Tandem reaction between chalcone epoxides and 2-naphthyl ethers to construct complex naphtho[2,1-b]furans

Article abstract of DOI:10.1016/j.tetlet.2012.12.078

The reaction of chalcone epoxides with 2-naphthyl ethers can be initiated by stable triarylaminium salt. And after subsequent aerobic oxidative aromatization in one pot, a series of polysubstituted naphtho[2,1-b]furans were delivered.

Full text of DOI:10.1016/j.tetlet.2012.12.078

Tetrahedron Letters 54 (2013) 1145–1148
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Tandem reaction between chalcone epoxides and 2-naphthyl ethers
to construct complex naphtho[2,1-b]furans
⇑
⇑
Congde Huo , Jinzhu An, Xiaolan Xu, Xiaodong Jia, Xicun Wang , Lisheng Kang
Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu 730070, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of chalcone epoxides with 2-naphthyl ethers can be initiated by stable triarylaminium salt.
And after subsequent aerobic oxidative aromatization in one pot, a series of polysubstituted naphtho[2,1-
b]furans were delivered.
Received 8 September 2012
Revised 15 December 2012
Accepted 18 December 2012
Available online 28 December 2012
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Chalcone epoxide
2-Naphthyl ether
Naphtho[2,1-b]furan
Radical cation
Triarylaminium salt
Chalcone epoxides are an important class of compounds in view
of distinct structural features. They are readily prepared and they
are interesting intermediates in organic synthesis.1 And during
our studies on the radical cation mediated transformations of chal-
cone epoxides,2 we have demonstrated that tris(4-bromophenyl)-
aminium hexachloro-antimonate (TBPA+ÅSbCl6À), a well known
single electron oxidant, could efficiently initiate the cycloaddition
of chalcone epoxides with olefins to construct tetrahydrofurans,2a
the cycloaddition of chalcone epoxides with imines to construct
1,3-oxazolidines,2b the Friedel–Crafts (FC) reaction between chal-
In this Letter, a direct transformation of chalcone epoxides with
2-naphthyl ethers into complex naphtho[2,1-b]furans were devel-
oped in one pot with a simple and efficient tandem procedure.
As shown in Scheme 1, firstly, we investigated the reaction of
chalcone epoxide 1a with anisole (6) as a model reaction under
the previously optimized reaction conditions (5 mol %
TBPA+ÅSbCl6 in CHCl3 at room temperature).2 FC product 8 was
À
achieved with good yield. The structures of 8 were fully character-
ized and its stereochemistry was determined by X-ray crystallo-
graphic analysis.5 A similar FC reaction occurred between 1a and
cone epoxides and heteroarenes to construct b-heteroaryl
a
-ke-
1-methoxynaphthalene (7) to produce b-functionalized a-ketol
tols,2c and the FC alkylation/annulation cascade reaction between
chalcone epoxides and 2-naphthols to construct 1,2-dihydronaph-
tho[2,1-b]furans.2d
diastereomers 9 and 10 in good yield. However, when 2-methoxy-
naphthalene (2a) was employed as a nucleophile, it is of impor-
tance to note that a FC alkylation/annulation cascade reaction
took place smoothly to give the 1,2-dihydronaphtho[2,1-b]furans
3a and 4a. This is very interesting because the cleavage of aromatic
C–O bonds is usually difficult.6 Recently, a few examples of the
selective cleavage of aromatic C–O bonds from aryl alkyl ethers
have been investigated in the presence of transition metals7 or
inorganic base.8 The structures of 3a and 4a were characterized
by 1H NMR, 13C NMR, HRMS, and comparison with authentic sam-
ples we synthesized before.2d And then after using our developed
aerobic oxidative aromatization strategy in one pot,2d the 1,2-dihy-
dro diastereomers can be efficiently transformed to the corre-
sponding naphtho[2,1-b]furans 5a.9
Arene ring-fused furan derivatives exist widely in natural prod-
ucts and have been extensively investigated due to their biological
and pharmacological activities.3,4 Among them, benzofurans have
been studied widely, and numerous synthetic methods have been
developed.3 At the meantime, naphthofuran derivatives have also
been isolated from various natural sources, and are well known
for various types of biological activities. However, the reports on
the synthesis of naphthofurans are relatively limited.4 Therefore,
the development of a versatile method to synthesize polysubstitut-
ed naphtho[2,1-b]furans is highly desired.
We then optimized the reaction condition with chalcone epox-
ide 1a and 2-naphthyl methyl ether 2a as the model compounds,
and the results were shown in Table 1. The best yield (80%) was
achieved with 5 mol % TBPA+ÅSbCl6À in CHCl3 at room temperature
⇑
Corresponding authors.
E-mail addresses: huocongde1978@hotmail.com (C. Huo), wangxicun@nwnu.
edu.cn (X. Wang).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.078

1146
C. Huo et al. / Tetrahedron Letters 54 (2013) 1145–1148
OMe
OMe
8
6
O
TBPA SbCl6
rt, 0.5 h
OH
MeO
72 %
OMe
OMe
OMe
9
10
O
7
+
O
O
O
TBPA SbCl6
rt, 0.5 h
MeO
OH
32 %
1a
OH
38 %
MeO
MeO
2a
OMe
TBPA SbCl6
3a
4a
+
O
O
O
O
rt, 0.5 h
MeO
MeO
DDQ/NaNO2/O2
/AcOH, reflux
O
O
MeO
5a 60 %
Scheme 1.
FeCl3, and FeCl2, were also evaluated, and were found to be ineffec-
tive for this conversion. Oxidant ceric ammonium nitrate (CAN)
was also examined. No products were observed with a catalytic
amount of CAN.
Table 1
Reaction condition optimization
Conditions
NMR yield (%)
5% TBPA,+Å CH2Cl2, rt, 0.5 h
5% TBPA,+Å CH2Cl3, rt, 0.5 h
5% TBPA,+Å ClCH2Ch2Cl2, rt, 0.5 h
5% TBPA,+Å MeCN, rt, 0.5 h
5% TBPA,+Å EtOAc, rt, 0.5 h
5% TBPA,+Å Acetone, rt, 0.5 h
2% TBPA,+Å CH2Cl3, rt, 0.5 h
1% TBPA,+Å CH2Cl3, rt, 0.5 h
5% TBPA,+Å CH2Cl3, reflux, 0.5 h
5% TsOH, CHCl3, rt, 0.5 h
5% AlCl3, CHCl3, rt, 0.5 h
5% InCl3, CHCl3, rt, 0.5 h
5% ZnCl2, CHCl3, rt, 0.5 h
5% FeCl3, CHCl3, rt, 0.5 h
5% FeCl2, CHCl3, rt, 0.5 h
5% CAN, CHCl3, rt, 0.5 h
75
80
With the optimized conditions in hand, the reaction procedure
was carried out as follows. To a CHCl3 solution (10 mL) of the Chal-
cone epoxides (1, 1 mmol) and 2-naphthyl ethers (2, 1 mmol) was
added a catalytic amount of TBPA+ÅSbCl6À (0.05 mmol) in portion at
ambient temperature under stirring. The reaction completed with-
in an hour as monitored by TLC. Then AcOH (1 mL), DDQ (5 mol %),
and NaNO2 (10 mol %) were added, and the reaction mixture was
heated under reflux for 6 h under O2 atmosphere. Then the solvent
was evaporated and the residue was purified by column chroma-
tography over silica gel to afford the naphtho[2À,1-b]furans.5
The generality and scope of this TBPA+ÅSbCl6 initiated one pot
tandem reaction between chalcone epoxides and 2-naphthyl
ethers were shown in Table 2. Chalcone epoxides with electron rich
aryl groups as R1 substituents were propitious to the reaction and
gave the products smoothly (Table 2, entries 1–11). The reason lies
in that the extra stability of benzylic cation intermediate was pro-
vided by electron rich R1 substituents.2c It should be noted that
with all changes in the R2 substituents, electron rich aryls (Table 2,
entries 2–3), electron deficient aryls (Table 2, entries 4–6), and
heteroaryls (Table 2, entries 7 and 8) were all tolerant of the reac-
tion conditions well. While chalcone epoxides without strong elec-
tron donating group bearing on R1 substituents showed no desired
69
NR
NR
NR
72
30
71
NR
NR
NR
NR
NR
NR
NR
The bold values highlight the key changings of the reaction conditions.
and the yield remained as high as 72% when 2 mol % initiator was
used. The reaction completed within half an hour as monitored by
TLC. Other chlorinated solvents such as ClCH2CH2Cl and CH2Cl2
also gave 3a and 4a in 69% and 75%, respectively. And the yield
was slightly decreased when the reaction was performed under re-
flux condition. Brönsted acid TsOH, Lewis acids AlCl3, InCl3, ZnCl2,

C. Huo et al. / Tetrahedron Letters 54 (2013) 1145–1148
1147
Table 2
Reaction of chalcone epoxides with 2-naphthyl ethers
R'
1, TBPA SbCl6 (5 mol %)
R'
O
2, DDQ (5 mol %)/NaNO2 (10 mol %)/O2
O
+
R1
R2
R1
R2
O
OR
CHCl3, rt to reflux, in One Pot
O
Entry
1
1
2
5
Isolated yield (%)
R1
R2
OMe
(1a) 4-MeO-C6H4
C6H5
(2a)
(5a)
60
2
3
4
5
6
7
8
9
10
11
12
13
14
(1b) 4-MeO-C6H4
(1c) 4-MeO-C6H4
(1d) 4-MeO-C6H4
(1e) 4-MeO-C6H4
(1f) 4-MeO-C6H4
(1g) 4-MeO-C6H4
(1h) 4-MeO-C6H4
(1i) Piperonyl
(1j) 3,4,5-(MeO)3-C6H2
(1k) 4-BnO-C6H4
(1l) C6H5
(1m) 4-Me-C6H4
(1n) 4-Cl-C6H4
4-MeO-C6H4
4-Me-C6H4
4-Cl-C6H4
4-Br-C6H4
4-CN-C6H4
2-Furanyl
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(2a)
(5b)
(5c)
(5d)
(5e)
(5f)
(5g)
(5h)
(5i)
(5j)
(5k)
(5l)
(5m)
(5n)
51
61
68
59
57
66
50
66
63
50
—
1-Methyl-1H-indole-3-yl
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
—
—
MeO
OMe
15
16
(1a) 4-MeO-C6H4
(1a) 4-MeO-C6H4
C6H5
C6H5
(2b)
(5o)
(5p)
39
53
OMe
(2c)
Br
OMe
17
(1a) 4-MeO-C6H4
C6H5
(2d)
(5q)
43
OHC
OMe
18
19
(1a) 4-MeO-C6H4
(1a) 4-MeO-C6H4
C6H5
C6H5
(2e)
(5r)
(5a)
40
33
NC
OBn
(2f)
OMe
20
(1a) 4-MeO-C6H4
C6H5
(2g)
(5s)
—
X
X = MeO, Me, Br, NO2
products with 2-methoxynaphthalene under the same experimen-
tal conditions (Table 2, entries 12–14).
decomposition of chalcone epoxide 1a itself is faster than cross
reaction.
The scope of the 2-naphthyl ether component in this reaction
had also been evaluated. The derivatives with electron donating
groups (Table 1, entry 15) and with electron withdrawing groups
(Table 1, entries 16–18) were all transformed into the correspond-
ing naphthofurans with moderate to good yields. 2-Naphthyl ben-
zyl ether can also be subjected to the same transformation (Table 1,
entry 19).
As mentioned in Scheme 1, the reaction of chalcone epoxide 1a
with anisole gave FC product in good yield. We envisioned that if
the para position in anisole was occupied by substituent groups,
the reaction with chalcone epoxides may have occurred at the
ortho position of anisoles and gave the similar benzofuran products
just like the reaction of chalcone epoxides with 2-naphthyl ethers
to give naphthofurans. Unfortunately, the reaction between chal-
cone epoxide 1a and MeOC6H4X (X = MeO, Me, Br, NO2) gave rise
to complex reaction mixtures and did not lead to the designed
products (Table 2, entry 20). A plausible explanation is that the
A plausible radical cation mediated chain mechanism for our
work was proposed in Scheme 2. The chalcone epoxide (1) was first
activated by single electron oxidation to give distonic10 radical cat-
ion intermediate 11. 2-Naphthyl ether was then electrophilic at-
tacked by 11 to form the dihydrofurylium distonic radical cation
intermediate 12. After a sequential nucleophilic ring closing (5-
exo-trig), 12 was transformed into radical cation intermediate 13.
And then the radical cation intermediate 14 was constructed by
leaving a molecule of alcohol from intermediate 13. Compound
14 would then undergo single electron transfer from substrate 1
to produce the product and regenerate intermediate 11 at the same
time. Chain propagation continued until all substrates were con-
verted into the products 3 and 4.
In conclusion, a direct transformation of chalcone epoxides
with 2-naphthyl ethers into complex naphtho[2,1-b]furans was
developed in one pot with
procedure.
a simple and efficient tandem

1148
C. Huo et al. / Tetrahedron Letters 54 (2013) 1145–1148
OR
R2
Nucleophilic
H
H
H
OR
OR
Ring Close
5-exo-trig
O
R1
R1
O
O
R1
O
O
O
12
13
14
R2
R2
- ROH
2a
O
Electrophilic
Attack
OR
O
R1
R2
O
R1
R2
O
11
SET
Initiation
O
O
R1
R1
R2
R2
3&4
O
O
Substrate 1
Aromatization
Product 5
Scheme 2. Proposed mechanism.
4. (a) Haselgrove, T.; Jevric, M.; Taylor, D. Tetrahedron 1999, 55, 14739–14762; (b)
Arrault, A. Synthesis 1999, 1241–1245; (c) Park, K. K.; Jeong, J. Tetrahedron 2005,
61, 545–553; (d) Pan, C.; Yu, J.; Zhou, Y.; Wang, Z.; Zhou, M.-M. Synlett 2006,
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17393; (f) Adib, M.; Mahdavi, M.; Bagherzadeh, S.; Bijanzadeh, H. Synlett 2009,
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Halawa, A. H. A.; El-Agrody, A. M. Molecules 2011, 16, 307–318.
5. The X-ray crystal data (excluding structure factors) of compounds 8 have been
deposited with the Cambridge Crystallographic Data Centre as supplementary
publication no CCDC 896936. Copy of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 (0)
1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgments
We thank the National Natural Science Foundation of China
(21262029, 21002080) and the Specialized Research Fund for the
Doctoral Program of Higher Education (20106203120003) of the
Education Ministry for financially supporting this work.
Supplementary data
6. Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36, 255–263.
7. (a) Wenkert, E.; Michelotti, E. L.; Swindell, C. S. J. Am. Chem. Soc. 1979, 101,
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Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
12.078.
References and notes
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b]furan-2-yl)(phenyl)methanone (5a). Yellow block crystals, mp 145–147 °C. 1
H
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NMR (CDCl3, 400 MHz) d 7.98–7.89 (m, 4H), 7.80 (d, J = 8.3 Hz, 1H), 7.74 (d,
J = 9.0 Hz, 1H), 7.56–7.33 (m, 7H), 6.99 (d, J = 8.6 Hz, 2H), 3.89 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d 184.8, 159.6, 152.9, 147.8, 137.5, 132.3, 131.3, 131.1, 131.0,
130.2, 129.7, 129.2, 128.8, 128.0, 126.9, 125.1, 124.6, 123.2, 122.1, 114.0, 112.7,
55.3.
2-Hydroxy-3,3-bis(4-methoxyphenyl)-1-phenylpropan-1-one
(8).
Colorless solid. 1H NMR (400 MHz,CDCl3): d = 7.88 (d, J = 8.0 Hz, 2H), 7.84 (t,
J = 7.5 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 6.83–6.87 (m, 4H),
6.71 (d, J = 8.7 Hz, 2H), 5.79 (dd, J = 2.4, 7.3 Hz, 1H), 4.42 (d, J = 2.2 Hz, 1H), 3.79
(s, 3H), 3.73 (s, 3H), 3.64 (d, J = 7.3 Hz, 1H). 13C NMR (100 MHz): d 200.7, 158.5,
158.2, 134.4, 134.2, 133.9, 130.6, 130.4, 129.5, 129.0, 128.6, 113.8, 113.4, 75.6,
55.3, 55.1, 52.9.
10. Distonic ions are chemical species that contain both a radical and an ionic site
on different atoms of the same molecule. Review see: Stirk, K. M.; Kiminkinen,
L. K. M.; Kenttamaa, H. I. Chem. Rev. 1992, 92, 1649–1665.