Ga(OTf)3-mediated synthesis of substituted benzofurans

Article abstract of DOI:10.1016/j.tet.2016.07.007

A synthetic procedure, for the synthesis of a series of functionalized benzofurans 3–5 and benzonaphthofurans 6, starting from intermolecular O-alkylation of α-bromoaryl ketones 2 with potassium oxygenated phenoxides 1 followed by Ga(OTf)₃-catalyzed direct intramolecular cyclodehydration of the resulting α-aryloxyaryl ketones, has been developed. The use of various metal triflates was investigated for a facile approach and efficient transformation. Pentacyclic benzophenanthrofurans 7 were prepared via photolytic annulations of 5.

Full text of DOI:10.1016/j.tet.2016.07.007

Tetrahedron 72 (2016) 5132e5141
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ga(OTf)3-mediated synthesis of substituted benzofurans
*
Heui-Sin Wang, Chieh-Kai Chan, Meng-Yang Chang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 June 2016
Received in revised form 28 June 2016
Accepted 2 July 2016
Available online 4 July 2016
A synthetic procedure, for the synthesis of a series of functionalized benzofurans 3e5 and benzonaph-
thofurans 6, starting from intermolecular O-alkylation of
genated phenoxides 1 followed by Ga(OTf)3-catalyzed direct intramolecular cyclodehydration of the
resulting -aryloxyaryl ketones, has been developed. The use of various metal triflates was investigated
a-bromoaryl ketones 2 with potassium oxy-
a
for a facile approach and efficient transformation. Pentacyclic benzophenanthrofurans 7 were prepared
via photolytic annulations of 5.
Keywords:
Ga(OTf)3
Ó 2016 Elsevier Ltd. All rights reserved.
Benzofurans
Cyclodehydration
Scholl annulation
1. Introduction
OTf
TMS
OH
Substituted arene-fused furans are of great interest because of
their useful biological and pharmacological activities.1 Accordingly,
there exists a wide selection of methods for the synthesis of this key
benzofuran core via metal-promoted intramolecular annulation.
The bond formation of a furan motif could be divided into four
synthetic routes (Scheme 1),2e5 including (1) O-arylation of eno-
lates (PdII, CuI; a bond formation),2 (2) cycloisomerization of o-
functionalized phenols (RuII, RhI, PdII, ZnII/CuI, CuII, CuI, Pd0/CuI;
b bond formation),3aeg (3) oxidative dehydration of a benzyl alco-
hol (IrIII)4a or ring-closing metathesis of a diene (RuII, c bond for-
mation),4b and (4) ene reaction of alkynyl benzyne (Pd0)5a or
a Claisen rearrangement/oxidative cyclization of an allyl aryl ether
(PdII; d bond formation).5b However, intermolecular annulations
are also popular routes to such benzofurans6 among the existing
methods. Development of a new, single-step route for the simul-
taneous bond formation and ring-construction of benzofurans from
readily available starting materials still represents a continuing
need in the organic synthetic field.
O
CN
O
O
O
Ir(III), Cossy
Ru(II), de Konig
Pd(II), Youn
Pd(0), Ma
d
c
b
O
a
O
Br
Br
O
O
Br
OH
OH
Ga(III), the work
Pd(II), Willis
Cu(I), Dominguez
Ru(II), Saa
Cu(I), Wu
Pd(0)/Cu(I), Lautens
Rh(I), Lautens
Pd(II), Aurrecoechea
Zn(II)/Cu(I), Nakamura
Cu(II), Hirano
Scheme 1. Metal-promoted intramolecular annulations.
a
-bromoaryl ketones with a phenoxide followed by intramolecular
cyclodehydration of the resulting a-aryloxyaryl ketones. To the best
of our knowledge, for the synthesis of benzofurans, no literature on
the Ga(III)-mediated intramolecular annulation has been reported.
Among the many metal triflates catalysts recently studied, Ga(OTf)3
is an inexpensive, oxygen-tolerant, catalytic, efficient Lewis acid.9
Olah10 and other researchers11 have reported that Ga(OTf)3 dem-
onstrates high chemo- and regioselectivity, good yields, excellent
stability, and recyclability in a variety of transformations. Along this
line, we planned to take advantage of the intrinsically high catalytic
ability of Ga(OTf)3 to construct the benzofuran system.12 Initially,
we designed a route to benzofuran 3a, starting from model mate-
rials of potassium 3,4,5-trimethoxyphenoxide (1a, generated from
the reaction of 3,4,5-trimethoxyphenol and KOH(aq) and then re-
2. Results and discussion
As part of our efforts in the development of metal triflate-
promoted robust and efficient reactions,7,8 we have now stream-
lined the Ga(OTf)3-mediated synthesis of substituted benzofurans
(from d bond formation) via the intermolecular O-alkylation of
moval of H2O) and
a-bromoacetophenone (2a). As shown in
* Corresponding author. E-mail address: mychang@kmu.edu.tw (M.-Y. Chang).
http://dx.doi.org/10.1016/j.tet.2016.07.007
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
5133
Scheme 2, an intermolecular SN2 O-alkylation provided
a
-aryloxy
On the basis of an acidic
a
-proton of MeNO2 (pKa¼17.2) or EtNO2
ketone A. Subsequently, 3a was obtained in a 76% yield via 2 mol %
of Ga(OTf)3-promoted tandem intramolecular cyclodehydration of
A in DMF at 25 ꢀC for 5 h under open-vessel conditions.
(pKa¼16.7), the competitive deprotonation of 1a could be a possible
reason for lower yields of 3a. Entries 10e11 show that no desired 3a
was observed due to the poor solubility of CH2Cl2 and CHCl3. By the
involvement of DMSO, a complex mixture was detected (entry 12).
By elevating the reaction temperature (25 ꢀC/100 ꢀC, entry 13), 3a
was decreased to a 58% yield under entry 1 conditions. Without the
addition of Ga(OTf)3, only A (88%) was formed (entry 14). By the
involvement of 2 mol % TfOH (entries 15e16), two solvent (CH2Cl2
and DMF) were examined. For the combination of 2 mol % TfOH/
CH2Cl2, no desired 3a was detected. And, 2 mol % TfOH/DMF pro-
vided 3a in 50% yield.13 In entry 17, by the combination of Ga(OTf)3
(2 mol %) and TfOH (2 mol %), the yield of 3a was maintained (70%).
According to the above results, we believe that the 2 mol %
Ga(OTf)3/DMF system would be the optimal combination for gen-
erating 3a. With optimal conditions (Table 1, entry 1), we further
explored the substrate scope of the reaction, and the results are
shown in Table 2. For R, Ar and Y substituents of 1 and 2, the di-
versified, well-tolerated groups produced 3aes (70%e87%, entries
1e19), 4aeg (64%e73%, entries 20e26) and 5aei (56%e67%, entries
27e36) in moderate to good yields. Different substituents of 1
(RO¼MeO, CH2O2, n¼1e3) and 2 (Ar¼Ph, 3-MeOC6H4, 4-MeOC6H4,
4-CF3C6H4, 4-FC6H4, 4-PhC6H4, 2-naphthalene, 4-MeC6H4, 3,4-
nucleophilic substitution
MeO
cyclodehydration
MeO
MeO
Ph
O
Ph
Ga(OTf)
5 h
MeO
MeO
MeO
O
O
Ph
MeO
MeO
DMF
3
+
5 h
O
Br
OK
MeO
1a
2a
A
3a (76%)
Scheme 2. Ga(OTf)3-promoted route.
To control the reaction conditions (25 ꢀC, DMF, 5 h), the use of
various commercially available metal triflates was investigated for
direct transformation. Among the screened catalysts, which in-
cluded 2 mol % of AgOTf, LiOTf, Ba(OTf)2, Mg(OTf)2, Ca(OTf)2,
Ni(OTf)2, Sn(OTf)2, Zn(OTf)2, Cu(OTf)2, Hg(OTf)2, Al(OTf)3, Fe(OTf)3,
Yb(OTf)3, In(OTf)3, Ce(OTf)3, Sm(OTf)3, Gd(OTf)3, La(OTf)3, Sc(OTf)3,
Nd(OTf)3, Y(OTf)3, Dy(OTf)3, and Bi(OTf)3, only Sn(OTf)2 and Bi(OTf)3
provided better yields of 3a (entries 2e3, 70% and 62%). In(OTf)3
provided a 48% yield of 3a along with an 18% yield of A (entry 4). In
comparison with these metal triflates, Ga(OTf)3 is an optimal catalyst
for the generation of 3a. Furthermore, controlling the Ga(OTf)3 as the
catalyst, the factors of equivalency, concentration, time and solvent
were studied next. When using 5 mol % of Ga(OTf)3, the isolated
yield was similar to that of 2 mol % (entry 5). No obvious changes
Table 2
Synthesis of 3e5a
Ar
O
Ar
Y
Ga(OTf)
DMF
3
+
(RO)
(RO)
n
n
Y
occurred
when
decreasing
the
reaction
concentration
O
Br
OK
(5 mL/10 mL) or extending the time (5 h/10 h), as shown in
entries 6e7, respectively. After changing the solvents (from DMF to
MeNO2, EtNO2, CH2Cl2, CHCl3, and DMSO), different results were
observed. In entries 8e9, the results showed that MeNO2 and EtNO2
provided 3a in 48% and 50% yields, respectively, along with the
isolation of 3,4,5-trimethoxyphenol (12% and 8%, respectively).
1
2
3-5
Entry
1, (RO)n]
2, Ar], Y]
2a, Ph, H
2b, 3-MeOC6H4, H
2b, 3-MeOC6H4, H
2a, Ph, H
Yield (%)b
3, 4, 5
1
2
3
4
5
6
7
8
1a, 3,4,5-(MeO)3
1b, 3,5-(MeO)2
1a, 3,4,5-(MeO)3
1c, 3,4-(MeO)2
1d, 3,4-CH2O2
1d, 3,4-CH2O2
1d, 3,4-CH2O2
1d, 3,4-CH2O2
1d, 3,4-CH2O2
1d, 3,4-CH2O2
1d, 3,4-CH2O2
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
3a, 76
3b, 70
3c, 73
3d, 78
3e, 77
3f, 80
3g, 87
3h, 78
3i, 76
3j, 78
3k, 82
3l, 84
3m, 84
3n, 83
3o, 85
3p, 80
3q, 80
3r, 80
3s, 84
4a, 64
4b, 66
4c, 68
4d, 66
4e, 73
4f, 68
4g, 70
5a, 63
5b, 64
5c, 65
5d, 67
5e, 62
5f, 60
5g, 63
5h, 60
5i, 63
5j, 56
Table 1
2a, Ph, H
Reaction conditionsa
2b, 3-MeOC6H4, H
2c, 4-MeOC6H4, H
2d, 4-CF3C6H4, H
2e, 4-FC6H4, H
2f, 4-PhC6H4, H
2g, 2-naphthalene, H
2a, Ph, H
2c, 4-MeOC6H4, H
2h, 4-MeC6H4, H
2f, 4-PhC6H4, H
2d, 4-CF3C6H4, H
2i, 3,4-CH2O2C6H3, H
2j, 3,4-Cl2C6H3, H
2g, 2-naphthalene, H
2k, Ph, allyl
2k, Ph, allyl
2k, Ph, allyl
2l, Ph, benzyl
2m, 4-MeOC6H4, allyl
2n, 4-MeC6H4, allyl
2o, 4-PhC6H4, allyl
2p, Ph, Ph
2p, Ph, Ph
2p, Ph, Ph
MeO
MeO
MeO
Ph
O
Ph
MeO
MeO
MeO
MeO
MeO
MeO
O
O
Ph
solvent M(OTf)
3
+
9
5 h
or TfOH
time
O
Br
OK
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
1a
2a
3a
A
Entry
Catalysts (mol %)
Solvent (mL)
Time (h)
3a (%)b
1
2
3
4
5
6
7
8
Ga(OTf)3 (2)
Sn(OTf)3 (2)
Bi(OTf)3(2)
In(OTf)3 (2)
Ga(OTf)3 (5)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (2)
Ga(OTf)3 (0)
TfOH (2)
DMF (5)
DMF (5)
DMF (5)
DMF (5)
DMF (5)
DMF (10)
DMF (5)
MeNO2 (5)
EtNO2 (5)
CH2Cl2 (5)
CHCl3 (5)
DMSO (5)
DMF (5)
DMF (5)
CH2Cl2 (5)
DMF (5)
DMF (5)
5
5
5
5
5
5
10
5
5
5
5
5
5
5
5
5
5
76
70
62
48c (67)d
76
68
70
1a, 3,4,5-(MeO)3
1c, 3,4-(MeO)2
1d, 3,4-CH2O2
1e, 3-MeO
1e, 3-MeO
1e, 3-MeO
48e
50e
ef
9
10
11
12
13
14
15
16
17
ef
eg
58h
1e, 3-MeO
1e, 3-MeO
ei
ef
1c, 3,4-(MeO)2
1b, 3,5-(MeO)2
1d, 3,4-CH2O2
1a, 3,4,5-(MeO)3
1e, 3-MeO
TfOH (2)
Ga(OTf)3 (2)/TfOH (2)
50
70
2p, Ph, Ph
2p, Ph, Ph
a
The reactions were run on a 1.0 mmol scale with 1a, 2a (1.05 equiv), 25 ꢀC.
Isolated yields.
18% of A was isolated.
40 h.
3,4,5-Trimethoxyphenol was obtained (for entry 8, 12%; entry 10, 8%).
No reaction.
Complex mixture.
100 ꢀC.
2q, 4-FC6H4, Ph
2r, 4-MeOC6H4, Ph
2q, 4-FC6H4, Ph
2q, 4-FC6H4, Ph
2q, 4-FC6H4, Ph
b
c
d
e
f
1e, 3-MeO
1b, 3,5-(MeO)2
1d, 3,4-CH2O2
1a, 3,4,5-(MeO)3
g
h
i
a
The reactions were run on a 1.0 mmol scale with 1, 2 (1.05 equiv), DMF (5 mL),
25 ꢀC, 5 h; then Ga(OTf)3 (2 mol %), 25 ꢀC, 5 h.
b
88% of A was isolated.
Isolated yields.

5134
H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
CH2O2C6H3, 3,4-Cl2C6H3; Y¼allyl, benzyl, Ph) did not affect the one-
pot procedure. The structures of 5c, 5d and 5j were determined by
single-crystal X-ray crystallography.14
electron withdrawing groups. Even after increasing the catalytic
amounts (10 mol %), the results were still similar. Based on the
observations, the electron withdrawing nitrophenyl or carbox-
yphenyl group inhibit the Ga(OTf)3-catalyzed direct intramolecular
cyclodehydration of 1 and 2. We envisioned that the para-oxy-
genated aryl group is a key substituent for generating the benzo-
furan skeleton.
The proposed mechanism of 3a is illustrated in Scheme 3. Be-
ginning with 1a, O-alkylation of 1a with 2a generates A in DMF. The
initial coordination of A with Ga(OTf)3 to the carbonyl oxygen can
induce subsequent intramolecular cyclization. Through the para-
methoxy group of aromatic moiety promoted nucleophilic attack
on the intermediate I, II is formed. Following the deprotonation of
II by in situ generated triflate ion, III is afforded. Then, III traps the
proton of TfOH to lead IV and the resulting triflate ion. Furthermore,
para-methoxy group promotes the removal of Ga(OTf)2(OH). Fi-
nally, 3a is produced via triflate ion mediated deprotonation of V.
Subsequently, Ga(OTf)3 is regenerated by forming Ga(OTf)2(OH)
and TfOH in situ.
MeO
O
O
MeO
MeO
6a (60% for 1e)
6b (60% for 1c)
O
Ga(OTf)
3
+
(RO)
n
DMF
Br
OK
1e, 1c, 1d, 1a
MeO
2s
MeO
MeO
O
O
OTf
TfO
O
O
OTf
Ga
MeO
MeO
MeO
Ga(OTf)
6c (58% for 1d)
6d (54% for 1a)
3
O
Ph
MeO
MeO
MeO
MeO
O
O
Ph
MeO
O
Ph
DMF
+
Br
OK
MeO
O
I
O
(
)
n
Ga(OTf)
DMF
3
KBr
+
1a
2a
A
O
O
MeO
MeO
Br
MeO
OK
6e (50% for 2t)
6f (45% for 2u)
1e
2t, n = 1
2u, n = 2
TfO
OTf
TfO
OTf
TfO
OTf
TfO
Ga
O
Ga
Ga
O
MeO
IV
MeO
MeO
OTf
H
OTf
H
Ph
H
O
MeO
MeO
MeO
Ph
MeO
Ph
Scheme 4. Synthesis of 6aef.
MeO
O
O
MeO
O
III
II
Ga(OTf) (OH)
2
P
P
Ga(OTf) + H
O
2
3
+
TfOH
hυ, I , EtOAc
MeO
V
2
Ph
MeO
Ph
MeO
MeO
MeO
MeO
H
(RO)
(RO)
n
n
O
O
O
OTf
O
O
7a-7i
P = H, F, MeO
3a
5a-c, 5e-j
Scheme 3. Proposed mechanism.
MeO
MeO
MeO
Changing skeleton 2 from acyclic a-bromoketone to bicyclic a-
bromotetralone, the synthesis of benzonaphthofurans was in-
vestigated via the reaction of 1a and 1cee with 2s, as shown in
Scheme 4. For reaction of 1e and 2s, an inseparated mixture of 6a
and its dihydroisomer 6ae1 with a ratio of 3:1 was isolated in a 60%
yield. The similar result was performed for the formation of 6c (see
Supplementary data). Fully conjugated tetracycles 6b and 6d were
generated in 60% and 54% yields, respectively via the tandem
dehydrogenative process. Next, Ga(OTf)3-mediated treatment of 1e
O
O
O
MeO
MeO
7a (80%, for 5a)
7b (83%, for 5b)
F
7c (84%, for 5c)
OMe
MeO
MeO
MeO
O
O
O
MeO
MeO
7d (88%, for 5e)
F
7e (86%, for 5f)
7f (85%, for 5g)
with monocyclic a-bromoketone 2teu afforded 6e and 6f in 50%
F
F
and 45% yields, respectively. For the provided yields, 6 and 5 were
similar but were accessed in lower yields than them of 3 and 4. The
structure of 6c was determined by single-crystal X-ray crystallog-
raphy.14 To extend the application of this domino route, photolytic
Scholl annulation of diarylbenzofurans 5aec and 5eej was further
explored (Scheme 5).15,16 A number of processes are available for
the Scholl reaction. Of these methods used in the previous litera-
ture, the photolytic Scholl oxidative annulation provides the most
convenient operation and higher yields. By the addition of molec-
ular iodine and 1,2-epoxybutane, pentacyclic functionalized ben-
zophenanthrofurans 7aei were isolated in 80%e88% yields by the
irradiation of 5aec and 5eej in EtOAc at rt for 50 h under a 254 nm
wavelength irradiation. The structural skeletons of 7f and 7i were
determined by single-crystal X-ray crystallography.14 To compare
with 1aee with the electron-donating groups, the substrates 1feh
with the electron-withdrawing group (R1¼CHO, NO2) were exam-
ined, as shown in Scheme 6. Treatment of 1feh with 2c furnished
8aec in 75%e91% yields with no observation of benzofuran 9. For
the generating benzofuran skeleton, the results showed that the
efficiency of Ga(OTf)3 was limited in the case of substrates with
MeO
MeO
MeO
MeO
MeO
O
O
O
O
O
7g (83%, for 5h)
7h (83%, for 5i)
7i (85%, for 5j)
Scheme 5. Synthesis of 7aef.
OMe
1
2
OMe
OMe
1
2
1
2
R
R
R
R
R
R
O
+
O
O
Ga(OTf)
DMF
3
OK
O
Br
1
2
2c
8a (91%)
8b (82%)
8c (75%)
9
1f, R = CHO, R = H
(not detected)
1
2
1g, R = CHO, R = OMe
1
2
1h, R = NO , R = OMe
2
Scheme 6. Synthesis of 8aec.

H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
5135
In further work, a one-pot synthesis of benzofuran was studied
by the involvement of different potassium salts, as shown in
Scheme 7. Under the above conditions, K2CO3, t-BuOK and KH
provided 3a in similar yields (60%, 63% and 60%). Although the
isolated yield was low, this one-pot process by using bases/DMF
was convenient.
13C NMR (100 MHz, CDCl3):
133.88, 133.08, 128.83 (2ꢁ), 128.12 (2ꢁ), 92.93 (2ꢁ), 71.32, 60.95,
56.13 (2ꢁ); Anal. Calcd for C17H18O5: C, 67.54; H, 6.00. Found: C,
67.68; H, 6.15.
d
194.58, 154.62, 153.73 (2ꢁ), 134.57,
4.3. A representative synthetic procedure of skeletons 3, 4, 5
and 6 is as follows
MeO
MeO
Ph
o
Base (1.0 equiv), DMF, 25 C, 5 h
MeO
MeO
MeO
MeO
O
Ph
Bromides 2 (1.05 mmol) was added to a solution of crude oxy-
genated phenoxides 1 (1.0 mmol, prepared from phenols and
aqueous KOH) in DMF (5 mL) at 25 ꢀC. The reaction mixture was
stirred at 25 ꢀC for 5 h. Ga(OTf)3 (10 mg, 0.02 mmol) was added to
the reaction mixture at 25 ꢀC. The reaction mixture was stirred at
25 ꢀC for 5 h. The reaction mixture was concentrated and extracted
with CH2Cl2 (3ꢁ10 mL). The combined organic layers were washed
with brine, dried, filtered and evaporated to afford crude product
under reduced pressure. Purification on silica gel (hexanes/
EtOAc¼4/1e1/1) afforded 3, 4, 5 and 6.
+
o
O
then Ga(OTf) (2 mol %), 25 C, 5 h
3
OH
Br
2a 60% (for K CO ); 63% (for t-BuOK); 60% (fro KH)
3a
2
3
Scheme 7. One-pot synthesis of 3a.
3. Conclusion
In summary, we have developed a method for the synthesis of
a series of functionalized benzofurans 3e5 and benzonaphthofur-
ans 6 by the intermolecular O-alkylation of
with potassium oxygenated phenoxides 1 followed by Ga(OTf)3-
catalyzed direct intramolecular cyclodehydration of the resulting
aryloxyaryl ketones. The use of various metal triflates was in-
vestigated for the one-pot facile approach and efficient trans-
formation. Pentacyclic benzophenanthrofurans 7 were prepared
via photolytic annulations of 5. The structures of the key products
were confirmed by X-ray crystallography. Further investigations
regarding the synthetic application of metal triflates are ongoing in
our laboratory.
a-bromoaryl ketones 2
4.3.1. 4,5,6-Trimethoxy-3-phenyl-benzofuran (3a). Yield¼76% (216
mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C17H17O4 285.1127,
a
-
found 285.1132; 1H NMR (400 MHz, CDCl3):
d 7.68e7.65 (m, 2H), 7.54
(s,1H), 7.45e7.41 (m, 2H), 7.38e7.34 (m, 1H), 6.90 (s,1H), 3.93 (s, 6H),
3.65 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
152.56, 152.27, 146.98,
140.44, 138.77, 131.81, 128.83 (2ꢁ), 127.95 (2ꢁ), 127.09, 122.61, 112.91,
91.41, 61.43, 61.32, 51.11; Anal. Calcd for C17H16O4: C, 71.82; H, 5.67.
Found: C, 71.93; H, 5.81.
4.3.2. 4,6-Dimethoxy-3-(3-methoxyphenyl)-benzofuran
(3b). Yield¼70% (199 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C17H17O4 285.1127, found 285.1131; 1H NMR (400 MHz, CDCl3):
4. Experimental section
4.1. General
d
7.54 (s, 1H), 7.34 (t, J¼8.0 Hz, 1H), 7.28 (t, J¼0.8 Hz, 1H), 7.25 (dd,
J¼0.8, 8.0 Hz, 1H), 6.93 (ddd, J¼0.8, 2.8, 8.4 Hz, 1H), 6.71 (d,
J¼2.0 Hz, 1H), 6.41 (d, J¼1.6 Hz, 1H), 3.88 (s, 6H), 3.84 (s, 3H); 13C
All other reagents and solvents were obtained from commercial
sources and used without further purification. Reactions were rou-
tinely carried out under an atmosphere of dry nitrogen with mag-
netic stirring. Products in organic solvents were dried with
anhydrous magnesium sulfate before concentration in vacuo. Melt-
ing points were determined with a SMP3 melting apparatus. 1H and
13C NMR spectra were recorded on a Varian INOVA-400 spectrom-
eter operating at 400 and at 100 MHz, respectively. Chemical shifts
NMR (100 MHz, CDCl3):
d 159.18, 159.10, 157.84, 154.53, 139.94,
133.58, 128.80, 122.62, 121.44, 114.75, 112.89, 109.61, 94.55, 88.29,
55.61, 55.28, 55.13.
4.3.3. 4,5,6-Trimethoxy-3-(3-methoxyphenyl)-benzofuran
(3c). Yield¼73% (229 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C18H19O5 315.1233, found 315.1235; 1H NMR (400 MHz, CDCl3):
d
7.55 (s, 1H), 7.33 (t, J¼8.4 Hz, 1H), 7.27e7.22 (m, 2H), 6.91 (ddd,
J¼0.8, 2.4, 8.4 Hz, 1H), 6.88 (s, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 3.86 (s,
3H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3):
159.28, 152.58,
(d) are reported in parts per million (ppm) and the coupling con-
stants (J) are given in Hertz. High resolution mass spectra (HRMS)
were measured with a mass spectrometer Finnigan/Thermo Quest
MAT 95XL. X-ray crystal structures were obtained with an Enraf-
Nonius FR-590 diffractometer (CAD4, Kappa CCD).
d
152.27, 146.95, 140.60, 138.80, 133.13, 128.91, 122.52, 121.16, 114.31,
112.87, 112.79, 91.42, 61.52, 61.32, 56.10, 55.08.
4.3.4. 5,6-Dimethoxy-3-phenyl-benzofuran (3d). Yield¼78% (198
mg); Colorless solid; mp¼94e96 ꢀC (recrystallized from hexanes and
EtOAc); HRMS (ESI, Mþþ1) calcd for C16H15O3 255.1021, found
4.2. 1-Phenyl-2-(3,4,5-trimethoxyphenoxy)-ethanone (A)
KOH (56 mg, 1.0 mmol) was added to a solution of 3,4,5-
trimethoxyphenol (184 mg, 1.0 mmol) in water (5 mL) at 25 ꢀC.
The reaction mixture was stirred at 100 ꢀC for 30 min. The reaction
mixture was concentrated to afford crude potassium phenoxide 1a
255.1024; 1H NMR (400 MHz, CDCl3):
d 7.69 (s, 1H), 7.64e7.61 (m,
2H), 7.50e7.46 (m, 2H), 7.40e7.36 (m, 1H), 7.24 (s, 1H), 7.09 (s, 1H),
3.94 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
150.37, 148.11, 146.66,
140.21 (2ꢁ), 132.23, 128.85 (2ꢁ), 127.19 (2ꢁ), 122.24, 118.13, 101.51,
under reduced pressure. Without purification,
a-bromoacetophe-
95.46, 56.35, 56.06.
none (2a, 210 mg, 1.05 mmol) was added to a solution of crude 1a in
DMF (5 mL) at 25 ꢀC. The reaction mixture was stirred at 25 ꢀC for
5 h. The reaction mixture was concentrated and extracted with
CH2Cl2 (3ꢁ10 mL). The combined organic layers were washed with
brine, dried, filtered and evaporated to afford crude product under
reduced pressure. Purification on silica gel (hexanes/EtOAc¼50/
1e10/1) afforded A. Yield¼86% (260 mg); Colorless solid;
mp¼106e109 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C17H19O5 303.1233, found 303.1236; 1H NMR
4.3.5. 5,6-Dioxymethylene-3-phenyl-benzofuran (3e). Yield¼77%
(183 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C15H11O3
239.0708, found 239.0712; 1H NMR (400 MHz, CDCl3):
d 7.72 (s,
1H), 7.63e7.60 (m, 2H), 7.52e7.47 (m, 2H), 7.42e7.39 (m, 1H), 7.23
(s, 1H), 7.07 (s, 1H), 6.01 (s, 2H); 13C NMR (100 MHz, CDCl3):
d
150.95, 146.28, 144.81, 140.69, 132.05, 128.86 (2ꢁ), 127.30, 127.25
(2ꢁ), 122.59, 119.63, 101.33, 98.70, 93.66.
(400 MHz, CDCl3):
d
8.01e7.99 (m, 2H), 7.64e7.60 (m, 1H),
4.3.6. 5,6-Dioxymethylene-3-(3-methoxyphenyl)-benzofuran
(3f). Yield¼80% (214 mg); Colorless solid; mp¼116e117 ꢀC
7.52e7.48 (m, 2H), 6.21 (s, 2H), 5.22 (s, 2H), 3.81 (s, 6H), 3.77 (s, 3H);

5136
H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C16H13O4 269.0814, found 269.0818; 1H NMR (400 MHz, CDCl3):
for C16H15O3 255.1021, found 255.1023; 1H NMR (400 MHz, CDCl3):
d
7.71 (s, 1H), 7.39 (t, J¼8.0 Hz, 1H), 7.21 (s, 1H), 7.19e7.14 (m, 2H),
d
7.71 (d, J¼8.8 Hz, 1H), 7.68 (s, 1H), 7.59 (d, J¼8.8 Hz, 2H), 7.11 (d,
J¼2.0 Hz, 1H), 7.04 (d, J¼8.8 Hz, 2H), 6.98 (dd, J¼2.0, 8.8 Hz, 1H),
3.89 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3):
158.94,
7.04 (s, 1H), 6.93 (dd, J¼2.4, 8.0 Hz,1H), 6.00 (s, 2H), 3.88 (s, 3H); 13
C
NMR (100 MHz, CDCl3):
d
159.95, 150.91, 146.27, 144.81, 140.81,
d
133.34, 129.88, 122.48, 119.69, 119.56, 112.95, 112.65, 101.34, 98.71,
93.65, 55.15.
158.04, 156.69, 139.59, 128.37 (2ꢁ), 124.51, 121.58, 120.38, 119.94,
114.30 (2ꢁ), 111.86, 96.06, 55.56, 55.18; Anal. Calcd for C16H14O3: C,
75.57; H, 5.55. Found: C, 75.68; H, 5.32.
4.3.7. 5,6-Dioxymethylene-3-(4-methoxyphenyl)-benzofuran
(3g). Yield¼87% (233 mg); Colorless solid; mp¼127e128 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C16H13O4 269.0814, found 269.1812; 1H NMR (400 MHz, CDCl3):
4.3.14. 6-Methoxy-3-(4-methylphenyl)-benzofuran (3n). Yield¼83%
(198 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C16H15O2
239.1072, found 239.1073; 1H NMR (400 MHz, CDCl3):
d 7.69 (d,
d
7.63 (s, 1H), 7.50 (d, J¼8.8 Hz, 2H), 7.15 (s, 1H), 7.03e6.99 (m, 3H),
J¼8.4 Hz, 1H), 7.69 (s, 1H), 7.54 (d, J¼8.0 Hz, 2H), 7.28 (d, J¼8.4 Hz,
6.00 (s, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
159.01,
2H), 7.08 (d, J¼2.4 Hz, 1H), 6.95 (dd, J¼2.4, 8.8 Hz, 1H), 3.88 (s, 3H),
150.89, 146.23, 144.77, 140.15, 128.46 (2ꢁ), 124.44, 122.23, 119.93,
114.39 (2ꢁ), 101.35, 98.70, 93.69, 55.29; Anal. Calcd for C16H12O4: C,
71.64; H, 4.51. Found: C, 71.76; H, 4.73.
2.42 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 158.10, 156.79, 140.03,
137.13, 129.60 (2ꢁ), 129.24, 127.21 (2ꢁ), 121.97, 120.54, 119.94,
111.97, 96.13, 55.71, 21.22.
4.3.8. 5,6-Dioxymethylene-3-(4-trifluoromethylphenyl)-benzofuran
(3h). Yield¼78% (239 mg); Colorless solid; mp¼152e154 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
4.3.15. 3-Biphenyl-4-yl-6-methoxy-benzofuran (3o). Yield¼85%
(255 mg); Colorless solid; mp¼112e114 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C21H17O2
301.1229, found 301.1234; 1H NMR (400 MHz, CDCl3):
C
16H10F3O3 307.0582, found 307.0588; 1H NMR (400 MHz, CDCl3):
d
7.74 (s,1H), 7.71 (d, J¼8.4 Hz, 2H), 7.67 (d, J¼8.4 Hz, 2H), 7.14 (s,1H),
d 7.81e7.67 (m, 8H), 7.54e7.51 (m, 2H), 7.45e7.41 (m, 1H), 7.15 (d,
7.03 (s, 1H), 6.02 (s, 2H); 13C NMR (100 MHz, CDCl3):
d
151.12, 146.65,
J¼2.0 Hz, 1H), 7.03 (dd, J¼2.4, 8.8 Hz, 1H), 3.92 (s, 3H); 13C NMR
145.19,141.43,135.85,127.36 (2ꢁ),125.93 (d, J¼3.8 Hz, 2ꢁ),125.85 (d,
(100 MHz, CDCl3): d 158.16, 156.86, 140.95, 140.36, 140.08, 131.15,
J¼3.8 Hz, 2ꢁ), 121.57, 119.09, 101.55, 98.42, 93.88.
128.79 (2ꢁ), 127.54 (2ꢁ), 127.33, 127.18, 126.93 (2ꢁ), 121.64,
120.53, 119.68, 112.10, 96.15, 96.15, 55.62.
4.3.9. 5,6-Dioxymethylene-3-(4-fluorophenyl)-benzofuran
(3i). Yield¼76% (195 mg); Colorless solid; mp¼76e78 ꢀC (recrystal-
lized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
4.3.16. 6-Methoxy-3-(4-trifluoromethylphenyl)-benzofuran
(3p). Yield¼80% (234 mg); Colorless solid; mp¼85e88 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C
15H10FO3 257.0614, found 257.0618; 1H NMR (400 MHz, CDCl3):
d
7.64 (s,1H), 7.55e7.50 (m, 2H), 7.18e7.12 (m, 2H), 7.11 (s,1H), 7.02 (s,
C
16H12F3O2 293.0789, found 293.0792; 1H NMR (400 MHz, CDCl3):
1H), 6.01 (s, 2H); 13C NMR (100 MHz, CDCl3):
d
162.18 (d, J¼245.6 Hz),
d
7.77 (s, 1H), 7.75e7.70 (m, 4H), 7.67 (d, J¼8.8 Hz, 1H), 7.09 (d,
150.92, 146.41, 144.94, 140.55, 128.89 (d, J¼7.6 Hz, 2ꢁ), 128.07 (d,
J¼3.0 Hz),121.74,119.61,115.88(d, J¼22.0 Hz, 2ꢁ),101.43, 98.45, 93.76.
J¼2.0 Hz, 1H), 6.98 (dd, J¼2.0, 8.8 Hz, 1H), 3.89 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d 158.42, 156.94, 141.06, 135.96, 129.48, 127.36
(2ꢁ), 125.90 (d, J¼3.0 Hz), 125.82 (d, J¼3.8 Hz), 121.04, 120.25 (2ꢁ),
119.15, 112.47, 96.26, 55.71; Anal. Calcd for C16H11F3O2: C, 65.76; H,
3.79. Found: C, 65.96; H, 3.61.
4.3.10. 3-Biphenyl-4-yl-5,6-dioxymethylene-benzofuran
(3j). Yield¼78% (245 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C21H15O3 315.1021, found 315.1023; 1H NMR (400 MHz, CDCl3):
d
7.75 (s, 1H), 7.72e7.64 (m, 6H), 7.50e7.46 (m, 2H), 7.40e7.36 (m,
1H), 7.23 (s, 1H), 7.05 (s, 1H), 6.02 (s, 2H); 13C NMR (100 MHz,
CDCl3): 151.07, 146.39, 144.94, 140.84, 140.65, 140.25, 131.09,
4.3.17. 6-Methoxy-3-(3,4-dioxymethylenephenyl)-benzofuran
(3q). Yield¼80% (214 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C16H13O4 269.0814, found 269.0821; 1H NMR (400 MHz, CDCl3):
d
128.84 (2ꢁ), 127.65 (4ꢁ), 127.39 (2ꢁ), 127.00, 122.29, 119.68, 101.43,
98.82, 93.80; Anal. Calcd for C21H14O3: C, 80.24; H, 4.49. Found: C,
80.48; H, 4.67.
d
7.64 (d, J¼8.8 Hz, 1H), 7.63 (s, 1H), 7.11e7.06 (m, 3H), 6.94 (dd,
J¼2.4, 8.8 Hz, 1H), 6.91 (dd, J¼0.8, 8.0 Hz, 1H), 6.01 (s, 2H), 3.88 (s,
3H); 13C NMR (100 MHz, CDCl3):
158.17, 156.73, 148.11, 147.00,
d
139.88, 126.00, 121.89, 120.78, 120.38, 119.88, 112.01, 108.81, 107.89,
101.13, 96.17, 55.73.
4.3.11. 5,6-Dioxymethylene-3-(2-naphthyl)-benzofuran
(3k). Yield¼82% (236 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C19H13O3 289.0865, found 289.0871; 1H NMR (400 MHz, CDCl3):
4.3.18. 6-Methoxy-3-(3,4-dichlorophenyl)-benzofuran
(3r). Yield¼80% (234 mg); Colorless solid; mp¼91e93 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
d
8.05 (d, J¼1.2 Hz, 1H), 7.93 (d, J¼8.4 Hz, 1H), 7.91e7.87 (m, 2H),
7.81 (s, 1H), 7.69 (dd, J¼2.0, 8.4 Hz, 1H), 7.56e7.49 (m, 2H), 7.31 (s,
1H), 7.08 (s, 1H), 6.03 (s, 2H); 13C NMR (100 MHz, CDCl3):
151.08,
d
C
15H11Cl2O2 293.0136, found 293.0141; 1H NMR (400 MHz, CDCl3):
146.38, 144.93, 141.12, 133.66, 132.60, 129.51, 128.59, 127.87, 127.71,
126.41, 125.92, 125.65, 125.64, 122.60, 119.72, 101.42, 98.85, 93.80.
d
7.85 (d, J¼2.0 Hz,1H), 7.57 (dd, J¼2.0, 8.4 Hz,1H), 7.44 (d, J¼8.4 Hz,
1H), 7.41 (d, J¼8.0 Hz, 1H), 7.02 (d, J¼2.0 Hz, 1H), 6.93 (d, J¼0.8 Hz,
1H), 6.85 (dd, J¼2.0, 8.4 Hz, 1H), 3.84 (s, 3H); 13C NMR (100 MHz,
4.3.12. 6-Methoxy-3-phenyl-benzofuran (3l). Yield¼84% (188 mg);
Colorless solid; mp¼45e48 ꢀC (recrystallized from hexanes and
EtOAc); HRMS (ESI, Mþþ1) calcd for C15H13O2 225.0916, found
CDCl3): d 158.60, 156.09, 152.61, 133.08, 131.66, 130.75, 130.66,
126.06, 123.48, 122.14, 121.32, 112.45, 102.65, 95.82, 55.74.
225.0921; 1H NMR (400 MHz, CDCl3):
d
7.75 (d, J¼8.8 Hz, 1H), 7.74
4.3.19. 6-Methoxy-3-(2-naphthyl)-benzofuran
(3s). Yield¼84%
(s, 1H), 7.69e7.65 (m, 2H), 7.52e7.48 (m, 2H), 7.42e7.37 (m, 1H),
(230 mg); Colorless solid; mp¼148e149 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C19H15O2
7.12 (d, J¼2.4 Hz, 1H), 6.99 (dd, J¼2.4, 8.8 Hz, 1H), 3.90 (s, 3H); 13C
NMR (100 MHz, CDCl3):
127.32, 127.30 (2ꢁ), 122.06, 120.50, 119.75, 112.04, 96.13, 55.65.
d
158.14, 156.81, 140.27, 132.17, 128.88 (2ꢁ),
275.1072, found 275.1077; 1H NMR (400 MHz, CDCl3):
d 8.12 (s, 1H),
7.94 (d, J¼8.8 Hz,1H), 7.90 (dt, J¼1.6, 8.4 Hz, 2H), 7.84 (s,1H), 7.83 (d,
J¼8.8 Hz, 1H), 7.74 (dd, J¼1.6, 8.4 Hz, 1H), 7.59e7.56 (m, 2H), 7.12 (d,
J¼2.4 Hz, 1H), 7.00 (dd, J¼2.4, 8.8 Hz, 1H), 3.91 (s, 3H); 13C NMR
4 . 3 .13 . 6 - M e t h o x y- 3 - ( 4 - m e t h o x y p h e nyl ) -b e n z o f u ra n
(3m). Yield¼84% (213 mg); Colorless solid; mp¼55e57 ꢀC
(100 MHz, CDCl3): d 158.22, 156.93, 140.71, 133.70, 132.63, 129.64,

H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
5137
128.56, 127.90, 127.74, 126.40, 125.90, 125.67 (2ꢁ), 122.07, 120.63,
7.42e7.38 (m,1H), 7.09 (d, J¼2.0 Hz,1H), 6.93 (dd, J¼2.4, 8.4 Hz,1H),
6.16e6.06 (m, 1H), 5.27e5.22 (m, 2H), 3.89 (s, 3H), 3.66 (dt, J¼1.6,
119.82, 112.16, 96.20, 55.71.
6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 157.75, 155.20, 151.15,
4.3.20. 2-Allyl-4,5,6-trimethoxy-3-phenyl-benzofuran
(4a). Yield¼64% (207 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C20H21O4 325.1440, found 325.1436; 1H NMR (400 MHz, CDCl3):
140.69, 139.87, 134.02, 131.64, 129.14 (2ꢁ), 128.81 (2ꢁ), 127.42 (2ꢁ),
127.33, 127.00 (2ꢁ), 121.85, 119.78, 117.00 (2ꢁ), 111.42, 95.93, 55.71,
31.37; Anal. Calcd for C24H20O2: C, 84.68; H, 5.92. Found: C, 84.93;
H, 6.21.
d
7.49e7.46 (m, 2H), 7.45e7.39 (m, 2H), 7.37e7.32 (m, 1H), 6.86 (s,
1H), 6.04e5.94 (m, 1H), 5.18e5.13 (m, 2H), 3.90 (s, 3H), 3.86 (s, 3H),
3.49 (s, 3H), 3.47 (dt, J¼1.6, 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
4.3.27. 6-Methoxy-2,3-diphenyl-benzofuran
(5a). Yield¼63%
d
151.70, 151.02 (2ꢁ), 146.66, 138.70, 134.11, 132.70, 130.03 (2ꢁ),
(189 mg); Colorless solid; mp¼116e118 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C21H17O2
301.1229, found 301.1234; 1H NMR (400 MHz, CDCl3):
127.80 (2ꢁ), 127.02, 117.30, 116.87, 114.82, 91.30, 61.47, 61.36, 56.32,
30.99.
d
7.67e7.64 (m, 2H), 7.54e7.26 (m, 9H), 7.13 (d, J¼2.0 Hz, 1H),
4.3.21. 2-Allyl-5,6-dimethoxy-3-phenyl-benzofuran (4b). Yield¼66%
(194 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C19H19O3
6.91 (dd, J¼2.0, 8.4 Hz, 1H), 3.91 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
158.40, 154.95, 149.58, 132.93, 130.84, 129.65 (2ꢁ),
295.1334, found 295.1335; 1H NMR (400 MHz, CDCl3):
d
7.52e7.49
128.90 (2ꢁ), 128.36 (2ꢁ), 127.89, 127.54, 126.56 (2ꢁ), 123.68,
(m, 4H), 7.41e7.36 (m, 1H), 7.06 (s, 1H), 7.01 (s, 1H), 6.09e5.99 (m,
1H), 5.20e5.14 (m, 2H), 3.93 (s, 3H), 3.89 (s, 3H), 3.58 (dt, J¼1.6,
120.19, 117.40, 111.90, 95.66, 55.74.
6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
151.08, 148.76, 147.61,
4.3.28. 5,6-Dimethoxy-2,3-diphenyl-benzofuran
(5b). Yield¼64%
146.51, 134.13, 132.78, 128.81 (4x), 127.10, 120.35, 117.68, 116.88,
101.27, 95.35, 56.50, 56.28, 31.33.
(211 mg); Colorless solid; mp¼162e164 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C22H19O3
331.1334, found 331.1341; 1H NMR (400 MHz, CDCl3):
d 7.62e7.59
4.3.22. 2-Allyl-5,6-dioxymethylene-3-phenyl-benzofuran
(4c). Yield¼68% (189 mg); Colorless solid; mp¼72e74 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
(m, 2H), 7.53e7.40 (m, 5H), 7.32e7.23 (m, 3H), 7.13 (s, 1H), 6.90 (s,
1H), 3.98 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
149.61,
148.64, 148.39, 146.76, 133.09, 130.88, 129.64 (2ꢁ), 129.00 (2ꢁ),
128.32 (2ꢁ), 127.71, 127.54, 126.37 (2ꢁ), 122.10, 117.69, 101.11, 95.09,
56.38, 56.27; Anal. Calcd for C22H18O3: C, 79.98; H, 5.49. Found: C,
80.26; H, 5.21.
C
18H15O3 279.1021, found 279.1023; 1H NMR (400 MHz, CDCl3):
d
7.50e7.45 (m, 4H), 7.39e7.34 (m, 1H), 6.99 (s, 1H), 6.96 (s, 1H),
6.08e5.98 (m, 1H), 5.97 (s, 2H), 5.19e5.18 (m, 1H), 5.16e5.14 (m,
1H), 3.56 (dt, J¼1.6, 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
151.48, 149.24, 145.67, 144.46, 134.06, 132.53, 128.80 (2ꢁ), 128.77
4.3.29. 5,7-Dimethoxy-2,3-diphenyl-benzofuran
(5c). Yield¼65%
(2ꢁ), 127.15, 121.79, 118.02, 116.91, 101.19, 98.42, 93.41, 31.35.
(215 mg); Colorless solid; mp¼129e131 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C22H19O3
4.3.23. 2-Benzyl-6-methoxy-3-phenyl-benzofuran (4d). Yield¼66%
(207 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C22H19O2
331.1334, found 331.1336; 1H NMR (400 MHz, CDCl3):
d 7.55e7.51
(m, 4H), 7.46e7.40 (m, 3H), 7.31e7.23 (m, 3H), 6.76 (d, J¼2.0 Hz,1H),
315.1385, found 315.1388; 1H NMR (400 MHz, CDCl3):
d 7.54e7.46
6.35 (d, J¼2.0 Hz, 1H), 3.90 (s, 3H), 3.69 (s, 3H); 13C NMR (100 MHz,
(m, 5H), 7.41e7.24 (m, 6H), 7.02 (d, J¼2.0 Hz, 1H), 6.89 (dd, J¼2.4,
CDCl3):
d
159.18, 155.79, 154.84, 148.55, 133.67, 130.92, 130.62 (2ꢁ),
8.8 Hz, 1H), 4.20 (s, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3):
128.19 (2ꢁ), 127.90 (2ꢁ), 127.42, 127.13, 126.40 (2ꢁ), 117.37, 113.07,
94.50, 87.88, 55.65, 55.33; Anal. Calcd for C22H18O3: C, 79.98; H,
5.49. Found: C, 80.10; H, 5.53. Single-crystal X-ray diagram: crystal
of compound 5c was grown by slow diffusion of EtOAc into a so-
lution of compound 5c in CH2Cl2 to yield colorless prisms. The
compound crystallizes in the triclinic crystal system, space group
d
157.82, 155.26, 151.42, 138.13, 132.62, 128.93 (2ꢁ), 128.81 (2ꢁ),
128.59 (2ꢁ), 128.44 (2ꢁ), 127.21, 126.50, 121.99, 119.85, 118.06,
111.48, 95.97, 55.74, 32.87.
4.3.24. 2-Allyl-6-methoxy-3-(4-methoxyphenyl)-benzofuran
(4e). Yield¼73% (215 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C19H19O3 295.1334, found 295.1337; 1H NMR (400 MHz, CDCl3):
ꢀ
ꢀ
ꢀ
Pe1, a¼8.0579(6) A, b¼9.5536(7) A, c¼11.1123(8) A,
V¼841.99(11) A , Z¼2, dcalcd¼1.303 g/cm3, F(000)¼318, 2
q
range
3
ꢀ
d
7.44e7.39 (m, 3H), 7.04e7.03 (m, 2H), 7.02 (s, 1H), 6.90 (dd, J¼2.4,
1.840e26.514ꢀ, R indices (all data) R1¼0.0914, wR2¼0.1212.
8.4 Hz,1H), 6.10e6.00 (m, 1H), 5.21e5.18 (m, 1H), 5.17e5.15 (m, 1H),
3.87 (s, 3H), 3.86 (s, 3H), 3.57 (dt, J¼2.0, 6.4 Hz, 2H); 13C NMR
4. 3. 30. 5, 6-Dioxymethylene-2, 3-diphenyl-benzofuran
(5d). Yield¼67% (210 mg); Colorless solid; mp¼137e138 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C21H15O3 315.1021, found 315.1025; 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3):
d 158.75, 157.66, 155.09, 150.59, 134.17, 129.93
(2ꢁ), 124.89, 122.20, 119.69, 116.95, 116.84, 114.21 (2ꢁ), 111.26,
95.90, 55.74, 55.29, 31.28.
d
7.61e7.58 (m, 2H), 7.48e7.39 (m, 5H), 7.32e7.23 (m, 3H), 7.06 (s,
4.3.25. 2-Allyl-6-methoxy-3-(4-methylphenyl)-benzofuran
(4f). Yield¼68% (189 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C19H19O2 279.1385, found 279.1389; 1H NMR (400 MHz, CDCl3):
1H), 6.86 (s, 1H), 5.99 (s, 2H); 13C NMR (100 MHz, CDCl3):
d
150.09,
149.22, 146.48, 144.75, 132.88, 130.82, 129.65 (2ꢁ), 128.96 (2ꢁ),
128.36 (2ꢁ), 127.80, 127.61, 126.37 (2ꢁ), 123.70, 118.03, 101.31,
98.47, 93.28; Anal. Calcd for C21H14O3: C, 80.24; H, 4.49. Found: C,
80.48; H, 4.80. Single-crystal X-ray diagram: crystal of compound
5d was grown by slow diffusion of EtOAc into a solution of com-
pound 5d in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P 21/c,
d
7.44 (d, J¼8.4 Hz, 1H), 7.39 (d, J¼8.0 Hz, 2H), 7.29 (d, J¼7.6 Hz, 2H),
7.04 (d, J¼2.4 Hz, 1H), 6.87 (dd, J¼2.4, 8.4 Hz, 1H), 6.09e5.99 (m,
1H), 5.21e5.15 (m, 2H), 3.86 (s, 3H), 3.58 (dt, J¼2.0, 6.0 Hz, 2H), 2.42
(s, 3H); 13C NMR (100 MHz, CDCl3):
d 157.68, 155.14, 150.84, 136.82,
134.13, 129.62, 129.44 (2ꢁ), 128.71 (2ꢁ), 122.10, 119.78, 117.26,
3
ꢀ
ꢀ
ꢀ
ꢀ
116.87, 111.29, 95.93, 55.76, 31.31, 21.22.
a¼11.1460(14) A, b¼6.0896(6) A, c¼22.939(3) A, V¼1523.2(3) A ,
Z¼4, dcalcd¼1.371 g/cm3, F(000)¼656, 2
q
range 1.815e26.465ꢀ, R
indices (all data) R1¼0.0712, wR2¼0.1104.
4.3.26. 2-Allyl-3-biphenyl-4-yl-6-methoxy-benzofuran
(4g). Yield¼70% (238 mg); Colorless solid; mp¼123e124 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C24H21O2 341.1542, found 341.1547; 1H NMR (400 MHz, CDCl3):
4.3.31. 4,5,6-Trimethoxy-2,3-diphenyl-benzofuran (5e). Yield¼62%
(223 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C23H21O4
d
7.75e7.68 (m, 4H), 7.61 (d, J¼8.4 Hz, 2H), 7.55e7.48 (m, 3H),
361.1440, found 361.1445; 1H NMR (400 MHz, CDCl3):
d 7.56e7.52

5138
H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
(m, 4H), 7.48e7.39 (m, 3H), 7.30e7.21 (m, 3H), 6.95 (s, 1H), 3.95 (s,
3H), 3.90 (s, 3H), 3.51 (s, 3H); 13C NMR (100 MHz, CDCl3):
152.40,
150.68, 149.20, 147.04, 138.90, 133.38, 130.62, 130.31 (2ꢁ), 128.17
(2ꢁ), 128.12 (2ꢁ), 127.58, 127.33, 126.30 (2ꢁ), 117.13, 116.63, 91.08,
61.26, 61.22, 56.19; Anal. Calcd for C23H20O4: C, 76.65; H, 5.59.
Found: C, 76.87; H, 5.83.
cm3, F(000)¼792, 2
q
range 1.870e25.148ꢀ, R indices (all data)
R1¼0.2231, wR2¼0.3689.
d
4.3.37. 9-Methoxy-benzo[b]naphtho[1,2-d]furan
(6a). Yield¼60%
(148 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C17H13O2
249.0916, found 249.0923; For major compound 6a; 1H NMR
(400 MHz, CDCl3):
d
8.55 (dd, J¼8.4 Hz, 1H), 8.23 (d, J¼8.8 Hz, 1H),
4.3.32. 3-(4-Fluorophenyl)-6-methoxy-2-phenyl-benzofuran
(5f). Yield¼60% (191 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C21H16FO2 319.1134, found 319.1137; 1H NMR (400 MHz, CDCl3):
8.01 (dd, J¼8.4 Hz, 1H), 7.85 (d, J¼8.8 Hz, 1H), 7.74 (d, J¼9.2 Hz, 1H),
7.69 (dt, J¼1.2, 8.4 Hz, 1H), 7.54 (dt, J¼1.2, 8.4 Hz, 1H), 7.22 (d,
J¼2.4 Hz, 1H), 7.08 (dd, J¼2.4, 8.4 Hz, 1H), 3.94 (s, 3H); 13C NMR
d
7.65e7.62 (m, 2H), 7.50e7.47 (m, 2H), 7.36e7.29 (m, 4H), 7.21e7.16
(m, 2H), 7.12 (d, J¼2.0 Hz, 1H), 6.91 (dd, J¼2.4, 8.8 Hz, 1H), 3.90 (s,
3H); 13C NMR (100 MHz, CDCl3):
154.90, 149.67, 131.29 (d, J¼8.3 Hz, 2ꢁ), 130.66, 128.82 (d, J¼3.0 Hz),
128.42 (2ꢁ), 128.00, 126.52 (2ꢁ), 123.54, 119.94, 116.36, 115.98 (d,
J¼22.0 Hz, 2ꢁ), 112.01, 95.68, 55.71.
(100 MHz, CDCl3): d 158.99, 157.25, 154.17, 130.50, 129.12, 128.02,
127.02, 126.84, 125.80, 124.29, 123.45, 122.51, 122.10, 112.51, 111.54,
96.63, 55.72.
d
162.27 (d, J¼245.6 Hz), 158.45,
4. 3. 38. 9,10-Dimethoxy-benzo[b]naphtho[1, 2-d]furan
(6b). Yield¼60% (167 mg); Colorless solid; mp¼160e163 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C18H15O3 279.1021, found 279.1024; 1H NMR (400 MHz, CDCl3):
4.3.33. 6-Methoxy-3-(4-methoxyphenyl)-2-phenyl-benzofuran
(5g). Yield¼63% (208 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C22H19O3 331.1334, found 331.1341; 1H NMR (400 MHz, CDCl3):
d
8.48 (d, J¼8.4 Hz, 1H), 8.00 (d, J¼8.4 Hz, 1H), 7.82 (d, J¼9.2 Hz, 1H),
7.74 (s, 1H), 7.70 (d, J¼8.8 Hz, 1H), 7.69 (dt, J¼1.2, 8.4 Hz, 1H), 7.53
d
7.71e7.68 (m, 2H), 7.40 (d, J¼8.8 Hz, 2H), 7.39 (d, J¼8.4 Hz, 1H),
(dt, J¼1.2, 8.4 Hz,1H), 7.20 (s, 1H), 4.09 (s, 3H), 4.00 (s, 3H); 13C NMR
7.36e7.25 (m, 3H), 7.13 (d, J¼2.4 Hz, 1H), 7.04 (d, J¼8.8 Hz, 2H), 6.92
(100 MHz, CDCl3): d 154.07, 150.85, 148.96, 146.40, 130.39, 129.13,
(dd, J¼2.4, 8.8 Hz, 1H), 3.91 (s, 3H), 3.90 (s, 3H); 13C NMR (100 MHz,
128.51, 126.68, 126.65, 124.17, 123.13, 117.86, 116.44, 112.56, 103.66,
95.67, 56.69, 56.21.
CDCl3):
d
159.03, 158.32, 154.87, 149.28, 130.98, 130.72 (2ꢁ), 128.31
(2ꢁ), 127.71, 126.40 (2ꢁ), 124.95, 123.87, 120.15, 117.03, 114.36 (2ꢁ),
111.78, 95.61, 55.67, 55.18.
4.3.39. 9,10-Dioxymethylene-benzo[b]naphtho[1,2-d]furan
(6c). Yield¼58% (152 mg); Colorless solid; mp¼136e138 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C17H11O3 263.0708, found 263.0713; For major compound 6c; 1H
4.3.34. 3-(4-Fluorophenyl)-5,6-dimethoxy-2-phenyl-benzofuran
(5h). Yield¼60% (209 mg); Colorless solid; mp¼166e168 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H18FO3 349.1240, found 349.1248; 1H NMR (400 MHz,
NMR (400 MHz, CDCl3):
d
8.44 (d, J¼8.4 Hz, 1H), 7.99 (d, J¼8.0 Hz,
1H), 7.81 (d, J¼8.8 Hz, 1H), 7.73 (s, 1H), 7.69 (d, J¼8.8 Hz, 1H), 7.68
CDCl3):
7.21e7.15 (m, 2H), 7.12 (s, 1H), 6.84 (s, 1H), 3.97 (s, 3H), 3.88 (s, 3H);
13C NMR (100 MHz, CDCl3):
d 7.58e7.55 (m, 2H), 7.49e7.44 (m, 2H), 7.33e7.24 (m, 3H),
(dt, J¼1.2, 8.4 Hz, 1H), 7.53 (dt, J¼1.2, 8.4 Hz, 1H), 7.16 (s, 1H), 6.08 (s,
2H); 13C NMR (100 MHz, CDCl3):
d 154.42, 151.35, 146.92, 144.75,
d
162.29 (d, J¼245.6 Hz), 149.72, 148.61,
130.42, 129.15, 128.49, 126.80, 126.76, 124.26, 123.07, 117.87, 117.77,
112.55,101.68,100.61, 94.07. Single-crystal X-ray diagram: crystal of
compound 6c was grown by slow diffusion of EtOAc into a solution
of compound 6c in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the orthorhombic crystal system, space group P 21 21
148.48, 146.85, 131.31 (d, J¼7.6 Hz, 2ꢁ), 130.77, 128.98 (d, J¼3.0 Hz),
128.41 (2ꢁ), 127.85, 126.33 (2ꢁ), 122.04, 116.68, 116.10 (d,
J¼22.0 Hz, 2ꢁ), 100.86, 95.14, 56.40, 56.29; Anal. Calcd for
C
22H17FO3: C, 75.85; H, 4.92. Found: C, 75.98; H, 5.18.
3
ꢀ
ꢀ
ꢀ
ꢀ
21, a¼3.9329(11) A, b¼21.721(7) A, c¼27.730(8) A, V¼2368.9(12) A ,
4.3.35. 3-(4-Fluorophenyl)-5,6-dioxymethylene-2-phenyl-benzofu-
ran (5i). Yield¼63% (209 mg); Colorless solid; mp¼118e120 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C21H14FO3 333.0927, found 333.0931; 1H NMR (400 MHz,
Z¼8, dcalcd¼1.471 g/cm3, F(000)¼1088, 2
q
range 1.191e26.475ꢀ, R
indices (all data) R1¼0.1694, wR2¼0.1253.
4.3.40. 9,10,11-Trimethoxy-benzo[b]naphtho[1,2-d]furan
(6d). Yield¼54% (166 mg); Colorless solid; mp¼95e97 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
CDCl3):
7.18e7.14 (m, 2H), 7.05 (s, 1H), 6.80 (s, 1H), 5.99 (s, 2H); 13C NMR
(100 MHz, CDCl3):
d 7.57e7.55 (m, 2H), 7.45e7.41 (m, 2H), 7.33e7.27 (m, 3H),
d
162.33 (d, J¼245.6 Hz), 150.21, 149.19, 146.56,
C
19H17O4 309.1127, found 309.1128; 1H NMR (400 MHz, CDCl3):
144.84, 131.31 (d, J¼7.6 Hz, 2ꢁ), 130.64, 128.77, 128.44 (2ꢁ), 127.93,
126.33 (2ꢁ), 123.59, 116.99, 116.07 (d, J¼22.0 Hz, 2ꢁ), 101.37, 98.22,
93.35.
d
9.31 (d, J¼8.4 Hz, 1H), 7.98 (d, J¼8.0 Hz, 1H), 7.86 (d, J¼9.2 Hz, 1H),
7.70 (d, J¼8.8 Hz, 1H), 7.69 (dt, J¼1.2, 8.4 Hz, 1H), 7.52 (dt, J¼1.2,
8.4 Hz, 1H), 7.03 (s, 1H), 4.15 (s, 3H), 4.00 (s, 3H), 3.99 (s, 3H); 13C
NMR (100 MHz, CDCl3):
d 153.87, 153.34, 152.93, 147.77, 139.14,
4.3.36. 3-(4-Fluorophenyl)-4,5,6-trimethoxy-2-phenyl-benzofuran
(5j). Yield¼56% (212 mg); Colorless solid; mp¼132e134 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H20FO4 379.1346, found 379.1351; 1H NMR (400 MHz,
130.75, 128.85, 128.56, 127.55, 126.89, 126.64, 124.22, 118.56, 112.20,
112.14, 91.74, 61.92, 61.38, 56.34.
4.3.41. 7-Methoxy-1,2,3,4-tetrahydro-dibenzofuran (6e). Yield¼50%
(101 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd for C13H15O2
CDCl3):
6.93 (s, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.51 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d 7.51e7.45 (m, 4H), 7.31e7.23 (m, 3H), 7.16e7.11 (m, 2H),
203.1072, found 203.1074; 1H NMR (400 MHz, CDCl3):
d 7.27 (d,
d
162.28 (d, J¼244.9 Hz), 152.58, 150.73, 149.49,
J¼8.4 Hz, 1H), 6.98 (d, J¼2.0 Hz, 1H), 6.83 (dd, J¼2.0, 8.4 Hz, 1H),
147.01, 138.99, 132.08 (d, J¼7.6 Hz, 2ꢁ), 130.53, 129.32 (d,
J¼3.0 Hz), 128.34 (2ꢁ), 127.82, 126.42 (2ꢁ), 116.51, 116.12, 115.22
(d, J¼21.3 Hz, 2ꢁ), 91.18, 61.35, 61.29, 56.31; Anal. Calcd for
3.84 (s, 3H), 2.74e2.70 (m, 2H), 2.61e2.57 (m, 2H), 1.95e1.89 (m,
2H), 1.87e1.80 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 157.08, 155.15,
152.93, 122.38, 118.28, 112.51, 110.35, 96.19, 55.75, 23.37, 22.92,
22.67, 20.47.
C
23H19FO4: C, 73.01; H, 5.06. Found: C, 73.32; H, 4.95. Single-
crystal X-ray diagram: crystal of compound 5j was grown by
slow diffusion of EtOAc into a solution of compound 5j in CH2Cl2
to yield colorless prisms. The compound crystallizes in the
4.3.42. 2-Methoxy-6,7,8,9-tetrahydro-5H-10-oxa-benzo[a]azulene
(6f). Yield¼45% (97 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
for C14H17O2 217.1229, found 217.1231; 1H NMR (400 MHz, CDCl3):
ꢀ
monoclinic crystal system, space group P 21/c, a¼10.908(7) A,
3
ꢀ
ꢀ
ꢀ
b¼13.050(9) A, c¼13.425(9) A, V¼1908(2) A , Z¼4, dcalcd¼1.317 g/
d
7.26 (d, J¼8.4 Hz, 1H), 6.95 (d, J¼2.0 Hz, 1H), 6.84 (dd, J¼2.0,

H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
5139
8.4 Hz, 1H), 3.84 (s, 3H), 2.90 (t, J¼6.0 Hz, 2H), 2.67 (t, J¼6.0 Hz, 2H),
1.88e1.76 (m, 6H); 13C NMR (100 MHz, CDCl3):
157.06, 155.23,
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
d
for C21H14FO2 317.0978, found 317.0985; 1H NMR (400 MHz, CDCl3):
154.04, 124.04, 118.27, 115.49, 110.35, 95.69, 55.72, 30.46, 29.02,
28.28, 26.42, 23.21.
d
8.56 (d, J¼8.4 Hz, 1H), 8.46 (dd, J¼5.6, 8.8 Hz, 1H), 8.40 (dd, J¼1.6,
8.4 Hz, 1H), 8.34 (dd, J¼2.8, 11.2 Hz, 1H), 8.11 (d, J¼8.8 Hz, 1H),
7.74e7.64 (m, 2H), 7.47 (dt, J¼2.4, 8.4 Hz, 1H), 7.26 (d, J¼2.0 Hz, 1H),
7.06 (dd, J¼2.0, 8.4 Hz, 1H), 3.96 (s, 3H); 13C NMR (100 MHz, CDCl3):
4.4. A representative synthetic procedure of skeleton 7 is as
follows
d
160.44 (d, J¼241.9 Hz), 158.82, 157.07, 129.78 (d, J¼7.6 Hz), 127.65,
126.83, 126.65, 126.46, 125.70 (d, J¼9.1 Hz), 124.76, 123.51, 122.49,
121.60, 121.29, 115.85 (d, J¼23.5 Hz), 111.88, 105.23, 104.56, 109.08
(d, J¼22.0 Hz), 96.76, 55.78.
Skeleton 5 (0.3 mmol) and I2 (100 mg, 0.4 mmol) was dissolved in
EtOAc (20 mL) at 25 ꢀC in a pyrax glass tube. Then, 1,2-epoxybutane
(150 mg, 2.0 mmol) was added to the reaction mixture at 25 ꢀC. The
pyrax glass tube with the reaction mixture was irradiated under
4.4.6. 6,11-Dimethoxy-13-oxa-indeno[1,2-l]phenanthrene
(7f). Yield¼85% (84 mg); Colorless solid; mp¼156e158 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H17O3 329.1178, found 329.1182; 1H NMR (400 MHz, CDCl3):
ꢀ
ꢀ
a nitrogen atmosphere with a lamp (
l
¼2540 A) at 25 C for 50 h. The
solvent was evaporated to afford crude product. The residue was
diluted with aqueous Na2S2O3 (10%, 10 mL) solution, and the re-
action mixture was extracted with EtOAc (2ꢁ20 mL). Purification on
silica gel (hexanes/EtOAc¼4/1e2/1) afforded skeleton 7.
d
8.60 (d, J¼8.0 Hz, 1H), 8.40e8.36 (m, 2H), 8.11e8.08 (m, 2H),
7.70e7.61 (m, 2H), 7.36e7.33 (m, 1H), 7.24 (dd, J¼0.8, 2.0 Hz, 1H),
7.08 (ddd, J¼0.8, 2.4, 8.4 Hz, 1H), 4.02 (s, 3H), 3.94 (s, 3H); 13C NMR
4. 4.1. 11-Methoxy-13-oxa-indeno[1, 2-l]phenanthrene
(7a). Yield¼80% (72 mg); Colorless solid; mp¼157e159 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C21H15O2 299.1072, found 299.1074; 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3): d 158.59, 157.05, 157.01, 149.40, 129.45, 129.13,
127.05, 125.99, 125.17, 123.32, 122.49, 122.43, 121.66, 121.18, 118.78,
116.55, 114.48, 111.54, 105.81, 96.64, 55.72, 55.45. Single-crystal X-
ray diagram: crystal of compound 7f was grown by slow diffusion
of EtOAc into a solution of compound 7f in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the monoclinic crystal sys-
d
8.80 (dd, J¼1.2, 8.0 Hz, 1H), 8.76 (dd, J¼1.6, 8.0 Hz, 1H), 8.60 (dd,
J¼1.2, 8.0 Hz, 1H), 8.47 (dd, J¼1.6, 7.2 Hz, 1H), 8.24 (d, J¼8.4 Hz, 1H),
7.79e7.65 (m, 4H), 7.31 (d, J¼2.0 Hz, 1H), 7.10 (dd, J¼2.0, 8.4 Hz, 1H),
ꢀ
ꢀ
ꢀ
tem, space group P c, a¼23.874(4) A, b¼4.0071(7) A, c¼17.265(3) A,
3.97 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
158.73, 157.15, 150.76,
V¼1563.3(5) A , Z¼4, dcalcd¼1.395 g/cm3, F(000)¼688, 2
q range
3
ꢀ
129.88, 128.34, 128.15, 127.30, 127.11, 126.52, 125.01, 124.09, 123.75,
123.40, 122.26, 121.91, 121.26, 118.90, 114.60, 111.83, 96.80, 55.81;
Anal. Calcd for C21H14O2: C, 84.54; H, 4.73. Found: C, 84.69; H, 4.97.
0.901e26.392ꢀ, R indices (all data) R1¼0.0816, wR2¼0.1105.
4.4.7. 6-Fluoro-10,11-dimethoxy-13-oxa-indeno[1,2-l]phenanthrene
(7g). Yield¼83% (86 mg); Colorless solid; mp¼192e194 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H16FO3 347.1084, found 347.1091; 1H NMR (400 MHz, CDCl3):
4.4.2. 10,11-Dimethoxy-13-oxa-indeno[1,2-l]phenanthrene
(7b). Yield¼83% (82 mg); Colorless solid; mp¼122e124 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H17O3 329.1178, found 329.1182; 1H NMR (400 MHz, CDCl3):
d
8.57 (d, J¼8.8 Hz, 1H), 8.43e8.38 (m, 2H), 8.35 (dd, J¼2.4, 7.2 Hz,
1H), 7.73 (dt, J¼1.2, 8.0 Hz, 1H), 7.67 (dt, J¼1.2, 8.0 Hz, 1H), 7.62 (s,
1H), 7.48 (dt, J¼2.4, 8.4 Hz,1H), 7.28 (s,1H), 4.09 (s, 3H), 4.03 (s, 3H);
d
8.76 (d, J¼8.4 Hz, 1H), 8.72 (dd, J¼1.6, 8.8 Hz, 1H), 8.48 (dd, J¼0.8,
8.0 Hz, 1H), 8.41 (dd, J¼2.0, 8.0 Hz, 1H), 7.77e7.63 (m, 4H), 7.70 (s,
13C NMR (100 MHz, CDCl3):
d
160.36 (d, J¼241.8 Hz), 150.76, 150.08,
1H), 7.27 (s, 1H), 4.09 (s, 3H), 4.02 (s, 3H); 13C NMR (100 MHz,
148.86, 146.62, 129.76 (d, J¼8.4 Hz), 128.84 (d, J¼3.8 Hz), 127.68,
126.36, 125.40 (d, J¼8.3 Hz), 124.80, 123.52, 122.59, 121.18, 116.78,
115.74 (d, J¼22.7 Hz), 114.58, 109.17 (d, J¼21.9 Hz), 103.21, 95.87,
56.75, 56.28; Anal. Calcd for C22H15FO3: C, 76.29; H, 4.37. Found: C,
76.42; H, 4.58.
CDCl3):
d 150.73, 150.63, 148.67, 146.52, 129.68, 129.62, 128.30,
128.05, 127.13, 127.05, 126.33, 124.86, 123.73, 123.34, 122.29, 121.10,
117.12, 114.79, 103.49, 95.82, 56.72, 56.25.
4.4.3. 9,11-Dimethoxy-13-oxa-indeno[1,2-l]phenanthrene
(7c). Yield¼84% (83 mg); Colorless solid; mp¼167e169 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H17O3 329.1178, found 329.1186; 1H NMR (400 MHz, CDCl3):
4.4.8. 6-Fluoro-10,11-dioxymethylene-13-oxa-indeno[1,2-l]phenan-
threne (7h). Yield¼83% (82 mg); Colorless solid; mp>250 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C21H12FO3 331.0771, found 331.0778; 1H NMR (400 MHz, CDCl3):
d
9.53 (dd, J¼1.2, 8.4 Hz, 1H), 8.77e8.72 (m, 2H), 8.44e8.42 (m, 1H),
7.72e7.61 (m, 4H), 6.89 (d, J¼2.0 Hz, 1H), 6.51 (d, J¼2.0 Hz, 1H), 4.11
(s, 3H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3):
159.80, 158.16,
d
8.60 (d, J¼8.0 Hz, 1H), 8.46e8.37 (m, 3H), 7.69 (s, 1H), 7.76e7.66
(m, 2H), 7.52e7.48 (m, 1H), 7.25 (s, 1H), 6.11 (s, 2H); 13C NMR
(100 MHz, CDCl3):
d
154.45, 149.58, 129.68, 128.26, 128.18, 128.05, 126.83, 126.80,
126.22, 124.80, 123.17, 123.15, 122.02, 121.13, 116.09, 109.39, 94.81,
88.81, 55.74 (2ꢁ).
d
160.48 (d, J¼244.6 Hz), 151.35, 150.31, 146.86,
145.05, 129.95, 127.76, 126.52, 125.42 (d, J¼8.4 Hz), 124.73, 123.57,
123.45, 122.61, 121.26, 118.17, 115.90 (d, J¼22.8 Hz), 109.25 (d,
J¼22.8 Hz), 102.21, 101.77, 100.20, 94.31.
4.4.4. 9,10,11-Trimethoxy-13-oxa-indeno[1,2-l]phenanthrene
(7d). Yield¼88% (95 mg); Colorless solid; mp¼146e148 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H19O4 359.1283, found 359.1284; 1H NMR (400 MHz, CDCl3):
4.4.9. 6-Fluoro-9,10,11-trimethoxy-13-oxa-indeno[1,2-l]phenan-
threne (7i). Yield¼85% (96 mg); Colorless solid; mp¼159e161 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H18FO4 377.1189, found 377.1195; 1H NMR (400 MHz, CDCl3):
d
9.42 (dd, J¼1.2, 8.4 Hz, 1H), 8.78 (dd, J¼0.4, 8.0 Hz, 1H), 8.76e8.74
(m, 1H), 8.45e8.43 (m, 1H), 7.79e7.64 (m, 4H), 6.12 (s, 1H), 4.15 (s,
3H), 4.02 (s, 3H), 4.01 (s, 3H); 13C NMR (100 MHz, CDCl3):
153.02,
d
9.31 (dd, J¼6.0, 9.2 Hz, 1H), 8.47 (d, J¼8.0 Hz, 1H), 8.29 (dd, J¼1.2,
d
7.6 Hz, 1H), 8.25 (dd, J¼2.4, 7.6 Hz, 1H), 7.64 (dt, J¼1.2, 8.0 Hz, 1H),
7.58 (dt, J¼1.2, 8.0 Hz, 1H), 7.43 (ddd, J¼2.4, 7.6, 8.8 Hz, 1H), 7.01 (s,
1H), 4.12 (s, 3H), 4.01 (s, 3H), 3.99 (s, 3H); 13C NMR (100 MHz,
152.84, 150.35, 147.64, 139.40, 129.97, 128.15, 128.02, 127.59, 127.23,
126.94, 126.56, 124.93, 123.29, 123.21, 122.01, 121.26, 115.93, 112.78,
91.96, 62.02, 61.40, 56.33; Anal. Calcd for C23H18O4: C, 77.08; H,
5.06. Found: C, 77.29; H, 5.32.
CDCl3):
d
160.42 (d, J¼242.6 Hz), 153.02, 152.65, 149.57 (d,
J¼2.3 Hz), 147.38, 139.18, 129.68 (d, J¼7.6 Hz), 129.56 (d, J¼8.4 Hz),
128.99 (d, J¼3.8 Hz), 127.33, 126.36, 124.35 (d, J¼1.5 Hz), 123.19,
122.04, 121.16, 115.51, 115.46 (d, J¼22.0 Hz), 112.33, 108.38 (d,
J¼22.7 Hz), 91.81, 61.85, 61.31, 56.25; Anal. Calcd for C23H17FO4: C,
4.4.5. 6-Fluoro-11-methoxy-13-oxa-indeno[1,2-l]phenanthrene
(7e). Yield¼86% (82 mg); Colorless solid; mp¼176e178 ꢀC

5140
H.-S. Wang et al. / Tetrahedron 72 (2016) 5132e5141
73.40; H, 4.55. Found: C, 73.72; H, 4.61. Single-crystal X-ray dia-
gram: crystal of compound 7i was grown by slow diffusion of EtOAc
into a solution of compound 7i in CH2Cl2 to yield colorless prisms.
The compound crystallizes in the monoclinic crystal system, space
afforded 3a. Yield¼60% (170 mg, for K2CO3); 63% (179 mg, for t-
BuOK); 60% (170 mg, for KH).
Acknowledgements
ꢀ
ꢀ
ꢀ
group P 21/n, a¼4.3936(2) A, b¼25.2310(12) A, c¼15.8224(7) A,
3
V¼1744.79(14) A , Z¼4, dcalcd¼1.433 g/cm3, F(000)¼784, 2
q
range
ꢀ
The authors would like to thank the Ministry of Science and
Technology of the Republic of China for its financial support (MOST
104-2113-M-037-012).
1.525e26.381ꢀ, R indices (all data) R1¼0.0998, wR2¼0.1902.
4.5. A representative synthetic procedure of compounds 8aec
is as follows
Supplementary data
2-Bromo-1-(4-methoxyphenyl)ethanone
(2c,
240
mg,
Experimental procedure and scanned photocopies of NMR
(CDCl3) spectral data were supported.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.07.007.
1.05 mmol) was added to a solution of crude phenoxides 1feg
(1.0 mmol, prepared from phenols and aqueous KOH) in DMF (5 mL)
at 25 ꢀC. The reaction mixture was stirred at 25 ꢀC for 5 h. Ga(OTf)3
(10 mg, 0.02 mmol) was added to the reaction mixture at 25 ꢀC. The
reaction mixture was stirred at 25 ꢀC for 5 h. The reaction mixture
was concentrated and extracted with CH2Cl2 (3ꢁ10 mL). The com-
bined organic layers were washed with brine, dried, filtered and
evaporated to afford crude product under reduced pressure. Purifi-
cation on silica gel (hexanes/EtOAc¼10/1e6/1) afforded 8.
References and notes
1. (a) Hou, X.-L.; Yang, Z.; Wong, H. N. C. Prog. Heterocycl. Chem. 2002, 14, 139; (b)
Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 2001, 2491; (c) Horton, D. A.; Bourne,
G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893; (d) Miyata, O.; Takeda, N.; Naiti, T.
Heterocycles 2009, 78, 843; (e) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108,
3395; (f) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644; (g) Alonso, F.; Be-
letskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079; (h) Cacchi, S.; Fabrizi, G.;
Goggiamani, A. Org. Biomol. Chem. 2011, 9, 641.
4.5.1. 3-[2-(4-Methoxyphenyl)-2-oxo-ethoxy]-benzaldehyde
(8a). Yield¼91% (246 mg); Colorless solid; mp¼68e70 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
2. Intramolecular annulation of a bond formation, for PdII, see: (a) Willis, M. C.;
Taylor, D.; Gillmore, A. T. Org. Lett. 2004, 6, 4755 For CuI, see; (b) Carril, M.;
SanMartin, R.; Tellitu, I.; Dominguez, E. Org. Lett. 2006, 8, 1467.
C
d
16H15O4 271.0970, found 271.0976; 1H NMR (400 MHz, CDCl3):
3. Intramolecular annulation of b bond formation, for RuII, see: (a) Varela-Fer-
nandez, A.; Gonzalez-Rodriguez, C.; Varela, J. A.; Castedo, L.; Saa, C. Org. Lett.
2009, 11, 5350 For RhI, see; (b) Isono, N.; Lautens, M. Org. Lett. 2009, 11, 1329 For
PdII, see; (c) Martinez, C.; Alvarez, R.; Aurrecoechea, J. M. Org. Lett. 2009, 11,
1083 For ZnII/CuI, see; (d) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Org.
Lett. 2006, 8, 2803 For CuII, see; (e) Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2011, 13, 2395 For CuI, see; (f) Ye, S.; Liu, G.; Pu, S.; Wu, J. Org. Lett. 2012, 14, 70
For Pd0/CuI, see; (g) Nagamochi, M.; Fang, Y.-Q.; Lautens, M. Org. Lett. 2007, 9,
2955 For PhI(OAc)2, see; (h) Singh, F. V.; Wirth, T. Synthesis 2012, 44, 1171 For n-
BuLi, see; (i) Liu, Y.; Ma, S. Org. Lett. 2012, 14, 720 For I2 or NBS, see; (j) Kong, Y.;
Yu, L.; Fu, L.; Cao, J.; Lai, G.; Cui, Y.; Hu, Z.; Wang, G. Synthesis 2013, 45, 1975 For
PhSeCl, see; (k) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292.
4. Intramolecular annulation of c bond formation, for IrIII, see: (a) Anxionnat, B.;
Pardo, D. G.; Ricci, G.; Rossemn, K.; Cossy, J. Org. Lett. 2013, 15, 3876 For RuII, see;
(b) van Otterlo, W. A.; Morgans, G. L.; Madeley, L. G.; Kuzvidza, S.; Moleele, S. S.;
Thornton, N.; de Koning, C. B. Tetrahedron 2005, 61, 7746 For Ph3P, see; (c) Syu,
S.-e.; Lee, Y.-T.; Jang, Y.-J.; Lin, W. Org. Lett. 2011, 13, 2970.
9.95 (s, 1H), 7.99 (d, J¼9.2 Hz, 2H), 7.50 (dt, J¼1.6, 7.6 Hz, 1H), 7.46
(t, J¼7.6 Hz, 1H), 7.39 (dd, J¼1.2, 2.8 Hz, 1H), 7.28e7.25 (m, 1H), 6.98
(d, J¼9.2 Hz, 2H), 5.31 (s, 2H), 3.89 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
192.05, 191.87, 164.21, 158.72, 137.80, 130.41 (2ꢁ), 130.25,
127.36, 124.22, 122.14, 114.11 (2ꢁ), 113.04, 70.39, 55.55.
4.5.2. 4-Methoxy-3-[2-(4-methoxyphenyl)-2-oxo-ethoxy]-benzalde-
hyde (8b). Yield¼82% (246 mg); Colorless solid; mp¼93e95 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C17H17O5 301.1076, found 301.1081; 1H NMR (400 MHz, CDCl3):
d
9.71 (s, 1H), 7.92 (d, J¼9.2 Hz, 2H), 7.41 (dd, J¼2.0, 8.4 Hz, 1H), 7.26
(d, J¼2.0 Hz, 1H), 6.94 (d, J¼8.4 Hz, 1H), 6.89 (d, J¼9.2 Hz, 2H), 5.34
(s, 2H), 3.89 (s, 3H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3):
5. Intramolecular annulation of d bond formation, for Pd0, see: (a) Yuan, W.; Ma, S.
Org. Lett. 2014, 16, 193 For PdII, see; (b) Youn, S. W.; Eom, J. I. Org. Lett. 2005, 7,
3355; (c) Zhao, B.; Lu, X. Org. Lett. 2006, 8, 5987 For CuII, see; (d) Shibata, T.;
Hashimoto, Y. k.; Otsuka, M.; Tsuchikama, K.; Endo, K. Synthesis 2011, 2075 For
MeLi, see; (e) Kraus, G. A.; Kim, I. Org. Lett. 2003, 5, 1191.
d
191.53, 190.46, 163.90, 154.69, 147.92, 130.08 (2ꢁ), 129.63, 127.13,
127.04, 113.86 (2ꢁ), 111.26, 110.92, 70.60, 55.98, 55.31.
4.5.3. 2-(2-Methoxy-5-nitrophenoxy)-1-(4-methoxyphenyl)-etha-
none (8c). Yield¼75% (234 mg); Colorless solid; mp¼142e143 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C16H16NO6 318.0978, found 318.0981; 1H NMR (400 MHz,
6. For selected examples on intermolecular annulations, see: (a) McKiernan, G. J.;
Hartley, R. C. Org. Lett. 2003, 5, 4389; (b) Schevenels, F.; Marko, I. E. Org. Lett.
2012, 14, 1298; (c) Zhou, L.; Shi, Y.; Xiao, Q.; Liu, Y.; Ye, F.; Zhang, Y.; Wang, J. Org.
Lett. 2011, 13, 968; (d) da Luca, L.; Giacomelli, G.; Nieddu, G. J. Org. Chem. 2007,
72, 3955; (e) Dudley, M. E.; Morshed, M. M.; Hosssain, M. M. Synthesis 2006,
1711; (f) Osyanin, V. A.; Osipov, D. V.; Demidov, M. R.; Klimochkin, Y. N. J. Org.
Chem. 2014, 79, 1192; (g) Liang, Y.; Tao, L.-M.; Zhang, Y.-H. Synthesis 2008, 3988;
(h) Wang, S.; Li, P.; Yu, L.; Wang, L. Org. Lett. 2011, 13, 5968; (i) Wang, J.-R.;
Manabe, K. J. Org. Chem. 2010, 75, 5340; (j) Kumar, M. P.; Liu, R.-S. J. Org. Chem.
2006, 71, 4951; (k) Byers, P. M.; Rashid, J. I.; Mohamed, R. K.; Alabugin, I. V. Org.
Lett. 2012, 14, 6032; (l) Yuan, H.; Bi, K.-J.; Li, B.; Yue, R.-C.; Ye, J.; Shen, Y.-H.;
Shan, L.; Jin, H.-Z.; Sun, Q.-Y.; Zhang, W. D. Org. Lett. 2013, 15, 4742; (m) Hen-
drickson, J. B.; Walker, M. A. Org. Lett. 2000, 2, 2729; (n) Murakami, K.; Yor-
imitsu, H.; Osuka, A. Angew. Chem., Int. Ed. 2014, 53, 7510; (o) Lee, D.-H.; Kwon,
K.-H.; Yi, C. S. J. Am. Chem. Soc. 2012, 134, 6571; (p) Wan, J.-P.; Wang, H.; Liu, Y.;
Ding, H. Org. Lett. 2014, 16, 5160; (q) Huang, X.-C.; Liu, Y.-L.; Liang, Y.; Pi, S. F.;
Wang, F.; Li, J.-H. Org. Lett. 2008, 10, 1525; (r) Lu, B.; Wang, B.; Zhang, Y.; Ma, D. J.
Org. Chem. 2007, 72, 5337; (s) Yoshioka, E.; Tanaka, H.; Kohtani, S.; Miyabe, H.
Org. Lett. 2013, 15, 3938; (t) Geary, L. M.; Hultin, P. G. Org. Lett. 2009, 11, 5478;
(u) Eidamshaus, C.; Burch, J. D. Org. Lett. 2008, 10, 4211.
CDCl3):
J¼2.4 Hz, 1H), 6.97 (d, J¼8.8 Hz, 2H), 6.93 (d, J¼9.2 Hz, 1H), 5.41 (s,
2H), 3.98 (s, 3H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3):
191.16,
d
7.97 (d, J¼8.8 Hz, 2H), 7.91 (dd, J¼2.8, 9.2 Hz, 1H), 7.64 (d,
d
164.22, 154.93, 147.30, 141.12, 130.25 (2ꢁ), 127.12, 118.65, 114.11
(2ꢁ), 110.47, 108.62, 70.91, 56.45, 55.51.
4.6. A one-pot synthetic procedure of 3a is as follows
Base (1.0 mmol; for K2CO3, 140 mg; for t-BuOK, 115 mg; for KH,
35% in mineral oil, 115 mg) was added to a solution of 3,4,5-
trimethoxyphenol (184 mg, 1.0 mmol) in DMF (5 mL) at 25 ꢀC.
The reaction mixture was stirred at 25 ꢀC for 10 min
a-Bromoace-
tophenone (2a, 210 mg, 1.05 mmol) was added to the reaction
mixture at 25 ꢀC. The reaction mixture was stirred at 25 ꢀC for 5 h.
Ga(OTf)3 (10 mg, 0.02 mmol) was added to the reaction mixture at
25 ꢀC. The reaction mixture was stirred at 25 ꢀC for 5 h. The reaction
mixture was concentrated and extracted with CH2Cl2 (3ꢁ10 mL).
The combined organic layers were washed with brine, dried, fil-
tered and evaporated to afford crude product under reduced
pressure. Purification on silica gel (hexanes/EtOAc¼4/1e1/1)
7. For Bi(OTf)3, see: (a) Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Org. Lett. 2015, 17, 3142;
(b) Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Org. Lett. 2015, 17, 1264; (c) Chan, C.-K.;
Chen, Y.-C.; Chen, Y.-L.; Chang, M.-Y. Tetrahedron 2015, 71, 9187 For In(OTf)3,
see; (d) Chang, M.-Y.; Lu, Y.-J.; Cheng, Y.-C. Tetrahedron 2015, 71, 6840 For
Sc(OTf)3, see; (e) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K.; Huang, G. G. Tetrahedron
2015, 71, 2095 For Fe(OTf)3, see; (f) Chang, M.-Y.; Chen, Y.-H.; Cheng, Y.-C.
Tetrahedron 2016, 72, 518.
8. For selected reviews on the metal triflate-mediated reactions, see: (a) Land-
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Lee, S. Tetrahedron Lett. 2008, 6579; (c) Belhomme, M.-C.; Poisson, T.; Pan-
necoucke, X. J. Org. Chem. 2014, 79, 7205 For Amberlyst 15, see; (d) Habermann,
J.; Ley, S. V.; Smits, R. J. Chem. Soc., Perkin Trans. 1 1999, 2421; (e) Santini, C.;
Berger, G. D.; Han, W.; Mosley, R.; MacNaul, K.; Berger, J.; Doebber, T.; Wu, M.;
Moller, D. E.; Tolman, R. L.; Sahoo, S. Bioorg. Med. Chem. Lett. 2003, 13, 1277.
13. (a) Habermann, J.; Ley, S. V.; Smits, R. J. Chem. Soc., Perkin Trans. 11999, 2421; (b)
Wang, B.; Hu, J.; Zhang, F.; Zheng, H. Heterocycles 2016, 92, 103.
14. CCDC. 1453905 (5c), 1453903 (5d), 1453908 (5j), 1453906 (6c), 1453907 (7f),
and 1453904 (7i), contain the supplementary crystallographic data for this
paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax:
44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk).
11. Other examples on the Ga(OTf)3-mediated reactions, see: (a) Kobayashi, S.; Ko-
moto, I.; Matsuo, J.-I. Adv. Synth. Catal. 2001, 343, 71; (b) Yang, F.; An, W.; Qian, Z.;
Yu, T.; Du, Y.; Ma, L.; Wang, X.; Meng, T.; Shen, J. RSC Adv. 2015, 5, 32015; (c)
Alcaide, B.; Almendros, P.; Herrera, F.; Luna, A.; de Orbe, M. E.; Torres, M. R. J. Org.
Chem. 2015, 80, 4157; (d) Zhou, H.; Zhu, D.; Xie, Y.; Huang, H.; Wang, K. J. Org.
Chem. 2010, 75, 2706; (e) Su, W.; Chen, J.; Wu, H.; Jin, C. J. Org. Chem. 2007, 72,
4524; (f) Deng, X.-M.; Sun, X.-L.; Tang, Y. J. Org. Chem. 2005, 70, 6537; (g) Xi, Y.;
Wang, D.; Ye, X.; Akhmedov, N. G.; Petersen, J. L.; Shi, X. Org. Lett. 2014, 16, 306.
15. For selected examples on the Scholl annulation, see: (a) King, B. T.; Kroulik, J.;
Robertson, C. R.; Rempala, P.; Hilton, C. L.; Korinek, J. D.; Gortari, L. M. J. Org.
Chem. 2007, 72, 2279; (b) Simpson, C. D.; Mattersteig, G.; Martin, K.; Gherghel,
L.; Bauer, R. E.; Rader, H. J.; Mullen, K. J. Am. Chem. Soc. 2004, 126, 3139; (c)
McKillop, A.; Turrell, A. G.; Young, D. W.; Taylor, E. C. J. Am. Chem. Soc. 1980, 102,
6504; (d) Churruca, F.; SanMartin, R.; Carril, M.; Urtiaga, M. K.; Solans, X.;
Tellitu, I.; Dominguez, E. J. Org. Chem. 2005, 70, 3178; (e) Navale, T. S.; Thakur,
K.; Rathore, R. Org. Lett. 2011, 13, 1634; (f) Zhang, X.; Jiang, X.; Zhang, K.; Mao, L.;
Luo, J.; Chi, C.; Chan, H. S. O.; Wu, J. J. Org. Chem. 2010, 75, 8069.
12. Intramolecular annulation of
a-phenoxy ketone, for p-TsOH, see: (a) Lee, J. H.;
Kim, M.; Kim, I. J. Org. Chem. 2014, 79, 6153 For BCl3, see; (b) Kim, I.; Lee, S.-H.;
16. Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Tetrahedron 2015, 71, 782.