Novel NMR chiral solvating agents derived from (1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination for chiral carboxylic acids

Article abstract of DOI:10.1016/j.tetasy.2006.03.011

A series of new compounds, (1R,2R)-1-(1′,8′-naphthalimide)-2-aminocyclohexane 1 and its 4′-derivatives 2 and 3 derived from (1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. ¹H NMR spectroscopy was employed to i

Full text of DOI:10.1016/j.tetasy.2006.03.011

Tetrahedron: Asymmetry 17 (2006) 916–921
Novel NMR chiral solvating agents derived from
(1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination
for chiral carboxylic acids
Xuemei Yang,a,b Guitao Wang,a Cheng Zhong,a Xiaojun Wua and Enqin Fua,*
aDepartment of Chemistry, Wuhan University, Wuhan 430072, China
bSchool of Basic Medical Science, Guangdong Medical College, Dongguan 523808, China
Received 10 January 2006; accepted 16 March 2006
Available online 12 April 2006
Abstract—A series of new compounds, (1R,2R)-1-(10,80-naphthalimide)-2-aminocyclohexane 1 and its 40-derivatives 2 and 3 derived from
(1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. 1H NMR spectroscopy was employed to investigate
their enantiodiscriminating ability. Compared with a-phenylethylamine, a commercially available chiral solvating agent (CSA), these
compounds exhibited better enantiodiscriminating ability toward the chiral carboxylic acids we had chosen, distinguishing them as prom-
ising and practical CSAs.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
acids.10–12 In particular, CSAs that can lead to clear base-
line separation of the multiplet of the probe group in two
enantiomers are rare.
Chiral carboxylic acids are basic building blocks of many
natural products, biological molecules, and drugs.1–3
Although significant progress has been made for the asym-
metric synthesis of chiral carboxylic acids, the search for
highly enantioselective and practical catalysts has been
continuously a very interesting topic.1–6 The application
of high throughput combinatorial techniques has greatly
facilitated research in this field,6 hence it has given rise to
an increasing demand for rapid and accurate methods to
measure the enantiomeric composition of chiral carboxylic
acids. Apart from other analytical methods, such as
HPLC7 and GC8 on chiral stationary phases, the use of
chiral solvating agents (CSAs)9–11 for NMR spectroscopy
is a satisfactory and convenient method to meet this
demand. The method only needs the preparation of a mix-
ture of CSA with the chiral analyte in a suitable deuterated
solvent and the recording of a routine NMR spectrum.
Comparing with HPLC and GC, this method has another
advantage that it can provide direct structural and dynamic
information of host–guest complexes in solution.
In our previous work, we have already synthesized some
chiral macrocyclic polyamines derived from natural amino
acids and tartaric acid.13–16 1H NMR spectroscopy was
employed to investigate their enantiodiscriminating abil-
ity.17,18 The results revealed that all these compounds
exhibited good enantiodiscriminating ability toward the
chiral carboxylic acids we had chosen.
Recently we have made another approach to obtain more
effective and practically applicable CSAs for chiral carb-
oxylic acids. A class of compounds (1R,2R)-1-(10,80-naphthal-
imide)- 2-aminocyclohexane 1 and its 40-derivatives 2 and 3
derived from (1R,2R)-diaminocyclohexane (DACH) was
designed and synthesized. The structure of 1–3 involves
an amino group and a large aromatic system, attached to
two chiral centers of (1R,2R)-diaminocyclohexane, respec-
tively. It is expected that the formation of host–guest dia-
stereomeric complexes,19,20 will be achieved mainly
through interaction of the amino group and the carboxyl
group in the chiral carboxylic acid, but the p–p interaction
may also play some important role if the chiral carboxylic
acid also contains an aromatic moiety. The most important
role of the aromatic systems is that its anisotropic influence
may cause the chemical shift non-equivalences (DDd) of the
In contrast to the CSAs for chiral amines and alcohols,
there are less reports about CSAs for chiral carboxylic
*
Corresponding author. Tel.: +86 27 87219044; fax: +86 27 68756757;
e-mail: fueq@whu.edu.cn
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.03.011

X. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 916–921
917
probe groups of the two enantiomers of the chiral guests.
The non-equivalence (DDd) is the difference of the chemical
shifts of corresponding protons of two enantiomers of the
guests in the presence of the CSAs. The cyclohexane block
in the designed host molecules can stabilize the position of
two substituted groups on the chiral centers, thus the fixed
conformation is expected to benefit the formation of diaste-
reomeric host–guest complexes, and improve the enantio-
selective recognition ability.
racemic compounds of a-methoxyphenylacetic acid
(MPAA), dibenzoyltartaric acid (DBTA), and some chiral
drugs such as naproxen, ibuprofen, and ketoprofen. The
N-derivatives of some amino acids, including phthalyl ala-
nine, phthalyl leucine, p-tolylsulfonyl alanine (Ts-alanine),
p-tolylsulfonyl valine (Ts-valine), p-nitrobenzenesulfonyl
alanine (p-Nbs-alanine), and o-nitrobenzenesulfonyl
alanine (o-Nbs-alanine), were also synthesized as guests to
further investigate the relationship of the guest structure
with recognition ability. To evaluate the enantiodiscrimi-
nating capabilities of 1–3, (S)-a-phenylethylamine (PEA),
a commercially available CSA,11 was also utilized as the
reference CSA to recognize those guests we chose.
2. Results and discussion
Compounds 1–3 (Scheme 1) were synthesized by the reac-
tion of (1R,2R)-DACH with the appropriate 1,8-naphtha-
lic anhydride and characterized by MS, 1H NMR, 13C
NMR, IR, and EA. The synthetic procedure was simple
and convenient, and the yields for 1–3 were 93.5%,
95.0%, and 92.5% based on DACH, respectively.
Table 1 summarizes the chemical shift non-equivalences
(DDd) of CH3 and CH in the chiral carbon (or CH3 in iso-
propyl group) of the chiral carboxylic acid guests in the
presence of 1 equiv of 1–3 or PEA, respectively. From
Table 1 we can see that any of compounds 1–3 has led to
a clear baseline separation of the methine proton quartets
of phthalyl alanine, p-tolylsulfonyl alanine (Ts-alanine),
p-tolylsulfonyl valine (Ts-valine), p-nitrobenzenesulfonyl
alanine (p-Nbs-alanine), and o-nitrobenzenesulfonyl ala-
nine (o-Nbs-alanine). The DDd of the methine proton of
Ts-alanine was 58.8 Hz in the presence of compound 1
(see Fig. 2). The largest DDd of the methine proton was
up to 104.1 Hz with compound 2 as CSA. We further
noticed that only compound 3 could enantiodiscriminate
DBTA and phthalyl leucine.
The crystal structure of compound 1 was obtained via
X-ray single crystal structure analysis.21 The molecular
structure is shown in Figure 1, which is consistent with
the stable conformation we expected. It is noteworthy that
the torsion angle of H–C13–N1–C11 is approximately
178ꢁ, which means that the naphthalene plane is almost
parallel to the C13–H bond, also indicating that the naph-
thalene plane is perpendicular to the chair-like cyclohexane
plane.
Compounds 1–3 also show good enantiodiscriminating
ability for some chiral drugs such as naproxen, ibuprofen,
and ketoprofen. As for the DDds of a-CH3 of these guests,
1–3 could lead to the larger DDds than PEA. Particularly,
when ketoprofen was chosen as the guest, 1–3 could lead
to clear separation of the methyl proton doublet peaks,
based on which the enantiomeric composition could be
determined (see Fig. 3). Although the DDds of the CH of
these guests were larger in the presence of PEA than in
the presence of 1–3, clear baseline separation of the proton
signal still could not observed by using PEA.
From the data in Table 1, it is clear that compared with
PEA, 1–3 exhibited better chiral recognition ability (larger
DDd) toward the derivatives of amino acids than the other
guests in this work. For example, in the case of p-Nbs-ala-
nine, PEA showed no enantiodiscrimination while 1–3
exhibited good enantioselective ability, the DDds of CH
Figure 1. ORTEP drawing of the molecular structure of 1.
1H NMR spectroscopy was utilized to investigate the
enantiodiscriminating ability of 1–3, and the guests include
R
(R) (R)
ethanol or DMF
O
O
H2N
N
(R) (R)
+
reflux, N2, 4-5h
H2N
NH2
O
O
O
R
1 (R,R)- R=H
2 (R,R)- R=Br
3 (R,R)- R=N(CH3)2
Scheme 1. The synthetic route to 1–3.

918
X. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 916–921
Table 1. Chemical shift non-equivalences (DDd, 300 MHz) for 1:1 diastereoisomeric complexes of 1–3 and PEA with racemic guests in CDCl3 at 25 ꢁC
Guests
DDd (Hz)b
1
2
3
PEA
37.2
OCH3
COOH
MPAA
CH
15.3(S)
16.5(S)
47.1(S)
CH3
COOH
Naproxen
Ibuprofen
CH
CH3
6.9
13.5
7.5
7.2
6.9
11.4
6.3
—
a
H3CO
CH3
CH
CH3
6.6
11.7
4.5
6.6
3.0
8.7
18.6
6.9
COOH
O
O
CH3
Ketoprofen
DBTA
CH
CH3
7.2
15.9
4.5
18.0
7.2
25.2
18.6
3.3
COOH
O
H
H
Ph
COOH
O Ph
CH
0.0
0.0
38.1(D)c
30.0
HOOC
O
CH3
O
COOH
N
Phthalyl alanine
CH
CH3
62.4(D)
10.2(D)
43.2(D)
0.0
38.4(D)
3.9(D)
17.7
—
a
O
O
COOH
a
a
N
Phthalyl leucine
Ts-alanine
CH
—
—
31.2(D)
3.9
O
CH3
O
S
O
a
CH
CH3
58.8(D)
14.7(D)
104.1(D)
44.4(D)
—
6.3
3.0
N
H3C
COOH
H
15.6(D)
O
S
O
a
Ts-valine
CH
CH3
46.8(D)
45.6(L)
42.0(D)
46.5(L)
—
0.0
0.0
N
H
H3C
O2N
COOH
35.7(L)
CH3
COOH
O
S
O
p-Nbs alanine
CH
CH3
30.0
17.7
36.6
5.7
36.0
18.0
0.0
0.0
N
H
CH3
O
N
S
COOH
o-Nbs alanine
CH
CH3
60.9
15.6
62.7
7.8
42.3
13.5
6.6
0.0
H
O
NO2
a The peaks of hosts overlapped with the peaks of the probe groups of guests.
b In brackets: configuration of the enantiomer corresponding to the signal at higher field.
c The mole ratio of CSA and guest is 2:1.
˚
being 30.0, 36.6, and 36.0 Hz, for 1–3, respectively. The
results imply that the molecular structure of 1–3 fits the
above guests better than that of PEA does. According to
the crystallographic data for the structure of 1 and the data
for PEA from a computer simulation (Hyperchem 7.0), the
distance (4.5–7.0 A) between the amino group and the aryl
˚
group in 1 is larger than that (2.4–5.0 A) in PEA. It means
that the larger distance between the amino group and the
aryl group in 1–3 is more suitable to match the distance
of the carboxyl group and the aryl group in any of the

X. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 916–921
919
Figure 2. 1H NMR spectra of equimolar mixtures (20 mM each) of Ts-alanine/1: (a) Ts-L-alanine and 1; (b) Ts-D-alanine and 1; (c) Ts-L/D-alanine and 1;
(d) Ts-L/D-alanine without 1.
MPAA were illustrated in Figure 4, showing a minimum
of DdX at X = 0.5, which indicates that a 1:1 instantaneous
complex was formed. The Job plots we have got indicated
that 1–3 form 1:1 instantaneous complexes with all these
enantiomerically pure guests, respectively.
-0.02
-0.04
-0.06
-0.08
-0.10
-0.12
-0.14
-0.16
-0.18
-0.20
(S)-MPAA (-CH)
(R)-MPAA (-CH)
0.0
0.2
0.4
0.6
0.8
1.0
X
Figure 3. 1H NMR (300 Hz, CDCl3, 25 ꢁC, ppm referred to TMS as
external standard) spectral regions corresponding to CH3 protons of
racemic ketoprofen (20 mM): (a) equimolar mixture 1/racemic ketoprofen;
(b) equimolar mixture 2/racemic ketoprofen; (c) equimolar mixture
3/racemic ketoprofen; (d) free racemic ketoprofen.
Figure 4. Job plots of 1 with (R)- and (S)-MPAA [X = molar fraction of
MPAA, Dd = chemical shift change of the methine of (R)- and (S)-
MPAA].
We also performed the titration curves of 1–3 with these
enantiomerically pure guests, respectively. The association
constants with 1–3 were determined from the titration
curves by a nonlinear least-squares fitting method (Table
2).22 It showed that the (S)-MPAA was more strongly
bound to 1–3 than the (R)-enantiomer was, and the D-
enantiomer of Ts-alanine was more strongly bound to 1
and 3 than the L-enantiomer was. It is clear that the asso-
ciation constants of 1–3 to Ts-alanine are about 1 order of
magnitude higher than those to MPAA, showing that the
structure of 1–3 matched Ts-alanine much better than that
of MPAA.
above derivatives of amino acid, so it is favorable to the
formation of the instantaneous complexes of 1–3 with these
guests.
1
The H NMR spectra of 1–3 with several enantiomerically
pure guests in a variety of ratios in CDCl3 at a constant
total concentration of 3.0 · 10ꢀ3 M were obtained. The
stoichiometric ratio of the host–guest complex was deter-
mined according to Job’s method of continuous
variations.22 The Job plots of 1 with (R)-MPAA and (S)-

920
X. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 916–921
Table 2. Association constants Ka (mol/l)ꢀ1of 1–3 with chiral carboxylic
acids
0.024 mol) in DMF (50 ml). Refluxing was continued for
4 h. Then the solution was decanted into cold water
(1400 ml) and left overnight. Then, the precipitates were
collected and then recrystallized twice from ethanol to give
Entry
CSAs
Guests
Ka (mol/l)ꢀ1
Ka(S or D)/
Ka(R or L)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
1
1
1
2
2
2
2
3
3
3
3
3
3
(R)-MPAA
(S)-MPAA
Ts-D-Alanine
Ts-L-Alanine
(R)-MPAA
(S)-MPAA
Ts-D-Alanine
Ts-L-Alanine
(R)-MPAA
(S)-MPAA
Ts-D-Alanine
Ts-L-Alanine
D-DBTA
(1.6 0.1) · 103
(4.4 1.8) · 103
(2.2 1.1) · 104
(1.8 0.5) · 104
(1.6 0.1) · 103
(2.9 0.6) · 103
(1.4 0.4) · 104
(1.8 0.6) · 104
(2.0 0.3) · 103
(4.8 1.3) · 103
(2.1 1.1) · 104
(1.4 0.8) · 104
(1.6 0.3) · 102
(2.1 0.3) · 102
2.75
1.22
1.81
0.78
2.40
1.50
0.76
pale yellow needle crystal 1, yield 93.5%, mp: 230–233 ꢁC;
20
½aꢁD ¼ þ2:3 (c 2.5, CHCl3); 1H NMR (300 MHz, CDCl3,
ppm): d = 7.75–8.55 (m, 6H, 6ArH), 4.72–4.81 (td, 1H,
3
3Jae = 3.3 Hz, Jaa = 10.8 Hz, CHN), 3.71–3.80 (td, 1H,
3
3Jae = 3.6 Hz, Jaa = 11.1 Hz, CHNH2), 1.19–2.54 (m,
10H, 4CH2, 2NHH); 13C NMR (75 MHz, CDCl3, ppm):
d = 165.7, 164.6, 133.8, 131.7, 131.0, 128.5, 127.1, 123.5,
122.8, 61.2, 50.7, 37.6, 29.0, 26.5, 25.8; MS: m/z 295
(M++1, 100%); Anal. Calcd (%) for C18H18N2O2: C,
73.45; N, 9.52; H, 6.16. Found (%): C, 73.14; N, 9.23; H,
6.21. IR (KBr, cmꢀ1): m 3436, 2933, 2859, 1690, 1657,
1625, 1588, 1342, 1238, 777.
L-DBTA
4.2.2. (1R,2R)-1-(40-Bromo-10,80-naphthalimide)-2-amino-
cyclohexane 2. To a solution of 4-bromo-1,8-naphthalic
anhydride (2.77 g, 0.010 mol) in ethanol/DMF (1:2)
(90 ml), refluxed under a nitrogen atmosphere, was added
the solution of DACH (1.37 g, 0.012 mol) in ethanol/
DMF (1:2) (30 ml). Refluxing was continued for 5 h. Then
the solution was decanted into cold water (1000 ml) and
left overnight. Then, the precipitates were collected and
3. Conclusion
Compounds 1–3, which have a unique structure, were
designed and synthesized conveniently and efficiently. The
unique structure contains a cyclohexane block, making
the substituent groups on the two chiral centers adopt a
fixed dimensional position and constant distance. 1H
NMR spectroscopy was employed to investigate their
enantiodiscriminating ability. Compared to a-phenylethyl-
amine, a commercially available chiral solvating agent
(CSA), all these compounds exhibited better enantiodis-
criminating ability toward the chiral carboxylic acids stud-
ied in this work. The excellent enantioselectivity, simple
synthetic procedure, and the high synthetic yields make
them promising and practical CSAs.
then recrystallized twice from ethanol to give pale yellow
20
solid 2, yield 95.0%, mp: 211–213 ꢁC; ½aꢁD ¼ ꢀ12:8 (c
0.065, CHCl3); 1H NMR (300 MHz, CDCl3, ppm):
3
d = 7.78–8.59 (m, 5H, 5ArH), 4.69–4.77 (td, 1H, Jae
=
=
3
3
3.3 Hz, Jaa = 11.1 Hz, CHN), 3.68–3.77 (td, 1H, Jae
3
3.9 Hz, Jaa = 10.8 Hz, CHNH2), 1.20–2.53 (m, 10H, 4CH2,
2NHH); 13C NMR (75 MHz, CDCl3, ppm): d = 165.1,
164.0, 133.1, 132.6, 131.9, 131.2, 130.6, 130.1, 129.3,
128.3, 123.3, 122.8, 61.3, 50.7, 37.8, 29.0, 26.5, 25.8; MS:
m/z 375 (M++1 100%); Anal. Calcd (%) for C18H17-
BrN2O2: C, 57.92; N, 7.51; H, 4.59. Found (%): C, 58.37;
N, 7.66; H, 4.61. IR (KBr, cmꢀ1): m 3436, 3089, 3070,
2932, 2854, 1700, 1661, 1587, 1405, 1344, 1237, 1186,
780.
4. Experimental
4.1. General methods
4.2.3. (1R,2R)-1-[40-(N,N-Dimethylamino)-10,80-naphthal-
NMR spectra were recorded in CDCl3 on Varian Mercury
VX300 FT-NMR spectrometer (1H at 300 MHz and 13C at
75 MHz) operating at 298 K. IR spectra were performed
on a Nicolet 170SX FT-IR spectrometer in KBr pellets.
Mass spectra were recorded on a VJ-ZAB-3F-Mass Spec-
trometer using the FAB technique. The elemental analysis
was performed on a Calo-Erba elemental analyzer (Model
1106). Optical rotations were measured with a Perkin
Elmer polarimeter (Model 341) using the sodium D line
at 589 nm.
imide]-2-aminocyclohexane
3. 4-Bromo-1,8-naphthalic
anhydride was converted to 4-N,N-dimethylamino-1,8-
naphthalic anhydride as described in the literature.24 To
a solution of 4-N,N-dimethylamino-1,8-naphthalic anhy-
dride (1.20 g, 0.0050 mol) in ethanol (100 ml), refluxed
under a nitrogen atmosphere, was added the solution of
DACH (0.68 g, 0.0060 mol) in ethanol (30 ml). Refluxing
was continued for 5 h. Then the solution was decanted into
cold water (500 ml) and left overnight. Then, the precipi-
tates were collected and then recrystallized twice from
ethanol to give yellow needle crystal 3, yield 92.5%,
20
mp: 183–184 ꢁC; ½aꢁD ¼ ꢀ16:0 (c 0.025, CHCl3); 1H
(1R,2R)-1,2-Diaminocyclohexane (DACH) is available by
resolution of the crude commercial racemate with tartaric
acid.23
NMR (300 MHz, CDCl3, ppm): d = 7.10–8.55 (m, 5H,
5ArH), 4.73–4.80 (t, 1H, J = 9.9 Hz, CHN), 3.73–3.82
3
3
3
(td, 1H, Jae = 3.9 Hz, Jaa = 10.2 Hz, CHNH2), 3.09 (s,
6H, 2CH3) 1.19–2.54 (m, 10H, 4CH2, 2NHH); 13C NMR
(75 MHz, CDCl3, ppm): d = 166.2, 165.5, 133.3, 132.5,
131.6, 131.2, 130.9, 130.6, 125.3, 125.1, 113.5, 60.9, 50.7,
45.1, 37.3, 29.0, 26.5, 25.8; MS: m/z 338 (M++1, 100%);
Anal. Calcd (%) for C20H23N3O2: C, 71.19; N, 12.45; H,
6.87. Found (%): C, 70.83; N, 12.41; H, 7.15. IR (KBr,
4.2. Preparation of 1–3
4.2.1. (1R,2R)-1-(10,80-Naphthalimide)-2-aminocyclohexane
1. To a solution of 1,8-naphthalic anhydride (3.96 g,
0.020 mol) in DMF (150 ml), refluxed under a nitrogen
atmosphere, was added the solution of DACH (2.74 g,

X. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 916–921
921
cmꢀ1): m 3381, 3078, 2926, 2852, 2798, 1690, 1643, 1587,
1389, 1359, 1241, 1132, 1082, 1002, 784, 760.
3. Nicolaou, K. C.; Snyder, S. A. Classics in Total Synthesis II;
Wiley-VCH: Weinheim, 2003.
4. Pu, L. Chem. Rev. 2004, 104, 1687–1716.
5. Lin, J.; Rajaram, A. R.; Pu, L. Tetrahedron 2004, 60, 11277–
11281.
4.3. NMR shift experiments
6. Taran, F.; Gauchet, C.; Mohar, B.; Meunier, S.; Valleix, A.;
Renard, P. Y.; Ger’minon, C.; Grassi, J.; Wagner, A.;
Mioskowski, C. Angew. Chem., Int. Ed. 2002, 41, 124–127.
7. Allenmark, S. G. Chromatographic Enantioseparation: Meth-
ods and Applications; Elliss Horwood: Chichester, 1988.
8. Schurig, V.; Nowotny, H. P. Angew. Chem. 1990, 102, 969–
1108.
Samples for analysis were obtained by mixing equimolar
amounts of 1–3 with the guests in CDCl3, making the con-
centrations of the hosts (or guests) normally 20 mM.
4.4. Evaluation of the stoichiometric ratio of the host–guest
complex (Job plots)
9. Pirkle, W. H.; Hoover, D. J. Top. Stereochem. 1982, 13, 263–
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10. Parker, D. Chem. Rev. 1991, 91, 1441–1457.
11. Wenzel, T. J.; Wilcox, J. D. Chirality 2003, 15, 256–270.
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127, 7996–7997.
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The stoichiometric ratio of the host–guest complex was
determined according to Job’s method of continuous vari-
ations. Equimolar amounts of host and guest compounds
were dissolved in CDCl3. These solutions were distributed
among nine NMR tubes, with the molar fractions X of host
and guest in the resulting solutions increasing (or
decreased) from 0.1 to 0.9 (and vice versa). The complexa-
tion induced shifts (Dd) were multiplied by X and plotted
against X itself (Job plot).
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4.5. NMR host–guest titrations
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Asymmetry 2004, 15, 2491–2497.
The resulting solution of the guest compound, dissolved in
the appropriate amount of solvent with a concentration of
3.0 · 10ꢀ3 M, was evenly distributed among 10 NMR
tubes. The host compound was also dissolved in the appro-
priate amount of solvent and added in increasing amounts
to the NMR tubes, so that the ratio of the host to the guest
of the 10 tubes was 0, 0.13, 0.40, 0.80, 1.33, 2.00, 2.67, 4.00,
5.33, 8.00, respectively. Ka was calculated by a nonlinear
least-squares fitting method from the observed Dd values
and the respective host and guest concentrations.
´
19. Chinchilla, R.; Foubelo, F.; Najera, C.; Yus, M. Tetrahedron:
Asymmetry 1995, 6, 1877–1880.
20. Parker, D.; Taylor, R. J. Tetrahedron 1987, 43, 5451–5456.
21. Crystallographic data for the structure of compound 1 have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication numbers CCDC
267790. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: +44(0) 1223 336033 or e-mail: deposit@ccdc.
cam.ac.uk]. Crystal data of 1: C18H18N2O2, M = 294.35,
˚
orthorhombic, space group P2(1)2(1)2(1), a = 7.2900(15) A,
A representative example is given below: compound 1 ver-
sus (S)-MPAA in CDCl3. Weighed amounts: compound 1:
29.40 mg in 1.00 ml; (S)-MPAA: 4.15 mg in 5.00 ml. Ka(S)
[Mꢀ1] = (4.4 1.8) · 103.
3
˚
˚
˚
b = 16.646(3) A, c = 24.201(5) A, V = 2936.8(10) A , D =
1.331 g/cm3, l = 0.088 mmꢀ1, F(000) = 1240, Z = 8, R1 =
0.0571, xR2 = 0.1056. Data collection for the crystal struc-
ture determination was carried out on a R-AXIS-IV diffrac-
˚
tometer using Mo Ka radiation (k = 0.71073 A) at
a
temperature of 291 (2) ꢁC. Of the 7048 reflections measured
in the 2.15 6 h 6 23.50ꢁ range, 4231 reflections were unique
and 2717 reflections with I > 2r(I) were used in structure
solution and refinement. Rint = 0.0776. w ¼ 1=½r2ðF o2Þþ
Acknowledgement
The authors are grateful to the National Natural Science
Foundation of China (No. 20272045) for financial support.
2
ð0:0441PÞ þ 0:0000Pꢁ, where P ¼ ðF 2o þ 2F c2Þ=3. The struc-
ture was solved by direct method using SHELXL-97. All of the
non-hydrogen atoms were refined by full-matrix least-squares
methods using anisotropic displacement parameters.
22. Fielding, L. Tetrahedron 2000, 56, 6151–6170.
23. Galsbol, F.; Steenbol, P.; Sorensen, B. S. Acta Chem. Scand.
1972, 26, 3605–3611.
References
1. Coppola, G. M.; Schuster, H. F. a-Hydroxyl Acids in
Enantioselective Synthesis; VCH: Weinheim, 1997.
2. Hanessian, S. Total synthesis of Natural Products: The Chiron
Approach; Pergamon: Oxford, 1983.
24. Zhu, J.; Su, J.; Chen, K.; Tian, H. J. East China Univ. Sci.
Tech. 1999, 25, 170–173.