An efficient method to synthesize benzofurans and naphthofurans

Article abstract of DOI:10.1055/s-2006-944204

A new method for synthesis of benzofurans and naphthofurans from 2-hydroxystilbene derivatives via an intermolecular cyclization is reported in this study with up to 94% isolated yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-944204

LETTER
1657
An Efficient Method to Synthesize Benzofurans and Naphthofurans
S
ynthesis of Benz
h
ofurans and
o
Naphthofura
n
ns gfeng Pan,a Jie Yu,a Yuqing Zhou,a Zhiyong Wang,*a Ming-Ming Zhoub
a
Hefei National Laboratory for Physical Science at Microscale and Department of Chemistry, University of Science and Technology
of China, Hefei, Anhui, 230026, P. R. of China
Fax +86(551)3603185; E-mail: zwang3@ustc.edu.cn
b
Department of Physiology and Biophysics, Mount Sinai School of Medicine,
New York University, One Gustave L. Levy Place, New York, NY 10029-6574, USA
Received 16 February 2006
I
Abstract: A new method for synthesis of benzofurans and naphtho-
furans from 2-hydroxystilbene derivatives via an intermolecular
cyclization is reported in this study with up to 94% isolated yield.
O
OH
2 (trans)
Key words: benzofuran, naphthofuran, iodine, cyclization, syn-
thesis
+
I
1
O
Arene ring-fused furans exist widely in natural products
and bioactive compounds as key structural element,1 and
have attracted attention much to their effective synthe-
sis.1g,2 One common approach to the synthesis of this class
of compounds is iodocyclization of 2-(1-alkynyl)phe-
nols.2f Here, we report a new method to synthesize benzo-
furans and naphthofurans and discuss its possible reaction
mechanism.
3 (cis)
O
Scheme 1
meters and found that the reaction was sensitive to the
amount of I2, solvent and base. For instance, increasing
the amount of I2 in the reaction from 3 to 8 equivalents,
resulted in a steady increase of the reaction yield; and
without the base, the reaction yield was reduced to 20%.
We found that among the inorganic and organic bases
tested that include NaH, Na2CO3, K2CO3, triethylamine
and pyridine, K2CO3 was the most effective one. As for
the solvent, THF was the best among many screened.
Temperature had little effect on the reaction, as shown
from 0–60 °C. Subsequent reactions were, therefore,
carried out at room temperature. Under these optimized
reaction conditions, PBF was isolated in 65% yield.5
Initially, we wanted to employ the iodocyclization of 1 to
diastereoselectively generate 2-aryl-3-iododihydrobenzo-
furan 2 or 3 (Scheme 1) to extend our previous study on
the synthesis of 2-aryldihydrobenzofuran.3 Following the
reported procedure,4 I2 (1.2 mmol) solution in acetonitrile
(3 mL) was added dropwise to a mixture of 1 (1 mmol),
NaHCO3 (1.2 mmol) and acetonitrile (2 mL) at 0 °C with
stirring. The resulting iodocyclization product was a
mixture of 2 and 3 with a low yield of 4%, although the
majority of the starting material was recovered. The steric
hindance and conjugation effect of the phenyl groups
connecting both ends of the double bond may account for
the poor yield of the reaction. To improve the reaction
yield, I2 was raised to 3 mmol. This did not result in any
significant change of the total yield of 2 and 3, but un-
expectedly led to formation of large amount of 2-phenyl-
benzofuran (PBF, 27%). We postulated that PBF was
generated via elimination of HI from 2 and 3. To investi-
gate this hypothesis, the mixture of 2 and 3 isolated from
the reaction was redissolved in acetonitrile (2 mL). Subse-
quently, NaHCO3 (2 mmol) and I2 (3 mmol) were added
to the solution at 0 °C. However, no PBF was found. This
suggested that PBF must have been formed via other
mechanisms.
Performing this reaction with hydroxystilbene derivatives
led to further understanding of its mechanism (Table 1).
As shown with entries 1–4 and 7–12, the reaction
appeared to favor electron-donating substitution groups
on the ring B. However, an electron-withdrawing sub-
stitution on the ring A can cause an increase in the yield
(entry 6). Replacing the benzene by naphthalene not only
reduced the required ammount of iodine but also im-
proved the yield (entries 2 and 9). Different positioning of
substitution on the ring B also influenced the yield. For
example, shifting a substitution from para- to ortho-posi-
tion with respect to the double bond reduced the yield (en-
tries 13, 14 and 15), possibly because of enhanced steric
hindrance. Two methoxy groups on the meta-positions of
the ring B reduced the yield (entry 16). Some mono- and
disubstituted arene ring-fused furans can also be synthe-
sized by this method (entries 17, 18, 20–22). However, it
appeared that aromaticity of the ring B was indispensable
in order to secure an acceptable yield (entry 19).
To understand the underlying mechanisms and to improve
reaction yield, we investigated several reaction para-
SYNLETT 2006, No. 11, pp 1657–1662
1
2
.0
7
.2
0
0
6
Advanced online publication: 04.07.2006
DOI: 10.1055/s-2006-944204; Art ID: W03406ST
© Georg Thieme Verlag Stuttgart · New York

1658
C. Pan et al.
LETTER
Table 1 Synthesis of Benzofurans and Naphthofurans
Entry
Starting material
Product
Isolated yield (%)
A
R
R
B
O
OH
1
2
3
4
R = Cl
43
65
67
90
R = H
R = CH3
R = OOCCH3
H3CO
H3CO
5
6
79
75
O
OH
Br
Br
O
OH
X
O
X
OH
7
8
X = OCH3
91a
87a
90a
90a
59a
X = CH3
X = H
9
10
11
12
X = Cl
X = COOCH3
X = NO2
a,b
–
Y
Y
O
OH
13
14
15
Y = Cl
87a
71a
83a
Y = Br
Y = OCH3
OCH3
OCH3
OCH3
OCH3
16
17
74a
O
OH
80a
O
OH
Synlett 2006, No. 11, 1657–1662 © Thieme Stuttgart · New York

LETTER
Synthesis of Benzofurans and Naphthofurans
1659
Table 1 Synthesis of Benzofurans and Naphthofurans (continued)
Entry
Starting material
Product
Isolated yield (%)
18
56a
N
N
O
O
OH
19
20
21
15a
86
O
O
O
O
OH
OH
O
89a
O
O
OH
OH
22
90a
a 3 Equiv of iodine were used.
b Inseperable mixture was obtained.
On the basis of our experimental results, we proposed a
plausible mechanism for the reaction as follows
(Scheme 2). Firstly, 2-hydroxystilbene is activated by
converting to its potassium salt 4, which is oxidized to
yield a cationic intermediate 5. Then, compound 5 cycliz-
es to 6. The resulting 6 and 7 give rise to the product after
losing a proton. This proposed mechanism explains our
experimental observations. For instance, it predicts that
naphthol is more liable to be oxidized than phenol; and
thus less iodine (lower concentration) is required to trans-
fer the substituted naphthol to the corresponding interme-
diate 5. In the subsequent cyclization step, a possible 4p-
electrocyclic reaction or a [3+2] cycloaddition reaction is
involved. The double bond between C(1) and C(2)
(Scheme 2) acts as an electron-donor, whereas the phen-
oxonium cation is an electron acceptor. Substituents that
increase electron density of the electron donor or reduce
electron density of the electron acceptor would favor the
reaction. In the following deprotonation step, the con-
jugating effect of the aromatic substituent (ring B) pro-
motes the formation of the double bond and stabilizes the
product.
K2CO3
4
OK
OH
I2
oxidation
2
B
cyclization
1
A
O
6
5
O
O
H
–H+
O
7
Scheme 2
resulting reaction mixture by GCMS helped identify
quinone 10 and trace amount of 3-methyl-2-phenylbenzo-
furan. The former may form by oxidation of the interme-
diate 9 by I2. In this case, the intermediate 9 cannot be
immediately consumed via the path shown in Scheme 2
due to the lack of eliminable proton on C(1). As a result,
it was oxidized and subsequently hydrolyzed to generate
the product 10. Note that the origin of the new oxygen
According to the proposed mechanism, transformation of
hydroxystilbene to PBF involves elimination of a proton
from intermediate 7. A methyl-substituted hydroxystil-
bene 8 was employed as the starting material to further
investigate this reaction (Scheme 3). Analysis of the atom of 10 has proved to be from water by depleting the
Synlett 2006, No. 11, 1657–1662 © Thieme Stuttgart · New York

1660
C. Pan et al.
LETTER
molecular oxygen of saturated NaHCO3 aqueous solution, The results described above argue that oxidation from the
and the reaction atmosphere. Without water, the reaction intermediate 5 to a quinone (Scheme 2) may compete with
could not produce quinone but an inseparable mixture. the cyclization, which implies that its suppressive factors
The formation of 3-methyl-2-phenylbenzofuran likely in- would improve the yield of arene ring-fused furan. This
volve migration of the methyl group from C(1) to C(2), a prediction was indeed validated by the experiments in
typical characteristic of carbocations. In an effort to trap Scheme 5. Blocking the para- and ortho-position to the
the cationic intermediate 7 (Scheme 2), we added a large hydroxy group excluded any further oxidation, thereby
excess of tetrabutylammonium salt (5–20 equiv) such as yielding the best result. Collectively, these results support
fluoride, chloride, bromide or iodide to the reaction the possible existance of the intermediates 5 and 7 in the
with the hope that the haloid anion and carbocation may proposed mechanism.
form 3-halo-2-phenyldihydrobenzofuran. However, this
attempt failed possibly due to additives’ negligible effect
on the reaction. Other stronger nucleophiles such as
sodium methoxide or potassium methoxide (3–20 equiv)
also failed because of the relatively slower rate of inter-
molecular nucleophilic reaction than that of elimination
I2 (8 equiv),
K2CO3 (8 equiv)
O
OH
THF
16 (94%)
reaction. We finally resorted to intramolecular trapping by
using 2,2¢-dihydroxystilbene (12) as the starting material
(Scheme 4). After optimizing the ammount of iodine
Scheme 5
needed in the reaction, the expected product 15 was
isolated in 41% yield.
In conclusion, we have developed in this study a new
method for efficient synthesis of benzofuran and naphtho-
furan derivatives, and proposed a plausible mechanism of
this reaction. Its facile starting materials and easy experi-
mental manipulation, coupled with reasonably good
yields makes this method a promising choice for different
synthetic applications.
OH
8
oxidation
2
Acknowledgment
1
O
We are grateful to National Nature Science Foundation of China
(No. 20472078 and 30572234 to ZYW), and to the US National
Institutes of Health (to MMZ) for their support of this study.
11
9
O
further
oxidation
References and Notes
O
hydrolysis
(1) (a) Halabalaki, M.; Aligiannis, N.; Papoutsi, Z.; Mitakou, S.;
Moutsatsou, P.; Sekeris, C.; Skaltsounis, A.-L. J. Nat. Prod.
2000, 63, 1672. (b) Pacher, T.; Seger, C.; Engelmeier, D.;
Vajrodaya, S.; Hofer, O.; Greger, H. J. Nat. Prod. 2002, 65,
820. (c) Durani, N.; Jain, R.; Saeed, A.; Dikshit, D. K.;
Durani, S.; Kapil, R. S. J. Med. Chem. 1989, 32, 1700.
(d) Ohemeng, K. A.; Appollina, M. A.; Nguyen, V. N.;
Schwender, C. F.; Singer, M.; Steber, M.; Ansell, J.;
Argentieri, D.; Hageman, W. J. Med. Chem. 1994, 37, 3663.
(e) Pieters, L.; Dyck, S. V.; Gao, M.; Bai, R.; Hamel, E.;
Vlietinck, A.; Lemiere, G. J. Med. Chem. 1999, 42, 5475.
(f) Wallez, V.; Durieux-Poissonnier, S.; Chavatte, P.;
Boutin, J. A.; Audinot, V.; Nicolas, J.-P.; Bennejean, C.;
Delagrange, P.; Renard, P.; Lesieur, D. J. Med. Chem. 2002,
45, 2788. (g) Park, K. K.; Jeong, J. Tetrahedron 2005, 61,
545; and references cited therein.
O
O
O
10
trace
27%
Scheme 3
HO
O
I2 (4 equiv)
K2CO3 (4 equiv)
12
OH
O
THF
15 (41%)
(2) (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev.
2003, 103, 893; and references cited therein. (b) Willis, M.
C.; Taylor, D.; Gillmore, A. T. Org. Lett. 2004, 6, 4755.
(c) McKiernan, G. J.; Hartley, R. C. Org. Lett. 2003, 5,
4389. (d) Kraus, G. A.; Zhang, N.; Verkade, J. G.;
Nagarajan, M.; Kisanga, P. B. Org. Lett. 2000, 2, 2409.
(e) Clerici, A.; Porta, O. J. Org. Chem. 1990, 55, 1240.
(f) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70,
10292; and references cited therein. (g) Kraus, G. A.;
Schroeder, J. D. Synlett 2005, 2504.
KO
O
O
13
14
O
Scheme 4
Synlett 2006, No. 11, 1657–1662 © Thieme Stuttgart · New York

LETTER
Synthesis of Benzofurans and Naphthofurans
1661
(3) Pan, C.; Ma, Z.; Yu, J.; Zhang, Z.; Hui, A.; Wang, Z. Synlett
2005, 1922.
(4) (a) Rychnovsky, S. D.; Bartlett, P. A. J. Am. Chem. Soc.
1981, 103, 3963. (b) Pan, C.-F.; Zhang, Z.-H.; Sun, G.-J.;
Wang, Z.-Y. Org. Lett. 2004, 6, 3059.
(5) Optimized Procedure for the Synthesis of the PBF.
Hydroxystilbene (1 mmol) was dissolved in 7 mL of anhyd
THF, and then K2CO3 (8 mmol) was added with stirring at
r.t. After 5 min, I2 (8 mmol) was added in one portion. The
mixture was stirred at r.t. for 2 h, and then sat. aq NaHCO3
solution (20 mL) was added. NaHSO3 was slowly added to
the system until the excess I2 was completely reduced. The
system was subsequently extracted with Et2O, 3 × 20 mL.
The organic layer was dried over anhyd MgSO4, evaporated,
and purified by chromatography on silica gel to give the
product.
(m, 1 H), 7.50–7.44 (m, 1 H), 7.37 (s, 1 H), 7.02–6.98 (m, 2
H), 3.86 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 159.97,
155.73, 152.21, 130.59, 128.90, 127.68, 126.30, 126.23,
124.91, 124.71, 124.58, 123.73, 123.62, 114.47, 112.33,
99.01, 55.49. IR (film): 1606, 1498, 1251, 1024 cm–1.
HRMS: m/z calcd for C19H14O2: 274.0994; found: 274.0987.
2-(4-Methylphenyl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.15 (d, J = 8.2 Hz, 1 H), 7.93 (d, J = 8.2
Hz, 1 H), 7.81 (d, J = 8.1 Hz, 2 H), 7.72–7.65 (m, 2 H), 7.60–
7.55 (m, 1 H), 7.50–7.45 (m, 2 H), 7.27 (d, J = 8.1 Hz, 2 H),
2.40 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 155.80,
152.30, 138.34, 130.56, 129.63, 128.89, 128.06, 127.72,
126.25, 124.97, 124.74, 124.58, 123.59, 112.35, 99.83,
21.46. IR (film): 2916, 2857, 1501, 1384 cm–1. HRMS:
m/z calcd for C19H14O: 258.1045; found: 258.1053.
2-Phenylnaphtho[2,1-b]furan: 1H NMR (300 MHz,
CDCl3): d = 8.17 (dd, J = 0.6, 7.8 Hz, 1 H), 7.96–7.91 (m, 3
H), 7.74–7.67 (m, 2 H), 7.62–7.57 (m, 1 H), 7.52–7.45 (m, 4
H), 7.38–7.33 (m, 1 H). 13C NMR (75 MHz, CDCl3):
d = 155.53, 152.51, 130.80, 130.59, 128.96, 128.94, 128.38,
127.77, 126.38, 125.31, 124.80, 124.69, 123.59, 112.41,
100.58. IR (film): 3053, 2924, 2854, 1628, 1603, 1488 cm–1.
HRMS: m/z calcd for C18H12O: 244.0888; found: 244.0890.
2-(4-Chlorophenyl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.15 (d, J = 8.1 Hz, 1 H), 7.94 (d, J = 8.1
Hz, 1 H), 7.84 (d, J = 8.6 Hz, 2 H), 7.73 (d, J = 9.0 Hz, 1 H),
7.67 (d, J = 9.0 Hz, 1 H), 7.62–7.57 (m, 1 H), 7.52–7.47 (m,
2 H), 7.43 (d, J = 8.6 Hz, 2 H). 13C NMR (75 MHz, CDCl3):
d = 154.33, 152.55, 134.08, 130.58, 129.23, 129.17, 128.96,
127.69, 126.50, 125.93, 125.65, 124.81, 124.56, 123.52,
112.32, 100.98. IR (film): 1585, 1481, 1383, 1277, 1266,
1167 cm–1. HRMS: m/z calcd for C18H1135ClO: 278.0498;
found: 278.0511.
2-(4-Chlorophenyl)benzofuran: 1H NMR (300 MHz,
CDCl3): d = 7.78 (dd, J = 6.5, 1.8 Hz, 2 H), 7.59–7.49 (m, 2
H), 7.41 (d, J = 6.5 Hz, 2 H), 7.32–7.20 (m, 2 H), 7.00 (s, 1
H). 13C NMR (75 MHz, CDCl3): d = 155.07, 154.94, 124.48,
129.28, 129.19, 126.44, 126.29, 124.71, 123.25, 121.15,
111.34, 101.90. IR (film): 1580, 1487, 1451, 1404, 1256,
1093 cm–1. HRMS: m/z calcd for C14H935ClO: 228.0342;
found: 228.0351.
2-Phenylbenzofuran: 1H NMR (400 MHz, CDCl3):
d = 7.87 (dd, J = 8.5, 1.4 Hz, 2 H), 7.52–7.23 (m, 7 H), 7.03
(d, J = 0.9 Hz, 1 H). 13C NMR (100 MHz, CDCl3):
d = 155.94, 154.91, 130.52, 129.25, 128.80, 128.56, 124.96,
124.27, 122.95, 120.91, 111.19, 101.31. IR (film): 2926,
2856, 1562, 1470, 1455, 1121 cm–1. HRMS: m/z calcd for
C14H10O: 194.0732; found: 194.0728.
2-(4-Methylphenyl)benzofuran: 1H NMR (300 MHz,
CDCl3): d = 7.75 (d, J = 8.1 Hz, 2 H), 7.57–7.49 (m, 2 H),
7.26–7.21 (m, 4 H), 6.95 (s, 1 H), 2.39 (s, 3 H). 13C NMR (75
MHz, CDCl3): d = 156.36, 154.94, 138.72, 129.62, 129.51,
127.92, 125.05, 124.13, 123.00, 120.88, 111.23, 100.70,
21.51. IR (film): 2919, 1617, 1502, 1450, 1258, 1167, 1111,
1034 cm–1. HRMS: m/z calcd for C15H12O: 208.0888; found:
208.0885.
Methyl 4-(Naphtho[2,1-b]furan-2-yl)benzoate: 1H NMR
(300 MHz, CDCl3): d = 8.17–8.11 (m, 3 H), 7.97–7.93 (m, 3
H), 7.75 (d, J = 8.9 Hz, 1 H), 7.71 (d, J = 8.9 Hz, 1 H), 7.62–
7.58 (m, 2 H), 7.53–7.47 (m, 1 H), 3.94 (s, 3 H). 13C NMR
(75 MHz, CDCl3): d = 166.85, 154.28, 153.05, 134.77,
130.65, 130.35, 129.54, 129.04, 127.80, 126.71, 126.30,
124.98, 124.54, 124.45, 123.56, 112.41, 102.72, 52.31.
IR (film): 1715, 1607, 1435, 1411, 1340, 1278, 1179, 1107
cm–1. HRMS: m/z calcd for C20H14O3: 302.0943; found:
302.0951.
4-(Benzofuran-2-yl)phenyl Acetate: 1H NMR (300 MHz,
CDCl3): d = 7.87 (d, J = 8.9 Hz, 2 H), 7.59–7.56 (m, 1 H),
7.53–7.50 (m, 1 H), 7.31–7.16 (m, 4 H), 6.98 (d, J = 0.9 Hz,
1 H), 2.32 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 169.35,
155.25, 155.02, 150.92, 129.30, 128.35, 126.15, 124.45,
123.11, 122.12, 121.05, 111.27, 101.50, 21.20. IR (film):
2927, 1750, 1498, 1451, 1374, 1218, 1194 cm–1. HRMS:
m/z calcd for C16H12O3: 252.0786; found: 252.0790.
2-(2-Methoxyphenyl)benzofuran: 1H NMR (300 MHz,
CDCl3): d = 8.07 (dd, J = 7.7, 1.7 Hz, 1 H), 7.60–7.58 (m, 1
H), 7.5 (d, J = 7.9 Hz, 1 H), 7.35 (d, J = 0.5 Hz, 1 H), 7.32–
7.18 (m, 3 H), 7.10–6.99 (m, 2 H), 4.00 (s, 3 H). 13C NMR
(75 MHz, CDCl3): d = 156.63, 154.03, 152.31, 129.93,
129.35, 127.18, 124.22, 122.76, 121.15, 120.89, 119.52,
111.17, 110.94, 106.45, 55.54. IR (film): 3063, 2936, 2837,
1603, 1585, 1493, 1448, 1282, 1249, 1018 cm–1. HRMS:
m/z calcd for C15H12O2: 224.0837; found: 224.0831.
5-Bromo-2-phenylbenzofuran: 1H NMR (300 MHz,
CDCl3): d = 7.84 (dd, J = 8.5, 1.5 Hz, 2 H), 7.72–7.68 (m, 1
H), 7.47–7.36 (m, 5 H), 6.95 (s, 1 H). 13C NMR (75 MHz,
CDCl3):d = 157.35, 153.72, 131.33, 130.02, 129.11, 128.96,
127.19, 125.18, 123.59, 116.13, 112.70, 100.74. IR (film):
3091, 2923, 2853, 1605, 1578, 1491, 1450, 1440 cm–1.
HRMS: m/z calcd for C14H979BrO: 271.9837; found:
271.9833.
2-(2-Chlorophenyl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.20 (dd, J = 8.1, 0.5 Hz, 1 H), 8.10 (dd,
J = 7.9, 1.7 Hz, 1 H), 8.00 (d, J = 0.5 Hz, 1 H), 7.94 (d,
J = 7.9 Hz, 1 H), 7.75 (d, J = 9.0 Hz, 1 H), 7.67 (d, J = 9.0
Hz, 1 H), 7.62–7.57 (m, 1 H), 7.52–7.46 (m, 2 H), 7.41–7.35
(m, 1 H), 7.29–7.23 (m, 1 H). 13C NMR (75 MHz, CDCl3):
d = 151.87, 151.47, 130.99, 130.52, 129.15, 128.89, 128.80,
128.74, 127.95, 127.06, 126.52, 126.03, 124.73, 124.44,
123.60, 112.16, 106.50. IR (film): 3060, 2924, 1629, 1590,
1521, 1469, 1385, 1172 cm–1. HRMS: m/z calcd for
C18H1135ClO: 278.0498; found: 278.0505.
2-(2-Bromophenyl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.21 (d, J = 8.1 Hz, 1 H), 8.03–8.01 (m, 2
H), 7.95 (d, J = 8.1 Hz, 1 H), 7.77–7.66 (m, 3 H), 7.63–7.58
(m, 1 H), 7.52–7.40 (m, 2 H), 7.24–7.17 (m, 1 H). 13C NMR
(75 MHz, CDCl3): d = 152.60, 152.00, 134.40, 131.15,
130.49, 129.62, 129.16, 128.89, 127.92, 127.59, 126.52,
125.99, 124.73, 124.20, 123.60, 120.48, 112.23, 106.18. IR
(film): 2925, 1626, 1585, 1465, 1416, 1384, 1168 cm–1.
HRMS: m/z calcd for C18H1179BrO: 321.9993; found:
321.9985.
2-(4-Methoxyphenyl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.14 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 8.0
Hz, 1 H), 7.87–7.83 (m, 2 H), 7.70–7.64 (m, 2 H), 7.60–7.54
2-(2-Methoxyphenyl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.22 (d, J = 8.0 Hz, 1 H), 8.12 (dd,
J = 7.7, 1.7 Hz, 1 H), 7.94 (d, J = 8.0 Hz, 1 H), 7.83 (s, 1 H),
Synlett 2006, No. 11, 1657–1662 © Thieme Stuttgart · New York

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C. Pan et al.
LETTER
7.73–7.66 (m, 2 H), 7.61–7.55 (m, 1 H), 7.49–7.44 (m, 1 H),
7.35–7.29 (m, 1 H), 7.13–7.07 (m, 1 H), 7.03 (d, J = 8.3 Hz,
1 H), 4.05 (s, 3 H). 13C NMR (75 MHz, CDCl3): d = 156.35,
151.87, 151.49, 130.51, 129.07, 128.86, 128.00, 126.90,
126.20, 125.12, 125.07, 124.47, 123.72, 120.97, 119.70,
112.24, 111.22, 105.53, 55.62. IR (film): 3058, 3000, 1626,
1597, 1584, 1491, 1462, 1445, 1380, 1250 cm–1. HRMS:
m/z calcd for C19H14O2: 274.0994; found: 274.0991.
2-(3,5-Dimethoxyphenyl)naphtho[2,1-b]furan: 1H NMR
(300 MHz, CDCl3): d = 8.16 (d, J = 8.1 Hz, 1 H), 7.94 (d,
J = 8.1 Hz, 1 H), 7.74–7.67 (m, 2 H), 7.62–7.57 (m, 1 H),
7.50–7.46 (m, 2 H), 7.09 (d, J = 1.3 Hz, 2 H), 6.48 (s, 1 H),
3.90 (s, 6 H). 13C NMR (75 MHz, CDCl3): d = 161.33,
155.34, 152.45, 132.51, 130.58, 128.95, 127.76, 126.43,
125.47, 124.73, 124.60, 123.59, 112.39, 102.91, 101.10,
100.99, 55.63. IR (film): 3002, 2936, 2837, 1597, 1561,
1460, 1424, 1385, 1266, 1204, 1157 cm–1. HRMS: m/z calcd
for C20H16O3: 304.1099; found: 304.1099.
CDCl3): d = 153.93, 150.80, 131.56, 131.30, 128.72, 127.96,
126.82, 124.43, 122.45, 119.39, 111.37, 111.04, 9.55.
IR (film): 3059, 2924, 1600, 1450, 1259, 1211, 1109, 1068
cm–1. HRMS: m/z calcd for C15H12O: 208.0888; found:
208.0895.
2,3-Diphenylnaphtho[2,1-b]furan: 1H NMR (300 MHz,
CDCl3): d = 7.90 (d, J = 8.0 Hz, 1 H), 7.76–7.70 (m, 2 H),
7.57–7.52 (m, 8 H), 7.40–7.35 (m, 1 H), 7.29–7.19 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 151.52, 150.17, 134.84,
131.05, 130.98, 130.67, 129.46, 129.06, 128.49, 128.27,
127.86, 126.32, 126.08, 124.34, 123.72, 123.16, 119.65,
112.27. IR (film): 3056, 2925, 2854, 1602, 1524, 1502,
1483, 1443, 1393, 1344, 1393 cm–1. HRMS: m/z calcd for
C24H16O: 320.1201; found: 320.1193.
3-Methyl-2-phenylnaphtho[1,2-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.37 (d, J = 8.3 Hz, 1 H), 7.94–7.87 (m, 3
H), 7.68–7.44 (m, 6 H), 7.39–7.33 (m, 1 H), 2.55 (s, 3 H). 13
NMR (75 MHz, CDCl3): d = 150.26, 149.27, 131.79,
131.71, 128.71, 128.49, 127.58, 126.55, 126.49, 126.26,
125.00, 123.10, 121.33, 120.25, 118.05, 112.60, 9.71.
IR (film): 2923, 1604, 1491, 1446, 1384 cm–1. HRMS:
m/z calcd for C19H14O: 258.1045; found: 258.1051.
C
2-(Naphthalen-1-yl)naphtho[2,1-b]furan: 1H NMR (300
MHz, CDCl3): d = 8.56 (d, J = 8.1 Hz, 1 H), 8.21 (d, J = 8.1
Hz, 1 H), 7.98–7.88 (m, 4 H), 7.75 (s, 2 H), 7.63–7.50 (m, 6
H). 13C NMR (75 MHz, CDCl3): d = 155.17, 152.67, 134.15,
130.78, 130.58, 129.44, 128.95, 128.78, 128.50, 127.83,
127.28, 127.01, 126.45, 126.23, 125.68, 125.45, 125.39,
124.71, 124.45, 123.62, 112.49, 105.08. IR (film): 3053,
2924, 1629, 1524, 1509, 1385 cm–1. HRMS: m/z calcd for
C22H14O: 294.1045; found: 294.1032.
2-(2-Phenylprop-1-enyl)cyclohexa-2,5-diene-1,4-dione:
1H NMR (300 MHz, CDCl3): d = 7.68–7.63 (m, 2 H), 7.59–
7.55 (m, 2 H), 7.38–7.21 (m, 4 H), 7.09 (t, J = 7.5 Hz, 1 H),
1.83 (d, J = 0.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3):
d = 201.74, 171.39, 138.38, 138.33, 128.71, 128.26, 125.36,
124.89, 124.76, 122.28, 119.63, 113.52, 24.46. IR (film):
2926, 2855, 1721, 1612, 1476, 1462 cm–1. HRMS: m/z calcd
for C15H12O2: 204.0837; found: 224.0829.
4-(Naphtho[2,1-b]furan-2-yl)pyridine: 1H NMR (300
MHz, CDCl3): d = 8.70–8.67 (m, 2 H), 8.16 (dd, J = 8.0, 2.2
Hz, 1 H), 7.95 (d, J = 8.1 Hz, 1 H), 7.80–7.59 (m, 6 H), 7.54–
7.51 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = 152.96,
152.18, 150.28, 137.26, 130.43, 128.88, 127.55, 126.80,
126.70, 124.97, 123.96, 123.29, 118.29, 112.14, 103.82.
IR (film): 1602, 1538, 1519, 1414, 1384 cm–1. HRMS:
m/z calcd for C17H11NO: 245.0841; found: 245.0839.
Methyl Naphtho[2,1-b]furan-2-carboxylate: 1H NMR
(300 MHz, CDCl3): d = 8.14 (d, J = 7.9 Hz, 1 H), 8.00 (s, 1
H), 7.95 (d, J = 7.9 Hz, 1 H), 7.86 (d, J = 9.0 Hz, 1 H), 7.70–
7.61 (m, 2 H), 7.56–7.51 (m, 1 H), 4.01 (s, 3 H). 13C NMR
(75 MHz, CDCl3): d = 159.98, 154.17, 144.90, 130.65,
129.33, 129.13, 128.13, 127.43, 125.56, 123.44, 122.86,
113.10, 112.84, 52.44. IR (film): 2952, 1731, 1586, 1551,
1439, 1331, 1282, 1227, 1206, 1171, 1117 cm–1. HRMS:
m/z calcd for C14H10O3: 226.0630; found: 226.0644.
3-Methyl-2-phenylbenzofuran: 1H NMR (300 MHz,
CDCl3): d = 7.81 (dd, J = 8.5, 1.3 Hz, 2 H), 7.52–7.45 (m, 4
H), 7.38–7.24 (m, 3 H), 2.48 (s, 3 H). 13C NMR (75 MHz,
4b,9b-Dihydrobenzo[b]benzofuro[2,3-d]furan: 1H NMR
(300 MHz, CDCl3): d = 7.53 (dd, J = 0.8, 7.5 Hz, 2 H), 7.30–
7.25 (m, 2 H), 6.99–6.94 (m, 2 H), 6.86 (d, J = 8.2 Hz, 2 H),
6.28 (s, 2 H). 13C NMR (75 MHz, CDCl3): d = 160.18,
131.46, 126.68, 124.56, 121.27, 110.95, 86.59. IR (film):
3051, 2923, 2852, 1602, 1483, 1464, 1326, 1314, 1241,
1225, 1173 cm–1. HRMS: m/z calcd for C14H10O2: 210.0681;
found: 210.0678.
5,7-Di-tert-butyl-2-phenylbenzofuran: 1H NMR (300
MHz, CDCl3): d = 7.86 (dd, J = 7.5, 1.4 Hz, 2 H), 7.47–7.24
(m, 5 H), 6.97 (s, 1 H), 1.58 (s, 9 H), 1.39 (s, 9 H). 13C NMR
(75 MHz, CDCl3): d = 155.27, 151.47, 145.87, 133.90,
131.10, 129.51, 128.91, 128.34, 124.91, 119.25, 115.17,
101.60, 35.04, 34.71, 32.09, 30.24. IR (film): 3108, 2958,
2867, 1607, 1466, 1406, 1391, 1362, 1280, 1244, 1163
cm–1. HRMS: m/z calcd for C22H26O: 306.1984; found:
306.1973.
Synlett 2006, No. 11, 1657–1662 © Thieme Stuttgart · New York