New chiral auxiliaries derived from (S)-α-phenylethylamine as chiral solvating agents for carboxylic acids

Article abstract of DOI:10.1016/j.tetasy.2007.03.030

The two new diastereoisomeric chiral auxiliaries 1a and 1b were synthesized conveniently and effectively. ¹H NMR was employed to investigate their chiral recognition ability. Compared with (S)-PEA, these new chiral auxiliaries exhibited better

Full text of DOI:10.1016/j.tetasy.2007.03.030

Tetrahedron: Asymmetry 18 (2007) 832–837
New chiral auxiliaries derived from (S)-a-phenylethylamine
as chiral solvating agents for carboxylic acids
Wenge Wang, Fengnian Ma, Xiumin Shen and Cong Zhang*
College of Chemistry, Beijing Normal University, Beijing 100875, China
Received 29 January 2007; revised 22 March 2007; accepted 30 March 2007
Abstract—The two new diastereoisomeric chiral auxiliaries 1a and 1b were synthesized conveniently and effectively. 1H NMR was
employed to investigate their chiral recognition ability. Compared with (S)-PEA, these new chiral auxiliaries exhibited better enantio-
selectivity towards the carboxylic acids we had chosen.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Ph
Ph
H
NMe2
H
NMe2
N
N
In view of the importance of chiral carboxylic acids in bio-
logical and pharmaceutical chemistry,1–4 there is a demand
for the development of fast and accurate methodologies for
the determination of the enantiomeric composition of these
chiral compounds. Apart from chromatographic5 and cap-
illary electrophoretic6 methods, NMR spectroscopy using
chiral solvating agents (CSAs) is an efficient and conve-
nient method to meet this need.7–9 There have already been
a few reports of the use of chiral amines as CSAs in this
domain.10–13 As a simple but powerful chiral adjuvant, chiral
a-phenylethylamine (PEA) as well as some of its derivatives
has also been applied for chiral carboxylic acid analysis but
generally its 1H chemical shift non-equivalences are too
small to realize baseline resolution;14–18 so further attempts
to modify the structure of chiral PEA are worth studying.
Recently, we reported a novel chiral macrocyclic com-
pound with (S)-PEA as the chiral source, which shows excel-
lent discriminating ability as a CSA for a broad variety of
1a
1b
Figure 1. The structures of newly designed auxiliaries 1a and 1b.
of stereogenic centres may afford an important increase
in the enantiodiscriminating abilities of these two diastereo-
isomers.20 With this in mind, we envisioned the possibility of
using these chiral diamines as CSAs for the effective analysis
of the enantiomeric excess of carboxylic acids. Herein, we
report the synthesis of chiral auxiliaries 1a and 1b as well
as their enantiodiscriminating abilities for carboxylic acids
1
by H NMR spectroscopy.
1
carboxylic acids by H NMR spectroscopy.19 In this work,
some structural modifications have been made on (S)-PEA
in order to further augment its chiral recognition ability.
We designed the new chiral auxiliaries 1a and 1b with (S)-
PEA as the chiral source (see Fig. 1) and expect that the
incorporation of two anisotropic groups (naphthyl and phe-
nyl attached by methyl as well as dimethylamino) can con-
tribute to the modification of the differential magnetic
influence of (S)-PEA. In addition, increasing the number
2. Results and discussion
Chiral diamines 1a and 1b were efficiently synthesized by
the reaction of intermediate 3 (prepared by the Grignard
addition of compound 2) with trifluoroacetic anhydride,
and then with (S)-a-PEA (see Scheme 1). The structures
of these chiral compounds were characterized by 1H
NMR, 13C NMR, IR, MS and EA. The crystal structure
of 1b was studied by X-ray single crystal structure analy-
sis.21 The molecular structure of compound 1b is shown
*
Corresponding author. Tel.: +86 13825661820; fax: +86 10 58210397;
e-mail: czhang@bnu.edu.cn
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.03.030

W. Wang et al. / Tetrahedron: Asymmetry 18 (2007) 832–837
833
NMe2
NMe2 OH
investigate further the enantiodiscriminating capacities of
these chiral diamines. As a reference CSA, (S)-PEA was
also utilized to recognize these carboxylic acids in order
to evaluate the chiral recognition abilities of these modified
chiral diamines for carboxylic acids.
MgBr
CHO
THF
+
0 ˚C -r.t.
3
2
Ph
Ph
Table 1 summarizes the chemical shift non-equivalences
(DDd) of CH, CH3 and NHTs of these guests in the pres-
ence of compounds 1a, 1b and (S)-PEA, respectively.
H
NMe2
H
NMe2
N
N
1) (CF3CO)2O, CH2Cl2
2) (S)-PEA, CH2Cl2
+
0 ˚C
Table 1. Measurements of 1H chemical shift non-equivalences (DDd,
500 MHz) of racemic guests in the presence of an equimolar amount of 1a,
1b and (S)-PEA in CDCl3 at 25 ꢁC
1a
1b
Guest
Signal
DDda (Hz)
Scheme 1. The synthetic route to compounds 1a and 1b.
1a
1b
(S)-PEA
4
5
a-H
a-H
a-H
a-H
a-H
OCH3
CH3
41.6 (S)
30.4
45.0
34.7
23.8
10.3
12.2
0
46.5
129.8 (D)
183.3
37.0 (D)
152.6 (D)
21.1
34.3 (S)
33.3
65.4
36.2
38.5
5.2
53.9
32.7
0
17.4
0
21.8
0
12.3
0
0
15.5
0
0
0
0
in Figure 2, which indicates the newly prepared stereogenic
centre induced by (S)-PEA is the (R)-configuration.
6
7
8
9
10
11
a-H
NHTs
NHTs
NHTs
a-CH3
NHTs
CH
12b
13b
14
0
0
46.4 (D)
0
7.9
0
14.5
15c
a In brackets: configuration of the enantiomer corresponding to the signal
at higher field.
b The chemical shift non-equivalences of the methyl proton of CH(CH3)2
for 12 and CH2CH(CH3)2 for 13 are large (see Fig. 5).
c The molar ratio of CSA and guest is 2:1.
Figure 2. The molecular structure of compound 1b.
For mandelic acid 4 and its derivatives 5–8, the methine
proton signals of all guests were shifted upfield in the pres-
ence of hosts 1a and 1b, suggesting deprotonation of the
carboxylic group. Furthermore, these observed signals
were all split into two peaks due to the different interac-
tions of the two enantiomers of the substrate with the
CSA. Generally, the chemical shift non-equivalences we
observed were all large enough to afford baseline resolution
for accurate integration. For example, the addition of hosts
1a and 1b to racemic 4 in CDCl3 caused remarkable upfield
shifts of the methine proton signal of 4 and these methine
signals were split into two singlets with the separation
between the two peaks being 41.6 Hz and 34.4 Hz, respec-
tively. The chemical shift non-equivalence of the methine
proton was only 17.4 Hz with (S)-PEA as the CSA under
the same condition. We also observed the larger upfield
shifts of the methine proton of chiral acid 4 towards (S)-
4 in the presence of compound 1a and 1b, which reveals
that these chiral diamines have stronger chiral recognition
abilities than with (R)-4.22 The largest DDd value of the
methine proton was up to 65.4 Hz when acid 6 served as
the guest in the presence of 1b while under the identical
conditions host 1a and (S)-PEA only induced non-equiva-
lences of 45.0 Hz and 21.8 Hz, respectively (see Fig. 4).
This indicates that these new host compounds 1a and
1b exhibit better enantioselectivity in comparison with
1
With these desired diamines in hand, we utilized H NMR
(500 MHz) spectroscopy to study the chiral recognition
abilities of compounds 1a and 1b, and guests (see Fig. 3)
include racemic compounds of mandelic acid 4 and some
of its derivatives 5–9, non-aromatic lactic acid 10 and
dicarboxylic acid 15. In addition, the N-derivatives of some
amino acids, including p-tolylsulfonyl phenylglycine
(Ts-phenylglycine) 11, p-tolylsulfonyl valine (Ts-valine)
12, p-tolylsulfonyl leucine (Ts-leucine) 13 and p-tolylsulfon-
yl alanine (Ts-analine) 14, were also chosen as guests to
4 (R=H, X=OH,Y=H)
Y
X
5 (R=p-Cl, X=OH, Y=H)
6 (R=o-Cl, X=OH, Y=H)
7 (R=p-OCH3, X=OH, Y=H)
8 (R=o-OCH3, X=OH, Y=H)
9 (R=H, X=OCH3, Y=H)
OH
CO2H
COOH
R
10
PhCOO
CO2H
CO2H
11 R= Ph
NHTs
CO2H
12 R= CH(CH3)2
13 R= CH2CH(CH3)2
14 R= CH3
PhCOO
R
15
Figure 3. The structures of the guests used herein.

834
W. Wang et al. / Tetrahedron: Asymmetry 18 (2007) 832–837
PEA. For instance, in the case of 12, compound 1b and
(S)-PEA showed no enantiodiscrimination while com-
pound 1a induced the non-equivalence of the proton signal
of NHTs up to 129.8 Hz (see Fig. 5). Here, the two diaste-
reoisomers behave quite differently towards the same guest,
demonstrating that the ‘matched couple’ is represented by
diastereoisomer 1a while 1b is the ‘mismatched couple’.20
In addition, the non-equivalent two methyl protons of
compound 12 also obtained good chiral recognition. The
two doublets of the methyl proton signals of D-12 were
shifted upfield about 0.20 ppm and 0.34, while only about
0.12 ppm and 0.19 ppm when L-12 served as a chosen ana-
lyte. On the contrary, we observed that all NH protons
from these guests 11–14 resonate at lower field upon the
addition of compound 1a, which can be interpreted as
the formation of a stronger intramolecular hydrogen bond
with the carboxylate anion thus formed.23 The largest DDd
value of the NHTs proton was up to 183.3 Hz, which was
achieved upon the addition of an equimolar amount of 1a
into racemic 13 in CDCl3. Dicarboxylic acid 15 also
obtained good chiral recognition in the presence of
compound 1a–1b and (S)-PEA with the molar ratio of host
and guest being 2:1.
d
c
b
a
5.70 5.60 5.50 5.40 5.30 5.20 5.10
ppm
1
Figure 4. A portion of the H NMR (500 MHz) spectra of (a) racemic 6;
(b) 1a and racemic 6; (c) 1b and racemic 6; (d) (S)-PEA and racemic 6.
(S)-PEA. Although the chiral discrimination was also
observed for the MeO signals of acid 9, which are farther
from the stereogenic centre, the chemical shift difference
between the diastereomeric complexes was insufficient for
quantitative analysis. This example also indicates that the
a-hydroxyl group in the substrate play an important role
for the establishment of hydrogen bonding with NH or N
on host compounds. The methyl proton of aliphatic acid
10 was acquired good chiral recognition with compounds
1a and 1b as CSAs, which demonstrated the aromatic ring
in the substrate was not necessary for chiral recognition,
while no enantiomeric discrimination occurred with
(S)-PEA as the CSA. From these analytical data, it is clear
that compared with (S)-PEA, chiral hosts 1a and 1b
exhibited better chiral recognition abilities towards these
mentioned carboxylic acids 4–10.
A knowledge of the stoichiometry of the associate is impor-
tant in determining the structure of the complexes. Nine
samples of a constant total concentration (4 mM) were pre-
pared containing variable ratios of compound 1b and (R)-4
1
or (S)-4. The H NMR spectra of these samples were re-
corded and chemical shift variations were observed for
the methine proton of the acid (R)-4 or (S)-4. The stoichio-
metry of the host–guest complex was determined accord-
ing to Job’s method of continuous variation.24 The Job
plots for the complexation of compound 1b with (R)-4
and (S)-4 were illustrated in Figure 6, affording a maximum
of DdX at X = 0.5, which means that compound 1b forms a
In Table 1, we can see that compound 1a showed an excel-
lent enantiodiscriminating ability towards the derivatives
of amino acids as compared with compound 1b and (S)-
L
L
D
D
L
D
c
b
a
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
ppm
Figure 5. 1H NMR spectra (500 MHz) of equimolar mixtures (4 mM each) of 12/1a at 25 ꢁC in CDCl3: (a) compound 1a; (b) free racemic 12; (c)
enantiomerically enriched 12 (L:D = 3:1) and compound 1a.

W. Wang et al. / Tetrahedron: Asymmetry 18 (2007) 832–837
835
0.3
0.25
0.2
(S)-enantiomer was more strongly bound to 1a or 1b than
the (R)-enantiomer. In order to investigate the intrinsic
chemical shift non-equivalence of the two diastereoiso-
meric instantaneous complexes, we performed the 1D
GOESY spectra of the complexes formed from 1a with
an equimolar amount of (R)-4 or (S)-4, but no intermolec-
ular NOE phenomena was observed. The incorporation of
two anisotropic groups into host molecules may play an
important role for the excellent chiral recognition abilities
by the combination of steric and electrical factors.
0.15
0.1
0.05
0
1b+(R)-4
1b+(S)-4
0
0.2
0.4
0.6
0.8
1
Finally, we attempted to demonstrate the accuracy of this
enantiomeric excess determination method. With this
aim, we prepared seven samples containing different pro-
portions of both enantiomers of 4, and analyzed their enan-
tiomeric compositions in the presence of compound 1a by
X
Figure 6. Job plots for the complexation of compound 1b with (R)-4 and
(S)-4. (X = [1b]/([1b] + [4]); Dd = variation of the chemical shift of the
observed proton).
1
using H NMR method (see Fig. 8). The results, which
were calculated based on the integrations of the corre-
sponding methine proton signals, are within 1% of the
actual enantiopurity of these samples and thus, demon-
strate the high accuracy of this method.
1:1 instantaneous complex with (R)- or (S)-4 under these
experimental conditions. In order to further demonstrate
this result, we also studied the stoichiometry of compound
1a with L-15 (see Fig. 7). For compound 1a, a maximum
was observed when compound 1a versus L-15 was 1:2
(X = 0.67), indicating that host 1a formed a 1:2 instanta-
neous complex with L-15. These data further indicated that
one molecule of chiral diamine 1a or 1b can bind with one
molecule of mono-carboxylic acid to form a complex under
the experimental conditions.
19%(20%) ee
100
80
R2 =0.9995
41% (40%) ee
60
60% (60%) ee
40
20
81% (80%) ee
0.3
0.25
0.2
0
0
20 40 60 80 100
% ee (prepared)
94% (95%) ee
4.90
4.80
4.70
4.60
ppm
Figure 8. (a) Partial 1H NMR (500 MHz) spectra of (S)-4 with various
enantiomeric purities (4 mM) in the presence of an equimolar amount of
compound 1a. (b) Correlation between the observed and prepared % ee
values.
0.15
0.1
0.05
0
0
0.2
0.4
0.6
0.8
1
3. Conclusion
X
Figure 7. Job plots for the complexation of compound 1a with L-15.
(X = [1a]/([1a] + [15]); Dd = variation of the chemical shift of the observed
proton).
In conclusion, the two new chiral auxiliaries 1a and 1b
derived from (S)-PEA have been synthesized conveniently
and effectively, and have been proved to be effective chiral
NMR solvating agents for chiral carboxylic acids.
Compared with (S)-PEA, a commercially available chiral
solvating agent, these host compounds exhibited better
enantiodiscriminating abilities towards the chiral carbox-
ylic acids investigated in this work with a few exceptions.
In particular, compound 1a exhibited excellent chiral rec-
ognition ability for the N-derivatives of some amino acids.
In order to further evaluate the discriminating abilities of
1a and 1b, we performed the titration curves of 1a and
1b with chiral mandelic acid. The association constants of
1a and 1b with (S)-4 and (R)-4 were determined from the
titration curves by the non-linear least-squares fitting
method (Table 2).24 From Table 2, it was seen that the
Table 2. Association constants Ka (mol/l)ꢀ1 of 1a and 1b with (S)- or (R)-
mandelic acid in CDCl3
4. Experimental
Entry
CSAs
Guests
Ka (mol/l)ꢀ1
Ka(S)/Ka(R)
4.1. General methods
1
2
3
4
1a
1a
1b
1b
(S)-4
(R)-4
(S)-4
(R)-4
(2.2 0.6) · 104
(1.2 0.4) · 104
(1.2 0.3) · 104
(9.5 1.7) · 103
1.8
IR spectra were obtained on a Nicolet 360 Avatar IR spec-
trometer as KBr pellets. NMR spectra were recorded on
Avance 500 Bruker spectrometer (1H at 500 MHz and
1.2

836
W. Wang et al. / Tetrahedron: Asymmetry 18 (2007) 832–837
13C at 125 MHz). Mass spectra were recorded on Trace MS
2000-Mass Spectrometer using the EI technique. Elemental
analysis was performed on Vario E1 elemental analyzer.
Optical rotations were measured with a Perkin–Elmer
Model 343 polarimeter using the sodium D line at 589 nm.
C28H30N2: C, 85.24; N, 7.10; H, 7.66. Found: C, 84.99;
N, 7.09; H, 7.93; IR (KBr): 3480, 3037, 2859, 2823, 2780,
1597, 1496, 1452, 1160, 776 cmꢀ1
.
20
Compound 1b: Mp 135–136 ꢁC; ½aꢁD ¼ ꢀ12:6 (c 1.35,
1
CHCl3); H NMR (500 MHz, CDCl3, ppm): d 6.94–8.34
The solvents (dichloromethane and THF) were analytical
and dried thoroughly. (S)-PEA is commercially available
in its pure form. 2-(N,N-Dimethylamino)-5-methylbenz-
aldehyde 2 (DMAMB) was prepared according to the
literature.25
(m, 15H, 15ArH), 6.04 (s, 1H, CHN), 3.77 (q, 1H,
J = 6.7 Hz, PhCHN), 2.43 (s, 6H, 2NCH3), 2.15 (s, 3H,
ArCH3), 1.50 (d, 3H, J = 6.7 Hz, PhCHCH3); 13C NMR
(125 MHz, CDCl3, ppm): d 149.3, 145.3, 140.0, 138.6,
134.0, 133.4, 132.4, 129.8, 128.4, 128.3, 128.1, 127.3,
127.1, 126.9, 125.5, 125.4, 125.2, 124.6, 124.0, 120.3, 55.8,
53.4, 45.4, 23.1, 20.9; MS: m/z 295 (M++1); Anal. Calcd
for C28H30N2: C, 85.24; N, 7.10; H, 7.66. Found: C,
85.20; N, 7.00; H, 7.79; IR (KBr): 3488, 3028, 2852,
4.2. Preparation of compounds 1 and 3
4.2.1. [2-(Dimethylamino)-5-methylphenyl]-(1-naphthyl)met-
hanol 3. Under a nitrogen atmosphere, a solution of
DMAMB (0.82 g, 0.005 mol) in THF (10 ml) was added
dropwise in an ice-water bath to a THF solution of
naphth-1-ylmagnesium bromide prepared from 1-bromo-
naphthalene (2.07 g, 0.01 mol) and magnesium (0.25 g,
0.0102 mol), and the mixture was stirred at room tempera-
ture for 7 h. The additive complex was treated with a solu-
tion of NH4Cl 5% and extracted with portions of ethyl
acetate. The organic layer was washed with brine and dried
over Na2SO4, evaporated and purified by flash chromato-
graphy to give a white solid 3 (1.33 g, 91.2%). Mp 108–
2818, 2777, 1592, 1499, 1451, 1161, 784 cmꢀ1
.
4.3. NMR shift experiments
NMR shift experiments were performed on a 500 MHz
NMR spectrometer at 25 ꢁC. Samples for analysis were
prepared by mixing equimolar amounts of compounds
1a, 1b and (S)-PEA with the guests studied herein in
CDCl3, making the concentrations of the hosts (or guests)
normally 4 mM.
1
110 ꢁC; H NMR (500 MHz, CDCl3, ppm): d = 6.80–8.21
4.4. Studies of the stoichiometry of the host–guest complex
(Job plots)
(m, 10H, 10ArH), 6.62 (s, 1H, CHOH), 2.82 (s, 6H,
2NCH3), 2.15 (s, 3H, ArCH3). 13C NMR (125 MHz,
CDCl3, ppm): d = 149.6, 139.4, 137.4, 137.4, 134.8, 134.0,
131.6, 129.5, 129.1, 128.6, 128.2, 125.9, 125.5, 125.3,
125.0, 121.4, 72.7, 45.9, 20.9. MS: m/z 291 (M+); Anal.
Calcd for C20H21NO: C, 82.44; N, 4.81; H, 7.26. Found:
C, 82.32; N, 4.58; H, 7.59; IR (KBr): 3158, 3051, 2861,
Compound 1b, (R)-4 and (S)-4 were separately dissolved in
CDCl3 with a concentration of 4 mM. These solutions were
distributed among nine NMR tubes, with the molar frac-
tions X of the guest in the resulting solutions increasing
from 0.1 to 0.9, and the total concentration of host and
guest was 4 mM. The complexation induced shifts (Dd)
were multiplied by X and plotted against X itself to afford
a 1:1 (host to guest) binding model. The same procedure
was performed to investigate the stoichiometry for 1a with
L-15.
2829, 2777, 1508, 1493, 1455, 1165, 946, 793 cmꢀ1
.
4.2.2. N,N,4-Trimethyl-2-[(S)-{[(S)-1-phenylethyl]amino}(1-
naphthyl)methyl]aniline 1a and N,N,4-trimethyl-2-[(R)-{[(S)-
1-phenylethyl]amino}(1-naphthyl)methyl] aniline 1b. To a
mixture of
3 (1.16 g, 0.004 mol) and tri-ethylamine
(0.48 g, 0.0048 mol) in CH2Cl2 (10 ml), a solution of
(CF3CO)2O (1.00 g, 0.0048 mol) in dry CH2Cl2 (10 ml)
was added at 0 ꢁC. The mixture was stirred at 0 ꢁC for
1 h. A solution of (S)-PEA (0.72 g, 0.006 mol) in dry
CH2Cl2 (10 ml) was added at 0 ꢁC. After 15 h, the mixture
was treated with cold water and extracted with portions of
CH2Cl2. The organic phase was washed with brine and
dried over Na2SO4, evaporated and purified by flash chro-
matography to give a white solid 1a (0.61 g, 38.7%) and a
white solid 1b (0.69 g, 43.8%), respectively.
4.5. NMR host–guest titrations
1H NMR titrations were performed by adding incremental
amounts of a CDCl3 solution of the host to nine NMR
tubes containing a solution of the corresponding (S)-4 or
(R)-4 also in CDCl3 .The final concentration of (S)-4 or
(R)-4 in all tubes was adjusted to be 2 mM while the guest
concentration varied from 0 to 10 mM. The 1H NMR spec-
trum of each sample was recorded on a 500 MHz spectro-
mer. Assuming a 1:1 complexation, Ka was calculated by
the non-linear least-squares fitting method from the
observed Dd values and the respective host and guest
concentrations.
20
Compound 1a: Mp 113–114 ꢁC; ½aꢁD ¼ þ113:2 (c 1.55,
1
CHCl3); H NMR (500 MHz, CDCl3, ppm): d 7.10–7.89
(m, 15H, 15ArH), 6.21 (s, 1H, CHN), 3.76 (q, 1H,
J = 6.5 Hz, PhCHN), 2.48 (s, 6H, 2NCH3), 2.36 (s, 3H,
ArCH3), 1.40 (d, 3H, J = 6.6 Hz, PhCHCH3); d 7.09–7.88
(m, 15H), 6.20 (s, 1H), 3.76 (q, 1H, J = 6.5 Hz), 2.48 (s,
6H), 2.36 (s, 3H ), 1.40 (d, 3H, J = 6.6 Hz); 13C NMR
(125 MHz, CDCl3, ppm): d 150.5, 145.7, 139.9, 137.9,
134.0, 133.2, 132.0, 129.4, 128.5, 127.4, 127.3, 127.1,
125.7, 125.4, 125.3, 124.8, 124.2, 120.6, 55.7, 52.9, 45.5,
23.0, 21.3; MS: m/z 295 (M++1); Anal. Calcd for
4.6. Evaluation of the accuracy of this determining method
To demonstrate the accuracy of our method for the deter-
mination of the enantiomeric excess of carboxylic acids, we
prepared seven samples containing 4 with 0%, 20%, 40%,
60%, 80%, 95% and 100% ee, respectively. All samples were
prepared by adding 1 equiv of compound 1a in the solu-
tions of 4 (4 mM in CDCl3) and their enantiomeric compo-

W. Wang et al. / Tetrahedron: Asymmetry 18 (2007) 832–837
837
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sitions were determined in the presence of compound 1a by
using the 1H NMR method. The results, which were calcu-
lated based on the integrations of the methine proton sig-
nals, are shown in Figure 8a. The linear correlation
between the observed and prepared % ee values was also
obtained (see Fig. 8b).
Acknowledgement
20. Anna, I.; Debora, B.; Gloria, U.-B.; Federica, B.; Piero, S.
Eur. J. Org. Chem. 2001, 2177–2184.
The authors thank the National Natural Science Founda-
tion of China (No. 201720080) for supporting this work.
21. Crystallographic data for the structure of compound 1b have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 631527.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB21EZ,
UK [fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk]. Crystal data of 1b: C28H30N2, M = 394.54,
References
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˚
orthorhombic, space group P2(1)2(1)2, a = 8.8823(13) A,
3
˚
˚
˚
b = 15.578(2) A, c = 16.682(3) A, V = 2308.3(6) A , D =
1.135 g/cm3, l = 0.066 mmꢀ1, F(000) = 848, Z = 4, R1 =
0.0409, xR2 = 0.0833. Data collection for the crystal struc-
ture determination was carried out on a diffractometer using
˚
a temperature of
MoKa radiation (k = 0.71073 A) at
294(2) K. Of the 13,141 reflections measured in the
1.79 6 h 6 26.40ꢁ range, 2691 reflections were unique and
1612 reflections with I > 2r(I) were used in structure solution
2
and refinement, Rint = 0.0534. w ¼ 1=½r2ðF o2Þ þ ð0:0371PÞ þ
0:36269Pꢁ, where P ¼ ðF o2 þ 2F 2cÞ=3. The structure was solved
by direct method using SHELXL-97. All of the non-hydrogen
atoms were refined by full-matrix least-square methods using
anisotropic displacement parameters.
`
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´
´
23. Gonzalez-Alvarez, A.; Alfonso, I.; Gotor, V. Tetrahedron
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