Synthesis and enantioselective fluorescent sensors for amino acid derivatives based on BINOL

Article abstract of DOI:10.1080/10610271003713920

Four novel derivatives of 1,1′-bi-2-naphthol have been prepared and the structures of these compounds characterised by IR, MS, 1H and 13C NMR spectroscopy and elemental analysis. The enantioselective recognition of these sensors has been studied by fluorescence titration and 1H NMR spectroscopy. The sensors exhibited different chiral recognition abilities towards N-Boc-protected amino acid anions and formed 1:1 complexes between the host and the guest. Sensors exhibit excellent enantioselective fluorescent recognition ability towards the amino acid derivatives.

Full text of DOI:10.1080/10610271003713920

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Supramolecular Chemistry
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Synthesis and enantioselective fluorescent sensors for
amino acid derivatives based on BINOL
a b
c
b
b
b
Kuo-Xi Xu
, Li-Rong Yang , Yu-Xia Wang , Jin Zhao & Chao-Jie Wang
a
Institute of Fine Chemical and Engineering, Henan University , Kaifeng, Henan, 475004,
P.R. China
b
Henan University, Key Lab of Natural Medicinal and Immunal Engineering , Kaifeng, Henan,
4
75004, P.R. China
c
Institute of Molecule and Crystal Engineering, Henan University , Kaifeng, Henan, 475004,
P.R. China
Published online: 19 Aug 2010.
To cite this article: Kuo-Xi Xu , Li-Rong Yang , Yu-Xia Wang , Jin Zhao & Chao-Jie Wang (2010) Synthesis and enantioselective
fluorescent sensors for amino acid derivatives based on BINOL, Supramolecular Chemistry, 22:10, 563-570, DOI:
10.1080/10610271003713920
To link to this article: http://dx.doi.org/10.1080/10610271003713920
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Supramolecular Chemistry
Vol. 22, No. 10, October 2010, 563–570
Synthesis and enantioselective fluorescent sensors for amino acid derivatives based on BINOL
a,b
Kuo-Xi Xu , Li-Rong Yang , Yu-Xia Wang , Jin Zhao and Chao-Jie Wang *
c
b
b
b
a
b
Institute of Fine Chemical and Engineering, Henan University, Kaifeng, Henan 475004, P.R. China; Key Lab of Natural Medicinal and
c
Immunal Engineering, Henan University, Kaifeng, Henan 475004, P.R. China; Institute of Molecule and Crystal Engineering, Henan
University, Kaifeng, Henan 475004, P.R. China
(
Received 18 July 2009; final version received 8 February 2010)
0
Four novel derivatives of 1,1 -bi-2-naphthol have been prepared and the structures of these compounds characterised by IR,
1
MS, H and C NMR spectroscopy and elemental analysis. The enantioselective recognition of these sensors has been
13
1
studied by fluorescence titration and H NMR spectroscopy. The sensors exhibited different chiral recognition abilities
towards N-Boc-protected amino acid anions and formed 1:1 complexes between the host and the guest. Sensors exhibit
excellent enantioselective fluorescent recognition ability towards the amino acid derivatives.
Keywords: anions; fluorescence sensor; enantioselective recognition; NMR spectroscopy
1
.
Introduction
2. Results and discussion
Chiral recognition of racemic compounds exists exten-
sively in nature. To understand biological process,
synthetic chiral receptors were prepared to bind the chiral
guest selectively (1), these have the ability of discriminat-
ing the enantiomers. The crucial points in the molecular
design of chemosensors are how to achieve the specific
recognition of a certain molecule and how to transduce the
recognition event into a signal (2). Many efforts involve the
covalent linking of an optical signalling unit (a chromo-
phore or a fluorophore) to a specific receptor for the chiral
molecules (3). On the basis of their respective advantages,
we attempt to design some receptors with optical response
to the enantiomers in the recognition interaction, which
may offer a simple method to explore the recognition
2.1 Synthesis
The synthesis of sensors (S)-1, (S)-2 and (R)-1, (R)-2 was
started from commercially available S- or R-1,BINOL, as
shown in Scheme 1. The hydroxyl groups of BINOL were
0
protected as methoxymethyl (MOM) ethers to get 2,2 -Bis-
0
methoxymethoxy-1,1 -binaphthyl, (S)-4 (8). The resulting
compound (S)-4 was subjected to ortholithiation, followed
0
by carboxylation to give the corresponding 3,3 -
dicarboxylic acid derivatives (S)-5 or (S)-6, which was
hydrolysed by the treatment with hydrogen chloride in
absolute C H OH to give sensors. In order to understand
2
5
the functions of the aryl hydroxyl groups in the chiral
recognition in (S)-1, we synthesised compound (S)-3
where the hydroxyls are selectively protected with methyl
groups (Scheme 1). In this compound, the two aryl
hydroxyls are protected. In order to study how the aryl
hydroxyls and BINOL groups in (S)-1 and (S)-2 influenced
the enantioselective fluorescent recognition, (R)-1 and
(R)-2, the enantiomers of (S)-1 and (S)-2, were also
prepared. The structures of all these compounds were
process for more information. Over the last two decades,
0
1,1 -bi-2-naphthol (BINOL) and its derivatives have been
extensively used in chiral recognition and asymmetric
catalysis (4). Because of the fluorescence properties of the
naphthalene groups in these compounds, their fluorescence
responses towards various chiral molecules have also been
investigated (5, 6). Enantioselective recognition of amino
acid and its derivatives is important in asymmetric
synthesis and drug discovery (7). Herein, we describe the
development of four novel BINOL derivatives (Scheme 1);
their chiral recognition ability towards amino acid
derivatives, the enantiomers of the N-Boc-protected alanine
1
13
characterised by IR, MS, H and C NMR spectroscopy
and elemental analysis. They are readily soluble in
common organic solvents such as CHCl , CH Cl ,
3
2
2
CH OH, DMSO and DMF.
3
2
.2 Fluorescence spectra study
or phenylalanine anions by fluorimetric titration in CHCl .
3
1
H NMR experiments suggested that the hydrogen-bonding
interaction between the host and guest was the main factor
in the recognition process.
The properties of the chiral recognition of sensors (S)-1
and (S)-2 were investigated in the absence and the
presence of the S- and R-N-Boc-protected alanine anion
*Corresponding author. Email: wcjaxq@henu.edu.cn
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2010 Taylor & Francis
DOI: 10.1080/10610271003713920
http://www.informaworld.com

5
64
K.-X. Xu et al.
O
O
O
OEt
OEt
OEt
OEt
OH
OH
ClMOM
OMOM 1. BuLi
OMOM
OMOM
OMOM
HCl
OH
OH
OH
OH NaH
2.CO(OEt)2
OEt
OEt
O
O
O
S-4
S-5
S-1
R-1
O
O
O
COOEt
COOEt
COOEt
OH
OH
1
. BuLi
OMOM
OMOM
Conc.HCl
OH
OH
OMOM
OMOM
2
.(COOEt)2
COOEt
COOEt
COOEt
O
O
O
S-4
S-6
S-2
R-2
O
C
O
OEt
OEt
Me SO
OH
OH
2
4
OMe
OMe
OEt
C
OEt
O
O
S-1
S-3
Scheme 1. Synthesis of the sensors S-1, S-2, R-1 and R-2.
(
Ala) and N-Boc-protected phenylalanine anion (Phe), in
R-Ala formed a 1:1 complex. For a complex of 1:1
stoichiometry, the association constant (Kass) can be
calculated using Equation (1) from the Origin 7.0 software
package (9).
which amino groups were protected by the tert-
butyloxycarbonyl functionality. In each case, tetrabuty-
lammonium was used as the counter cation, which could
increase the reaction between the sensor and guest by
hydrogen bondings. Because there was almost no change
observed on the UV–vis spectra of sensors upon the
addition of guest anions, the interaction between the host
and the anion was only evaluated by fluorescent spectra.
Figures 1 and 2 show the fluorescence emission spectra
of the sensor (S)-1 with different concentrations of R- or
n
I ¼ I þ ðX 2 X Þ=2C C þ C þ 1=K
0
lim
0
0
H
G
ass
o
ð1Þ
2
1=2
2½ðC þ C þ 1=K Þ 2 4C C ꢀ
H
G
ass
H
G
;
where I represents the fluorescence intensity, C and CG
H
are the host and the guest concentrations and C is the
0
S-Ala anions in CHCl . Gradually increasing the
3
initial concentration of the host (10). The association
constants (K ) and correlation coefficients (R) obtained
concentration of the R-enantiomer caused the fluorescence
2
5
ass
emission intensities of (S)-1 (1.25 £ 10 M) at 369 nm
by a nonlinear least squares analysis of I vs. C and C are
H
G
(
l
¼ 282 nm) to decrease remarkably (Figure 1).
ex
listed in Table 1.
The quenching efficiency was 5.91% with 10 equiv. of
R-Ala anion, when 500 equiv. of R-Ala anion was added,
the fluorescence quenching efficiency was 59.35%. Upon
the addition of S-Ala anion, the quenching efficiency was
The continuous variation methods were also employed
to determine the stoichiometric ratio of the sensor (S)-1
with guests (S- and R-Ala anions). The total concentration
26
of the host and the guest was constant (1.0 £ 10 M) in
3
0.18% with 10 equiv. of S-Ala anion. When 500 equiv. of
CHCl , with a continuously variable molar fraction of the
3
R-Ala anion was added, the fluorescence quenching
efficiency was 67.33% (Figure 2). The different quenching
efficiencies indicated excellent enantioselective recog-
nition ability of the sensor (S)-1 between R- and S-Ala
anion. Such a large difference in fluorescence quenching
implies that the sensor (S)-1 can be used as a sensitive
enantioselective fluorescent sensor for Ala anions.
host ([H]/([H] þ [G])). Figure 3 shows the Job plots of the
receptor (S)-1 with S- and R-Ala anion (at 369 nm,
lex ¼ 282 nm). When the molar fraction of the host was
0
.50, the fluorescence intensity reached a maximum,
which demonstrated that the sensor (S)-1 formed a 1:1
complex with S- and R-Ala anions, respectively (11).
Similar phenomena were observed when S- or R-Phe
anions were added into a solution of sensor (S)-1. The
result of a nonlinear curve fitting (at 369 nm) indicates that
Satisfactory nonlinear curve fitting (the correlation
coefficient is over 0.99) confirmed that (S)-1 and the S- or

Supramolecular Chemistry
565
800
700
600
500
400
300
200
800
600
400
200
0
0
100
200
300
400
500
[G]/[H]
350
400
450
Wavelength (nm)
500
2
5
Figure 1. Fluorescence spectra of the receptor (S)-1 (1.25 £ 10 M) with S-Ala anion in CHCl
0, 20, 40, 60, 80, 100, 200, 300, 400 and 500, lex ¼ 282 nm. Inset: changes in the fluorescence intensity of (S)-1 at 369 nm upon the
addition of S-Ala anion. The line shown is a line-fitted curve. The correlation coefficient (R) of the nonlinear curve fitting is 0.9957.
3
. The anion equivalents are: 0, 2, 4, 6, 8,
1
800
800
600
400
200
0
700
600
500
400
300
0
100
200
300
400
500
[G]/[H]
350
400
450
Wavelength (nm)
500
2
5
Figure 2. Fluorescence spectra of the receptor (S)-1 (1.25 £ 10 M) with R-Ala anion in CHCl
0, 20, 40, 60, 80, 100, 200, 300, 400 and 500, lex ¼ 282 nm. Inset: changes in the fluorescence intensity of (S)-1 at 369 nm upon the
addition of R-Ala anion. The line shown is a line-fitted curve. The correlation coefficient (R) of the nonlinear curve fitting is 0.9943.
3
. The anion equivalents are: 0, 2, 4, 6, 8,
1

5
66
K.-X. Xu et al.
Table 1. Association constants (Kass), correlation coefficients (R), enantioselectivities (Kass(S)/Kass(R)), Gibbs free energy changes
calculated from DG
(
2DG
0
), and DDG
0
0
for the complexation of sensors (S)-1, (S)-2 and (R)-1, (R)-2 with S-/R-guests in CHCl
3
at 258C.
a
21 b,c
ass (M
21
)
21
)
Entry
Host
Guest
K
)
R
K
ass(S)/Kass(R)
2DG
0
(kJmol
DDG
0
(kJmol
4
3
4
3
4
4
4
4
4
4
4
4
4
4
4
4
1
2
3
4
5
6
7
8
9
(S)-1
(S)-1
(S)-1
(S)-1
(S)-2
(S)-2
(S)-2
(S)-2
(R)-1
(R)-1
(R)-1
(R)-1
(R)-2
(R)-2
(R)-2
(R)-2
S-Ala
R-Ala
S-Phe
R-Phe
S-Ala
R-Ala
S-Phe
R-Phe
S-Ala
R-Ala
S-Phe
R-Phe
S-Ala
R-Ala
S-Phe
R-Phe
(4.91 ^ 0.42) £ 10
(8.93 ^ 0.51) £ 10
(3.87 ^ 0.36) £ 10
(7.68 ^ 0.48) £ 10
(5.89 ^ 0.24) £ 10
(1.86 ^ 0.19) £ 10
(4.53 ^ 0.37) £ 10
(1.61 ^ 0.08) £ 10
(1.27 ^ 0.51) £ 10
(4.69 ^ 0.27) £ 10
(4.02 ^ 0.29) £ 10
(1.11 ^ 0.24) £ 10
(2.51 ^ 0.19) £ 10
(5.97 ^ 0.38) £ 10
(2.93 ^ 0.68) £ 10
(5.01 ^ 0.63) £ 10
0.9957
0.9943
0.9925
0.9986
0.9937
0.9926
0.9947
0.9954
0.9921
0.9938
0.9941
0.9957
0.9914
0.9961
0.9939
0.9922
26.78
5.50
5.04
22.55
26.19
22.18
27.23
24.37
26.58
24.02
23.43
26.67
26.28
23.09
25.12
27.26
25.00
26.83
24.23
24.01
22.86
22.56
3.24
3.17
2.81
1
1
1
1
1
1
1
0
1
2
3
4
5
6
1/3.69
1/3.62
1/2.39
1/1.71
3.19
2.14
1.83
a
Ala and Phe tetrabutylammonium salts, the amino group was protected by a tert-butyloxycarbonyl function.
The data were calculated from results of fluorescence titrations in CHCl
All error values were obtained from nonlinear curve fitting.
b
c
3
.
a 1:1 complex was formed between the sensor (S)-1 and S-
or R-Phe (see Table 1). In addition, the association
Similar phenomena were observed when R- or S-Ala, Phe
(5
anions were added into a solution (1.25 £ 10 M) of
sensor (S)-2, respectively. Upon the addition of R- or
S-guest, the different fluorescent quenching degree of the
sensor (S)-2 was observed. The quenching efficiencies of
S-N-Boc-protected amino acid anions were much higher
than the R-N-Boc-protected amino acid anions. Satisfac-
tory nonlinear curve fitting (the correlation coefficient is
over 0.99) confirmed that the sensor (S)-2 formed a 1:1
complex with the R- and S-guest anion (13).
constants (K ) were different (see Table 1) (K
ass
¼
ass(S)
4
21
21
(
3.87 ^ 0.36) £ 10 M
,
DG ¼ 226.19 kJ mol
,
0
3
21
K
¼ (7.68 ^ 0.48) £ 10 M
and DG ¼ 222.18 -
ass(R)
0
2
kJmol ), yielding a S/R selectivity [K
1
/K
ass(S) ass(R)
] of 5.04
,
2
1
for the Phe anions and a DDG value of 24.01 kJmol
0
demonstrating that sensor (S)-1 has good chiral recog-
nition ability towards the enantiomers of Phe anions.
The decrease in fluorescence intensity of the excimer
upon the addition of the anion is similar to the anion-
induced fluorescence decrease reported previously (12).
The fluorescence responses of sensor (S)-3 and in the
presence of both enantiomers of Ala and Phe were
investigated. When (S)-3 was treated with them, no
fluorescence quenching was observed, this demonstrates
that the interaction of the hydroxyl protons with the amino
acid anion is essential for the fluorescence quenching of
(S)-1. This also indicates that hydrogen bonding plays an
important role in the interaction between the host and the
guest and leads to the easier signal transductions of chiral
recognition by fluorescence method.
650
600
550
500
450
400
350
300
250
200
150
100
(
(
S)–1+R–Ala
S)–1+S–Ala
–I
0
I
We also prepared (R)-1 and (R)-2, the enantiomers
of (S)-1 and (S)-2, and studied its interaction with S- or
R-Ala, Phe anions, which showed the opposite enantios-
electivity. That is, the enantiomer of R-Ala, Phe anion,
quenched the fluorescence of (R)-1 and (R)-2 more
efficiently than S-guest. The result of fluorescence titration
indicated that the enantiomers of guest anions interacted
with (R)-1, (R)-2 and (S)-1, (S)-2 in a similar fashion.
According to Table 1, it indicates that the interaction
of sensors (S)-1, (S)-2 with the S-Ala or S-Phe anions is
better than that with the R-Ala or R-Phe anions, which is
probably due to the S-amino acid anions having a
more complementary structure with sensors (S)-1, (S)-2.
50
0
0.0
0.2
0.4
0.6
0.8
1.0
[H]/([H]+[G])
Figure 3. Job plots of the receptor (S)-1 with S- and R-Ala
anions (369 nm, lex ¼ 282 nm). The total concentration of the
3 0
. I ,
2
6
host ([H]) and the guest ([G]) is 1.0 £ 10 M in CHCl
fluorescence intensity of (S)-1 and I, fluorescence intensity of
S)-1 in the presence of the guest.
(

Supramolecular Chemistry
567
A
B
C
D
3.80
4.13
4.15
4.12
1
Figure 4. The changes in H NMR spectra of CH proton of the guest in the absence and the presence of the host at 258C
2
3
(
[(S)-1] ¼ [guest] ¼ 4.0 £ 10 M) in CDCl at 400 MHz. (A) The methine proton signals of racemic Ala anion; (B) the methine proton
3
signals of racemic Ala anion in the presence of an equimolar amount of the sensor (S)-1; (C) the methine proton signals of S-Ala anion in
the presence of an equimolar amount of the sensor (S)-1 and (D) the methine proton receptor on signals of R-Ala anion in the presence of
an equimolar amount of the sensor (S)-1.
The Phe anion has a structure similar to that of the Ala
anion, but the association constants for the association of
the receptors with the Phe anion are smaller than those for
the Ala anion, which could be attributed to the greater
steric hindrance of the phenyl ring relative to the methyl
group. The sensors (S)-1, (S)-2 and (R)-1, (R)-2 all exhibit
good chiral recognition ability towards the enantiomers of
the Ala and Phe anions, which indicates that the
preorganised structure of the chiral centre of binaphthyl
unit plays important roles in the enantioselective
recognition process.
suggesting that the amide group of the Ala anion
participated in the association process. The above results
indicate that (S)-1 has a stronger interaction with the S-Ala
anion than with its R-enantiomer. This indicated that the
interaction between the host and the guest also happened
by multiple hydrogen bondings.
3.
Conclusion
In summary, four novel chiral fluorescent sensors (S)-1,
(S)-2 and (R)-1, (R)-2 were synthesised and their
enantioselective recognition was studied by fluorescence
1
titration and H NMR spectroscopy. The sensors (S)-1, (S)-
1
.3 H NMR study
2
2 and (R)-1, (R)-2 exhibit different chiral recognition
abilities towards some enantiomers of amino acid
derivatives and form 1:1 complexes with the guest
molecules (15). It is clear that the nature of the sensor,
good structural preorganisation, multiple hydrogen-bond-
ing interactions and complementary chiral-centre inter-
actions inducement may be responsible for the
enantiomeric recognition of anionic guests. The sensors
1
H NMR experiments were undertaken to assess the chiral
recognition properties between the sensor (S)-1 and chiral
anionic guest because NMR spectroscopy can provide
structural and dynamic information directly (14). Chiral
recognition studies were carried out with a 400-MHz NMR
1
spectrometer using the sensor (S)-1 by H NMR in CDCl
as chiral solvating agent at room temperature.
3
(
S)-1, (S)-2 and (R)-1, (R)-2 are promising in their use
Ala anions were chosen as the probe. The spectra of the
sensor (S)-1 and its complex with equimolar amounts of
racemic Ala anions are shown in Figure 4. When treated
with equimolar amounts of the sensor (S)-1, the CH proton
of racemic Ala anion cleaved into a more complicated
signal pattern (Figure 4(B)) with a downfield shift (from
d ¼ 3.83 to 4.13 ppm). The interaction of the sensor (S)-1
with S-Ala shows that the CH proton has a larger downfield
shift (from d ¼ 3.83 to 4.15 ppm, Dd ¼ 0.32 ppm,
Figure 4(C)) than that of the CH proton of R-enantiomer
as fluorescence sensors for amino acid derivatives.
The remarkably different fluorescent responses that result
from complexation reveal that (S)-1, (S)-2 and (R)-1, (R)-2
could be used as fluorescent chemosensors for the N-Boc-
protected alanine anion or N-Boc-protected phenylalanine
anion in the future.
4.
Experimental
4
.1 Materials and methods
(
from d ¼ 3.83 to 4.12 ppm, Dd ¼ 0.29 ppm, Figure 4(D)).
1
Moreover, the signals of the ZOH proton in the H NMR
spectra of the sensor (S)-1 downfield shifted and almost
disappeared, while the signals of the peaks of binaphthyl
fragments are downfield shifted and broadened with the
addition of the guest. The signal of the amide (NH) group
linked to the Boc moiety was also clearly downfield shifted
from d ¼ 5.91 to 6.04 (Dd ¼ 0.13 ppm) for the S-Ala
anion, whereas the R-Ala anion downfield shifted from
d ¼ 5.91 to 5.98 (Dd ¼ 0.07 ppm) for the R-Ala anion,
The reagents used were of commercial origin and were
employed without further purification. Purifications by
column chromatography were carried out over silica gel
(230–400 mesh). The IR spectra were performed on a
1
13
Nicolet 670 FT-IR spectrophotometer. H NMR and
C
NMR spectra were recorded on a Bruker AV-400
spectrometer. Mass spectra were determined by ESI
recorded on an Esquire 3000 LC-MS mass instrument.
Optical rotations were taken on a Perkin-Elmer Model 341

5
68
K.-X. Xu et al.
þ
polarimeter. Fluorescence spectra were obtained with an F-
000 FL spectrophotometer. Elemental analyses were
1239, 750; ESI-MS m/z: 598 ((M þ Na þ 1) , 100);
7
C H O : calcd. C 66.89, H 5.26; (S)-6, found C 66.72, H
3
2 30 10
performed by the Vario Elemental CHSN-O microanalyser.
All other commercially available reagents were used
without further purification. The anions were used as their
tetrabutylammonium salts. The N-protected (by the tert-
butyloxycarbonyl functionality) amino acid derivatives
were synthesised according to a literature method (16).
5.31; (R)-6, found C 69.75, H 5.30.
4.3 General procedure for the synthesis of compound
(
S)-1, (R)-1 and (S)-2, (R)-2
After compound (S)-5, (R)-5, (S)-6 or (R)-6 (2.0 mmol) was
dissolved in 20 ml absolute ethanol and conc. HCl (5 ml),
the mixture was stirred at room temperature overnight. The
resulting yellow solution was concentrated with a rotary
evaporator. Water (10 ml) was then added, and the solution
was extracted with ethyl acetate (20 ml £ 3). The combined
4
(
.2 General procedure for the synthesis of compounds
S)-5, (R)-5 and (S)-6, (R)-6
0
0
Under nitrogen, 2,2 -Bis-MOM-1,1 -binaphthyl, (S)-4 or
(R)-4 (5.0 mmol, 1.87 g) was dissolvedin ether(100 ml) in a
flask equipped with a side arm and a magnetic stirring bar.
extract was dried over Na SO . After the removal of the
2
4
solvent, the residue was purified by column chromatog-
raphy on silica gel eluted with hexane–ethyl acetate (30:1),
to give (S)-1, (R)-1 or (S)-2, (R)-2, as a yellow solid.
The solution was cooled to 08C, and n- BuLi (25.0 mmol,
2
.5 M in hexane, 10 ml) was added dropwise. The reaction
2
D
0
(
CHCl ). The optical purity of (S)-1 was 94% ee as
S)-1: 84% yield (0.72 g); ½aꢀ ¼ 297.9 (c ¼ 0.24,
mixture was stirred for about 3 h at 08C, then dry carbonic
acid diethyl ester or oxalic acid diethyl ester (25.0 mmol)
was slowly added. The reaction was allowed to warm to
3
determined using HPLC-Chiralcel OD column (solvent:
i
hexane– PrOH 9/1). (R)-1 was also prepared from (R)-5
room temperature overnight. Saturated aqueous NH Cl
4
with the same procedure. (R)-1, 79% yield (0.68 g);
1
solution was added to quench the reaction. The organic
layer was separated, and the aqueous layer was extracted
with ethyl acetate (20 ml £ 3). The combined organic
extracts were washed with brine, and dried over Na SO .
2
0
½
aꢀ ¼ þ95.2 (c ¼ 0.24, CHCl ); H NMR (CDCl3,
D
3
400 MHz): d (ppm) 10.83 (s, 2H, ZOH), 8.70 (s, 2H, Ar-
H), 7.94–7.92 (m, 2H, Ar-H), 7.35–7.33 (m, 4H, Ar-H),
2
4
7
.17–7.15 (m, 2H, Ar-H), 4.52 (q, J ¼ 6.4 Hz, 2H), 4.97
After the removal of the solvent, the residue was purified by
column chromatography on silica gel. Elution with
hexane–ethyl acetate (50:1), Rf ¼ 0.5 (hexane–ethyl
acetate ¼ 10:1), gave the compound (S)-5, (R)-5 or (S)-6 or
(
q, J ¼ 7.2 Hz, ZCH Z, 4H), 1.51 (t, J ¼ 6.8 Hz, ZCH ,
2
3
1
H); C NMR (CDCl , 100 MHz): d (ppm) 186.4, 154.7,
3
6
1
1
1
1
7
3
35.2, 132.6, 132.1, 130.1, 129.6, 128.2, 124.6, 124.1,
2
00.2, 56.9; IR (KBr/cm ): 3449, 3067, 2934, 1759,
1
(
R)-6, as a yellow solid.
þ
2
D
0
658, 1392, 1238, 751; ESI-MS m/z: 453 ((M þ Na) ,
(
S)-5: 54% yield (1.46 g); ½aꢀ ¼ 289.6 (c ¼ 0.50,
00); C H O : calcd. C 72.55, H 5.15; (S)-5, found C
26 22 6
CHCl ); (R)-5 was also prepared from (R)-4 with the same
3
20
2.47, H 5.19; (R)-5, found C 72.49, H 5.18.
20
procedure. (R)-5, 51% yield (1.38 g); ½aꢀ ¼ þ87.7
D
1
(
CHCl ). The optical purity of (S)-2 was 97% ee as
determined using HPLC-Chiralcel OD column (solvent:
i
hexane– PrOH 20/3). (R)-2 was also prepared from (R)-6
S)-2: 81% yield (0.79 g), ½aꢀ ¼ þ91.8 (c ¼ 0.25,
(
c ¼ 0.24, CHCl ); H NMR (CDCl , 400 MHz): d (ppm)
D
3
3
8
.39 (s, 2H, Ar-H), 7.74–7.71 (m, 2H, Ar-H), 7.25–7.21
m, 4H, Ar-H), 7.12–7.08 (m, 2H, Ar-H), 5.04 (d,
3
(
J ¼ 6.4 Hz, 2H), 4.99–4.95 (m, ZCH Z, 6H), 3.11 (s,
2
1
3
with the same procedure. (R)-2, 76% yield (0.74 g);
1
6
H, ZCH ), 1.49 (t, J ¼ 6.8 Hz, ZCH , 6H); C NMR
3
3
2
D
0
½
aꢀ ¼ 288.3 (c ¼ 0.25, CHCl ); H NMR (CDCl3,
(
CDCl , 100 MHz): d (ppm) 184.2, 153.6, 134.8, 132.1,
3
3
400 MHz): d (ppm) 10.89 (s, 2H, ZOH), 8.77 (s, 2H, Ar-
H), 7.99–7.97 (m, 2H, Ar-H), 7.38–7.36 (m, 4H, Ar-H),
1
5
1
31.4, 129.8, 129.1, 127.5, 124.2, 124.0, 100.1, 58.1, 57.6,
2
1
6.9, 18.4; IR (KBr/cm ): 3449, 3067, 2934, 1759, 1658,
þ
7
4
1
1
.19–7.17 (m, 2H, Ar-H), 4.97 (q, J ¼ 7.2 Hz, ZCH Z,
392, 1238, 751; ESI-MS m/z: 542 ((M þ Na þ 1) , 100);
2
1
3
H), 1.53 (t, J ¼ 6.8 Hz, ZCH , 6H); C NMR (CDCl ,
C H O : calcd. C 69.49, H 5.83; (S)-5, found C 69.32,
0 30 8
3
3
3
00 MHz): d (ppm) 194.7, 175.8, 157.8, 136.7, 133.5,
32.6, 130.7, 129.9, 128.5, 124.8, 124.4, 57.1, 18.5; IR
2
KBr/cm ): 3454, 3071, 2937, 1764, 1748, 1662, 1397,
H 5.88; (R)-5, found C 69.37, H 5.86.
2
D
0
(
S)-6: 71% yield (2.04 g); ½aꢀ ¼ þ77.9 (c ¼ 0.25,
1
(
CHCl ); (R)-6 was also prepared from (R)-5 with the same
3
þ
20
1
1
C H O : calcd. C 69.13, H 4.56; (S)-1, found C 69.07,
239, 750; ESI-MS m/z: 509 ((M þ Na) , 100);
procedure. (S)-5, ½aꢀ ¼ 275.8 (c ¼ 0.50, CHCl ); H
D
3
NMR (CDCl , 400 MHz): d (ppm) 8.47 (s, 2H, Ar-H),
3
28 22 8
H 4.61; (R)-1, found C 69.10, H 4.59.
7
7
5
.91–7.87 (m, 2H, Ar-H), 7.26–7.21 (m, 4H, Ar-H),
.14–7.10 (m, 2H, Ar-H), 5.09 (d, J ¼ 6.4 Hz, 2H),
.04–5.00 (m, ZCH Z, 6H), 3.17 (s, 6H, ZCH ), 1.51 (t,
2
3
1
3
4.4 Synthesis of compound (S)-3
J ¼ 6.8 Hz, ZCH , 6H); C NMR (CDCl , 100 MHz):
3
3
d (ppm) 197.1, 179.6, 159.3, 137.6, 134.1, 133.2, 131.9,
30.8, 128.9, 125.7, 125.1, 101.4, 59.7, 58.3, 57.8, 18.5; IR
Under nitrogen and ice bath, the solution of Me SO
2
4
1
(2.5 mmol) in anhydrous CHCl3 (10 ml) was added
dropwise to the stirred solution of compound (S)-1
2
KBr/cm ): 3454, 3071, 2937, 1764, 1748, 1662, 1397,
1
(

Supramolecular Chemistry
0.43 g, 1.0 mmol) in anhydrous CHCl (20 ml), and the References
569
(
3
mixture was stirred at room temperature overnight. Water
30 ml) was then added. The organic layer was separated
and dried over Na SO . After the removal of the solvent,
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(
(
b) Rossi, S.; Kyne, G.M.D.; Turner, L.; Wells, N.J.;
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2
4
the residue was purified by column chromatography on
silica gel eluted with hexane–ethyl acetate (30:1), to give
(
(
(
(
(
(
(
(
S)-3, as a yellow solid. Seventy-nine percentage yield
1
(
2
0
0.36 g); ½aꢀ ¼ 292.6 (c ¼ 0.20, CHCl ); H NMR
(2) Hembury, G.A.; Borovkov, V.V.; Inoue, Y. Chem. Rev.
2008, 108, 1–73.
D
3
CDCl , 400 MHz): d (ppm) 8.38 (s, 2H, Ar-H), 7.76–7.72
3
(
3) (a) Demirtas, H.N.; Bozkurt, S.; Durmaz, M.; Yilmaz, M.;
Sirit, A. Tetrahedron 2009, 65, 3014–3018. (b) Xu, K.X.;
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Asymmetry 2009, 20, 1690–1696.
m, 2H, Ar-H), 7.27–7.23 (m, 4H, Ar-H), 7.15–7.11
m, 2H, Ar-H), 4.99 (q, J ¼ 7.2 Hz, ZCH Z, 4H), 2.58
2
1
3
s, 6H), 1.54 (t, J ¼ 6.8 Hz, ZCH , 6H); C NMR
3
CDCl , 100 MHz): d (ppm) 184.1, 153.2, 134.4, 131.9,
3
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1
IR (KBr/cm ): 3444, 3063, 2931, 1757, 1659, 1392,
31.5, 130.0, 129.1, 126.7, 124.1, 123.8, 60.4, 56.9, 18.4;
2
1
þ
1
C H O : calcd. C 73.35, H 5.72; found C 69.27, H 5.69.
241, 753; ESI-MS m/z: 481 ((M þ Na) , 100).
2
8 26 6
(
5) (a) Irie, M.; Yorozu, T.; Hayashi, K. J. Am. Chem. Soc.
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pipettes and volumetric flasks. The tetrabutylammonium
salts were prepared by adding 1 equiv. of tetrabutylam-
monium hydroxide in methanol to a solution of the
corresponding N-Boc-protected alanine or phenylalanine
in methanol, and stock solutions of the salts were prepared
(
g) Kubo, Y. Synlett 1999, 2, 161–174. (h) Beer, G.;
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4
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in CHCl . The resulting syrup was dried under high
3
(
b) Wang, Q.; Chen, X.; Tao, L.; Wang, L.; Xiao, D.; Yu,
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3
(
R)-1 and (R)-2 were prepared as stock solutions in CHCl3.
85. (d) Lu, Q.S.; Dong, L.; Zhang, J.; Li, J.; Jiang, L.;
The test solutions were prepared by adding different
volumes of anionic solution to a series of test tubes, and
then the same amount of stock solution of the host
compound was added to each of the test tubes and diluted
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3
minutes, the test solutions were analysed immediately.
(
(
6
1
6, 481–487. (b) Stock, H.T.; Kellogg, R.M. J. Org. Chem.
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.6 Experimental procedure for the Job plots
Stock solutions of the host (S)-1 and the S-Ala, R-Ala
tetrabutylammonium salts in CHCl3 system (the total
2
6
concentration of the host and the guest is 1.0 £ 10 M)
were freshly prepared. The compound (S)-1 and Phe
solutions were added to the test tubes in ratios of 9:1, 8:2 to
2
002, 4, 3203–3205.
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(
(
9
0:10, respectively. After being shaken for several minutes,
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We thank the National Natural Science Foundation of China
(Grant No. 20872027/B0206) and the Education Department of
Henan Province of China (2010B150004) for financial support.

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