6,6′-Bis-substituted BINOL boronic acids as enantioselective and chemoselective fluorescent chemosensors for d-sorbitol

Article abstract of DOI:10.1016/j.tet.2007.11.061

A new chiral fluorescent BINOL boronic acid 1 has been synthesized. The chiral recognition properties of 1 are drastically different from BINOL boronic acid c. Sensor 1 shows improved enantioselectivity as well as chemoselectivity toward sugar alcohols, s

Full text of DOI:10.1016/j.tet.2007.11.061

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1309e1315
www.elsevier.com/locate/tet
6,60-Bis-substituted BINOL boronic acids as enantioselective and
chemoselective fluorescent chemosensors for D-sorbitol
Xiaofen Liang a, Tony D. James b, Jianzhang Zhao a,
*
a State Key Laboratory of Fine Chemicals, Dalian University of Technology, 158 Zhongshan Road, Dalian 116012, PR China
b Department of Chemistry, University of Bath, Bath BA2 7AY, UK
Received 26 August 2007; received in revised form 15 November 2007; accepted 20 November 2007
Available online 22 November 2007
Abstract
A new chiral fluorescent BINOL boronic acid 1 has been synthesized. The chiral recognition properties of 1 are drastically different from
BINOL boronic acid c. Sensor 1 shows improved enantioselectivity as well as chemoselectivity toward sugar alcohols, such as D-sorbitol
and D-mannitol.The enantioselectivity of sensor 1 toward D-sorbitol (KR/KS) is 1:35 (pH 9.0), and the chemoselectivity for D-sorbitol/D-mannitol
is 20:1.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: BINOL boronic acid; Chiral recognition; Enantioselective sensors; Sugar alcohols
1. Introduction
Czarnik have shown that 2- and 9-anthryboronic acid could be
used to detect saccharides,15 however, with simple boronic acids,
saccharide binding requires a high pH of the solution. To over-
come this disadvantage, molecular fluorescent sensors that con-
tain a boronic acid group and an amine group have been
developed.16,17 With these systems binding is strong even at neu-
tral pH. Thereafter many boronic sensors based on this structure
motif have been employed to recognize saccharides.13e34
Sugar alcohols, such as D-sorbitol and D-mannitol, are bio-
active metabolic intermediates and have been used as medi-
cines. Therefore, it is necessary to develop fluorescent
sensors for these chiral polyhydroxyl compounds. To our sur-
prise, very few fluorescent sensors for these important sugar
alcohols have been reported to date. The diboronic acid with
a small binding pocket was synthesized and was shown to
be selective for small saccharides such as D-sorbitol (Scheme
1, a).18 However, the binding constants are small. An achiral
boronic acid sensor for sorbitol was reported (Scheme 1,
b).27c To the best of our knowledge, only compounds c and
d have been reported as chiral fluorescent chemosensors for
sugar alcohols (Scheme 1).31e33 The BINOL diboronic acid
c is not selective for D-sorbitol.32 In order to develop improved
fluorescent chiral discriminating systems for sugar alcohols,
As the chemistry of saccharides and related compounds
plays a significant role in the metabolic pathways of living
organisms, detecting the presence and concentration of biologi-
cally important sugars (glucose, fructose, galactose, etc.) and
other chiral molecules in aqueous solution is necessary in a va-
riety of medicinal and industrial contexts.1e8 The recognition
ability of many synthesized receptors is based on hydrogen
bonding or complexation interactions.9e12 The efficiency of
such interactions has been well demonstrated in nonaqueous
systems, but in aqueous media, hydrogen bonding between
the solvent and analytes will compete with hydrogen bonding
between the sensor and analytes. However, a boronic acid
readily forms covalent bonds with saccharides in aqueous
media, and this unique recognition mechanism represents an
important alternative binding force for the recognition of sac-
charides and related molecular species in aqueous media.
Recently, much attention has been paid to boron-containing
sensors,13e32 including simple boronic acids. Yoon and
* Corresponding author. Fax: þ86 411 3960 8007.
E-mail address: zhaojzh@dlut.edu.cn (J. Zhao).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.061

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X. Liang et al. / Tetrahedron 64 (2008) 1309e1315
B(OH)2
(OH)2B
N
B(OH)2
N
1.0
0.8
0.6
0.4
0.2
0.0
N
B(OH)2
a
b
(HO)2B
N
N
B(OH)2
O
O
(OH)2B
N
N
200
250
300
350
400
450
500
(HO)2B
Wavelength / nm
d
c
Figure 1. Normalized excitation (cross) and emission spectrum (circles) of
chiral boronic acid sensor R-1. 9.26ꢁ10ꢂ6 mol dmꢂ3 of sensor in 5ꢁ10ꢂ2 mol
dmꢂ3 NaCl ionic buffer (52.1% methanol in water). pH¼1.99, lex at 305 nm,
lem at 374 nm.
Scheme 1. Fluorescent chemosensors for sugar alcohols.
we synthesized sensor 1 (R and S ) and the interaction of the
two enantiomers with saccharides was investigated. It is found
that sensor 1 shows a drastically different binding profile from
its regioisomer (Scheme 1, c),32 and is sensitive, highly enan-
tioselective, and chemoselective for sugar alcohols, such as
D-sorbitol and D-mannitol.
in 74% yield. Compound 3 was formylated with n-BuLi and
DMF in dry THF and 4 was obtained in 66.2% yield. Reduc-
tive amination with methylamine and NaBH4 led to 5 in 79.6%
yield. Reaction of R-5 with 2-formylphenylboronic acid,
followed by NaBH4 reduction, gave the fluorescent sensor
R-1 in 54.5% yield. S-1 was prepared with similar methods.
The excitation and emission fluorescence spectrum of sen-
sor R-1 is shown in Figure 1. An emission maxima at 374 nm
(lex at 305 nm) was observed. The excitation wavelength and
emission wavelength of sensor R-1 are red-shifted compared
to that of the reported boronic acid (Scheme 1, c) (lex at
289 nm, lem at 358 nm), which is a regioisomer of sensor 1.32,35
It is known that the fluorescence response of the boronic
acid chemosensors as well as the binding of the boronic acid
with polyhydroxyl or hydroxyl acid is pH-dependent there-
fore, the fluorescenceepH profile of sensor 1 in the presence
of various analytes was investigated since this would allow
a rapid preview of the optimal pH region of the boronic acid
sensors. As an example, the results observed for sensors R-1
and S-1 with D-sorbitol and xylitol are shown in Figure 2. In
the presence of D-sorbitol, sensors R-1 and S-1 display differ-
ent fluorescence responses (Fig. 2). The apparent pKa value of
R-1 is 5.32ꢀ0.08 and this value shifts to 7.66ꢀ0.14 in the
presence of D-sorbitol. Large fluorescence changes were ob-
served in the pH range of 6e10. In this range, the fluorescence
enhancement is high and the enantioselective recognition by
the boronic acid sensors for D-sorbitol is significant.
2. Results and discussion
The synthesis of sensor 1 is summarized in Scheme 2.
Treatment of R-2 with bromine at room temperature gave 3
In the presence of xylitol, which is an achiral sugar alcohol,
no enantioselectivity was observed. The apparent pKa value of
R-1 is 5.32ꢀ0.08 and in the presence of xylitol this value shifts
to 9.94ꢀ0.03. Similarly, the pKa of S-1 is 5.31ꢀ0.14 and in the
presence of xylitol this value shifts to 9.90ꢀ0.03. This result
gives a negative control for the chiral recognition of the D-sor-
bitol by R- and S-1.
Scheme 2. Synthesis of the fluorescent sensors R-1 and S-1.

X. Liang et al. / Tetrahedron 64 (2008) 1309e1315
1311
(a)
(a)
180
150
120
90
1.3
1.2
1.1
R-1, blank
S-1, blank
R-1, sorbitol
S-1, sorbitol
1.0
60
R-1, D-Sobitol
S-1, D-Sobitol
0.000
0.004
0.008
0.012
[sorbitol] / mol dm-3
2
4
6
8
10
12
pH
1.6
1.4
1.2
1.0
(b)
(b)
150
120
90
R-1, blank
S-1, blank
R-1, Xylitol
S-1, Xylitol
S-1, Xylitol
R-1, Xylitol
60
0.00
0.02
0.04
0.06
[Xylitol] / mol dm-3
3
6
9
12
pH
Figure 3. Relative fluorescence intensity of sensors R-1 and S-1 versus concen-
tration of D-sorbitol (a) and xylitol (b). lex at 305 nm, lem at 374 nm, pH¼9.0,
9.26ꢁ10ꢂ6 mol dmꢂ3 of sensors in 0.05 mol dmꢂ3 NaCl ionic buffer (52.1%
methanol in water).
Figure 2. Fluorescence intensityepH profile of sensors R-1 and S-1 versus
D-sorbitol(a) and xylitol (b). lex at 305 nm, lem at 374 nm, 9.26ꢁ10ꢂ6 mol dmꢂ3
of sensors in 5.0ꢁ10ꢂ2 mol dmꢂ3 NaCl ionic buffer (52.1% methanol in water),
[D-sorbitol] and [xylitol]¼5.0ꢁ10ꢂ2 mol dmꢂ3
.
Titrations with D-glucose were also carried out (pH 6.0 and
8.0). No enantioselective recognition by the boronic acid
sensors 1 for D-glucose was observed at pH 8.0. At pH 6.0,
the enantioselectivity of the boronic acid sensors R-1 and
S-1 for D-glucose is KR/KS¼1.4:1 (Table 1). These values are
similar to those reported for the regioisomers (Scheme 1, c).32
The fluorescence enhancement of R-1 was similar to S-1 in
the presence of D-glucose at pH 8.0. The binding constant
Titrations of the sensors with D-sorbitol were carried out at
pH 6.0, 8.0, and 9.0 to determine the binding constants. At pH
9.0, a significant fluorescence enhancement was observed with
S-1 in the presence of D-sorbitol, whereas with R-1, smaller
fluorescence enhancement was observed (Fig. 3). The binding
constants of the sensors with the D-sorbitol are also signifi-
cantly different. The binding constant of S-1 with D-sorbitol
is (9.30ꢀ1.75)ꢁ103 Mꢂ1, while the binding constant of R-1
with D-sorbitol is only (2.63ꢀ1.55)ꢁ102 Mꢂ1, thus the enan-
tioselectivity is KR/KS¼1:35. Based on the fluorescence
enhancement, the response selectivity was calculated as
FR/FS¼(KRꢁFR)/(KSꢁFS)¼1:42. As a control experiment, no
enantioselectivity was observed when using achiral xylitol
(Fig. 3b).
of R-1 sensor with the D-glucose is (2.42ꢀ0.69)ꢁ102 Mꢂ1
,
while the binding constant of S-1 with the D-glucose is
(2.32ꢀ0.40)ꢁ102 Mꢂ1, the enantioselectivity is weak (Table 1).
The recognition of sugar acids with sensor 1 was also stu-
died. Titrations of the sensor with sodium D-gluconate were
carried out at pH 3.0 and 6.0. At pH 3.0, the fluorescence inten-
sity of sensor R-1 and S-1 decreased in the presence of sodium

1312
X. Liang et al. / Tetrahedron 64 (2008) 1309e1315
Table 1
Fluorescence enhancement F on binding and enantioselectivity (KR/KS) of sensors R-1 and S-1a
Analytes
pH
R-1
S-1
Response selectivityb
K
F/F0
K
F/F0
KR/KS
R/S
D-Tartaric acid
L-Tartaric acid
D-Gluconate
6.0
6.0
3.0
6.0
6.0
8.0
9.0
6.0
7.0
8.5
9.0
6.0
8.0
(1.72ꢀ0.41)ꢁ105
(6.54ꢀ1.73)ꢁ104
(5.99ꢀ1.30)ꢁ103
(1.50ꢀ0.19)ꢁ104
(1.09ꢀ0.15)ꢁ103
(1.13ꢀ0.36)ꢁ103
(2.63ꢀ1.55)ꢁ102
(5.16ꢀ0.49)ꢁ102
(3.24ꢀ0.29)ꢁ102
(2.45ꢀ0.40)ꢁ102
(1.16ꢀ0.16)ꢁ102
(2.01ꢀ0.33)ꢁ102
(2.42ꢀ0.69)ꢁ102
1.49
1.50
0.88
1.38
1.30
1.21
1.12
1.37
1.52
1.30
1.46
1.36
1.24
(8.43ꢀ2.70)ꢁ104
(1.26ꢀ0.45)ꢁ105
(3.02ꢀ1.66)ꢁ103
(4.52ꢀ0.56)ꢁ104
(5.88ꢀ0.94)ꢁ103
(1.13ꢀ0.25)ꢁ104
(9.30ꢀ1.75)ꢁ103
(2.82ꢀ0.19)ꢁ102
(1.35ꢀ0.67)ꢁ103
(3.02ꢀ0.52)ꢁ102
(0.65ꢀ0.07)ꢁ102
(1.46ꢀ0.15)ꢁ102
(2.32ꢀ0.40)ꢁ102
1.67
1.48
0.90
1.30
1.31
1.32
1.33
1.50
1.41
1.38
1.54
1.32
1.26
2.04:1
1:1.93
1.98:1
1:3.01
1:5.39
1:10.0
1:35.4
1.83:1
1:4.17
1:1.23
1.78:1
1.38:1
1.04:1
1.82:1
1:1.90
1.94:1
1:2.84
D-Sorbitol
1:5.43
1:10.9
1:42.0
D-Mannitol
1.67:1
1:3.87
1:1.31
Xylitol
D-Glucose
1.69:1
1.42:1
1.02:1
a
9.26ꢁ10ꢂ6 mol dmꢂ3 R-1 or S-1 in 0.05 mol dmꢂ3 NaCl ionic buffer (52.1% methanol in water), lex at 305 nm, lem at 374 nm. Constants determined by fitting
a 1:1 binding model to I/I0. r2¼0.99 in most cases. F values agree well with the experimental results.
b
Response selectivity¼(KRꢁFR)/(KSꢁFS).
D-gluconate. A significant fluorescence reduction was observed
with R-1 in the presence of sodium D-gluconate compared to
that of S-1. The binding constant of R-1 with sodium D-gluco-
nate is (5.99ꢀ1.30)ꢁ103 Mꢂ1, whilst the binding constant of
S-1 with sodium D-gluconate is (3.02ꢀ1.66)ꢁ103 Mꢂ1, the
enantioselectivity is KR/KS¼1.98:1 (Table 1).
the present sensor for D-sorbitol is 5e10 fold higher than
that of compound a (Scheme 1), which is an achiral
sensor.18,33
We have demonstrated that the chirality of the sensors can
be used to improve the enantioselectivity as well as the che-
moselectivity.33 Similar results are also found for sensor 1,
with R-1, the selectivity for sorbitol over mannitol is 2:1 (at
pH 6). With S-1, however, the chemoselectivity increases to
20:1. Similar results are also found for other analytes. For ex-
ample, the selectivity for sorbitol over glucose at pH 8.0 is 5:1.
With S-1, the chemoselectivity is improved to nearly 50:1.
Fluorescence lifetimes of the sensors with and without the
analytes were studied and the preliminary results are listed in
Table 2. Longer fluorescence lifetimes were observed for the
sensor in the presence of D-sorbitol. This is consistent with
the fluorescence enhancement as well as the photo-induced
electron transfer (PET) mechanism of the sensor. Furthermore,
a longer lifetime was found for S-1 compared to R-1, which is
consistent with the fact that S-1 gives a tighter binding with
D-sorbitol. For D-gluconate, no significant changes were ob-
served for the fluorescence lifetimes. The variation of the fluo-
rescence lifetimes of the chemosensor in the presence of
analytes is interesting. In principle, especially for those with
longer emission lifetimes, this kind of response can be used
for the technique of fluorescence lifetime imaging microscopy
(FLIM), which is intrinsically superior to intensity-based
analysis.
The regioisomer of sensor 1, compound c (Scheme 1), was
reported to be highly enantioselective for tartaric acid, and
a novel fluorescence response profile was found that either an
increased or diminished fluorescence response was observed
in the presence of the enantiomers of tartaric acids.32 For sensor
1, however, only minor enantioselectivity was found for tartaric
acid (Fig. 4 and Table 1). The apparent pKa of the sensor 1 is
5.23ꢀ0.05. With tartaric acid, this value changed to
8.36ꢀ0.13 (for D-tartaric acid) and 9.08ꢀ0.02 (for L-tartaric
acid). The fluorescence enhancement of the D- and L-tartaric
acid is nearly the same. Therefore, there is no significant enan-
tioselectivity for tartaric acid. The binding constant study
proved this (Fig. 4b). The binding constants of R-1 with
D- and L-tartaric acid at pH 6.0 are (1.72ꢀ0.41)ꢁ105 Mꢂ1
and (6.54ꢀ1.73)ꢁ104 Mꢂ1, respectively.
The binding of the sensor 1 with other sugar alcohols, such
as D-mannitol was also investigated and the binding constants,
fluorescent enhancement, and enantioselectivities (KR/KS) are
listed in Table 1.
The data in Table 1 indicate that this system is highly enan-
tioselective and sensitive for D-sorbitol, compared to a reported
BINOL boronic acid, which shows no enantioselectivity for D-
sorbitol (Scheme 1, c).32 Sensor 1 shows an enantioselectivity
of 1:35 with D-sorbitol versus 1:1 for the previously reported
chiral sensor (Scheme 1, c).32 An improved chemoselectivity
of 20:1 with sorbitol/mannitol was also observed, compared
to a chemoselectivity of 10:1 for the previously reported sensor
(Scheme 1, c).32
3. Conclusions
In summary, new BINOL fluorescent chiral chemosensors
1 were synthesized and a different recognition profile to that
of the regioisomeric chemosensor (Scheme 1, c) was observed.
The new chiral sensor gives higher binding constants for
sugar alcohols. An improved response selectivity was observed
for D-sorbitol/D-mannitol. The chemoselectivity between
D-sorbitol/D-glucose is also improved compared to the achiral
Binding with sugar alcohols is pH-dependent. Sensor 1 is
more selective for D-sorbitol over D-mannitol, compared to
the reported chiral sensor (Scheme 1, d) and the binding of

X. Liang et al. / Tetrahedron 64 (2008) 1309e1315
4. Experimental
1313
(a) 180
4.1. General
160
Fluorescence spectra were measured on a F4500 fluoro-
spectrometer (Hitachi) and CRT 970 fluorescence spectrome-
ter. A 0.05 M NaCl (52.1% methanol in water, w/w) ionic
buffer was used in the experiment. The final concentration
of the sensors was fixed at 9.26ꢁ10ꢂ6 mol dmꢂ3 (by dilution
of a stock solution of the sensor into the buffer by more than
500 times). All pH measurements were recorded on a Delta
320 Microprocessor pH meter (Mettler Toledo), which was
routinely calibrated using standard buffer solutions. The fluo-
rescence emission spectra of the sensors, with or without the
analytes, were recorded as the pH was changed from pH 2
to 12 in approximate intervals of 0.5 pH units. The pH was
controlled using minimum volumes of sodium hydroxide and
hydrochloric acid solutions. The fluorescence spectra of the
sensors in the presence of the analytes were recorded as in-
creasing amounts of the analyte were added to the solution.
For all titrations the final pH was controlled to within less
than 0.03 units of the desired pH. The fluorescence lifetime
was measured with frequency-domain instrument of Chronos
95145 Fluorescence Lifetime Spectrometer (ISS, Inc., Cham-
paign, IL, USA) with 9 KHze1.2 GHz signal generator. The
phase angle and the modulation ratio were recorded with scan-
ning of the modulation frequency. The regression of the exper-
imental curves was carried out with the software VINCI
Analysis (BETA 1.6). Titration curves were generated using
the Origin 5.0 (Microcal software). The binding constants
were calculated using custom-written nonlinear least-square
curve-fitting programs implemented within SigmaPlot 2000
(SPSS Inc.).
140
120
100
80
R-1, blank
R-1, D-tartaric acid
R-1, L-tartaric acid
60
2
4
6
8
10
pH
(b)
1.4
1.2
1.0
R-1, D-tartaric acid
R-1, L-tartaric acid
0.000
0.002
0.004
0.006
4.2. (R)- and (S )-6,60-Dibromo-2,20-dimethoxy-1,10-
binaphthalene (3)
[D- or L-tartaric acid] / mol dm-3
Figure 4. Fluorescence intensityepH profile of R-1 sensor versus D- or
L-tartaric acid (a) and the titration curve of R-1 with L- and D-tartaric acid at
pH 6.0 (b). lex at 295 nm, lem at 372 nm, 9.26ꢁ10ꢂ6 mol dmꢂ3 of sensor in
2.5ꢁ10ꢂ2 mol dmꢂ3 NaCl ionic buffer (52.1% methanol in water), [L- and
(R)-2,20-Dimethoxy-1,10-binaphthalene(2)(3.14 g,50 mmol)
was dissolved in CH2Cl2 (100 mL) and stirred at 0 ꢃC (ice/water
bath). Bromine (1.13 mL, 44 mmol) was added in one portion
with vigorous stirring and a stream of nitrogen was bubbled
through the solution to remove the evolving HBr gas. The reac-
tion mixture was stirred for additional 5 h while the flask was
allowed to warm to room temperature. The nitrogen flow was
stopped and the yellow solution was allowed to stand over-
night. A 20 mL of 10% NaHSO3 solution was added with
a vigorous stir to quench the excess bromine. The colorless
organic layer was separated, washed with 10% NaHSO3
solution and water, dried over MgSO4 and the solvent was re-
moved under reduced pressure to give 3.50 g of white amor-
D-tartaric acid]¼5.0ꢁ10ꢂ2 mol dmꢂ3
.
sensors. Our future aim will be to design chiral sensors, which
are specific for other biologically interesting sugar alcohols.
Table 2
Fluorescence lifetimes of sensor R-1 and S-1 in the presence of D-sorbitol and
sodium D-gluconate
Sensor/analytes
R-1 t (ns)
S-1 t (ns)
Blank sensora
D-Sorbitola
Blank sensorb
D-Gluconateb
a
4.52ꢀ0.01
5.08ꢀ0.01
5.82ꢀ0.02
5.86ꢀ0.02
4.81ꢀ0.01
5.74ꢀ0.01
5.71ꢀ0.02
5.71ꢀ0.02
1
phous powder (74%). H NMR (400 MHz, CDCl3) 8.01 (s,
2H), 7.87 (d, 2H, J¼8.0 Hz), 7.44 (d, 2H, J¼8.0 Hz), 7.26 (d,
2H, J¼8.0 Hz), 6.92 (d, 2H, J¼8.0 Hz), 3.76 (s, 6H); 13C
NMR (100 MHz, CDCl3) 155.3, 132.5, 130.4, 130.1, 129.9,
128.9, 127.1, 119.2, 117.6, 115.1, 56.7. APCI positive m/z
472.9.
2.23ꢁ10ꢂ5 mol dmꢂ3 R-1 and S-1 in 0.05 mol dmꢂ3 NaCl ionic buffer
(52.1% methanol in water), at pH 7.5, [D-sorbitol]¼9.15ꢁ10ꢂ3 mol dmꢂ3
.
b
8.38ꢁ10ꢂ6 mol dmꢂ3 R-1 and S-1 in 0.05 mol dmꢂ3 NaCl ionic buffer
(52.1% methanol in water), at pH 2.5, [D-gluconate]¼6.88ꢁ10ꢂ3 mol dmꢂ3
.

1314
X. Liang et al. / Tetrahedron 64 (2008) 1309e1315
4.3. (R)- and (S )-2,20-Dimethoxy-[1,10] binaphthalene-
1.09 mmol). The mixture was allowed to react for 2 h, at which
time 10 equiv of sodium borohydride (185 mg, 4.87 mmol) was
added. The mixture was stirred for an additional 1 h. The sol-
vent was removed in vacuum, and the resulting solid was redis-
solved in 30 mL of water and the aqueous phrase was extracted
with methylene chloride (3ꢁ50 mL). The organic phase was
dried over MgSO4. The solvent was removed under vacuum
and the crude product was purified with column chromatog-
raphy (Al2O3, dichloromethane/methanol¼50:1, v/v). A white
solid was obtained (R-1) (182 mg, 54.5%). 1H NMR
(400 MHz, CDCl3/CD3OD) 7.89 (d, 2H, J¼8.0 Hz), 7.68e
7.69 (m, 2H), 7.39 (d, 2H, J¼8.0 Hz), 7.21e7.25 (m, 6H),
7.06 (d, 4H, J¼8.0 Hz), 6.98 (d, 2H, J¼8.0 Hz), 3.68e3.70
(m, 14H), 2.15 (br, 6H). 13C NMR (100 MHz, CDCl3) 155.2,
140.5, 135.12, 132.30, 130.2, 129.5, 128.9, 128.3, 128.1,
127.8, 127.7, 126.4, 124.8, 118.4, 113.3, 62.9, 61.9, 54.9,
35.8. TOF EI-MSþ 335.0063 ([Mþ2H]2þ), 651.0013
([MꢂH2OþH]þ). S-1 was synthesized with similar methods.
1H NMR (400 MHz, CDCl3/CD3OD) 8.00 (d, 2H, J¼8.0 Hz),
7.81 (br, 2H), 7.49 (d, 2H, J¼8.0 Hz), 7.29e7.34 (m, 6H),
7.16 (d, 4H, J¼8.0 Hz), 7.08 (d, 2H, J¼8.0 Hz), 3.79e3.81
(m, 14H), 2.31 (br, 6H). TOF EI-MS (positive) m/z
335.1179 ([Mþ2H]2þ), 651.2379 ([MꢂH2OþH]þ).
6,60-dicarbaldehyde (4)
Under nitrogen atmosphere, 1.0 g of (R)-6,60-dibromo-2,20-
dimethoxy-1,10-binaphthalene (3) (2.12 mmol) was dissolved
in 60 mL of dry THF. The stirred solution was cooled to
ꢂ78 ꢃC in dry ice/acetone bath, and 1.7 mL of n-BuLi (2.5 M
in n-hexane, 4.25 mmol) was added slowly to keep the temper-
ature below ꢂ70 ꢃC. After 5e6 h of stirring at this temperature,
0.5 mL of dry N,N-dimethylformamide (6.46 mmol) was added
slowly to keep the temperature below ꢂ50 ꢃC. After stirring for
45 min at this temperature, the reaction mixture was poured
into HCl/ice water (pH<1) under vigorous stirring. The mix-
ture was extracted with 3ꢁ50 mL CH2Cl2. The combined or-
ganic phases were washed twice with water and dried over
MgSO4. The solvent was removed under reduced pressure to
give an oil. In order to obtain an analytical sample, the oil was
submitted to column chromatography on silica using CH2Cl2 as
eluting agent to give 0.52 g of white amorphous powder. Yield:
66.2%; 1H NMR (400 MHz, CDCl3) 10.10 (s, 2H), 8.38 (s, 2H),
8.17 (d, 2H, J¼8.0 Hz), 7.69 (d, 2H, J¼8.0 Hz), 7.54 (d, 2H,
J¼8.0 Hz), 7.14 (d, 2H, J¼8.0 Hz), 3.82 (s, 6H); 13C NMR
(100 MHz, CDCl3) 192.2, 157.7, 137.3, 135.3, 132.4, 132.0,
128.2, 126.0, 123.6, 119.0, 114.5, 56.7. APCI positive m/z
371.1 ([MþH]þ).
Acknowledgements
4.4. (R)- and (S )-2,20-Dimethoxy-N,N0-dimethyl-1,10-
This work is financially supported by the National Natural
Science Foundation of China (NSFC 20634040 and
20642003), the Scientific Research Foundation for the Re-
turned Overseas Chinese Scholars (Ministry of Education),
Science Research Foundation of Dalian University of Techno-
logy, and French CNRS GDRI ‘PHENICS’ no. 93.
binaphthalene-6,60-dimethanamine (5)
Methylamine (17 mL, 33% by weight, 8 M solution in abso-
lute ethanol, 135 mmol) was added under nitrogen atmosphere
to (R)-2,20-dimethoxy-[1,10]-binaphthalenyl-6,60-dicarbalde-
hyde (4) (0.5 g, 1.25 mmol), the reaction mixture was stirred
at room temperature for 18 h. Then NaBH4 (0.7 g, 18.4 mmol)
was added in one portion. The solution was stirred for another
2 h until the Schiff base was completely reduced to amine (mon-
itored with TLC, silica gel, dichloromethane/petroleum
ether¼2:1, v/v). The solution was concentrated under reduced
pressure and the residuewas mixedwith 50 mL water. The aque-
ous solution was extracted with dichloromethane (3ꢁ100 mL).
The combined organic phase was dried over MgSO4 and the sol-
vent was removed under reduced pressure to give the amine as
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