Concise synthesis of binaphthol-derived chiral dicarboxylic acids

Article abstract of DOI:10.1016/j.tet.2015.05.041

Abstract 3,3'-Disubstituted 1,1'-binaphthyl-2,2'-dicarboxylic acids (1) were synthesized in three or four steps from commercially available BINOL via carbon dioxide fixation with organolithium to incorporate the carboxylic acid moieties, followed by either carboxylate-directed ortho-C-H arylation or Suzuki cross-coupling. This method provides easy access to various types of axiially chiral dicarboxylic acids, which should be useful for studies of chiral Br?nsted acid-catalyzed asymmetric reactions.

Full text of DOI:10.1016/j.tet.2015.05.041

Accepted Manuscript
Concise synthesis of binaphthol-derived chiral dicarboxylic acids
Hiromichi Egami, Kentaro Sato, Junshi Asada, Yuji Kawato, Yoshitaka Hamashima
PII:
S0040-4020(15)00699-7
10.1016/j.tet.2015.05.041
TET 26759
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 2 April 2015
Revised Date: 8 May 2015
Accepted Date: 11 May 2015
Please cite this article as: Egami H, Sato K, Asada J, Kawato Y, Hamashima Y, Concise synthesis of
binaphthol-derived chiral dicarboxylic acids, Tetrahedron (2015), doi: 10.1016/j.tet.2015.05.041.
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Concise synthesis of binaphthol-derived
chiral dicarboxylic acids
Leave this area blank for abstract info.
Hiromichi Egami, Kentaro Sato, Junshi Asada, Yuji Kawato, Yoshitaka Hamashima
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan
Ar
OH
OH
CO2H
CO2H
3 or 4 steps
Ar

1
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Tetrahedron
journal homepage: www.elsevier.com
Concise synthesis of binaphthol-derived chiral dicarboxylic acids
Hiromichi Egami, Kentaro Sato, Junshi Asada, Yuji Kawato, Yoshitaka Hamashima
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
3,3’-Disubstituted 1,1’-binaphthyl-2,2’-dicarboxylic acids (1) were synthesized in three or four
steps from commercially available BINOL via carbon dioxide fixation with organolithium to
incorporate the carboxylic acid moieties, followed by either carboxylate-directed ortho-C–H
arylation or Suzuki cross-coupling. This method provides easy access to various types of axiially
chiral dicarboxylic acids, which should be useful for studies of chiral Brønsted acid-catalyzed
asymmetric reactions.
Available online
ords:
2009 Elsevier Ltd. All rights reserved.
chiral dicarboxylic acid
reductive CO2 fixation
directed C-H arylation
Suzuki cross coupling
organocatalyst
1. Introduction
bromination, 4) Suzuki-Miyaura cross-coupling to install aryl
groups at the 3,3’ positions, and 5) deprotection of the TMSethyl
group.5,6 We thought that C–H functionalization might be an
effective approach to reduce the number of steps.
Chiral Brønsted acid catalysis is a major research target in the
field of asymmetric organocatalysis.1 Since the asymmetric
Mukaiyama-aldol reaction and Mannich-type reactions were
independently reported by Akiyama’s and Terada’s groups in
2004,2 binaphthol-derived chiral phosphoric acids have been
widely used as chiral Brønsted acid catalysts.3 In contrast, little
work has been done on asymmetric catalysis with chiral
carboxylic acids. Momiyama and Yamamoto reported a highly
enantioselective nitroso aldol reaction with a chiral mandelic acid
analog in 2005.4 In 2007, Hashimoto and Maruoka developed a
chiral dicarboxylic acid having a 1,1’-binaphthyl framework,5
which catalyzed various C–C bond-forming reactions.6
BINOL is an important chiral source that is commercially
available at reasonable cost, and we thought that it might be
suitable for a more efficient synthesis of 2. Several relevant
reactions have been reported, though these methods have some
drawbacks. In 1993, Takaya reported a palladium-catalyzed
carbonylation of BINOL-ditriflate to give the corresponding
methyl ester, but this method requires toxic CO gas and relatively
expensive triflating reagents.8 In 2006, Schlosser reported a
unique method utilizing Wittig [1,2]-rearrangement of a di-
allylated BINOL derivative, although several additional steps are
required to generate the carboxylic acid.9 As for CO2 fixation,
Hoshi and Hagiwara synthesized 2 from chiral 2,2’-dibromo-
1,1’-binaphthyl via lithiation with t-BuLi, though the starting
bromide is more expensive than BINOL, and partial racemization
was observed when n-BuLi was used.10
Despite the great potential of axially chiral dicarboxylic
acids,6 3,3’-disubstituted 1,1’-binaphthyl-2,2’-dicarboxylic acids
(1) have seen only limited application, probably due to the
unavailability of a cost-effective and concise synthetic method.
Although the original synthetic route to 1 is reliable,5 there is
much room for improvement in terms of atom and step economy.
First, the starting 1,1’-binaphthyl-2,2’-dicarboxylic acid (2) was
prepared from 1-bromo-2-methylnaphthalene in six steps,
including optical resolution of racemic 2 with chiral 1-
(cyclohexyl)ethyl-1-amine according to Seki’s procedure
(Scheme 1).7 From the viewpoint of atom economy, a procedure
that does not require a resolution process would be more
favorable. Second, Maruoka’s synthesis of 1 required five steps
On the other hand, we have been investigating catalytic
asymmetric halo-functionalization of alkenes.11 In this context,
we became interested in using a chiral dicarboxylic acid
framework in the design of novel halogenation catalysts.
Therefore, we needed to devise a practical protocol for rapid
preparation of various derivatives. Considering the structure of 1,
we planned a synthetic strategy consisting of two stages: 1)
construction of 1,1’-binaphthyl-2,2’-dicarboxylic acid from
BINOL and 2) substitution at the 3,3’-positions. We envisaged
that a short-step synthesis of 1 would be possible if we could
from
2,
i.e.,
1)
acid
chloride
formation,
2)
trimethylsilyl(TMS)ethyl ester formation with expensive 2-
trimethylsilylethanol, 3) ortho-magnesiation followed by
———
Corresponding author. Tel.: +81-054-264-5672; fax: +81-054-264-5672; e-mail: hamashima@u-shizuoka-ken.ac.jp

2
Tetrahedron
ACCEPTED MANUSCRIPT
NaH (2.1 eq.)
THF
0°C, 0.5 h
achieve facile incorporation of CO2 to afford 2 and combine it
O
P(OEt)2
with directed palladium-catalyzed ortho-C–H functionalization,
which has been actively investigated. In this report, we disclose a
short-step synthesis of chiral 3,3’-disubstituted 1,1’-binaphthyl-
2,2’-dicarboxylic acid derivatives (1) from commercially
available BINOL.
OH
O
O
OH
O
;
P(OEt)2
O
P(OEt)2
(2.1 eq.)
rt, 1 h
Cl
(S)-BINOL
3: quant.
Table 1
Previous synthesis (Maruoka et al.)
Li/naphthalene
CO2
Li
Li
CO2H
CO2H
Ar
5 steps
6 steps
THF
CO2H
CO2H
CO2H
CO2H
CH3
Br
4
2
Ar
Scheme 2. Reductive CO2 fixation of 3
2
1
This time
Reductive
CO2
fixation
Ar
Cross
coupling
Table 1. Optimization of the conditions for di-lithiation of 3a
OH
OH
CO2H
CO2H
CO2H
CO2H
Entry
Li/naphthalene
Temp. (°C)
Time (h)
Yield of 2
(%)b
(equiv.)
Ar
1
2
3
4
5
6
7
8
9c
4
6
8
6
6
6
6
6
6
-78
-78
-78
0
0.5
0.5
0.5
0.5
0.5
0.25
1
12
82
82
9
2
1
(S)-BINOL
Scheme 1. Our synthetic plan
rt
5
2. Results and discussions
-78
-78
-78
-78
44
68
54
89
Aiming first at the preparation of 1,1’-binaphthyl-2,2’-
dicarboxylic acid (2), the backbone of our target compound
(Scheme 1), we focused on reaction of organolithium species
with CO2. To apply this transformation to our synthesis, 1,1’-
binaphthyl-2,2’-dilithium (4) should be generated in situ under
mild conditions (Scheme 2). Although there is no report on the
generation of such dilithium species from a BINOL derivative,
with the exception of 2,2’-dibromo-1,1’-binaphthyl, 10 boronation
and iodination via lithiation by reduction of an aryl diethyl
phosphate with lithium-naphthalenide has been reported.12,13
With reference to these reports, we examined reductive CO2
fixation onto the binaphthyl backbone via lithium-naphthalenide
reduction after phosphate formation on BINOL.
2
0.5
a The reactions were carried out in THF on a 0.5 mmol scale, unless otherwise
mentioned.
b Isolated yield.
c Run with 2 g (3.5 mmol) of 3.
Having established a highly efficient route to 1,1’-binaphthyl-
2,2’-dicarboxylic acid (2), we next turned our attention to
functionalization at the 3,3’ positions. Inspired by recent
advances in C–H activation chemistry,14 we planned to examine
palladium-catalyzed C–H coupling reactions. It was encouraging
that the carboxylate group had been reported to act as a directing
group in palladium-catalyzed ortho-C–H arylation of benzoic
acid derivatives with aryl boronates and/or aryl iodides.15
Furthermore, some of these reactions were applicable to
sterically hindered benzoic acids with a substituent at the other
ortho-position.
According to Yu’s procedure,15a the dicarboxylic acid 2 was
subjected to oxidative C–H coupling reaction with phenyl
boronate in the presence of benzoquinone and Ag2CO3 in t-
BuOH (Scheme 3). But, even when the amount of the reagents
and reaction time were increased, the reaction was not complete,
resulting in the formation of a mono-functionalized product with
recovery of the starting material. Therefore, we next examined
the reaction with iodobenzene. Daugulis disclosed carboxylate-
directed ortho-C–H coupling reactions of benzoic acid
derivatives using the combination of Pd(OAc)2 and AgOAc in
AcOH,15b but this reaction did not work in our case. Larrosa
subsequently reported a catalytic system that is also applicable to
2-substituted benzoic acids by suppressing protodecarboxylation
of the carboxyl group.15c According to their protocol, ortho-C–H
coupling reaction of 2 was carried out with a catalytic amount of
As shown in Scheme 2, the hydroxyl groups of BINOL
reacted smoothly with diethyl chlorophosphate to provide 3 in
quantitative yield. Optimization of the reaction conditions for
dilithiation of 3 and CO2 fixation was conducted (Table 1). Six
equivalents of lithium naphthalenide was enough to generate the
dilithium species 4 (entries 1-3). The reactions at 0 °C and room
temperature resulted in low yield of 2, and this was attributed to
deprotonation of THF by the generated organolithium species to
give the corresponding protonated by-product (entries 4 and 5).
In addition, it was found that the reduction time for the
generation of 4 was important: a longer or shorter reaction time
afforded only moderate yield (entries 6-8). Based on these results,
we selected the conditions of entry 2 as the optimal reaction
conditions. To our delight, the reaction could be carried out on a
2 g scale without difficulty, providing the desired di-acid in 89%
isolated yield (entry 9). It should be noted that the reaction
occurred without significant loss of enantiomer excess (99% ee),
as confirmed by HPLC analysis.10

3
I
Pd(OAc)2 in the presence of Ag2CO3 and K2CO3 (Table 2). When
A
CCEPTED MANUSCRIPT
sec-BuLi, TMEDA
THF, -40 °C, 2 h;
4 equivalents of iodobenzene with respect to 2 (2 equivalents for
each CO2H group) was used, the desired compound 1a was
obtained in 64% yield after 24 hours (entry 1). The chemical
yield was further improved when the amount of iodobenzene was
increased, and 1a was obtained in 81% yield. Under these
reaction conditions, other iodoarenes underwent the desired
coupling reaction, affording the products 1b and 1c without
difficulty (entries 3,4), although a sterically hindered iodoarene
could not be used (entry 5). In contrast to alkyl-substituted
iodoarenes, compounds having either electron-donating or
electron-withdrawing groups did not react well under the
optimized conditions (Table 2, entries 6,7), although the reason
for this is not clear.
CO2H
CO2H
CO2H
CO2H
then I2
I
2
5: 50%
Ar
Pd(OAc)2 (5 mol %)
KOH (9 eq.)
CO2H
CO2H
5
+
Ar B(OH)2
(3 eq.)
H2O
µW (120 °C), 1 h
Ar
1
CF3
OCH3
Table 2. C-H di-arylation of 2 using Ar-Ia
Ar =
CF3
1c: 68% yield
1e: 67% yield
1g: 56% yield
Pd(OAc)2 (5 mol %)
Ar
Ag2CO3 (1.1 eq.)
K2CO3 (1 eq.)
Ar-I (6 eq.)
Scheme 3. Suzuki-Miyaura cross-coupling reaction of 5
CO2H
CO2H
CO2H
CO2H
AcOH, 120 °C, 24 h
3. Conclusion
Ar
2
1
We have established an efficient synthetic method for the
preparation of chiral 3,3’-disubstituted 1,1’-binaphthyl-2,2’-
dicarboxylic acids from commercially available BINOL. The key
steps are reductive CO2 fixation of aryl phosphate and C–H
functionalization at the ortho-position of the carboxyl group. In
the case of heterofunctionalized coupling partners, the synthesis
was achieved by way of Suzuki-Miyaura cross-coupling reaction.
We believe that this straightforward synthetic method will
facilitate applications of chiral 1,1’-binaphthyl-2,2’-dicarboxylic
acids as asymmetric organocatalysts.
Entry
Ar
1
Yield of 1 (%)b
1c
2
3
4
5
6
7
C6H5
C6H5
1a
1a
1b
1c
1d
1e
1f
64
81
3,5-Me2-C6H3
2-naphthyl
91
46
2,4,6-Me3-C6H2
4-MeO-C6H4
4-Cl-C6H4
n.r.
34
<10
4. Experimental section
a The reactions were carried out with Pd(OAc)2 (5 mol %), Ag2CO3 (1.1
equiv.), K2CO3 (1 equiv.) and iodoarene (6 equiv.) in AcOH on a 0.25 mmol
scale, unless otherwise mentioned.
4.1. General
1H and 19F NMR spectra were measured on a JEOL JNM-
b Isolated yield.
ECA-500 spectrometer at 500 and 470 MHz, respectively. 13C
c 4 equivalents of PhI were used.
NMR spectra were recorded on
a JEOL JNM-ECA-500
spectrometer at 125 MHz. Chemical shifts are reported downfield
from TMS (= 0) or a solvent20 for H NMR. For 13C NMR,
1
chemical shifts are reported in the scale relative to a solvent.20
For 19F NMR, chemical shifts are reported in the scale relative to
a CFCl3 external standard (0 ppm). Infrared spectra were
In place of C–H activation, we expected that cross-coupling
reactions of 3,3’-dihalo-1,1’-binaphthyl-2,2’-dicarboxylic acid
with semi-metal reagents such as aryl boronic acid should work
well, since several examples of cross-coupling reaction of 2-
halobenzoic acids with aryl boronic acids have been reported.16
To this end, we modified Yang’s protocol for the synthesis of
3,3’-dihalogenated variants via the formation of the tetra-anion
species, since their method provided low yields when the reaction
was carried out at low temperature (–90 °C).17 To our delight,
measured on
a Shimazu IRPrestige-21; only diagnostic
absorptions are listed below. ESI-MS was taken on Bruker
micrOTOF-QII-RSL. Column chromatography was performed
with silica gel N-60 (40-100 m) purchased from Kanto
Chemical Co., Inc.. TLC analysis was performed on Silica gel 60
F254-coated glass plates (Merck). Visualization was accomplished
by means of ultraviolet (UV) irradiation at 254 nm or by spraying
12-molybdo(VI)phosphoric acid ethanol solution as the
developing agent.
treatment of
2
with sec-BuLi/TMEDA18 at –40 °C and
subsequent iodination with molecular iodine afforded di-iodide 5
in 50% isolated yield (Scheme 3). Under the micro-wave
conditions,16,19 Suzuki-Miyaura cross-coupling of 5 with aryl
boronic acids including compounds having heterofunctional
groups proceeded without difficulty to afford the coupling
products 1c, 1e and 1g in good yield. This method is
supplementary to the above-mentioned direct C–H arylation,
which would provide facile access to a wide variety of 1,1’-
binaphthyl-2,2’-dicarboxylic acids 1.
4.2. Synthesis of (S)-1,1’-binaphthyl-2,2’-bis(diethylphosphate)
321
To a solution of (S)-BINOL (1.0 g, 3.5 mmol) in THF (10 mL)
was added NaH (60% in oil, 0.3 g, 7.5 mmol) at 0 °C. The
mixture was stirred for 30 min, then diethyl chlorophosphate (1.1
mL, 7.6 mmol) was added, and stirring was continued for 30 min
at room temperature. The reaction was quenched with aqueous
saturated NH4Cl and the mixture was extracted with ethyl

4
Tetrahedron
acetate. The organic layer was dried over Na2SO4 and filtered.
(hexane/ethyl acetate = 4/1 with 1% AcOH) to provide 1a (100
ACCEPTED MANUSCRIPT
The filtrate was concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel
(hexane/ethyl acetate = 1/1) to provide the diethylphosphate 3 as
a colorless solid (1.95 g, quant.); [α]D -5.1 (c 0.85, CHCl3); H
NMR (500 MHz, CDC13): = 0.85 (t, J = 6.3 Hz, 6H), 1.06 (t, J
= 6.3 Hz, 6H), 3.46-3.52 (m, 4H), 3.67-3.79 (m, 4H), 7.27-7.33
(m, 4H), 7.42-7.45 (m, 2H), 7.79 (d, J = 9.2 Hz, 2H), 7.90 (d, J =
8.0 Hz, 2H), 7.97 (d, J = 9.2 Hz, 2H); 13C NMR (125 MHz,
mg, 81%) as a colorless solid.
4.4.1. (S)-1,1’-binaphthyl-3,3’-diphenyl-2,2’-
dicarboxylic acid (1a)5 , 6 c
20
1
Analytical data for this compound were identical with
reported data: [α]D -16.6 (c 0.90, CHCl3); H NMR (500 MHz,
CDC13): = 7.13 (d, J = 8.6 Hz, 2H), 7.30-7.34 (m, 2H), 7.40-
δ
20
1
δ
7.43 (m, 2H), 7.45-7.49 (m, 4H), 7.51-7.55 (m, 2H), 7.60 (d, J =
7.4 Hz, 4H), 7.95 (d, J = 8.0 Hz, 2H), 8.04 (s, 2H); 13C NMR
(125 MHz, CDC13):
CDC13):
δ = 15.5, 15.7, 64.0, 64.3, 119.1, 121.5, 125.3, 126.1,
δ = 126.7, 127.7, 127.9, 128.0, 128.2, 128.6,
126.9, 127.8, 129.9, 130.7, 133.5, 146.7; IR (CHCl3): 3061,
2931, 2911, 1624, 1593, 1508, 1475, 1394, 1361, 1265, 1165,
1066, 1011, 868, 854, 816 cm−1; HRMS (ESI) calcd. for
C28H32O8P2Na m/z 581.1465 [M+Na]+, found 581.1481.
128.7, 130.3, 131.3, 132.2, 132.9, 133.7, 136.3, 139.9, 171.4; IR
(CHCl3): 3061, 2928, 2855, 1748, 1662, 1454, 1373, 1273, 1109,
897 cm−1; HRMS (ESI) calcd. for C34H21O4 m/z 493.1434
[M−H]−, found 493.1414.
4.3. Reductive CO2 fixation of 3 to provide (S)-1,1’-binaphthyl-
2,2’-dicarboxylic acid 2
4.4.2. (S)-1,1’-binaphthyl-3,3’-bis(3,5-
dimethylphenyl)-2,2’-dicarboxylic acid (1b)
20
1
Lithium (20.8 mg, 3.0 mmol) and naphthalene (384.5 mg, 3.0
mmol) were weighed into a flask, which had been flame-dried
under vacuum. The flask was evacuated and refilled with argon,
and THF (5 mL) was added to it. The mixture was stirred for 3 h
at room temperature, then cooled to -78 °C. A solution of 3
(279.3 mg, 0.5 mmol) in THF (5 mL) was slowly added to the
mixture using a cannula. After stirring for 30 min, carbon dioxide
was bubbled to the reaction mixture. Stirring was continued for 2
h, then the mixture was allowed to warm to room temperature,
and the reaction was quenched with aqueous 1 N HCl. The whole
was extracted with diethyl ether, and then 1 N NaOH was added
to the organic phase. The resulting aqueous layer was washed
with diethyl ether. The aqueous phase was acidified with 1 N
HCl, and extracted with ethyl acetate. The organic phase was
washed with brine, dried over MgSO4, and filtered. The filtrate
was concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (hexane/ethyl
acetate 4/1 with 1% AcOH) to give the dicarboxylic acid 2 (140.3
mg, 82%) as a colorless solid. The obtained compound was
identified by comparison of the analytical data with reported
values.10 The optical purity of the product was determined to be
[α]D 1.2 (c 2.26, CHCl3); H NMR (500 MHz, CDC13):
δ =
2.38 (s, 12H), 7.04 (s, 2H), 7.11 (d, J = 8.6 Hz, 2H), 7.20 (s, 4H),
7.30 (t, J = 7.4 Hz, 2H), 7.52 (t, J = 7.4 Hz, 2H), 7.93 (d, J = 8.0
Hz, 2H), 8.00 (s, 2H); 13C NMR (125 MHz, CDC13):
δ = 21.3,
126.5, 126.6, 127.5, 127.8, 128.1, 129.5, 130.1, 131.2, 132.3,
132.7, 133.6, 136.5, 138.0, 139.9, 171.8; IR (CHCl3): 2922,
1746, 1668, 1602, 1363, 1288, 895, 852 cm−1; HRMS (ESI)
calcd. for C38H29O4 m/z 549.2060 [M−H]−, found 549.2033.
4.4.3. (S)-1,1’-binaphthyl-3,3’-bis(2-naphthyl)-
2,2’-dicarboxylic acid (1c)
[α]D20 74.2 (c 0.49, CHCl3); 1H NMR (500 MHz, CDC13):
δ =
7.18 (d, J = 8.6 Hz, 2H), 7.33 (dt, J = 1.2, 7.5 Hz, 2H), 7.50-7.76
(m, 7H), 7.70 (dd, J = 1.8, 8.6 Hz, 2H), 7.88-7.93 (m, 7H), 7.96
(d, J = 8.0 Hz, 2H), 8.06 (s, 2H), 8.12 (s, 2H); 13C NMR (125
MHz, CDC13):
δ = 126.2, 126.4, 126.7, 126.8, 127.6, 127.7,
127.9, 128.1, 128.2, 130.5, 131.3, 132.7, 132.9, 133.0, 133.3,
133.6, 136.2, 137.5, 172.0; IR (CHCl3): 3057, 2928, 2855, 1748,
1668, 1456, 1362, 1271, 895, 858 cm−1; HRMS (ESI) calcd. for
C42H25O4 m/z 593.1747 [M−H]−, found 593.1737.
26
>99% by chiral HPLC analysis; [α]D -76.4 (c 0.90, CHCl3,
>99% ee sample); 1H NMR (500 MHz, CDC13):
δ = 6.90 (d, J =
4.5. Diiodination of 1,1’-binaphthyl-2,2’-dicarboxylic acid 2 to
give 517
8.6 Hz, 2H), 7.13-7.16 (m, 2H), 7.46-7.50 (m, 2H), 7.91 (d, J =
8.4 Hz, 2H), 7.96 (d, J = 8.6 Hz, 2H), 8.13 (d, J = 9.2 Hz, 2H);
To a solution of 2 (684 mg, 2 mmol) and TMEDA (2 mL, 13.4
mmol) in THF (10 mL) was added sec-BuLi solution in
cyclohexane (1.0 M, 12 mL, 12 mmol) at -40 °C. The mixture
was stirred for 2 h at -40 °C, and then iodine (2g, 15.8 mmol)
solution in THF (10 mL) was added to it. The solution was
stirred for additional 2 h at -40 °C, then quenched with aqueous
Na2S2O3 and extracted with ethyl acetate after acidifying with 1N
HCl. The organic layer was dried over Na2SO4, and filtered. The
filtrate was evaporated under reduced pressure and the residue
was re-dissolved in MeOH. Silica gel was added to the mixture
and the organic solvent was removed under reduced pressure.
The compound was purified by column chromatography on silica
gel (hexane/ethyl acetate = 1/1 with 1% AcOH) to provide 5
(0.59 g, 50%). Analytical data for the isolated compound were
13C NMR (125 MHz, CDC13):
δ = 125.5, 126.5, 126.6, 127.4,
127.8, 128.0, 132.8, 135.3, 141.8, 172.1; IR (CHCl3): 1703,
1597, 1470, 1285 cm-1; HRMS (ESI) calcd. for C22H13O4 m/z
341.0808 [M−H]−, found 341.0805. Daicel CHIRALCEL OD-H
(φ 0.46 cm x 25 cm), n-hexane/EtOH = 90/10 with 1% CF3CO2H,
flow rate 1.0 mL/min, detection at 254 nm, tR = 9.1 min (R), 12.7
min (S).
4.4. Typical experimental procedure for Pd-catalyzed C–H
coupling at the ortho-position of the carboxylic acid using
iodoarenes
Compound 2 (85.6 mg, 0.25 mmol), Pd(OAc)2 (5.6 mg, 10
mol %), Ag2CO3 (76 mg, 1.1 equiv.), and K2CO3 (35 mg, 1
equiv.) were weighed into a Schlenk tube with J Young
greaseless stopcock, which had been flame-dried under vacuum.
The tube was evacuated and back-filled with argon. Then, AcOH
(0.13 mL) and iodobenzene (167 µL, 6 equiv.) were added. The
mixture was stirred for 24 h at 120 °C, then allowed to cool to
room temperature, and extracted with ethyl acetate. The organic
layer was washed with brine, dried over Na2SO4, and filtered.
The filtrate was concentrated under reduced pressure and the
residue was purified by column chromatography on silica gel
20
1
identical with reported values: [α]D -117.3 (c 0.72, CHCl3); H
NMR (500 MHz, CD3OD): = 7.07 (d, J = 8.5 Hz, 2H), 7.36-
7.39 (m, 2H), 7.55-7.58 (m, 2H), 7.92 (d, J = 8.5 Hz, 2H), 8.68
(s, 2H); 13C NMR (125 MHz, CD3OD):
= 89.0, 129.0, 129.1,
δ
δ
129.6, 129.9, 133.8, 135.2, 136.7, 140.1, 142.0, 172.4; IR
(CHCl3): 1749, 1711, 1364 cm−1; HRMS (ESI) calcd. for
C22H11I2O4 m/z 592.8741 [M−H]−, found 592.8763.

5
5. Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2007, 129,
4.6. Typical experimental procedure for Suzuki-Miyaura
coupling of 5
ACCEPTED MANUSCRIPT
10054-10055.
6. (a) Hashimoto, T.; Hirose, M.; Maruoka, k. J. Am. Chem. Soc.
2008, 130, 7556-7557; (b) Hashimoto, T.; Uchiyama, N.;
Maruoka, K. J. Am. Chem. Soc. 2008, 130, 14380-14381; (c)
Hashimoto, T.; Kimura, H.; Nakatsu, H.; Maruoka, K. J. Org.
Chem. 2011, 76, 6030-6037; (d) Hashimoto, T.; Omote, M.;
Maruoka, K. Angew. Chem. Int. Ed. 2011, 50, 3489-3492; (e)
Hashimoto, T. Omote, M.; Maruoka, K. Angew. Chem. Int. Ed.
2011, 50, 8952-8955; (f) Hashimoto, T.; Kimura, H.; Kawamata,
Y.; Maruoka, K. Nature Chem. 2011, 3, 642-646; (g) Hashimoto,
T.; Kimura, H.; Kawamata, Y.; Maruoka, K. Angew. Chem. Int.
Ed. 2012, 51, 7279-7281; (h) Hashimoto, T.; Isobe, S.; Callens, C.
K. A.; Maruoka, K. Tetrahedron 2012, 68, 7630-7635.
7. (a) Seki, M.; Yamada, S.; Kuroda, T.; Imashiro, R.; Shimizu, T.
Synthesis 2000, 32, 1677-1680; (b) Seki, M. Synlett 2008, 19, 164-
176.
8. Ohta, T.; Ito, M.; Inagaki, K.; Takaya, H. Tetrahedron Lett. 1993,
34, 1615-1616.
9. Schlosser, M.; Bailly, F. J. Am. Chem. Soc. 2006, 128, 16042-
16043.
10. Hoshi, T.; Nozawa, E.; Katano, M.; Suzuki, T.; Hagiwara, H.
Tetrahedron Lett. 2004, 45, 3485-3487.
11. (a) Ikeuchi, K.; Ido, K.; Yoshimura, S.; Asakawa, T.; Inai, M.;
Hamashima, Y.; Kan, T. Org. Lett. 2012, 14, 6016-6019; (b)
Ikeuchi, K.; Hayashi, M.; Yamamoto, T.; Inai, M.; Asakawa, T.;
Hamashima, Y.; Kan, T. Eur. J. Org. Chem. 2013, 2013, 6789-
6792; (c) Kawato, Y.; Kubota, A.; Ono, H.; Egami, H.;
Hamashima, Y. Org. Lett. 2015, 17, 1244-1247.
Compound 5 (29.7 mg, 0.05 mmol), Pd(OAc)2 (0.5 mg, 5 mol
%), and 2-naphthylboronic acid (25.8 mg, 0.15 mmol) were
weighed into a Schlenk flask. Water (1 mL) was added. After
stirring for 10 min at room temperature, KOH (25.2 mg, 0.45
mmol) was added to the mixture. The mixture was heated up
under micro-wave irradiation to 120 °C for 1 h, and then
extracted with ethyl acetate after acidifying with 1N HCl. The
organic layer was dried over MgSO4, and filtered. The filtrate
was concentrated under reduced pressure and the residue was
purified by column chromatography on silica gel (hexane/ethyl
acetate = 4/1 with 1% AcOH) to provide 1c (20.1 mg, 68%) as a
colorless solid.
4.6.1. (S)-1,1’-binaphthyl-3,3’-bis(4-
methoxyphenyl)-2,2’-dicarboxylic acid (1e)
[α]D20 27.9 (c 1.64, CHCl3); 1H NMR (500 MHz, CDC13):
δ =
3.86 (s, 6H), 6.99 (td, J = 2.9, 9.2 Hz, 4H), 7.12 (d, J = 8.6 Hz,
2H), 7.30 (dt, J = 1.1, 7.5 Hz, 2H), 7.50-7.53 (m, 6H), 7.93 (d, J
= 8.6 Hz, 2H), 8.00 (s, 2H); 13C NMR (125 MHz, CDC13):
δ =
55.3, 114.1, 126.6, 127.4, 127.9, 128.1, 129.8, 130.1, 131.0,
132.3, 132.3, 132.7, 133.7, 135.8, 159.3, 171.9; IR (CHCl3):
2936, 2839, 1744, 1611, 1514, 1240, 1036, 835 cm−1; HRMS
(ESI) calcd. for C36H25O6 m/z 553.1646 [M−H]−, found 553.1625.
12. Ishihara, K.; Inanaga, K.; Kondo, S.; Funahashi, M.; Yamamoto,
H. Synlett 1998, 9, 1053-1056.
13. Kawabata, H.; Omura, K.; Uchida, T.; Katsuki, T. Chem. Asian J.
2007, 2, 248-256.
4.6.2. (S)-1,1’-binaphthyl-3,3’-bis[3,5-
bis(trifluoromethyl) phenyl] -2,2’-dicarboxylic acid
(1g)5
14. For selected reviews on C-H coupling reactions, see: (a) Arockiam,
P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879-
5918; (b) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc.
Chem. Res. 2012, 45, 788-802; (c) Powers, D. C.; Ritter, T. Acc.
Chem. Res. 2012, 45, 840-850; (d) Neufeldt, S. R.; Sanford, M. S.
Acc. Chem. Res. 2012, 45, 936-946; (e) Mousseau, J. J.; Charette,
A. B. Acc. Chem. Res. 2013, 46, 412-424; (f) Wencel-Delord, J.;
Colobert, F. Chem. Eur. J. 2013, 19, 14010-14017; (g) Engle, K.
M; Yu, J.-Q. J. Org. Chem. 2013, 78, 8927-8955; (h) Rossi, R.;
Bellina, F.; Lessi, M.; Manzini, C. Adv. Synth. Catal. 2014, 356,
17-117; (i) Shi, G.; Zhang, Y. Adv. Synth. Catal. 2014, 356, 1419-
1442; (j) Thirunavukkarasu, V. S.; Kozhushkov, S. I.; Ackermann,
L. Chem. Commun. 2014, 50, 29-39.
15. For selected reports on ortho-C-H coupling reaction of benzoic
acid derivatives with iodoarenes, see: (a) Giri, R. G.; Maugel, N.;
Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q.
J. Am. Chem. Soc. 2007, 129, 3510-3511; (b) Chiong, H. A.; Pham,
Q.-N.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 9879-9884; (c)
Arroniz, C.; Ironmonger, A.; Rassias, G.; Larrosa, I. Org. Lett.
2013, 15, 910-913; (d) Arroniz, C.; Denis, J. G.; Ironmonger, A.;
Rassias, G.; Larrosa, I. Chem. Sci. 2014, 5, 3509-3514.
16. (a) Bumagin, N. A.; Bykov, V. V. Tetrahedron 1997, 42, 14437-
14450; (b) Korolev, D. N.; Bumagin, N. A. Tetrahedron Lett.
2005, 46, 5751-5754; (c) Korolev, D. N.; Bumagin, N. A.
Tetrahedron Lett. 2006, 47, 4225-4229.
Analytical data for this compound were identical with
20
1
reported values: [α]D -30.5 (c 0.58, CHCl3); H NMR (500
MHz, CD3OD): = 7.11 (d, J = 8.5 Hz, 2H), 7.35-7.38 (m, 2H),
7.55-7.58 (m, 2H), 8.01 (s, 2H), 8.09 (d, J = 8.5 Hz, 2H), 8.19 (s,
2H), 8.28 (s, 4H); 13C NMR (125 MHz, CD3OD):
= 122.9,
δ
δ
125.8 (q, J = 271.8 Hz), 128.6 (q, J = 8.3 Hz), 129.4, 129.8,
130.5, 131.3, 132.4 (q, J = 3.6 Hz), 133.6 (q, J = 33.4 Hz), 134.3,
134.6, 135.4, 135.6, 138.1, 145.8, 175.5; 19F NMR (375 MHz,
CD3OD):
δ = -64.1 (s); IR (CHCl3): 1749, 1667, 1377, 1280,
1184, 1142 cm−1; HRMS (ESI) calcd. for C38H17F12O4 m/z
765.0930 [M−H]−, found 765.0941.
Acknowledgments
This work was supported by Grant-in-Aid for Scientific
Research on Innovative Areas “Advanced Molecular
Transformations by Organocatalysts,” a grant from Astellas
Foundation for Research on Metabolic Disorders, and grant for
Platform for Drug Discovery, Informatics and Structural Life
Science from The Ministry of Education, Culture, Sports,
Science and Technology, Japan.
17. Yang, D.; Wong, M.-K.; Yip, Y.-C.; Wang, X.-C.; Tang, M.-W.;
Zheng, J.-H.; Cheung, K.-K. J. Am. Chem. Soc. 1998, 120, 5943-
5952.
18. For examples on ortho-lithiation of carboxylic acids with organo-
lithium reagents, see: (a) Nguyen, T.-H.; Chau, N. T. T.; Castanet,
A.-S.; Nguyen, K. P. P.; Mortier, J. Org. Lett. 2005, 7, 2445-2448;
(b) Nguyen, T.-H.; Castanet, A.-S.; Mortier, J. Org. Lett. 2006, 8,
765-768; (c) Tilly, D.; Samanta, S. S.; Castanet, A.-S.; De, A.;
Mortier, J. Eur. J. Org. Chem. 2006, 2006, 174-182.
19. Selected reviews on cross-coupling reaction of organoboron
compounds: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457-2483; (b) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004,
2419-2440; (c) Suzuki, A.; Yamamoto, Y. Chem. Lett. 2011, 40,
894-901; (d) Suzuki, A. Angew. Chem. Int. Ed. 2011, 50, 6722-
6737.
20. Fulmer, G. R.; Miller, A. J. M.; Sherden, N. H.; Gottlieb, H. E.;
Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.; Goldberg, K. I.
Organometallics 2010, 29, 2176-2179.
21. Hatano, M.; Miyamoto, T.; Ishihara, K. J. Org. Chem. 2006, 71,
6474-6464.
References and notes
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