Enantioselective oxidative-coupling of polycyclic phenols

Article abstract of DOI:10.1016/j.tet.2014.01.017

Enantioselective oxidative-coupling of polycyclic phenols, such as 2-anthracenol, 9- or 3-phenanthrol, and 5-chrysenol was established by using vanadium(V/IV) catalysis under air or O₂ as a co-oxidant. In the vanadium catalyzed reaction, the co

Full text of DOI:10.1016/j.tet.2014.01.017

Tetrahedron 70 (2014) 1786e1793
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Enantioselective oxidative-coupling of polycyclic phenols
Shinobu Takizawa a, Junpei Kodera a, Yasushi Yoshida a, Makoto Sako a,
,
,
*
Stefanie Breukers a b, Dieter Enders b, Hiroaki Sasai a
a The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan
b Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Enantioselective oxidative-coupling of polycyclic phenols, such as 2-anthracenol, 9- or 3-phenanthrol,
and 5-chrysenol was established by using vanadium(V/IV) catalysis under air or O2 as a co-oxidant. In the
vanadium catalyzed reaction, the corresponding coupling products were obtained in good to excellent
yields with up to 93% enantiomeric excess.
Received 25 December 2013
Received in revised form 10 January 2014
Accepted 13 January 2014
Available online 17 January 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Enantioselective
Vanadium
Polycyclic phenol
Oxidative-coupling
1. Introduction
Enantioselective vanadium-mediated oxidative couplings,
which occur via a favorable one-electron phenolic oxidation, pro-
The preparation of optically pure 1,10-bi-2-naphthol (BINOL) and
its derivatives is of great importance because of their wide utility in
asymmetric synthesis.1 Among the synthetic methods to access
enantiomerically pure BINOLs, the asymmetric and catalytic oxi-
dative coupling of 2-naphthols is one of the most straightforward
processes.2,3 Polycyclic biphenols, such as bianthracenol 1a,
biphenanthrols 1b, c, and bichrysenol 1d are also useful as chiral
BINOL derivatives (Fig. 1).4e6 Despite their potential applications,
no efficient enantioselective catalytic oxidative-coupling of the
polycyclic phenols 2 to yield 1 has been achieved due to the facile
over-oxidation of the product and/or side-reaction of the substrate.
ceed under mild reaction conditions and tolerate several functional
groups; this has a further advantage that only water is formed as
a side product.3 Previously, we reported a dinuclear vanadium(V)
complex (Ra,S,S)-3 possessing two active sites in a single molecule,
which promotes the enantioselective oxidative coupling of 2-
naphthols under air as a co-oxidant through a dual activation
mechanism (Fig. 2)3meo
.
Fig. 2. Dinuclear vanadium(V) complexes, (Ra,S,S)-3.
We envisioned that, under the mild reaction conditions, the
dinuclear vanadium(V) complex could work as a chiral catalyst for
the oxidative-coupling of these easily oxidized polycyclic phenols 2
without the formation of any side-products. In this manuscript, we
describe the first enantioselective catalytic coupling of 2-
anthracenol (2a), 3-phenanthrol (2c), and 5-chrysenol (2d), and
Fig. 1. Chiral polycyclic biphenol derivatives.
* Corresponding author. Tel.: þ81 6 6879 8465; fax: þ81 6 6879 8469; e-mail
address: sasai@sanken.osaka-u.ac.jp (H. Sasai).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.01.017

S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
1787
the efficient enantioselective catalytic coupling of 9-phenanthrol
(2b)3o using chiral vanadium(V) complexes, in detail.
to reduction in the enantioselectivity of the product (entries 2e4).
The reaction rate of mononuclear vanadium complex (S)-5a, which
has only one catalytically active center, was quite low in com-
parison with that of (Ra,S,S)-3a, while using 10 mol % of the cat-
alyst (S)-5a (entry 5). The higher reaction rate and
enantioselectivity using dinuclear complex (Ra,S,S)-3a than those
obtained using a mononuclear (S)-5a catalyzed reaction are at-
tributable to the simultaneous activation3meo of two molecules of
2a. Optically pure 1a could be obtained after a recrystallization
from hexane/CH2Cl2 (entry 1).
2. Results and discussion
2.1. Enantioselective coupling of anthracenol 2a
In 2013, Takahashi reported the first catalytic oxidative cou-
pling of 2-anthracenol (2a) with 5 mol % of MnI2, yielding bian-
thracenol 1a in 74% yield.4b However, no catalytic asymmetric
synthesis of 1a has been achieved. Furthermore, 1a is easily over-
oxidized to the ether derivative 4a. To our delight, (Ra,S,S)-3a was
found to promote the oxidative coupling reaction of 2a to yield 1a
without the formation of 4a (Table 1). The reaction with 5 mol % of
(Ra,S,S)-3a at ꢀ10 ꢁC under air produced 1a in 80% yield with 85%
ee (entry 1). The lowering of the reaction temperature to ꢀ20 ꢁC
or the use of the complex (Ra,S,S)-3b with H8-BINOL backbone led
2.2. Enantioselective coupling of phenanthrols 2b and c
An effective and enantioselective synthesis of 9,90-bi(10-
phenanthrol) (1b) via the oxidative coupling of 9-phenanthrol
(2b) has also been a challenge in the oxidative-coupling reactions
because 2b is easily oxidized to the corresponding quinone de-
rivative, phenanthrene-9,10-dione (4b).5 The results of coupling 2b
using vanadium complexes are shown in Table 2. The dinuclear
vanadium catalyst (Ra,S,S)-3a was found to promote the oxidative
coupling reaction of 2b to give 1b in high yields without the for-
mation of 4b. Among the reaction solvents studied, CH2Cl2 pro-
vided the highest reaction rate with high enantioselectivity,
producing biphenanthrol 1b in 94% yield with 88% ee (entry 4).
Although the reaction proceeded under air, the ee of 1b decreased
slightly to 76% (entry 6). At ꢀ10 ꢁC under O2, the reaction with
5 mol % of (Ra,S,S)-3a produced 1b in quantitative yield and with
93% ee (entry 8). The enantioselective coupling of 2b on a gram
scale (6.0 g, entry 9) led to 1b in 90% yield with 90% ee. Optically
pure 1b could be obtained after a single recrystallization from
hexane/acetone (entries 8 and 9).
Next, we focused on the coupling reaction of 3-phenanthrol (2c)
to give 4,40-bi(3-phenanthrol) (1c), which could be readily applied
to construct hetero[7]helicenes.5m During our screening of condi-
tions (Table 3), the dinuclear vanadium complex (Ra,S,S)-3b in
(CH2Cl)2 was found to exhibit moderate asymmetric induction to
produce 1c in 32% yield with 65% ee (entry 3). The yield of 1c was
increased to 48% at 60 ꢁC; however, the enantioselectivity de-
creased to 43% ee (entry 6). Insufficient improvement in chemical
yield was observed even when a quantitative amount of the va-
nadium complex was employed (entry 9). A product inhibition
Table 1
Enantioselective coupling of 2-anthracenol (2a)
Entry
Vanadium complex
(mol %)
Temp (ꢁC)
Yield of
isolated
product %
ee %a
1
2
3
4
5
(Ra,S,S)-3a (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3a (5)
(Ra,S,S)-3b (5)
(S)-5a (10)
ꢀ10
ꢀ10
ꢀ20
ꢀ20
ꢀ10
80
91
60
80
47
85 (>99)b
51
74
49
29
a
Determined using HPLC (Daicel Chiralpak AD-H).
After a single recrystallization.
b
Table 2
Enantioselective coupling of 9-phenanthrol (2b)
Entry
Vanadium complex (mol %)
Solvent
Atmosphere
Temp (ꢁC)
Time (h)
Yield of isolated product %
ee %a
1
2
3
4
5
6
7
8
9d
(Ra,S,S)-3a (5)
(Ra,S,S)-3a (5)
(Ra,S,S)-3a (5)
(Ra,S,S)-3a (5)
(Ra,S,S)-3a (5)
(Ra,S,S)-3a (5)
(S)-5a (10)
MeCN
Toluene
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
O2
O2
O2
O2
O2
Air
O2
O2
O2
ꢀ5
ꢀ5
70
72
60
36
24
74
48
48
48
92
80
90
94
92
80
29
89
86
54
88
ꢀ5
ꢀ5
0
84
ꢀ5
76
ꢀ10
ꢀ10
ꢀ10
10b
(Ra,S,S)-3a (5)
(Ra,S,S)-3a (5)
100 (80)c
90 (79)c
93 (>99)c
90 (>99)c
a
Determined using HPLC (Daicel Chiralpak AD-H).
The major product has (R)-configuration.
After a single recrystallization.
6.0 g scale.
b
c
d

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S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
Table 3
Enantioselective coupling of 3-phenanthrol (2c)
Entry
Vanadium complex (mol %)
Solvent
Atmosphere
Temp (ꢁC)
Yield of isolated product %
ee %a
1
2
3
4
5
6
7
8
(Ra,S,S)-3a (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (5)
(Ra,S,S)-3b (100)
(S)-5a (10)
CH2Cl2
CH2Cl2
(CH2Cl)2
Toluene
(CH2Cl)2
(CH2Cl)2
CHCl3
CHCl3
CHCl3
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
O2
O2
O2
O2
O2
O2
Air
O2
O2
O2
O2
O2
10
10
10
39
30
32
15
9
48
30
32
45
25
32
28
40
42
65
20
67
43
69
68
67
10
12
rac
10
ꢀ10
60
10
10
10
10
10
10
9
10
11
12
(S)-5b (10)
(S)-5c (10)
a
Determined using HPLC (Daicel Chiralpak OD-H).
might be responsible for the low conversion of the coupling of 2c.
To establish the reason for the low conversion of 2c, the reactions of
2-naphthol (2e) or 6-methoxy-2-naphthol (2f) in the presence of
1c or 2c were investigated (Scheme 1). After mixing (Ra,S,S)-3b and
biphenanthrol 1c in (CH2Cl)2 under air for 24 h, 2-naphthol (2e)
was added to the reaction mixture. The coupling reaction of 2e
proceeded smoothly to give BINOL 1e in 86% yield, and biphe-
nanthrol 1c was recovered quantitatively (Eq. 1). Similarly, catalyst
(Ra,S,S)-3b was mixed with phenanthrol 2c for 24 h, followed by the
addition of 2-naphthol (2e); however, almost no BINOL 1e was
formed, and biphenanthrol 1c was obtained in 30% yield (Eq. 2).
When 6-methoxy-2-naphthol (2f), a highly reactive substrate for
the coupling, was added after mixing catalyst (Ra,S,S)-3b and
phenanthrol 2c for 24 h, the coupling products 1f and c were ob-
tained in 90% yield and 35% yield, respectively (Eq. 3). In all cases,
no hetero-cross-coupling product was formed.3n The reason for the
low conversion of 2c remains unclear; however, given the results of
the coupling reactions, our previously proposed reaction mecha-
nism3meo might be in agreement with an intramolecular coupling
as shown in Scheme 2. The dinuclear vanadium(V) complex reacts
with two molecules of 2c resulting in Ia. The C-4 position of the
substrates approaches each other by the rotation of the binaphthyl
Scheme 1. Coupling of 2-naphthols 2e or 2f in the presence of 1 equiv of biphenanthrol 1c or phenanthrol 2c.

S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
1789
Scheme 2. Enantioselective homo-coupling of 2c.
axis yielding Ib, which is then intramolecularly coupled after
3. Application of coupling product 1 to enantioselective di-
a single electron transfer to a vanadium(V) species III via in-
termediate II. However, intermediate III would be very stable,
resulting in the slow release of 1c from III. As a result, low con-
version was observed when 2c was used as a substrate for the
homo-coupling using catalyst (Ra,S,S)-3b.
rect aza-hetero-DielseAlder reaction
Chiral phosphoric acids have emerged as a class of powerful
organocatalysts7 for the activation of imine functional groups,
resulting in a number of asymmetric additions of various nucle-
ophiles to imines. In 2006, Gong8a and Rueping8b independently
reported the direct aza-hetero-DielseAlder reaction of 2-
cyclohexenone (7) with aldimines 8 to produce isoquinuclidines.
To confirm the ability of polycyclic biphenols 1 in asymmetric
catalysis, the corresponding chiral phosphoric acids 6 were pre-
pared from the coupling product 1 and then tested on the aza-
hetero-DielseAlder reaction (Table 5).8a Chiral phosphoric acids
6a, c, and e could promote the reaction, but only afforded the
racemic product 9a (entries 1, 3, and 5). The 9,90-bi(10-
phenanthrol)- and bichrysenol-derived catalysts 6b and d could
provide better asymmetric environments than those of catalysts
6a, c, and e because of the additional two or four aromatic rings
near the phosphoric acid group, leading to the formation of
product 9a with up to 53% ee (entry 4). In comparison with the
best result obtained using catalyst 6f, reported by Rueping
(Scheme 3),8b our catalyst 6d would still need an increased bulk to
create an efficient chiral environment for the aza-hetero-Diel-
seAlder reaction.
2.3. Enantioselective coupling of chrysenol 2d
Bichrysenol 1d is expected to create an effective asymmetric
environment because of the additional aromatic ring adjacent to
the hydroxy group.1 The oxidative coupling of 5-chrysenol (2d) was
also conducted using dinuclear vanadium(V) complexes (Ra,S,S)-3
(Table 4). However, racemic 1d was obtained when 5 mol % of
(Ra,S,S)-3a or 3b was used at ꢀ10 ꢁC under O2 (entry 1). These re-
sults may be attributed to the steric obstruction close to the re-
action site of the dinuclear complex. Therefore, we tested
mononuclear vanadium complexes 5, which possess less steric
hindrance. As expected, the mononuclear vanadium complexes
could promote the coupling of 2d enantioselectively. In this cou-
pling reaction, the aromatic substitutions on catalysts 5 made
a significant impact on the enantioselectivity of 1d. As shown in
Table 4, catalysts (S)-5b and d, bearing a 5- or 6-substituent on the
aromatic ring of the catalyst, exhibited good asymmetric induction
in 1d (entries 3 and 5, 71% ee and 61% ee, respectively). In contrast,
3- and/or 4-mono- or disubstituted catalysts gave 1d with <30% ee
(entries 2 and 6e8). Among the reaction conditions we screened,
mononuclear vanadium catalyst 5b in CH2Cl2 led to coupling with
the highest ee (75%). Finally, optically pure 1d was readily obtained
by a recrystallization from a hexane/CH2Cl2 mixed solvent system
(entry 11).
4. Transformation of polycyclic biphenol
In order to improve the chiral catalyst efficiency of the poly-
cyclic biphenol, various transformations of 1b were tested
(Scheme 4). The reaction of 1b using PtO2 (1 equiv) in glacial
acetic acid under H2 (1 atm) at room temperature led to

1790
S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
Table 4
Enantioselective coupling of 5-chrysenol (2d)
Entry
Vanadium complex (mol %)
Solvent
Temp (ꢁC)
Time (h)
Yield of isolated product %
ee %a
1
2
3
4
5
6
7
8
(Ra,S,S)-3a (5) or 3b (5)
(S)-5a (10)
(S)-5b (10)
(S)-5c (10)
(S)-5d (10)
(S)-5e (10)
(S)-5f (10)
(S)-5g (10)
(S)-5b (10)
(S)-5b (10)
(S)-5b (10)
(S)-5b (10)
(S)-5b (10)
(S)-5b (10)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ20
Rt
ꢀ10
ꢀ10
ꢀ10
ꢀ10
24
24
24
24
24
24
24
24
24
24
36
36
36
36
54 or 55
67
55
40
32
47
48
43
52
54
83
36
55
rac
30
71
38
61
9b
20b
27b
68
9
10
11
12
13
14
25
75 (>99)c
63
CCl4
Toluene
64
24
45
a
Determined using HPLC (Daicel Chiralpak AD-H).
The major product has (R)-configuration.
After a single recrystallization.
b
c
complete conversion to give H16-biphenanthrol 10 in 80% yield.9
The methyl capped biphenanthrol 115a underwent bromination
by using N-bromosuccinimide (NBS), providing the 6,60-dibro-
minated compound 12 quantitatively. The methyl capped dibro-
mobiphenanthrol 12 could be a versatile intermediate for further
derivatization. Thus, 12 was treated with Pd(PPh3)4, PhB(OH)2,
and Na2CO3 in 1,2-dimethoxyethane (DME) at reflux temperature
providing 14. The methoxy derivatives were easily deprotected in
the presence of BBr3, which provided diols 13 or 15 in good
yields.
Table 5
Direct organocatalytic enantioselective DielseAlder reaction of 2-cyclohexenone (7) and aldimines 8
Entry
Phosphoric acids
Ar1
Ar2
8
Yield of isolated product % (ratio endo/exo)
ee % of endoa
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6d
6d
6d
Ph
Ph
Ph
Ph
Ph
Ph
4-BreC6H4
4-BreC6H4
4-BreC6H4
4-BreC6H4
4-BreC6H4
4-MeOeC6H4
4-MeOeC6H4
4-BreC6H4
8a
8a
8a
8a
8a
8b
8c
8d
80 (60/40), 9a
52 (67/32), 9a
63 (60/40), 9a
54 (78/22), 9a
50 (69/31), 9a
74b (79/21), 9b
92 (77/23), 9c
51 (75/25), 9d
rac
25
rac
53
rac
36
34
46
2-Naphthyl
2-FeC6H4
a
Determined using HPLC (Daicel Chiralcel OD-H for 9a and 9d; Daicel Chiralpak AD for 9b; Daicel Chiralpak AD-H for 9c).
144 h.
b

S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
1791
Scheme 3. Enantioselective DielseAlder reaction reported by Rueping.8b
NMR 400, 600 or 700 MHz, 13C NMR 100, 150 or 175 MHz, 51V NMR
158 MHz). 1H NMR spectra are reported as follows: chemical shift in
parts per million relative to the chemical shift of CHCl3 at 7.26 ppm,
integration, multiplicities (s¼singlet, d¼doublet, q¼quartet,
t¼triplet, m¼multiplet), and coupling constants (Hertz). 13C NMR
spectra are reported in ppm relative to the central line of triplet for
CDCl3 at 77 ppm. 51V NMR spectra were recorded with VOCl3 as an
external standard (0 ppm). FT-MS spectra were obtained with LTQ
Orbitrap XL (Thermo Fisher Scientific). ESI-MS spectra were ob-
tained with JMS-T100LC (JEOL). FAB-MS spectra were obtained with
JMS-700 (JEOL). Optical rotations were measured with JASCO P-
1030 polarimeter. HPLC analyses were performed on a JASCO HPLC
system (JASCO PU 980 pump and UV-975 UV/Vis detector) using
a mixture of hexane and 2-propanol as eluents. FT-IR spectra were
recorded on a JASCO FT-IR system (FT/IR4100). Mp was measured
with SHIMADZU DSC-60. Column chromatography on SiO2 was
performed with Kishida Silica Gel (63e200
mm). Commercially
available organic and inorganic compounds were used without
further purification except for the solvent, which was distilled from
sodium/benzophenone or CaH2.
6.2. General procedure for coupling reactions using vana-
dium complexes
A test tube was charged with a halogenated solvent (1.0 mL)
solution of coupling substrate (0.2 mmol) under air or O2 atmo-
sphere. Vanadium catalyst (0.01 or 0.02 mmol, 5 or 10 mol %) was
added to the solution. The reaction mixture was stirred until the
reaction had reached completion by monitoring with TLC analysis.
Then the reaction mixture was directly purified by silica gel column
chromatography eluting with ethyl acetate/n-hexane to give the
coupling product.
(S)-1a4: 85% ee, [
(CDCl3)
a
]
22 þ513.3 (c 0.3, CHCl3, for 97% ee); 1H NMR
D
d
8.52 (s, 2H), 8.20 (d, J¼9.6 Hz, 2H), 7.99 (d, J¼8.4 Hz, 2H),
7.73 (s, 2H), 7.61 (d, J¼8.4 Hz, 2H), 7.47 (d, J¼9.6 Hz, 2H), 7.39 (t,
J¼8.4 Hz, 2H), 5.21 (br s, 2H); Daicel Chiralpak AD-H column, 2-
propanol/n-hexane¼3/17, flow rate 1.0 mL/min, 30.4 min (R-iso-
Scheme 4. Transformation of 1b.
5. Conclusions
mer) and 41.9 min (S-isomer).
(S)-1b5a: >99% ee, [
a
]
ꢀ65.7 (c 1.2, CHCl3, for >99% ee); 1H
23
D
We have developed a vanadium-mediated enantioselective
catalytic oxidative-coupling of polycyclic phenols 2; various phe-
nols were successfully employed with 5 or 10 mol % of the catalyst
to give the corresponding biphenols 1 in good to excellent yields
with up to 93% ee. The conversion of 1 to the corresponding
phosphoric acids was achieved and utilized them in the hetero-
DielseAlder reaction. Further transformations of 1 were carried out
and their use in asymmetric catalysis is currently under
investigation.
NMR (CDCl3)
d
8.81 (d, J¼8.2 Hz, 2H), 8.75 (d, J¼8.2 Hz, 2H), 8.46 (d,
J¼8.2 Hz, 2H), 7.84e7.80 (m, 2H), 7.74e7.71 (m, 2H), 7.55e7.52 (m,
2H), 7.37e7.33 (m, 2H), 7.28e7.24 (m, 2H), 5.55 (br s, 2H); Daicel
Chiralpak AD-H column, 2-propanol/n-hexane¼3/17, flow rate
1.0 mL/min, 21.0 min (R-isomer) and 23.0 min (S-isomer).
(R)-1c5m: 69% ee, [
(CDCl3)
a
]
24 ꢀ59.1 (c 0.8, CHCl3, for 95% ee); 1H NMR
D
d
8.09 (d, J¼8.7 Hz, 2H), 8.03 (d, J¼8.7 Hz, 2H), 7.86e7.82 (m,
4H), 7.74 (d, J¼8.7 Hz, 2H), 7.45 (d, J¼8.7 Hz, 2H), 7.41e7.38 (m, 2H),
6.96e6.92 (m, 2H), 5.03 (br s, 2H); Daicel Chiralpak OD-H column,
2-propanol/n-hexane¼3/7, flow rate 0.5 mL/min, 16.4 min (S-iso-
6. Experimental section
6.1. General information
mer) and 32.7 min (R-isomer).
22
(S)-1d: 75% ee, [
a
]
þ213.5 (c 0.1, CHCl3, for 96% ee); 1H NMR
D
(CDCl3)
d
9.80 (d, J¼8.4 Hz, 2H), 8.92 (d, J¼9.2 Hz, 2H), 8.90 (d,
J¼8.4 Hz, 2H), 8.19 (d, J¼9.2 Hz, 2H), 8.07e8.05 (m, 2H), 7.69e7.59
(m, 6H), 7.39 (t, J¼7.8 Hz, 2H), 7.29 (d, J¼7.8 Hz, 2H), 6.32 (br s, 2H);
1H-, 13C-, and 51V NMR spectra were recorded with JEOL JMN
ECS400 FT NMR, JNM ECA600 FT NMR or Bruker AVANCE II (1H
13C NMR (CDCl3)
d 152.6, 133.1, 132.2, 131.7, 130.7, 129.9, 129.1, 128.4,

1792
S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
127.9, 127.0, 126.5, 125.7, 124.9, 124.7, 123.8, 121.1, 120.3, 109.8;
6.6. Transformation of (S)-1b
HRMS (ESI-TOF): calcd for C36H22O2Na [MþNa]þ 509.1517, found:
m/z 509.1511; IR (KBr): 3457, 2989, 1763, 1376, 1242, 1056 cmꢀ1
;
6.6.1. Preparation of (S)-10. To a 5 mL round-bottomed flask at rt
was added (S)-1b (50 mg, 0.13 mmol), and PtO2 (31.7 mg,
0.12 mmol) in glacial acetic acid (1.5 mL). The flask was furnished
with a stream of hydrogen (1 atm) at rt. After stirring for 5 days, the
reaction mixture was filtered by Celite to remove PtO2. The mother
liquid was washed with H2O, and then evaporated. The crude was
purified by column chromatography to give (S)-10 in 80% yield
Daicel Chiralpak AD-H column, 2-propanol/n-hexane¼3/17, flow
rate 1.0 mL/min, 11.9 min (S-isomer) and 23.2 min (R-isomer).
6.3. Preparation of mononuclear vanadium complex (S)-5b
A
round bottomed flask was charged with 2-hydroxy-1-
(42 mg, 0.10 mmol) as a pale brown solid.
21
naphthaldehyde (1.46 mmol), which were prepared according to
the known method, (S)-tert-leucine (1.60 mmol), MS 3A (0.73 g)
and EtOH (25 mL). The reaction mixture was refluxed at 80 ꢁC and
consumption of the aldehyde substrate was monitored by TLC. After
evaporation of EtOH, the residue was suspended in CH2Cl2 (15 mL)
and then VOCl3 (3.21 mmol) was added. The reaction mixture was
stirred for 12 h, and filtered by Celite to remove MS 3A. The filtrate
was evaporated and the resulting black solid was dissolved in
MeOH and the solvent was evaporated again. The residue was
collected by filtration and washed sequentially with water and
ether, and then dried in a vacuum to give (S)-5b in 58% yield as
a black powder.
(S)-10: Mp 177e179 ꢁC; >99% ee, [
a
]
ꢀ32.9 (c 0.5, CHCl3, for
D
>99% ee); 1H NMR (CDCl3):
d
4.60 (br, s, 2H), 2.78e2.43 (m, 12H),
149.1,
2.35e2.08 (m, 4H), 1.94e1.54 (m, 16H); 13C NMR (CDCl3):
d
137.3, 132.6, 127.7, 121.7, 115.6, 27.7, 26.7, 26.2, 23.7, 23.3, 23.1, 22.9,
22.2; HRMS (ESI-TOF): calcd for C28H34O2Na [MþNa]þ 425.2451,
found: m/z 425.2452; IR (KBr): 3517, 2928, 2860, 1438, 1301,
1212 cmꢀ1
.
6.6.2. Preparation of (S)-11. To
a
solution of (S)-1b (1.0 g,
2.58 mmol) in anhydrous acetone (20 mL) was added to anhydrous
K2CO3 (1.43 g, 10.4 mmol) and methyl iodide (1.83 g, 12.9 mmol).
The reaction mixture was heated at 50 ꢁC under Ar atmosphere for
4 h. After cooling to rt, the volatiles were removed in vacuum and
the residues were washed with CH2Cl2. The organic layers were
dried over anhydrous Na2SO4 and then evaporated. The crude was
purified by column chromatography to give (S)-11 in 80% yield
(0.85 g, 2.06 mmol) as a white solid.
(S)-5b: 1H NMR (CD3OD):
d
9.48 (s, 1H), 8.29 (d, J¼8.6 Hz, 1H),
8.09 (d, J¼9.1 Hz, 1H), 7.87 (d, J¼8.6 Hz, 1H), 7.63 (t, J¼7.2 Hz, 1H),
7.43 (t, J¼7.2 Hz, 1H), 7.14 (d, J¼9.1 Hz, 1H), 4.37 (s, 1H), 1.28 (s, 9H);
13C NMR (CD3OD);
d 180.3, 165.8, 163.3, 138.7, 134.9, 130.5, 130.04,
130.00, 125.4,121.4, 120.9, 112.6, 85.4, 38.3, 28.2; 51V NMR (CD3OD):
d
ꢀ558.3; HRMS (ESI-TOF): calcd for C18H20NO5VNa
(S)-115a: Mp 255e257 ꢁC; >99% ee, [
a]
D
25 þ35.8 (c 1.0, CHCl3, for
[MeOHþOMeþNa]þ 404.0678, found: m/z 404.0674; IR (KBr):
>99% ee); 1H NMR (CDCl3)
d
8.84 (d, J¼8.1 Hz, 2H), 8.77 (d, J¼8.3 Hz,
3233, 2961, 1672, 1612, 1335, 971 cmꢀ1
.
2H), 8.34 (d, J¼9.5 Hz, 2H), 7.80e7.70 (m, 4H), 7.58e7.55 (m, 2H),
7.34e7.33 (m, 4H), 3.57 (s, 6H); 13C NMR (CDCl3)
152.7, 132.9, 132.0,
128.2,128.1,127.2,126.9ꢂ2,126.8,125.5,123.6,122.9,122.7,122.3, 61.2.
d
6.4. Preparation of organocatalyst (S)-6d
6.6.3. Preparation of (S)-12. To solution of (S)-11 (50 mg,
a
The organocatalyst (S)-6d was prepared according to the liter-
0.12 mmol) in MeCN (2 mL) was gradually added to NBS (107 mg,
0.6 mmol). The reaction mixture was stirred for 2 h under reflux
conditions. The volatiles were removed in vacuum and the residues
were washed with water, brine, and CH2Cl2. The organic layers
were dried over anhydrous Na2SO4 and then evaporated. The crude
was purified by column chromatography to give (S)-12 in quanti-
ature method.8a
22
(S)-6d: [
a
]
þ822.0 (c 0.2, CHCl3, for 96% ee); 1H NMR (CDCl3)
D
d
9.71 (d, J¼7.6 Hz, 2H), 8.75e8.63 (m, 4H), 7.90e7.19 (m, 14H); 13
C
NMR (CDCl3)
d 146.68, 146.62, 143.2, 140.7, 133.0, 131.61, 131.25,
129.8, 129.2, 128.5, 128.2, 127.6, 127.3, 126.7, 126.4, 125.9, 125.0,
123.5, 123.0, 122.6, 120.7; 31P NMR (CDCl3)
d
1.62; HRMS (ESI-TOF):
tative yield (68 mg, 0.12 mmol).
23
calcd for C36H21O4PNa [MþNa]þ 571.1070, found: m/z 571.1072; IR
(S)-12: Mp 282e284 ꢁC; >99% ee, [
a
]
ꢀ17.4 (c 1.0, CHCl3, for
D
(KBr): 3438, 2938, 1744, 1365, 1211, 1090 cmꢀ1
.
>99% ee); 1H NMR (CDCl3)
2H), 8.33e8.32 (m, 2H), 7.79e7.74 (m, 4H), 7.43e7.39 (m, 2H),
7.17e7.13 (m, 2H), 3.55 (s, 6H); 13C NMR (CDCl3)
153.2, 131.4, 131.0,
d
8.89 (d, J¼2.0 Hz, 2H), 8.74e8.72 (m,
d
6.5. General procedure for direct organocatalytic enantiose-
lective DielseAlder reaction of 2-cyclohexenone (7) and aldi-
mines 8
130.2, 129.8, 128.3, 128.2, 127.7, 127.6, 125.6, 123.7, 123.0, 121.3,
120.1, 61.3; HRMS (ESI-TOF): calcd for C30H20Br2O2Na [MþNa]þ
594.9702, found: m/z 594.9702; IR (KBr): 3071, 2947, 1588, 1428,
1118, 1086 cmꢀ1
.
2-Cyclohexenone (7) (0.07 mL, 0.73 mmol) was added to a vial
containing aldimines 8 (0.073 mmol) and a catalytic amount of
phosphoric acid 6 (5 mol %) in toluene (0.27 mL) at rt. After vig-
orously stirring the mixture for 72 h, the reaction mixture was di-
rectly purified by column chromatography on silica gel to afford 9.
6.6.4. Preparation of (S)-13. To a solution of (S)-12 (200 mg,
0.36 mmol) in CH2Cl2 (4 mL) was slowly added to BBr3 (1 M solution
in CH2Cl2) (0.76 mL, 0.76 mmol) at 0 ꢁC under Ar atmosphere. The
reaction mixture was stirred for overnight. After addition of water
(1 mL), the mixture was extracted with CH2Cl2. The organic layers
were washed with water, brine, and dried over anhydrous Na2SO4.
After the evaporation, (S)-13 was obtained in 70% yield (130 mg,
endo-9c: 34% ee, [
(CDCl3)
a
]
20 þ32.7 (c 0.6, CHCl3, for 34% ee); 1H NMR
D
d
7.83e7.74 (m, 4H), 7.45e7.39 (m, 3H), 6.75 (dd, J¼6.6,
2.2 Hz, 2H), 6.66 (dd, J¼6.6, 3.2 Hz, 2H), 4.72 (s, 1H), 4.50 (s, 1H),
3.70 (s, 3H), 2.88e2.83 (m, 2H), 2.49 (dd, J¼18.8, 2.7 Hz, 1H),
2.37e2.29 (m, 1H), 2.25e2.15 (m, 1H), 2.11e2.03 (m, 1H), 1.81e1.74
0.25 mmol) as a white solid.
25
(S)-13: Mp 303e305 ꢁC; >99% ee, [
a
]
ꢀ49.6 (c 0.5, CHCl3, for
D
(m, 1H); 13C NMR (CDCl3)
d
211.8, 152.1, 142.5, 139.6, 133.6, 133.0,
>99% ee); 1H NMR (CDCl3)
d
8.85 (d, J¼2.0 Hz, 2H), 8.70 (d, J¼8.3 Hz,
128.9, 128.1, 127.7, 126.1, 125.8, 124.6, 123.8, 114.8, 114.6, 66.5, 55.6,
52.0, 49.3, 46.2, 22.8, 22.3; HRMS (ESI-TOF): calcd for C24H23NO2Na
[MþNa]þ 380.1621, found: m/z 380.1621; IR (KBr): 3422, 2948,
2372, 1721, 1510, 1248 cmꢀ1; Daicel Chiralpak AD-H column, 2-
propanol/n-hexane¼1/20, flow rate 1.0 mL/min, 28.8 min (minor
isomer) and 39.8 min (major isomer).
2H), 8.44 (d, J¼8.3 Hz, 2H), 7.85e7.81 (m, 2H), 7.76e7.72 (m, 2H),
7.41 (dd, J¼8.8, 2.0 Hz, 2H), 7.06 (d, J¼8.8 Hz, 2H), 5.58 (s, 2H); 13
C
NMR (CDCl3)
d 149.9, 131.0, 130.8, 130.2, 128.8, 128.7, 127.7, 126.7,
125.9, 125.1, 123.7, 122.8, 119.2, 106.3; HRMS (ESI-TOF): calcd for
C
28H14Br2O2Na [MeH2þNa]þ 564.9233, found: m/z 564.9231; IR
(KBr): 3488, 1591, 1491, 1423, 1207, 1002, 672 cmꢀ1
.

S. Takizawa et al. / Tetrahedron 70 (2014) 1786e1793
1793
6.6.5. Preparation of (S)-14. To
a
solution of (S)-12 (50 mg,
References and notes
0.09 mmol) in DME (1.5 mL) and 2 M aq Na2CO3 (0.25 mL) was
added to PhB(OH)2 (27 mg, 0.22 mmol) and Pd(PPh3)4 (10 mg,
0.009 mmol) under Ar atmosphere. The reaction mixture was
heated at 80 ꢁC for 8 h. After filtration, the mixture was extracted
with CH2Cl2. The organic layers were washed with water, brine, and
dried over anhydrous Na2SO4 and then evaporated. The crude was
purified by column chromatography to give (S)-14 in 79% yield
(39 mg, 0.07 mmol) as a white solid.
1. (a) Pu, L. Chem. Rev. 1998, 98, 2405; (b) Brunel, J. M. Chem. Rev. 2007, 107, PR1; (c)
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Zhou, Q.-L., Ed.; Wiley-VCH GmbH & KGaA: Weinheim, Germany, 2011; (d) Allen,
S. A.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013, 113,
6234.
2. Recent reviews and reports on asymmetric oxidative coupling of 2-naphthols,
see: (a) Punniyamurthy, T.; Rout, L. Coord. Chem. Rev. 2008, 252, 134; (b) Taki-
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akami, S.; Higashimura, H. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 5872;
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(S)-14: >99% ee, [
a
]
22 ꢀ2.1 (c 0.5, CHCl3, for >99% ee); 1H NMR
D
(CDCl3)
d
9.00 (d, J¼1.7 Hz, 2H), 8.96e8.93 (m, 2H), 8.39 (m, 2H),
7.83e7.74 (m, 8H), 7.61e7.58 (m, 2H), 7.52e7.34 (m, 8H), 3.63 (s,
6H); 13C NMR (CDCl3)
d
152.8, 141.3, 138.3, 132.1, 128.9, 128.5, 128.4,
127.5, 127.3, 127.1, 126.4, 123.7, 123.0, 122.1, 121.2, 120.8, 115.3, 61.4
(One peak is merged with other peak.); HRMS (ESI-TOF): calcd for
C
42H30O2Na [MþNa]þ 589.2138, found: m/z 589.2140; IR (KBr):
3416, 2841, 1593, 1227, 1080, 700 cmꢀ1
.
6.6.6. Preparation of (S)-15. To
a solution of (S)-14 (40 mg,
0.071 mmol) in CH2Cl2 (4 mL) was slowly added to BBr3 (1 M so-
lution in CH2Cl2) (0.18 mL, 0.18 mmol) at 0 ꢁC under Ar atmosphere.
The reaction mixture was stirred for overnight. After addition of
water (1 mL), the mixture was extracted with CH2Cl2. The organic
layers were washed with water, brine, and dried over anhydrous
Na2SO4. After the evaporation, (S)-15 was obtained in quantitative
yield (38 mg, 0.071 mmol) as a white solid.
25
(S)-15: Mp 184e186 ꢁC; >99% ee, [
a]
ꢀ51.7 (c 0.5, CHCl3, for
D
>99% ee); 1H NMR (CDCl3)
d
8.96 (d, J¼1.7 Hz, 2H), 8.92e8.90 (m,
4. (a) Bell, F.; Waring, D. H. J. Chem. Soc. 1949, 267; (b) Zhang, S.; Wang, Y.; Song, Z.;
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5. (a) Yamamoto, K.; Fukushima, H.; Okamoto, Y.; Hatada, K.; Nakazaki, M. J. Chem.
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M. Chem. Lett. 1988, 8, 1371; (g) Yamamura, K.; Ono, S.; Ogoshi, H.; Masuda, H.;
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G. Tetrahedron: Asymmetry 1995, 6, 779; (l) Lin, Y.; Chien, L. C. Tetrahedron:
Asymmetry 1998, 9, 63; (m) Nakano, K.; Hidehira, Y.; Takahashi, K.; Hiyama, T.;
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7. Selected reviews for chiral phosphoric acids as organocatalysts, see: (a) Akiyama,
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6H), 7.63e7.59 (m, 2H), 7.50e7.48 (m, 4H), 7.40e7.36 (m, 4H), 5.61
(s, 2H); 13C NMR (CDCl3)
d 149.6, 141.3, 137.7, 132.1, 130.9, 128.9,
128.3, 127.5, 127.3, 127.1, 125.6, 125.15, 125.13, 123.7, 122.8, 121.5,
107.0 (One peak is merged with other peak.); HRMS (ESI-TOF):
calcd for C40H24O2Na [MeH2þNa]þ 559.1669, found: m/z 559.1667;
IR (KBr): 3416, 2841, 1593, 1227, 1080, 700 cmꢀ1
.
Acknowledgements
This work was supported by the CREST project of the Japan
Science and Technology Corporation (JST), Grant-in-Aid for Scien-
tific Research on Innovative Areas ‘Advanced Molecular Trans-
formations by Organocatalysts’ from the Ministry of Education,
Culture, Sports, Science and Technology (MEXT), and the JSPS Jap-
aneseeGerman Graduate Externship, Japan. We thank the Deut-
sche Forschungsgemeinschaft (scholarship for S.B., the
International Research Training Group ‘Selectivity in Chemo- and
Biocatalysis’dSeleca, Germany). We acknowledge the technical
staff of the Comprehensive Analysis Center of ISIR, Osaka University
(Japan).
9. Kim, J. G.; Camp, E. H.; Walsh, P. J. Org. Lett. 2006, 8, 4413.