, NaI, reflux, 12–24 h; (ii) o-DCB, reflux, 8–10 h.
SYNTHESIS 2009, No. 4, pp 0674–0680
Advanced online publication: 27.01.2009
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x
.
x
x
.2
0
0
9
DOI: 10.1055/s-0028-1083339; Art ID: Z21908SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Bis-Fused Benzofurans
675
Table 1 Optimization for the Cyclization of 3a to 4aa
Table 2 Summarized Results of the Cyclization Strategya
Entry Substrateb
Time Product
(min)
Yield
(%)c
O
OH
OH
O
3a
4a
O
OH
1
60
70
Entry Catalystb
Base
–
Solventc Temp TimeYield
(h) (%)d
OH
O
3a
1
2
3
4
5
6
7
8
9
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
MeCN r.t.
10 NRe
10 26
4a
20 mol% K2CO3 MeCN r.t.
40 mol% K2CO3 MeCN r.t.
60 mol% K2CO3 MeCN r.t.
100 mol% K2CO3 MeCN r.t.
200 mol% K2CO3 MeCN r.t.
200 mol% K2CO3 MeCN r.t.
2
3
60
80
70
5
5
5
1
1
1
1
35
41
55
70
dec.
25
30
HO
OH
O
O
3b
4b
O
65
HO
OH
O
200 mol% Et3N
MeCN 70 °C
3c
4c
200 mol% Cs2CO3 MeCN r.t.
200 mol% K2CO3 MeCN r.t.
OH
OH
O
10 Pd(OAc)2
10 NRe
10 30
10 25
10 30
10 20
4
5
60
55
11 Pd(PPh3)2Cl2 200 mol% K2CO3 MeCN r.t.
O
12 Pd(PPh3)4
13 PdCl2
200 mol% K2CO3 MeCN r.t.
200 mol% K2CO3 DMSO r.t.
3d
4d
OH
14 PdCl2
200 mol% K2CO3 DMF
r.t.
O
a In all the cases 200 mol% of 1,4-dihydroxybenzene was used.
b Amount of catalyst used: 20 mol%.
c Amount of solvent used: 5 mL.
d Isolated yields are reported.
45
traced
HO
O
e NR = no reaction.
f Optimized conditions.
3e
4e
a All reactions were carried out under the optimized reaction condi-
The first set of experiments was carried out with 3a as a
model substrate. The substrate 3a was initially allowed to
react in MeCN at room temperature for 10 hours in the
presence of a catalytic amount of PdCl2 (20 mol%) in con-
junction with two equivalents of hydroquinone (HQ) as an
oxidant. No reaction occurred under this condition
(Table 1, entry 1). However, when the same reaction was
performed in the presence of 20 mol% of a base such as
K2CO3, the desired doubly fused five-member cyclized
product 4a was obtained in 26% yield. The rest of the
starting material remained unchanged. Reaction of the
substrate 3a with 40, 60, and 100 mol% of K2CO3 for one
hour afforded 35, 41, and 55% yield, respectively, of the
cyclized product 4a. No further improvement of the yield
was observed when the reaction was conducted for a long-
er time, even up to five hours (Table 1, entries 2–4). Inter-
estingly, when the reaction was carried out by increasing
the mol% of the base to 200% the yield of the cyclized
product was increased to 70%. This suggests that deproto-
nation of the phenolic hydroxyl group is necessary for the
reaction to occur. We have again conducted the same re-
tions.
b In each case the substrate was taken 100 mg per 5 mL of MeCN so-
lution.
c Isolated yields are reported.
d Complicated reaction mixtures were found and traces of
products from TLC observation and consequently no spectral data
were provided.
action at higher temperature (70 °C), which resulted only
in a complicated reaction mixture instead of the desired
cyclized product. Among the several solvents examined,
MeCN was found to be of choice, whereas DMF and
DMSO gave poor yields of the cyclized product. The ef-
fect of base was also examined and K2CO3 was found to
be superior to Et3N and Cs2CO3. Catalyst also played an
important role in this cyclization strategy and the results
obtained are shown in Table 1.
It is noted that the reaction did not occur at all in the ab-
sence of HQ. All the reactions were carried out in the pres-
ence of two equivalents of HQ as an oxidant. Therefore,
to generalize the synthetic protocol we have also carried
Synthesis 2009, No. 4, 674–680 © Thieme Stuttgart · New York

676
K. C. Majumdar et al.
PAPER
out the reaction with substrates 3b–e and all the substrates some important bioactive natural products such as radula-
afforded the corresponding cyclized products 4b–d ex- nin,12 helianuols13 and pterulone14 as well as in some mod-
cept the substrate 3e. TLC analysis of the crude reaction ern pharmaceuticals which have lipoxegenase inhibition
mixture showed that substrate 3e preferentially underwent activity15, angiotensin II receptor antagonists property and
decomposition, with the formation of a small amount of antipsychotic activity.16 The importance of RCM reaction
the desired product 4e, which, however, due to the com- has been enhanced by combining various protocols either
plexity of the mixture, could not be isolated in pure state. in tandem17 or in sequence to it. Recently, we have
The results are summarized in Table 2.
reported18 the application of tandem Claisen rearrange-
ment and RCM reaction as new route to synthesize a num-
ber of medium-sized heterocyclic compounds.
The formation of the bisbenzofuran 4a may be rational-
ized as follows. The amount of base plays an important
role in the cyclization and therefore, deprotonation of the Therefore, development of a new synthetic route to these
phenolic hydroxyl group to form the dianion 5 is required ring systems is of great interest from the fact that bisben-
for the reaction to occur successfully. After the formation zoxepines and bisbenzoxocines remained largely unex-
of the dianion 5, the reaction may proceed in two ways ei- plored till date. This may be due to the lack of general
ther by a 5-exo-trig or a 6-endo-trig mode of cyclization. methods for their synthesis, except a few.19
However, formation of the six-membered products corre-
sponding to 6-endo-trig mode of cyclization could not be
detected in the reaction mixture. Therefore, the reaction
proceeds through the 5-exo-trig mode of cyclization and
The starting materials 14a–d for this study were prepared
by a sequence of reactions, that is, simple diallylation,
Claisen rearrangement followed by another diallylation
(Scheme 3). Here it is important to note that the Claisen
this may occur via the two pathways such as path a or path
rearrangements of this type of diallylated naphthalene
b. In path a, initially, the double bond is activated through
systems are known to be probablematic.20 Several groups
the coordination of the Pd catalyst with the p-bond allyl
have carried out this Claisen rearrangement in N,N-dieth-
ylaniline as solvent. In this case, workup and isolation of
moiety to generate the intermediate 6 and subsequently, a
5-exo-trig intramolecular nucleophilic attack of the oxy-
the products is not as simple as in the case of o-dichlo-
gen at the activated double bond may occur to generate the
robenzene, which we have used for the rearrangement to
intermediate 8. A b-H elimination from the intermediate 8
obtain consistent and improved yield of the rearranged
products.
can produce the bisbenzofuran derivative 9 followed by a
[1,3] prototopic shift afforded the desired product 4a. On
To test the premise, dichloromethane solution of 14a and
the other hand, path b involves a double bond insertion
commercially available Grubbs I catalyst was stirred at
into the Pd–O bond of the phenoxypalladium intermediate
room temperature under nitrogen atmosphere. The reac-
tion proceeded smoothly to give the oxepine derivative
15a in 90% yield. Substrate 14b–d reacted accordingly to
give products 15b–d in 60–85% yields (Scheme 3).
7, followed by protonolysis to afford the product 4a
(Scheme 2).
We next turned our attention to synthesize the bisbenz-
oxepines and bisbenzoxocines by the application of the
In conclusion, we have demonstrated that a simple cata-
two-directional ring-closing metathesis (RCM) approach.
lytic system consisting of PdCl2 in conjunction with 200
Our interest on this synthesis lies on the fact that the ben-
mol% of K2CO3 as the base and in the presence of 1,4-di-
zo-fused oxepine and oxocine derivatives are prevalent in
PdCl2
OH
O
O
K2CO3
PdCl2
path a
3a
OH
5
O
6
O
Cl2Pd
PdCl
Cl
Pd
path b
O
O
O
8
ClPd
Me
7
O
O
Pd
Cl
O
O
O
9
4a
Scheme 2 Probable mechanistic pathway of the double cyclization
Synthesis 2009, No. 4, 674–680 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis-Fused Benzofurans
677
after column chromatographic separation using PE–EtOAc (9:1);
yield: 228 mg (95%); yellow solid; mp 130–132 °C.
IR (KBr): 3344, 1610 cm–1.
OH
O
OH
(ii)
(i)
1H NMR (400 MHz, CDCl3): d = 3.55 (d, J = 5.8 Hz, 4 H, CH2),
5.10–5.25 (m, 4 H, =CH2), 5.49 (s, 2 H, OH), 6.02–6.11 (m, 2
H, =CH), 7.19 (d, J = 8.5 Hz, 2 H, ArH), 7.68 (d, J = 8.5 Hz, 2 H,
ArH).
12a
13a
1a
OH
O
OH
(iii)
13C NMR (100 MHz, CDCl3): d = 35.6, 113.7, 116.9, 125.1, 127.8,
O
O
130.4, 136.1, 149.4.
(iv)
MS: m/z = 240 (M+).
Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C, 79.81; H,
7.83.
14a
15a
O
O
R
3b
OH
(i)
O
R
Yield: 80%; yellow liquid.
IR (neat): 3340, 1612 cm–1.
OH
(ii)
1e
1H NMR (400 MHz, CDCl3): d = 3.73 (d, J = 6.0 Hz, 4 H, CH2),
5.02–5.25 (m, 4 H, =CH2), 5.34 (s, 2 H, OH), 6.25–6.30 (m, 2
H, =CH), 6.97 (d, J = 8.6 Hz, 2 H, ArH), 7.59 (d, J = 8.6 Hz, 2 H,
ArH).
OH
2e R = H
O
R
R
3e R = H
OH
R
12b R = Me
13b R = Me
(iii)
R
MS: m/z = 240 (M+).
O
O
Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C, 80.07; H,
6.88.
(
)
n
(iv)
(
)
n
R
3c
R
O
14b R = H, n = 1
14c R = H, n = 2
14d R = CH3, n = 1
(
)
n
O
n
15b R = H, n = 1
15c R = H, n = 2
15d R = Me, n = 1
Yield: 90%; yellow liquid.
IR (neat): 3341, 1610 cm–1.
(
)
1H NMR (400 MHz, CDCl3): d = 3.30 (d, J = 6.1 Hz, 4 H, CH2),
4.95 (s, 2 H, OH), 5.1–15.15 (m, 4 H, =CH2), 5.94–6.01 (m, 2
H, =CH), 6.34 (s, 1 H, ArH), 6.78 (s, 1 H, ArH).
Scheme 3 Reagents and conditions: (i) respective allyl bromide, an-
hyd K2CO3, NaI, acetone, reflux, 12–24 h; (ii) o-DCB, reflux, 8–12 h;
(iii) respective allyl bromide, anhyd K2CO3, NaI, acetone, reflux, 10–
20 h; (iv) Grubbs I catalyst, CH2Cl2, r.t., 15–25 min.
MS: m/z = 190 (M+).
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.59; H,
7.63.
hydroxybenzene (HQ) as an oxidant can be used for the
construction of bis-fused benzofuran or naphthofuran ring
system. On the other hand, sequential double-Claisen re-
arrangement and two-directional ring-closing metathesis
gives a direct synthesis of hitherto unreported benzo-
fused bisoxepine and bisoxocine derivatives in good
yields. The synthesized compounds may prove to be of
biological importance.
3d
Yield: 87%; white solid; mp 104–106 °C.
IR (KBr): 3345, 1607 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.31 (d, J = 6.4 Hz, 2 H, CH2),
3.40 (d, J = 6.4 Hz, 2 H, CH2), 4.59 (s, 2 H, OH), 5.06–5.16 (m, 4
H, =CH2), 5.90–6.00 (m, 2 H, =CH), 6.58 (s, 1 H, ArH), 6.62 (s, 1
H, ArH).
MS: m/z = 190 (M+).
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded for KBr discs and NMR spectra
were determined for solutions in CDCl3 with TMS as internal stan-
dard. Silica gel (60–120 mesh) was used for chromatographic sepa-
ration. Silica gel-G [E. Merck, India) was used for TLC. Petroleum
ether (PE) refers to the fraction boiling between 60 and 80 °C.
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.89; H,
7.31.
Cyclization of Compounds 3a–e to 4a–e; 2,7-Dimethyl-
furo[2¢,3¢:5,6]naphtho[2,1-b]furan (4a); Typical Procedure
Substrate 3a (100 mg, 0.416 mmol), K2CO3 (115 mg, 0.83 mmol),
HQ (91 mg, 0.82 mmol), PdCl2 (1.4 mg, 8.3 × 10–5 mmol) were
treated in MeCN (5 mL) at r.t. for 1 h. After completion of the reac-
tion, the mixture was poured into H2O (10 mL) and extracted with
CH2Cl2 (3 × 15 mL). The combined CH2Cl2 extracts were washed
with H2O (3 × 10 mL) and dried (Na2SO4). The solvent was re-
moved and the residual mass was purified by column chromatogra-
phy over silica gel using PE–EtOAc (99:1) as eluent to afford 4a;
yield: 168 mg (70%); white solid; mp 199–201 °C.
Precursors 3a–e; 2,6-Diallylnaphthalene-1,5-diol (3a); Typical
Procedure
A mixture of the compound 1a (1 mmol), allyl bromide (2.3 mmol)
and anhyd K2CO3 (4 g) were refluxed in anhyd acetone (50 mL) on
a water bath for 12 h. The mixture was cooled, filtered, and the sol-
vent was removed. The residual mass was extracted with CH2Cl2
(3 × 15 mL) and dried (Na2SO4). After removal of CH2Cl2, the re-
sidual mass was subjected to column chromatography over silica
gel using PE–EtOAc (49:1) as eluent to afford the desired diallyl de-
rivatives 2a. Compound 2a was refluxed in o-DCB (5 mL) for about
8 h. The mixture was allowed to cool and directly subjected to col-
umn chromatography over silica gel. Pure product 3a was isolated
IR (KBr): 2922, 1597 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.56 (s, 6 H, CH3), 6.50 (s, 2
H, =CH), 7.62 (d, J = 8.5 Hz, 2 H, ArH), 8.02 (d, J = 8.5 Hz, 2 H,
ArH).
Synthesis 2009, No. 4, 674–680 © Thieme Stuttgart · New York

678
K. C. Majumdar et al.
PAPER
13C NMR (125 MHz, CDCl3): d = 14.6, 104.1, 115.2, 118.6, 119.8,
124.1, 143.7, 154.6.
H, =CH), 6.15–6.23 (m, 2 H, =CH), 7.31 (d, J = 8.7 Hz, 2 H, ArH),
7.82 (d, J = 8.72 Hz, 2 H, ArH).
HRMS: m/z calcd for C16H12O2: 237.0938 [M + H]; found:
MS: m/z = 348 [M+].
237.0910 [M + H].
Anal. Calcd for C24H28O2: C, 82.72; H, 8.10. Found: C, 82.88; H,
7.93.
Anal. Calcd for C16H12O2: C, 81.34; H, 5.12. Found: C, 81.53; H,
4.89.
14b
4b
Yield: 80%; yellow liquid.
Yield: 80%; white solid; mp 218–220 °C.
IR (KBr): 2910, 1600 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.54 (s, 6 H, CH3), 6.98 (s, 2
H, =CH), 7.54 (d, J = 8.8 Hz, 2 H, ArH), 7.71 (d, J = 8.8 Hz, 2 H,
ArH).
13C NMR (75 MHz, CDCl3): d = 14.2, 103.0, 109.9, 122.6, 124.6,
126.9, 152.5, 154.5.
MS: m/z = 236 (M+).
IR (neat): 2927, 1604 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.55 (d, J = 6.3 Hz, 2 H, CH2),
3.85 (d, J = 5.6 Hz, 2 H, CH2), 4.47 (d, J = 5.12 Hz, 2 H, OCH2),
4.66 (d, J = 4.32 Hz, 2 H, OCH2), 4.98–5.03 (m, 2 H, =CH2), 5.08–
5.11 (m, 2 H, =CH2), 5.26–5.32 (m, 2 H, =CH2), 5.41–5.52 (m, 2
H, =CH2), 5.95–6.20 (m, 4 H, =CH), 7.22 (d, J = 8.9 Hz, 1 H, ArH),
7.29 (d, J = 8.6 Hz, 1 H, ArH), 7.66 (d, J = 8.8 Hz, 1 H, ArH), 7.98
(d, J = 9.04 Hz, 1 H, ArH).
MS: m/z = 320 [M+].
Anal. Calcd for C16H12O2: C, 81.34; H, 5.12. Found: 81.09; H, 5.19.
Anal. Calcd for C22H24O2: C, 82.46; H, 7.55. Found: C, 82.31; H,
7.39.
4c
Yield: 70%; viscous liquid.
IR (neat): 2927, 1603 cm–1.
14c
Yield: 70%; yellow liquid.
1H NMR (400 MHz, CDCl3): d = 2.40 (s, 6 H, CH3), 6.26 (s, 1
H, =CH), 6.46 (s, 1 H, =CH), 6.71 (d, J = 8.4 Hz, 1 H, ArH), 7.13
(d, J = 8.3 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 14.3, 102.0, 107.1, 117.7, 129.8,
130.2, 133.2, 159.8.
IR (neat): 2922, 1609 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.61 (q, J = 6.1 Hz, 2 H, CH2),
2.63 (q, J = 6.2 Hz, 2 H, CH2), 3.60 (d, J = 6.2 Hz, 2 H, =CHCH2),
3.56 (d, J = 6.1 Hz, 2 H, =CHCH2), 3.97 (t, J = 6.7 Hz, 2 H, OCH2),
4.07 (t, J = 6.7 Hz, 2 H, OCH2), 5.21–5.25 (m, 4 H, =CH2), 5.07–
5.15 (m, 4 H, =CH2), 5.94–6.20 (m, 4 H, =CH), 7.20–7.27 (m, 2 H,
ArH), 7.71 (d, J = 8.8 Hz, 1 H, ArH), 7.96 (d, J = 9.0 Hz, 1 H, ArH).
MS: m/z = 186 (M+).
Anal. Calcd for C12H10O2: C, 77.40; H, 5.41. Found: C, 77.64; H,
5.61.
MS: m/z = 348 [M+].
Anal. Calcd for C24H28O2: C, 82.72; H, 8.10. Found: C, 82.86; H,
8.19.
4d
Yield: 55%; yellow liquid.
IR (neat): 2921, 1600 cm–1.
14d
Yield: 75%; yellow liquid.
IR (neat): 2916, 1602 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.41 (s, 6 H, CH3), 6.23 (s, 1
H, =CH), 6.44 (s, 1 H, =CH), 6.81 (s, 1 H, ArH), 7.31 (s, 1 H, ArH).
1H NMR (400 MHz, CDCl3): d = 1.36 (d, J = 6.9 Hz, 3 H, CH3),
1.54 (d, J = 6.9 Hz, 3 H, CH3), 4.09 (q, J = 6.9 Hz, 1 H, CH3CH),
4.46 (d, J = 5.1 Hz, 2 H, OCH2), 4.55 (q, J = 6.9 Hz, 1 H, CH3CH),
4.64 (d, J = 4.1 Hz, 2 H, OCH2), 5.03–5.09 (m, 4 H, =CH2), 5.25–
5.49 (m, 4 H, =CH2), 6.03–6.37 (m, 4 H, =CH), 7.19–7.28 (m, 2 H,
ArH), 7.89 (d, J = 9.2 Hz, 1 H, ArH), 7.97 (d, J = 9.2 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 14.6, 107.8, 117.8, 130.8, 133.2,
156.8.
MS: m/z = 186 (M+).
Anal. Calcd for C12H10O2: C, 77.40; H, 5.41. Found: C, 77.61; H,
5.49.
MS: m/z = 348 [M+].
Precursors 14a–d for Metathesis Reaction; General Procedure
A mixture of C,C-diallylated derivative of 1,5-dihydroxynaphtha-
lene (1 mmol) or 1,6-dihydroxynaphthalene (1 mmol), substituted
allyl bromide/allyl bromide/homoallyl bromide (2.2 mmol), and an-
hyd K2CO3 (3 g) was refluxed in anhyd acetone (50 mL) on a water
bath for 10–20 h. The mixture was cooled, filtered, and the solvent
was removed. The residual mass was extracted with CH2Cl2 (3 × 15
mL) and the combined CH2Cl2 layers were dried (Na2SO4). After re-
moval of CH2Cl2, the residual mass was subjected to column chro-
matography over silica gel using PE–EtOAc (98:2) as eluent to
afford the desired O,C-diallyl derivatives 14a–d.
Anal. Calcd for C24H28O2: C, 82.72; H, 8.10. Found: C, 82.56; 7.99.
Two-Directional Ring-Closing Metathesis of the Compounds
14a–d; 1,8-Dimethyl-1,4,8,11-tetrahydrooxepi-
no[2¢,3¢:5,6]naphtho[1,2-b]oxepine (15a); Typical Procedure
To a magnetically stirred solution of 14a in degassed anhyd CH2Cl2
(10 mL), was added dropwise a solution of Grubbs I catalyst (10
mol%) in degassed CH2Cl2 (5 mL) under N2. After completion of
the reaction within 15 min, the solvent was removed and the residue
was subjected to column chromatography over silica gel using PE–
EtOAc (97:3) as eluent to give 15a; yield: 263 mg (90%); white sol-
id; mp 200–202 °C.
14a
IR (KBr): 2929, 1611 cm–1.
Yield: 85%; yellow liquid.
IR (neat): 2920, 1605 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.37 (d, J = 6.9 Hz, 6 H, CH3),
4.12 (q, J = 6.6 Hz, 2 H, CH3CH), 4.48 (d, J = 5.4 Hz, 4 H, OCH2),
5.04 (d, J = 12.0 Hz, 4 H, =CH2), 5.31 (d, J = 10.2 Hz, 2 H,
=CHaHb), 5.49 (d, J = 17.3 Hz, 2 H, =CHaHb), 6.03–6.11 (m, 2
1H NMR (400 MHz, CDCl3): d = 1.51 (d, J = 7.3 Hz, 6 H, CH3),
3.67 (q, J = 6.42 Hz, 2 H, CH3CH), 4.53 (d, J = 16.7 Hz, 2 H, =CH),
4.70 (dd, J = 1.5 Hz, 16.7 Hz, 2 H, =CH), 5.49 (dd, J = 1.0 Hz, 12.6
Hz, 2 H, OCHaHb), 5.85–5.91 (m, 2 H, OCHaHb), 7.24 (d, J = 8.5
Hz, 2 H, ArH), 7.88 (d, J = 8.5 Hz, 2 H, ArH).
Synthesis 2009, No. 4, 674–680 © Thieme Stuttgart · New York

PAPER
Synthesis of Bis-Fused Benzofurans
679
13C NMR (125 MHz, CDCl3): d = 22.1, 38.6, 70.1, 117.6, 126.6,
126.7, 128.9, 132.7, 135.7, 153.2.
References
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MS: m/z = 292 [M+].
Anal. Calcd for C20H20O2: C, 82.16; H, 6.89. Found: C, 81.91; H,
6.77.
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15b
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Yield: 70%; colorless liquid.
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IR (neat): 2928, 1609 cm–1.
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3.89 (d, J = 6.3 Hz, 2 H, CH2), 4.65 (m, 4 H, =CH and OCHaHb are
overlapped), 5.50 (t, J = 10.6 Hz, 2 H, =CH), 5.94–6.02 (m, 2 H,
OCHaHb), 7.16 (d, J = 8.7 Hz, 1 H, ArH), 7.27 (d, J = 8.9 Hz, 1 H,
ArH), 7.68 (d, J = 8.7 Hz, 1 H, ArH), 8.08 (d, J = 8.9 Hz, 1 H, ArH).
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13C NMR (100 MHz, CDCl3): d = 31.5, 31.7, 69.7, 69.9, 114.8,
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MS: m/z = 264 [M+].
Anal. Calcd for C18H16O2: C, 81.79; H, 6.10. Found: C, 81.93; H,
6.21.
15c
Yield: 85%; colorless liquid.
IR (neat): 2929, 1613 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.49 (d, J = 5.3 Hz, 2 H, CH2),
2.55 (d, J = 5.3 Hz, 2 H, CH2), 3.53 (d, J = 7.0 Hz, 2 H, CH2), 3.83
(d, J = 7.5 Hz, 2 H, CH2), 4.08 (t, J = 4.6 Hz, 2 H, OCH2), 4.16 (t,
J = 4.9 Hz, 2 H, OCH2), 5.56–5.64 (m, 2 H, =CH), 5.98–6.04 (m, 1
H, =CH), 6.14–6.17 (m, 1 H, =CH), 7.19 (d, J = 8.8 Hz, 1 H, ArH),
7.32 (d, J = 8.6 Hz, 1 H, ArH), 7.73 (d, J = 8.4 Hz, 1 H, ArH), 7.94
(d, J = 9.0 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 29.4, 29.6, 33.6, 34.7, 73.9, 76.6,
115.7, 117.1, 117.6, 119.1, 122.3, 124.2, 125.2, 128.9, 133.7, 134.6,
135.8, 137.3, 151.0, 152.8.
MS: m/z = 292 [M+].
Anal. Calcd for C20H20O2: C, 82.16; H, 6.89. Found: C, 82.37; H,
7.07.
15d
Yield 60%; colorless liquid.
IR (neat): 2927, 1611 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.51 (d, J = 7.1 Hz, 6 H, CH3),
3.62 (q, J = 7.1 Hz, 1 H, CH3CH), 4.18 (q, J = 7.1 Hz, 1 H, CH3CH),
4.40–4.91 (m, 4 H, OCH2), 5.49 (d, J = 11.2 Hz, 1 H, =CH), 5.57 (d,
J = 11.6 Hz, 1 H, =CH), 5.87–6.21 (m, 2 H, =CH), 7.23–7.42 (m, 2
H, ArH), 7.71–7.77 (m, 1 H, ArH), 8.10 (d, J = 8.8 Hz, 1 H, ArH).
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Acknowledgment
We thank the CSIR (New Delhi) and the DST (New Delhi) for fi-
nancial assistance. Two of us (B.C. and S.C.) are grateful to the
CSIR (New Delhi) for the research fellowships.
Synthesis 2009, No. 4, 674–680 © Thieme Stuttgart · New York

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K. C. Majumdar et al.
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