M-CPBA/TFA: An efficient nonmetallic reagent for oxidative coupling of 1,2-diarylethylenes

Article abstract of DOI:10.1016/j.tet.2010.09.101

A mild synthesis of a series of phenanthrenes with different substituents on the phenanthrene ring is described. The method involves intramolecular oxidative coupling of a variety of 1,2-diarylethylene derivatives in the presence of m-chloroperoxybenzoic acid (m-CPBA) in trifluoroacetic acid (TFA) to yield phenanthrenes in high yields. The present approach solves a key step for the synthesis of polycyclic structures related to an alkaloid tylophorine.

Full text of DOI:10.1016/j.tet.2010.09.101

Tetrahedron 66 (2010) 9135e9140
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
m-CPBA/TFA: an efficient nonmetallic reagent for oxidative coupling
of 1,2-diarylethylenes
*
Kailiang Wang, Yanna Hu, Meng Wu, Zheng Li, Zhihui Liu, Bo Su, Ao Yu, Yu Liu, Qingmin Wang
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 July 2010
Received in revised form 28 September 2010
Accepted 29 September 2010
Available online 15 October 2010
A mild synthesis of a series of phenanthrenes with different substituents on the phenanthrene ring is
described. The method involves intramolecular oxidative coupling of a variety of 1,2-diarylethylene
derivatives in the presence of m-chloroperoxybenzoic acid (m-CPBA) in trifluoroacetic acid (TFA) to yield
phenanthrenes in high yields. The present approach solves a key step for the synthesis of polycyclic
structures related to an alkaloid tylophorine.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
m-CPBA/TFA
Nonmetallic reagent
Intramolecular oxidative coupling
Phenanthrene ring
1. Introduction
yields restrict the practical application of this method. The main
limitations to the Pschorr synthesis are difficulties in obtaining
The phenanthroindolizidine and phenanthroquinolizidine al-
kaloids are structurally related groups of pentacyclic natural
products.1 Since the first isolation of (ꢀ)-tylophorine in 1935,2
more than 60 alkaloids and their seco analogues have been repor-
ted.3 These alkaloids exhibit interesting pharmacological proper-
ties.1,3,4 Among these interesting biological activities, antitumor
activity is most notable,3,4g,5 and thus, it is responsible for synthetic
attention.3,6 The synthesis of polymethoxy-substituted phenan-
threne unit is the key step in the preparation of these alkaloids.3,6
Therefore, development of an effective protocol to access poly-
methoxy-substituted phenanthrenes is noteworthy. Pschorr
proposed the first synthesis of phenanthrene core in 1896,7 the first
step of this reaction was a Perkin condensation between the so-
starting materials and in decarboxylating the phenanthrene de-
rivative. Problems connected with the preparation of o-nitro-
benzaldehydes are sometimes the determining factors in the
usefulness of the Pschorr synthesis. Metal-based intramolecular
oxidative coupling to yield the phenanthrene ring by using vana-
dium oxytrifluoride (VOF3),6d,9 thallium(III) triflouroacetate
(TTFA),10 lead(IV) tetraacetate (Pb(OAc)4)11 has been developed.
However, these coupling reactions require large excess amount of
metal salts, extensive application of these organic metallic reagents
has been limited by high toxicity, severe conditions, and low yields.
Moreover, these heavy metals can contaminate the final products.
We have recently reported the use of large excess iron(III) chloride
(FeCl3) and catalytic amount of FeCl3 for the synthesis of poly-
methoxy-substituted phenanthrene derivatives by oxidative cou-
dium salt of phenylacetic acid and o-nitrobenzaldehyde; o-nitro-a-
phenylcinnamic acid was formed. The nitro group was then
reduced using an ammoniacal solution of ferrous sulfate, and the
amino acid produced was diazotized. On shaking the diazonium
salt with dilute sulfuric acid and copper powder, nitrogen was
eliminated and ring closure led to the formation of 9-phenan-
threnecarboxylic acid. When heated, this acid lost carbon dioxide
and formed phenanthrene. And the Pschorr reaction has been
widely used and become a classical method to synthesize phen-
anthrene ring system.8 But the long linear sequence and low overall
pling of substituted methyl (E)-a
-phenyl cinnamates.12 These two
methods also suffer from difficulty in separation of organic and
inorganic products relatively due to introducing metallic reagent.
Therefore, the development of more efficient organic nonmetallic
coupling reagents for the construction of phenanthrene derivatives
is highly desirable.
m-Chloroperoxybenzoic acid (m-CPBA) is the one of choice for
laboratory-scale experiments because it is very efficient and it can
be easily and safely handled in very clean reactions. m-CPBA has
been extensively investigated as an oxidizing agent for oxidation of
unsaturated compounds, organic sulfur compounds, organic ni-
trogen compounds, aldehydes, ketones, quinones, organic iodine
compounds, and so on. m-CPBA has also been used for the
* Corresponding author. Tel./fax: þ86 (0)22 23499842; e-mail address:
wangqm@nankai.edu.cn (Q. Wang).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.101

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K. Wang et al. / Tetrahedron 66 (2010) 9135e9140
determination of structure and analysis of organic compounds.13
However, the use of nonmetallic m-CPBA as sole oxidative cou-
pling reagent for the direct construction of phenanthrenes rather
than epoxy compounds and its scope and limitations remain un-
known. In this paper, we report the efficiency of the system
m-CPBA/TFA for oxidative coupling of 1,2-diarylethylenes to
phenanthrenes under very mild conditions.
Table 3
Effect of temperature on coupling of 1aa
Entry
Temp (ꢁC)
t (h)
LC conv. (%)
LC yield (%)
1
2
3
4
5
ꢀ15
0
18
6
67
91
100
100
100
66
89
98
94
95
25
40
70
2
0.25
0.25
a
Conditions: 1a (358 mg, 1.0 mmol), 1.5 equiv of m-CPBA, CF3COOH act as sol-
2. Results and discussion
vent, 0.01 mol/L.
of m-CPBA, TFA as solvent, the concentration of the substrate was
0.05 mol/L, at room temperature.
Subsequently, various simple structure 1,2-diarylethylenes were
tested as substrates for the intramolecular oxidative coupling to
form phenanthrene rings under the above optimized conditions
(Table 4). To avoid side-reactions such as epoxidation of the ethylene
As a starting point, we chose (E)-methyl-2,3-bis(3,4-dimethox-
yphenyl)acrylate (1a) as standard substrate to investigate suitable
reaction conditions for the desired intramolecular oxidative cou-
pling reaction. The results are summarized in Table 1.
Table 1
Effect of amount of m-CPBA on coupling of 1aa
Table 4
OCH3
OCH3
Substrate scope of intramolecular oxidative coupling using m-CPBAa
H3CO
H3CO
H3CO
Entry
1
Substrate
Product
t (h)
Yieldb (%)
COOCH3
COOCH3
m-CPBA
CF3COOH, r.t
0.5
96
H3CO
OCH3
OCH3
1a
1b
Entry
m-CPBA (equiv)
t (h)
LC conv.b (%)
LC yieldb (%)
2
3
0.7
1.3
92
96
1
2
3
4
5
1.1
1.2
1.3
1.4
1.5
6
6
6
1.2
1.2
73
80
91
98
100
57
70
84
90
94
a
Conditions: 1a (358 mg, 1.0 mmol), CF3COOH (10 mL) acts as solvent.
Conversion and yield were determined by HPLC.
b
The desired coupling product 1b was not obtained with m-CPBA
as sole oxidant when dichloromethane acts as solvent. When or-
ganic acid trifluoroacetic acid (CF3COOH) acts as solvent, the cou-
pling reaction proceeded successfully at room temperature (Table
1), showing that acidic environment is an indispensable condition
for intramolecular coupling of 1a. Increasing the amount of m-CPBA
had great influence on the conversions and yields (Table 1, entries
1e5). Quantitative conversion and almost quantitative yield were
obtained by using 1.5 equiv of m-CPBA as oxidant (Table 1, entry 5).
Concentration effecton coupling reaction of 1a is showninTable 2,
which shows that the reaction can be performed in a wide range of
concentrationwithexcellentyieldsatroomtemperature.Theyieldsof
1b also increased gradually when the concentration decreased.
4
0.5
86
5
6
7
1b
0.7
96
95
93
Table 2
Effect of concentration on coupling of 1aa
Entry
Concn (mol/L)
t (h)
LC conv. (%)
LC yield (%)
0.75
0.85
1
2
3
4
0.1
1.0
1.0
0.7
0.5
98
100
100
100
93
92
95
99
0.05
0.025
0.01
a
Conditions: 1a (358 mg, 1.0 mmol), 1.5 equiv of m-CPBA, CF3COOH act as sol-
vent, room temperature.
2b
3b
In order to further optimize the reaction conditions, the reaction
was studied with different temperatures as shown in Table 3. Re-
action times were shorter when the temperature became higher.
Almost quantitative yield was obtained at room temperature (Table
3, entry 3), which evidences the efficiency of the m-CPBA/TFA
system to get the intramolecular oxidative coupling.
8
2.5
82
Considering operational simplicity and large-scale synthesis, the
optimized reaction conditions were summarized as follows: 1.5 equiv

K. Wang et al. / Tetrahedron 66 (2010) 9135e9140
9137
Table 4 (continued)
shown in Fig. 1, a signal at g¼2.006 was observed, which is as-
signable to a radical species derived from 1a and it has no hyperfine
splitting (Fig. 1a). The signal was not observed after the treatment
of 1a in CH2Cl2 (Fig. 1b). Acidic environment is indispensable for
protonation of m-CPBA and increases its oxidation ability.
Entry
Substrate
Product
t (h)
Yieldb (%)
94
9
2a/7a¼1:1
2b
1
a
10c
1b
0.85
93
g = 2.006
a
Substrate: 1.0 mmol.
Yield of the isolated products.
m-CPBA (3.0 equiv) was used.
b
c
unit, we deactivated the double bond by introduction of a carbonyl
or cyano substituent. Both E-isomer substrates 1ae4a and Z-isomer
substrates 5ae8a, which have an electron-withdrawing group on
the double bond and electron-donating groups on the phenyls were
found to react smoothly and gave the corresponding coupling
products rather than epoxy products in excellent yields (82e96%),
suggesting that configuration of the double bond has no effect to the
intramolecular oxidative coupling. As we all know, Perkin conden-
sation of the appropriate benzeneacetic acid with the corresponding
aromatic aldehyde invariablyyield a mixtureof E-isomeras the main
product and Z-isomeras the minor product,9a,14 such as 2a and 7a. So
we selected the mixture of 2a and 7a as substrate to test this method
and gave the same oxidative coupling product 2b in the presence of
m-CPBA at room temperature in 94% yield (Table 4, entry 9). In
contrast to the Pschorr synthesis of phenanthrene, the reaction
makes full use of the minor (Z)-isomer 7a, which was a byproduct in
the Pschorr reaction. In addition, a larger-scale reaction (50-fold
scaled up) showed the same result as for the small one. Therearealso
certainverydefinite limitationstothe Pschorr synthesis. Some of the
limitations arise as a result of side reaction: reduction and/or hy-
3460
3480
3500
3520
3540
3560
G
b
2000 2250 2500 2750 3000 3250 3500 3750 4000 4250 4500 4750 5000
[G]
droxylation may replace coupling, and where the a-phenyl nucleus
Fig. 1. ESR spectra of m-CPBA-mediated oxidative coupling. (a) m-CPBA/TFA was
treated with 1a, after 6 min, the spectrum was measured. (b) Compound 1a was dis-
solved in CH2Cl2 and the spectrum was measured.
of the cinnamic acid derivative is unsymmetrically substituted, two
isomeric coupling products are possible. Interestingly, oxidative
coupling and dehydrogenation of 9a was successfully achieved in
one pot by using 3.0 equiv of m-CPBA and gave 1b in 93% yield (Table
4, entry 10). Thus, this facile and efficient synthesis of phenanthrene
derivatives by using m-CPBA/TFA system solved the key step for the
synthesis of polycyclic structures related to an alkaloid tylophorine.
To our delight, the m-CPBA/TFA system has become successful as
an effective organic nonmetallic oxidant for intermolecular CeC
bond formation, initiating an oxidative aniline coupling reaction
between 2-naphthylamine (10a) moieties at room temperature and
gave binaphthyl amine (10b) in 85% isolated yield. The coupling of 2-
naphthylamine has been investigated via complex process with low
yields15 and our simple reaction scheme is given below (Scheme 1).
Based on the above experimental results, we propose the re-
action mechanism for the present oxidative coupling (Scheme 2).
This reaction can be divided into three steps. The first step proceeds
via a one-electron transfer from substrate E-1a or Z-7a to m-CPBA
to give the reduced form m-chlorobenzoic acid and radical cationic
species, which was attacked by another rich-electronic phenyl ring
to form new CeC bond. At last, one electron is lost and dehy-
droaromatization to give the corresponding biaryl coupling product
1b. Compound Z-7a also proceeds via CeC bond rotation.
3. Conclusion
In summary, as an effort to develop green chemistry in the field
of chemical synthesis, we have developed an efficient synthetic
approach for the direct construction of polymethoxy-substituted
phenanthrene rings using nonmetallic m-chloroperoxybenzoic acid
(m-CPBA) as sole oxidant in trifluoroacetic acid (TFA), which solved
the key step in the preparation of polycyclic natural alkaloid tylo-
phorine. This method has also been applied to intermolecular biaryl
coupling of 2-naphthylamine in excellent yield. The present system
has the following significant advantages: (i) CeC bonds can be
formed efficiently starting directly from arenes rather than epoxi-
dation; (ii) simple workup procedures, mild conditions, large-scale
preparation, and high yields; (iii) the use of easily available and
nontoxic m-CPBA as oxidant and TFA can be recycled and reused.
Such reactions present the most direct and efficient synthetic
methods of CeC bond formation and provide a foundation for the
m-CPBA (1.5 equiv)
NH2
NH2
NH2
CF3COOH, r.t
85%
10a
10b
Scheme 1. Synthesis of binaphthyl amine (10b).
No mechanism has yet been formulated for the above coupling
reactions employing m-CPBA/TFA reagent. The nonstereospecificity
of our coupling reaction (Table 4, entries 1e8) implied that the
reaction proceed via free radical species. To further clarify the
mechanism of the present m-CPBA-mediated oxidative coupling,
the ESR spectrum was then measured for the coupling of 1a. As

9138
K. Wang et al. / Tetrahedron 66 (2010) 9135e9140
OCH3
OCH3
OCH3
OCH3
H3CO
H3CO
H3CO
H3CO
-e, -H+
H3CO
O2-
COOCH3
COOCH3
COOCH3
O1-
-e
COOCH3
H
H3CO
H3CO
H3CO
OCH3
OCH3
OCH3
OCH3
1b
E-1a
-2H+
-e
OCH3
OCH3
OCH3
OCH3
H3CO
H3CO
H3CO
H3CO
H3CO
COOCH3
COOCH3
O2-
O1-
COOCH3
COOMe
OCH3
-e
OCH3
H
H
OCH3 H3CO
Z-7a
OCH3
OCH3
OCH3
Scheme 2. Tentative mechanism for m-CPBA-mediated intramolecular oxidative coupling.
next generation of chemical syntheses with an eye on green
chemistry. Further studies on synthetic applications of m-CPBA/TFA
system are in progress.
d 12.50 (br, 1H), 7.68 (s, 1H), 6.54e6.98 (m, 6H), 3.74 (s, 3H), 3.69 (s,
3H), 3.66 (s, 3H), 3.45 (s, 3H).
4.2.3. Methyl (E)-2-(3,4-methylenedioxyphenyl)-3-(3,4-dimethoxy-
phenyl)acrylate (3a). Yield 68%, mp 101e103 ꢁC; 1H NMR
4. Experimental
4.1. General
(400 MHz, CDCl3)
d 7.77 (s, 1H), 6.83e6.87 (m, 2H), 6.72e6.75 (m,
3H), 6.55 (d, 4JHH¼1.6 Hz, 1H), 5.98 (s, 2H), 3.86 (s, 3H), 3.79 (s, 3H),
3.54 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 52.4, 55.2, 55.8, 101.1,
108.9, 110.4, 110.5, 112.5, 123.4, 125.4, 127.3, 129.5, 129.9, 140.7, 147.1,
148.0, 148.2, 150.0, 168.5. HRMS (ESI) m/z calcd for C19H18O6Na
(MþNa)þ 365.0996, found 365.0993.
The melting points were determined on an X-4 binocular mi-
croscope melting point apparatus (Beijing Tech Instruments Co.,
Beijing, China) and uncorrected. 1H NMR spectra were obtained
using a Bruker AC-P 300 and a Varian Mercury Plus 400 MHz
4.2.4. Methyl (E)-2-(3,4-dimethoxyphenyl)-3-(3,4-ethylenedioxyphe
spectrometers. Chemical shift values (d) are given in parts per
nyl)acrylate (4a). Yield 62%, mp 124e125 ꢁC; 1H NMR (400 MHz,
million and are downfield from internal tetramethylsilane. Ele-
mental analysis was performed on an MT-3 elemental analyzer.
HRMS was obtained on FT-ICR MS (Ionspec, 7.0 T). HPLC spectra
were obtained on a Shimadzu LC-20AT instrument. ESR spectrum
was obtained on Bruker EMX-6/1 instrument. All anhydrous sol-
vents were dried and purified by standard techniques just before
use. m-Chloroperoxybenzoic acid (m-CPBA) (a purity of 85%) and
trifluoroacetic acid (TFA) were commercially available and used
without further purification. Substrate 10a was commercially
available and used without further purification.
3
CDCl3)
d
7.69 (s, 1H), 6.89 (d, JHH¼8.0 Hz, 1H), 6.57e6.79 (m, 5H),
4.16e4.21 (m, 4H), 3.92 (s, 3H), 3.81 (s, 3H), 3.78 (s, 3H). 13C NMR
(100 MHz, CDCl3) 52.3, 55.8, 55.9, 64.0, 64.5, 114.4, 112.8, 117.0,
d
119.6, 122.1, 124.7, 128.2, 128.4, 130.2, 140.0, 143.0, 144.6, 148.6,
149.1, 168.7. Anal. Calcd for C20H20O6: C, 67.41; H, 5.66. Found: C,
67.31; H, 5.69.
4.3. General procedure for the preparation (Z)-2,3-bis(3,4-
dimethoxyphenyl)acrylic acid (7a) and (Z)-methyl-2,3-bis(3,4-
dimethoxyphenyl)acrylate (5a)
4.2. General procedure for the preparation of (E)-methyl-2,3-
disubstituted phenylacrylate
In the procedure for the synthesis of (E)-2,3-bis(3,4-dimethoxy-
phenyl)acrylic acid (2a), in the last step the aqueous layer was
acidified carefully with concentrated hydrochloric acid (pH¼5) to
afford the main product acid E-acrylic acid 2a as precipitate, which
was collected with 70% yield. And then the filtrate was acidified with
concentrated hydrochloric acid (pH¼3) to afford (Z)-2,3-bis(3,4-
dimethoxyphenyl)acrylic acid (7a) as precipitate with 15% yield.
Methylation of 7a with diazomethane afforded the corresponding
methyl ester, and recrystallization from petroleum ether and ethyl
acetate afforded the pure 5a as a white solid with 86% yield.
(E)-2,3-Disubstituted phenyl acrylic acids were obtained by
condensation of the appropriate aldehyde with the relevant
substituted phenyl acetic acid by the method of Halton and co-
workers9a or by the procedure devised by Baker and co-workers.14c
Esterification of the above acids with methanol and sulfuric acid in
the usual manner afforded the methyl ester, and recrystallization
from ethanol afforded the pure product as a white solid.
4.2.1. Methyl (E)-2,3-bis(3,4-dimethoxyphenyl)acrylate (1a). Yield
92%, mp 127e128 ꢁC (lit.9a mp 127e128 ꢁC); 1H NMR (400 MHz,
3
CDCl3)
d
7.76 (s, 1H), 6.91 (d, JHH¼8.00 Hz, 1H), 6.81(d,
4.3.1. (Z)-Methyl-2,3-bis(3,4-dimethoxyphenyl)acrylate
(5a). Mp
6.99e6.94
4JHH¼2.00 Hz, 1H), 6.80 (d, 4JHH¼1.60 Hz, 1H), 6.76 (d, 4JHH¼1.60 Hz,
148e149 ꢁC (lit.17 mp 148 ꢁC); 1H NMR (300 MHz, CDCl3)
d
3
4
1H), 6.71 (d, JHH¼8.40 Hz, 1H), 6.51 (d, JHH¼2.00 Hz, 1H), 3.89 (s,
(m, 4H), 6.89 (s,1H), 6.84e6.88 (m, 4H), 3.92 (s, 3H), 3.90 (s, 6H), 3.88
(s, 3H), 3.81 (s, 3H).
3H), 3.84 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.48 (s, 3H).
4.2.2. (E)-2,3-Bis(3,4-dimethoxyphenyl)acrylic acid (2a). Yield 70%,
mp 214e216 ꢁC (lit.16 mp 216e217 ꢁC); 1H NMR (400 MHz, DMSO)
4.3.2. (Z)-2,3-Bis(3,4-dimethoxyphenyl)acrylic acid (7a). Mp 170e
171 ꢁC (lit.17 mp 170e171 ꢁC); 1H NMR (300 MHz, CDCl3)
d 7.01e7.06

K. Wang et al. / Tetrahedron 66 (2010) 9135e9140
9139
(m, 4H), 6.95 (s, 1H), 6.84e6.90 (m, 2H), 3.92 (s, 3H), 3.91 (s, 3H),
3.90 (s, 3H), 3.86 (s, 3H).
149.2, 168.2. Anal. Calcd for C20H20O6: C, 67.79; H, 5.12. Found: C,
67.90; H, 5.17.
4. 3. 3. (Z)-2 , 3 -Bis(3, 4-d i methoxyphenyl )ac rylo nitrile
(6a). Compound 6awas prepared according to the known literature in
96% yield,18 mp 151e152 ꢁC (lit.18 mp 154e155 ꢁC); 1H NMR (400 MHz,
4.4.5. 2,3,6,7-Tetramethoxyphenanthrene-9-carbonitrile (6b). Yield
95%, mp 266e268 ꢁC (lit.20 mp 267e269 ꢁC); 1H NMR (400 MHz,
CDCl3)
d 8.05 (s, 1H), 7.78 (s, 1H), 7.75 (s, 1H), 7.57 (s, 1H), 7.22 (s,
3
3
CDCl3)
d
7.67 (d, JHH¼2.01 Hz, 1H), 7.35 (m, 2H), 7.24(dd, JHH¼8.41,
1H), 4.15 (s, 3H), 4.14 (s, 3H), 4.10 (s, 3H), 4.05 (s, 3H).
3
3
4JHH¼2.22 Hz, 1H), 7.13 (d, JHH¼2.18 Hz, 1H), 6.93 (dd, JHH¼8.47,
4.54 Hz, 2H), 3.98 (s, 3H), 3.97 (s, 3H), 3.95 (s, 3H), 3.93 (s, 3H).
4.4.6. 1,10-Binaphthyl-2,20-diamine (10b). Yield 85%, mp 190e192 ꢁC
(lit.21 mp 189e191 ꢁC); 1H NMR (300 MHz, CDCl3)
d 7.78e7.82 (m,
4.3.4. Methyl (Z)-2-(3,4-methylenedioxyphenyl)-3-(3,4-dimethoxy-
4H), 7.06e7.25 (m, 8H), 2.56e3.88 (br, 4H); HRMS (ESI) m/z calcd for
phenyl)acrylate (8a). Mp 74e76 ꢁC; 1H NMR (400 MHz, CDCl3)
C20H16N2 (MþH)þ 285.1386, found 285.1390.
d
6.79e6.94 (m, 7H), 5.98 (s, 2H), 3.89 (s, 3H), 3.87 (s, 3H), 3.80(s,
3H). 13C NMR (100 MHz, CDCl3)
d
51.3, 54.7, 54.8, 100.3, 105.5, 107.4,
Acknowledgements
109.7, 109.9, 119.3, 120.4, 127.4, 128.9, 130.2, 131.7, 146.6, 147.0, 147.7,
148.1, 169.5. HRMS (ESI) m/z calcd for C19H18O6Na (MþNa)þ
365.0996, found 365.0993.
We thank the National Key Project for Basic Research
(2010CB126100) and the National Natural Science Foundation of
China (20872072) and China Postdoctoral Science Foundation
(20090460057).
4.3.5.
a
-(30,40-Dimethoxybenzyl)-methyl 3,4-dimethoxyphenylacetate
(9a). Compound 9a was prepared by catalytic hydrogenation of 1a
by 10% Pd/C catalyst and gave a white solid in 96% yield, mp
100e101 ꢁC; 1H NMR (400 MHz, CDCl3)
d 6.82 (m, 3H), 6.71 (d,
Supplementary data
3JHH¼8.1 Hz, 1H), 6.65 (d, 3JHH¼8.2 Hz, 1H), 6.60 (s, 1H), 3.87 (s, 3H),
3.86 (s, 3H), 3.84 (s, 3H), 3.80 (s, 3H), 3.75 (dd, 3JHH¼8.6, 6.9 Hz, 1H),
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.09.101. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
2
3
3.62 (s, 3H), 3.31 (dd, JHH¼13.7 Hz, JHH¼8.6 Hz, 1H), 2.96 (dd,
2JHH¼13.7 Hz, JHH¼6.9 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 39.6,
3
52.0, 53.3, 55.7, 55.8, 55.9, 111.0, 111.1, 111.1, 112.2, 120.3, 120.9, 131.1,
131.6, 147.5, 148.3, 148.6, 149.0, 174.1. HRMS (ESI) m/z calcd for
C20H24O6Na (MþNa)þ 383.1463, found 383.1468.
References and notes
4.4. General procedure for oxidative coupling
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To a solution of 1ae8a, or 10a (1.0 mmol) in CF3COOH (20 mL)
was added m-CPBA (0.3 g, 1.5 mmol, a purity of 85%). The mixture
was stirred at room temperature for an appropriate time as shown
in Table 4. CF3COOH was recycled by rotary evaporator. CH2Cl2
(100 mL) and water (30 mL) were added and stirred. The organic
phase was washed with water (2ꢂ20 mL) again, dried over MgSO4,
filtered, and concentrated in vacuo and the residue obtained was
determined by HPLC analysis and purified by flash chromatography
on silica gel to give the desired product.
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4.4.1. Methyl
(1b). Yield 96%, mp 202e203 ꢁC (lit.18 mp 202e204 ꢁC); 1H NMR
(400 MHz, CDCl3) 8.65 (s,1H), 8.43 (s,1H), 7.81 (s,1H), 7.77 (s,1H), 7.27
2,3,6,7-tetramethoxyphenanthrene-9-carboxylate
d
6. (a) Bhakuni, D. S. J. Indian Chem. Soc. 2002, 79, 203e210; (b) Kim, S.; Lee, J.; Lee,
T.; Park, H. G.; Kim, D. Org. Lett. 2003, 5, 2703e2706; (c) Kim, S.; Lee, T.; Lee, E.;
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(s, 1H), 4.14 (s, 3H), 4.13 (s, 3H), 4.08 (s, 3H), 4.04 (s, 3H), 4.02 (s, 3H).
4.4.2. 2,3,6,7-Tetramethoxyphenanthrene-9-carboxylicacid(2b). Yield
92%, mp 285e287 ꢁC (lit.19 mp 280e282 ꢁC); 1H NMR (400 MHz,
€
Wang, Q.; Huang, R. J. Org. Chem. 2007, 72, 8416e8421; (f) Wang, K. L.; Lu, M. Y.;
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DMSO)
d 12.87 (br, 1H), 8.53 (s, 1H), 8.40 (s, 1H), 8.03 (s, 1H), 7.99 (s,
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1H), 7.55 (s, 1H), 4.04 (s, 3H), 4.03 (s, 3H), 3.89 (s, 3H), 3.87 (s, 3H).
4.4.3. Methyl
carboxylate (3b). Yield 96%, mp 209e210 ꢁC; 1H NMR (400 MHz,
CDCl3) 8.47 (s, 1H), 8.36 (s, 1H), 7.87 (s, 1H), 7.72 (s, 1H), 7.24 (s,
1H), 6.12 (s, 2H), 4.12 (s, 3H), 4.03 (s, 3H), 4.01 (s, 3H). 13C NMR
(100 MHz, CDCl3) 52.1, 55.9, 56.0, 100.1, 101.5, 102.5, 104.4, 108.8,
2,3-dimethoxy-6,7-methylenedioxyphenanthrene-9-
d
d
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123.1, 124.5, 125.1, 126.6, 127.3, 130.0, 147.7, 147.8, 149.0, 151.1, 168.2.
Anal. Calcd for C19H16O6: C, 67.05; H, 4.74. Found: C, 66.98; H, 4.60.
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4.4.4. Methyl 2,3-ethylenedioxyphenyl-6,7-dimethoxyphenanthrene-
9-carboxylate (4b). Yield 86%, mp 209e210 ꢁC; 1H NMR (400 MHz,
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CDCl3)
d 8.58 (s, 1H), 8.33 (s, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 7.37 (s,
€
1H), 4.40 (d, 4JHH¼1.2 Hz, 4H), 4.09 (s, 3H), 4.06 (s, 3H), 4.00 (s, 3H);
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13C NMR (100 MHz, CDCl3)
d 52.0, 55.8, 64.4, 64.7, 103.0, 106.9,
2009, 74, 935e938.
108.9, 115.6, 122.5, 123.7, 125.0, 127.6, 130.4, 143.4, 145.8, 148.9,
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