A simple and efficient oxidative coupling of aromatic nuclei mediated by manganese dioxide

Article abstract of DOI:10.1055/s-0029-1219237

Oxidative intramolecular coupling of the aryl rings of various stilbenes for direct construction of the phenanthrene ring system is promoted efficiently by manganese dioxide-trifluoroacetic acid at room temperature in excellent yields. This approach is also applied to the intermolecular biaryl coupling of 2-naphthols, 2-naphthalenethiol, 2-naphthylamine, a phenol ether and a phenol under very mild conditions. An electron-transfer mechanism is proposed in which manganese dioxide acts as a two-electron oxidant.

Full text of DOI:10.1055/s-0029-1219237

PAPER
1083
A Simple and Efficient Oxidative Coupling of Aromatic Nuclei Mediated by
Manganese Dioxide
Manganese
D
ioxid
a
e
M
ediated
i
O
xida
l
tive Co
i
uplingang Wang, Yanna Hu, Zheng Li, Meng Wu, 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, P. R. of China
Fax +86(22)23499842; E-mail: wang98h@263.net; E-mail: wangqm@nankai.edu.cn
Received 6 November 2009; revised 4 December 2009
terials could be used directly without prior functionaliza-
Abstract: Oxidative intramolecular coupling of the aryl rings of
tion, and the sole by-product would be two equivalents of
various stilbenes for direct construction of the phenanthrene ring
system is promoted efficiently by manganese dioxide–trifluoroace-
tic acid at room temperature in excellent yields. This approach is
hydrogen cations (H+). As such, the development of high-
ly regioselective methods for the construction of carbon–
also applied to the intermolecular biaryl coupling of 2-naphthols, 2- carbon bonds starting from arenes remains an ongoing
naphthalenethiol, 2-naphthylamine, a phenol ether and a phenol un-
synthetic challenge.
der very mild conditions. An electron-transfer mechanism is pro-
posed in which manganese dioxide acts as a two-electron oxidant.
Manganese(IV) dioxides have been extensively investi-
gated as oxidants, ion exchangers, and as soft magnetic
Key words: oxidative coupling, aromatic nuclei, manganese diox-
ide, phenanthrenes, intermolecular biaryl coupling
and electrode materials in lithium–manganese dioxide
batteries.13 They have been used for a wide range of indus-
trial applications such as ozone decomposition, photocat-
alytic oxidation of organic pollutants, nitric oxide
The construction of biaryl bonds has been studied in de-
reduction, selective oxidation of carbon monoxide, de-
tail, and various methods have been developed to synthe-
composition of hydrogen peroxide, and so on.14 However,
size natural products and important chiral auxiliaries for
to the best of our knowledge, relatively little is known
asymmetric synthesis via biaryl bond formation.1,2 Exam-
about manganese(IV) dioxide mediated intramolecular
ples include phenanthroindo(quino)lizidine alkaloids and
and intermolecular biaryl coupling reactions.15 Herein, we
1,1¢-binaphthalene derivatives. The synthesis of the
report a manganese(IV) dioxide mediated oxidative cou-
phenanthrene ring system is a key step in the preparation
pling of aromatic nuclei to form a new carbon–carbon
of such alkaloids.3 Some of the reported methods require
bond from unfunctionalized arenes under very mild con-
substrates bearing suitable functionalization.4 Metal-
ditions.
based intramolecular oxidative couplings to yield phenan-
In order to establish mild reaction conditions for the oxi-
dative coupling, we examined the intramolecular coupling
of methyl (2E)-2,3-bis(3,4-dimethoxyphenyl)acrylate
(1a) as a model compound (Table 1).
threne rings, without prior functionalization, using thalli-
um(III) trifluoroacetate (TTFA),1a,5 iron(III) chloride,
iron(III) perchlorate,6 lead(IV) tetraacetate [Pb(OAc)4],7
vanadium oxytrifluoride (VOF3) and vanadium oxy-
trichloride (VOCl3)8 have also been developed. 1,1¢-Bi-
naphthols (BINOL) have gained considerable attention in
asymmetric synthesis.2 They are typically prepared using
iron(III) or copper(II) transition metal complexes, al-
though the use of titanium(IV), vanadium(V) and rutheni-
um(III) has also been reported.9 Extensive application of
these coupling reagents is often limited by their high tox-
icity, the need for harsh reaction conditions, problems
with catalyst–product separation, and low yields.
The desired coupling product 1b was not obtained using
two equivalents of manganese dioxide as the oxidant
(Table 1, entry 1). When organic acids such as trifluoro-
acetic acid, trichloroacetic acid and tribromoacetic acid
were added, the coupling reaction proceeded successfully
and gave phenanthrene 1b in 99%, 99% and 86% yields,
respectively (Table 1, entries 2–4), showing that an acidic
environment was essential. The reaction time was signifi-
cantly longer when trichloroacetic acid and tribromoace-
tic acid were used. p-Toluenesulfonic acid and
methanesulfonic acid were efficient acids giving 1b in
89% and 73% yields, respectively (Table 1, entries 5 and
8). Acetic acid and cyanoacetic acid did not promote any
coupling – probably due to their weak acidity which was
insufficient to activate the manganese dioxide (Table 1,
entries 6 and 7). Decreasing the amount of manganese di-
oxide greatly influenced the conversions and yields; a
quantitative yield of 1b was obtained using one equivalent
(Table 1, entry 9), while the use of 0.8 and 0.5 equivalents
gave 1b in 76% and 62% yields, respectively (Table 1, en-
tries 10 and 11). The coupling also proceeded in quantitative
The most common method for biaryl carbon–carbon bond
construction is via cross-coupling between two suitably
functionalized starting materials.10,11 However, taking into
consideration operational simplicity, the availability of
starting materials, and environmental factors, a more at-
tractive approach to phenanthrenes and biaryls would in-
volve direct oxidative coupling of two unfunctionalized
arenes.1a,5–9,12 In such a transformation, both starting ma-
SYNTHESIS 2010, No. 7, pp 1083–1090
x
x
.
x
x
.2
0
1
0
Advanced online publication: 20.01.2010
DOI: 10.1055/s-0029-1219237; Art ID: F21409SS
© Georg Thieme Verlag Stuttgart · New York

1084
K. Wang et al.
PAPER
yield under an inert atmosphere (Table 1, entry 12). The
use of the mineral acids, concentrated hydrochloric acid
and dilute sulfuric acid (25%) gave 1b in 69% and 77%
yields, respectively, which indicated that this reaction was
not sensitive to water (Table 1, entries 13 and 14).
Table 2 Effect of Temperature and Concentration on the Intramo-
lecular Coupling of 1aa
Entry
Concn
(mol/L)
Temp
(°C)
Time
(h)
Conversion Yield
(%)b
100
100
100
89
(%)b
100
99
1
2
3
4
5
6
7
8
0.1
0
25
72
25
25
25
25
25
6
The effect of temperature and concentration on the in-
tramolecular coupling reaction of biaryl 1a is shown in
Table 2. The results illustrate that the coupling could be
performed over wide temperature (0–72 °C) and concen-
tration (0.01–0.5 mol/L) ranges to afford excellent yields
of phenanthrene 1b.
0.1
2
0.1
0.5
2.7
2
93
0.01
0.02
0.05
0.2
89
100
99
100
99
Consequently, the optimized reaction conditions for the
oxidative coupling were as follows: one equivalent of
manganese dioxide, a substrate concentration of 0.1 mol/
L, room temperature, and trifluoroacetic acid as the pro-
moter and solvent.
2.6
2
99
99
0.5
2.3
100
100
a Reaction conditions: 1a (0.5 mmol), MnO2 (0.5 mmol), TFA as sol-
vent.
Table 1 Effect of Acids on the Intramolecular Manganese Dioxide
Mediated Coupling of 1aa
b Conversion and yield were determined by HPLC.
OMe
OMe
MeO
MeO
MeO
Various stilbenes were tested as substrates in intramolec-
ular oxidative couplings using the optimized conditions to
give the corresponding phenanthrenes (Table 3). Both E-
and Z-stilbenes possessing an electron-withdrawing group
at the double bond were found to react smoothly to give
the corresponding coupled products in excellent yields
(Table 3, entries 1–6). In addition, a large-scale reaction
(50-fold scale) gave an identical result to that obtained
from the small-scale procedure. Interestingly, oxidative
coupling and dehydrogenation of 7a was successfully
achieved in one pot using two equivalents of manganese
dioxide to give phenanthrene 1b in 93% yield (Table 3,
entry 7). By contrast, stilbene 8a with no substituent on
the aryl groups, and stilbene 9a possessing an electron-
withdrawing group on one of the aromatic rings did not
give the corresponding coupled products (Table 3, entries
8 and 9).
O
O
MnO2
acid
OMe
OMe
MeO
OMe
OMe
1a
1b
Entry MnO2 Acid (equiv)
(equiv)
Time Conversion Yield
(h)
(%)b
(%)b
1
2
2
none
6
0
0
2
TFAc
1
100
100
93
99
99
86
89
0
3
2
Cl3CCOOH (10)
Br3CCOOH (10)
PTSA (10)
MeCOOHc
NCCH2COOH (10)
MsOHc
24
36
23
15
15
6
4
2
We have also applied this approach to intermolecular bi-
aryl coupling reactions (Table 4). Various 2-naphthols
10a–12a reacted to give the corresponding 1,1¢-binaph-
thols 10b–12b, respectively (Table 4, entries 1–5). The
use of methanesulfonic acid instead of trifluoroacetic acid
resulted in increased yields of the coupled products
(Table 4, entries 1–4). Simultaneous carbon–carbon and
sulfur–sulfur bond formation in naphthalene-2-thiol (13a)
was accomplished readily to give 3,4-dithia-diben-
zo[c,g]phenanthrene (13b) in 76% yield (Table 4, entry
6). Naphthalen-2-amine (14a) was coupled using manga-
nese dioxide to give 1,1¢-binaphthyl-2,2¢-diamine (14b) in
55% yield (Table 4, entry 7). A similar reaction of 3,4-
dimethoxytoluene (15a) gave the coupled biphenyl 15b in
56% yield (Table 4, entry 8). As a preliminary attempt to
further the application of manganese dioxide, the coupling
reaction of 2,6-di-tert-butylphenol (16a) was carried out
to yield diphenoquinone 16b in 88% yield (Table 4, entry
9), however, none of the expected biphenol was detected.
This reaction would appear to be similar to the enzymatic
reaction of laccase.16
5
2
97
6
2
0
7
2
0
0
8
2
100
100
77
73
100
76
62
100
69
77
9
1
TFAc
2
10
11
12d
13e
14e
0.8
0.5
1
TFAc
10
6
TFAc
63
TFAc
2
100
94
1
concd HCl (1 mL)
25% H2SO4 (2 mL)
24
15
1
78
a Reaction conditions: MnO2, acid, 1a (0.5 mmol, 0.1 mol/L), CH2Cl2
(5.0 mL) (unless otherwise noted), r.t.
b Conversion and yield were determined by HPLC.
c The acid also acts as the solvent.
d Reaction under an N2 atmosphere.
e MeCN was used as the solvent.
Synthesis 2010, No. 7, 1083–1090 © Thieme Stuttgart · New York

PAPER
Manganese Dioxide Mediated Oxidative Coupling
1085
a
Table 3 An Investigation of the Substrate Scope of the Intramolecular Oxidative Coupling Using MnO2
Entry
Substrate
Product
Time
(h)
Conversion Yield
(%)b
(%)c
OMe
OMe
MeO
MeO
CO2Me
CO2Me
1
1a
1b
2
100
98
94
95
98
91
95
MeO
MeO
MeO
MeO
OMe
OMe
OMe
OMe
CO2H
CO2H
2
3
4
5
6
2a
3a
4a
5a
6a
2b
3b
1b
5b
2b
8
100
MeO
O
MeO
O
OMe
OMe
O
O
CO2Me
CO2Me
2
97
MeO
MeO
MeO
MeO
OMe
OMe
OMe
OMe
COOMe
CO2Me
2
99
OMe
OMe
OMe
MeO
MeO
OMe
OMe
OMe
OMe
MeO
CN
CN
12
99
MeO
MeO
OMe
OMe
OMe
OMe
MeO
COOH
CO2H
6
100
MeO
OMe
OMe
Synthesis 2010, No. 7, 1083–1090 © Thieme Stuttgart · New York

1086
K. Wang et al.
PAPER
a
Table 3 An Investigation of the Substrate Scope of the Intramolecular Oxidative Coupling Using MnO2 (continued)
Entry
Substrate
Product
Time
(h)
Conversion Yield
(%)b (%)c
OMe
OMe
MeO
MeO
MeO
MeO
CO2Me
CO2Me
7d
7a
1b
4.5
98
93
OMe
OMe
COOMe
8
9
8a
9a
no product
no product
6
6
0
0
0
0
COOH
Cl
a MnO2 (0.5 mmol).
b Conversion was determined by HPLC.
c Yield of isolated product.
d MnO2 (1.0 mmol).
a
Table 4 An Investigation of the Substrate Scope of the Intermolecular Oxidative Coupling Using MnO2
Entry
Substrate
Product
Time
(h)
Conversion Yield
(%)b
(%)c
1
5.5
8
100
100
56
73
OH
OH
10a
10b
2d
OH
Br
Br
Br
3
17
17
100
100
52
64
OH
OH
11a
11b
4d
OH
COOMe
COOMe
OH
OH
OH
5
6
12a
13a
12b
13b
9.5
100
100
55
76
COOMe
S
S
24
SH
Synthesis 2010, No. 7, 1083–1090 © Thieme Stuttgart · New York

PAPER
Manganese Dioxide Mediated Oxidative Coupling
1087
Table 4 An Investigation of the Substrate Scope of the Intermolecular Oxidative Coupling Using MnO2a (continued)
Entry
Substrate
Product
Time
(h)
Conversion Yield
(%)b
(%)c
NH2
NH2
7
14a
14b
24
100
55
NH2
OMe
OMe
OMe
OMe
8e
15a
16a
15b
16b
1.2
100
100
56
88
MeO
OMe
t-Bu
O
t-Bu
t-Bu
9f
8
O
HO
t-Bu
t-Bu
t-Bu
a Reaction conditions: substrate (1 mmol), MnO2 (1 mmol), TFA (10 mmol), CH2Cl2 (10 mL), r.t.
b Conversion was determined by HPLC.
c Yield of isolated product.
d MsOH (10 mmol) was used as the acid.
e Conversion was determined by GC.
f Conversion was determined by 1H NMR spectroscopy.
No mechanism has yet been postulated for the above cou- radical cation in similar species has been provided by an-
pling reactions employing manganese dioxide, however, odic oxidation studies.18 To further clarify the mechanism
similar oxidants such as thallium trifluoroacetate17 are be- of the present manganese dioxide mediated oxidative cou-
lieved to promote electron transfer and to form radical cat- pling the electron spin resonance (ESR) spectrum was re-
ions with electron-rich substrates. Taking substrates 1a corded for the coupling reaction of 1a. As shown in
and 10a as examples, the carbon–carbon bond formation Figure 1, a sharp signal at g = 2.005 was observed, which
could occur via coupling of a pair of radical cations can be assigned to a bis-radical cation derived from 1a.
(Scheme 1). Strong evidence for the formation of a bis- Stoichiometrically, one mole of manganese dioxide can
OMe
OMe
OMe
OMe
MeO
MeO
MeO
MeO
Mn(IV) Mn(II)
– 2e–
COOMe
COOMe
COOMe
COOMe
– 2H+
H
H
MeO
MeO
MeO
MeO
OMe
OMe
OMe
OMe
1a
1b
Mn(II)
– 2e–
Mn(IV)
– 2H+
O
O
H
OH
OH
H
2
2
H
H
OH
OH
H
10a
10b
Scheme 1 Proposed mechanisms for the manganese dioxide mediated intra- and intermolecular oxidative coupling reactions
Synthesis 2010, No. 7, 1083–1090 © Thieme Stuttgart · New York

1088
K. Wang et al.
PAPER
Agilent 6890N instrument. HPLC spectra were recorded using Ag-
ilent 1100 and Shimadzu LC-20AT instruments. The ESR spectrum
was recorded on a Bruker EMX-6/1 instrument. All solvents were
dried and purified by standard techniques prior to use. Petroleum
ether (PE) refers to the fraction boiling in the 60–90 °C range. MnO2
(99% purity, 2 mm particle size, or powder) is commercially avail-
able from J & K Chemical Ltd or Alfa Aesar China (Tianjin Co.,
Ltd.), respectively, and was used without further purification. Col-
umn chromatography was carried out on 400–600 mesh silica gel
(Qingdao Haiyang Chemical Co., Ltd., China). Substrates 10a–16a
were purchased from Alfa Aesar China (Tianjin Co., Ltd.). Sub-
strates 1a–9a were prepared according to the literature6 and prod-
ucts 1b, 2b, 5b, 10b–12b and 14b–16b were identified by
comparison of their melting points and 1H NMR spectroscopic data
with those reported in the literature (see characterization data for
references).
oxidize one mole of stilbene 1a to give one mole of 1b,
showing that reduction of manganese dioxide is a two-
electron transfer process. This was further confirmed by
the ESR spectrum shown in Figure 1; the multiple peaks
(A = 94 gauss) can be assigned to a manganese center. An
acidic environment is required for the protonation of man-
ganese dioxide and to increase its oxidative ability. Based
on the above experimental results, we propose the reac-
tion mechanism depicted in Scheme 1 for the present oxi-
dative couplings.
Perkin Condensation; Typical Procedure
(3,4-Dimethoxyphenyl)acetic acid (98.0 g, 0.5 mol), 3,4-dimeth-
oxybenzaldehyde (90.0 g, 0.54 mol), Ac2O (200 mL) and Et3N (100
mL) were heated at reflux for 20 h with the exclusion of moisture.
The soln was allowed to cool to r.t., H2O (400 mL) was added, and
the mixture was stirred for 1 h. The reaction mixture was poured
into aq K2CO3 soln (350.0 g in 800 mL of H2O) and heated at reflux
until nearly all the gummy material had dissolved. The soln was
cooled, extracted with Et2O (3 × 120 mL), and carefully acidified
with concd HCl (pH 4–5) to produce a white precipitate. The solid
was collected and recrystallized from MeOH to give acid 2a.
(2E)-2,3-Bis(3,4-dimethoxyphenyl)acrylic Acid (2a)
White solid; yield: 118.7 g (69%); mp 214–216 °C (Lit.19 mp 216–
217 °C).
1H NMR (400 MHz, DMSO-d6): d = 12.50 (br s, 1 H), 7.68 (s, 1 H),
6.98–6.54 (m, 6 H), 3.74 (s, 3 H), 3.69 (s, 3 H), 3.66 (s, 3 H), 3.45
(s, 3 H).
Figure 1 ESR spectrum of the manganese dioxide mediated oxida-
tive coupling. Manganese dioxide (1 equiv) was treated with 1a (0.5
mmol) in trifluoroacetic acid and the spectrum recorded after 45 mi-
nutes
In summary, we have developed manganese dioxide me-
diated intramolecular and intermolecular oxidative cou-
plings of arenes. The mechanistic investigation suggests
that the reaction probably proceeds via homolytic cou-
pling of two radical species with manganese dioxide act-
ing as a two-electron oxidant. The present system has the
following advantages: (i) carbon–carbon bonds can be
formed from arenes without prior functionalization, (ii)
the coupling has been applied to both intramolecular and
intermolecular reactions, (iii) the reaction conditions are
mild and the work-up procedures are simple with high
yields being obtained, (iv) the procedure can be scaled-up,
and (v) manganese dioxide is a readily available oxidant.
Further studies on the synthetic applications of this car-
bon–carbon bond forming reaction are in progress.
Methyl (2E)-2,3-Bis(3,4-dimethoxyphenyl)acrylate (1a)
2,3-Bis(3,4-dimethoxyphenyl)acrylic acid 2a (3.44 g, 10.0 mmol)
was dissolved in a solution of 1.5% concd H2SO4 in anhyd MeOH
(150 mL), and the resulting solution was heated to reflux for 10 h.
After evaporating the solvent under reduced pressure, CHCl3 (100
mL) and H2O (50 mL) were added to the residual oil. The mixture
was washed with 10% NaHCO3 (50 mL), H2O (40 mL), and brine,
and dried over Na2SO4. The solvent was evaporated to afford the
crude product which was recrystallized from EtOH to give 1a.
White solid; yield: 3.29 g (92%); mp 127–128 °C (Lit.8b mp 127–
128 °C).
1H NMR (400 MHz, CDCl3): d = 7.76 (s, 1 H), 6.91 (d, 3JHH = 8.0
Hz, 1 H), 6.81 (d, 4JHH = 2.0 Hz, 1 H), 6.80 (d, 4JHH = 1.6 Hz, 1 H),
6.76 (d, 4JHH = 1.6 Hz, 1 H), 6.71 (d, 3JHH = 8.4 Hz, 1 H), 6.51 (d,
4JHH = 2.0 Hz, 1 H), 3.89 (s, 3 H), 3.84 (s, 3 H), 3.81 (s, 3 H), 3.79
(s, 3 H), 3.48 (s, 3 H).
Methyl (2E)-2-(1,3-Benzodioxol-5-yl)-3-(3,4-dimethoxyphe-
nyl)acrylate (3a)
White solid; yield: 68%; mp 101–103 °C.
1H NMR (400 MHz, CDCl3): d = 7.77 (s, 1 H), 6.87–6.83 (m, 2 H),
6.75–6.72 (m, 3 H), 6.55 (d, 4JHH = 1.6 Hz, 1 H), 5.98 (s, 2 H), 3.86
(s, 3 H), 3.79 (s, 3 H), 3.54 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 168.5, 150.0, 148.2, 148.0, 147.1,
140.7, 129.9, 129.5, 127.3, 125.4, 123.4, 112.5, 110.5, 110.4, 108.9,
101.1, 55.8, 55.2, 52.4.
Melting points were determined on an X-4 binocular microscope
melting point apparatus (Beijing Tech Instruments Co., Beijing,
China) and are uncorrected. H NMR spectra were obtained using
1
Bruker AC-P 300 and Varian Mercury Plus 400 MHz spectrome-
ters. Chemical shifts (d) are given in ppm and are downfield with re-
spect to the internal standard TMS. 13C NMR spectra were recorded
using Bruker AC-P 300 (at 75 MHz) or AV 400 (at 100 MHz) spec-
trometers with CDCl3 as the solvent. Chemical shifts (d) are report-
ed in ppm with respect to the solvent peak (77.0 ppm). HRMS
spectra were obtained using FT-ICR MS (Ionspec, 7.0T) instrumen-
tation. Elemental analyses were determined on a Yanaco CHN
Corder MT-3 elemental analyzer. GC spectra were obtained on an
HRMS (ESI): m/z calcd for C19H18O6Na: 365.0996; found:
365.0993.
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PAPER
Manganese Dioxide Mediated Oxidative Coupling
1089
Methyl (2E)-2,3-Diphenylacrylate (8a)
r.t. for 2 h. The mixture was diluted with CH2Cl2 (50 mL) and H2O
(20 mL). The organic phase was washed with H2O (3 × 20 mL),
dried over MgSO4, filtered, and concd in vacuo to yield pure 1b (as
determined by HPLC analysis).
White solid; yield: 60%; mp 76–77 °C (Lit.8b mp 76–77 °C).
1H NMR (400 MHz, CDCl3): d = 7.86 (s, 1 H), 7.38–7.35 (m, 3 H),
7.23–7.14 (m, 5 H), 7.04–7.02 (m, 2 H), 3.79 (s, 3 H).
Methyl 2,3,6,7-Tetramethoxyphenanthrene-9-carboxylate (1b)
(2E)-3-(4-Chlorophenyl)-2-phenylacrylic Acid (9a)
White solid; yield: 98%; mp 202–203 °C (Lit.8e mp 202–204 °C).
White solid; yield: 60%; mp 207–209 °C (Lit.20 mp 210–211 °C).
1H NMR (400 MHz, CDCl3): d = 8.65 (s, 1 H), 8.43 (s, 1 H), 7.81
(s, 1 H), 7.77 (s, 1 H), 7.27 (s, 1 H), 4.14 (s, 3 H), 4.13 (s, 3 H), 4.08
(s, 3 H), 4.04 (s, 3 H), 4.02 (s, 3 H).
1H NMR (400 MHz, DMSO-d6): d = 12.79 (s, 1 H), 7.73 (s, 1 H),
7.38–7.03 (m, 9 H).
(2Z)-2,3-Bis(3,4-dimethoxyphenyl)acrylic Acid (6a)
2,3,6,7-Tetramethoxyphenanthrene-9-carboxylic Acid (2b)
The same procedure as that used for the synthesis of 2a was fol-
lowed, except in the last step the aq layer was acidified carefully
with concd HCl (pH 5) to afford a precipitate of 2a as the major
product which was obtained in 69% yield after filtration. The filtrate
was acidified with concd HCl (pH 3) to afford (Z)-2,3-bis(3,4-
dimethoxyphenyl)acrylic acid (6a) as a precipitate. Recrystalliza-
tion from a mixture of PE–EtOAc afforded pure 6a.
White solid; yield: 94%; mp 285–287 °C (Lit.23 mp 280–282 °C).
1H NMR (400 MHz, DMSO-d6): d = 12.87 (br s, 1 H), 8.53 (s, 1 H),
8.40 (s, 1 H), 8.03 (s, 1 H), 7.99 (s, 1 H), 7.55 (s, 1 H), 4.04 (s, 3 H),
4.03 (s, 3 H), 3.89 (s, 3 H), 3.87 (s, 3 H).
Methyl 2,3-Dimethoxyphenanthro[2,3-d][1,3]dioxole-6-oate
(3b)
White solid; yield: 15%; mp 170–171 °C (Lit.21 mp 170–171 °C).
White solid; yield: 95%; mp 209–210 °C.
1H NMR (300 MHz, CDCl3): d = 7.06–7.01 (m, 4 H), 6.95 (s, 1 H),
6.90–6.84 (m, 2 H), 3.92 (s, 3 H), 3.91 (s, 3 H), 3.90 (s, 3 H), 3.86
(s, 3 H).
1H NMR (400 MHz, CDCl3): d = 8.47 (s, 1 H), 8.36 (s, 1 H), 7.87
(s, 1 H), 7.72 (s, 1 H), 7.24 (s, 1 H), 6.12 (s, 2 H), 4.12 (s, 3 H), 4.03
(s, 3 H), 4.01 (s, 3 H).
Methyl (2Z)-2,3-Bis(3,4-dimethoxyphenyl)acrylate (4a)
To a stirred solution of stilbene 6a (1.72 g, 5 mmol) in CH2Cl2 was
added ethereal diazomethane at 0 °C until the substrate 6a had dis-
appeared, as indicated by TLC; the mixture was stirred at r.t. for an
additional 1 h. The solvent was allowed to evaporate and the residue
was recrystallized from a mixture of PE–EtOAc to afford methyl es-
ter 4a.
White solid; yield: 1.54 g (86%); mp 148–149 °C (Lit.21 mp
148 °C).
1H NMR (300 MHz, CDCl3): d = 6.99–6.94 (m, 4 H), 6.89–6.84 (m,
3 H), 3.92 (s, 3 H), 3.90 (s, 6 H), 3.88 (s, 3 H), 3.81 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 168.2, 151.1, 149.0, 147.8, 147.7,
130.0, 127.3, 126.6, 125.1, 124.5, 123.1, 108.8, 104.4, 102.5, 101.5,
100.1, 56.0, 55.9, 52.1.
Anal. Calcd for C19H16O6: C, 67.05; H, 4.74. Found: C, 66.98; H,
4.60.
2,3,6,7-Tetramethoxyphenanthrene-9-carbonitrile (5b)
Yellow solid; yield: 91%; mp 266–268 °C (Lit.22 mp 267–269 °C).
1H NMR (400 MHz, CDCl3): d = 8.05 (s, 1 H), 7.78 (s, 1 H), 7.75
(s, 1 H), 7.57 (s, 1 H), 7.22 (s, 1 H), 4.15 (s, 3 H), 4.14 (s, 3 H), 4.10
(s, 3 H), 4.05 (s, 3 H).
(2Z)-2,3-Bis(3,4-dimethoxyphenyl)acrylonitrile (5a)
Intermolecular Oxidative Coupling; Typical Procedure
Compound 5a was prepared according to a literature procedure.22
To a soln of 10a (144 mg, 1.0 mmol) in CH2Cl2 (10.0 mL) at r.t. was
added MnO2 (88.9 mg, 1.0 mmol) and TFA (1.14 g, 10.0 mmol).
The mixture was stirred at r.t. for 5.5 h and then diluted with CH2Cl2
(50 mL) followed by H2O (20 mL). The organic phase was washed
with H2O (3 × 20 mL), dried over MgSO4, filtered and concentrated
in vacuo. The crude material was purified by flash column chroma-
tography on silica gel (PE–EtOAc, 2:1) to give product 10b.
Yellow solid; yield: 96%; mp 151–152 °C (Lit.22 mp 154–155 °C).
1H NMR (400 MHz, CDCl3): d = 7.67 (s, 1 H), 7.37–7.34 (m, 2 H),
7.24 (d, 3JHH = 8.4 Hz, 1 H), 7.13 (s, 1 H), 6.94–6.90 (m, 2 H), 3.98
(s, 3 H), 3.97 (s, 3 H), 3.95 (s, 3 H), 3.93 (s, 3 H).
Methyl 2,3-Bis(3,4-dimethoxyphenyl)propanoate (7a)
Methyl (2E)-2,3-bis(3,4-dimethoxyphenyl)acrylate (1a) (358 mg, 1
mmol) was dissolved in EtOH (200 mL) and 10% Pd/C (100 mg)
was added. H2 gas was bubbled through the soln which was stirred
for 3 h. The catalyst was removed by filtration and the filtrate was
concd in vacuo to afford pure 7a.
1,1¢-Binaphthalene-2,2¢-diol (10b)
White solid; yield: 56%; mp 216–218 °C (Lit.24 mp 217–218 °C).
1H NMR (400 MHz, CDCl3): d = 7.98 (s, 1 H), 7.95 (s, 1 H), 7.90
(s, 1 H), 7.89 (s, 1 H), 7.40–7.36 (m, 4 H), 7.33–7.29 (m, 2 H), 7.17
(s, 1 H), 7.15 (s, 1 H), 5.06 (s, 2 H).
White solid; yield: 96%; mp 100–101 °C.
1H NMR (400 MHz, CDCl3): d = 6.83–6.79 (m, 3 H), 6.74 (d,
3JHH = 8.4 Hz, 1 H), 6.65 (d, 3JHH = 8.0 Hz, 1 H), 6.60 (s, 1 H), 3.87
(s, 3 H), 3.86 (s, 3 H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.74 (t, 3JHH = 7.6
Hz, 1 H), 3.62 (s, 3 H), 3.32 (dd, 2JHH = 13.6 Hz, 3JHH = 8.4 Hz, 1
H), 2.95 (dd, 2JHH = 13.6 Hz, 3JHH = 6.9 Hz, 1 H).
6,6¢-Dibromo-1,1¢-binaphthalene-2,2¢-diol (11b)
White solid; yield: 52%; mp 200–202 °C (Lit.25 mp 197–198 °C).
1H NMR (400 MHz, CDCl3): d = 8.05 (s, 2 H), 7.90 (s, 1 H), 7.88
(s, 1 H), 7.40–7.36 (m, 4 H), 6.97 (s, 1 H), 6.95 (s, 1 H), 5.04 (s, 2
H).
13C NMR (75 MHz, CDCl3): d = 174.1, 149.0, 148.6, 148.3, 147.5,
131.6, 131.1, 120.9, 120.3, 112.2, 111.1, 111.1, 111.0, 55.9, 55.8,
55.7, 53.3, 52.0, 39.6.
Dimethyl2,2¢-Dihydroxy-1,1¢-binaphthalene-3,3¢-dicarboxylate
(12b)
White solid; yield: 55%; mp 285–287 °C (Lit.26 mp 280–283 °C).
HRMS (ESI): m/z calcd for C20H24O6Na: 383.1463; found:
383.1468.
1H NMR (400 MHz, CDCl3): d = 10.73 (s, 2 H), 8.70 (s, 2 H), 7.94–
7.91 (m, 2 H), 7.36–7.33 (m, 4 H), 7.18–7.15 (m, 2 H), 4.06 (s, 6 H).
Intramolecular Oxidative Coupling; Typical Procedure
To a soln of 1a (179 mg, 0.5 mmol) in TFA (5.0 mL) was added
MnO2 (44.4 mg, 0.5 mmol) and the reaction mixture was stirred at
3,4-Dithia-dibenzo[c,g]phenanthrene (13b)
Light-yellow solid; yield: 76%; mp 180–181 °C.
Synthesis 2010, No. 7, 1083–1090 © Thieme Stuttgart · New York

1090
K. Wang et al.
PAPER
1H NMR (400 MHz, CDCl3): d = 8.52 (s, 1 H), 8.50 (s, 1 H), 7.85
(s, 1 H), 7.83 (s, 1 H), 7.76–7.74 (m, 2 H), 7.67–7.59 (m, 4 H), 7.53–
7.50 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 134.0, 133.3, 133.0, 132.0, 128.4,
127.8, 127.1, 126.5, 126.4, 124.4.
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Anal. Calcd for C20H12S2: C, 75.91; H, 3.82. Found: C, 76.11; H,
3.72.
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44, 4046. (b) Campeau, L. C.; Parisien, M.; Jean, A.;
Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581. (c)Lafrance,
M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem.
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(b) Li, Z. P.; Li, C. J. J. Am. Chem. Soc. 2005, 127, 6968.
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46, 6505.
1,1¢-Binaphthalene-2,2¢-diamine (14b)
Brown solid; yield: 55%; mp 190–192 °C (Lit.27 mp 189–191 °C).
1H NMR (300 MHz, CDCl3): d = 7.82–7.78 (m, 4 H), 7.25–7.06 (m,
8 H), 3.88–2.56 (br s, 4 H).
4,4¢,5,5¢-Tetramethoxy-2,2¢-dimethylbiphenyl (15b)
White solid; yield: 56%; mp 121–122 °C (Lit.28 mp 121–122 °C).
1H NMR (400 MHz, CDCl3): d = 6.77 (s, 2 H), 6.65 (s, 2 H), 3.91
(s, 6 H), 3.83 (s, 6 H), 2.02 (s, 6 H).
3,3¢,5,5¢-Tetra-tert-butyl-1,1¢-bi(cyclohexa-2,5-dien-1-ylidene)-
4,4¢-dione (16b)
(12) (a) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97,
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L.; Lanni, E. L.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128,
14047.
Red solid; yield: 88%; mp 244–246 °C (Lit.29 mp 246 °C).
1H NMR (400 MHz, CDCl3): d = 7.71 (s, 4 H), 1.37 (s, 36 H).
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Acknowledgment
We are grateful to the National Key Project for Basic Research
(2010CB126100) and the National Natural Science Foundation of
China (20872072) for financial support.
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Synthesis 2010, No. 7, 1083–1090 © Thieme Stuttgart · New York