Iron(III) chloride catalyzed oxidative coupling reaction of 1,2-diarylethylene derivatives

Article abstract of DOI:10.1002/cjoc.201300308

A nontoxic FeCl₃ catalyzed intramolecular oxidative coupling reaction was developed for mild synthesis of a series of phenanthrenes with different substituents. The method involves cross dehydrogenative coupling of a variety of 1,2-diarylethyle

Full text of DOI:10.1002/cjoc.201300308

FULL PAPER
DOI: 10.1002/cjoc.201300308
Iron(III) Chloride Catalyzed Oxidative Coupling Reaction of
1,2-Diarylethylene Derivatives
Derong Ji, Lidan Su, Keqing Zhao, Biqin Wang, Ping Hu, Chun Feng, Shikai Xiang, Hua Yang,*
and Chenggang Zhang*
College of Chemistry and Materials, Sichuan Normal University, Chengdu, Sichuan 610066, China
A nontoxic FeCl3 catalyzed intramolecular oxidative coupling reaction was developed for mild synthesis of a
series of phenanthrenes with different substituents. The method involves cross dehydrogenative coupling of a vari-
ety of 1,2-diarylethylene derivatives with di-tert-butylperoxide (DTBP) as a sole oxidant at room temperature in
CH2Cl2/TFA (9∶1 V/V) to yield phenanthrenes in good to excellent yields.
Keywords oxidative coupling, 1,2-diarylethylene, phenanthrene, iron(III) chloride, DTBP
Introduction
Scheme 1
R
R
Nowadays, metal catalysts are essential instruments
in the toolbox of organic chemists. As one of the most
abundant metals on the earth, iron salts and its com-
pounds attracted much attention. Because most of them
were cheap, low toxic, non-toxic and environmentally
friendly, iron-catalyzed reactions were reported fre-
quently, such as olefin hydrogenation,[1] olefin reduc-
tion,[2] olefin epoxidation,[3] construction of C － N
bond,[4] C － O bond,[5] C － C bond[6] and some
C-complex bonds.[7] Among them, C－C bond-forming
is one of the core tasks in organic synthesis. Recently,
iron-catalyzed cross-dehydrogenative-coupling reaction
(CDC) to form C－C bond became a hotspot.[8]
R
R
R
R
R1
R
R
R
phenanthrene
R
1,2-diarylethylene
R1 = N2+Cl-, Pschorr reaction
R1 = H, CDC reaction
R
R
Phenanthrene ring is an important unit of many
natural products, for example, tylophora alkaloids
(Scheme 1). These alkaloids have polycyclic structures
and many bioactivities, especially antitumor activity,
which aroused great interest of chemists and pharma-
ceutical scientists.[9,10] The key step of constructing such
alkaloids and their analogs is the preperation of poly-
methoxy-substituted phenanthrene.[11] Therefore, a sim-
ple and efficient method for such phenanthrenes is note-
worthy.
Pschorr reaction has been widely used in synthesis
of phenanthrene core, in which an arenediazonium salt
was used to effect intramolecular coupling.[11] But ap-
plication of this classical method was restricted by te-
dious linear procedure and low overall yield. Transition
metal catalysts were widely used in cross coupling reac-
tions for biaryl C－C bond between two functionalized
starting materials.[12] Cross-dehydrogenative-coupling
reaction (CDC) avoids the need for preparing pre-func-
N
R
R
tylophora alkaloid
tionalized materials and makes organic synthesis sim-
pler and more efficient. Subsequently, many methods
have been developed, for example, using vanadium
oxytrifluoride (VOF3),[13] thallium(III) trifluoroacetate
(TIFA),[14] lead(IV) tetraacetate [Pb(OAc)4][15] as oxi-
dants. However, high toxicity, stringent conditions, low
yields and the high prices limit the extensive application
of these methods. A most attractive approach to the
phenanthrene ring would be the direct oxidative cou-
pling of unfunctionalized 1,2-diphenylethylenes and
anologes,[16] in which the only byproduct would be 2
equiv. of H＋; IR on salts caught much attention as a
mild oxidant for C－C coupling reaction.[17] Wang re-
*
E-mail: scsdyh@126.com; zhangcg2008@yahoo.com.cn; Tel.: 0086-028-84760802
Received April 14, 2013; accepted June 12, 2013; published online July 5, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300308 or from the author.
Chin. J. Chem. 2013, 31, 1045—1053
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Ji et al.
FULL PAPER
ported the synthesis of polymethoxy-substituted methyl
phenanthrene-9-carboxylate from methyl 2,3-diphenyl-
cinnamate with 3.5 equiv. FeCl3 as an oxidant.[18] This
method suffers from difficulty in purification producure.
Recently, they realized above transformation by FeCl3
or NaNO2 as catalyst.[19]
Herein, we report a successful catalyst (5－20 mol%
FeCl3 with di-tert-butylperoxide as sole oxidant) for the
intramolecular oxidative coupling reaction of unfunc-
tionalized 2,3-diphenylacrylic acids and their deriva-
tives at room temperature in CH2Cl2/TFA to give poly-
substituted phenanthrenes in good to excellent yields.
The desired product 2a was obtained in 85% yield
with 25 mol% FeCl3 as the catalyst and DTBP as the
oxidant (Table 1, Entry 1). Without iron(III) chloride,
the reaction gave only 15% isolated yield (Table 1, En-
try 2), indicating the importance of FeCl3. To investi-
gate the influence of nitromethane which dissolves
FeCl3, both FeCl3 and DTBP were excluded, no product
was obtained (Table 1, Entry 3), suggesting the influ-
ence of minor nitromethane could be omitted. When
CH2Cl2 as solvent without TFA, the yield of 2a de-
creased from 85% to 61%, due to some unreacted sub-
strate (Table 1, Entry 4). The results (Table 1, Entries 1
and 4) probably came from the different oxidizability of
＋
＋
DTBP which cycles Fe2 to Fe3 . The oxidizability was
promoted in the presence of TFA. Decreasing the
amount of FeCl3 (10 mol%, 5 mol%, and 2 mol%), the
isolated yield reached up to 92% (Table 1, Entries 5, 6,
7). Then, with 5 mol% FeCl3 unchanged, 1.2 equiv. or
1.5 equiv. DTBP were used seperately to cycle catalyst,
the yields decreased from 92% to 81% around, as a re-
sult of some unreacted substrate (Table 1, Entries 8, 9).
Concentration effects on the coupling reaction were
surveyed (Table 1, Entries 10, 11). Surprisingly, the
reaction of 0.02 mmol/mL concentration gave 94%
yield, which was higher than the yield of the reaction in
0.01 mmol/mL (Entry 6, 92% yield). In 0.01 mmol/mL
concentration reaction, minor coupling product 2b was
obtained, while in 0.02 mmol/mL concentration reaction,
2b was not observed. The reaction of 0.05 mmol/mL
concentration gave moderate yield because substrate 1a
did not reacted completely. As mentioned above, TFA
was crucial to the coupling reaction. When the concen-
tration of TFA decreased (Table 1, Entry 12), the sub-
strate 1a did not reacted completely, giving desired
product 2a with only 74% yield.
Further experiments showed this coupling reaction
was sensitive to the solvent and the acid. With toluene
instead of CH2Cl2, 43% yield was obtained (Table 1,
Entry 13). While in CH3CN, the reaction did not oc-
curred (Table 1, Entry 14). With CH3SO3H or
CCl3COOH instead of TFA, the two reactions gave poor
yields (Table 1, Entries 15, 16).
Consequently, the optimized reaction conditions
were summarized as follows: with 5 mol% FeCl3 and
2.0 equiv. of DTBP, 0.02 mmol/mL of the substrate in
CH2Cl2/TFA (9∶1, V/V) was stirred at room tempera-
ture for 6 h.
Results and Discussion
Firstly, (E)-methyl 2,3-bis(3,4-dimethoxyphenyl)
acrylate (1a) was used as the substrate to investigate
proper reaction conditions for the desired coupling reac-
tion. The results were summarized in Table 1.
Table 1 Optimization of the FeCl3-catalyzed intramolecular
coupling reactiona
OMe
OMe
MeO
MeO
MeO
FeCl3
DTBP
COOMe
COOMe
solvent, r.t.
MeO
OMe
OMe
1a
2a
Conc./
Entry
FeCl3/mol% DTBP/equiv. Solventb Yieldc/%
(mol•L－
)
1
1
2
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.02
0.05
0.02
0.02
0.02
0.02
0.02
25
0
2.0
2.0
0
9∶1
9∶1
9∶1
85
15
ND
61
91
92
82
81
84
94
74
74
43
ND
38
53
3
0
4
25
10
5
2.0
2.0
2.0
2.0
1.2
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
10d
5
9∶1
9∶1
6
7
2
9∶1
8
5
9∶1
9
5
9∶1
10
11
12
13
14
15
16
5
9∶1
5
9∶1
5
9.5∶0.5
9∶1e
9∶1f
9∶1g
9∶1h
5
5
Various 1,2-diaryethylene derivatives were tested as
substrates for the intramolecular oxidative coupling to
construct phenanthrene rings under above optimized
conditions (Table 2).
5
5
a
Reaction conditions: 1a (0.2 mmol), FeCl3 (0－25 mol%), and
(E)-1b, having an electron-withdrawing group
(－COOH) on the double bond, reacted smoothly under
optimized conditions and gave the desired product 2b in
96% yield (Table 2, Entry 2). The coupling reactions of
(E)-1c and (E)-1d also gave excellent yields (Table 2,
Entries 3, 4). (Z)-Substrates (1e, 1f, 1h, 1g, 1k) were
DTBP (0－200 mol%) in 10 mL of solvent were stirred at room
temperature for 6 h. b Solvent is a mixture of 9 mL dry CH2Cl2
and 1 mL TFA unless mentioned. c Isolated yield. d 10 mL dry
f
CH2Cl2 without TFA. e 9 mL dry toluene and 1 mL TFA. 9 mL
g
dry CH3CN and 1 mL TFA. 9 mL dry CH2Cl2 and 1 mL
CH3SO3H. h 9 mL dry CH2Cl2 and 1 mL CCl3COOH.
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Iron(III) Chloride Catalyzed Oxidative Coupling Reaction of 1,2-Diarylethylene Derivatives
Table 2 Substrate scope of intramolecular oxidative coupling using FeCl3 as catalyst with DTBP as sole oxidanta
Entry
Substrate
Product
FeCl3 (mol%)/t (h)
Yieldb/%
OMe
OMe
MeO
MeO
MeO
MeO
1
5/6
94
COOMe
COOMe
OMe
OMe
1a
2a
OMe
OMe
MeO
MeO
MeO
MeO
2
3
4
5/6
5/6
5/6
96
90
93
COOH
COOMe
COOH
COOH
OMe
OMe
1b
2b
O
O
O
O
COOMe
MeO
MeO
OMe
OMe
1c
2c
O
O
O
O
COOH
MeO
MeO
OMe
OMe
1d
2d
OMe
MeO
5
5/6
93
2a
MeOOC
OMe
OMe
OMe
1e
MeO
6
5/6
94
2b
HOOC
OMe
OMe
1f
Chin. J. Chem. 2013, 31, 1045—1053
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Ji et al.
FULL PAPER
Continued
Entry
Substrate
Product
FeCl3 (mol%)/t (h)
Yieldb/%
O
O
7
5/6
90
2c
MeOOC
OMe
OMe
1g
O
O
8
5/6
5/6
92
94
80
2d
HOOC
OMe
OMe
1h
9
1b＋1f
2b
MeO
MeO
MeO
MeO
COOMe
COOMe
10
20/10
OMe
OMe
1i
2i
OMe
OMe
11
12
13
20/10
20/11
10/12
70
COOMe
COOMe
MeO
MeO
OMe
OMe
1j
2j
OMe
OMe
MeO
MeO
MeO
MeO
36
COOMe
COOMe
1k
2k
OMe
OMe
MeO
MeO
89
CN
NC
MeO
OMe
OMe
OMe
1l
2l
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Chin. J. Chem. 2013, 31, 1045—1053

Iron(III) Chloride Catalyzed Oxidative Coupling Reaction of 1,2-Diarylethylene Derivatives
Continued
Yieldb/%
Entry
Substrate
Product
FeCl3 (mol%)/t (h)
O
O
O
O
14
10/12
83
CN
NC
MeO
OMe
OMe
OMe
1m
2m
OMe
OMe
MeO
MeO
15
20/16
70
CONEt2
CONEt2
MeO
MeO
OMe
OMe
1n
2n
OMe
OMe
MeO
MeO
16
20/16
65
NH
O
NH
O
MeO
MeO
2o
1o
a
Reaction conditions: 1a (0.2 mmol), FeCl3 (5－20 mol%), and DTBP (0.4 mmol) reacted in the mixture of 9 mL dry CH2Cl2 and 1 mL
TFA at room temperature for given time. b Isolated yield.
tried in the same condition, and similar yields were ob-
tained (Table 2, Entries 5－8), indicating the configura-
tion of substrates has little influence on the reaction. It
was confirmed by the reaction of the mixture of 1b and
1f as substrate in the same condition (Table 2, Entry 9).
Methoxyl group number and position effects on the
reaction were suveyed. The reactions of (E)-1i and
(E)-1j with three methoxyl groups on two phenyls gave
quite good yields with 20 mol% catalyst and prolonged
time (Table 2, Entries 10 and 11). Exceptionally, sub-
strate 1k gave only 36% yield, in which the position of
the three methoxyl groups was different from 1i and 1j
(Table 2, Entry 12).
by one-electron transfer of the substrate 1a. Then the
new C－C bond formed after the radical cation was at-
tacked by another electron-rich benzene ring. Next, the
reaction undergone a deprotonation. Finally, under the
same effect of FeCl3 dehydrogenation restored aro-
maticity to afford the coupling product 2a. When reac-
tion happened to Z-configuration substrate 1e, the
Z-configuration radical cation formed firstly.
E-Configuration radical cation generated after an allylic
radical isomerization. Then electrophilic C－C bond-
forming and deprotonation gave the same product 2a.
Experimental
Subsequently, we focused on the substitute on the
olefinic bond. When －CN instead of －COOH or
－COOCH3, the substrates reacted completely with
good yields (Table 2, Entries 13, 14). To our best
known, substrates with acylamino group on the double
bond were not investigated. When two kinds of amides
were chosen as substrates, the reactions also gave mod-
erate yields with 20 mol% catalyst and extended time
(Table 2, Entries 15, 16).
According to the experimental results and references,
the probably mechanism was provided for the coupling
reaction (Scheme 2).[18,19] Firstly, under the action of
FeCl3, an E-configuration radical cation was generated
General experimental section
All reactions were performed under nitrogen atmos-
phere unless stated. FeCl3 is commercially available
from the Shanghai Shanpu Chemicals Co., Ltd. The
DTBP (di-tert-butylperoxide) was purchased from the
Shanghai Taitan Technology Co., Ltd. Trifluoroacetic
acid (TFA) was provided by Shanghai Darui Fine
Chemicals Co., Ltd. All of the solvents, such as di-
chloromethane, acetonitrile, and toluene, were pur-
chased from Kelong Chemical Reagent (Chengdu,
China) and were dried and purified by standard tech-
1
niques just before use. H NMR and 13C NMR spectra
Chin. J. Chem. 2013, 31, 1045—1053
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Scheme 2
OMe
MeO
MeO
COOMe
FeCl3
-e, - H+
OMe
OMe
2a
OMe
MeO
OMe
OMe
MeO
MeO
MeO
MeO
MeO
H
+
COOMe
COOMe
- H+
COOMe
FeCl3
-e
COOMe
H
+
H
MeO
MeO
OMe
OMe
OMe
OMe
1a
Fe3+
OMe
OMe
OMe
1a or 1e
MeO
MeO
t-BuOH
MeO
COOMe
COOMe
COOMe
H+
+
+
+
H
H
H
Fe2+
MeO
OMe
OMe
DTBP
2a
OMe
OMe
OMe
-e
FeCl3
OMe
MeO
COOMe
H
OMe
OMe
1e
precipitate. The solid was collected and dried to give 1b
as a white solid. The solution was continued to be
acidified with concentrated hydrochloric acid to produce
another white precipitate. The solid was collected and
dried to give 1f as a white solid. By following the same
procedure as above, 1d and 1h were obtained.
(E)-2,3-Bis(3,4-dimethoxyphenyl)acrylic acid (1b)
Yield 75%. m.p. 214－216 ℃;[22] 1H NMR (400 MHz,
CDCl3) δ: 7.87 (s, 1H), 6.94－6.92 (d, J＝8.0 Hz, 1H),
6.86－6.84 (m, 2H), 6.81 (s, 1H), 6.74－6.72 (d, J＝8.0
Hz, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.82 (s, 3H), 3.49 (s,
3H).
(Z)-2,3-Bis(3,4-dimethoxyphenyl)acrylic acid (1f)
Yield 12%. m.p. 170－172 ℃;[22] 1H NMR (400 MHz,
CDCl3) δ: 7.06－7.02 (m, 4H), 6.94 (s, 1H), 6.90－6.84
(m, 2H), 3.92－3.90 (m, 9H), 3.86 (s, 3H).
(E)-2-(3,4-Dimethoxyphenyl)-3-(3,4-methylenedi-
oxyphenyl)acrylic acid (1d) Yield 63%. m.p. 200－
202 ℃;[23] 1H NMR (400 MHz, DMSO) δ: 12.59 (brs,
1H, COOH), 7.62 (s, 1H), 6.98－6.96 (d, J＝8.0 Hz,
1H), 6.84－6.82 (m, 2H), 6.74－6.73 (m, 1H), 6.68－
were recorded using a Varian Mercury Plus 400 MHz
and a Bruker Avance 600 MHz spectrometer. HRMS
were recorded on a BioTOF Q mass spectrometer
(ESIMS). The melting points were determined on an
X-4 binocular microscope melting point apparatus
(Shanghai Precision Tech Instruments Co., Shanghai,
China) and were uncorrected.
General procedure for the preparation of 2,3-disub-
stituted phenyl acrylic acid
A mixture of homoveratric acid (9.8 g, 0.05 mol),
veratraldehyde (9.13 g, 0.055 mol), acetic anhydride (20
mL) and triethylamine (100 mL) was stirred and heated
at reflux for 24 h at the nitrogen atmosphere.[20,21] Water
(50 mL) was added after the solution was cooled to
room temperature. The mixture was then poured into
aqueous potassium carbonate (75.0 g in 475 mL water)
and refluxed until nearly all of the gummy material was
dissolved. The solution obtained was cooled and ex-
tracted with ether (50 mL×3), and carefully acidified
with concentrated hydrochloric acid to produce a white
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Chin. J. Chem. 2013, 31, 1045—1053

Iron(III) Chloride Catalyzed Oxidative Coupling Reaction of 1,2-Diarylethylene Derivatives
6.66 (m, 1H), 6.40 (s, 1H), 5.97 (s, 2H), 3.78 (s, 3H),
3.67 (s, 3H).
3.46 (s, 3H).
Methyl (E)-2-(3,4-dimethoxyphenyl)-3-(4-meth-
(Z)-2-(3,4-Dimethoxyphenyl)-3-(3,4-methylenedi-
oxyphenyl)acrylic acid (1h) Yield 25%. m.p. 151－
152 ℃;[23] 1H NMR (400 MHz, CDCl3) δ: 7.04－7.02
(m, 1H), 7.00－6.99 (m, 2H), 6.96－6.94 (m, 1H), 6.90
(s, 1H), 6.88 (d, J＝8.0 Hz, 1H), 6.81 (d, J＝8.0 Hz,
1H), 5.99 (s, 2H), 3.91 (s, 3H), 3.90 (s, 3H).
oxyphenyl)acrylate (1j) Yield 83%. m.p. 112－113
℃;[25] 1H NMR (400 MHz, CDCl3) δ: 7.78 (s, 1H), 7.12
－7.08 (m, 1H), 6.89 (d, J＝8.0 Hz, 1H), 6.81－6.76 (m,
2H), 6.74 (d, J＝1.6 Hz, 1H), 6.71 (d, J＝8 Hz, 1H),
3.90 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.55 (s, 3H).
Methyl (E)-2-(4-methoxyphenyl)-3-(3,4-dimeth-
oxyphenyl)acrylate (1k) Yield 82%. m.p. 91－92
℃;[26] 1H NMR (400 MHz, CDCl3) δ: 7.76 (s, 1H),
7.18 (d, J＝8.0 Hz, 2H), 6.95 (d, J＝8.0 Hz, 2H), 6.82
(d, J＝1.2 Hz, 1H), 6.72 (d, J＝8.0 Hz, 1H), 6.48 (d,
J＝1.2 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H),
3.46 (s, 3H).
General procedure for the preparation of methyl
2,3-disubstituted phenylacrylate
Esterification of 1b (17.2 g, 0.05 mol) with methanol
(150 mL) and sulfuric acid (3 mL) in the usual manner
and recrystallization from ethyl acetate afforded the
pure 1a as a white solid. Using the same procedure
described, 1c, 1e, 1g, 1k, 1i and 1j were obtained.
Methyl (E)-2,3-bis(3,4-dimethoxyphenyl)acrylate
(1a) Yield 83%. m.p. 127－128 ℃;[21] 1H NMR (400
MHz, CDCl3) δ: 7.76 (s, 1H), 6.92 (d, J＝8.0 Hz, 1H),
6.82 (d, J＝8.0 Hz, 2H), 6.78 (d, J＝1.2 Hz, 1H), 6.72
(d, J＝8.0 Hz, 1H), 6.53 (s, 1H), 3.90 (s, 3H), 3.84 (s,
3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.49 (s, 3H).
Procedure for the preparation of (Z)-2,3-disubsti-
tuted phenyl acrylonitrile
A mixture of cyanide (1.77 g, 0.01 mol), veratralde-
hyde (1.83 g, 0.011 mol), ethanol (62.0 mL), and so-
dium ethoxide (0.75 g) was stirred and heated at reflux
for 2 h. A yellow solid appeared after the solution was
cooled to room temperature. The mixture was filtered
and washed with water (100 mL×3) and ethanol (20
mL).[19] The solid was collected and dried to give 1l as a
yellow solid. By following the same procedure as above,
1m was obtained.
(Z)-2,3-Bis(3,4-dimethoxyphenyl)acrylonitrile (1l)
Yield 88%. m.p. 152－153 ℃;[27] 1H NMR (400 MHz,
CDCl3) δ: 7.67 (d, J＝2.0 Hz, 1H), 7.36－7.34 (m, 2H),
7.27－7.23 (m, 1H), 7.12 (d, J＝2.0 Hz, 1H), 6.94 (d,
J＝4.0 Hz, 1H), 6.92 (d, J＝4.0 Hz, 1H), 3.97 (s, 3H),
3.96 (s, 3H), 3.95 (s, 3H), 3.93 (s, 3H).
Methyl (E)-2-(3,4-dimethoxyphenyl)-3-(3,4-meth-
ylenedioxyphenyl)acrylate (1c) Yield 82%. m.p. 158
－160 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.79 (s, 1H),
6.90 (d, J＝8.0 Hz, 1H), 6.78－6.74 (m, 2H), 6.72 (d,
J＝1.6 Hz, 1H), 6.67 (d, J＝8.0 Hz, 1H), 6.41 (d, J＝
1.6 Hz, 1H), 5.90 (s, 2H), 3.92 (s, 3H), 3.82 (s, 3H),
3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 168.6,
149.1, 148.6, 147.4, 140.2, 129.9, 128.8, 128.2, 126.8,
121.9, 112.5, 111.3, 109.5, 109.5, 108.1, 101.2, 55.9,
55.8, 52.4; IR (KBr) ν: 2998, 2953, 2937, 2835, 1706,
－
1
1604, 1583, 1503, 1485, 1227, 1026 cm ; HRMS (ESI)
m/z calcd for C19H18O6Na ([M＋Na]＋) 365.0996, found
365.0993.
(Z)-2-(3,4-Dimethoxyphenyl)-3-(3,4-methylenedi-
oxyphenyl)acrylonitrile (1m) Yield 91%. m.p. 147－
149 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.56 (d, J＝1.6
Hz, 1H), 7.31 (s, 1H), 7.27 (d, J＝8 Hz, 1H), 7.24－
7.21 (m, 1H), 7.11 (d, J＝2 Hz, 1H), 6.91 (d, J＝8 Hz,
1H), 6.88 (d, J＝8 Hz, 1H), 6.05 (s, 2H), 3.96 (s, 3H),
3.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 149.7,
149.3, 149.1, 148.2, 140.2, 140.1, 128.1, 127.4, 125.4,
118.7, 111.1, 108.9, 108.6, 108.5, 107.9, 101.7, 56.0,
55.9; IR (KBr) ν: 2968, 2922, 2835, 2208, 1603, 1520,
Methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)acrylate
(1e) Yield 78%. m.p. 148－150 ℃;[19] 1H NMR (400
MHz, CDCl3) δ: 6.99－6.94 (m, 4H), 6.89－6.84 (m,
3H), 3.92 (s, 3H), 3.90 (s, 6H), 3.88 (s, 3H), 3.81 (s,
3H).
Methyl (Z)-2-(3,4-dimethoxyphenyl)-3-(3,4-meth-
ylenedioxyphenyl)acrylate (1g) Yield 79%. m.p. 124
1
－126 ℃; H NMR (400 MHz, CDCl3) δ: 6.97－6.96
－
1
1463, 1253, 1034, 792 cm ; HRMS (ESI) m/z calcd for
(m, 2H), 6.87 (s, 1H), 6.85－6.84 (m, 3H), 6.79 (d, J＝
8.0 Hz, 1H), 5.98 (s, 2H), 3.91 (s, 6H), 3.90 (s, 3H),
3.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 170.3,
149.2, 148.9, 147.8, 147.6, 133.1, 129.9, 129.8, 129.7,
122.8, 119.2, 111.0, 109.1, 108.4, 107.7, 101.2, 56.0,
55.9, 52.4; IR (KBr) ν: 3011, 2963, 2935, 2838, 1721,
1601, 1581, 1506, 1465, 1257, 1223, 1033, 868, 813
C18H15NO4Na ([M＋Na]＋) 332.0893, found 332.0883.
Procedure for the preparation of (Z)-2,3-bis(3,4-di-
methoxyphenyl)bisacetamide (1n)
A mixture of 1b (1.0 g, 0.05 mol) and SOCl2 (2.0
mL) was refluxed for 3 h. The unreacted SOCl2 was
distilled from the solution. Diethylamine (2.0 mL) and
dichloromethane (5.0 mL) were added into the mixture
and stirred for 3 h at room temperature. The solution
was washed with water and extracted with dichloro-
methane (20 mL×3). The organic phase was dried over
MgSO4, filtered, concentrated by rotary evaporator and
separated by chromatographic column to give the de-
sired product 1n as a yellow solid.
－
1
cm ; HRMS (ESI) m/z calcd for C19H18O6Na ([M＋
Na]＋) 365.0996, found 365.0997.
Methyl (E)-2-(3,4-dimethoxyphenyl)-3-(4-meth-
oxyphenyl)acrylate (1i) Yield 86%. m.p. 113－114
℃;[24] 1H NMR (400 MHz, CDCl3) δ: 7.76 (s, 1H),
7.17 (d, J＝8.0 Hz, 2H), 6.94 (d, J＝8.0 Hz, 2H), 6.84
(d, J＝1.2 Hz, 1H), 6.72 (d, J＝8.0 Hz, 1H), 6.48 (d,
J＝1.6 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H),
Chin. J. Chem. 2013, 31, 1045—1053
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1051

Ji et al.
FULL PAPER
(Z)-2,3-Bis(3,4-dimethoxyphenyl)bisacetamide
(1n) Yield 39%. m.p. 103－105 ℃; H NMR (400
(400 MHz, CDCl3) δ: 8.65 (s, 1H), 8.45 (s, 1H), 7.88－
7.84 (m, 2H), 7.81 (d, J＝2.0 Hz, 1H), 4.11 (s, 3H),
4.08 (s, 3H), 4.03 (s, 3H), 4.01 (s, 3H).
Methyl 2,6,7-trimethoxyphenanthrene-9-carboxy-
late (2j) Yield 70%. m.p. 153－154 ℃;[19] 1H NMR
(400 MHz, CDCl3) δ: 8.54 (s, 1H), 8.42 (d, J＝8 Hz,
1H), 8.40 (s, 1H), 7.91 (s, 1H), 7.36－7.33 (m, 1H),
7.27 (d, J＝8 Hz, 1H), 4.11 (s, 3H), 4.07 (s, 3H), 4.03 (s,
3H), 3.96 (s, 3H).
Methyl 2,3,6-trimethoxyphenanthrene-9-carboxy-
late (2k) Yield 36%. m.p. 158－159 ℃;[19] 1H NMR
(400 MHz, CDCl3) δ: 8.91 (d, J＝8.0 Hz, 1H), 8.27 (s,
1H), 7.84 (d, J＝12.0 Hz, 2H), 7.26 (d, J＝12.0 Hz, 2H),
4.10 (s, 3H), 4.01 (s, 3H), 4.08 (s, 3H), 4.00 (s, 3H).
2,3,6,7-Tetramethoxyphenanthrene-9-carbonitrile
(2l) Yield 89%. m.p. 266－268 ℃;[27] 1H NMR (400
MHz, CDCl3) δ: 7.99 (s, 1H), 7.73 (s, 1H), 7.71 (s, 1H),
7.50 (s, 1H), 7.18 (s, 1H), 4.15 (s, 3H), 4.14 (s, 3H),
4.08 (s, 3H), 4.05 (s, 3H).
1
MHz, CDCl3) δ: 6.94 (d, J＝1.2 Hz, 1H), 6.91 (d, J＝4
Hz, 1H), 6.80－6.77 (m, 2H), 6.72 (d, J＝8 Hz, 1H),
6.69 (s, 1H), 6.57 (s, 1H), 6.92 (d, J＝4 Hz, 1H), 3.87 (s,
3H), 3.85 (s, 3H), 3.74 (s, 3H), 3.57 (s, 3H), 3.44－3.40
(m, 4H), 1.17 (s, 3H), 0.97 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 171.2, 148.8, 148.5, 148.4, 148.0, 136.3,
128.3, 128.2, 128.1, 128.0, 122.6, 121.5, 111.8, 110.9,
110.5, 55.8, 55.7, 55.5, 55.4, 42.9, 39.1, 13.9, 12.7; IR
(KBr) ν: 2966, 2934, 2835, 1624, 1580, 1513, 1463,
－
1
1421, 1257, 1132, 1024, 764 cm ; HRMS (ESI) m/z
calcd for C23H29NO5Na ([M＋Na]＋) 422.1938, found
422.1954.
General procedure for oxidative coupling reaction
A solution of 1b (or 1f) (0.2 mmol, 68.8 mg) in di-
chloromethane (9 mL) was added FeCl3 (0.01 mmol,
1.63 mg) (FeCl3 was dissolved in dry nitromethane,
0.04 g/mL), DTBP (0.4 mmol, 58.4 mg) and CF3COOH
(1 mL) at nitrogen atmosphere. The mixture was stirred
at room temperature for 6 h and then quenched by water
(10 mL). The aqueous phase was extracted with di-
chloromethane (10 mL×3). The combined organic
phase was dried over MgSO4, filtered, concentrated by
rotary evaporator and separated by chromatographic
column to give the desired product 2b as a light yellow
solid. Coupling reactions of the other substrates fol-
lowed the same procedure.
2,3,6,7-Tetramethoxyphenanthrene-9-carboxylic
acid (2b) Yield 96%. m.p. 283－285 ℃;[22] 1H NMR
(400 MHz, CDCl3) δ: 12.86 (brs, 1H, COOH), 8.55 (s,
1H), 8.42 (s, 1H, H-3'), 8.05 (s, 1H), 8.01 (s, 1H), 7.56
(s, 1H), 4.06 (s, 3H), 4.05 (s, 3H), 3.92 (s, 3H), 3.89 (s,
3H).
2,3-Methylenedioxy-6,7-dimethoxyphenanthrene-
9-carbonitrile (2m) Yield 83%. m.p. 246－248 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.99 (s, 1H), 7.81 (s,
1H), 7.72 (s, 1H), 7.52 (s, 1H), 7.20 (s, 1H), 6.16 (s, 2H),
4.12 (s, 3H), 4.09 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 150.4, 150.1, 150.0, 147.6, 132.2, 128.3, 125.6, 124.5,
124.0, 118.7, 105.9, 105.8, 105.3, 102.8, 101.9, 100.2,
56.1, 56.0; IR (KBr) ν: 2923, 2218, 1624, 1529, 1504,
－
1
1471, 1277, 1228, 1040, 843 cm ; HRMS (ESI) m/z
calcd for C18H13NO4Na ([M＋Na]＋) 330.0737, found
330.0727.
2,3,6,7-Tetramethoxyphenanthrene-9-bisacet-
1
amide (2n) Yield 70%. m.p. 155－157 ℃; H NMR
(400 MHz, CDCl3) δ: 7.79 (s, 1H), 7.77 (s, 1H), 7.49 (s,
1H), 7.19 (s, 1H), 7.14 (s, 1H), 4.14 (s, 3H), 4.13 (s, 3H),
4.04 (s, 3H), 3.97 (s, 3H), 3.47－3.41 (m, 1H), 3.17－
3.14 (m, 2H), 1.42－1.38 (m, 3H), 1.05－1.02 (m, 3H);
13C NMR (100 MHz, CDCl3) δ: 170.6, 149.6, 149.3,
148.9, 131.1, 125.3, 124.6, 124.4, 122.6, 121.5, 121.4,
108.3, 105.0, 102.8, 102.5, 56.1, 56.05, 56.0, 55.7, 43.1,
38.8, 14.4, 13.0; IR (KBr) ν: 2978, 2934, 2832, 1621,
Methyl
2,3,6,7-Tetramethoxyphenanthrene-9-
carboxylate (2a) Yield 94%. m.p. 203－204 ℃;[19]
1H NMR (400 MHz, CDCl3) δ: 8.65 (s, 1H), 8.42 (s,
1H), 7.80 (s, 1H), 7.76 (s, 1H), 7.26 (s, 1H), 4.14 (s, 3H),
4.13 (s, 3H), 4.08 (s, 3H), 4.04 (s, 3H), 4.02 (s, 3H).
Methyl
2,3-methylenedioxy-6,7-dimethoxyphe-
－
1
1509, 1475, 1427, 1252, 1123, 1044, 841, 751 cm ;
HRMS (ESI) m/z calcd for C23H27NO5Na ([M＋Na]＋)
420.1781, found 420.1784.
nanthrene-9-carboxylic (2c) Yield 90%. m.p. 210－
1
213 ℃; H NMR (400 MHz, CDCl3) δ: 8.60 (s, 1H),
8.34 (s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.22 (s, 1H),
6.12 (s, 2H), 4.09 (s, 3H), 4.07 (s, 3H), 4.01 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ: 168.1, 149.9, 149.2, 148.9,
147.1, 130.5, 128.7, 125.6, 125.4, 124.1, 122.1, 106.5,
106.4, 102.5, 101.5, 100.2, 55.9, 55.8, 52.1; IR (KBr) ν:
2997, 2947, 2834, 1706, 1595, 1500, 1434, 1348, 1257,
3,4-Dihydro-dibenzo[f,h]isoquinolin-1-one
(2o)
Yield 65%. m.p. 245－248 ℃;[29] 1H NMR (400 MHz,
CDCl3) δ: 9.29 (d, J＝9.0 Hz, 1H), 7.93 (s, 1H), 7.87 (d,
J＝2.1 Hz, 1H), 7.36 (s, 1H), 7.28－7.26 (m, 1H), 6.18
(s, 1H), 4.14 (s, 3H), 4.06 (s, 3H), 4.02 (s, 3H), 3.65 (s,
2H), 3.33 (t, J＝6.2 Hz, 2H). HRMS (ESI) m/z calcd for
C20H20O4 ([M＋H]＋) 338.1387, found 338.1381.
－
1
1257, 1136, 1034 cm ; HRMS (ESI) m/z calcd for
C19H16O6Na ([M＋Na]＋) 363.0839, found 363.0841.
2,3-Methylenedioxy-6,7-dimethoxyphenanthrene-
9-carboxylate acid (2d) Yield 93%. m.p. 265－266
℃;[23] 1H NMR (400 MHz, CDCl3) δ: 8.60 (s, 1H), 8.34
(s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.22 (s, 1H), 6.12 (s,
2H), 4.09 (s, 3H), 4.07 (s, 3H), 4.01 (s, 3H).
Conclusions
In summary, as an effort to develop facile and green
method for direct construction of the phenanthrene ring,
a nontoxic FeCl3-catalyzed intramolecular oxidative
coupling reaction was developed with di-tert-butyl-
peroxide (DTBP) as sole oxidant at room temperature in
Methyl 3,6,7-trimethoxyphenanthrene-9-carboxy-
late (2i) Yield 80%. m.p. 147－148 ℃;[28] 1H NMR
1052
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 1045—1053

Iron(III) Chloride Catalyzed Oxidative Coupling Reaction of 1,2-Diarylethylene Derivatives
Y.; Kim, J. D. J. Org. Chem. 2007, 72, 4886.
CH2Cl2/TFA to yield polymethoxy-substituted phenan-
threnes in moderate to excellent yields. This method has
several advantages: (i) satisfactory atom economy: C－
C bonds can be formed starting directly from unfunc-
tionalized 2,3-diphenylacrylic acid and derivatives. (ii)
only 5%－20% FeCl3 as catalyst: easily available and
nontoxic. (iii) mild reaction conditions and simple
workup procedures. Further study on the effect of sub-
stituted groups on two benzene rings and olefinic bond
is in progress.
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Acknowledgement
The authors are grateful to Sichuan Provincial Edu-
cation Department (No.12ZA141) and Key Laboratory
of Advanced Functional Materials of Sichuan Province
Higher Education System (No.KFKT2013-01) for fi-
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Chin. J. Chem. 2013, 31, 1045—1053
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1053