Synthesis of axially chiral amino acid derivatives via the selective monoesterification of 1,1′-biaryl-2,2′-dicarboxylic acids

Article abstract of DOI:10.1055/s-0032-1318506

Axially chiral amino acid derivatives were synthesized via a selective single-step monoesterification of 1,1′-binaphthyl-2,2′-dicarboxylic acids. In the presence of Ag₂CO₃, the alkylative monoesterification of a 1,1′-binaphthyl-2,2′-dicarboxylic acid with an alkyl halide proceeded selectively in a single operation. Curtius rearrangement of the monomethyl ester and successive alcoholysis of the corresponding isocyanate afforded the N-protected binaphthyl amino acids. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0032-1318506

1312▌
PAPER
paper
Synthesis of Axially Chiral Amino Acid Derivatives via the Selective
Monoesterification of 1,1′-Biaryl-2,2′-dicarboxylic Acids
Selective Monoesterification of 1,1′-Biaryl-2,2′-dicarboxylic Acids
Takumi Furuta,* Masanori Nikaido, Junya Yamamoto, Toshifumi Kuribayashi, Takeo Kawabata
Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011, Japan
Fax +81(774)383197; E-mail: furuta@fos.kuicr.kyoto-u.ac.jp
Received: 22.01.2013; Accepted after revision: 06.03.2013
Applications of amino acids as chiral building blocks re-
quire a variety of N-protected derivatives; however, the
synthetic route to (S)-2 (Scheme 1) is hardly applicable
to other N-protected amino acids, such as N-Cbz and
Abstract: Axially chiral amino acid derivatives were synthesized
via a selective single-step monoesterification of 1,1′-binaphthyl-
2,2′-dicarboxylic acids. In the presence of Ag2CO3, the alkylative
monoesterification of a 1,1′-binaphthyl-2,2′-dicarboxylic acid with
an alkyl halide proceeded selectively in a single operation. Curtius N-Alloc derivatives, due to the need for individual optimi-
rearrangement of the monomethyl ester and successive alcoholysis
of the corresponding isocyanate afforded the N-protected binaph-
thyl amino acids.
zation and the optical resolution in each case.
An improved synthetic strategy toward achieving access
to N-Cbz 7 and N-Alloc amino acids 8 was envisioned
through the synthesis, via Curtius rearrangement, of the
optically active monomethyl ester 10, which enabled the
Key words: unnatural amino acid, monoesterification, half-ester,
biaryl, axial chirality
introduction of a variety of N-protecting groups during the
latter stages of synthesis (Scheme 2). However, during an
Unnatural amino acids have attracted considerable atten-
investigation of Scheme 2, we noticed that the selective
tions as chiral organocatalysts,1 ligands,2 and as versatile
monomethyl esterification of 1,1′-binaphthyl-2,2′-dicar-
building blocks for peptide mimetics.3 We developed (S)-
boxylic acid (9), yielding 10, proved to be difficult, even
2-amino-2′-carboxy-1,1′-binaphthalene (1) and its N-Boc
though the transformation initially appeared to be quite
derivative (S)-2 as unique axially chiral amino acid deriv-
simple.
atives, prepared via the phosphine ligand-free Pd-cata-
lyzed domino coupling4 of 3 to 4 and the subsequent
lactam ring opening of 5 with sodium alkoxide of (S)-
phenylethanol (6). Diastereomer separation of the corre-
sponding esters was achieved by fractional crystallization
and successive removal of the ester moiety yielded the op-
tically active N-Boc amino acid (S)-2 (Scheme 1).5 We
also demonstrated that (S)-2 is useful as a chiral building
block for artificial dipeptides.5
COOH
COOH
COOMe
COOH
COOH
NHR
7: R = Cbz
8: R = Alloc
10
9
Scheme 2 Synthetic strategy via selective monoesterification and
Curtius rearrangement
O
H
Pd2(dba)3
N
Compound 9 was derivatized through a selective monoes-
terification in the context of catalyst preparation in an
asymmetric synthesis.6 For example, monomethyl ester
(R)-10 was obtained via selective demethylation of the
corresponding dimethyl ester (R)-117 by BBr3 in 36%
yield with 55% recovery of (R)-11 (Figure 1).6a As an al-
ternative to the monoesterification of 9, monoglycidyl es-
ter (R)-12 was obtained by preparing the cyclic anhydride
(R)-13, followed by ring-opening with glycidol in 80%
yield (Figure 1).6b–d Although the yield of (R)-12 was sat-
isfactory, two manipulation steps were required from di-
carboxylic acid 9.
PMB
K2CO3
DMF
N
PMB
Br
O
100 °C
3
4
HO
Ph
COOH
NHR
O
6
N
Boc
(S)-1: R = H
(S)-2: R = Boc
5
Scheme 1 Previous synthesis of (S)-1 and (S)-2
Thus, there is a need for the development of a selective
single-step monoesterification method that can yield the
corresponding half-ester. To the best of our knowledge,
no precedent example has been reported describing the
highly selective monoesterification of a symmetric 1,1′-
biaryl-2,2′-dicarboxylic acid in a single operation with an
SYNTHESIS 2013, 45, 1312–1318
Advanced online publication: 10.04.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318506; Art ID: SS-2013-F0057-OP
© Georg Thieme Verlag Stuttgart · New York

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Selective Monoesterification of 1,1′-Biaryl-2,2′-dicarboxylic Acids
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COOMe
COOMe
COOH
COOH
COO
COOMe
COOH
O
COOH
14
15
(R)-11
(R)-12
Figure 2 Structures of 14 and its monomethyl ester 15
O
1,1′-biaryl-2,2′-dicarboxylic acid would be possible under
mild basic conditions in the presence of a weak base, such
as a metal carbonate, due to the predominant formation of
the monocarboxylate ion of a dicarboxylic acid.
O
O
(R)-13
The alkylative monoesterification of 9 was first examined
using three equivalents of MeI in the presence of 0.5
equivalent of Ag2CO3 in a series of solvents at room tem-
perature (Table 1). Ag2CO3 was selected as the base on the
expectation that silver cations activate alkyl iodides and
can, therefore, increase the chemical yield of 10. As ex-
pected, monomethyl ester 10 was obtained as the major
product in a variety of solvents without the substantial for-
mation of the dimethyl ester 11, except for one reaction
conducted in MeCN (Table 1, entry 1). In DMF and
CHCl3, the esterifications proceeded to yield 10 in 71%
and 77% yield, respectively, with the concomitant forma-
tion of a small amount of 11 within 36 hours (Table 1, en-
tries 2 and 5). In acetone, 10 was selectively obtained in
48% yield without overesterification to 11 (Table 1, entry
3). Given the selectivity and low toxicity of acetone, this
solvent was used during subsequent optimization studies,
the results of which are presented in Table 2.
Figure 1 Structures of 1,1′-binaphthyl-2,2′-dicarboxylic acid deriv-
atives
acceptable yield.8 Herein, we describe the selective sin-
gle-step monoesterification of 9 and successive transfor-
mation of monomethyl ester 10 to various N-protected
axially chiral amino acid derivatives.
To achieve the selective monoesterification of 9, we fo-
cused on the differences between the acidities of each car-
boxy group. A recent X-ray crystallographic analysis of a
derivative of 9 indicated the presence of an intramolecular
hydrogen bonding interaction between the carboxy
groups in the binaphthyl system, which led to differences
in the acidity of each carboxy group.9 The two pKa values
in 1,1′-biphenyl-2,2′-dicarboxylic acid (14) were found to
be typical (Figure 2). The 1st pKa and 2nd pKa values of
14 were reported to be 4.88 and 8.73, respectively, in an
80% aqueous 2-methoxyethanol solution.10 The 1st pKa of
14 (4.88) was smaller than the pKa (7.02) of the corre-
sponding monomethyl ester 15.10a
The reaction mixture was warmed to 40 °C for 12 hours,
which improved the yield of 10 to 92% along with a small
amount of 11 (8%) (Table 2, entry 1). A decrease in the
quantity of MeI reduced the yield (entry 2). An increase in
the quantity of Ag2CO3 also diminished the yield of 10 by
Given the large differences in their pKa values, we antici-
pated that the selective alkylative monoesterification of a
Table 1 Monomethyl Esterification of 9 with MeI in the Presence of Ag2CO3
MeI
(3.0 equiv)
Ag2CO3
(0.5 equiv)
COOH
COOH
COOMe
COOH
COOMe
COOMe
+
solvent, r.t.
36 h
9
10
11
Entry
Solvent
10 (%)a
11 (%)a
1
2
3
4
5
6
MeCN
DMF
74
71
48
21
77
55
26
3
acetone
THF
<1
<1
4
CHCl3
toluene
5
a Determined by the integration of 1H NMR signals in the presence of 1,4-dimethoxybenzene as an internal standard.
© Georg Thieme Verlag Stuttgart · New York Synthesis 2013, 45, 1312–1318

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T. Furuta et al.
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Table 2 Optimization of Monomethyl, Benzyl, and Allyl Esterification of 9
R-X (3.0 equiv)
base (0.5 equiv)
COOR
COOH
COOR
COOR
COOH
COOH
additive (3.0 equiv)
+
acetone, 40 °C
12 h
10: R = Me
16: R = Bn
18: R = allyl
9
11: R = Me
17: R = Bn
19: R = allyl
Entry
RX
Additive
Base
Monoester
Yield (%)
Diester
Yield (%) (%)
1a
2a
3a
4a
5a
6a
7
MeI
–
Ag2CO3
Ag2CO3
Ag2CO3
Na2CO3
K2CO3
10
10
10
10
10
10
16
16
18
18
92
66
68
36
63
45
–
11
11
11
11
11
11
17
17
19
19
8
3
MeIb
–
c
MeI
–
34
20
<1
<1
–
MeI
–
MeI
–
MeI
–
Cs2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
BnBr
–
8
BnBr
TBAI
–
75
54
72
18
<1
28
9
allyl bromide
allyl bromide
10
TBAI
a The yields of 10 and 11 were determined by the integration of 1H NMR signals in the presence of 1,4-dimethoxybenzene as an internal stan-
dard.
b MeI (1.0 equiv) was used.
c Ag2CO3 (1.0 equiv) was used.
forming significant quantities of 11 (entry 3). Replacing acid (14) was selectively converted into 15 in 90% yield
Ag2CO3 with other carbonate bases, such as Na2CO3, (Scheme 3).
K2CO3, and Cs2CO3, decreased the yield of 10 in all cases
(entries 4–6). The reduced yields of 10 suggested that the
silver cation activated MeI under the reaction conditions.
MeI (3.0 equiv)
Ag2CO3 (0.5 equiv)
R
R
COOH
COOH
R
R
COOMe
COOH
Optically active (R)-10 was also prepared from (R)-911 via
the optimized conditions (Table 2, entry 1). Under the
conditions, no racemization was observed by HPLC anal-
ysis with a chiral stationary phase.
acetone, 40 °C
12 h
14: R = H
15: R = H (90%)
21: R = Me (89%)
20: R = Me
Alkylative monoesterification reactions are applicable to
benzyl and allyl esterification. Upon treatment of 9 with
benzyl bromide in the presence of three equivalents of the
additive TBAI, the esterification proceeded smoothly to
afford monobenzyl ester 166c in 75% yield with the con-
comitant formation of the dibenzyl ester 17 (Table 2, entry
8). In the absence of TBAI, the benzyl esterification did
not proceed at all (entry 7). Monoallyl ester 18 was ob-
tained in the presence of TBAI in 72% yield (entry 10). In
contrast to the benzyl esterification reaction, 18 was ob-
tained in 54% yield without the addition of TBAI (entry
9). Although the yield of 18 was unsatisfactory in this
case, the overesterified product 19 was not observed, sug-
gesting that this approach may be of practical utility.
Scheme 3 Monomethyl esterification of 1,1′-biphenyl-2,2′-dicar-
boxylic acid derivatives
The axially chiral 6,6′-dimethyl-1,1′-biphenyl-2,2′-dicar-
boxylic acid (20) was transformed to 216a in 89% yield.
Cyclic anhydride (R)-22 (Figure 3) derived from configu-
rationally stable (R)-20 was found to be racemized by
heating at 85 °C in DME.12 This suggested that some care
should be taken with racemization, at which point the op-
tically active biphenyl monoester was prepared by open-
ing a cyclic anhydride with an alcohol under heating
conditions. The selective monoesterification described
here is suitable for preparing axially chiral 1,1′-biphenyl-
2,2′-dicarboxylic acid derivatives due to the mild reaction
conditions, which do not require a racemizable cyclic an-
hydride as an intermediate.
The optimized conditions (Table 2, entry 1) were next ap-
plied to other biaryls. 1,1′-Biphenyl-2,2′-dicarboxylic
Synthesis 2013, 45, 1312–1318
© Georg Thieme Verlag Stuttgart · New York

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Selective Monoesterification of 1,1′-Biaryl-2,2′-dicarboxylic Acids
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1) DPPA, Et3N
toluene, 90 °C
KOH
H2O
COOMe
NHCbz
COOH
NHCbz
(R)-10
2) BnOH
toluene, 50 °C
THF
81%
94%
(R)-23
(R)-7
1) DPPA, Et3N
toluene, 90 °C
KOH
H2O
COOH
COOMe
NHAlloc
2) AllylOH
toluene, 50 °C
THF
54%
NHAlloc
74%
(R)-8
(R)-24
Scheme 4 Transformation to the N-protected axially chiral amino acids
Merck Kieselgel 60 F254, respectively. Silica gel chromatography
was carried out Wakogel C-200, Fuji Silysia BW-1277H, or Nacalai
Tesque Silica gel 60 (150–325 mesh). Anhyd MeCN, CHCl3, and
toluene were purchased from Kanto Chemical Co., Inc. Anhyd ace-
tone, THF, and DMF were purchased from Wako Pure Chemical In-
dustries, Ltd.
O
O
O
Monomethyl Esterification of 9 (Table 2, Entry 1)
(R)-22
To a solution of 1,1′-binaphthyl-2,2′-dicarboxylic acid (9; 50 mg,
0.15 mmol, 1.0 equiv), and Ag2CO3 (20 mg, 73 μmol, 0.5 equiv) in
acetone (2.0 mL) was added MeI (27 μL, 0.44 μmol, 3.0 equiv) at
r.t. After stirring at 40 °C for 12 h, the reaction was quenched with
2 M aq HCl (5.0 mL), and extracted with EtOAc (2 × 20 mL). The
combined organic layers were washed with H2O (20 mL), dried
(Na2SO4), filtered, and concentrated in vacuo. The yields of the
monomethyl ester 106a (92%) and the dimethyl ester 117 (8%) were
determined by the integration of 1H NMR signals in the presence of
1,4-dimethoxybenzene as an internal standard.
Figure 3 Structure of cyclic anhydride (R)-22
With the selective monoesterification conditions in hand,
we investigated the transformation of (R)-10 to the corre-
sponding N-protected axially chiral amino acids (Scheme
4). Curtius rearrangement of (R)-10 in the presence of di-
phenylphosphoryl azide (DPPA) proceeded to give the
isocyanate intermediate, and the subsequent addition of
benzyl alcohol or allyl alcohol to the intermediate afford-
ed (R)-23 and (R)-24 in 94% and 74% yield, respectively.
During these transformations, no racemization was ob-
served by HPLC analysis with chiral stationary phase.
Successive hydrolysis of (R)-23 and (R)-24 afforded the
corresponding N-Cbz and N-Alloc amino acids (R)-7 and
(R)-8, respectively.
(R)-2′-(Methoxycarbonyl)-1,1′-binaphthalene-2-carboxylic
Acid [(R)-10]6a
Optically active (R)-911 (>99% ee) was also converted to (R)-106a
(>99% ee) without racemization under the optimized conditions.
Optical purity of (R)-106a was confirmed by the optical rotation and
HPLC analysis with a chiral stationary phase; [α]D20 +45.3 (c 1.02,
CHCl3) (>99% ee) {Lit.6a [α]D22 +43.7 (c 1.07, CHCl3)}.
HPLC: Chiralpak AD-H (0.46 × 25 cm), hexane–i-PrOH (60:40),
0.5 mL/min, 254 nm, tR = 19.8 min (R), 23.0 min (S).
In conclusion, we have developed a readily accessible
route to axially chiral N-protected amino acids via a selec- Monobenzyl Esterification of 9 (Table 2, Entry 8)
To a solution of 9 (50 mg, 0.15 mmol), Ag2CO3 (20 mg, 73 μmol),
and TBAI (162 mg, 0.44 mmol) in acetone (2.0 mL) was added ben-
zyl bromide (52 μL, 0.44 mmol) at r.t. After stirring at 40 °C for 12
h, the mixture was directly evaporated in vacuo. The residue was
tive single-step monoesterification of the 1,1′-biaryl-2,2′-
dicarboxylic acids. The variety of the binaphthyl N-pro-
tected amino acid was expanded by synthesizing the N-
Cbz and N-Alloc derivatives. The selective monoesterifi-
cation was characterized by mild conditions and a simple
procedure. This protocol would be valuable as a pivotal
transformation of the axially chiral 1,1′-biaryl-2,2′-dicar-
boxylic acids.13
purified by preparative TLC (SiO2, hexane–EtOAc, 1:1) to give the
monobenzyl ester 166c and dibenzyl ester 17, respectively.
1,1′-Binaphthyl-2,2′-dicarboxylic Acid Monobenzyl Ester (16)6c
Yield: 47 mg (75%); colorless solid; mp 154–155 °C.
IR (KBr): 1239, 1279, 1691, 1722, 3062 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.76–4.92 (m, 2 H), 6.82 (d,
J = 8.2 Hz, 2 H), 6.90–7.40 (m, 2 H), 7.06–7.22 (m, 5 H), 7.48 (t,
J = 7.8 Hz, 2 H), 7.84 (t, J = 6.0 Hz, 2 H), 7.93 (d, J = 8.2 Hz, 1 H),
7.94–8.20 (m, 2 H), 8.18 (d, J = 8.7 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 66.8, 126.0, 126.3, 126.7, 127.1,
127.3, 127.7, 127.86, 127.90, 127.93, 127.99, 128.03, 128.2, 132.8,
134.9, 135.05, 135.14, 139.6, 140.8, 167.1, 171.1.
NMR spectra were recorded on a JEOL JMN 400 spectrometer,
chemical shifts being given in ppm units. IR spectra were recorded
on a JASCO FT/IR-300 spectrometer. Specific rotation was mea-
sured with a Horiba SEPA-200 automatic digital polarimeter. MS
spectra were recorded on a JEOL JMS-700 mass spectrometer.
Melting points were measured with a Yanako melting points appa-
ratus. TLC analysis and preparative TLC were performed on com-
mercial glass plates bearing a 0.25 mm layer and 0.5 mm layer of
MS (FAB): m/z = 432 (M)+, 433 (M + H)+, 455 (M + Na)+.
© Georg Thieme Verlag Stuttgart · New York
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T. Furuta et al.
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HRMS (FAB): m/z calcd for C29H20O4 (M)+: 432.1362; found:
432.1357.
Monomethyl Esterification of 6,6′-Dimethyl-1,1′-biphenyl-2,2′-
dicarboxylic Acid (21)
To a solution of 20 (101 mg, 0.38 mmol), and Ag2CO3 (52 mg, 0.19
mmol, 0.5 equiv) in acetone (4.0 mL) was added MeI (70 μL, 1.13
mmol, 3.0 equiv) at r.t. After stirring at 40 °C for 12 h, the reaction
was quenched with 2 M aq HCl (5.0 mL), and extracted with EtOAc
(2 × 20 mL). The combined organic layers were washed with H2O
(20 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The
residue was purified by column chromatography (SiO2, hexane–
EtOAc, 1:1) to afford the monomethyl ester 21;6a yield: 95 mg
(89%); colorless prisms (hexane–EtOAc); mp 136–137 °C.
1,1′-Binaphthyl-2,2′-dicarboxylic Acid Dibenzyl Ester (17)
Yield: 14 mg (18%); pale yellow oil.
IR (KBr): 1132, 1237, 1276, 1723, 2952, 3033, 3062, 3427 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.84 (ABq, JAB = 12.4 Hz,
ΔνAB = 12.9 Hz, 2 H), 6.84 (d, J = 7.3 Hz, 4 H), 7.03 (d, J = 8.7 Hz,
2 H), 7.10–7.26 (m, 8 H), 7.49 (d, J = 8.2 Hz, 2 H), 7.87 (d, J = 8.7
Hz, 4 H), 8.09 (d, J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 66.6, 126.1, 126.7, 127.2, 127.3,
127.6, 127.8, 127.9, 128.1, 128.2, 132.9, 134.8, 135.3, 140.0, 166.7.
MS (FAB): m/z = 522 (M)+, 523 (M + H)+, 545 (M + Na)+.
HRMS (FAB): m/z calcd for C36H26O4 (M)+: 522.1831; found:
Transformation of (R)-10 to (R)-Methyl 2′-(Benzyloxycarbonyl-
amino)-1,1′-binaphthalene-2-carboxylate [(R)-23]
To a solution of (R)-10 (>99% ee) (320 mg, 0.90 mmol) in toluene
(10 mL) were added DPPA (0.21 mL, 0.99 mmol) and Et3N (0.38
mL, 2.7 mmol) at 0 °C under an argon atmosphere. After stirring for
1.5 h at 90 °C, the reaction mixture was cooled to r.t. and treated
with BnOH (0.10 mL, 0.99 mmol). The mixture was stirred for 3 h
at 50 °C. The reaction was quenched with 2 M aq HCl (20 mL), and
extracted with EtOAc (2 × 40 mL). The combined organic layers
were washed with 2 M aq NaOH (20 mL), brine (20 mL), dried
(Na2SO4), filtered, and concentrated in vacuo to give a residue. The
residue was purified by column chromatography (SiO2, hexane–
EtOAc, 6:1) to afford (R)-23; yield: 390 mg (94%); colorless nee-
dles (hexane–toluene); mp 152 °C; [α]D20 +36 (c 1.3, CHCl3) (>99%
ee). Optical purity of (R)-23 (>99% ee) was confirmed by HPLC
analysis with a chiral stationary phase.
522.1845.
Monoallyl Esterification of 9 (Table 2, Entry 10)
To a solution of 9 (50 mg, 0.15 mmol), Ag2CO3 (20 mg, 73 μmol),
and TBAI (162 mg, 0.44 mmol) in acetone (2.0 mL) was added allyl
bromide (38 μL, 0.44 mmol) at r.t. After stirring at 40 °C for 12 h,
the mixture was directly evaporated in vacuo. The residue was pu-
rified by preparative TLC (SiO2, hexane–EtOAc, 1:1) to give the
monoallyl ester 18 and the diallyl ester 19.
1,1′-Binaphthyl-2,2′-dicarboxylic Acid Monoallyl Ester (18)
Yield: 40 mg (72%); colorless solid; mp 129–131 °C.
IR (KBr): 1241, 1280, 1692, 3062, 3426 cm–1.
HPLC: Chiralpak AD-H (0.46 × 25 cm), hexane–i-PrOH (80:20),
1.0 mL/min, 254 nm, tR = 23.0 min (S), 52.6 min (R).
IR (KBr): 1595, 1722, 2949, 3060, 3327, 3418 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.26–4.42 (m, 2 H), 4.88–5.00 (m,
2 H), 5.32–5.48 (m, 1 H), 6.94–7.04 (m, 2 H), 7.14–7.24 (m, 2 H),
7.44–7.54 (m, 2 H), 7.84–8.00 (m, 4 H), 8.04–8.18 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 65.5, 118.0, 125.8, 126.1, 126.6,
126.8, 127.1, 127.25, 127.29, 127.3 127.7, 127.9, 128.0, 131.5,
132.8, 134.9, 135.1, 139.6, 140.7, 166.8, 171.0.
MS (FAB): m/z = 382 (M)+, 383 (M + H)+, 405 (M + Na)+.
HRMS (FAB): m/z calcd for C25H18O4 (M)+: 382.1205; found:
1H NMR (400 MHz, CDCl3): δ = 3.46 (s, 3 H), 5.04 (ABq,
J
AB = 12.4 Hz, ΔνAB = 15.3 Hz, 2 H), 6.30 (br s, 1 H), 6.80 (d,
J = 8.2 Hz, 1 H), 7.12–7.38 (m, 9 H), 7.55 (t, J = 7.3 Hz, 1 H), 7.87
(d, J = 8.2 Hz, 1 H), 7.92–8.12 (m, 4 H), 8.34 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 52.2, 66.8, 124.6, 125.0, 125.9,
126.5, 126.9, 127.6, 127.9, 128.1, 128.15, 128.22, 128.4, 128.8,
129.2, 129.9, 130.4, 132.4, 132.8, 133.7, 134.9, 135.2, 135.8, 153.6,
167.5.
MS (FAB): m/z = 461 (M)+, 462 (M + H)+, 484 (M + Na)+.
HRMS (FAB): m/z calcd for C30H23NO4 (M)+: 461.1627; found:
382.1207.
1,1′-Binaphthyl-2,2′-dicarboxylic Acid Diallyl Ester (19)
Yield: 17 mg (28%); colorless oil.
IR (KBr): 1133, 1725 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.30–4.39 (m, 4 H), 4.90–5.00 (m,
4 H), 5.34–5.50 (m, 2 H), 7.09 (d, J = 8.7 Hz, 2 H), 7.20–7.28 (m, 2
H), 7.46–7.54 (m, 2 H), 7.93 (d, J = 8.2 Hz, 2 H), 8.00 (d, J = 8.7
Hz, 2 H), 8.20 (d, J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 65.4, 117.9, 126.0, 126.7, 127.3,
127.7, 127.87, 127.90, 131.7, 134.9, 140.2, 166.5.
461.1627.
Hydrolysis of (R)-23 to 2′-(Benzyloxycarbonylamino)-1,1′-bi-
naphthalene-2-carboxylic Acid [(R)-7]
To a solution of (R)-23 (34 mg, 74 μmol) in THF–MeOH–H2O
(2:1:1, 8.0 mL) was added KOH (30 mg, 0.53 mmol) at r.t. After
stirring for 12 h at r.t., the reaction was quenched with 2 M aq HCl
(10 mL), and extracted with EtOAc (2 × 20 mL). The combined or-
ganic layers were washed with brine (20 mL), dried (Na2SO4), fil-
tered, and concentrated in vacuo to give (R)-7. Recrystallization
from hexane–toluene afforded (R)-7 as colorless needles; yield: 27
mg (81%); mp 235 °C; [α]D20 +38 (c 0.4, THF) (>99% ee). Optical
purity of (R)-7 (>99% ee) was confirmed by HPLC analysis with a
chiral stationary phase.
MS (FAB): m/z = 422 (M)+, 423 (M + H)+, 445 (M + Na)+.
HRMS (FAB): m/z calcd for C28H22O4 (M)+: 422.1518; found:
442.1517.
Monomethyl Esterification of 1,1′-Biphenyl-2,2′-dicarboxylic
Acid (15)
To a solution of 14 (71 mg, 0.29 mmol) and Ag2CO3 (40 mg, 0.15
mmol, 0.5 equiv) in acetone (4.0 mL) was added MeI (55 μL, 0.88
mmol, 3.0 equiv) at r.t. After stirring at 40 °C for 12 h, the reaction
was quenched with 2 M aq HCl (5.0 mL), and extracted with EtOAc
(2 × 20 mL). The combined organic layers were washed with H2O
(20 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The
residue was purified by column chromatography (SiO2, hexane–
EtOAc, 1:1) to afford the monomethyl ester 15; yield: 67 mg (90%);
colorless prisms (MeOH–H2O); mp 102–103 °C (Lit.10b mp 107–
108.5 °C)
HPLC: Chiralpak ID (0.46 × 25 cm), hexane–i-PrOH (60:40), 1.0
mL/min, 254 nm, tR = 10.9 min (S), 15.0 min (R).
IR (KBr): 1503, 1603, 1722, 3057, 3414 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 4.95 (s, 2 H), 6.73 (d, J = 8.7
Hz, 1 H), 6.99 (d, J = 8.7 Hz, 1 H), 7.06–7.12 (m, 2 H), 7.14–7.32
(m, 5 H), 7.33–7.40 (m, 1 H), 7.54–7.62 (m, 5 H), 7.86–7.97 (m, 2
H), 8.00 (d, J = 8.7 Hz, 1 H), 8.04–8.11 (m, 2 H), 8.14 (d, J = 8.7
Hz, 1 H), 8.28 (br s, 1 H).
13C NMR (100 MHz, THF-d8): δ = 66.8, 122.4, 125.1, 126.1, 126.8,
127.2, 127.8, 128.46, 128.53, 128.67, 128.70, 128.9, 129.0, 129.3,
131.7, 132.1, 133.7, 134.2, 135.6, 136.1, 136.3, 137.9, 154.7, 168.5.
Synthesis 2013, 45, 1312–1318
© Georg Thieme Verlag Stuttgart · New York

PAPER
Selective Monoesterification of 1,1′-Biaryl-2,2′-dicarboxylic Acids
1317
MS (FAB): m/z = 447 (M)+, 448 (M + H)+, 470 (M + Na)+.
HRMS (FAB): m/z calcd for C29H21NO4 (M)+: 447.1471; found:
Acknowledgment
This work was supported by Grant-in-Aid for Scientific Research
(C) from Ministry of Education, Culture, Sports, Science and Tech-
nology, Japan.
447.1469.
Transformation of (R)-10 to (R)-Methyl 2′-(Allyloxycarbonyl-
amino)-1,1′-binaphthalene-2-carboxylate [(R)-24]
To a solution of (R)-106a (>99% ee) (100 mg, 0.28 mmol) in toluene
(10 mL) were added DPPA (85 μL, 0.39 mmol) and Et3N (68 μL,
0.84 mmol) at r.t. under an argon atmosphere. After stirring for 2 h
at 90 °C, the reaction mixture was cooled to r.t. and treated with al-
lyl alcohol (25 μL, 0.37 mmol). The mixture was stirred for 10 h at
50 °C. The reaction was quenched with H2O (20 mL) and extracted
with EtOAc (2 × 20 mL). The combined organic layers were
washed with brine (20 mL), dried (Na2SO4), filtered, and concen-
trated in vacuo. The residue was purified by column chromatogra-
phy (SiO2, hexane–EtOAc, 3:1) to afford (R)-24; yield: 86 mg
References
(1) For reviews of amino acids as organocatalysts, see: (a) List,
B. Acc. Chem. Res. 2004, 37, 548. (b) Notz, W.; Tanaka, F.;
Barbas, C. F. III Acc. Chem. Res. 2004, 37, 580. (c) List, B.
Chem. Commun. 2006, 819.
(2) For a review of amino acids as ligands, see: Ma, D.; Cai, Q.
Acc. Chem. Res. 2008, 41, 1450.
(3) For reviews of amino acids as building blocks for
peptidomimetics, see: (a) Seebach, D.; Gardiner, J. Acc.
Chem. Res. 2008, 41, 1366. (b) Horne, W. S.; Gellman, S. H.
Acc. Chem. Res. 2008, 41, 1399.
(4) Furuta, T.; Kitamura, Y.; Hashimoto, A.; Fujii, S.; Tanaka,
K.; Kan, T. Org. Lett. 2007, 9, 183.
(5) Furuta, T.; Yamamoto, J.; Kitamura, Y.; Hashimoto, A.;
Masu, H.; Azumaya, I.; Kan, T.; Kawabata, T. J. Org. Chem.
2010, 75, 7010.
(6) For examples, see: (a) Hikichi, K.; Kitagaki, S.; Anada, M.;
Nakamura, S.; Nakajima, M.; Shiro, M.; Hashimoto, S.
Heterocycles 2003, 61, 391. (b) Seki, M.; Kuruda, T.;
Yamanaka, T.; Imashiro, R.; Shibatani, T. Patent
WO9952891, 1999. (c) Seki, M. Synlett 2008, 164.
(d) Kuroda, T.; Imashiro, R.; Seki, M. J. Org. Chem. 2000,
65, 4213.
20
(74%); colorless oil; [α]D +21 (c 1.1, CHCl3). Optical purity of
(R)-24 (>99% ee) was confirmed by HPLC analysis with a chiral
stationary phase.
HPLC: Chiralpak AD-H (0.46 × 25 cm), hexane–i-PrOH (80:20),
1.0 mL/min, 254 nm, tR = 9.9 min (S), 23.8 min (R).
IR (KBr): 1502, 1725, 3030, 3417 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.49 (s, 3 H), 4.42–4.59 (m, 2 H),
5.10–5.20 (m, 2 H), 5.74–5.88 (m, 1 H), 6.27 (br s, 1 H), 6.80 (d,
J = 8.7 Hz, 1 H), 7.13–7.19 (m, 1 H), 7.22 (d, J = 8.2 Hz, 1 H),
7.28–7.40 (m, 2 H), 7.54–7.60 (m, 1 H), 7.84 (d, J = 7.8 Hz, 1 H),
7.94–8.03 (m, 2 H), 8.04–8.14 (m, 2 H), 8.33 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 52.2, 65.8, 118.1, 120.1, 124.6,
125.0, 125.9, 126.5, 127.0, 127.6, 127.9, 128.2, 128.3, 128.8, 129.2,
129.9, 130.4, 132.3, 132.4, 132.8, 133.7, 134.9, 135.2, 153.4, 167.6.
(7) Ohta, T.; Ito, M.; Inagaki, K.; Takaya, H. Tetrahedron Lett.
1993, 34, 1615.
MS (FAB): m/z = 411 (M)+, 412 (M + H)+, 434 (M + Na)+.
(8) Selective monoesterification of aliphatic dicarboxylic acids,
and aromatic o- and p-dicarboxylic acids has been reported;
for examples, see: (a) Ogawa, H.; Chihara, T.; Taya, K.
J. Am. Chem. Soc. 1985, 107, 1365. (b) Ogawa, H.;
Ichimura, Y.; Chihara, T.; Teratani, S.; Taya, K. Bull. Chem.
Soc. Jpn. 1986, 59, 2481. (c) Chihara, T. J. Chem. Soc.,
Chem. Commun. 1980, 1215. (d) Mal, D. Synth. Commun.
1986, 16, 331. (e) Ogawa, H.; Hiraga, N.; Chihara, T.;
Teratani, S.; Taya, K. Bull. Chem. Soc. Jpn. 1988, 61, 2383.
(f) de la Zerda, J.; Barak, G.; Sasson, Y. Tetrahedron 1989,
45, 1533. (g) Nishiguchi, T.; Ishii, Y.; Fujisaki, S. J. Chem.
Soc., Perkin Trans. 1 1999, 3023. (h) Levonis, S. M.;
Bornaghi, L. F.; Houston, T. A. Aust. J. Chem. 2007, 60,
821.
(9) Hashimoto, T.; Kimura, H.; Nakatsu, H.; Maruoka, K.
J. Org. Chem. 2011, 76, 6030.
(10) (a) Bowden, K.; Hojatti, M. J. Chem. Soc., Perkin Trans. 2
1990, 1201. (b) Sawaki, Y.; Foote, C. S. J. Am. Chem. Soc.
1983, 105, 5035.
(11) For the preparation of (R)-9, see: (a) Seki, M.; Yamada, S.;
Kuroda, T.; Imashiro, R.; Shimizu, T. Synthesis 2000, 1677.
(b) See also ref. 6c.
(12) Hatsuda, M.; Hiramatsu, H.; Yamada, S.; Shimizu, T.; Seki,
M. J. Org. Chem. 2001, 66, 4437.
HRMS (FAB): m/z calcd for C26H21NO4 (M)+: 411.1471; found:
411.1472.
Hydrolysis of (R)-24 to 2′-(Allyloxycarbonylamino)-1,1′-bi-
naphthalene-2-carboxylic Acid [(R)-8]
To a solution of (R)-24 (189 mg, 0.46 mmol) in THF–MeOH–H2O
(2:1:1, 12 mL) was added KOH (104 mg, 1.8 mmol) at r.t. After stir-
ring at r.t. for 6 h, the reaction was quenched with 2 M aq HCl (20
mL), and extracted with EtOAc (2 × 40 mL). The combined organic
layers were washed with brine (20 mL), dried (Na2SO4), filtered,
and concentrated in vacuo. The residue was purified by column
chromatography (SiO2, hexane–EtOAc, 1:2) to afford (R)-8; yield:
98 mg (54%); colorless oil; [α]D20 +75 (c 0.4, CHCl3). Optical purity
of (R)-8 (>99% ee) was confirmed by HPLC analysis with a chiral
stationary phase.
HPLC: Chiralpak ID (0.46 × 25 cm), hexane–i-PrOH (60:40), 0.5
mL/min, 254 nm, tR = 14.5 min (S), 20.1 min (R).
IR (CHCl3): 1502, 1599, 1697, 2851, 2920, 3062, 3418 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.45 (d, J = 5.5 Hz, 2 H), 5.00–
5.15 (m, 2 H), 5.65–5.80 (m, 1 H), 6.02–6.06 (br s, 1 H), 6.10–6.50
(br s, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 7.06–7.20 (m, 2 H), 7.20–7.38
(m, 2 H), 7.52–7.59 (m, 1 H), 7.85 (d, J = 8.2 Hz, 1 H), 7.95 (d,
J = 8.7 Hz, 2 H), 8.04 (d, J = 8.7 Hz, 1 H) 8.09 (d, J = 8.7 Hz, 1 H),
8.10–8.40 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 65.8, 118.0, 120.4, 124.8, 125.0,
126.2, 126.5, 127.1, 127.5, 127.9, 128.1, 128.4, 128.80, 128.84,
129.1, 130.6, 132.1, 132.4, 132.8, 133.4, 135.5, 135.9, 153.7, 171.4.
(13) (R)-9 provides a framework for chiral catalysis and ligands
in a variety of asymmetric reactions; for examples, see:
(a) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.;
Zheng, J.-H.; Cheung, K.-K. J. Am. Chem. Soc. 1996, 118,
491. (b) Yang, D.; Wang, X.-C.; Wong, M.-K.; Yip, Y.-C.;
Tang, M.-W. J. Am. Chem. Soc. 1996, 118, 11311. (c) 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,
MS (FAB): m/z = 397 (M)+, 398 (M + H)+, 420 (M + Na)+.
HRMS (FAB): m/z calcd for C25H19NO4 (M)+: 397.1314; found:
397.1314.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1312–1318

1318
T. Furuta et al.
PAPER
5943. (d) Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc.
2007, 129, 10054. (e) Hashimoto, T.; Hirose, M.; Maruoka,
K. J. Am. Chem. Soc. 2008, 130, 7556. (f) Hashimoto, T.;
Uchiyama, N.; Maruoka, K. J. Am. Chem. Soc. 2008, 130,
14380. (g) Hashimoto, T.; Kimura, H.; Maruoka, K.
Kimura, H.; Maruoka, K. Angew. Chem. Int. Ed. 2010, 49,
6844. (i) Hashimoto, T.; Kimura, H.; Nakatsu, H.; Maruoka,
K. J. Org. Chem. 2011, 76, 6030. (j) Hashimoto, T.; Kimura,
H.; Kawamata, Y.; Maruoka, K. Nat. Chem. 2011, 3, 642.
(k) Ishitani, H.; Achiwa, K. Synlett 1997, 781. (l) See also
refs. 6 and 9.
Tetrahedron: Asymmetry 2010, 21, 1187. (h) Hashimoto, T.;
Synthesis 2013, 45, 1312–1318
© Georg Thieme Verlag Stuttgart · New York