A novel method for the synthesis of (R)-2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic acid by asymmetric oxidative coupling of a chiral β-naphthol derivative catalyzed by CuCl

Article abstract of DOI:10.1016/S0957-4166(02)00507-4

Asymmetric oxidative coupling of (S)-1-(3-hydroxy-2-naphthylcarbonyl)pyrrolidine-2-carboxylic acid methyl ester 1 catalyzed by CuCl afforded (S,S,R)-2,2′-dihydroxy-3,3′-bis(2-methoxycarbonyl-1- pyrrolidinylcarbonyl)-1,1′-binapthalene 2 with diastereomeric excess up to 65.9%. (R)-BINOL-3,3′-diacid 3 was obtained in 30% overall yield and 97% e.e. by separating the diastereomers and hydrolyzing 2.

Full text of DOI:10.1016/S0957-4166(02)00507-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1937–1940
A novel method for the synthesis of
(R)-2,2%-dihydroxy-1,1%-binaphthyl-3,3%-dicarboxylic acid by
asymmetric oxidative coupling of a chiral b-naphthol derivative
catalyzed by CuCl
Zhuo-qun Xin,a Chao-shan Da,a Shou-liang Dong,a Da-xue Liu,a Jie Weia and Rui Wanga,b,
*
aDepartment of Biochemistry & Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China
bState Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, China
Received 26 July 2002; accepted 22 August 2002
Abstract—Asymmetric oxidative coupling of (S)-1-(3-hydroxy-2-naphthylcarbonyl)pyrrolidine-2-carboxylic acid methyl ester 1
catalyzed by CuCl afforded (S,S,R)-2,2%-dihydroxy-3,3%-bis(2-methoxycarbonyl-1-pyrrolidinylcarbonyl)-1,1%-binapthalene 2 with
diastereomeric excess up to 65.9%. (R)-BINOL-3,3%-diacid 3 was obtained in 30% overall yield and 97% e.e. by separating the
diastereomers and hydrolyzing 2. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
We then examined the CuCl-catalyzed asymmetric oxi-
dative coupling reaction of (S)-1 under an oxygen
atmosphere (1 atm) (Scheme 2). Five different solvents
were tested, and the results are summarized in Table 1
(entries 1–4, 8). The best chemical yield and
diastereomeric excess (d.e.) were obtained with absolute
MeOH, and it had been reported that the water in the
solvent affected the stereoselectivity of the asymmetric
coupling of 2-naphthol.5 Surprisingly, only a trace of
product was observed when the reaction was completed
in CH2Cl2, which had previously been successfully
employed in the catalytic oxidative coupling of 2-naph-
thols.6 Reactions completed in MeOH gave generally
good yields and diastereoselectivities and thus, MeOH
was used in experiments designed to further optimize
the reaction. As shown in Table 1, the yield and the
diastereoselectivity of the reaction were dependent on
Derivatives of optically active 1,1%-binapthyl-3,3%-dicar-
boxylic acid (BINOL-3,3%-diacid) have been widely uti-
lized as chiral inducers in highly stereoselective
reactions because of their C2-symmetry and molecular
flexibility.1 Although syntheses of some optically pure
BINOL derivatives by asymmetric oxidative coupling
of naphthol derivatives have been successfully devel-
oped,2 optically active BINOL-3,3%-diacid was prepared
either from optically active BINOL or by resolution of
the racemic mixture.1e,3 Herein, we wish to report asym-
metric oxidative coupling of a chiral b-naphthol deriva-
tive, and an additional method for the synthesis of
diastereomerically pure BINOL-3,3%-diacid by this
asymmetric oxidative coupling reaction.
2. Results and discussion
In view of the successful stereoselective coupling of
b-naphthols catalyzed by CuCl complexed with a chiral
diamine derived from (S)-proline,4 we designed the
chiral b-naphthol derivative (S)-1. We prepared (S)-1
in 76% yield using commercially available 3-hydroxy-2-
naphthoic acid and (S)-proline methyl ester (Scheme 1).
Scheme 1. Reagents and conditions: (i) SOCl2, reflux, 1 h; (ii)
Et3N, (S)-proline methyl ester, DCM, rt, 4 h.
* Corresponding author. Tel.: 86-931-891-2567; fax: 86-931-891-2561;
e-mail: wangrui@lzu.edu.cn
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00507-4

1938
Z. Xin et al. / Tetrahedron: Asymmetry 13 (2002) 1937–1940
Several analogs of compound 2 have been designed
and synthesized by Reetz’s research group for applica-
tion as HIV-protease inhibitors.7 They were prepared
with BINOL-3,3%-diacid and amino acid esters. In this
paper we have developed another potential synthetic
method by oxidative coupling reaction.
After the asymmetric coupling was finished, we sepa-
rated the mixture of diastereomers by silica gel column
chromatography to provide (S,S,R)-2 with 97% d.e.
Hydrolyzing (S,S,R)-2 in 6 M aqueous HCl afforded
(R)-BINOL-3,3%-diacid in 74% yield with 97% e.e.
(Scheme 3). The enantiomeric excess of 3 was deter-
mined by HPLC analysis using a Chiralpak® AD
column after compound 3 was esterified with MeOH.4
Scheme 2.
the amount of CuCl (entries 5–8). The best ratio of
catalyst to starting material for diastereoselectivity was
25 mol% and the yield was also high (d.e. 65.9%, yield
80%, entry 6). The effect of reaction temperature on
the stereoselectivity was also examined (entries 8–10).
Higher stereoselectivity was observed at lower reaction
temperature. When the reaction temperature was low-
ered from room temperature to −20°C, the d.e. value
increased from 52.7 to 64.5%. However, it took a
relatively long time for the reaction to reach comple-
tion, and the chemical yield was poor from reactions
completed at low temperature.
Kozlowski et al.2f reported the chiral diamine–copper
complex-catalyzed enantioselective oxidation coupling
of 2-methoxycarbonyl-3-naphthol, in which the effect
of the C-3 substituents is important for high enantio-
selectivity. Specifically an ester group at the C-3 posi-
tion is optimal, affording e.e. of up to 91%. It can be
seen from our results that the presence of an amide
group in the same position is also very promising.
Additionally, the inflexibility of the pyrrolidine ring
may possibly contribute to some extent to the high
stereoselectivity.
HPLC analysis was used to assign the absolute
configuration of the coupling product 2. We first pre-
pared diastereomerically pure (S,S,R)-2 from (R)-
BINOL-3,3%-diacid in the same way as for the
preparation of 1. The absolute configuration was then
assigned by comparing the retention time of the cou-
pling product 2 with that of diastereomerically pure
(S,S,R)-2 in HPLC. The diastereomeric excess of the
coupling product 2 was determined by the same HPLC
analysis.
We also employed the unnatural (R)-proline as the
starting material using the same procedure, and
another enantiomer of 2 was obtained. The mechanism
of this kind of CuCl-catalyzed asymmetric oxidative
coupling reaction is unknown at present.
Scheme 3.
Table 1. The effect of solvents, amount of CuCl and temperature on the asymmetric coupling of 1
Entry
Solvent
CuCl (mol%)
Temperature (°C)
Time (h)
Yield (%)a
D.e. (%)b
Configurationc
1
2
3
4
5
6
7
8
CH2Cl2
THF
100
100
100
50
50
25
rt
rt
rt
rt
rt
rt
rt
rt
48
24
24
12
12
48
48
12
24
120
Trace
40
9
74
82
80
75
79
71
50
–
–
46.4
45.7
19.9
55.0
65.9
51.7
52.7
57.8
64.5
S,S,R
S,S,R
S,S,R
S,S,R
S,S,R
S,S,R
S,S,R
S,S,R
S,S,R
Toluene
95% MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
10
100
100
100
9
10
0
−20
a Isolated yield.
b The d.e. values were determined by HPLC.
c The absolute configuration was assigned using HPLC by comparing the retention time of the coupling product 2 with that of diastereomerically
pure (S,S,R)-2 derived from (R)-BINOL-3,3%-diacid.

Z. Xin et al. / Tetrahedron: Asymmetry 13 (2002) 1937–1940
1939
3. Conclusion
times. The combined organic layers were dried over
MgSO4 and concentrated. The residue was separated by
chromatography on a silica gel (CH2Cl2: MeOH=60:
1) to give (S)-1 as white crystals (2.27 g, 76%). Mp:
138–142°C; [h]1D8=−58.7 (c 0.476, EtOAc); 1H NMR
(CDCl3, l ppm): 1.85–2.23 (m, 3H), 2.30–2.55 (m, 1H),
3.81 (s, 3H), 3.87–4.04 (m, 2H), 4.76 (t, 1H), 7.20–7.40
(m, 2H), 7.40–7.56 (m, 1H), 7.58–7.85 (m, 2H), 8.04 (s,
1H), 9.99 (br, 1H); IR (KBr): 3399, 3217, 1679, 1513,
1442, 1322, 1281, 1216, 1142, 1073 cm−1; MS m/z: 299
(M+), 239, 171, 142; Anal. Calcd for C17H17NO4: C,
68.22; H, 5.72; N, 4.68; Found: C, 68.08; H, 5.44; N,
4.74%.
We have demonstrated that oxidative coupling of the
chiral 3-hydroxy-2-naphthoic acid derivative (S)-1 cata-
lyzed by CuCl under O2 afforded the corresponding
coupling product (S,S,R)-2 with d.e. of 65.9%. Low
reaction temperature, an optimal amount (25 mol%) of
CuCl and the use of dry MeOH solvent were necessary
to give satisfactory yields and diastereoselectivity in the
asymmetric coupling reaction. Hydrolyzing (S,S,R)-2,
which was purified by silica gel column chromatogra-
phy afforded (R)-BINOL-3,3%-diacid 3 in 30% overall
yield with 97% e.e.
4.3. General procedure for asymmetric coupling of 1
4. Experimental
4.1. General
To a solution of (S)-1 (0.30 g, 1 mmol) in absolute
MeOH (5 mL) was added CuCl (0.025 g, 0.25 mmol).
The mixture was stirred under an oxygen atmosphere (1
atm) at room temperature for 48 h. After the reaction
was complete, the diastereomeric excess of the coupling
product was determined by HPLC analysis on a C-18
column (MeOH: H2O=9: 7, 1 mL/min, (S,S,R) 7.2 min
and (S,S,S) 11.2 min). Then the solvent was evaporated
and the residue was purified using silica gel column
chromatography (CH2Cl2: MeOH=50:1). The yield of
the diastereomeric mixture was 80% (0.24 g, 65.9%
d.e.), while the yield of the compound (S,S,R)-2 was
53% (0.16 g, 97% d.e.). Mp: 135–138; [h]2D0=−10 (c
Reactions were monitored by thin-layer chromatogra-
phy (TLC). All yields reported refer to isolated materi-
als. Solvents were dried according to established
procedures by distillation under argon atmosphere from
the appropriate drying agent. Column chromatography
purifications were carried out using silica gel. Melting
points are uncorrected and recorded on X-4 melting
1
point apparatus. H NMR spectra were measured on
Bruker DRX-200 NMR. IR spectra were obtained on
Nicolet AVATAR 360 FT-IR. Optical rotations were
measured with Perkin–Elmer 341 polarimeter. Mass
spectra were recorded on VG-FAB mass spectrometor.
Elemental analyses were performed on Carlo-Erba-1106
elemental analyzer. Diastereomeric excess determina-
tion was carried out using HPLC with Waters C-18
column on a Waters HPLC instrument with 996 UV
detector, and enantiomeric excess was determined by
HPLC with Daicel Chiralpak® AD column.
1
1.12, CH3OH); H NMR (CDCl3, l ppm): 1.85–2.20
(m, 6H), 2.32–2.55 (m, 2H), 3.80 (s, 6H), 3.90–4.15 (m,
4H), 4.77 (t, 2H), 7.0–7.15 (m, 2H), 7.20–7.40 (m, 4H),
7.75–7.90 (m, 2H), 8.21 (s, 2H), 10.1 (br, 2H); FAB-MS
m/z: 597.3 (M++1); IR: 3387, 2490, 2361, 1642, 1397,
1206, 1150 cm−1.
4.4. Synthesis of (R)-BINOL-3,3%-diacid 3
4.2. Synthesis of (S)-1-(3-hydroxy-2-naphthylcar-
(S,S,R)-2 (0.6 g, 1 mmol) was added into 6 M aqueous
HCl (10 mL), and the mixture was heated under reflux
for 0.5 h. The pH of the mixture was modified to pH 2
by adding solid Na2CO3 and extracted with ethyl ace-
tate three times. The combined organic layers were
washed with brine, dried over anhydrous MgSO4, and
then concentrated under reduced pressure. The residue
was triturated with chloroform and the resulting crys-
tallines 3 (0.28 g, 74%) were collected by filtration. Mp
>290°C; [h]2D0=+180 (c 1.08, pyridine), Lit. [h]2D5=+189
(c 1.06, pyridine);1e 1H NMR ((CD3)2CO, l ppm): 3.34
(s, 2H), 7.09–7.15 (m, 2H), 7.33–7.41 (m, 4H), 8.01–8.09
(m, 2H), 8.79 (S, 1H); FAB-MS m/z: 375.2 (M++1); IR:
3058, 2578, 1664, 1504, 1454, 1277, 1209, 747 cm−1. The
enantiomeric excess of 3 were determined by HPLC
analysis after compound 3 was esterified with MeOH.
HPLC: Chiralpak® AD column, hexane–isopropyl alco-
hol 9:1, 1 mL/min, 11.0 (S) and 20.0 (R) min.
bonyl)pyrrolidine-2-carboxylic acid methyl ester 1
Method 1: To a solution of (S)-proline (4.6 g, 40 mmol)
in absolute methanol (40 mL) was added dropwise
SOCl2 (4.0 mL, 55 mmol) at −30°C. After warming to
room temperature the reaction mixture was heated
under reflux for 1 h.8 The solvent was removed com-
pletely. The residue was dissolved in dry CH2Cl2 (20
mL) and then triethylamine (5.6 mL, 40 mmol) was
dropped into the mixture at 0°C. The mixture was used
for the next step without purification.
Method 2: A solution of 3-hydroxy-2-naphthoic acid
(1.88 g, 10 mmol) in SOCl2 was heated under reflux for
1 hr. The resulting acid chloride was dissolved in dry
DCM (10 mL) after removal of SOCl2.
The solution of acid chloride was added into the mix-
ture which contained (S)-proline methyl ester at 0°C,
after warming to room temperature the reaction mix-
ture was stirred for 4 h. The mixture was filtered by
suction through a Bu¨chner funnel, and the filtrate was
concentrated in vacuo. The residue was acidified to pH
2 with 5% HCl and extracted with ethyl acetate three
Acknowledgements
We are very grateful to the National Natural Science
Foundation of China (No. 29972016, and QT Pro-

1940
Z. Xin et al. / Tetrahedron: Asymmetry 13 (2002) 1937–1940
&
gram), the Hong Kong Polytechnic University ASD
Fund and the Teaching and Research Award Program
for Outstanding Young Teachers in Higher Education
Institutions of the Ministry of Education of China for
financial supports.
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