Chiral Dinuclear Vanadium Complex-Mediated Oxidative Coupling of Resorcinols

Article abstract of DOI:10.1021/acs.joc.8b02494

A method for the highly regio- and enantioselective oxidative coupling of resorcinols has been established by using dibrominated dinuclear vanadium(V) catalyst 1c under air. When resorcinols bearing an aryl substituent were applied as substrates to the co

Full text of DOI:10.1021/acs.joc.8b02494

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Note
Chiral Dinuclear Vanadium Complex-
mediated Oxidative Coupling of Resorcinols
Makoto Sako, Takanori Aoki, Nadine Zumbrägel, Lukas
Schober, Harald Gröger, Shinobu Takizawa, and Hiroaki Sasai
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02494 • Publication Date (Web): 01 Dec 2018
Downloaded from http://pubs.acs.org on December 2, 2018
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The Journal of Organic Chemistry
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Chiral Dinuclear Vanadium Complex-mediated Oxidative Coupling of
Resorcinols
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Makoto Sako, Takanori Aoki, Nadine Zumbrägel, Lukas Schober,†,‡ Harald Gröger, Shinobu
†
†
†,‡
‡
,
†
,†
Takizawa,* Hiroaki Sasai*
†The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki-shi, Osaka 567-0047, Ja-
pan
‡Chair of Organic Chemistry I, Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany
ABSTRACT: A method for the highly re-
gio- and enantioselective oxidative cou-
pling of resorcinols has been established by
using dibrominated dinuclear vanadium(V)
catalyst 1c under air. When resorcinols
bearing an aryl substituent were applied as
substrates to the coupling, axially chiral bi-
resorcinols were obtained as single regioi-
somers in high yield with up to 98% ee.
4
5
Optically pure 1,1’-bi-2-phenol derivatives are an important
class of chiral compounds in asymmetric synthesis because these
compounds serve as chiral ligands for various transition metals, or-
oxidative coupling of phenol derivatives using peroxide initiators,
6
7
hypervalent iodines, and electrochemical methods.
Resorcinol (benzene-1,3-diol) is an important raw material for
the synthesis of pharmaceuticals and other organic products. Di-
meric resorcinols, i.e., biresorcinols, are also an attractive species
because of their high potential as bioactive compounds, chiral rea-
gents, and functional materials. Recently, Kozlowski et al. demon-
strated the first enantioselective oxidative coupling of these deriv-
atives using 20 to 40 mol% of a chiral mononuclear vanadium com-
1,2
ganocatalysts, and bioactive compounds (Figure 1). To date, var-
ious synthetic approaches of optically active 1,1’-bi-2-phenol de-
rivatives such as (A) kinetic resolution of racemic compounds or
atropselective transformation of prochiral compounds, (B) a chiral-
ity transfer such as from central chirality to axial chirality, and (C
and D) an enantioselective coupling of phenol derivatives have
8
1
been developed by numerous chemists (Scheme 1). Among the
9
plex. However, the regio- and enantioselective oxidative coupling
protocols for the catalytic synthesis of biphenol derivatives, oxida-
tive coupling of phenol derivatives is one of the most straightfor-
ward and sustainable protocols as it requires no pre-activation for
the coupling partners. However, the number of methods for the en-
antioselective synthesis of axially chiral biphenols is still limited
due to high oxidation potentials requiring strong oxidants and harsh
condition, especially when compared to that for the catalytic asym-
metric synthesis of 1,1’-bi-2-naphthol (BINOL) using chiral metal
catalysts [mononuclear metal catalysts: Smrćina and Koćovský (Cu
3
a
3b
3c,d
1
993), Nakajima (Cu 1999), Katsuki (Ru 2000, Fe 2009),
3
e
3f
3g
Kozlowski (Cu 2001), Uang (V 2001), Chen (V 2001), Iwa-
sawa (V 2004), Habaue (V, Cu 2005), and Pappo (Fe 2016).
dinuclear metal complex: Gong (V 2002), Gao (Cu 2003), Sasai
and Takizawa (V 2004) ]. Accordingly, significant research ef-
3
h
3i,j
3k
3
l
3m
3n
forts have been dedicated to the development of protocols for the
Scheme 1. Representative strategies for optically active 1,1’-bi-2-
phenol derivatives.
Figure 1. Chiral 1,1’-bi-2-phenol derivatives.
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of phenols remains challenging owing to their inherently high num-
Table 1. Screening of reaction conditions.a
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9
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5
6
ber of reactive sites leading to regioisomers. Herein, we report the
highly regio- and enantioselective oxidative coupling of resorcinols
to provide biresorcinols using a chiral dinuclear vanadium catalyst
(
Scheme 2). When resorcinols bearing an aryl substituent were ap-
plied as substrates to the coupling, axially chiral biresorcinols were
obtained as single regioisomers in high yield, up to 98% ee.
entry
catalyst
Solvent
(ClCH
yield
%)b
ee
(%)c
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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9
0
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0
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0
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3
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9
0
(
1
2
3
4
5
6
7
8
9
(R
(R
(R
(R
(R
(R
a
,S,S)-1a
a
,S,S)-1a
a
,S,S)-1a
a
,S,S)-1a
a
,S,S)-1a
a
,S,S)-1a
2
)
2
2
41
16
10
25
41
64
15
33
65
(Cl
2
CH)
44
Scheme 2. Enantioselective oxidative coupling of resorcinol de-
rivatives catalyzed by chiral dinuclear vanadium complexes.
CCl
4
97
o-Cl
2
C
6
H
4
58
We have previously developed chiral dinuclear vanadium com-
plex-mediated enantioselective coupling reactions of 2-naphthol
derivatives to produce BINOLs with high enantioselectivities. In
that system, the two vanadium atoms in the complex simultane-
ously activate two molecules of 2-naphthols, resulting in a high re-
o-Me
2
C
6
H
4
73
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
86
(S
a
,S,S)-1a
–27
28
3
n,10
(S,S)-4
action rate and high enantioselectivity.
In the present study, we
initially screened reaction conditions using the resorcinol deriva-
tive 2a as a model substrate (Table 1). Due to low solubility of res-
orcinols in organic solvent, all reactions led to heterogeneous ca-
talysis. Among the solvents tested (entries 1-6), toluene (PhMe)
gave the best results (3a in 64% NMR yield with 86% ee) (entry 6).
(R
(R
(R
(R
(R
a
,S,S)-1b
a
,S,S)-1c
a
,S,S)-1c
a
,S,S)-1c
a
,S,S)-1c
19
87 (80)d
6
97 (99)e
1
1
1
0
1f
2g
70
72
80
90
92
98
13h
When the diastereomeric complex (S
a
,S,S)-1a was used as a cata-
lyst, both the chemical yield and ee of 3a decreased (entry 7). The
dinuclear vanadium catalyst (S,S)-4 possessing a biphenyl skeleton
did not improve the outcomes (entry 8). On the basis of these results,
it appears that when the axial chirality of the binaphthyl skeleton
and the central chirality of amino acid moieties in an (R
figured complex are matched, the coupling reaction is significantly
accelerated. Catalyst (R ,S,S)-1b bearing an i-Pr group instead of a
t-Bu group on the amino acid moiety led to a lower yield and enan-
tioselectivity (entry 9). Finally, the bromo-substituted catalyst
a
(R ,S,S)-1c significantly promoted the reaction to afford the desired
aThe reaction of 2a (0.1 mmol) with 5 mol% of vanadium com-
plex (0.005 mmol) was conducted in the solvent (0.5 mL) at
b
1
7
0 °C under air (1 atm). Yields were determined via H NMR
spectroscopy using 1,3,5-trimethoxybenzene as an internal
standard. Ee values were determined using HPLC (DAICEL
CHIRALPAK IA). Isolated yield. After a single recrystalli-
a
,S,S)-con-
c
d
e
a
f
g
zation from EtOAc and hexane. Under O
2
(1 atm). At 50 °C.
h
At 80 °C.
11
product 3a in 80% isolated yield with 97% ee (entry 10). Under
atmosphere, oligomeric side-products were formed owing to
O
2
over-oxidative coupling between 3a and 2a, resulting in a lower
chemical yield of 3a (entry 11). The reaction at 50 °C decreased the
reaction rate (entry 12), while higher reaction temperature also re-
sulted in lower product yield in analogy to the reaction under O
entry 13). Optically pure 3a is readily obtained by a single recrys-
2
(
tallization of the enantiomerically enriched product from EtOAc
and hexane (entry 10). The absolute configuration of 3a provided
by (R ,S,S)-1c was determined to be the S form on the basis of the
a
Flack parameter obtained via X-ray crystallographic analysis.
a
the conversion of 2a with 2.5 mol% of (R ,S,S)-1c, leading to com-
parable results (Scheme 3, 84% yield, 97% ee).
Subsequently, substrate scope and limitations were explored un-
der optimal conditions (Scheme 3). Resorcinol derivatives 2b–l
bearing an electron-donating or electron-withdrawing substituent at
the ortho-, meta-, or para-position of the aryl group were converted
to the corresponding products 3b–j in good yields with high enan-
tioselectivities, excluding 3k and 3l. Although the reaction of 2m
possessing a 2-naphthyl group proceeded smoothly to give 3m in
78% yield with 85% ee, only a trace amount of 1-naphthyl-substi-
tuted 3n was afforded together with the unreacted starting material.
Thus, the coupling reaction was suppressed by a bulky substituent
close to the coupling position. Methyl-substituted 3o and 3p were
obtained in 93% yield with 88% ee and 77% yield with 36% ee,
respectively. Bromo-substituted 2q also undergoes the coupling re-
action to afford 3q in 49% yield with 70% ee. This type of reaction
also proceeded smoothly on a 1.0 mmol scale as demonstrated for
Accordingly, we conducted several control experiments to get
insight into the reaction mechanism (Scheme 4). When a half motif
of dinuclear vanadium complex (S)-5 (10 mol%) was used in the
coupling of 2a, 70% conversion of 2a was achieved with (R)-3a
being afforded in 15% yield with 15% ee (Scheme 4A). Thus, the
dinuclear vanadium structure (5 mol%) is important for an effective
activation of 2a and stereocontrol coupling to afford the product 3a
in high yield (87%) with high enantioselectivity (97%). The use of
Me-protected 2r, possessing just one hydroxy group, or the 1,2-
dihydroxy derivative 2s as the starting material gave a complex
mixture (Scheme 4B). Thus, the hydroxy groups on 1,3-position of
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The Journal of Organic Chemistry
coupling of resorcinol derivatives with high enantiocontrol, the
coupling event would proceed through a known dual-activation
1
2
3
4
5
6
7
8
9
3
n,10
mechanism
). As the newly developed bromo-substituted dinuclear vanadium
catalyst (R ,S,S)-1c proved to be effective for the oxidative cou-
a
involving a 1:2 complex of (R ,S,S)-1c and 2a (eq.
1
a
pling of resorcinol derivatives, other phenol derivatives were also
investigated. When monohydroxyphenol derivatives 3,5-dime-
thylphenol and 2,3,5-trimethylphenol, which were coupling precur-
9
b
sors reported by Kozlowski et al., were employed under our
standard conditions, the corresponding coupling products are ob-
tained in very poor yields.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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In conclusion, we have developed a protocol for highly regio-
and enantioselective oxidative coupling of resorcinol derivatives to
produce axially chiral biphenols. Our catalytic system provided
complementary results to Kozlowski’s report. The newly devel-
oped chiral dinuclear dibromo-vanadium complex exhibited high
catalytic activity resulting from its double activation of resorcinol
derivatives. Additional investigation of the reaction mechanism
from both experimental and theoretical perspectives is now in pro-
gress.
9
b
aThe reaction of 2 (0.1 mmol) with 5 mol % of catalyst (R
a
,S,S)-1c
(
(
0.005 mmol) was carried out in PhMe (0.5 mL) at 70 °C under air
1 atm) for 24-48 h. Yield of isolated product. Ee values were de-
b
4
termined by HPLC. In PhMe/CCl (2/3).
Scheme 3. Substrate scope and limitations.a
EXPERIMENTAL SECTION
. General Methods. H-, 13C-, and 19F-NMR spectra were rec-
1
1
the arene are essential and participate in the dinuclear vanadium
activation. Since the present reaction system is heterogeneous in
toluene, further mechanistic studies such as kinetic studies to de-
termine the order dependence on the vanadium catalyst could not
be performed. To verify whether there is a relation between the re-
activity and the oxidation potential of starting materials, cyclic
voltammetry analysis was performed (Scheme 4C). Although cou-
pling precursor 2k (0.99 eV) showed similar oxidation potential
value such as 2a (0.96 eV), 2g (1.01 eV), 2i (1.07 eV) and 2m (0.99
eV), no reaction proceeded and 2k was recovered quantitatively.
Thus, it is difficult to estimate and rationalize the reactivity based
on oxidation potential.
orded with JEOL JMN ECS400 FT NMR, JNM ECA600 FT NMR
1
3
or Bruker AVANCE II (1H-NMR 400, 600 or 700 MHz, C-NMR
1
9
1
100, 150 or 175 MHz, F-NMR 565 MHz. H-NMR spectra are
reported as follows: chemical shift in ppm relative to the chemical
shift of tetramethylsilane (TMS) at 0 ppm, integration, multiplici-
ties (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet),
13
and coupling constants (Hz). C-NMR spectra reported in ppm rel-
ative to the central line of triplet for CDCl
tiplet for CD OD at 49 ppm. CF CO H used as external standards
for F-NMR. FT-MS spectra were obtained with LTQ Orbitrap XL
Thermo Fisher Scientific). ESI-MS and APCI-MS spectra were
3
at 77 ppm and of mul-
3
3
2
1
9
(
recorded on a Thermo Fisher LTQ ORBITRAP XL. Optical rota-
tions were measured with JASCO P-1030 polarimeter. HPLC anal-
yses 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). Column chromatography on SiO was
2
performed with Kanto Silica Gel 60 (40-100 μm). Commercially
available organic and inorganic compounds were used without fur-
Despite the reaction mechanism for the catalytic cycle remaining
unclear, the key step for the highly regio- and enantioselective cou-
pling is clearly the C–C bond-forming process. Since our chiral di-
nuclear vanadium complex distinctively prompted the oxidative
ther purification. CV was performed in CH
solution containing 0.1 M tetrabutylammonium hexafluorophos-
phate (TBAPF ) as a supporting electrolyte, on a BAS CV-620C
voltammetric analyzer using a platinum disk as the working elec-
trode, platinum wire as the counter electrode, and Ag/AgNO as the
2 2
Cl /acetonitrile (10/1)
6
3
–
1
reference electrode at a scan rate of 100 mV s . The measured po-
tentials were calibrated using a ferrocene/ferrocenium (Fc/Fc+) re-
dox couple as an internal standard.
2
. Procedure and Experimental Data for Resorcinol deriva-
tives.
Preparation of [1,1'-biphenyl]-3,5-diol (2a).12 A suspension of
-bromo-3,5-dimethoxybenzene (10.39 g, 47.9 mmol), phenyl-
boronic acid (6.71 g, 55.0 mmol), Pd(PPh (1.02 g, 0.880 mmol)
and Na CO (9.89 g, 93.3 mmol) in THF/water (5/1, 280 mL) was
stirred for 12 h under reflux condition. After cooling, the reaction
mixture was filtrated through Celite, quenched with sat. NH Cl aq.,
1
3 4
)
2
3
4
Scheme 4. Additional experiments related to the clarification
of the reaction mechanism.
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Page 4 of 8
and extracted with ethyl acetate. The combined organic layers were
dried over anhydrous Na SO , filtered, and evaporated under vac-
uum. The crude product was purified by silica column chromatog-
raphy (hexane/EtOAc = 20/1) to afford 3,5-dimethoxy-1,1'-bi-
4'-fluoro-[1,1'-biphenyl]-3,5-diol (2i).13 342.4 mg, 90% yield (2
steps from 1-bromo-3,5-dimethoxybenzene). White solid. H NMR
(400 MHz, Acetone-D6): δ 8.35 (s, 2H), 7.56-7.61 (m, 2H), 7.14-
7.20 (m, 2H), 6.57 (d, J = 2.3 Hz, 2H), 6.36 (t, J = 2.3 Hz, 1H).
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
4
phenyl in 50% yield (5.16 g). BBr
mmol) was added to a solution of 3,5-dimethoxy-1,1'-biphenyl
5.16 g, 24.1 mmol) in CH Cl (120 mL) at 0 °C. The mixture was
stirred for 12 h at room temperature. After cooling to 0 °C, the re-
action was quenched with sat. NaHCO aq. The aqueous layer was
extracted with CH Cl . The combined organic layers were dried
over anhydrous Na SO , filtered, and evaporated under vacuum.
The crude product was purified by silica column chromatography
hexane/acetone = 2/1) to afford 2a in 95% yield (4.26 g, white
3
(1.0 M in CH
2
Cl
2
, 72 mL, 72
'-choloro-[1,1'-biphenyl]-3,5-diol (2j).14 162.5 mg, 58% yield
2 steps from 1-bromo-3,5-dimethoxybenzene). White solid. H
4
1
(
(
2
2
NMR (400 MHz, Acetone-D6): δ 8.43 (s, 1H), 7.57 (d, J = 8.7 Hz,
H), 7.43 (d, J = 8.7 Hz, 2H), 6.59 (d, J = 2.2 Hz, 2H), 6.37 (t, J =
.2 Hz, 1H).
2
2
3
2
2
5
-(naphthalen-2-yl)benzene-1,3-diol (2m). 234.2 mg, 46% yield
2
4
1
(
2 steps from 1-bromo-3,5-dimethoxybenzene). White solid. H
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR (400 MHz, Acetone-D6): δ 8.35 (s, 2H), 8.08 (d, J = 1.8 Hz,
1H), 7.96 (dd, J = 6.9, 2.5 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.90
(
1
solid). White solid. H NMR (400 MHz, Acetone-D6): δ 8.29 (s,
H), 7.53-7.56 (m, 2H), 7.38-7.43 (m, 2H), 7.29-7.34 (m, 1H), 6.61
(d, J = 2.3 Hz, 2H), 6.36 (t, J = 2.3 Hz, 1H).
b, 2c, 2e, 2f, 2g, 2i, 2j, 2m, and 2n were prepared following the
procedure for 2a.
'-fluoro-[1,1'-biphenyl]-3,5-diol (2b). 155.9 mg, 53% yield (2
(
(
dd, J = 6.9, 2.5 Hz, 1H), 7.73 (dd, J = 8.7, 1.8 Hz, 1H), 7.47-7.54
2
1
3
1
m, 2H), 6.76 (d, J = 2.3 Hz, 2H), 6.41 (t, J = 2.3 Hz, 1H). C{ H}
NMR (100 MHz, Acetone-D6): δ 159.9, 143.9, 139.4, 134.7, 133.7,
29.1, 129.0, 128.4, 127.1, 126.7, 126.1, 106.7, 102.7. (One carbon
2
1
+
is overlapping.) HRMS (ESI) m/z: [M + Na] Calcd for
16 2
C H12NaO 259.0730; Found 259.0730. IR (KBr): 3343, 1606,
2
1
-1
steps from 1-bromo-3,5-dimethoxybenzene). White solid. H NMR
600 MHz, Acetone-D6): δ 8.37 (s, 2H), 7.45 (td, J = 7.8, 1.4 Hz,
H), 7.35-7.38 (m, 1H), 7.24 (td, J = 7.8, 1.4 Hz, 1H), 7.17-7.20
m, 1H), 6.54 (s, 2H), 6.39 (s, 1H). C{ H} NMR (150 MHz, Ac-
etone-D6): δ 160.4 (d, JC–F = 246.3 Hz), 159.4, 138.4, 131.4 (d,
C–F = 2.9 Hz), 130.0 (d, JC–F = 8.6 Hz), 129.9, 125.4 (d, JC–F =
.8 Hz), 116.8 (d, JC–F = 23.0 Hz), 108.4, 102.9. F{ H} NMR
(565 MHz, Acetone-D6): δ -118.6. HRMS (APCI) m/z: [M + H]
Calcd for C12 205.0659; Found 205.0655. IR (KBr): 3325,
1475, 1153, 1006, 815, 743, 687 cm . mp: 170–172 °C.
(
1
(
5-(naphthalen-1-yl)benzene-1,3-diol (2n).15 352.0 mg, 46%
yield (2 steps from 1-bromo-3,5-dimethoxybenzene). White solid.
1
3
1
1
H NMR (400 MHz, CDCl
3
): δ 7.95 (d, J = 8.2 Hz, 1H), 7.89 (d, J
1
=
8.2 Hz, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.39-7.52 (m, 4H), 6.54 (d,
J = 2.3 Hz, 2H), 6.44 (t, J = 2.3 Hz, 1H), 4.88 (s, 2H).
3
3
4
J
2
19
1
3
+
Preparation of 3'-methoxy-[1,1'-biphenyl]-3,5-diol (2d). A sus-
pension of 5-bromobenzene-1,3-diol (199.2 mg, 1.05 mmol), (3-
H
10FO
2
-
1
methoxyphenyl)boronic acid (185.7 mg, 1.22 mmol), Pd(PPh
3 4
)
1
9
609, 1510, 1476, 1445, 1162, 1008, 835, 799, 741, 681 cm . mp:
8–100 °C.
'-methyl-[1,1'-biphenyl]-3,5-diol (2c). 51.9 mg, 28% yield (2
(
34.8 mg, 0.030 mmol) and Na CO (237.0 mg, 2.24 mmol) in
2
3
THF/water (5/1, 4.5 mL) was stirred for 12 h under reflux condition.
After cooling, the reaction mixture was filtrated through Celite,
3
1
steps from 1-bromo-3,5-dimethoxybenzene). White solid. H NMR
400 MHz, Acetone-D6): δ 8.30 (s, 1H), 7.33-7.37 (m, 2H), 7.28 (t,
J = 7.3 Hz, 1H), 7.14 (d, J = 7.3 Hz, 1H), 6.59 (d, J = 2.3 Hz, 2H),
.35 (t, J = 2.3 Hz, 1H), 2.36 (s, 3H). C{ H} NMR (100 MHz,
CDCl ): δ 156.9, 144.1, 140.3, 138.3, 128.6, 128.4, 127.8, 124.1,
107.0, 101.6, 21.5. HRMS (ESI) m/z: [M + H] Calcd for C13H O
13 2
quenched with sat. NH
combined organic layers were dried over anhydrous Na
4
Cl aq., and extracted with ethyl acetate. The
SO , fil-
(
2
4
tered, and evaporated under vacuum. The crude product was puri-
fied by silica column chromatography (hexane/EtOAc = 3/1) to af-
13
1
6
3
1
ford 2d in 41% yield (93.1 mg, white solid). H NMR (400 MHz,
+
CDCl
3
): δ 7.33 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 7.8 Hz, 1H), 7.07 (t,
2
1
01.0916; Found 201.0907. IR (KBr): 3380, 1603, 1483, 1256,
156, 1003, 776, 691 cm . mp: 72–74 °C.
J = 2.3 Hz, 1H), 6.90 (dd, J = 7.8, 2.5 Hz, 1H), 6.64 (d, J = 2.3 Hz,
-
1
13
1
2H), 6.35 (s, 1H), 5.06 (s, 2H), 3.85 (s, 3H). C{ H} NMR (100
MHz, CDCl ): δ 159.8, 156.9, 143.9, 141.9, 129.7, 119.5, 113.2,
112.7, 107.0, 101.8, 55.3. HRMS (ESI) m/z: [M + H] Calcd for
13 13 3
C H O 217.0865; found 217.0856. IR (KBr): 3258, 1597, 1581,
3
'-fluoro-[1,1'-biphenyl]-3,5-diol (2e). 162.6 mg, 56% yield (2
3
1
+
steps from 1-bromo-3,5-dimethoxybenzene). White solid. H NMR
600 MHz, Acetone-D6): δ 8.40 (s, 1H), 7.42-7.45 (m, 1H), 7.38 (d,
J = 7.6 Hz, 1H), 7.27-7.28 (m, 1H), 7.08 (td, J = 8.2, 2.3 Hz, 1H),
.60 (d, J = 2.1 Hz, 2H), 6.38 (s, 1H). C{ H} NMR (150 MHz,
Acetone-D6): δ 164.0 (d, JC–F = 243.5 Hz), 159.9, 144.5, 142.6,
(
-1
1477, 1287, 1161, 1045, 1005, 693 cm . mp: 61–63 °C.
13
1
6
2
h and 2l were prepared following the procedure for 2d. 2r was
1
prepared following the procedure for 2d using 3-bromo-5-methox-
yphenol instead of 5-bromobenzene-1,3-diol with phenylboronic
acid.
3
2
131.3 (d, JC–F = 8.6 Hz), 123.5, 114.7 (d, JC–F = 21.1 Hz), 114.2
2
19
1
(
d, JC–F = 23.0 Hz), 106.4, 103.1. F{ H} NMR (565 MHz, Ace-
+
tone-D6): δ -114.7. HRMS (APCI) m/z: [M + H] Calcd for
205.0659; Found 205.0655. IR (KBr): 3232, 1585, 1510,
12
4
'-methyoxy-[1,1'-biphenyl]-3,5-diol (2h). 329.4 mg, 71%
12 2
C H10FO
1
-
1
yield. White solid. H NMR (400 MHz, CDCl
3
): δ 7.47 (d, J = 8.7
1
475, 1265, 1159, 1007, 797, 679 cm . mp: 136–138 °C.
Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 6.60 (d, J = 2.1 Hz, 2H), 6.30 (t,
J = 2.3 Hz, 1H), 3.85 (s, 3H).
3
'-chloro-[1,1'-biphenyl]-3,5-diol (2f). 216.3 mg, 70% yield (2
1
steps from 1-bromo-3,5-dimethoxybenzene). White solid. H NMR
400 MHz, Acetone-D6): δ 8.39 (s, 2H), 7.55-7.56 (m, 1H), 7.50-
7.52 (m, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.34-7.37 (m, 1H), 6.60 (d,
4
'-(methoxymethoxy)-[1,1'-biphenyl]-3,5-diol (2l). 200.4 mg,
(
1
5
7% yield. White solid. H NMR (400 MHz, Acetone-D6): δ 8.28
1
3
1
(s, 1H), 7.49 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.56 (d,
J = 2.0 Hz, 2H), 6.32 (t, J = 2.0 Hz, 1H), 5.21 (s, 2H), 3.43 (s, 3H).
J = 2.3 Hz, 2H), 6.39 (t, J = 2.3 Hz, 1H). C{ H} NMR (100 MHz,
Acetone-D6): δ 159.9, 144.2, 142.4, 134.9, 131.2, 128.0, 127.4,
13
1
+
C{ H} NMR (100 MHz, Acetone-D6): δ 159.7, 157.8, 143.6,
35.5, 128.5, 117.2, 106.0, 102.0, 95.0, 56.0. HRMS (ESI) m/z: [M
1
26.1, 106.4, 103.2. HRMS (APCI) m/z: [M + H] Calcd for
1
12 2
C H10ClO 221.0364; Found 221.0360. IR (KBr): 3187, 1604,
+
-
1
+ H] Calcd for C14
3402, 3334, 1613, 1450, 1362, 1224, 1173, 1078, 903 cm . mp:
72–174 °C.
5-methoxy-[1,1'-biphenyl]-3-ol (2r). 1.11 g, 93% yield. yellow
14 4
H O 247.0970; Found 247.0963. IR (KBr):
1
566, 1320, 1211, 1157, 1081, 779, 725 cm . mp: 112–114 °C.
-
1
4
'-methyl-[1,1'-biphenyl]-3,5-diol (2g).12 153.3 mg, 69% yield
1
1
(
2 steps from 1-bromo-3,5-dimethoxybenzene). White solid. H
1
2
NMR (400 MHz, Acetone-D6): δ 8.27 (s, 2H), 7.44 (d, J = 8.2 Hz,
2H), 7.22 (d, J = 8.2 Hz, 2H), 6.58 (d, J = 2.1 Hz, 2H), 6.33 (t, J =
2.1 Hz, 1H), 2.33 (s, 3H).
1
oil. H NMR (400 MHz, CDCl
3
): δ 7.53-7.56 (m, 2H), 7.40-7.44
(
1
m, 2H), 7.33-7.37 (m, 1H), 6.73-6.72 (m, 1H), 6.66 (t, J = 2.1 Hz,
H), 6.41 (t, J = 2.1 Hz, 1H), 4.99 (s, 1H), 3.84 (s, 3H).
ACS Paragon Plus Environment

Page 5 of 8
The Journal of Organic Chemistry
Preparation of methyl 3',5'-dihydroxy-[1,1'-biphenyl]-4-carbox-
ylate (2k). The procedure followed that for preparation of com-
pound 2a to give corresponding carboxylic acid, which is subjected
3. Procedure and Experimental Data for Vanadium Complex
(R ,S,S)-1c.
To a solution of (R)-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-di-
carbaldehyde (217.1 mg, 0.634 mmol) in CH Cl was added Br
0.12 mL, 2.34 mmol) at 0 °C. The mixture was stirred for 24 h at
room temperature. After cooling to 0 °C, the reaction was quenched
with 20 % Na SO aq. The aqueous layer was extracted with
CH Cl . The combined organic layers were dried over anhydrous
Na SO , filtered, and evaporated under vacuum. The crude product
was recrystallized from CH Cl to afford (R)-6,6'-dibromo-2,2'-di-
1
5
1
2
3
4
5
6
7
8
9
a
under methylation protocol using conc. H
2 4
SO in MeOH to furnish
2
2
2
2
k. 150.2 mg, 32% yield (in 3 steps from 1-bromo-3,5-dimethox-
(
1
ybenzene). White solid. H NMR (400 MHz, Acetone-D6): δ 8.42
s, 1H), 8.05 (d, J = 8.2 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 6.67 (d,
(
2
3
J = 2.3 Hz, 2H), 6.42 (t, J = 2.1 Hz, 1H), 3.89 (s, 3H).
2
2
Preparation of 2-methyl-[1,1'-biphenyl]-3,5-diol (2o). A suspen-
sion of 2-bromo-4,6-dimethoxybenzaldehyde (148.1 mg, 0.604
mmol), Hydrazine monohydrate (60 µL, 1.23 mmol) and KOH
2
4
2
2
hydroxy-[1,1'-binaphthalene]-3,3'-dicarbaldehyde in 74% yield
(234.6 mg, yellow solid).
(
2 2
105.7 mg, 1.88 mmol) in (CH OH) (0.3 mL) was stirred for 3 h
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
under reflux condition. After cooling room temperature, water was
added to the reaction mixture and the organic layer was extracted
with ethyl acetate. The combined organic layers were dried over
(R)-6,6'-dibromo-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-di-
1
carbaldehyde. H NMR (400 MHz, CDCl
3
): δ 10.60 (s, 1H), 10.19
(
s, 1H), 8.26 (s, 1H), 8.16 (d, J = 1.8 Hz, 1H), 7.47 (dd, J = 8.7, 1.8
anhydrous Na
2
SO
4
, filtered, and evaporated under vacuum. The
13
1
Hz, 1H), 7.05 (d, J = 8.7 Hz, 1H). C{ H} NMR (100 MHz,
CDCl ): δ 196.6, 154.0, 137.3, 135.7, 133.9, 131.6, 128.6, 126.5,
22.6, 118.4, 116.4. HRMS (APCI) m/z: [M + H] Calcd for
498.9181; found 498.9171. IR (KBr): 3052, 3847,
crude product was purified by silica column chromatography (hex-
ane/EtOAc = 40/1) to afford 1-bromo-3,5-dimethoxy-2-methylben-
zene in 54% yield (75.1 mg, colorless oil).
3
+
1
22 2 4
C H13Br O
1
-1
1-bromo-3,5-dimethoxy-2-methylbenzene. H NMR (400 MHz,
1654, 1630, 1492, 1340, 1285, 1172, 1069, 929, 797, 485 cm . mp:
>300 °C. [훼]D +244.8 (c 0.10, CHCl ).
3
18
CDCl
3
): δ 6.70 (d, J = 2.3 Hz, 1H), 6.38 (d, J = 2.3 Hz, 1H), 3.79
1
3
1
(s, 3H), 3.77 (s, 3H), 2.22 (s, 3H). C{ H} NMR (100 MHz,
A round-bottomed flask was charged with (R)-6,6'-dibromo-2,2'-
dihydroxy-[1,1'-binaphthalene]-3,3'-dicarbaldehyde (233.5 mg,
3
CDCl ): δ 158.7, 158.5, 125.4, 119.1, 108.1, 97.8, 55.7, 55.5, 14.9.
+
HRMS (APCI) m/z: [M – Br] Calcd for C
9
H
11
O
2
151.0754; Found
0
(
O
.467 mmol), L-tert-leucine (135.2 mg, 1.03 mmol), VOSO
372.7 mg, 2.06 mmol), MS 3A (397 mg), CH OH (23 mL) under
(balloon). The reaction mixture was refluxed, and the consump-
4 2
•xH O
1
1
51.0753. IR (KBr): 2997, 2964, 1603, 1570, 1488, 1461, 1218,
3
-1
150, 1039 cm .
suspension of 1-bromo-3,5-dimethoxy-2-methylbenzene
417.4 mg, 1.81 mmol), phenyl boronic acid (249.3 mg, 2.04 mmol),
Pd(PPh (52.2 mg, 0.0450 mmol) and Na CO (387.3 mg, 3.65
2
A
tion of (R)-6,6'-dibromo-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-
1
(
dicarbaldehyde was monitored by H NMR. The resulting solution
3
)
4
2
3
was gradually cooled down to room temperature and filtered
through Celite to remove MS 3A. The filtrate was evaporated, and
mmol) in THF/water (5/1, 11 mL) was stirred for 12 h under reflux
condition. After cooling, the reaction mixture was filtrated through
the resulting black solid was dissolved in CH
2
Cl
2
and washed with
SO and con-
,S,S)-1c
Celite, quenched with sat. NH
etate. The combined organic layers were dried over anhydrous
Na SO , filtered, and evaporated under vacuum. The crude product
4
Cl aq., and extracted with ethyl ac-
H
2
O. The organic phase was dried over anhydrous Na
2
4
centrated in vacuum to give desired vanadium complex (R
a
2
4
in 87% yield (361.7 mg, dark green solid).
was purified by silica column chromatography (hexane/EtOAc =
40/1) to afford 3,5-dimethoxy-2-methyl-1,1'-biphenyl in 37% yield
(153.7 mg, colorless oil).
3,5-dimethoxy-2-methyl-1,1'-biphenyl. 1H NMR (400 MHz,
1
(R
a
,S,S)-1c. H NMR (400 MHz, MeOH-d4): δ 8.94 (s, 2H), 8.44
(
s, 2H), 8.27 (d, J = 1.8 Hz, 2H), 7.66 (d, J = 9.2 Hz, 2H), 7.48 (dd,
J = 9.2, 1.8 Hz, 2H), 4.21 (s, 2H), 1.26 (s, 18H). C{ H} NMR
(175 MHz, MeOH-d4): δ 167.7, 137.0, 136.8, 133.6, 132.2, 130.5,
13
1
CDCl
3
): δ 7.39-7.43 (m, 2H), 7.30-7.36 (m, 3H), 6.47 (d, J = 2.3
129.7, 125.3, 118.8, 118.6, 83.7, 38.8, 28.1. HRMS (APCI) m/z:
+
Hz, 1H), 6.41 (d, J = 2.3 Hz, 1H), 3.85 (s, 3H), 3.80 (s, 3H), 2.03
[M – H
870.9264.
. Typical Procedure for Enantioselective Oxidative Cou-
2
O + H] Calcd for C34
H31Br
2
N
2
O
9
V
2
870.9270; found
1
3
1
(s, 3H). C{ H} NMR (100 MHz, CDCl
3
): δ 158.7, 158.0, 143.4,
1
42.1, 129.2, 128.0, 126.8, 116.6, 105.7, 97.3, 55.6, 55.4, 12.7.
4
+
HRMS (APCI) m/z: [M + H] Calcd for C24
H16FO 339.1185; found
pling of Phenols 2. A test tube was charged with resorcinols 2 (0.1
mmol, 1 eq), dinuclear vanadium catalyst (5 mol %) and PhMe (0.5
mL) under air at 70 °C. The mixture was stirred for 24-48 h. The
reaction mixture was then filtered through a short pad of silica gel
and the solvent was evaporated. The crude product was purified by
silica column chromatography (hexane/acetone = 3/2) to afford bi-
resorcinols 3.
3
39.1175. IR (KBr): 2998, 2939, 1603, 1484, 1414, 1221, 1057,
-
1
751, 703 cm .
BBr (1.0 M in CH
tion of 3,5-dimethoxy-2-methyl-1,1'-biphenyl (138.3 mg, 0.606
mmol) in CH Cl (3.0 mL) at 0 °C. The mixture was stirred for 12
h at room temperature. After cooling to 0 °C, the reaction was
quenched with sat. NaHCO aq. The aqueous layer was extracted
with CH Cl . The combined organic layers were dried over anhy-
drous Na SO , filtered, and evaporated under vacuum. The crude
3
2 2
Cl , 1.8 mL, 1.8 mmol) was added to a solu-
2
2
3
[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-tetraol (3a). 15.6 mg,
2
2
1
8
4% yield. White solid. H NMR (400 MHz, Acetone-D6): δ 8.19
2
4
(
6
s, 2H), 7.60 (s, 2H), 6.99-7.08 (m, 6H), 6.68 (d, J = 7.3 Hz, 4H),
.42 (d, J = 2.3 Hz, 2H), 6.13 (d, J = 2.3 Hz, 2H). C{ H} NMR
product was purified by silica column chromatography (hex-
ane/EtOAc = 3/1) to afford 2-methyl-[1,1'-biphenyl]-3,5-diol (2o)
in 97% yield (118.3 mg, white solid).
13
1
(
1
100 MHz, Acetone-D6): δ 158.3, 158.1, 145.7, 142.7, 129.6, 127.7,
26.8, 114.2, 109.4, 102.1. HRMS (APCI) m/z: [M + H] Calcd for
+
1
2-methyl-[1,1'-biphenyl]-3,5-diol (2o). H NMR (400 MHz, Ac-
etone-D6): δ 8.18 (s, 1H), 8.02 (s, 1H), 7.38-7.41 (m, 2H), 7.27-
C H O 371.1278; found 371.1272. IR (KBr): 1469, 1699, 1588,
24 19 4
-
1
1455, 1301, 1168, 1012, 845, 771, 740 cm . mp: 243–245 °C. En-
antiomeric excess: 97%, determined by HPLC (Chiralpak IA, hex-
ane/2-propanol = 3/1; flow rate 1.0 mL/min; 25 °C; 254 nm) first
7
1
1
.33 (m, 3H), 6.41 (d, J = 2.3 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H),
.97 (s, 3H). C{ H} NMR (100 MHz, Acetone-D6): δ 157.2,
56.3, 144.6, 143.3, 129.8, 128.8, 127.4, 113.6, 108.9, 102.2, 12.8.
1
3
1
20
peak: t
EtOAc) for 97% ee.
,2'''-difluoro-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
R R
= 7.0 min, second peak: t = 13.7 min. [훼]D –130.3 (c 0.72,
+
HRMS (APCI) m/z: [M + H] Calcd for C13
H
13
O
2
201.0916; found
2
01.0909. IR (KBr): 3425, 3047, 2871, 1601, 1438, 1246, 1113,
2
-
1
972, 831, 759, 618 cm . mp: 157–159 °C.
1
tetraol (3b). 17.7 mg, 87% yield. White solid. H NMR (600 MHz,
Acetone-D6): δ 8.23 (s, 2H), 7.60 (s, 2H), 7.11-7.14 (m, 2H), 6.81-
9b
16
17
2
p , 2q , and 2s were prepared following reported method.
6
.86 (m, 4H), 6.69 (t, J = 7.2 Hz, 2H), 6.44 (d, J = 2.4 Hz, 2H), 6.14
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 8
1
3
1
(
t, J = 2.4 Hz, 2H). C{ H} NMR (150 MHz, Acetone-D6): δ 160.3
4,4'''-dimethyl-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
tetraol (3g). 18.1 mg, 91% yield. White solid. H NMR (400 MHz,
1
3
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(d, JC–F = 245.6 Hz), 158.2, 158.0, 139.0, 132.5 (d, JC–F = 2.9 Hz),
29.6 (d, 2JC–F = 14.5 Hz), 129.1 (d, JC–F = 7.2 Hz), 123.7 (d, JC–
3
4
Acetone-D6): δ 8.12 (s, 2H), 7.43 (s, 2H), 6.84 (d, J = 7.8 Hz, 4H),
6.63 (d, J = 7.8 Hz, 4H), 6.39 (d, J = 2.3 Hz, 2H), 6.13 (d, J = 2.3
1
F
= 2.9 Hz), 115.8 (d, 2JC–F = 21.7 Hz), 114.9, 110.3, 102.7. F{ H}
19
1
1
3
1
NMR (565 MHz, Acetone-D6): δ -116.1. HRMS (APCI) m/z: [M
H] Calcd for C24
412, 1608, 1590, 1461, 1149, 1014, 1001, 749 cm . mp: >300 °C.
Hz, 2H), 2.21 (s, 6H). C{ H} NMR (100 MHz, Acetone-D6): δ
+
+
3
H
17
F
2
O
4
407.1089; found 407.1096. IR (KBr):
158.3, 158.0, 145.7, 139.9, 136.1, 129.5, 128.4, 114.2, 109.6, 101.9,
-1
+
21.0. HRMS (APCI) m/z: [M + H] Calcd for C26
H
23
O
4
399.1591;
Enantiomeric excess: 97%, determined by HPLC (Chiralpak IA,
hexane/2-propanol = 3/1; flow rate 1.0 mL/min; 25 °C; 254 nm)
found 399.1596. IR (KBr): 3459, 3047, 2923, 1606, 1584, 1449,
1334, 1245, 1171, 1013, 812 cm . mp: 298–300 °C. Enantiomeric
excess: 95%, determined by HPLC (Chiralpak IA, hexane/2-propa-
-
1
20
first peak: t
c 0.48, EtOAc) for 97% ee.
3,3'''-dimethyl-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
R
= 8.1 min, second peak: t
R
= 17.5 min. [훼]D –194.8
(
nol = 3/1; flow rate 1.0 mL/min; 25 °C; 254 nm) first peak: t
R
= 6.6
22
min, second peak: t
95% ee.
R
= 14.9 min. [훼]D –111.4 (c 0.53, EtOAc) for
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
tetraol (3c). 8.4 mg, 42% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 8.12 (s, 1H), 7.48 (s, 2H), 6.88-6.89 (m, 4H), 6.52-
4,4'''-dimethoxy-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
1
6
.55 (m, 2H), 6.43 (s, 2H), 6.41 (d, J = 2.3 Hz, 2H), 6.12 (d, J = 2.3
tetraol (3h). 20.0 mg, 93% yield. White solid. H NMR (400 MHz,
13
1
Hz, 2H), 2.14 (s, 6H). C{ H} NMR (100 MHz, Acetone-D6): δ
58.3, 158.1, 145.9, 142.6, 136.9, 130.5, 127.4, 127.4, 126.7, 114.3,
Acetone-D6): δ 8.11 (s, 2H), 7.40 (s, 2H), 6.65 (d, J = 8.7 Hz, 4H),
6.59 (d, J = 8.7 Hz, 4H), 6.38 (d, J = 2.3 Hz, 2H), 6.13 (d, J = 2.3
1
+
13
1
109.4, 101.9, 21.4. HRMS (APCI) m/z: [M + H] Calcd for
399.1591; found 399.1588. IR (KBr): 3360, 3047, 2915,
Hz, 2H), 3.71 (s, 6H). C{ H} NMR (100 MHz, Acetone-D6): δ
C
1
26
H
23
O
4
159.1, 158.3, 157.9, 145.4, 135.2, 130.6, 114.2, 113.2, 109.6, 101.8,
-
1
+
611, 1446, 1337, 1150, 1013, 784 cm . mp: 165–167 °C. Enanti-
55.3. HRMS (APCI) m/z: [M + H] Calcd for C26
H
23
O
6
431.1489;
omeric excess: 90%, determined by HPLC (Chiralpak IA, hex-
ane/2-propanol = 4/1; flow rate 1.0 mL/min; 25 °C; 254 nm) first
found 431.1496. IR (KBr): 3466, 2925, 1609, 1584, 1516, 1446,
-
1
1242, 1173, 1034, 826, 592 cm . mp: 252–254 °C. Enantiomeric
24
peak: t
EtOAc) for 90% ee.
,3'''-dimethoxy-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
R
= 8.6 min, second peak: t
R
= 16.3 min. [훼]D –146.2 (c 0.42,
excess: 96%, determined by HPLC (Chiralpak IA, hexane/2-propa-
nol = 3/1; flow rate 1.0 mL/min; 25 °C; 254 nm) first peak: t
R
= 9.2
22
min, second peak: t
96% ee.
R
= 20.0 min. [훼]D –88.8 (c 0.54, EtOAc) for
3
1
tetraol (3d). 16.1 mg, 75% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 8.18 (s, 2H), 7.60 (s, 2H), 6.92 (t, J = 8.2 Hz, 2H),
6.61-6.64 (m, 2H), 6.43 (d, J = 2.3 Hz, 2H), 6.29-6.31 (m, 4H), 6.17
4,4'''-difluoro-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
1
tetraol (3i). 16.9 mg, 83% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 8.22 (s, 1H), 7.70 (s, 1H), 6.77-6.83 (m, 4H), 6.66-
6.71 (m, 4H), 6.43 (d, J = 2.3 Hz, 2H), 6.13 (d, J = 2.3 Hz, 2H).
1
3
1
(d, J = 2.3 Hz, 2H), 3.58 (s, 6H). C{ H} NMR (100 MHz, Ace-
tone-D6): δ 159.5, 158.4, 158.1, 145.6, 144.0, 128.6, 122.0, 114.4,
+
13
1
1
1
14.3, 113.4, 109.4, 102.2, 55.0. HRMS (APCI) m/z: [M + H]
Calcd for C26
050, 2945, 2846, 1581, 1446, 1316, 1166, 1015, 849, 780, 697 cm
C{ H} NMR (150 MHz, Acetone-D6): δ 162.3 (d, JC–F = 242.8
3
H
23
O
6
431.1489; found 431.1494. IR (KBr): 3476,
Hz), 158.5, 158.2, 144.4, 138.8, 131.3 (d, JC–F = 8.7 Hz), 114.5 (d,
-
2
19
1
3
JC–F = 21.7 Hz), 114.3, 109.3, 102.3. F{ H} NMR (565 MHz,
1
+
.
mp: 231–233 °C. Enantiomeric excess: 93%, determined by
HPLC (Chiralpak IA, hexane/2-propanol = 4/1; flow rate 1.0
mL/min; 25 °C; 254 nm) first peak: t = 12.6 min, second peak: t
Acetone-D6): δ -117.3. HRMS (APCI) m/z: [M + H] Calcd for
407.1089; found 407.1085. IR (KBr): 3476, 3424,
24 17 2 4
C H F O
-
1
R
R
1607, 1582, 1514, 1451, 1334, 1227, 1170, 1014, 830 cm . mp:
4
=
25.7 min. [훼]2 –171.7 (c 0.48, EtOAc) for 93% ee.
287–289 °C. Enantiomeric excess: 80%, determined by HPLC
D
(
Chiralpak IA, hexane/2-propanol = 4/1; flow rate 1.0 mL/min;
25 °C; 254 nm) first peak: t = 8.2 min, second peak: t = 18.8 min.
훼] –131.6 (c 0.53, EtOAc) for 80% ee.
3,3'''-difluoro-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
1
R
R
tetraol (3e). 14.2 mg, 70% yield. White solid. H NMR (600 MHz,
Acetone-D6): δ 8.31 (s, 2H), 7.86 (s, 2H), 7.05-7.09 (m, 2H), 6.86
2
0
[
D
(
td, J = 8.1, 2.7 Hz, 2H), 6.52 (d, J = 8.1 Hz, 2H), 6.46 (d, J = 2.4
4,4'''-dichloro-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
tetraol (3j). The reaction was performed in PhMe/CCl (2/3). 16.5
1
3
1
Hz, 2H), 6.41-6.43 (m, 2H), 6.16 (d, J = 2.4 Hz, 2H). C{ H} NMR
4
1
1
(150 MHz, Acetone-D6): δ 162.7 (d, JC–F = 242.8 Hz), 158.6,
mg, 75% yield. White solid. H NMR (400 MHz, Acetone-D6): δ
8.25 (s, 1H), 7.76 (s, 1H), 7.07 (d, J = 8.2 Hz, 4H), 6.69 (d, J = 8.2
3
3
1
58.3, 145.0 ( JC–F = 7.2 Hz), 144.1, 129.5 (d, JC–F = 8.7 Hz), 125.5,
2
2
13
1
116.2 (d, JC–F = 21.7 Hz), 114.2, 113.5 (d, JC–F = 20.2 Hz), 109.2,
1
Hz, 4H), 6.44 (d, J = 2.3 Hz, 2H), 6.14 (d, J = 2.3 Hz, 2H). C{ H}
NMR (100 MHz, Acetone-D6): δ 158.6, 158.3, 144.2, 141.4, 132.5,
1
9
1
02.6. F{ H} NMR (565 MHz, Acetone-D6): δ -116.1. HRMS
+
(APCI) m/z: [M + H] Calcd for C24
H
17
F
2
O
4
407.1089; found
131.2, 127.9, 114.2, 109.3, 102.6. HRMS (APCI): calcd for
+
4
8
07.1094. IR (KBr): 3351, 1612, 1580, 1460, 1345, 1152, 1013,
00, 785 cm . mp: 214–216 °C. Enantiomeric excess: 87%, deter-
C
24
H17Cl
2
O
4
: m/z 439.0498 [M + H] , found 439.0503. IR (KBr):
-
1
3353, 1678, 1612, 1462, 1339, 1271, 1184, 1122, 1088, 1014, 876,
-1
mined by HPLC (Chiralpak IA, hexane/2-propanol = 3/1; flow rate
.0 mL/min; 25 °C; 254 nm) first peak: t = 6.1 min, second peak:
= 10.6 min. [훼]D –167.0 (c 0.40, EtOAc) for 87% ee.
,3'''-dichloro-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
828 cm . mp: 280–282 °C. Enantiomeric excess: 77%, determined
1
R
by HPLC (Chiralpak IA, hexane/2-propanol = 4/1; flow rate 1.0
20
t
R
mL/min; 25 °C; 254 nm) first peak: t
19.9 min. [훼]D –172.8 (c 0.45, EtOAc) for 77% ee.
R
= 7.7 min, second peak: t
R
=
22
3
1
tetraol (3f). 6.4 mg, 29% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 8.28 (s, 1H), 7.84 (s, 1H), 7.11-7.14 (m, 2H), 7.06
6,6'-di(naphthalen-2-yl)-[1,1'-biphenyl]-2,2',4,4'-tetraol (3m).
1
18.4 mg, 78% yield. White solid. H NMR (400 MHz, Acetone-
(
6
t, J = 7.8 Hz, 2H), 6.64-6.68 (m, 4H), 6.47 (d, J = 2.3 Hz, 2H),
.15 (d, J = 2.3 Hz, 2H). C{ H} NMR (100 MHz, Acetone-D6):
D6): δ 8.17 (s, 2H), 7.74-7.79 (m, 4H), 7.50 (d, J = 8.2 Hz, 2H),
7.37-7.44 (m, 6H), 6.87-6.90 (m, 4H), 6.49 (d, J = 2.3 Hz, 2H), 6.15
1
3
1
1
3
1
δ 158.7, 158.3, 144.7, 144.0, 133.4, 129.5, 129.4, 128.0, 126.9,
(d, J = 2.3 Hz, 2H). C{ H} NMR (100 MHz, Acetone-D6): δ
+
1
C
1
14.2, 109.1, 102.7. HRMS (APCI) m/z: [M + H] Calcd for
439.0504; found 439.0495. IR (KBr): 3360, 1594,
158.6, 158.3, 145.7, 140.5, 133.8, 133.0, 128.8, 128.4, 128.3, 128.1,
24
H
16Cl
2
O
4
126.7, 126.3, 126.3, 114.6, 109.7, 102.4. HRMS (APCI) m/z: [M +
-1
+
565, 1458, 1343, 1149, 1010, 787 cm . mp: decomposed at 95 °C.
H] Calcd for C32
H
23
O
4
471.1591; found 471.1596. IR (KBr): 3359,
-
1
Enantiomeric excess: 76%, determined by HPLC (Chiralpak IA,
hexane/2-propanol = 4/1; flow rate 1.0 mL/min; 25 °C; 254 nm)
3055, 1584, 1451, 1335, 1271, 1161, 1132, 1013, 817, 475 cm .
mp: 284–286 °C. Enantiomeric excess: 85%, determined by HPLC
(Chiralpak IA, hexane/2-propanol = 3/1; flow rate 1.0 mL/min;
20
first peak: t
R R
= 9.5 min, second peak: t = 18.8 min. [훼]D –171.9
(
c 0.22, EtOAc) for 76% ee.
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The Journal of Organic Chemistry
2
5 °C; 254 nm) first peak: t
R
= 8.4 min, second peak: t
R
= 16.1 min.
of Science (JSPS), the CREST project of the Japan Science and
Technology Corporation (JST), JST Advance Catalytic Transfor-
mation Program for Carbon Utilization (ACT-C), and the German
Academic Exchange Service (DAAD) and Japan Society for the
Promotion of Science (JSPS) within the joint DAAD-JSPS funding
program “DAAD PPP Japan 2017/2018” (DAAD grant no.
57345562). We acknowledge the technical staff of the Comprehen-
sive Analysis Center of ISIR, Osaka University (Japan). We thank
Professor Shuji Akai and Professor Takashi Ikawa at Osaka Uni-
versity for valuable discussion.
20
1
2
3
4
5
6
7
8
9
[훼] –25.0 (c 0.45, EtOAc) for 85% ee.
D
3
'',6'-dimethyl-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
1
tetraol (3o). 18.5 mg, 93% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 7.96 (s, 2H), 7.17-7.21 (m, 4H), 7.05-7.12 (m, 4H),
7
.01 (s, 2H), 6.51 (d, J = 7.8 Hz, 2H), 6.39 (s, 2H), 1.62 (s, 6H).
1
3
1
C{ H} NMR (100 MHz, Acetone-D6): δ 156.19, 155.00, 144.92,
1
1
3
41.56, 131.58, 129.55, 127.88, 127.17, 126.86, 114.89, 114.26,
01.83, 13.45. HRMS (APCI) m/z: [M + H] Calcd for C26
99.1591; found 399.1595. IR (KBr): 3469, 3054, 2915, 1594,
+
H
23
O
4
-
1
1424, 1306, 1250, 1128, 1054, 834, 701 cm . mp: 257–259 °C.
Enantiomeric excess: 88%, determined by HPLC (Chiralpak IA,
hexane/2-propanol = 3/1; flow rate 1.0 mL/min; 25 °C; 254 nm)
REFERENCES
(1) Recent reviews and reports on syntheses and applications of axually
chiral compounds, see: (a) Moustafa, G. A. I.; Oki, Y.; Akai, S.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
20
first peak: t
c 0.53, EtOAc) for 88% ee.
',5''-dimethyl-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
R R
= 6.9 min, second peak: t = 10.3 min. [훼]D –176.1
1 2
Lipase-Catalyzed Dynamic Kinetic Resolution of C - and C -
(
Symmetric Racemic Axially Chiral 2,2’-Dihydroxy-1,1’-biaryls.
Angew. Chem. Int. Ed. 2018, 57, 10278–10282. (b) Renzi, P.
Organocatalytic Synthesis of Axially Chiral Atropisomers. Org.
Biomol. Chem. 2017, 15, 4506–4516.
4
9b
1
tetraol (3p). 15.3 mg, 77% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 8.15 (s, 2H), 6.97-7.07 (m, 6H), 6.93 (s, 2H), 6.64-
(2) Selected reviews on bioactive compounds bearing chiral biaryls, see:
6
.67 (m, 4H), 6.22 (s, 2H), 2.16 (s, 6H). Enantiomeric excess: 36%,
determined by HPLC (Chiralpak IA, hexane/2-propanol = 4/1; flow
rate 1.0 mL/min; 25 °C; 254 nm) first peak: t = 21.2 min, second
= 25.1 min. [훼]D +52.6 (c 0.46, EtOAc) for 36% ee.
(a) Bringmann, G.; Gulder, T.; Gulder, T. A. M.; Breuning, M.
Atroposelective Total Synthesis of Axially Chiral Biaryl Natural
Products. Chem. Rev. 2011, 111, 563–639. (b) Kozlowski, M. C.;
Morgan, B. J.; Linton, E. C. Total Synthesis of Chiral Biaryl Natural
Products by Asymmetric Biaryl Coupling. Chem. Soc. Rev. 2009, 38,
3193–3207.
R
20
peak: t
R
4',5''-dibromo-[1,1':2',1'':2'',1'''-quaterphenyl]-3',4'',5',6''-
1
tetraol (3q). 12.9 mg, 49% yield. White solid. H NMR (400 MHz,
Acetone-D6): δ 8.75 (s, 2H), 7.89 (s, 2H), 7.03-7.13 (m, 6H), 6.65-
6
δ 155.2, 155.0, 144.3, 141.6, 129.4, 128.0, 127.3, 114.8, 109.6, 98.4.
HRMS (APCI) m/z: [M – Br] Calcd for C24
found 447.0224. IR (KBr): 3485, 3059, 2958, 1698, 1597, 1560,
1413, 1239, 1178, 1044, 781, 701 cm . mp: 123–125 °C. Enantio-
meric excess: 70%, determined by HPLC (Chiralpak IA, hexane/2-
propanol = 3/1; flow rate 1.0 mL/min; 25 °C; 254 nm) first peak: t
=
(
3) Selected examples of the chiral metal-catalyzed oxidative coupling
of 2-naphthols (pioneering works), see: (a) Smrćina, M.; Poláková,
J.; Vyskoćil, S.; Koćovský, P. Synthesis of Enantiomerically Pure
Binaphthyl Derivatives. Mechanism of the Enantioselective, Oxida-
tive Coupling of Naphthols and Designing a Catalytic Cycle. J. Org.
Chem. 1993, 58, 4534–4538. (b) Nakajima, M.; Miyoshi, I.; Ka-
nayama, K.; Hashimoto, S.-i.; Noji, M.; Koga, K. Enantioselective
Synthesis of Binaphthol Derivatives by Oxidative Coupling of Naph-
thol Derivatives Catalyzed by Chiral Diamine·Copper Complexes. J.
Org. Chem. 1999, 64, 2264–2271. (c) Irie, R.; Masutani, K.; Katsuki,
T. Asymmetric Aerobic Oxidative Coupling of 2-Naphthol Deriva-
tives Catalyzed by Photo-activated Chiral (NO)Ru(II)-salen Com-
plex. Synlett 2000, 1433–1436. (d) Egami, H.; Katsuki, T. Iron-Cata-
lyzed Asymmetric Aerobic Oxidation: Oxidative Coupling of 2-Naph-
thols. J. Am. Chem. Soc. 2009, 131, 6082–6083. (e) Li, X.; Yang, J.;
Kozlowski, M. C. Enantioselective Oxidative Biaryl Coupling Reac-
tions Catalyzed by 1,5-Diazadecalin Metal Complexes. Org. Lett.
1
3
1
.67 (m, 4H), 6.30 (s, 2H). C{ H} NMR (100 MHz, Acetone-D6):
+
4
H16BrO 447.0226;
-
1
R
20
15.9 min, second peak: t
R
= 28.5 min. [훼]D –316.5 (c 0.25,
EtOAc) for 70% ee.
ASSOCIATED CONTENT
Reaction optimization, compound characterization data, and HPLC
chromatograms. This material is available free of charge via the
Internet at http://pubs.acs.org.
2
001, 3, 1137–1140. (f) Chu, C.-Y.; Hwang, D.-R.; Wang, S.-K.;
Experimental procedures, spectroscopic data
Uang, B.-J. Chiral Oxovanadium Complex Catalyzed Enantioselec-
X-ray crystallographic data for (S)-3a (CCDC 1849069)
tive Oxidative Coupling of 2-Naphthols. Chem. Commun. 2001,
9
80–981. (g) Hon, S.-W.; Li, C.-H.; Kuo, J.-H.; Barhate, N. B.; Liu,
Y.-H.; Wang, Y.; Chen, C.-T. Catalytic Asymmetric Coupling of 2-
Naphthols by Chiral Tridentate Oxovanadium(IV) Complexes. Org.
Lett. 2001, 3, 869–872. (h) Tada, M.; Taniike, T.; Kantam, L. M.;
Iwasawa, Y. Chiral Self-dimerization of Vanadium Complexes on a
AUTHOR INFORMATION
Corresponding Author
sasai@sanken.osaka-u.ac.jp
taki@sanken.osaka-u.ac.jp
2
SiO Surface: The First Heterogeneous Catalyst for Asymmetric 2-
Naphthol Coupling. Chem. Commun. 2004, 2542–2543. (i) Habaue,
S.; Murakami, S.; Higashimura, H. New Asymmetric Vanadium Cat-
alyst for Highly Selective Oxidative Coupling Polymerization. J.
Polym. Sci., Part A: Polym. Chem. 2005, 43, 5872–5878. (j) Temma,
T.; Habaue, S. Highly Selective Oxidative Cross-coupling Polymer-
ization with Copper(I)-bisoxazoline Catalysts. J. Polym. Sci., Part A:
Polym. Chem. 2005, 43, 6287–6294. (k) Narute, S.; Parnes, R.; Toste,
F. D.; Pappo, D. Enantioselective Oxidative Homocoupling and
Cross-Coupling of 2-Naphthols Catalyzed by Chiral Iron Phosphate
Complexes. J. Am. Chem. Soc. 2016, 138, 16553–16560. (l) Luo, Z.;
Liu, Q.; Gong, L.; Cui, X.; Mi, A.; Jiang, Y. The Rational Design of
Novel Chiral Oxovanadium(IV) Complexes for Highly Enantioselec-
tive Oxidative Coupling of 2-Naphthols. Chem. Commun. 2002,
ORCID
Makoto Sako: 0000-0002-4268-7002
Nadine Zumbrägel: 0000-0002-3493-8852
Lukas Schober: 0000-0001-7106-2514
Harald Gröger: 0000-0001-8582-2107
Shinobu Takizawa: 0000-0002-9668-1888
Hiroaki Sasai: 0000-0002-7221-488X
Notes
The authors declare no competing financial interests.
9
14–915. (m) Gao, J.; Reibenspies, J. H.; Martell, A. E. Structurally
ACKNOWLEDGMENT
Defined Catalysts for Enantioselective Oxidative Coupling Reac-
tions. Angew. Chem. Int. Ed. 2003, 42, 6008–6012. (n) Somei, H.;
Asano, Y.; Yoshida, T.; Takizawa, S.; Yamataka, H.; Sasai, H. Dual
Activation in a Homolytic Coupling Reaction Promoted by an Enan-
tioselective Dinuclear Vanadium(IV) Catalyst. Tetrahedron Lett.
2004, 45, 1841–1844.
This work was supported by JSPS KAKENHI Grant Numbers
JP17H06834 in Grant-in-Aid for Research Activity Start-up,
JP16K08163 in Grant-in-Aid for Scientific Research (C),
JP17H05373 in Coordination Asymmetry, JP18H04412 in Middle
Molecular Strategy, The Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan Society for the Promotion
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Page 8 of 8
(
4) Recent reviews, see: (a) Yang, Y.; Lan, J.; You, J. Oxidative C–H/C–
H Coupling Reactions between Two (Hetero)arenes. Chem. Rev.
017, 117, 8787–8863. (b) Kozlowski, M. C. Oxidative Coupling in
Muscular, and Myocardial Necroses. Mol. Pharmaceutics 2016, 13,
232–240.
(9) (a) Kang, H.; Torruellas, C.; Liu, J.; Kozlowski, M. C. Total
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
Complexity Building Transforms. Acc. Chem. Res. 2017, 50, 638–
643. (c) Quideau, S.; Deffieux, D.; Pouységu, L. Oxidative Coupling
of Phenols and Phenol Ethers. In Comprehensive Organic Synthesis
II; Knochel, P. and Molander G. A., Eds; Oxford, UK; Elsevier:
Synthesis of Chaetoglobin A via Catalytic, Atroposelective
Oxidative Phenol Coupling. Org. Lett. 2018, 20, 5554–5558. (b)
Kang, H.; Lee, Y. E.; Reddy, P. V. G.; Dey, S.; Allen, S. E.; Niederer,
K. A.; Sung, P.; Hewitt, K.; Torruellas, C.; Herling, M. R.;
Kozlowski, M. C. Asymmetric Oxidative Coupling of Phenols and
Hydroxycarbazoles. Org. Lett. 2017, 19, 5505–5508. (c) Kang, H.;
Herling, M. R.; Niederer, K. A.; Lee, Y. E.; Reddy, P. V. G.; Dey,
S.; Allen, S. E.; Hewitt, P. S. K.; Torruellas, C.; Kim, G. J.; Ko-
zlowski, M. C. Enantioselective Vanadium-Catalyzed Oxidative
Coupling: Development and Mechanistic Insights. J. Org. Chem.
DOI: 10.1021/acs.joc.8b02083.
2
014; p 656.
(
5) Recent reports, see: (a) Wu, X.; Iwata, T.; Scharf, A.; Qin, T.; Reichl,
K. D.; Porco, J. A., Jr. Asymmetric Synthesis of Gonytolide A:
Strategic Use of an Aryl Halide Blocking Group for Oxidative
Coupling. J. Am. Chem. Soc. 2018, 140, 5969–5975. (b) Vershinin,
V.; Dyadyuk, A.; Pappo, D. Iron-catalyzed Selective Oxidative
Arylation of Phenols and Biphenols. Tetrahedron 2017, 73, 3660–
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
668. (c) Shalit, H.; Libman, A.; Pappo, D. meso-
(10) (a) Kim, H. Y.; Takizawa, S.; Sasai, H.; Oh, K. Reversal of
Enantioselectivity Approach to BINOLs via Single and Dual 2-
Naphthol Activation Modes. Org. Lett. 2017, 19, 3867–3870. (b)
Sako, M.; Takeuchi, Y.; Tsujihara, T.; Kodera, J.; Kawano, T.;
Takizawa, S.; Sasai, H. Efficient Enantioselective Synthesis of
Oxahelicenes Using Redox/Acid Cooperative Catalysts. J. Am. Chem.
Soc. 2016, 138, 11481–11484. (c) Takizawa, S.; Gröger, H.; Sasai,
H. Vanadium in Asymmetric Synthesis: Emerging Concepts in
Catalyst Design and Applications. Chem. Eur. J. 2015, 21, 8992–
8997.
(11) Halogenated BINOL catalysts exhibit better catalytic activity and
asymmetric induction than unsubstitued BINOLs, see (a) Huang, J.;
Wei, S.; Wang, L.; Zhang, C.; Li, S.; Liu, P.; Du, X.; Wang, Q.
Highly Enantioselective Catalytic Methyl Propiolate Addition to
both Aromatic and Aliphatic Aldehydes. Tetrahedron: Asymmetry
2016, 27, 428–435. (b) Gou, S.; Ye, Z.; Shi, L.; Qing, D.; Zhang, W.;
Wang, Y. Copper-catalyzed Asymmetric 1,4-Conjugate Addition of
Dialkylzinc to Enones. Appl. Organometal. Chem. 2010, 24, 517–
522. (c) Hashimoto, T.; Omote, M.; Hato, Y.; Kano, T.; Maruoka, K.
Asymmetric 1,3-Dipolar Cycloadditions of N-Benzyl and N-
Diphenylmethyl Nitrones and α,β-Unsaturated Aldehydes Catalyzed
by Bis-Titanium Chiral Lewis Acids. Chem. Asian. J. 2008, 3, 407–
412. (d) Bao, H.; Zhou, J.; Wang, Z.; Guo, Y.; You, T.; Ding, K.
Insight into the Mechanism of the Asymmetric Ring-Opening
Tetraphenylporphyrin Iron Chloride Catalyzed Selective Oxidative
Cross-Coupling of Phenols. J. Am. Chem. Soc. 2017, 139, 13404–
13413. (d) Mei, R.; Xu, D.; Hu, H.; Song, D.; Zhang, H.; Ma, D.; Xie,
X.; She, X. Biomimetic Total Syntheses of (+)-Dihydrolyfoline and
(−)-5-epi-Dihydrolyfoline. Org. Lett. 2015, 17, 2230–2233. (e)
Grant-Overton, S.; Buss, J. A.; Smith, E. H.; Gutierrez, E. G.;
Moorhead, E. J.; Lin, V. S.; Wenzel, A. G. Efficient Microwave
Method for the Oxidative Coupling of Phenols. Synth. Commun.
2
015, 45, 331–337.
(
6) Recent reviews and reports, see: (a) Kita, Y.; Morimoto, K.; Dohi, T.
Metal-free Oxidative Cross-Coupling Reaction of Aromatic
Compounds Containing Heteroatoms. Synlett 2017, 28, 1680–1694.
(b) Morimoto, K.; Sakamoto, K.; Ohshika, T.; Dohi, T.; Kita, Y.
Organo-Iodine(III)-Catalyzed Oxidative Phenol-Arene and Phenol-
Phenol Cross-Coupling Reaction. Angew. Chem. Int. Ed. 2016, 55,
3652–3656. (c) Morimoto, K.; Sakamoto, K.; Ohnishi, Y.; Miyamoto,
T.; Ito, M.; Dohi, T.; Kita, Y. Metal-Free Oxidative para Cross-
Coupling of Phenols. Chem. Eur. J. 2013, 19, 8726–8731.
(
7) Recent report, see: (a) Lips, S.; Wiebe, A.; Elsler, B.; Schollmeyer,
D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Synthesis of meta-
Terphenyl-2,2”-diols by Anodic C−C Cross-Coupling Reactions.
Angew. Chem. Int. Ed. 2016, 55, 10872–10876. (b) Elsler, B.; Wiebe,
A.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R.
Source of Selectivity in Oxidative Cross-Coupling of Aryls by
Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol. Chem. Eur. J.
Aminolysis
Catalyzed by Titanium/BINOLate/Water System: Evidence for the
Ti(BINOLate) -Bearing Active Catalyst Entities and the Role of
of
4,4-Dimethyl-3,5,8-trioxabicyclo[5.1.0]octane
2
015, 21, 12321–12325. (c) Elsler, B.; Schollmeyer, D.; Dyballa, K.
2
M.; Franke, R.; Waldvogel, S. R. Metal- and Reagent-Free Highly
Selective Anodic Cross-Coupling Reaction of Phenols. Angew.
Chem. Int. Ed. 2014, 53, 5210–5213.
Water. J. Am. Chem. Soc. 2008, 130, 10116–10127. (e) Chen, Z.;
Morimoto, H.; Matsunaga, S.; Shibasaki, M. Catalytic Asymmetric
Epoxidation of α-Methyl α,β-Unsaturated Anilides as Ester
Surrogates. Synlett 2006, 3529–3532.
(
8) Selected recent emxamples: Natural products; (a) Xiao, Z.; Li, Y.;
Gao, S. Total Synthesis and Structural Determination of the Dimeric
Tetrahydroxanthone Ascherxanthone A. Org. Lett. 2017, 19, 1834–
1837. (b) Richieu, A.; Peixoto, P. A.; Pouysegu, L.; Deffieux, D.;
(12) El-Deeb, I. Y.; Funakoshi, T.; Shimomoto, Y.; Matsubara, R.;
Hayashi, M. Dehydrogenative Formation of Resorcinol Derivatives
Using Pd/C–Ethylene Catalytic System. J. Org. Chem. 2017, 82,
2630–2640.
(13) Uchida, K.; Yoshida, S.; Hosoya, T. Controlled Generation of 3-Tri-
flyloxyarynes. Synthesis 2016, 48, 4099–4109.
(14) Dol, G. C.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Synthesis of
5-Substituted Resorcinol Derivatives via Cross-Coupling Reactions.
Eur. J. Org. Chem. 1998, 359–364.
(15) Percec, V.; Holerca, M. N.; Nummelin, S.; Morrison, J. J.; Glodde,
M.; Smidrkal, J.; Peterca, M.; Rosen, B. M.; Uchida, S.; Bala-
gurusamy, V. S.; Sienkowska, M. J.; Heiney, P. A. Exploring and
Expanding the Structural Diversity of Self-Assembling Dendrons
Quideau, S. Bioinspired Total Synthesis of (–)-Vescalin:
A
Nonahydroxytriphenoylated C-Glucosidic Ellagitannin. Angew.
Chem. Int. Ed. 2017, 56, 13833–13837. Chiral reagents; (c) Zhang,
Z. P.; Chen, C. Y.; Wang, Q.; Han, Z. Y.; Dong, X. Q.; Zhang, X. M.
New Tetraphosphite Ligands for Regioselective Linear
Hydroformylation of Terminal and Internal Olefins. Rsc Adv. 2016,
6
, 14559–14562. (d) Zhuang, Y.; He, Y.; Zhou, Z.; Xia, W.; Cheng,
C.; Wang, M.; Chen, B.; Zhou, Z.; Pang, J.; Qiu, L. Synthesis of a
Class of Chiral-Bridged Phosphoramidite Ligands and Their
Applications in the First Iridium-Catalyzed Asymmetric Addition of
Arylboronic Acids to Isatins. J. Org. Chem. 2015, 80, 6968–6975.
Functional materials; (e) Chen, E.; Chen, X.; Yuan, X.; Wei, S.; Zhou,
L.; Zhou, J.; Shen, J. One-pot Method to Prepare a Theranostic
Nanosystem with Magnetic Resonance Imaging Function and
Anticancer Activity through Multiple Mechanisms. Dalton Trans.
2 3
through Combinations of AB, Constitutional Isomeric AB , and AB
Biphenyl-4-Methyl Ether Building Blocks. Chem. Eur. J. 2006, 12,
6216–6241.
(16) Li, L.; Qiu, D.; Shi, J.; Li, Y. Vicinal Diamination of Arenes with
Domino Aryne Precursors. Org. Lett. 2016, 18, 3726–3729.
(17) Deng, L.; Sundriyal, S.; Rubio, V.; Shi, Z.; Song, Y. Coordination
Chemistry Based Approach to Lipophilic Inhibitors of 1-Deoxy-d-
xylulose-5-phosphate Reductoisomerase. J. Med. Chem. 2009, 52,
6539–6542.
2
017, 46, 5151–5158. (f) Li, J.; Zhang, J.; Yang, S.; Jiang, C.; Zhang,
D.; Jin, Q.; Wang, Q.; Wang, C.; Ni, Y.; Yin, Z.; Song, S. Synthesis
and Preclinical Evaluation of Radioiodinated Hypericin Dicarboxylic
Acid as a Necrosis Avid Agent in Rat Models of Induced Hepatic,
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