An efficient friedel-crafts/oxa-michael/aromatic annulation: Rapid access to substituted naphtho[2,1-b]furan, naphtho[1,2-b]furan, and benzofuran derivatives

Article abstract of DOI:10.1002/chem.201204221

Substituted naphthofurans and benzofurans are easily accessible by treatment of naphthols/substituted phenols with nitroallylic acetates through a substitution-elimination process promoted by cesium carbonate. Reactions between naphthols and aromatic/heteroaromatic-substituted nitroallylic acetates gave the desired functionalized naphthofurans in high to excellent chemical yields (14-97 %). On the other hand, treatment of phenol derivatives (i.e., 3-dimethylamino-, 3-methoxy-, and 3,5-dimethoxyphenol) with various nitroallylic acetates afforded the corresponding benzofurans in moderate to good chemical yields (24-91 %). The reaction proceeded through an interesting Friedel-Crafts S_N2' process followed by intramolecular oxa-Michael cyclization and subsequent aromatization. A plot of log (k/k_H) against Hammett constants σ_p showed satisfactory linearity with a positive ρ value, indicating that the initial Friedel-Crafts-type S_N2' process constituted the rate-determining step. This methodology has been applied to the synthesis of various novel C₂ and C₃ symmetric bis- and trisfurans by using catechol and phloroglucinol as the nucleophilic partners. The reactivity decreased when alkyl-substituted nitroallylic acetate systems were used. This might be related to the decreased electrophilic character of these substrates. Copyright

Full text of DOI:10.1002/chem.201204221

DOI: 10.1002/chem.201204221
An Efficient Friedel–Crafts/Oxa-Michael/Aromatic Annulation: Rapid
Access to Substituted Naphtho
N
ACHTUNGTREN[NUGN 1,2-b]furan, and
Shaik Anwar, Wan-Yun Huang, Chih-Hao Chen, You-Song Cheng, and
Kwunmin Chen*[a]
Abstract: Substituted naphthofurans
forded the corresponding benzofurans
in moderate to good chemical yields
(24–91%). The reaction proceeded
through an interesting Friedel–Crafts
SN2’ process followed by intramolecular
oxa-Michael cyclization and sub-
positive 1 value, indicating that the ini-
and benzofurans are easily accessible
by treatment of naphthols/substituted
phenols with nitroallylic acetates
tial Friedel–Crafts-type SN2’ process
constituted the rate-determining step.
This methodology has been applied to
the synthesis of various novel C2 and
C3 symmetric bis- and trisfurans by
using catechol and phloroglucinol as
the nucleophilic partners. The reactivi-
ty decreased when alkyl-substituted
through
a
substitution–elimination
process promoted by cesium carbonate.
Reactions between naphthols and aro-
matic/heteroaromatic-substituted nitro-
allylic acetates gave the desired func-
tionalized naphthofurans in high to ex-
cellent chemical yields (14–97%). On
the other hand, treatment of phenol
derivatives (i.e., 3-dimethylamino-, 3-
methoxy-, and 3,5-dimethoxyphenol)
with various nitroallylic acetates af-
A
A
plot of
log (k/kH) against Hammett constants
sp showed satisfactory linearity with a
nitroACTHNUTRGNEUGaN llylic acetate systems were used.
This might be related to the decreased
electrophilic character of these sub-
strates.
Keywords: benzofurans · Friedel–
Crafts reaction
· heterocycles ·
naphthofurans · nitroallylic acetate ·
synthetic methods
Introduction
Benzo- and naphthofurans are
arguably some of the most im-
portant types of heterocycles.[1]
They are present in many bio-
logically active natural products
and pharmaceutically active
agents, as exemplified by (Æ)-
laevigatin,[2] balsaminone A,[3]
rubioncolin B,[4] cannabifuran,[5]
and karnatakafurans A and B[6]
(Figure 1). Benzo- and naph-
thofurans are also useful syn-
thetic building blocks in organic
Figure 1. Benzo- and naphthofuran-containing natural products and related compounds.
synthesis and, as a consequence,
many efficient synthetic routes
have been devised for their synthetic acquisition. Most of
the reported methods have involved the use of versatile
starting substrates[7] and transition metals, such as rhodi-
um,[8] ruthenium,[9] palladium,[10] platinum,[11] iron,[12]
copper,[13] silver,[14] gold,[15] and zinc,[16] as well as Grignard
reagents.[17] However, these protocols are subject to some
limitations, such as harsh reaction conditions, low chemical
yields, or unsatisfactory scope and efficiency.[18] Alternative
routes for the synthesis of diverse naphthofuran and benzo-
[a] Dr. S. Anwar, W.-Y. Huang, C.-H. Chen, Y.-S. Cheng,
Prof. Dr. K. Chen
Chemistry Department, National Taiwan Normal University
88 Sec. 4, TingChow Rd., Taipei 116 (Taiwan)
Fax : (+886)2-29324249
E-mail: kchen@ntnu.edu.tw
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201204221.
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FULL PAPER
Table 1. Optimization of the reaction conditions for the synthesis of 2,3-
substituted naphthofurans.[a]
furan substitution patterns are required. The use of naph-
thols in Friedel–Crafts reactions has only rarely been report-
ed.[19] Therefore, there is a pressing need for the develop-
ment of alternative routes to functionalized naphthofurans
and benzofurans starting from naphthols and phenols.
Results and Discussion
Entry Base
Solvent Yield
[%][b]
Entry Base
Solvent Yield
[%][b]
1
2
3
4
5
6
Et3N
CH2Cl2 35
7
8
9
10
11[c]
12[c]
Cs2CO3 THF
58
Cs2CO3 dioxane 78
Cs2CO3 toluene 83
The use of enols/enamines as neutral nucleophilic partners
in organic reactions has become increasingly important in
organic synthesis. Previously, we reported an efficient syn-
thetic strategy for accessing tetrasubstituted furans that ex-
ploits a Feist–Bꢁnary-type reaction between electron-defi-
cient nitroallylic acetates 1 and 1,3-dicarbonyl compounds/
a-activated ketones. The corresponding multifunctional 3,5-
alkyl/aryl-2-carboxylate-4-keto/cyano tetrasubstituted furans
were typically obtained in respectable to excellent chemical
yields (52–99%).[20] These results encouraged us to explore
further the utilization of functionalized nitroallylic acetates.
We envisaged that structurally adorned naphthofurans and
benzofurans could be synthesized from nitroallylic acetates
and many commonly available substituted naphthol and
phenol derivatives (Scheme 1).
DIPEA CH2Cl2 43
Na2CO3 MeOH 53
K2CO3
Cs2CO3 MeOH 66
Cs2CO3 CH3CN 39
MeOH 55
Cs2CO3 DCE
Cs2CO3 CH2Cl2 84
Cs2CO3 CHCl3 91
73
[a] All reactions were performed by using nitroallylic acetate (31.4 mg,
0.11 mmol), 2-naphthol 2 (1.0 equiv), and base (1.0 equiv) in the indicat-
ed solvent at ambient temperature. DIPEA=N,N-diisopropylethylamine.
[b] Yield of the isolated product. [c] Reaction was carried out for 4 h.
diminished when acetonitrile was used instead (Table 1,
entry 6). The use of ethereal solvents such as THF or diox-
ane gave naphthofuran 3a in moderate chemical yields
(Table 1, entries 7 and 8). The chemical yield increased
when
a nonpolar solvent was used (Table 1, entry 9).
Among the chlorinated solvents tested, chloroform proved
to be the solvent of choice for this reaction (Table 1, en-
tries 10–12), the desired naphthoACTHUNTGRNEUNG[2,1-b]furan 3a being ob-
tained in 91% chemical yield within 4 h.
After optimization of the reaction conditions, we turned
our attention to substrate scope to assess the general utility
of this reaction of 2-naphthol and nitroallylic acetates
(Figure 2). The reaction was found to tolerate various aryl-
and heteroaryl-substituted nitroallylic acetates. Although
the chemical yields decreased when halogen substituents
were present in the starting substrates (Figure 2, 3b,c), a
methoxy substituent proved beneficial, such that the desired
product was obtained in 90% yield (Figure 2, 3d). Excellent
results were obtained when heteroaromatic nitroallylic ace-
Scheme 1. Retrosynthetic plan for the synthesis of substituted naphtho-/
benzofurans.
In our initial studies, 2-naphthol and nitroallylic acetate
1a were chosen as model substrates (Table 1). When the re-
action was attempted in the ab-
sence of a base, either at 08C
or at ambient temperature, the
corresponding naphtho
ACHTUNGTRENN[UNG 2,1-b]-
ACHTUNGTRENNUNG
then proceeded to test various
organic bases, but most of them
proved to be unproductive
(data not shown). Unsatisfacto-
ry chemical yields of product
3a were obtained in the pres-
ence of Et3N or DIPEA
(Table 1, entries 1 and 2). The
use of inorganic bases proved
beneficial, with Cs2CO3 giving
moderate yields of product 3a
in methanol (Table 1, entries 3–
5). However, the reaction rate Figure 2. The chemical structures of naphthoACTHNUTRGENUGN[2,1-b]furans 3a–g.
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4345

K. Chen et al.
tates were used under the opti-
mum reaction conditions
(Figure 2, 3e,f). The reactivity
and chemical yield decreased
significantly when an alkyl-sub-
stituted nitroallylic acetate was
used (Figure 2, 3g). The de-
creased electrophilic character
of the alkyl-substituted nitro-
ACHTUNGTRENNUNGallylic acetate as a Michael ac-
ceptor may be responsible for
this observation.
We next studied the synthesis
of various naphthofurans by
treating 1-naphthol with the ap-
propriate nitroallylic acetates
(Figure 3). It was observed that,
in comparison to 2-naphthol,
prolonged reaction times (up to
5 h) were required for the reac-
tions to reach completion. Irre-
spective of the substituent pres-
ent on the phenyl ring, func-
Figure 3. The chemical structures of naphthoACTHNUTRGNE[NUG 1,2-b]furans 4a–g.
tionalized naphthoACHTUNGTRNEU[NG 1,2-b]furan
derivatives 4a–f were obtained
in moderate to good chemical
yields (60–74%). Among the
different para-substituted nitro-
allylic acetates screened, it was
found that those bearing elec-
tron-donating
groups
per-
formed marginally better than
those bearing electron-with-
drawing groups (Figure 3, 4a–
d). Chemical yields were also
lower with 1-naphthols than
with 2-naphthols (Figure 2).
This could be due to a more
stabilized C1 enol intermediate
derived from 2-naphthol com-
Figure 4. The chemical structures of benzofurans 5a–g and 6a–c.
pared to the C2 enol derived
from 1-naphthol. A very low
yield (14%) was obtained with an aliphatic nitroallylic ace-
tate substrate under the present reaction conditions
(Figure 3, 4g).
the reaction was tolerant to various aryl and heteroaryl
groups in the starting nitroallylic acetates, and these sub-
strates gave benzofurans 5a–f in up to 91% chemical yield.
The structures of compounds 5d and 5 f were further con-
firmed by single-crystal X-ray analysis.[21] Not unexpectedly,
lower reactivity was again observed for the aliphatic sub-
strate (Figure 4, 5g). As expected, 3-methoxyphenol showed
lower reactivity towards nitroallylic acetates and two
regioisomers were isolated. For example, the use of 4-chlo-
Next, we studied the synthesis of benzofuran derivatives
by using various phenols with a view to expanding the scope
of the present protocol. It was anticipated that the phenol
derivatives would be less reactive and amenable to benzo-
furan synthesis by this methodology. Indeed, many of the
electron-rich phenols examined as nucleophiles failed to
give any of the desired products. To our delight, however,
three phenol derivatives were found to be suitable for this
reaction, albeit after prolonged reaction periods (24–48 h).
Treatment of the nitroallylic substrates with 3,5-dimethoxy-
phenol gave the corresponding benzofurans 5a–g in reason-
able to high chemical yields (Figure 4). It was observed that
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
48 h (Figure 4, 6a/6a’). These two regioisomers proved sepa-
rable and could be characterized by the coupling constant of
the ortho-hydrogen of 6a’ (Jmeta =2.0 Hz). Interestingly, for
the more reactive heterocyclic nitroallylic acetates, the para-
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Versatile Synthesis of Naphthofurans and Benzofurans
FULL PAPER
substituted regioisomers of 6b
and 6c were predominantly
formed.
The other neutral nucleophil-
ic partner that proved to be
well-suited for this reaction was
3-(dimethylamino)phenol.
Treatment of various nitroallyl-
ic acetates with 3-(dimethylami-
no)phenol gave the correspond-
ing adducts 7a–f in good chemi-
cal yields, with the para-substi-
tuted products predominating
(Figure 5, 7a–f). The structure
Figure 5. The chemical structures of benzofurans 7a–f.
of compound 7d was further
confirmed by single-crystal X-
ray analysis.[21] The coupling
constants of the characteristic
ortho-hydrogen atoms in 7a–f
were in the range 2.0–2.4 Hz.
The reactions of aliphatic sub-
strates with 3-(dimethylamino)-
phenol were found to proceed
sluggishly (data not shown).
The development of symmet-
Scheme 3. Mechanistic rationale for the formation of substituted naphthofuran derivatives.
rical compounds for use in
asymmetric catalysis and recognition has attracted much at-
tention and the synthesis and application of compounds
with C2 and C3 symmetry has been the topic of much recent
research interest.[22] In light of this, we decided to apply our
method to the synthesis of diverse C2- and C3-symmetric
furans under the optimized reaction conditions. Indeed,
treatment of nitroallylic acetates with phloroglucinol and
catechol led to trisfuran 8 and bisfuran 9 in chemical yields
of 24 and 40%, respectively (Scheme 2).
A reasonable mechanistic explanation of our new reaction
process is as follows. First, a Friedel–Crafts-type reaction of
1-naphthol with the nitroallylic acetate occurs through the
nucleophilic 2-carbon atom; it proceeds through an SN2’
process, which liberates acetic acid (Scheme 3). This is fol-
lowed by an intramolecular oxa-Michael cyclization by the
enol oxygen atom, which forms the five-membered dihydro-
furan ring (5-exo-trig addition). The preferential formation
of a five-membered ring over a six-membered ring is consis-
tent with Baldwinꢂs rules.[23] Subsequently, the energetically
favored aromatization of the furan core scaffold is achieved
by the elimination of nitrous acid.
To provide further insight into the mechanism, Hammett
correlation studies were carried out on the reactions of
1-naphthol with phenyl-substituted nitroallylic acetates bear-
ing electron-withdrawing (4-Cl-) and electron-donating
AHCTUNGRTEGNUN(N 4-OMe-) groups. A plot of log (k/kH) against the Hammett
constants sp showed satisfying linearity, with a correlation
coefficient of 0.9931 (Figure 6, top).[24] The positive 1 value
(+0.8317) can be qualitatively interpreted in terms of a de-
veloping negative charge in the transition state.[25] In addi-
tion, a further experiment was carried out in which deuterat-
ed 2,3,4,5,6,7,8-[d7]1-naphthol was treated with the same
substrates. The rate data were plotted as log (k/kH) versus sp
to give the equation: y=0.9159x+0.0281; R2 =0.9889
(Figure 6, bottom).[24] The positive 1 value (+0.9159) implies
that the initial Friedel–Crafts-type SN2’ process constituted
the rate-determining step.
Conclusion
We have developed an efficient new synthesis of substituted
naphthoACHTNUTRGENN[UG 2,1-b]furans, naphthoCAHTUNGTRENN[UGN 1,2-b]furans, and benzofurans
that proceeds through a novel Friedel–Crafts/oxa-Michael/
aromatic annulation reaction. The reaction involves an inter-
esting SN2’ and 5-exo-trig substitution–elimination process.
Scheme 2. The synthesis of benzofurans 8 and 9.
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4347

K. Chen et al.
the corresponding product, ethyl 2-(1-phenylnaphthoACTHNUGRTENUNG[2,1-b]furan-2-yl)
acetate (3a).
Ethyl 2-(1-phenylnaphthoACTHNUTRGNEUG[N 2,1-b]furan-2-yl)acetate (3a): White solid; m.p.
80.7–81.68C; 1H NMR (400 MHz, CDCl3): d=7.90 (d, 1H, J=8.0 Hz),
7.76–7.72 (m, 2H), 7.66 (d, 1H, J=8.8 Hz), 7.55–7.46 (m, 5H), 7.41–7.37
(m, 1H), 7.31–7.27 (m, 1H), 4.18 (q, 2H, J=7.2 Hz), 3.76 (s, 2H),
1.25 ppm (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=169.2,
151.9, 146.8, 133.2, 130.8, 130.4, 128.8, 128.7, 128.1, 128.0, 125.9, 125.5,
124.2, 123.1, 121.9, 121.6, 112.3, 61.3, 33.0, 14.1 ppm; IR (CH2Cl2): n˜ =
3063, 2974, 2915, 1738, 1572, 1447, 1395, 1318, 1189, 1100, 1034,
1005 cmÀ1; HRMS (ESI): m/z calcd for C22H18NaO3: 353.1154 [M+Na]+;
found: 353.1157.
Ethyl 2-[1-(4-chlorophenyl)naphthoACTHNUTRGENUGN[2,1-b]furan-2-yl]acetate (3b): Vis-
cous liquid; 1H NMR (500 MHz, CDCl3): d =7.92 (d, 1H, J=8.0 Hz),
7.74 (d, 1H, J=9.0 Hz), 7.71 (d, 1H, J=8.0 Hz), 7.66 (d, 1H, J=9.0 Hz),
7.52–7.48 (m, 4H), 7.43–7.40 (m, 1H), 7.34–7.31 (m, 1H), 4.18 (q, 2H,
J=9.0 Hz), 3.73 (s, 2H), 1.26 ppm (t, 3H, J=9.0 Hz); 13C NMR
(125 MHz, CDCl3): d=169.1, 151.9, 147.0, 134.1, 131.8, 131.7, 130.8,
129.0, 128.9, 127.9, 126.0, 125.7, 124.3, 122.9, 121.7, 120.5, 112.3, 61.4,
33.0, 14.1 ppm; IR (CH2Cl2): n˜ =2982, 2915, 2849, 1738, 1491, 1392, 1366,
1322, 1259, 1193, 1089, 1027, 990, 831, 806 cmÀ1; HRMS (ESI): m/z calcd
for C22H17ClNaO3: 387.0764 [M+Na]+; found: 387.0775.
Ethyl 2-[1-(4-bromophenyl)naphthoACTHNUTRGENUGN[2,1-b]furan-2-yl]acetate (3c): Vis-
cous liquid; 1H NMR (400 MHz, CDCl3): d =7.91 (d, 1H, J=8.0 Hz),
7.72 (t, 2H, J=8.0 Hz), 7.67–7.64 (m, 3H), 7.44–7.39 (m, 3H), 7.36–7.31
(m, 1H), 4.18 (q, 2H, J=7.2 Hz), 3.73 (s, 2H), 1.26 ppm (t, 3H, J=
7.2 Hz); 13C NMR (100 MHz, CDCl3): d =169.0, 151.9, 146.9, 132.2,
132.1, 132.0, 130.8, 128.9, 127.9, 126.0, 125.7, 124.3, 122.9, 122.3, 121.6,
120.5, 112.3, 61.4, 32.9, 14.1 ppm; IR (CH2Cl2): n˜ =3055, 2982, 2923, 1735,
1576, 1488, 1388, 1362, 1318, 1097 cmÀ1; HRMS (ESI): m/z calcd for
C22H17BrO3: 409.0439 [M+H]+; found: 409.0458.
Ethyl 2-[1-(4-methoxyphenyl)naphthoACTHNUTRGNEUGN[2,1-b]furan-2-yl]acetate (3d): Vis-
cous liquid; 1H NMR (400 MHz, CDCl3): d=7.90 (d, 1H, J=8.0 Hz),
7.78 (d, 1H, J=8.0 Hz), 7.72 (d, 1H, J=9.0 Hz), 7.65 (d, 1H, J=9.0 Hz),
7.45 (d, 2H, J=8.4 Hz), 7.39 (t, 1H, J=8.0 Hz), 7.30 (t, 1H, J=8.0 Hz),
7.06 (d, 2H, J=8.4 Hz), 4.18 (q, 2H, J=7.2 Hz), 3.91 (s, 3H), 3.75 (s,
2H), 1.25 ppm (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=
169.0, 151.9, 146.9, 132.2, 132.1, 132.0, 130.8, 128.9, 127.9, 126.0, 125.7,
124.3, 122.9, 122.3, 121.6, 120.5, 112.3, 61.4, 32.9, 14.1 ppm; IR (CH2Cl2):
n˜ =3048, 2923, 2834, 1735, 1598, 1576, 1510, 1462, 1392, 1248, 1179, 1027,
806 cmÀ1; HRMS (ESI): m/z calcd for C23H20NaO4: 383.1259 [M+Na]+;
found: 383.1271.
Figure 6. Hammett correlation of log (k/kH) versus sp. Data obtained by
using deuterated [D7]-1-naphthol in the reaction are plotted on the
bottom.
Ethyl 2-[1-(thiophen-2-yl)naphthoACTHNUTRGNE[UNG 2,1-b]furan-2-yl]acetate (3e): White
1
solid; m.p. 65.1–66.08C; H NMR (400 MHz, CDCl3): d=7.90 (d, 1H, J=
8.0 Hz), 7.86 (d, 1H, J=8.0 Hz), 7.73 (d, 1H, J=8.8 Hz), 7.64 (d, 1H, J=
8.8 Hz), 7.51 (dd, 1H, J=4.2, 2.2 Hz), 7.41 (dd, 1H, J=8.0, 7.2 Hz), 7.35
(dd, 1H, J=8.0, 7.2 Hz), 7.24–7.21 (m, 2H), 4.18 (q, 2H, J=7.2 Hz), 3.82
(s, 2H), 1.25 ppm (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=
168.9, 151.8, 148.8, 133.1, 130.8, 129.0, 128.8, 127.9, 127.6, 127.1, 126.1,
125.7, 124.4, 123.0, 122.3, 114.2, 112.2, 61.4, 33.1, 14.1 ppm; IR (CH2Cl2):
n˜ =3063, 2974, 2915, 2849, 1735, 1620, 1583, 1443, 1388, 1193, 1027, 1005,
802 cmÀ1; HRMS (ESI): m/z calcd for C20H16NaO3S: 359.0718 [M+Na]+;
found: 359.0726.
Functionalized naphthofurans and benzofurans can be readi-
ly prepared by treatment of different naphthols/phenols
with appropriate nitroallylic acetates in good to excellent
chemical yields. This methodology provides an easy new al-
ternative for the synthesis of naphtho- and benzofurans
having diverse substitution patterns under mild reaction
conditions. Adaptation of this process to the synthesis of
other heterocycles by using different nitroallylic acetate pre-
cursors is currently under investigation in our laboratory.
Ethyl 2-[1-(furan-2-yl)naphthoACHTUNTRGNEU[GN 2,1-b]furan-2-yl]acetate (3 f): Viscous
liquid; 1H NMR (400 MHz, CDCl3): d=7.95–7.91 (m, 2H), 7.74 (d, 1H,
J=9.0 Hz), 7.69 (d, 1H, J=0.8 Hz), 7.64 (d, 1H, J=9.0 Hz), 7.48–7.43
(m, 2H), 6.64–6.61 (m, 2H), 4.20 (q, 2H, J=7.2 Hz), 3.90 (s, 2H),
1.27 ppm (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=168.8,
152.1, 149.1, 146.0, 143.0, 130.9, 128.8, 127.7, 126.3, 126.0, 124.5, 123.6,
121.7, 112.2, 111.9, 111.3, 110.9, 61.5, 33.6, 14.1 ppm; IR (CH2Cl2): n˜ =
2915, 2849, 1735, 1458, 1373, 1178, 1027, 901 cmÀ1; HRMS (ESI): m/z
calcd for C20H17O4: 321.1127 [M+H]+; found: 321.1140.
Experimental Section
Typical procedure for the synthesis of naphthofurans: (E)-Ethyl 2-ace-
toxy-3-nitro-4-phenylbut-3-enoate (1a; 31.4 mg, 0.11 mmol) was added to
a stirred solution of 2-naphthol (2; 14.4 mg, 0.11 mmol) and cesium car-
bonate (35.8 mg, 0.11 mmol) in CHCl3 at ambient temperature. The mix-
ture was stirred until the starting material had been consumed, as deter-
mined by TLC analysis. The crude residue was directly purified by flash
column chromatography on silica gel (hexanes/ethyl acetate, 5:1) to give
Ethyl 2-(1-isobutylnaphthoACTHNUTRGNE[NUG 2,1-b]furan-2-yl)acetate (3g): White solid;
m.p. 49.2–51.08C; 1H NMR (400 MHz, CDCl3): d=8.21 (d, 1H, J=
8.0 Hz), 7.94 (d, 1H, J=8.0 Hz), 7.69 (d, 1H, J=8.8 Hz), 7.62–7.55 (m,
2H), 7.46 (dd, 1H, J=8.0, 7.6 Hz), 4.20 (q, 2H, J=7.2 Hz), 3.86 (s, 2H),
2.83 (d, 2H, J=7.2 Hz), 2.18 (sept, 1H, J=6.8 Hz), 1.26 (t, 3H, J=
7.2 Hz), 1.03 ppm (d, 6H, J=6.8 Hz); 13C NMR (100 MHz, CDCl3): d=
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Versatile Synthesis of Naphthofurans and Benzofurans
FULL PAPER
169.2, 152.2, 146.4, 130.7, 129.1, 128.4, 126.1, 125.2, 123.9, 123.1, 122.0,
7.2 Hz), 0.97 ppm (d, 6H, J=6.8 Hz); 13C NMR (100 MHz, CDCl3): d=
169.2, 149.7, 146.1, 131.3, 128.2, 126.1, 124.9, 124.8, 122.7, 121.3, 120.1,
118.5, 117.8, 61.2, 33.1, 33.0, 29.2, 22.6, 14.2 ppm; IR (CH2Cl2): n˜ =2849,
1742, 1473, 1381, 1263, 1185, 1027 cmÀ1; HRMS (ESI): m/z calcd for
C20H22NaO3: 333.1467 [M+Na]+; found: 333.1475.
118.5, 112.5, 61.3, 34.5, 32.9, 28.5, 22.4, 14.1 ppm; IR (CH2Cl2): n˜ =3055,
2959, 2923, 2856, 1738, 1462, 1392, 1263, 1189, 1023, 806, 735 cmÀ1
;
HRMS (ESI): m/z calcd for C20H22NaO3: 333.1467 [M+Na]+; found:
333.1477.
Ethyl 2-(3-phenylnaphthoACTHNUTRGNEUG[N 1,2-b]furan-2-yl)acetate (4a): Viscous liquid;
Ethyl 2-(4,6-dimethoxy-3-phenylbenzofuran-2-yl)acetate (5a): Viscous
liquid; 1H NMR (400 MHz, CDCl3): d=7.48–7.50 (m, 2H), 7.39–7.41 (m,
2H), 7.37–7.39 (m, 1H), 6.65 (d, 1H, J=2.0 Hz), 6.30 (d, 1H, J=2.0 Hz),
4.18 (q, 2H, J=7.0 Hz), 3.80 (s, 3H), 3.71 (s, 2H), 3.70 (s, 3H), 1.26 ppm
(t, 3H, J=7.0 Hz); 13C NMR (125 MHz, CDCl3): d=169.5, 158.9, 156.2,
154.4, 144.7, 132.4, 130.2, 127.6, 127.0, 119.5, 111.1, 94.4, 88.1, 61.2, 55.7,
55.3, 33.0, 14.1 ppm; IR (CH2Cl2): n˜ =2835 (w), 1736 (w), 1626 (s), 1504
(w), 1410 cmÀ1 (w); HRMS (FAB+): m/z calcd for C20H20O5: 340.1311
[M+]; found: 340.1309.
1H NMR (400 MHz, CDCl3): d=8.33 (d, 1H, J=8.4 Hz), 7.92 (d, 1H, J=
8.0 Hz), 7.69–7.64 (m, 2H), 7.61–7.57 (m, 3H), 7.53–7.51 (m, 3H), 7.41 (t,
1H, J=7.6 Hz), 4.23 (q, 2H, J=7.2 Hz), 3.97 (s, 2H), 1.28 ppm (t, 3H,
J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=169.4, 149.9, 146.0, 132.1,
131.5, 129.1, 128.9, 128.3, 127.5, 126.3, 125.1, 123.6, 123.5, 121.3, 121.0,
120.1, 118.5, 61.4, 33.6, 14.2 ppm; IR (CH2Cl2): n˜ =3055, 2982, 2922, 1735,
1580, 1443, 1377, 1252, 1182, 1027, 982 cmÀ1; HRMS (ESI): m/z calcd for
C22H18NaO3: 353.1154 [M+Na]+; found: 353.1157.
Ethyl 2-[3-(4-chlorophenyl)naphthoACTHNUTRGENUGN[1,2-b]furan-2-yl]acetate (4b): White
Ethyl 2-[4,6-dimethoxy-3-(para-tolyl)benzofuran-2-yl]acetate (5b): Vis-
cous liquid; 1H NMR (500 MHz, CDCl3): d=7.36 (d, 2H, J=7.5 Hz),
7.19 (d, 2H, J=7.5 Hz), 6.64 (d, 1H, J=2.0 Hz), 6.30 (d, 1H, J=2.0 Hz),
4.18 (q, 2H, J=7.0 Hz), 3.77 (s, 3H), 3.70 (s, 3H), 3.65 (s, 2H), 2.39 (s,
3H), 1.26 ppm (t, 3H, J=7.0 Hz); 13C NMR (125 MHz, CDCl3): d=
169.5, 158.8, 156.2, 154.4, 144.5, 136.6, 130.0, 129.4, 128.4, 119.4, 111.2,
94.4, 88.1, 61.2, 55.7, 55.3, 33.0, 21.2, 14.1 ppm; IR (CH2Cl2): n˜ =2805 (w),
1736 (w), 1626 (s), 1512 (w), 1492 cmÀ1 (w); HRMS (FAB+): m/z calcd
for C20H22O5: 354.1467 [M]+; found: 354.1462.
1
solid; m.p. 61.1–62.48C; H NMR (400 MHz, CDCl3): d=8.33 (d, 1H, J=
8.4 Hz), 7.93 (d, 1H, J=8.4 Hz), 7.68 (d, 1H, J=8.4 Hz), 7.61–7.57 (m,
2H), 7.55–7.51 (m, 2H), 7.51–7.49 (m, 3H), 4.23 (q, 2H, J=7.2 Hz), 3.94
(s, 2H), 1.29 ppm (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=
169.2, 149.9, 146.1, 133.6, 131.6, 130.5, 130.3, 129.2, 128.3, 126.4, 125.3,
123.7, 123.3, 121.2, 120.1, 120.0, 118.1, 61.5, 33.5, 14.1 ppm; IR (CH2Cl2):
n˜ =3055, 2923, 2841, 1735, 1491, 1377, 1255, 1189, 1086, 1027, 986 cmÀ1
HRMS (ESI): m/z calcd for C22H17ClO3: 364.0866 [M]+; found: 364.0875.
Ethyl 2-[3-(4-bromophenyl)naphtho[1,2-b]furan-2-yl]acetate (4c): White
;
AHCTUNGTRENNUNG
Ethyl
2-[4,6-dimethoxy-3-(4-methoxyphenyl)benzofuran-2-yl]acetate
1
solid; m.p. 89.2–91.18C; H NMR (400 MHz, CDCl3): d=8.33 (d, 1H, J=
8.0 Hz), 7.93 (d, 1H, J=8.4 Hz), 7.69–7.63 (m, 3H), 7.61–7.58 (m, 2H),
7.52–7.47 (m, 3H), 4.23 (q, 2H, J=7.2 Hz), 3.94 (s, 2H), 1.29 ppm (t, 3H,
J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=169.2, 149.9, 146.1, 132.1,
131.5, 131.0, 130.6, 128.3, 126.4, 125.3, 123.7, 123.2, 121.7, 121.2, 120.1,
120.0, 118.1, 61.5, 33.5, 14.1 ppm; IR (CH2Cl2): n˜ =3055, 2923, 2841, 1735,
1488, 1377, 1255, 1189, 1027, 986 cmÀ1; HRMS (ESI): m/z calcd for
C22H17BrNaO3: 431.0259 [M+Na]+; found: 431.0272..
(5c): Viscous liquid; 1H NMR (500 MHz, CDCl3): d=7.42 (d, 2H, J=
8.5 Hz), 6.92 (d, 2H, J=8.5 Hz), 6.64 (d, 1H, J=2.0 Hz), 6.30 (d, 1H, J=
2.0 Hz), 4.18 (q, 2H, J=7.0 Hz), 3.85 (s, 3H), 3.83 (s, 3H), 3.71 (s, 3H),
3.70 (s, 2H), 1.26 ppm (t, 3H, J=7.0 Hz); 13C NMR (125 MHz, CDCl3):
d=169.5, 158.8, 158.7, 156.1, 154.4, 144.4, 124.7, 119.0, 111.2, 94.3, 88.1,
61.2, 55.6, 55.3, 55.2, 33.0, 14.1 ppm; IR (CH2Cl2): n˜ =2835 (w), 1733 (w),
1626 (s), 1597 (w), 1509 cmÀ1 (w); HRMS (ESI): m/z calcd for
C21H22O6Na: 393.1314 [M+Na]+; found: 393.1310.
Ethyl
2-[3-(4-methoxyphenyl)naphtho
[1,2-b]furan-2-yl]acetate
(4d):
Ethyl 2-[3-(4-chlorophenyl)-4,6-dimethoxybenzofuran-2-yl]acetate (5d):
Colorless crystals; m.p. 76.0–77.38C; 1H NMR (500 MHz, CDCl3): d=
7.42 (d, 2H, J=8.5 Hz), 7.35 (d, 2H, J=8.5 Hz), 6.65 (d, 1H, J=1.5 Hz),
6.31 (d, 1H, J=1.5 Hz), 4.18 (q, 2H, J=7.0 Hz), 3.84 (s, 3H), 3.71 (s,
3H), 3.68 (s, 2H), 1.26 ppm (t, 3H, J=7.0 Hz); 13C NMR (125 MHz,
CDCl3): d=169.3, 159.0, 156.2, 154.2, 144.8, 133.0, 131.5, 130.9, 127.8,
118.5, 110.8, 94.5, 88.1, 61.3, 55.7, 55.3, 33.0, 14.1 ppm; IR (CH2Cl2): n˜ =
2829 (w), 2346 (w), 1733 (w), 1626 (s), 1498 (w), 1450 cmÀ1 (w); HRMS
(ESI): m/z calcd for C20H18O5Cl: 373.0852 [MÀH]À; found: 373.0843.
White solid; m.p. 85.2–86.38C; 1H NMR (400 MHz, CDCl3): d=8.33 (d,
1H, J=8.0 Hz), 7.93 (d, 1H, J=8.0 Hz), 7.68–7.63 (m, 2H), 7.59 (t, 1H,
J=8.0 Hz), 7.54–7.47 (m, 3H), 7.05 (d, 2H, J=8.8 Hz), 4.23 (q, 2H, J=
7.2 Hz), 3.95 (s, 2H), 3.89 (s, 3H), 1.29 ppm (t, 3H, J=7.2 Hz); 13C NMR
(100 MHz, CDCl3): d=169.5, 159.1, 149.8, 145.6, 131.5, 130.2, 128.3,
126.3, 125.1, 124.3, 123.8, 123.4, 121.3, 120.7, 120.1, 118.5, 114.4, 61.5,
55.4, 33.6, 14.2 ppm; IR (CH2Cl2): n˜ =2915, 2836, 1740, 1512, 1459, 1381,
1251, 1179 cmÀ1; HRMS (ESI): m/z calcd for C23H20NaO4: 383.1259
[M+Na]+; found: 383.1255.
¯
Crystal data for 5d at 200(2) K: C20H19ClO5, Mr 374.80; triclinic, P1; a=
Ethyl 2-[3-(thiophen-2-yl)naphthoACTHNUTRGNE[UNG 1,2-b]furan-2-yl]acetate (4e): White
5.4417(3), b=12.7807(7), c=13.8821(7) ꢃ; a=68.175(2), b=81.542(3),
1
solid; m.p. 61.4–62.88C; H NMR (400 MHz, CDCl3): d=8.32 (d, 1H, J=
8.4 Hz), 7.93 (d, 1H, J=8.4 Hz), 7.82 (d, 1H, J=8.4 Hz), 7.70 (d, 1H, J=
8.4 Hz), 7.59 (t, 1H, J=8.4 Hz), 7.49 (t, 1H, J=8.4 Hz), 7.42 (d, 1H, J=
4.8 Hz), 7.32 (d, 1H, J=3.6 Hz), 7.19 (dd, 1H, J=4.8, 3.6 Hz), 4.23 (q,
2H, J=7.2 Hz), 4.07 (s, 2H), 1.28 ppm (t, 3H, J=7.2 Hz); 13C NMR
(100 MHz, CDCl3): d=169.0, 149.8, 146.6, 133.1, 131.6, 128.3, 127.7,
126.4, 126.3, 125.5, 125.3, 123.7, 123.3, 121.1, 120.1, 118.5, 114.7, 61.5,
33.9, 14.1 ppm; IR (CH2Cl2): n˜ =3063, 2915, 2849, 1731, 1458, 1373, 1185,
1027, 920 cmÀ1; HRMS (ESI): m/z calcd for C20H16NaO3S: 359.0718
[M+Na]+; found: 359.0729.
g=80.867(3)8; V=880.82(8) ꢃ3, F
ACHTUNTRGNNEUG(000)=392, lAHCTUNGTREN(NUGN MoKa)=0.71073 ꢃ, Z=
2, D=1.413 gcmÀ3, 6219 reflections, 0 restraints, 235 parameters, R=
0.0511; wR2 =0.1304 for all data.
Ethyl 2-[4,6-dimethoxy-3-(thiophen-2-yl)benzofuran-2-yl]acetate (5e):
Viscous liquid; 1H NMR (500 MHz, CDCl3): d=7.36 (d, 1H, J=0.8 Hz),
7.22 (d, 1H, J=2.4 Hz), 7.08 (m, 1H), 6.63 (d, 1H, J=2.0 Hz), 6.33 (d,
1H, J=2.0 Hz), 4.18 (q, 2H, J=7.2 Hz), 3.83 (s, 3H), 3.82 (s, 2H), 3.77
(s, 3H), 1.26 ppm (t, 3H, J=7.2 Hz); 13C NMR (125 MHz, CDCl3): d=
169.2, 159.1, 156.1, 154.3, 145.8, 133.2, 128.1, 126.5, 125.8, 112.8, 110.9,
94.6, 88.1, 61.3, 55.7, 55.3, 33.4, 14.1 ppm; IR (CH2Cl2): n˜ =2966 (w), 2833
(w), 1738 (s), 1616 (s), 1498 (w), 1365 cmÀ1 (w); HRMS (ESI): m/z calcd
for C18H18O5NaS: 369.0773 [M+Na]+; found: 369.0768.
Ethyl 2-[3-(furan-2-yl)naphthoACTHNUGRTENUNG[1,2-b]furan-2-yl]acetate (4 f): White solid;
m.p. 65.2–66.48C; 1H NMR (400 MHz, CDCl3): d=8.31 (d, 1H, J=
8.0 Hz), 7.95–7.91 (m, 2H), 7.73 (d, 1H, J=8.4 Hz), 7.61–7.57 (m, 2H),
7.50 (ddd, 1H, J=8.0, 7.2, 0.8 Hz), 6.71 (d, 1H, J=3.6 Hz), 6.56 (dd, 1H,
J=3.6, 1.8 Hz), 4.25–4.20 (m, 4H), 1.27 ppm (t, 3H, J=7.2 Hz);
13C NMR (100 MHz, CDCl3): d=169.0, 149.9, 147.4, 146.1, 141.8, 131.5,
128.2, 126.4, 125.3, 123.7, 121.7, 121.1, 120.1, 119.0, 111.7, 111.3, 107.1,
61.4, 34.5, 14.1 ppm; IR (CH2Cl2): n˜ =2915, 2849, 1745, 1458, 1373, 1179,
1027, 901 cmÀ1; HRMS (ESI): m/z calcd for C20H17O4: 321.1127 [M+H]+;
found: 321.1140.
Ethyl 2-[3-(furan-2-yl)-4,6-dimethoxybenzofuran-2-yl]acetate (5 f): Color-
less crystals; m.p. 87.9–88.88C; 1H NMR (400 MHz, CDCl3): d=7.45 (d,
1H, J=4.0 Hz), 6.88 (d, 1H, J=4.0 Hz), 6.61 (d, 1H, J=2.0 Hz), 6.47 (d,
1H, J=2.0), 6.33 (d, 1H, J=2.5 Hz), 4.18 (q, 2H, J=7.2 Hz), 4.03 (s,
2H), 3.87 (s, 3H), 3.82 (s, 3H), 1.24 ppm (t, 3H, J=7.2 Hz); 13C NMR
(100 MHz, CDCl3): d=169.4, 159.0, 156.3, 154.0, 147.2, 145.7, 141.5,
111.1, 110.0, 109.5, 94.7, 88.1, 61.2, 55.6, 55.4, 34.4, 14.1 ppm; IR
(CH2Cl2): n˜ =2966 (w), 2826 (w), 1738 (s), 1620 (s), 1502 (w), 1325 cmÀ1
(w); HRMS (ESI): m/z calcd for C18H18O6Na: 353.1001 [M+Na]+; found:
353.0995. Crystal data for 5 f at 299(2) K: C18H18O6, Mr 330.32; monoclin-
ic, C2/c; a=38.5603(15), b=5.0508(2), c=18.3292(7) ꢃ; a=90(2), b=
Ethyl 2-(3-isobutylnaphthoACTHNUTRGNE[NUG 1,2-b]furan-2-yl)acetate (4g): White solid;
m.p. 69.2–72.68C; 1H NMR (400 MHz, CDCl3): d=8.28 (d, 1H, J=
8.4 Hz), 7.90 (d, 1H, J=8.4 Hz), 7.63 (d, 1H, J=8.4 Hz), 7.58–7.53 (m,
2H), 7.45 (td, 1H, J=8.4, 1.2 Hz), 4.20 (q, 2H, J=7.2 Hz), 3.87 (s, 2H),
2.58 (d, 2H, J=6.8 Hz), 2.04 (sept, 1H, J=6.8 Hz), 1.26 (t, 3H, J=
111.728(2), g=908; V=3316.2(2) ꢃ3, F
ACHTUNTRGNNEUG(000)=1392, lCAHTUNGTREN(NUGN MoKa)=0.71073 ꢃ,
Chem. Eur. J. 2013, 19, 4344 – 4351
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4349

K. Chen et al.
Z=8, D=1.323 gcmÀ3, 9395 reflections, 0 restraints, 217 parameters, R=
0.1113; wR2 =0.2056 for all data.
Ethyl 2-[4-(dimethylamino)-3-(4-methoxyphenyl)benzofuran-2-yl]acetate
(7c): Viscous liquid; 1H NMR (500 MHz, CDCl3): d=7.45 (d, 2H, J=
8.5 Hz), 7.38 (d, 1H, J=8.5 Hz), 7.01 (d, 2H, J=8.5 Hz), 6.84 (d, 1H, J=
2.0 Hz), 6.76 (dd, 1H, J=2.0, 8.5 Hz), 4.20 (q, 3H, J=7.0 Hz), 3.80 (s,
2H), 2.98 (s, 6H), 2.41 (s, 3H), 1.27 ppm (t, 3H, J=7.0 Hz); 13C NMR
(125 MHz, CDCl3): d=169.6, 158.9, 156.1, 149.3, 143.7, 129.9, 124.7,
119.7, 119.0, 118.9, 114.2, 110.1, 95.3, 77.2, 77.0, 76.7, 61.2, 55.3, 41.3, 33.4,
14.1 ppm; IR (CH2Cl2): n˜ =2877 (w), 2389 (w), 1733 (w), 1626 (s),
1512 cmÀ1 (w); HRMS (EI): m/z calcd for C21H23NO4: 354.1705 [M+H]+;
found: 354.1720.
Ethyl 2-(3-isobutyl-4,6-dimethoxybenzofuran-2-yl)acetate (5g): Viscous
liquid; 1H NMR (400 MHz, CDCl3): d=6.58 (d, 1H, J=2.0 Hz), 6.26 (d,
1H, J=2.0 Hz), 4.18 (q, 3H, J=7.2 Hz), 3.85 (s, 3H), 3.81 (s, 3H), 3.68
(s, 2H), 2.49 (d, 2H, J=8.5 Hz), 1.99 (sept, 1H, J=6.4 Hz), 1.25 (t, 3H,
J=7.2 Hz), 0.91 ppm (d, 6H, J=6.4 Hz); 13C NMR (100 MHz, CDCl3):
d=169.4, 158.6, 156.1, 154.4, 144.0, 116.8, 112.4, 93.8, 88.1, 61.1, 55.6,
55.3, 33.7, 32.6, 29.4, 22.3, 14.1 ppm; IR (CH2Cl2): n˜ =2937 (w), 1734 (w),
1598 (m), 1498 (m), 1458 (w), 1329 cmÀ1 (w); HRMS (ESI): m/z calcd for
C18H24O5Na: 343.1521 [M+Na]+; found: 343.1521.
Ethyl
2-[3-(4-chlorophenyl)-4-(dimethylamino)benzofuran-2-yl]acetate
(7d): Colorless crystals; m.p. 76.5–77.48C; 1H NMR (500 MHz, CDCl3):
d=7.48 (d, 2H, J=8.5 Hz), 7.43 (d, 2H, J=8.5 Hz), 7.37 (d, 1H, J=
9.0 Hz), 6.84 (d, 1H, J=2.0 Hz), 6.76 (dd, 1H, J=2.0, 8.5 Hz), 4.20 (q,
3H, J=7.0 Hz), 3.77 (s, 2H), 2.98 (s, 6H), 1.27 ppm (t, 3H, J=7.0 Hz);
13C NMR (125 MHz, CDCl3): d=169.3, 156.1, 149.4, 144.2, 133.1, 130.9,
130.0, 128.9, 119.5, 118.4, 118.2, 110.2, 95.1, 61.3, 41.2, 33.3, 14.1 ppm; IR
(CH2Cl2): n˜ =2977 (w), 2801 (w), 1739 (s), 1628 (s), 1509 cmÀ1 (w);
HRMS (EI): m/z calcd for C20H20ClNaNO3: 380.1030 [M+Na]+; found:
380.1048. Crystal data for 7d at 200(2) K; C20H20ClNO3, Mr 357.82; or-
thorhombic, Pbca; a=17.572(8), b=7.769(4), c=25.976(12) ꢃ; a=90(2),
Ethyl 2-[3-(4-chlorophenyl)-6-methoxybenzofuran-2-yl]acetate (6a): Vis-
cous liquid; 1H NMR (400 MHz, CDCl3): d=7.46–7.36 (m, 4H), 7.41 (d,
1H, J=8.8 Hz), 7.04 (d, 1H, J=2.0 Hz), 6.88 (dd, 1H, J=2.0, 8.4 Hz),
4.21 (q, 3H, J=7.2 Hz), 3.86 (s, 3H), 3.79 (s, 2H), 1.26 ppm (t, 3H, J=
7.2 Hz); 13C NMR (100 MHz, CDCl3): d=169.1, 158.2, 155.3, 145.7, 133.4,
130.5, 130.1, 129.1, 121.3, 118.8, 118.6, 111.9, 96.0, 77.3, 77.0, 76.6, 61.5,
55.7, 33.3, 14.1 ppm; IR (CH2Cl2): n˜ =2981 (w), 2833 (w), 1734 (s), 1623
(s), 1494 (s), 1435 cmÀ1 (w); HRMS (FAB+): m/z calcd for C19H17O4Cl:
344.0815 [M+]; found: 344.0816.
Ethyl 2-[3-(4-chlorophenyl)-4-methoxybenzofuran-2-yl]acetate (6a’; re-
gioisomer): Viscous liquid; 1H NMR (400 MHz, CDCl3): d=7.42 (d, 2H,
J=8.8 Hz), 7.38 (d, 2H, J=8.8 Hz), 7.23 (t, 1H, J=8.4 Hz), 7.13 (d, 1H,
J=8.0 Hz), 6.67 (d, 1H, J=8.0 Hz), 4.23 (q, 3H, J=7.0 Hz), 3.74 (s, 3H),
3.72 (s, 2H), 1.27 ppm (t, 3H, J=7.0 Hz); 13C NMR (100 MHz, CDCl3):
d=169.1, 155.3, 154.2, 146.0, 133.1, 131.6, 131.0, 127.8, 125.1, 118.6, 117.1,
104.5, 103.8, 61.4, 55.4, 33.0, 14.1 ppm; IR (CH2Cl2): n˜ =2981 (w), 2833
(w), 1734 (s), 1601 (s), 1494 (s), 1432 cmÀ1 (w); HRMS (FAB+): m/z
calcd for C19H17O4Cl: 344.0815 [M+H+]; found: 344.0816.
b=90, g=908; V=3546(3) ꢃ3, F
D=1.340 gcmÀ3
15372 reflections,
0.2387; wR2 =0.2788 for all data.
Ethyl 2-[4-(dimethylamino)-3-(thiophen-2-yl)benzofuran-2-yl]acetate
A
ACHTUGNTRENUN(GN MoKa)=0.71073 ꢃ, Z=8,
,
0
(7e): Viscous liquid; 1H NMR (400 MHz, CDCl3): d=7.58 (d, 1H, J=
8.8 Hz), 7.37 (d, 1H, J=5.2 Hz), 7.26 (d, 1H, J=3.6 Hz), 7.14 (dd, 1H,
J=4.8, 3.6 Hz), 6.81 (d, 1H, J=1.6 Hz), 6.77 (dd, 1H, J=2.0, 8.8 Hz),
4.20 (q, 3H, J=6.8 Hz), 3.92 (s, 2H), 2.98 (s, 6H), 1.27 ppm (t, 3H, J=
6.8 Hz); 13C NMR (100 MHz, CDCl3): d=169.2, 156.0, 149.5, 144.6, 133.7,
127.5, 125.6, 124.9, 120.0, 118.1, 113.2, 110.2, 95.1, 77.3, 77.0, 76.7, 61.4,
41.2, 33.8, 14.1 ppm; IR (CH2Cl2): n˜ =2915 (w), 2797 (w), 1738 (s), 1632
(s), 1502 cmÀ1 (s); HRMS (ESI): m/z calcd for C18H20NO3S: 330.1164
[M+H]+; found: 330.1159.
Ethyl 2-[4-methoxy-3-(thiophen-2-yl)benzofuran-2-yl]acetate (6b): Vis-
cous liquid; 1H NMR (400 MHz, CDCl3): d=7.65 (d, 1H, J=8.5 Hz),
7.51 (d, 1H, J=1.5 Hz), 7.01 (d, 1H, J=2.5 Hz), 6.92 (dd, 1H, J=2.5,
8.5 Hz), 6.63 (d, 1H, J=3.0 Hz), 6.52 (dd, 1H, J=1.5, 3.0 Hz), 4.20 (q,
3H, J=6.8 Hz), 4.06 (s, 2H), 3.87 (s, 3H), 1.28 ppm (t, 3H, J=6.8 Hz);
13C NMR (100 MHz, CDCl3): d=168.9, 158.3, 155.2, 146.2, 133.1, 127.6,
126.0, 125.3, 121.2, 120.3, 113.4, 111.9, 96.0, 61.5, 55.8, 33.8, 14.2 ppm; IR
(CH2Cl2): n˜ =2974 (w), 2833 (w), 1734 (s), 1623 (s), 1483 (w), 1292 cmÀ1
(w); HRMS (ESI): m/z calcd for C17H16ONaS: 339.0667 [M+H]+; found:
339.0663.
Ethyl 2-[4-(dimethylamino)-3-(furan-2-yl)benzofuran-2-yl]acetate (7 f):
Viscous liquid; 1H NMR (400 MHz, CDCl3): d=7.63 (d, 1H, J=8.4 Hz),
7.50 (d, 1H, J=1.6 Hz), 6.80–6.77 (m, 2H), 6.61 (d, 1H, J=1.6 Hz), 6.50
(dd, 1H, J=2.0, 3.2 Hz), 4.19 (q, 3H, J=7.2 Hz), 4.05 (s, 2H), 2.98 (s,
6H), 1.25 ppm (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3): d=
169.2, 156.2, 149.4, 147.9, 144.4, 141.4, 120.4, 116.4, 111.1, 110.3, 110.1,
106.6, 95.0, 77.3, 77.0, 76.7, 61.2, 41.2, 34.3, 14.1 ppm; IR (CH2Cl2): n˜ =
2988 (w), 2885 (w), 1734 (s), 1627 (s), 1505 cmÀ1 (s); HRMS (ESI): m/z
calcd for C18H19NO4Na: 336.1212 [M+Na]+; found: 336.1203.
Ethyl 2-[3-(furan-2-yl)-4-methoxybenzofuran-2-yl]acetate (6c): Viscous
liquid; 1H NMR (500 MHz, CDCl3): d=7.69 (d, 1H, J=8.5 Hz), 7.51 (d,
1H, J=1.5 Hz), 7.01 (d, 1H, J=2.5 Hz), 6.92 (dd, 1H, J=2.5, 8.5 Hz),
6.63 (d, 1H, J=3.0 Hz), 6.52 (dd, 1H, J=1.5, 3.0 Hz), 4.20 (q, 3H, J=
7.2 Hz), 4.06 (s, 2H), 3.87 (s, 3H), 1.26 ppm (t, 3H, J=7.2 Hz); 13C NMR
(125 MHz, CDCl3): d=167.0, 158.3, 155.2, 146.2, 133.1, 127.6, 126.0,
125.3, 121.2, 120.3, 113.4, 111.9, 96.0, 61.5, 55.8, 33.8, 14.2 ppm; IR
(CH2Cl2): n˜ =2974 (w), 2833 (w), 1734 (s), 1623 (s), 1483 (w), 1292 cmÀ1
(w); HRMS (ESI): m/z calcd for C17H16O5Na: 323.0895 [M+Na]+; found:
323.0894.
Ethyl
2-[5,8-di(ethyloxycarbonylmethyl)-3,6,9-triphenyldifur-
(8): Viscous liquid;
o[2’,3’:3,4:2’,3’:5,6]benzo[b]furan-2-yl]acetate
1H NMR (400 MHz, CDCl3): d=7.75 (d, 6H, J=8.4 Hz), 7.51 (t, 6H, J=
7.4 Hz), 7.45–7.41 (m, 3H), 4.20 (q, 6H, J=7.1 Hz), 3.87 (s, 6H),
1.24 ppm (t, 9H, J=7.1 Hz); 13C NMR (100 MHz, CDCl3): d=169.1,
145.4, 131.8, 129.6, 128.3, 127.5, 118.6, 109.9, 61.2, 33.4, 14.1 ppm; IR
(CH2Cl2): n˜ =3061, 2973, 1738, 1572, 1036, 1003 cmÀ1; HRMS (ESI): m/z
calcd for C42H36O9: 684.2359 [M]+; found: 684.2371.
Ethyl 2-[4-(dimethylamino)-3-phenylbenzofuran-2-yl]acetate (7a): Vis-
cous liquid; 1H NMR (500 MHz, CDCl3): d=7.52 (d, 2H, J=7.5 Hz),
7.48 (dd, 2H, J=7.8, 7.8 Hz), 7.41 (d, 1H, J=8.5 Hz), 7.37 (t, 1H, J=
7.5 Hz), 6.85 (d, 1H, J=2.5 Hz), 6.77 (dd, 1H, J=2.0, 8.5 Hz), 4.21 (q,
3H, J=7.0 Hz), 3.81 (s, 2H), 2.98 (s, 6H), 1.27 ppm (t, 3H, J=7.0 Hz);
13C NMR (125 MHz, CDCl3): d=169.5, 156.1, 149.4, 144.1, 132.5, 127.2,
119.8, 119.4, 118.6, 110.1, 95.2, 77.2, 76.9, 76.7, 61.3, 41.3, 33.4, 14.1 ppm;
IR (CH2Cl2): n˜ =2982 (w), 2801 (w), 2352 (w), 1733 (m), 1626 (s),
1501 cmÀ1 (w); HRMS (EI): m/z calcd for C20H21NO3: 324.1600 [M+H]+;
found: 324.1611.
Diethyl 2,2’-(3,6-diphenylbenzofuroACTHNUTRGENUGN[7,6-b]furan-2,7-diyl)diacetate (9):
Viscous liquid; 1H NMR (400 MHz, CDCl3): d=7.58 (d, 4H, J=7.2 Hz),
7.50 (t, 4H, J=7.5 Hz), 7.43–7.39 (m, 4H), 4.23 (q, 4H, J=7.1 Hz), 3.92
(s, 4H), 1.28 ppm (t, 6H, J=7.1 Hz); 13C NMR (100 MHz, CDCl3): d=
169.1, 146.2, 139.0, 131.9, 129.1, 128.9, 127.7, 126.6, 120.9, 115.0, 61.4,
33.4, 14.1 ppm; IR (CH2Cl2): n˜ =3060, 2974, 2915, 1734, 1570, 1447, 1034,
1005 cmÀ1; HRMS (ESI): m/z calcd for C30H26O6: 482.1729 [M]+; found:
482.1729.
Ethyl 2-[4-(dimethylamino)-3-(para-tolyl)benzofuran-2-yl]acetate (7b):
Viscous liquid; 1H NMR (500 MHz, CDCl3): d=7.44 (d, 2H, J=8.0 Hz),
7.41 (d, 1H, J=8.5 Hz), 7.27 (d, 2H, J=7.5 Hz), 6.84 (d, 1H, J=2.0 Hz),
6.76 (dd, 1H, J=2.0, 8.5 Hz), 4.21 (q, 3H, J=7.0 Hz), 3.80 (s, 2H), 2.98
(s, 6H), 2.41 (s, 3H), 1.27 ppm (t, 3H, J=7.0 Hz); 13C NMR (125 MHz,
CDCl3): d=169.6, 156.1, 149.4, 144.0, 136.9, 129.4, 128.7, 119.8, 119.3,
118.8, 110.1, 95.3, 77.2, 77.0, 76.7, 41.3, 33.4, 21.2, 14.1 ppm; IR (CH2Cl2):
n˜ =2977 (w), 2789 (w), 1736 (w), 1623 (s), 1507 cmÀ1 (w); HRMS (EI):
m/z calcd for C21H23NO3: 338.1756 [M+H]+; found: 338.1772.
Acknowledgements
We thank the National Science Council of the Republic of China (NSC
99–2113M-003–002-MY3 and NSC 99–2119M-003–001-MY2) and the
National Taiwan Normal University (100-D-06) for financial support of
4350
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 4344 – 4351

Versatile Synthesis of Naphthofurans and Benzofurans
FULL PAPER
this work. We thank Prof. C. F. Yao of National Taiwan Normal Universi-
ty for helpful discussion.
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Received: November 27, 2012
Published online: February 5, 2013
Chem. Eur. J. 2013, 19, 4344 – 4351
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4351