Semiconductor-mediated oxidative dimerization of 1-naphthols with dioxygen and O-demethylation of the enol-ethers by SnO2 without dioxygen

Article abstract of DOI:10.1016/j.tet.2004.09.003

Oxidative dimerization of 1-naphthols 1 with dioxygen in the presence of a semiconductor, such as SnO₂, ZrO₂, or activated charcoal, as a catalytic mediator takes place selectively to give the corresponding 2,2′-binaphthols 2 or 2,2′-binaphthyl-1,1′-quinones 3 in excellent yields without light irradiation. The catalytic activity of SnO ₂ could be fully restored by appropriate reactivation treatment after the oxidation. In addition, SnO₂ without dioxygen catalyzes selective O-demethylation of the enol-ethers 3 to 4. Graphical Abstract.

Full text of DOI:10.1016/j.tet.2004.09.003

Tetrahedron 60 (2004) 10681–10693
Semiconductor-mediated oxidative dimerization of 1-naphthols
with dioxygen and O-demethylation of the enol-ethers by SnO2
without dioxygen
*
Tetsuya Takeya, Tsuyoshi Otsuka, Iwao Okamoto and Eiichi Kotani
Showa Pharmaceutical University, 3-3165 Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Received 3 August 2004; revised 1 September 2004; accepted 1 September 2004
Available online 25 September 2004
Abstract—Oxidative dimerization of 1-naphthols 1 with dioxygen in the presence of a semiconductor, such as SnO2, ZrO2, or activated
charcoal, as a catalytic mediator takes place selectively to give the corresponding 2,20-binaphthols 2 or 2,20-binaphthyl-1,10-quinones 3 in
excellent yields without light irradiation. The catalytic activity of SnO2 could be fully restored by appropriate reactivation treatment after the
oxidation. In addition, SnO2 without dioxygen catalyzes selective O-demethylation of the enol-ethers 3 to 4.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Mn(III), Cu(II), etc., in homogeneous solution.2j–m In most
cases, however, the coupling reactions are not catalytic, but
require more-than-stoichiometric amounts of oxidants.
There are some exceptions employing such catalyst systems
as oxovanadium (IV)–amino acid complex, Ru (II)–salen
complex, etc., under dioxygen (O2) as coupling reagents.2j,3
In the oxidation of naphthols, the use of homogeneous
oxidants often leads to poor selectivity and low yield of the
desired products, accompanied with side reactions, so that
the reactions are difficult to control. Recently, solid Lewis
acids,4 such as FeCl3 have been used as heterogeneous
catalysts, either alone or in binary combinations such as
CuSO4/Al2O3 and FeCl3/montmorillonite, with aerial
oxygen or dioxygen for oxidative coupling of 2-naphthols.
Aryl–aryl bond formation is one of the most important tools
of modern organic synthesis. These bonds are found in
natural biaryls such as binaphthoquinones, binaphthols,
lignans, alkaloids, flavonoids, and coumarins,1 as well as in
many pharmaceuticals and agrochemicals.
In general, the methods for construction of aryl–aryl bonds
(biaryl frameworks) can be classified into two types: (i) the
oxidative (biomimetic) coupling of various aromatic
compounds using an electrochemical2a–i or a chemical
method2j–m,3,4 and (ii) a transition-metal-catalyzed coupling
of aryl halides, for example, the palladium-catalyzed Still
and Suzuki reactions.2j Oxidative coupling of hydroxy-
arenes (so-called oxidative dimerization of hydroxyarenes)
commonly involves oxidative dehydrogenation and sub-
sequent C–C or C–O coupling of the resulting arenyl
radical.
The replacement of current stoichiometric oxidations for the
production of fine chemicals with environmentally benign
catalytic oxidations is one of the major tasks in green
chemistry. Dioxygen seems to be an ideal oxidant for such
purposes, as well as for biomimetic synthesis of natural
products, because the supply is ample, and the molecule is
environmentally friendly and nontoxic. In addition,
dioxygen participates in many metabolic processes in
mammalians and plants.5
We have focused on the oxidative dimerization of naphthols
as a means to construct biaryl frameworks, aiming at
biomimetic synthesis of natural products such as binaphtho-
quinones and binaphthols. Various methods have been
developed for the preparation of binaphthols and their
derivatives by the oxidative coupling of naphthols using a
range of oxidants, such as metal salts, Ag(I), Pb(IV), Fe(III),
Recently, much attention has been focused on the use of
various semiconductor catalysts,6a,b particularly TiO2,6cto
achieve a variety of organic reactions and syntheses based
on the concept of green chemistry.7 Semiconductors (SC)
are usually used as sensitizers in heterogeneous photo-
catalytic oxidations. They are particularly useful from an
Keywords: Semiconductor; Dioxygen; Oxidative coupling; Demethylation;
Binaphthol.
* Corresponding author. Tel./fax: C81 427211579;
e-mail: takeya@ac.shoyaku.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.003

10682
T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
environmental viewpoint, because they are almost nontoxic,
stable, and inexpensive. Several such reactions have been
reported, including oxygenations and oxidative cleavage.6
From practical and environmental viewpoints, SC should be
advantageous as heterogeneous catalysts, and it is expected
that dioxygen can be effectively used for the facile
regeneration of such catalysts in a catalytic cycle. However,
to our knowledge, there has been no report to date on
oxidative dimerization of 1-naphthols (NPOH) with
dioxygen using SC in the absence of light irradiation.
obtained at all, and in this case 2a and 3a were obtained in
yields of 64 and 28%, respectively (entry 6). The reason for
this is discussed below. The catalyst (SnO2) could be easily
recovered by simple filtration and washing with CH2Cl2,
followed by drying at 130 8C for 12 h under reduced
pressure before re-use. The recovered SnO2 showed almost
unchanged catalytic reactivity, since repeated reaction (five
times) with 1a using the recovered SnO2 in MeCN under
identical conditions gave similar results to that of entry 6 in
all cases. However, recovered ZrO2 and Act-C did not re-
acquire full catalytic activity after the above reactivation
treatment.
In a previous communication,8c we reported that semi-
conductors efficiently mediate the oxidative dimerization of
1-naphthols (1; NPOH) to the corresponding 2,20-
binaphthyls in the presence of dioxygen (O2). Here, we
present the results of a detailed study of the oxidative
reaction of NPOH 1 with various SC/O2 systems.
Similar reactions were explored using 1b or 1c,11 which can
be precursors for the synthesis of binaphthyl natural
products (Table 1).10
In the case of 1b, the best result was obtained with the ZrO2/
O2 system in MeCN for 0.75 h, affording 3b selectively in
excellent yield (entry 9). The reaction with the SnO2/O2
system under similar conditions gave a complex mixture
containing a substantial amount of 2b. In order to isolate 2b,
we performed column chromatography of the reaction
mixtures under various conditions. However, all the
attempts were unsuccessful, producing mainly solid
mixtures of 2b and 3b. Therefore, the mixture of 2b and
3b was treated with benzyl bromide/K2CO3 to give 5 (81%)
as a major product together with nonreacted 3b (2%)
(entry 10).
2. Results and discussion
We investigated the oxidation of NPOH 1a–d, f (including
precursors for the synthesis of natural products) and the
naphthol ether 1e using several SCs6 [TiO2, Nb2O5, SnO2,
ZrO2, activated charcoal (Act-C),9 etc.] and solvents
saturated with dioxygen [CH2Cl2, MeCN, MeNO2, etc.]
without light irradiation. We found that the nature of the
major products depended upon the substrates (NPOH) in
oxidation with the SC/O2 system. In particular, there was a
difference between oxidation of 1a–c having a methoxyl
group and oxidation of 1f having a methyl group at the C-4
position. Three types of reactions in the presence of
semiconductors were found: (1) the oxidative dimerization
of NPOH 1a–c to 2,20-binaphthyls 2 and 3 under O2, (2)
selective demethylation of 2,20-binaphthyl-1,10-quinones
3a–c (enol-ethers) to 10-hydroxy-2,20-binaphthyl-1,4-
quinones 4 without O2, and (3) the oxidative conversion
of 1f to the naphthol trimers 8 and 9 under O2.
In the case of 1c, the best result was obtained with the SnO2/
O2 system in MeCN. This oxidative coupling was very
sluggish, but selectively afforded 2c in good yield (entry
13). In all experiments with 1c using various semi-
conductors, a longer period of reaction was required for
completion of the reaction, in comparison with the cases of
1a, b. This may be owing to the influence of the hydrogen-
bond formation12 between the hydroxyl proton (at C1) and
the methoxyl group (at C8) in 1c, as shown in Scheme 1,
though this remains to be confirmed.
2.1. Oxidative dimerization of NPOH 1a–1e with various
SC/O2 systems
When the a-naphthol 1d without substituents other than a
hydroxyl group at the C-1 position was used, the oxidative
biaryl coupling reaction did not proceed at all (entries 14–
16). In the case of the naphthol-ether 1e with the SnO2/O2
system, the reaction also did not proceed under similar
conditions (entry 17). No reaction of 1a with ZrO2 under air
took place at all under similar conditions (entry 18). Finally,
the reaction of 1b with the well-known oxidant Ag2O in
chloroform was examined, but gave only a mixture of the
coupling product and its oxidized quinone (entry 19).
Preliminary experiments on the oxidative dimerization were
done with NPOH 1a as a substrate using several SCs6 and
solvents saturated with dioxygen under various conditions,
and the results are shown in Table 1. The best result was
obtained with Act-C in CH2Cl2 (entry 1). That is, the
reaction of 1a using the Act-C/O2 reagent system in the
presence of O2 in CH2Cl2 afforded selectively the so-called
Russig’s Blue,10a 2,20-binaphthyl-1,10-quinone (3a; BNPQ),
in excellent yield. A similar result was obtained in the dark.
Noteworthy features of the above reactions were as follows.
The hydroxyl group in 1a–c was required for the formation
of the binaphthyl derivatives, based on the result of entry 17.
The SC-mediated oxidation of 1a–c in the presence of O2
made it possible to control the synthesis in the direction of
either 3 or 2. For example, the reaction of 1a or 1b with the
Act-C/O2 or the ZrO2/O2 system afforded the corresponding
3a or 3b, respectively, in excellent yield, while the reaction
of 1c with the SnO2/O2 system gave 2c in high yield. The SC
was essential for the catalysis of the present oxidation, since
the reaction did not proceed in its absence. The resulting
With the ZrO2/O2 system in CH2Cl2, BNPQ 3a was
obtained as a major product along with the ortho-
naphthoquinone5a as a by-product (entry 2). However,
good results were not obtained with the Nb2O5/O2 or the
TiO2/O2 system (entries 3 and 4). Furthermore, with the
SnO2/O2 system in CH2Cl2, 2,20-binaphthol (2a; BNPOH)
and 10-hydroxy-2,20-binaphthyl-1,4-quinone (4a; HBNPQ)
were obtained in yields of 67% and 28%, respectively (entry
5). A solvent effect of MeCN was only observed in the
reaction with the SnO2/O2 system. When MeCN was used in
place of CH2Cl2 under similar conditions, 4a was not

Table 1. Semiconductor-mediated oxidative dimerization of naphthols 1 in the presence of dioxygen (O2)a
Entry
NPOH
Reagent
Solvent
Temperature
(8C)
Time (h)
Product (isolated yield, %)
2
3
4
5
6
7
Act-Cb
ZrO2
Nb2O5
TiO2
SnO2
SnO2
SnO2
Act-Cb
ZrO2
SnO2
Act-Cb
ZrO2
SnO2
Act-Cb
ZrO2
SnO2
SnO2
ZrO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
23c
23
23
23
23
70
23
70
70
23
70
70
70
70
70
70
23
23
23
23
70
16
1.5
3.5
0.5
72
29
72
24
0.75
24
72
70
136
285
24
312
72
95
75
51
15
Trace
c
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1d
1e
1a
1b
2a
2a
17
43
20
4
18
28
67
64
81
28
6
44
96
2
MeNO2
MeCN
MeCN
CH2Cl2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
CH2Cl2
CHCl3
CH2Cl2
MeCN
20d
81d
11
9
9
10e
11
12e
13e
14
15
16
17
18g
19h
20
21
3
64
68
16
14
Trace
Trace
86
No reaction
2f
No reaction
No reaction
No reaction
1.5
0.5
22
Ag2O
SnO2
34
49
93
30d
8
29
14
i
ZrO2
0.75
a
General procedure: a slurry of semiconductor powder [Act-C (1 g),b SnO2 (5 g), ZrO2 (5 g), Nb2O5 (5 g), or TiO2 (1 g)] and 1a (0.25 mmol) in a dioxygen-saturated solvent (MeCN, CH2Cl2, or MeNO2) was
vigorously stirred at an appropriate temperature (23 or 70 8C) under normal laboratory light. Similar results were obtained in the dark. These semiconductors are commercially available (Wako Pure Chemical
Industries, Ltd., in Japan).
b
In our previous communication, we erroneously reported that when MeCN was used as a solvent at 70 8C, BNPQ 3a was obtained in this reaction of 1a.8c The solvent (MeCN) and the temperature (70 8C) should have
been given as CH2Cl2 and 23 8C.
c
d
e
f
With activated charcoal.
Yield from 1b.
Unreacted NPOHs 1 were also recovered: entry 10, 1b (14%); entry 12, 1c (8%); entry 13, 1c (12%).
7a (2%) along with a polymeric compound.
g
h
i
This reaction was carried out under air. CH2Cl2 as a solvent was used without any treatment.
With Ag2O (1.5 equiv) under air.
In our previous communication, we erroneously reported that when SnO2 was used as a reagent, BNPQ 3a was obtained in this reaction of 2a.8c SnO2 should have been written as ZrO2.

10684
T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
Scheme 1.
products 2, 3, and 4 would be useful synthetic intermediates
for naturally occurring diosindigo B, biramentaceone and
violet-quinone.10b,c
The proposed mechanism for the SC-mediated oxidative
dimerization of NPOH 1 using O2 is illustrated in Scheme 2.
This is analogous to that proposed for the oxidative reaction
of 1-naphthols with the SnCl4/O2 system reported pre-
viously by us.8d This reaction is initiated by the formation of
the electron donor–acceptor (EDA) complex A between 1
and a Lewis acid site on the SC surface.13a Subsequent
processes proceed on the SC surface. The SC, such as SnO2,
ZrO2 or Act-C, plays an important role in the present
oxidation. That is, it acts not only as a characteristic Lewis
In order to confirm the formation mechanism of 3 in the
present oxidation, the reaction of 2a with the ZrO2/O2
system in MeCN was carried out to give 3a in high yield
(entry 21 in Table 1). No reaction occurred in the absence of
O2 under similar conditions. The above results indicate that
the products 3 are produced via 2 by the oxidation of 1.
Scheme 2.

T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
10685
Scheme 3.
a
Table 2. Demethylation of the enol-ethers 3 to 4 with various reagents in the absence of O2
Entry
Substrate
Reagent
Solvent
Time (h)
Product (%)b
1
2
3
3a
3a
3b
3c
3a
3a
3a
SnO2
SnO2
SnO2
SnO2
ZrO2
Act-C
HCl
CH2Cl2
MeCN
19
72
2
4a (96)
No reaction
4b (95)
4c (93)
4a (12)
No reaction
4a (91)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
4
2
5c
6
72
72
8
7d
a
General procedure: a slurry of semiconductor powder [SnO2 (5 g), ZrO2 (5 g) or Act-C (1 g)] and 3 (0.25 mmol) in an argon-saturated solvent (CH2Cl2, or
MeCN) was vigorously stirred at 23 8C under normal laboratory light. Similar results were obtained in the dark.
Isolated yield.
Together with the recovered 3a (40%).
Using 10% HCl aq.
b
c
d
acid catalyst, but also as a mediator for electron transfer.
2.2. Selective demethylation of BNPQ 3 to HBNQ 4 with
various SCs without O2
Alternatively, O2 may act as a one-electron acceptor from
the anion-radical species (SC%K) and a one-proton acceptor
from the cation-radical species (NPOH%C) within complex
B. Finally, the resulting hydroperoxy radicals act as a two-
hydrogen acceptor from 2. Alternatively, o-naphthoquinone
6 and p-naphthoquinone 7 can be formed through coupling
between the hydroperoxy radical and the ortho-radical C or
the para-radical C.13b,c
Next, to throw light on whether HBNPQ 4 is formed by
acid-induced demethylation or oxidative demethylation of
the enol-ethers 3 in the reaction of 1 in CH2Cl2 (entries 4, 5,
and 9 in Table 1), the reactions of 3a–c with various
reagents in the absence of O2 in CH2Cl2 or MeCN were
examined (Scheme 3). The results are summarized in
Scheme 4.

10686
T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
Table 3. Oxidation of NPOH 1f with various SC/O2 systemsa
Entry
NPOH
Reagent
Time (h)
Product (%)b
2f
8
9
1fc
1
1f
1f
1f
1f
1f
1f
ZrO2
ZrO2
SnO2
Act-C
TiO2
6
6
144
144
6
14
14
-
99
-
2d
3
22
6
22
6
4
5
6
-
e
-
Nb2O5
24
24
10
10
8
a
General procedure: a slurry of semiconductor powder [SnO2 (5 g), ZrO2 (5 g) or Act-C (1 g)] and 1f (0.25 mmol) in a dioxygen-saturated MeCN was
vigorously stirred at 70 8C under normal laboratory light. Similar results were obtained in the dark.
Isolated yield.
Recovered 1f.
In an argon-saturated MeCN in the absence of O2.
Complex mixture.
b
c
d
e
Table 2. With SnO2 in CH2Cl2, selective demethylation of
in 4 from 3 requires a proton (HC) or a hydrogen source.
This suggests the participation of a Brønsted acid (Sn–OH)
site on the SnO2 surface, because proton sources, such as
water (H2O) and acids were not used in the work-up after the
reaction according to general procedure described in
Table 2. Early infrared studies (IR spectroscopy) of the
adsorption of carbon monoxide (CO) on the SnO2 surface
explicitly showed the existence of Sn–OH sites on the SnO2
3a–c proceeded efficiently to give 4a–c under mild
conditions in high yield (entries 1, 3, and 4). Similar results
were obtained in the dark. These results indicate that the
formation of 4 from 3 does not require dioxygen and light,
but requires SnO2.
Alternatively, the formation of the hydroxyl group (at C-10)
Table 4. 13C and 1H NMR spectral data (d/ppm) for compounds 8,a 9,a 10a and 11a
Carbon no.
8
9
10
11
13C
1Hb
13C
1Hb
13C
70.7
114.8
89.8
51.0
1Hb
13C
70.6
114.6
90.0
50.9
1Hb
1
2
3
4
186.4
109.2
89.0
186.4
109.2
89.1
5.13 bs
5.10 bs
5.17 s
5.17 s
5.10 s
5.08 s
50.4
50.4
4a
5
6
145.2
127.3
135.4
145.2
127.2
135.4
138.6
126.8
129.3
138.7
126.8
129.4
7.74 bd (7.9)
7.67 m
7.73 bd (8.2)
7.65 dt (1.2,
6.7)
7.80 bd (8.2)
7.47 m
7.79 bd (7.9)
7.47 dt (1.2,
6.1)
7
8
111.9
128.1
7.32 m
127.4
128.0
7.32 dt (1.2,
6.7)
7.99 dd (1.2,
6.7)
127.4
129.6
7.31 m
127.4
129.8
7.32 dt (1.2,
6.1)
7.52 bd (7.6)
8.00 dd (1.2,
6.7)
7.55 bd (7.6)
8a
10
129.0
151.9
127.2
120.1
128.6
133.1
124.4
126.4
125.7
122.4
120.8
138.2
142.7
127.4
130.3
128.6
125.0
119.9
126.1
123.8
119.8
26.2
129.07
151.6
127.1
120.1
128.7
133.1
124.4
126.4
125.7
122.5
120.9
139.8
141.1
111.0
129.11
129.0
124.5
124.2
126.2
121.0
120.2
26.1
134.3
151.5
127.1
120.8
128.2
132.8
124.3
126.0
125.3
122.0
120.6
139.5
142.7
111.7
128.8
128.4
125.0
123.6
125.8
120.1
119.7
29.7
134.4
151.4
127.2
120.7
128.1
132.7
124.2
125.9
125.2
121.7
120.6
139.6
142.5
111.0
128.7
128.4
124.5
123.6
125.6
120.3
120.1
29.4
20
30
40
7.42 bs
7.41 bs
7.45 bs
7.41 bs
4a0
50
7.88 m
7.46 bs
7.47 m
8.04 m
7.88 m
7.47 m
7.48 m
8.08 m
7.88 bd (8.6)
7.43 m
7.34 m
7.83 bd (9.2)
7.36 m
7.21 m
60
70
80
7.72 bd (8.2)
7.65 bd (8.2)
8a0
100
200
300
7.93 bs
7.00 bs
6.88 bs
7.05 bs
400
4a00
500
7.30 bd (8.6)
7.69 bt (8.2)
7.41 m
7.93 bd (8.9)
7.42 m
7.54 bt (7.0)
8.18 bd (8.6)
7.92 bd (8.6)
7.36 m
7.43 m
7.85 bd (9.2)
7.27 m
7.25 m
600
700
800
7.36 m
7.80 bd (8.2)
7.52 bd (7.6)
8a00
4-Me
40-Me
400-Me
1-OH
2.23 bs
2.67 bs
2.69 bs
2.19 bs
2.66 bs
2.64 bs
1.97 bs
2.66 bs
2.57 bs
2.84 bs
1.97 bs
19.6
19.6
19.5
19.6
19.4
19.6
19.54 or 19.50 2.652 bs
19.54 or 19.50 2.654 bs
2.90 bs
a
Data recorded in CDCl3 at 500 MHz (1H NMR) and 125 MHz (13C NMR). Assignments were based on 1H–1H COSY, 1H–13C COSY, HMBC and NOESY
spectra.
Coupling constants (J in Hz) are given in parentheses.
b

T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
10687
surface.14b Indeed, the reaction of 3a with HCl as a Brønsted
acid in place of SnO2 gave 4a in good yield (entry 7).
Accordingly, 4 is concluded to be formed by demethylation
of 3 at Sn–OH sites on the SnO2 surface.
In order to examine the reason why MeCN has the solvent
effect described above, the reaction of 3a using MeCN in
place of CH2Cl2 as a solvent was carried out under similar
conditions. Surprisingly, this reaction did not proceed at all
(entry 2). In the above case, as well as in the case of entry 6
in Table 1, 4a was presumably not obtained because the
interaction between the Sn–OH sites and the carbonyl group
in 3a is blocked by the MeCN molecules, which bind to the
Sn–OH sites; Yates and co-workers13c observed the
adsorption of MeCN on Brønsted acid sites of a metal
oxide surface, such as TiO2, by means of IR spectroscopy.
The reaction with ZrO2 under similar conditions gave 4a in
low yield, while no reaction occurred with Act-C. These
results indicate that the formation of 4 by the reaction of 1 or
3 can be well controlled when ZrO2 or Act-C catalyst and
MeCN are employed.
Figure 1. Characteristic peaks in the mass spectrum of 8.
2.3. Oxidative conversion of NPOH 1f to the naphthol
trimers 8 and 9 with various SC/O2 systems
The regiosubstitution was determined by means of a
NOESY experiment on 8, showing NOE effects between
3-H (ring A) and 300-H (ring C), and between 4-Me (ring A)
and 30-H (ring B), which correspond to the linkages between
the0 units, C3–O–C100, C2–O–C200 and C4–C20–C10, C2–O–
C2 (Scheme 4). In addition, this linkage between ring A and
ring B was confirmed by obs0ervation0 of the long-range
correlations of 4-CH3 and C2 , and 3 -H and C4 in the
HMBC spectrum of 8 (Table 5).
Interestingly, when we used NPOH 1f having a methyl
group (at C4) with various SC/O2 systems, a unique reaction
took place to afford the novel naphthol trimer 8 and 9 in all
cases, that is, the tricyclic adduct with two ether linkages
formed between ring A and ring C (Scheme 4 and Table 3).
The best result was obtained in the reaction with the SnO2/
O2 system in MeCN at 70 8C (entry 3).
The relative configuration in ring A was also confirmed by
the NOESY experiment on 8: NOE correlations were
observed between 3-H and 300-H, and 3-H and 30-H, showing
that structure 8 has the trans-configuration between C-3 and
C-4 in ring A (Scheme 4).
The structure of 8 was elucidated by means of detailed
1
analyses of the H and 13C NMR spectra with the aid of
various 2D NMR experiments (Table 4),15 and also by
chemical transformation to 10 as shown in Scheme 5. In
addition, the structure 8 was also supported by its mass
spectral fragmentation pattern (Fig. 1).
The reduction of 8 with NaBH4 yielded only one product 10
having a secondary hydroxyl group; the hydride attacked
from the less hindered b-face to produce the C1a-hydroxyl
group (Scheme 5). The relative stereostructure of the C1
position in ring A was characterized by observation of the
NOE correlations between 1-H and 8-H in 10 (Scheme 5).
Furthermore, on acetylation with acetic anhydride and
pyridine, 10 afforded a monoacetate 12. The structure of 9
was elucidated by similar analysis, and also by chemical
transformation to 11. In addition, the mass spectra of 9
showed a fragmentation pattern similar to that of 8.
The oxidative conversion of 1f to 8 and 9 can be explained
in terms of oxidative dehydrogenation, followed by C/C and
O/C radical couplings and the hetero Diels–Alder (HDA)
cycloaddition16 as illustrated in Scheme 6. This HDA
reaction is analogous to that reported previously by Moujir
et al.17a Firstly, the p-napthoquinone methide 17 is formed
by Cortho/Cpara coupling of the radical D generated by the
oxidative dehydrogenation of 1h with the SC/O2 system.
On the other hand, the radical D reacts with the
hydroperoxy radical13b,c generated from dioxygen (O2) to
give the o-napthoquinone 5e (refer to Scheme 4).
Subsequently, the HDA reaction of 17 with 5e takes place
Scheme 5.

10688
T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
Table 5. Long-range heteronuclear correlations (HMBC) for 8, 9, 10 and 11
1H position
8
9
10
11
1
1-OH
3
4-Me
5
6
—
—
—
—
C-8a
—
C-2, C-4a, C-8a
—
C-1, C-2, C-4a, C4-Me
C-3, C-4, C-4a, C-20
C-4, C-7, C-8a
C-4a, C-8
C-1, C-2, C-4, C-4a, C4-Me, C-20
C-3, C-4, C-4a, C-20
C-4, C-7, C-8a
C-4a, C-8
C-1, C-2, C-4, C-4a, C4-Me
C-3, C-4, C-4a, C-20
C-4, C-8a
C-4a
C-6
C-1, C-2, C-4, C-4a, C4-Me
C-3, C-4, C-4a, C-20
C-4, C-7, C-8a
C-4a, C-8
C-5, C-6, C-8a
C-1, C-4a, C-6
C-4, C-10, C-4a0, C40-Me
C-30, C-4a0
C-70, C-8a0
—
7
8
30
C-5, C-8a, C-8
C-1, C-4a, C-6
C-4, C-4a0, C40-Me
C-30, C40, C-4a0
C-40, C-70, C8a0
C-80
C-5, C-8a
C-1, C-4a, C-6
C-4, C-10, C-4a0, C40-Me
C-1, C-4a, C-6
C-4, C-10, C-4a0, C40-Me
C-30, C-4a0
40-Me
50
C-30, C-4a0
C-4a0, C-70, C-8a0
—
C-40, C-70
60
C-4a0, C-80
700
C-80
C-4a0, C-60
C-5000, C-80
C-500, C8a0
C-500
800
C-1 , C-4a00, C-600
C-100, C-200, C-4a00, C400-Me
C-300, C-4a00
C-100, C-4a0, C-60
C-1 , C-200, C-4a00, C400-Me
C-300, C-400
C-100, C-4a0, C-60
C-1 , C-200, C-4a00, C400-Me
C-300, C-400
300
C-100, C-200, C-4a00, C400-Me
400-Me
C-400
5
C-400, C-600, C-700
C-800
C-400, C-700, C-8a00
C-4a00, C-800
C400, C-700, C-8a00
C-4a00, C-800
C-500, C8a00
C-100, C-600
C-700, C-8a00
C-4a00, C-800
C-500
600
700
C-500, C-600
C-600
C-500, C-8a00
800
C-100, C-4a00, C-600
C-600
regioselectively to form the bicyclic cis-fused adducts 18
and 19.
(Fig. 2).16b,d Among four possible transition modes (I)–(IV),
in the formation of the anti-adduct 18 and the syn-adduct
19, both the anti (I) and syn (III) transition states can be
operative, respectively (Fig. 2). Alternatively, the
regioisomers 20 and 21 were not formed at all in this
reaction since the anti (II) and syn (IV) orientations are
not possible in the transition state because of steric
repulsion between the o-naphthoquinone ring (ring C) and
the methyl group or the NPOH group at the C4 position in
ring A.
Although the reason for the regioselective formation of 18
and 19 is unclear, a possible explanation is as follows. In
general, the HDA reaction proceed preferentially
through the endo-mode rather than the corresponding exo-
mode in the transition state.16g The p-napthoquinone
methide 17 has two p-faces, syn and anti, with
respect to the NPOH group at the C4-position in ring A
Scheme 6.

T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
10689
Figure 2. Four possible transition states in the hetero Diels–Alder reaction of p-napthoquinone methide 17 with o-napthoquinone 5e.
Finally, the tricyclic bridged adduct 8 or 9 is formed by
intramolecular O/C radical coupling in the biradical E or F,
which is generated by oxidative dehydrogenations of both
the enolate (ring A) and the naphthol sites (ring B) in 18 or
19, respectively (Scheme 6).
4. Experimental
4.1. General
All melting points are uncorrected. Infrared (IR) spectra
were recorded with a JASCO IR-700 spectrometer, and H
1
and 13C NMR spectra with JEOL JNM-AL300 and JNM-
alpha 500 spectrometers, with tetramethylsilane as an
internal standard (CDCl3, CD3COCD3 or CD3SOCD3
solution). Mass spectra were recorded on a JEOL JMS-
D300 or Shimadzu QP-5000 spectrometer. Elemental
analyses were done using a Yanaco CHN-MT-3 apparatus.
Merck Kieselgel 60 (230–400 mesh), Wako silica gel C-200
(200 mesh) and Merck Kieselgel 60 F254 were used for flash
column chromatography, column chromatography and thin-
layer chromatography (TLC), respectively. Each organic
extract was dried over MgSO4 or Na2SO4. The semi-
conductors, such as ZrO2 and activated charcoal powders,
are commercially available (Wako Pure Chemical
Industries, Ltd., Japan).
This proposed HDA reaction of p-napthoquinone methide
17 with o-napthoquinones 5e16a–c is attractive because of its
potential application to quinoid natural products synthesis,
and its possible involvement in the biosynthesis of natural
products including triterpene dimers or trimers with various
biological activities.17
In the results described above, a noteworthy difference in
the major product between oxidation with 1a–c and
oxidation with 1f as a substrate was observed. Oxidation
of 1a–c with the SC/O2 system afforded the corresponding
BNPOH 2 or BNPQ 3, whereas in the case of 1f, the
naphthol trimers 8 and 9 were obtained as the major
products. Although the reason for this difference is unclear,
some structural difference of the electron donor–acceptor
(EDA) complex formed between the semiconductors and
1a–c or 1f in the reaction process may be involved.
4.2. Synthesis of 1-naphthols 1a–h
Naphthols 1b,18a,b 1c,18d–f 1e,8b and 1f8a were synthesized
according to the protocol reported previously, and 1a and 1d
are commercially available (Tokyo Kasei Chemical
Industries, Ltd., Japan).
3. Conclusion
In this study, we found that heterogeneous SC, such as
SnO2, ZrO2 and Act-C, are efficient solid oxidation catalysts
for the oxidative dimerization of NPOH 1a–c to 2,20-
binaphthyl derivatives 2 or 3 using dioxygen as an oxidant.
In particular, SnO2 is a useful and convenient catalyst for
the selective synthesis of 2,20-binaphthols 2 and for
selective O-demethylation of the enol-ethers 3a–c to 4.
The SnO2-mediated oxidations appear to be environ-
mentally friendly, since the reagent is nontoxic and can be
recycled.
4.3. General procedure for oxidative dimerization of
NPOHs 1a–g with semiconductors in the presence of
dioxygen (O2) (the SC/O2 system)
A slurry of semiconductor powder [Act-C (1 g), SnO2 (5 g),
ZrO2 (5 g), Nb2O5 (5 g), or TiO2 (1 g)] and the selected
substrate 1 (0.28 mmol) in a dioxygen (O2)-saturated
solvent or an argon-saturated solvent (MeCN, CH2Cl2 or
CH3NO2; 15 ml) was vigorously stirred at 23 or 70 8C under

10690
T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
normal laboratory light. Then, the reaction mixture was
stirred in a sealed tube until disappearance of the substrate
(1-naphthols and 2,20-binaphthyls), except in cases where
the starting material was recovered. The insoluble reagent
was filtered off and washed with the solvents used, and then
the filtrate was evaporated. The residue was subjected to
flash column chromatography on silica gel.
tetramethoxy-7,70-dimethyl[2,20]binaphthalenylidene-1,10-
dione (3b). Yields are listed in Table 1.
Method B (entry 8) (with the Act-C/O2 system). Oxidation of
1b (50 mg, 0.23 mmol) with Act-C (1 g) in MeCN was
carried out at 70 8C for 24 h according to the general
procedure for the oxidative dimerization of NPOHs 1 with
the SC/O2 system. Benzylation of the resulting products was
carried out by the same procedure under the conditions
described above (method A) for benzylation of a mixture of
2b and 3b. The crude product was purified by flash column
chromatography on silica gel. The eluate with CH2Cl2–
hexane (1:2, v/v) gave 5, 3b, 6b and 7b. Yields are listed in
Table 1.
4.4. Oxidative dimerization of 1a with the SC/O2 system
Oxidation of 1a (50 mg, 0.29 mmol) was carried out
according to the general procedure for the oxidative
dimerization of NPOHs 1 with the SC/O2 system described
above. The crude product was subjected to flash column
chromatography on silica gel with the designated solvents as
follows: CH2Cl2–hexane (3:1; for 3a and 6a in Table 1);
CH2Cl2–hexane (1:2; for 2a, 3a, 4a and 6a in Table 1);
CH2Cl2–hexane (1:2; for 2a and 4a in Table 1); CH2Cl2–
hexane (1:2; for 2a and 3a in Table 1); yields are listed in
Table 1. Similar results were obtained when the reactions
were carried out in the dark.
Method C (entry 9) (with the ZrO2/O2 system). Oxidation of
1b (50 mg, 0.23 mmol) with ZrO2 (5 g) in MeCN was
carried out at 70 8C for 0.75 h according to the general
procedure for the oxidative dimerization of NPOHs 1 with
the SC/O2 system. The crude product was purified by
recrystallization from benzene to yield 3b (96%).
Method D (entry 10) (with the SnO2/O2 system). Oxidation
of 1b (50 mg, 0.23 mmol) with SnO2 (5 g) in CH2Cl2 was
carried out at 23 8C for 24 h according to the general
procedure for the oxidative dimerization of NPOHs 1 with
the SC/O2 system. Benzylation of the resulting oxidative
products was carried out by the same procedure under the
conditions described above (method A) for benzylation of a
mixture of 2b and 3b. The crude product was purified by
flash column chromatography on silica gel. The eluate with
hexane–AcOEt (10:1, v/v) gave 5, 3b, and 4b. Yields are
listed in Table 1. Similar results were obtained when the
reactions were carried out in the dark.
4.4.1. 4,40-Dimethoxy[2,20]binaphthalenyl-1,10-diol (2a).
Colorless needles (benzene), mp 223–224 8C. LR-MS m/z:
346 (MC). IR, 1H and 13C NMR data were described
previously by us.8b
4.4.2. 4,40-Dimethoxy[2,20]binaphthalenylidene-1,10-
dione (3a). Deep blue needles (benzene), mp 257–258 8C.
1
LR-MS m/z: 344 (MC). IR, H and 13C NMR data were
described previously by us.8b
4.4.3. 10-Hydroxy-40-methoxy[2,20]binaphthalenyl-1,4-
dione (4a). Deep violet needles (benzene), mp 189 8C.
1
LR-MS m/z: 330 (MC). IR, H and 13C NMR data were
4.5.1. 4,5,40,50-Tetramethoxy-7,70-dimethyl[2,20]bi-
naphthalenylidene-1,10-dione (3b). Deep blue powder
(benzene), mp 236.5–237.0 8C (lit.8a 236.5–237 8C). IR
described previously by us.8a
1
(KBr) cmK1: 1589, 1302, 1053. H NMR (CDCl3) d: 2.43
4.4.4. 4-Methoxy-1,2-naphthoquinone (6a). Yellow
needles (MeOH–hexane), mp 192–193 8C. LR-MS m/z:
188 (MC). IR, 1H and 13C NMR data were described
previously by us.8a
(6H, s, 7 and 70-Me), 3.92 (6H, s, 5 and 50-OMe), 4.05 (6H,
s, 4 and 40-OMe), 6.98 (2H, br s, 6 and 60-H), 7.70 (2H, br s,
8 and 80-H), 8.37 (2H, s, 3 and 30-H). 13C NMR (CDCl3) d:
0
21.8 (and -Me), 56.1 (4 and 40-OMe), 56.9 (5 and 50-OMe),
103.2 (C3 and C30), 1108.0 (C4a and C4a0), 118.2 (C6 and
C60), 121.7 (C8 and C8 ), 130.3 (C8a and C8a00), 133.6 (C2
and C20), 140.3 (C7 and C70), 156.1 (C4 and C4 ), 159.5 (C5
and C50), 188.9 (C1 and C10). LR-MS m/z: 432 (MC). HR-
MS calcd for C26H24O6: 432.1566. Found: 432.1563. Anal.
Calcd for C26H24O6: C, 72.21; H, 5.59. Found: C, 72.35; H,
5.56.
4.5. Oxidative dimerization of 1b with various reagents
Method A (entry 19) (with Ag2O). A solution of 1b (100 mg,
0.46 mmol) in CHCl3 (10 ml) containing 1.5 equiv of Ag2O
(160 mg, 0.69 mmol) was stirred at 23 8C in an air
atmosphere for 30 min. The solvent was removed and the
residue was subjected to flash column chromatography on
silica gel using CH2Cl2–AcOEt (20:1, v/v) as an eluent to
give a mixture of 2b and 3b, and 4,5-dimethoxy-7-methyl-
1,2-naphthoquinone (6b). Benzyl bromide (268 ml,
2.26 mmol) was added to a solution of the mixture of 2b
and 3b, and anhydrous K2CO3 (312 mg, 2.26 mmol) in dry
DMF (5 ml), and the solution was stirred vigorously at
23 8C for 15 min. The reaction mixture was poured into ice-
water, neutralized with 10% HCl, and extracted with
CH2Cl2. The organic layer was washed with H2O, dried
and concentrated. The residue was subjected to flash column
chromatography on silica gel. The eluate with hexane–
AcOEt (10:1, v/v) gave 1,10-dibenzyloxy-4,5,40,50-tetra-
methoxy[2,20]binaphthalenyl-1,10-diol (5) and 4,5,40,50-
4.5.2. 10-Hydroxy-5,40,50-trimethoxy-7,70-dimethyl[2,20]-
binaphthalenyl-1,4-dione (4b). Green granules (hexane–
AcOEt), mp 168.5–169.5 8C. IR (KBr) cmK1: 3418,02920,
1643, 1599. 1H NMR (CDCl3) d: 2.52 (6H, s, 7 and 7 -Me),
3.93 (3H, s, 50-OMe), 3.98 (3H, s, 40-OMe), 4.03 (3H, s,
5-OMe), 6.55 (1H, s, 30-H), 6.81 (1H, d, JZ1.5 Hz, 60-H),
7.01 (1H, s, 3-H), 7.17 (1H, d, JZ0.6 Hz, 6-H), 7.70 (1H,
dd, JZ0.6, 0.92 Hz, 8-H), 7.86 (1H, dd, JZ0.6, 0.92 Hz, 80-
H), 8.60 (1H, s, 10-OH). 13C NMR (CDCl3) d: 22.1 (C7 or
C70-Me), 22.3 (C7 or C70-Me), 56.40(C40-OMe), 56.5 (C5-
OMe), 57.3 (C50-OMe), 107.0 (C3 ), 110.6 (C60), 114.8
(C20), 115.7 (C80), 117.0 (C4a or C4a0), 117.7 (C4a or

T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
10691
C4a0), 119.0 (C6), 121.3 (C8), 129.8 (C8a0), 134.4 (C8a),
136.6 (C70), 141.03 (C3), 144.8 (C10), 146.4 (C7), 146.5
(C2), 151.04 (C4 ), 156.5 (C50), 159.6 (C5), 183.6 (C1),
188.3 (C4). LR-MS m/z: 418 (MC). HR-MS calcd for
C25H22O6: 418.1417. Found: 418.1432. Anal. Calcd for
C25H22O6: C, 71.76; H, 5.30. Found: C, 71.78; H, 5.35.
7.9 Hz, 70-H), 7.04 (1H, s, 3-H), 7.30 (1H, d, JZ8.2 Hz,
7-H), 7.37 (1H, t, JZ7.9, 8.5 Hz, 60-H), 7.66 (1H, t, JZ7.6,
8.2 Hz, 6-H), 7.76 (1H, dd, JZ0.9, 7.6 Hz, 5-H), 7.86 (1H,
dd, JZ1.1, 8.5 Hz, 50-H), 9.41 (1H, s, OH). 13C NMR
(CDCl3) d: 55.9 (C40-OMe), 56.1 (C8-OMe), 56.5 (C80-
OMe), 105.6 (C70), 107.1 (C30), 114.9 (C20), 115.3 (C8a0),
115.9 (C50), 117.80 (C7), 118.6 (C5), 121.1 (C8a), 126.3
(C60), 128.9 (C4a ), 134.35 (C3), 134.38 (C6), 134.41
(C4a), 146.3 (C10), 147.8 (C40), 150.9 (C2), 156.4 (C80),
159.6 (C8), 183.2 (C1), 185.3 (C4). LR-MS m/z: 390 (MC).
HR-MS calcd for C23H18O6: 390.1100. Found: 390.1170.
Anal. Calcd for C23H18O6: C, 70.76; H, 4.65. Found: C,
70.56; H, 4.62.
4.5.3. 1,10-Dibenzyloxy-4,5,40,50-tetramethoxy[2,20]-
binaphthalenyl-1,10-diol (5). Pale yellow powder
(AcOEt), mp 203.5–204.0 8C (lit.8a 203.5–204 8C). IR
1
(KBr) cmK0 1: 2922, 1604. H NMR (CDCl3) d: 2.50 (6H,
s, 7 and 7 -Me), 3.91 (6H, s, 4 and 40-OMe), 4.02 (6H, s, 5
and 50-OMe), 4.71 (4H, s, 2!–CH2–Ar), 6.78 (2H, d, JZ
1.29 Hz, 6 and 60-H), 7.17 (2H, s, 3 and 30-H), 7.20–7.30
(10H, m, Ar-H), 7.67 (2H, d, J0Z1.29 Hz, 8 and 80-H). 13C
NMR (CDCl3) d: 22.2 (7- and 7 -Me), 56.55 (5-OMe), 56.62
(4 and 40-OMe), 75.1 (–CH2–Ar), 108.3 (C3 and C30), 109.1
(C6 and C60), 114.5 (C8 and C80), 116.2 (C2 and C20), 127.5
(C4a and C4a0), 127.9 (Ar-C), 128.1 (Ar-C), 128.4 (Ar-C),
132.1 (C8a and C8a0), 136.7 (C7 and C70), 137.3 (Ar-C),
145.2 (C1 and C10), 152.8 (C4 and C40), 157.1 (C5 and C50).
LR-MS m/z: 614 (MC). HR-MS: calcd for C40H38O6:
614.2658. Found: 614.2642. Anal. Calcd for C40H38O6: C,
78.15; H, 6.23. Found: C, 78.13; H, 6.20.
4.7. Oxidation of 1d with the SC/O2 system
The reaction of 1d (50 mg, 0.35 mmol) was carried out
according to the general procedure for the oxidative
dimerization of NPOHs. The crude product was subjected
to flash column chromatography on silica gel with CH2Cl2–
hexane (2:1, v/v) to yield 1,4-naphthoquinone 7a, as yellow
needles (ethanol), mp 125–126 8C (lit.18g 128 8C). Yields
are listed in Table 1. Similar results were obtained when the
reactions were carried out in the dark. IR (KBr) cmK1
:
1659, 1587. 1H NMR (DMSO-d6) d: 7.08 (2H, s, 2 and 3-H),
7.88 (2H, dd, JZ3.3, 5.8 Hz, 6 and 7-H), 7.99 (2H, dd, JZ
3.3, 5.8 Hz, 5 and 8-H). LR-MS m/z: 158 [MC].
4.5.4. 4,5-Dimethoxy-7-methyl-1,2-naphthoquinone (6b).
Orange powder (CHCl3–hexane), mp 175.0–176.0 8C. IR,
1H and 13C NMR data were described previously by us.8a
4.8. Oxidation of 1e with the SC/O2 systems
4.5.5. 5-Methoxy-7-methyl-1,4-naphthoquinone (7b).
Yellow needles (benzene), mp 169.5–170 8C (lit.18e 164–
These reactions did not proceed.
1
166 8C). IR (KBr) cmK1: 1651, 1559. H NMR (CDCl3) d:
2.48 (3H, s, 7-Me), 4.00 (3H, s, 5-OMe), 6.84 (2H, s, 2 and
3-H), 7.11 (1H, s, 6-H), 7.55 (1H, s, 8-H). HR-MS calcd for
C12H10O3: 202.0627. Found: 202.0614.
4.8.1. General procedure for demethylation of BNPQ
3a–c to HBNPQ 4a–c with semiconductors in the absence
of O2. A slurry of semiconductor powder [SnO2 (5 g), ZrO2
(5 g), or Act-C (1 g)] and the selected substrate 3
(0.15 mmol) in a argon-saturated solvent (MeCN or
CH2Cl2; 15 ml) was vigorously stirred at 23 8C under
normal laboratory light. Then, the reaction mixture was
stirred in a sealed tube until disappearance of the substrate
(2,20-binaphthyls), except in cases where the starting
material was recovered. The insoluble reagent was filtered
off and washed with solvents used, and then the filtrate was
evaporated. The residue was subjected to flash column
chromatography on silica gel with the designated solvents as
follows: hexane–CH2Cl2 (1:1; for 4a in Table 2); CH2Cl2–
AcOEt (20:1; for 4b in Table 2); hexane–AcOEt (1:1; for 4c
in Table 2). Yields for 4a–c are listed in Table 2. Similar
results were obtained when the reactions were carried out in
the dark.
4.6. Oxidative dimerization of 1c with the SC/O2 system
Oxidation of 1c (50 mg, 0.25 mmol) was carried out
according to the general procedure for the oxidative
dimerization of NPOHs. The crude product was subjected
to flash column chromatography on silica gel with the
designated solvents as follows: hexane–AcOEt (3:1; for 2c,
3c and 4c in Table 1); hexane–AcOEt (3:1; for 2c in
Table 1); hexane–AcOEt (1:1; for 3c in Table 1). Yields for
2c, 3c and 4c are listed in Table 1. Similar results were
obtained when the reactions were carried out in the dark.
4.6.1. 4,40,8,80-Tetramethoxy-2,20-di-1,10-naphthol (2c).
Colorless needles (CHCl3–hexane), mp 207–209 8C. LR-
MS m/z: 406 (MC). IR, 1H and 13C NMR data were
described previously by us.8b
4.8.2. The reaction of 3a with HCl. A solution of 3a (1.0 g,
2.91 mmol) and 10% HCl (1.1 ml) in CH2Cl2 (100 ml) was
stirred at 23 8C for 8 h. The reaction mixture was poured
into ice-water and extracted with CH2Cl2. The organic layer
was washed with H2O, then dried and concentrated. The
residue was subjected to flash column chromatography on
silica gel using CH2Cl2–hexane (1:1, v/v) as an eluent to
give 4a (91%).
4.6.2. 4,8,40,80-Tetramethoxy[2,20]binaphthalenylidene-
1,10-dione (3c). Deep purple needles (CHCl3–hexane), mp
1
261–262 8C. LR-MS m/z: 404 (MC). IR, H and 13C NMR
data were described previously by us.8b
4.6.3. 10-Hydroxy-40,8,80-trimethoxy[2,20]binaphthal-
enyl-1,4-dione (4c). Deep purple needles (hexane–
1
AcOEt), mp 120–122 8C. IR (KBr) cmK1: 3394, 1607. H
4.9. Oxidation of 1f with the SC/O2 system
NMR (CDCl3) d: 3.95 (3H, s, OMe), 3.99 (3H, s, OMe),
4.01 (3H, s, OMe), 6.72 (1H, s, 30-H), 6.86 (1H, d, JZ
The reaction of 1f (50 mg, 0.32 mmol) was carried out

10692
T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
according to the general procedure for the oxidative
dimerization of NPOHs. The crude product was subjected
to flash column chromatography on silica gel with the
designated solvents as follows: CH2Cl2–hexane (1:2; for 2f,
8 and 9 in Table 3); CH2Cl2–hexane (1:2; for 8 and 9 in
Table 3). Yields are listed in Table 3. Similar results were
obtained when the reactions were carried out in the dark.
(87%) of 12, as colorless plates (benzene–hexane), mp
271.5–272.0 8C. IR (KBr) cmK1: 1746, 1661, 1620. 1H
NMR (CDCl3) d: 1.75 (3H, s, Me), 2.00 (3H, s, Me), 2.58
(3H, s, Me), 2.62 (3H, s, Me), 5.15 (1H, s, 3-H), 6.44 (1H, s,
1-H), 6.95 (1H, s, Ar-H), 7.21–7.52 (8H, m, Ar-H), 7.71
(1H, br d, JZ8.3 Hz, Ar-H), 7.85–7.90 (4H, m, Ar-H). HR-
MS calcd for C35H28O5: 528.1929. Found: 528.1916.
4.9.1. 4,40-Dimethyl[2,20]binaphthalenyl-1,10-diol (2f).
White amorphous powder (CHCl3–hexane), mp 219–
4.9.7. Acetylation of 11 with Ac2O/pyridine. Acetylation
of 11 (45 mg, 0.09 mmol) was carried out at 23 8C for 2 h by
the same procedure under the conditions described above
for acetylation of 10. The crude product was purified by
flash column chromatography on silica gel. The eluate with
CH2Cl2–hexane (1:1, v/v) gave 40 mg (82%) of 13 as
colorless plates (benzene–hexane), mp 261.0–262.0 8C. IR
1
220 8C. LR-MS m/z: 314 (MC). IR, H and 13C NMR data
were described previously by us.8b
4.9.2. Compound 8. Yellow powder (CHCl3–hexane), mp
C
over 300 8C. IR (KBr) cmK1: 1717, 1651, 1601. 1H and 13
1
(KBr) cmK1: 1746, 1653, 1617. H NMR (CDCl3) d: 1.75
NMR spectral data are listed in Table 4. HR-MS calcd for
C33H24O4: 484.1668. Found: 484.1675. Anal. Calcd for
C33H24O4: C, 81.80; H, 4.99. Found: C, 81.90; H, 5.01.
(3H, s, Me), 1.99 (3H, s, Me), 2.61 (3H, s, Me), 2.62 (3H, s,
Me), 5.11 (1H, s, 3-H), 6.39 (1H, s, 1-H), 6.99 (1H, br s,
Ar-H), 7.21–7.41 (7H, m, Ar-H), 7.47–7.53 (1H, m, Ar-H),
7.61–7.65 (1H, m, Ar-H), 7.82–7.88 (4H, m, Ar-H). HR-MS
calcd for C35H28O5: 528.1929. Found: 528.1958.
4.9.3. Compound 9. Pale yellow powder (CHCl3–hexane),
1
mp over 300 8C. IR (KBr) cmK1: 1717, 1608. H and 13C
NMR spectral data are listed in Table 4. HR-MS calcd for
C33H24O4: 484.1668. Found: 484.1693. Anal. Calcd for
C33H24O4: C, 81.80; H, 4.99. Found: C, 81.85; H, 4.96.
References and notes
4.9.4. Reduction of 8 with NaBH4. To a solution of 8
(30 mg, 0.06 mmol) in CH2Cl2 (10 ml) and MeOH (5 ml)
was added dropwise a solution of NaBH4 (20 mg,
0.53 mmol) in MeOH (2 ml) at 0 8C and the mixture was
stirred at room temperature for 15 min. The reaction
mixture was poured into ice-water and extracted with
CH2Cl2. The organic layer was washed with H2O, dried,
filtered, and evaporated in vacuo. The crude product was
purified by flash column chromatography on silica gel. The
eluate with CH2Cl2–hexane (1:1, v/v) gave 28 mg (93%) of
10, as colorless crystals (benzene–hexane), mp 278.5–
1. (a) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 977–991. (b) Swenton, J. S. Acc. Chem.
Res. 1983, 16, 74–81. (c) Progress in the Chemistry of Organic
Natural Products; Herz, W., Falk, H., Kirby, G. W., Moore,
R. E., Eds.; Springer: Wien, New York, 2001; Vol. 82, pp.
38–64. (d) Meyers, A. I.; Willemsen, J. J. Tetrahedron 1998,
54, 10493–10511.
2. (a) Kashiwagi, Y.; Ono, H.; Osa, T. Chem. Lett. 1993, 81–84.
(b) El-Seedi, H. R.; Yamamura, S.; Nishiyama, S. Tetrahedron
Lett. 2002, 43, 3301–3304. (c) El-Seedi, H. R.; Yamamura, S.;
Nishiyama, S. Tetrahedron 2002, 58, 7485–7489. (d) Shizuri,
Y.; Nakamura, K.; Yamamura, S. J. Chem. Soc. Chem.
Commun. 1985, 530–531. (e) Gates, B. D.; Dalidowicz, P.;
Tebben, A.; Wang, S.; Swenton, J.; S J. Org. Chem. 1992, 57,
2135–2143. (f) Kerns, M. L.; Conroy, S. M.; Swenton, J. S.
Tetrahedron Lett. 1994, 35, 7529–7532. (g) Chiba, K.; Jinno,
M.; Kuramoto, R.; Tada, M. Tetrahedron Lett. 1998, 39,
5527–5530. (h) Chiba, K.; Arakawa, T.; Tada, M. J. Chem.
Soc., Perkin Trans. 1 1998, 2939–2942. (i) Chiba, K.; Fukuda,
M.; Kim, S.; Kitano, Y.; Tada, M. J. Org. Chem. 1999, 64,
1
279.5 8C. IR (KBr) cmK1: 3562, 1653, 1612. H and 13C
NMR spectal data are listed in Table 4. HR-MS calcd for
C33H26O4: 486.1824. Found: 486.1807. Anal. Calcd for
C33H26O4: C, 81.46; H, 5.39. Found: C, 81.36; H, 5.40.
4.9.5. Reduction of 9 with NaBH4. Reduction of 9 (50 mg,
0.10 mmol) was carried out at 23 8C for 15 min by the same
procedure under the conditions described above for the
reduction of 8. The crude product was purified by flash
column chromatography on silica gel. The eluate with
CH2Cl2–hexane (1:1, v/v) gave 49 mg (98%) of 11, as
colorless crystals (benzene–hexane), mp 246–247 8C. IR
´
7654–7656. (j) Hassan, J.; Sevignon, M.; Gozzi, C.; Schlz, E.;
1
(KBr) cmK1: 3457, 1651, 1617. H and 13C NMR spectral
Lemarie, M. Chem. Rev. 2002, 102, 1359–1469. (k)
Bringnmann, G.; Tasler, S. Tetrahedron 2001, 57, 331–343.
(l) Tanoue, Y.; Sakata, K.; Hashimoto, M.; Morishita, S.;
Hamada, M.; Kai, N.; Nagai, T. Tetrahedron 2002, 58,
99–104. (m) Maiti, B. C.; Musgrave, O. C.; Skoyles, D.
J. Chem. Soc., Chem. Commun. 1976, 244–245.
data are listed in Table 4. HR-MS calcd for C33H26O4:
486.1824. Found: 486.1801. Anal. Calcd for C33H26O4: C,
81.46; H, 5.39. Found: C, 81.56; H, 5.42.
4.9.6. Acetylation of 10 with Ac2O/pyridine. Acetic
anhydride (1.5 ml) was added to a solution of 10 (40 mg,
0.08 mmol) in pyridine (0.5 ml) at 0 8C and the mixture was
stirred at room temperature for 2 h. The reaction mixture
was poured onto crushed ice and stirred at room temperature
for 1 h, and the whole was extracted with CHCl3. The
organic layer was washed with diluted HCl, and H2O, then
dried, filtered, and evaporated in vacuo. The crude product
was purified by flash column chromatography on silica gel.
The eluate with CH2Cl2–hexane (1:1, v/v) gave 38 mg
3. (a) Hwang, D.-R.; Chen, C.-P.; Uang, B.-J. J. Chem. Soc.,
Chem. Commun. 1999, 1207–1208. (b) Luo, Z.; Liu, Q.; Gong,
L.; Cui, X.; Mi, A.; Jiang, Y. Angew. Chem., Int. Ed. 2002, 41,
4532–4535. (c) Sharman, V. B.; Jain, S. L.; Sain, J. B.
Tetrahedron Lett. 2003, 44, 2655–2656.
4. (a) Corma, A.; Garcia, H. Chem. Rev. 2002, 102, 3837–3892.
(b) Li, T.-S.; Duan, H.-Y.; Li, B.-Z.; Tewari, B.-B.; Li, S.-H.
J. Chem. Soc., Perkin Trans. 1 1999, 291–293. (c) Sakamoto,
T.; Yonehara, H.; Pac, C. J. Org. Chem. 1997, 62, 3194–3199.

T. Takeya et al. / Tetrahedron 60 (2004) 10681–10693
10693
(d) Toda, F.; Tanaka, K.; Iwata, S. J. Org. Chem. 1989, 54,
3007–3009.
(H–H COSY); 13C–1H shift correlation spectroscopy (C–H
COSY), 1H-detected heteronuclear multiple bond connectivity
(HMBC); and nuclear Overhauser enhancement and exchange
spectroscopy (NOESY) experiments.
5. Barton, D. H. R. J. Mol. Catal. 1997, 117, 3–7.
6. (a) Maldotti, A.; Molinari, A.; Amadelli, R. Chem. Rev. 2002,
102, 3811–3836. (b) Hoffmann, M. R.; Martin, S. T.; Choi, W.;
Bahnemann, D. W. Chem. Rev. 1995, 95, 69–96. (c)
Fujishima, A.; Honda, K. Nature 1972, 238, 37–38. (d) Fox,
M. A. Top. Curr. Chem. 1987, 142, 71–99.
16. (a) Boger, D. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5,
Chapter 4.3, pp 451–512. (b) Jorgensen, K. A. Angew. Chem.,
Int. Ed. 2000, 39, 3558–3588. (c) Giraud, L.; Giraud, A.
Synthesis 1998, 1153–1160. (d) Nakayama, J. J. Synth. Org.
Chem. Jpn 2003, 61, 1106–1115. (e) Tietze, L. F.; Brumby, T.;
Pretor, M.; Remberg, G. J. Org. Chem. 1988, 53, 810–820. (f)
Pye, C. C.; Xidos, J. D.; Poirier, R. A.; Burnell, D. J. J. Phys.
Chem. A 1997, 101, 3371–3376. (g) Hoffmann, R.; Woodward,
R. B. J. Am. Chem. Soc. 1965, 87, 4388–4389. (h) Nair, V.;
Kumar, S. Tetrahedron 1996, 52, 4029–4040. (i) Nair, V.;
Mathew, B.; Radhakrishnan, K. V.; Rath, N. P. Tetrahedron
1999, 55, 11017–11026. (j) Nair, V.; Kumar, S. J. Chem. Soc.,
Perkin Trans. 1 1996, 443–447. (k) Nicolau, K. C.; Snyder,
S. A.; Montagnon, T.; Vassilikogiannakis, G. Angew. Chem.,
Int. Ed. 2002, 41, 1668–1698.
7. (a) Bergbreiter, D. E. Chem. Rev. 2002, 102, 3345–3384. (b)
Poliakoff, M.; Anastas, P. Nature 2001, 413, 257–258.
8. (a) Ogata, T.; Okamoto, I.; Kotani, E.; Takeya, T. Tetrahedron
2004, 60, 3941–3948. (b) Takeya, T.; Doi, H.; Ogata, T.;
Otsuka, T.; Okamoto, I.; Kotani, E. Tetrahedron 2004, 60,
6295–6310. (c) Otsuka, T.; Okamoto, I.; Kotani, E.; Takeya, T.
Tetrahedron Lett. 2004, 45, 2643–2647. (d) Ogata, T.;
Okamoto, I.; Doi, H.; Kotani, E.; Takeya, T. Tetrahedron
Lett. 2003, 44, 2041–2044.
9. Funabiki, T.; Ohashi, H.; Sugimoto, T.; Yoshida, S. J. Mol.
Catal. 1991, 69, 407–418.
10. (a) Calderon, J. S.; Thomson, R. H. J. Chem. Soc., Perkin
Trans. 1 1988, 583–586. (b) Maiti, B. C.; Musgrave, O. C.
J. Chem. Soc., Perkin Trans. 1 1986, 675–681. (c) Sankaram,
A. V. B.; Reddy, V. V. N.; Sidhu, G. S. Phytochemistry 1981,
20, 1093–1096.
17. (a) Gonzalez, A. G.; Alvarenga, N. L.; E-Braun, A.; Ravelo,
A. G.; Bazzocchi, I. L.; Moujir, L. Tetrahedron 1996, 52,
9597–9608. (b) Shirota, O.; Morita, H.; Takeya, K.; Itokawa,
H. Tetrahedron 1995, 51, 1107–1120. (c) Gonzalez, A. G.;
Alvarenga, N. L.; Bazzocchi, I. L.; Ravelo, A. G.; Moujir, L.
J. Nat. Prod. 1999, 62, 1185–1187. (d) Laschat, S. Angew.
Chem., Int. Ed. Engl. 1996, 35, 289–291. (e) Oikawa, H.; Yagi,
K.; Watanabe, K.; Honma, M.; Ichikawa, A. J. Chem. Soc.,
Chem. Commun. 1997, 97–98.
11. (a) Brimble, M. A.; Brenstrum, T. J. J. Chem. Soc., Perkin
¨
Trans. 1 2001, 1624–1634. (b) Bringmann, G.; Gotz, R.;
Keller, P. A.; Walter, R.; Boyd, M. R.; Lang, F.; Garcia, A.;
Walsh, J. J.; Tellitu, I.; Bhaskar, K. V.; Kelly, T. R. J. Org.
Chem. 1998, 63, 1090–1097.
12. In the 1H NMR spectra of NPOH 1a–c, the signal (d
10.50 ppm) of a hydroxyl proton at the C1-position in 1b
was observed at lower field than the corresponding signals (d
5.66 and 5.32 ppm) in 1a and 1c.
18. (a) Hannan, R. L.; Barber, R. B.; Rapoport, H. J. Org. Chem.
1979, 44, 2153–2158. (b) Wurm, G.; Goebler, B. Arch. Pharm.
1989, 322, 569–572. (c) Takeya, T.; Kajiyama, M.; Nakamura,
C.; Tobinaga, S. Chem. Pharm. Bull. 1999, 47, 209–219. (d)
Casey, C. P.; Jones, C. R.; Tukada, H. J. Org. Chem. 1981, 46,
2089–2092. (e) Casey, C. P.; Jones, C. R.; Tukada, H. J. Org.
Chem. 1998, 63, 1090–1097. (f) Laatsch, H. Liebigs Ann.
13. (a) Kamat, P. V. Chem. Rev. 1999, 93, 267–300. (b) Ingold,
K. U. Acc. Chem. Res. 1969, 2, 1–9. (c) Horswill, E. C.; Ingold,
K. U. Can. J. Chem. 1966, 44, 263–277.
´
14. (a) Sergent, N.; Gelin, P.; P-Camby, L.; Praliaud, H.; Thomas,
´
Chem. 1980, 4, 1321–1347. (g) Gonzalez, A. G.; Alvarenga,
G. Phys. Chem. Chem. Phys. 2002, 4, 4802–4808. (b) Zhuang,
J.; Rusu, C. N.; Yates, J. T. Jr. J. Phys. Chem. B 1999, 103,
6957–6967.
N. L.; E-Braun, A.; Ravelo, A. G.; Bazzocchi, I. L.; Moujir, L.
Tetrahedron 1996, 52, 9597–9608. (h) Saa, J. M.; Jeronimo,
M.; Rubido, C. J. Org. Chem. 1986, 51, 4471–4473.
1
15. 2D NMR experiments: H–1H shift correlation spectroscopy