Chiral amino alcohols derived from natural amino acids as chiral solvating agents for carboxylic acids

Article abstract of DOI:10.1016/j.tetasy.2008.04.030

Several chiral amino alcohols have been synthesized conveniently and effectively. ¹H NMR was utilized to investigate their enantiodiscriminating abilities. Chiral amino alcohols 2 and 4 were discovered as efficient CSAs for the determination of the enantiomeric compositions of chiral carboxylic acids. In particular, for the Ts-derivatives of amino acids studied herein, 4 could be used for the assignment of the absolute configurations of the Ts-derivatives of amino acids with a neutral side chain through the chemical shift non-equivalences of their NH (Ts) protons with certain confidence.

Full text of DOI:10.1016/j.tetasy.2008.04.030

Tetrahedron: Asymmetry 19 (2008) 1193–1199
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chiral amino alcohols derived from natural amino acids as chiral solvating
agents for carboxylic acids
*
Wenge Wang, Xiumin Shen, Fengnian Ma, Zijing Li, Cong Zhang
College of Chemistry, Beijing Normal University, Beijing 100875, China
a r t i c l e i n f o
a b s t r a c t
Several chiral amino alcohols have been synthesized conveniently and effectively. 1H NMR was utilized to
investigate their enantiodiscriminating abilities. Chiral amino alcohols 2 and 4 were discovered as
efficient CSAs for the determination of the enantiomeric compositions of chiral carboxylic acids. In
particular, for the Ts-derivatives of amino acids studied herein, 4 could be used for the assignment of
the absolute configurations of the Ts-derivatives of amino acids with a neutral side chain through the
chemical shift non-equivalences of their NH (Ts) protons with certain confidence.
Article history:
Received 3 March 2008
Accepted 23 April 2008
Available online 26 May 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
1
2
R
R
Ph
Ph
Ph
NH OH
2
R
OH
NMR spectroscopy using chiral solvating agents (CSAs) has pro-
ven to be of great utility for the determination of the enantiomeric
compositions of chiral molecules, as well as for the correlation of
absolute configurations.1–4 a-Amino acids are potentially useful
sources of chirality for the synthesis of chiral auxiliaries for asym-
metric synthesis and chiral recognition. It is very important to
check or ascertain the enantiomeric composition and absolute con-
figuration of amino acids, as well as other carboxylic acids in scien-
tific research. Although chiral amines5–17 and alcohols18–34 acting
as CSAs for this purpose have been well documented in the litera-
ture, the applications of chiral amino alcohols are relatively rare in
this field.35–40 Chiral amino alcohols 1–3 derived from a-amino
acids have been widely employed as chiral ligands in asymmetric
catalysis,41–48 but, to the best of our knowledge, there is no report
on the use of this type of chiral amino alcohols as a CSA for the
analysis of chiral carboxylic acids. Therefore, it is worth exploring
these chiral amino alcohols in this aspect. On the basis of experi-
mental results, we modified the structure of compound 2 further
by introducing an aryl group onto its nitrogen atom and synthe-
sized chiral amino alcohol 4 (see Fig. 1). We expected that incorpo-
rating the anisotropic group (phenyl attached by bromo as well as
dimethylamino) could contribute to the modification of the differ-
ential magnetic influence of compound 2. It is well known that
increasing the number of stereogenic centres can afford an impor-
tant increase in the enantiodiscriminating abilities of these two
diastereoisomers.17,49 With this in mind, we also synthesized com-
pounds 5a and 5b, and explored the possibility of using these chiral
amino alcohols as CSAs for the effective analysis of the enantio-
H N
2
1
2
1: R = Me CH, R = Ph
2
Br
NMe
2
1
2
2: R = PhCH , R = Ph
2
1
2
3: R = PhCH , R = H
2
4
Ph
Ph
Ph
Ph
Ph
NH OH
Ph
NH OH
Me
NMe
Me
NMe
2
2
5b
5a
Figure 1. The structures of amino alcohols 1–5.
meric excess of carboxylic acids. Herein, we report the facile syn-
thesis of chiral amino alcohols from -phenylalanine as well as
their applications as CSAs for the determination of enantiomeric
compositions of chiral carboxylic acids as well as for the assign-
ment of the absolute configurations of the Ts-derivatives of some
amino acids with neutral side chains.
L
2. Results and discussion
Chiral amino alcohols 1–3 were available by the literature
methods41–43 from
L-valine and L-phenylalanine, respectively.
Compound 2 reacted with aldehyde 6, and then was reduced by
NaBH4 to give target compound 4 in good yields. The amino
alcohols 5a and 5b were efficiently prepared by the reaction of
* Corresponding author. Tel.: +86 13825661820; fax: +86 10 58210397.
E-mail address: czhang@bnu.edu.cn (C. Zhang).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.04.030

1194
W. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 1193–1199
compound 7 with trifluoroacetic anhydride and then with amino
alcohol 2 in the presence of triethylamine (see Scheme 1). These
chiral amino alcohols were characterized by 1H NMR, 13C NMR,
IR, MS and EA. The crystal structure of 5b was studied by X-ray sin-
gle crystal structure analysis. The molecular structure of com-
pound 5b is shown in Figure 2, which indicates the newly built
8
9
R = (CH3)2CH
R = (CH3)2CHCH2
CO2H
NHTs
CO2H
N
NHTs
CO2H
Ts
10 R = CH3
11 R = Ph
12 R = PhCH2
13 R = CH3SCH2CH2
14 R = HOOCCH2
15
R
N
H
stereogenic centre induced by compound
2
is of an (R)-
configuration.50
OH
16
CO2H
R
PhCOO
PhCOO
CO2H
CO2H
OH
CO2H
Ph
Ph
Ph
NH OH
NMe
2
17 R = H
CHO
18 R = p-Cl
19 R = p-OCH3
1. 2 , CH2Cl2, Na2SO4
20
21
2. NaBH4, C2H5OH
Br
NMe
2
Figure 3. The structures of the guests used herein.
Br
6
4
Table 1
Measurements of 1H chemical shift non-equivalences (DDd, Hz, 500 MHz) of racemic
guests (4 mM) in the presence of an equimolar amount of 5a and 5b in CDCl3 at 25 °C
Me
NMe
2
1. (CF3CO)2O, Et3N, CH2Cl2
Guest
Signal
DDd (Hz)
OH
5a
+
5b
2. 2, CH2Cl2
5a
5b
8
TsNH
CaH
CH3(Ts)
0
0
19.0
40.0
17.5
15.0
7
12
13
17
TsNH
CaH
CH3(Ts)
0
0
6.0
10.5
22.5
8.5
Scheme 1. The synthesis of chiral amino alcohols 4 and 5.
TsNH
CaH
CH3(Ts)
0
0
21.0
35.5
29.4
27.9
CaH
0
2.1
Figure 2. The molecular structure of compound 5b.
With these desired chiral amino alcohols 1–5 in hand, we em-
ployed 1H NMR spectroscopy to study their enantiodiscriminating
abilities, and the guests included the Ts-derivatives of some a-ami-
no acids 8–16, a-hydroxyl acids 17–20 and dibenzoyl-tartaric acid
(DBTA) 21 (see Fig. 3). At the outset, we were interested in screen-
ing chiral amino alcohols 1–5 as CSAs for chiral carboxylic acids to
check if the structures of these amino acids and/or the introduction
of aryl groups have a great influence on their enantiodiscriminat-
ing properties. Under the same experimental conditions as de-
scribed in Table 1, compound 1 was capable of discriminating
the enantiomers of compound 8, obtaining appreciable non-equi-
valences of 15.9 Hz, 24.3 Hz and 36.6 Hz for proton signals of NH,
CaH and CH3(Ts), respectively. Using compound 2 towards the
same analyte, the chemical shift non-equivalence (DDd) of the
NH was up to 51.1 Hz but that of the CH3(Ts) only to 10.4 Hz
(see Fig. 4). As for the DDds of the CH of mandelic acid 17 and DBTA
21, compound 2 could lead to larger DDds than compound 1. In
Figure 4. Partial 1H NMR (500 MHz, CDCl3, 25 °C) spectra of enantiomerically
enriched 8 (
L:D = 3:1) (a) in the presence of an equimolar amount (4 mM) of: (b) 2;
(c) 4.

W. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 1193–1199
1195
fact, the CH resonances of 17 and 21 underwent small splittings of
3.6 Hz and 7.0 Hz in the presence of compound 1, whereas com-
pound 2 produced large doublings of 46.0 Hz and 170.1 Hz, which
were both large enough to afford baseline resolution for accurate
integration. These experimental data show that compound 2
exhibits a better enantiodiscriminating ability towards these car-
boxylic acids than compound 1. Comparatively, structurally simple
compound 3 could only differentiate compound 8 with a difference
of 2.6 Hz for the CH proton, while compound 17 merely induced a
minor separation of the CH proton (6.7 Hz). These data verify that
the introduction of two phenyls contribute to increasing the chiral
recognition ability of compound 2. Figure 4 shows the splitting of
the signals of protons TsNH, CaH, CH3(Ts) and CH3(valine) of com-
pound 8 after the addition of an equimolar amount of compound 2
and compound 4. Using compound 4, all alkyl protons signals of
compound 8 exhibited appreciable enantiodiscrimination (CbH
also see Fig. 8g); however, compound 2 could not discriminate be-
tween the CaH and CbH proton. This result demonstrates that it is
worthwhile introducing an anisotropic group on the nitrogen atom
of compound 2.
the (S,S)-diastereoisomer 5a is the ‘mismatched couple’.17,48 An
inspection of these data in Tables 1 and 2 clearly shows that com-
pounds 2 and 4 exhibit better enantiodiscriminating abilities than
compounds 5a and 5b towards these carboxylic acids as listed in
Table 1.
These good preliminary results encouraged us to further evalu-
ate the usefulness of compound 2 and compound 4 towards other
carboxylic acids. Table 2 summarizes the results of the examina-
tion of the enantiomeric discriminating abilities of compounds 2
and 4. Some assessments could be given comparing the DDds of
compounds 8–21. In general, using compound 4, in almost every
case, at least one resonance exhibits baseline separation, which is
suitable for the determination of the enantiomeric composition
of these chiral substrates. The largest DDd value was up to
331.6 Hz, which was achieved on the NHTs proton after the addi-
tion of an equimolar amount of compound 2 into compound 10
in CDCl3 (see Fig. 5). When polar compound 14 served as the ana-
lyte, compound 2 only could discriminate one of the CH2 with a dif-
ference of 20.1 Hz using CDCl3 (containing 4% CD3OD) as a solvent,
but compound 4 could induce this DDd to 55.9 Hz. The CaH and
CH3(Ts) protons of compound 14 underwent splittings of 26.8 Hz
and 5.5 Hz in the presence of compound 4 under the same exper-
imental conditions (see Fig. 6). Another example to demonstrate
the efficiency of compound 4 was that the CSA could differentiate
between the CaH and CH3(Ts) protons of compound 15 with the
separation being 19.1 Hz and 17.4 Hz, but the two probe protons
could not be resolved in the presence of compound 2.
From the experimental data of the protons in Table 1, we could
learn that the (S,R)-diastereoisomer 5b represents the matched
couple of the CSA towards the carboxylic acids listed, whereas
Table 2
Measurements of 1H chemical shift non-equivalences (DDd, 500 MHz) of chiral or
racemic guests in the presence of an equimolar amount of compounds 2 and 4 in
CDCl3 at 25 °C (unless indicated otherwise)
Guest
Signal
DDda (Hz)
2
4
8b
TsNH
CaH
CH3(Ts)
51.0(
0
10.4(
D
)
)
85.2(
54.3(
42.7(
L)
D
)
)
D
D
9b
TsNH
CaH
CH3(Ts)
128.2(
29.9(
4.9(
D
)
)
100.9(L)
D
)
46.5(
33.9(
D
)
)
D
)
D
10
TsNH
CaH
CH3(Ts)
CH3
331.6(
D
94.6(
27.7(
17.4(
55.3(
L
)
35.7(
0
D)
D
D
D
)
)
)
77.1(
D)
11
12
13
14c
TsNH
CaH
CH3(Ts)
174.0(
D
)
)
)
18.8(L)
5.0(D)
76.6(
0
D)
43.4(
D)
TsNH
CaH
CH3(Ts)
197.0(
D
14.5(
0
L)
Figure 5. Partial 1H NMR spectra (500 MHz) of equimolar mixtures (4 mM each) of
compounds 2 and 10 at 25 °C in CDCl3: (a) DL-10; (b) enantiomerically enriched 10
38.1(
0
D)
18.0(
D)
(L:D = 3:1) and compound 2.
TsNH
CaH
CH3(Ts)
135.6(
22.7(
3.3(
D
78.9(
26.0(
40.7(
L
)
)
)
D)
D
D)
D
CaH
CH3(Ts)
CHaHb
18.2(
0
L
)
26.8(
D)
5.5(D)
20.1(
D)
55.9(D
)
15
16
CaH
CH3(Ts)
0
0
19.1(
17.4(
L
)
L)
TsNH
CaH
CH3(Ts)
150.0(
17.9(
6.4(
D
)
24.1(
15.1(
17.3(
L)
D
)
D
)
)
L
)
D
17
18
19
CaH
CaH
CaH
CH3O
46.0
19.2
48.0
3.5
14.0
10.5
12.5
5.6
20
21
CH
CH
6.0
170.1
44.3
40.5
a
In brackets: configuration of the enantiomer corresponding to the signal at
higher field.
b
Figure 6. Partial 1H NMR spectra (500 MHz) of equimolar mixtures (4 mM each) of
compounds 4 and 14 at 25 °C in CDCl3 (4% CD3OD): (a) DL-14; (b) enantiomerically
The chemical shift non-equivalences of the methyl protons of CH(CH3)2 for 8
and CH2CH(CH3)2 for 9 are large (see Fig. 4).
c
Using CDCl3 (containing 4% CD3OD) as a solvent.
enriched 14 (L:D = 3:1) and compound 4.

1196
W. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 1193–1199
It is noteworthy that compound 2 seems to be sensitive to the
the CaH and the methyl signals of the D-enantiomer, which both
TsNH protons of the Ts-derivatives of amino acids, whereas com-
pound 4 is prone to determining the existence of the CaH and
CH3(Ts) protons. Considering the effectiveness of compounds 2
and 4 in enantiodiscriminating the Ts-derivatives of amino acids,
we turned our attention towards other carboxylic acids. As far as
a-hydroxyl carboxylic acids are concerned, compound 2 shows
better enantiomeric discrimination towards aromatic a-hydroxyl
acids than compound 4 does; however, compound 4 is preferable
for the analysis of alkyl hydroxyl acids such as lactic acid 20 (see
Fig. 7 and Table 2). The data concerning the enantioselectivity of
compounds 2 and 4 towards the derivatives of mandelic acid 18
and 19, non-aromatic hydroxyl acid 20 and dicarboxylic acid 21
are listed in Table 2.
resonated at higher field with the separations being 21.9 Hz and
19.3 Hz, respectively.
The experimental results of the molar ratio of compound 4/
compound 8 are shown in Figure 8. The trend is consistent with
studies of other CSAs, in which increasing the concentration of
the reagent promotes the formation of the diastereoisomeric com-
plexes and enhances the extent of enantiomeric discrimination in
the NMR spectrum. As far as the effect of the molar ratio CSA/sub-
strate is concerned, it is noteworthy that compound 4 also works
when this ratio is lowered to 0.6.
Figure 7. Partial 1H NMR spectra (500 MHz) of equimolar mixtures (4 mM) CSA/
racemic compound: (a) 20; (b) 2/20; (c) 4/20. (d) 21; (e) 2/21; (f) 4/ 21.
From Table 2, we can see that all discernible proton signals in
the
D-enantiomers of chiral Ts-derivatives of amino acids appear
consistently at a higher field relative to the same signals in the
L-
enantiomers in the presence of compound 2 only with two excep-
tions. One abnormal example appearing on the CaH proton of com-
pound 14 might be due to the existence of an additional carboxylic
acid moiety of the analyte structure; another anomalous one could
be observed on the CH3(Ts) protons signal of compound 16, which
might be due to the indolyl group to participating in the host–
guest interaction as well as its anisotropic influence on this probe
proton. For chiral compounds 8–14 as well as 16, using compound
4, all distinguishable CaH and CH3(Ts) in the
these guests consistently appear at a higher magnetic field relative
to the same signals of the -enantiomers, however, the -enantio-
D-enantiomers of
Figure 8. Evolution of partial 1H NMR spectra (500 MHz) of racemate 8 (4 mM)
when (a) 0 equiv, (b) 0.2 equiv, (c) 0.4 equiv, (d) 0.6 equiv, (e) 0.8 equiv, (f) 1.0
equiv, (g) 2.0 equiv of compound 4 are added. Samples dissolved in CDCl3 at 25 °C.
L
L
mers of these analytes exhibit the TsNH protons signals at a higher
field. This implies that the diastereoisomeric nature of the host–
guest complexes of the two enantiomers with compound 4 is more
significant in causing enantiomeric discrimination than the in-
equivalence in association constants.51 These results offer the pos-
sibility that compound 4 could be used for the assignment of the
absolute configurations in the Ts-derivatives of chiral amino acids
with neutral side chains. It could be seen that compound 4 could
Knowledge of the stoichiometry of the associate is important in
determining the structure of the complexes. Nine samples of a con-
stant total concentration (4 mM) were prepared containing vari-
able ratios of compound 4 and
of these samples were recorded and chemical shift variations were
observed for the CH3(Ts) proton of -11 or -11. The stoichiometry
L-11 or D
-11. The 1H NMR spectra
L
D
of the host–guest complex was determined according to Job’s
method of continuous variation.52 The Job plots for the complexa-
induce the CaH and CH3(Ts) protons signals of the L-enantiomer
of compound 15 to appear at higher field. This abnormal example
might be due to its rigid cyclic structure, as well as its structure de-
void of the TsNH proton. In order to examine further the applicabil-
ity of using compound 4 as the CSA for the assignment of the
absolute configurations of the Ts-derivatives of amino acids with
their chemical shift differences, we chose enantiomerically en-
tion of compound 4 with
affording a maximum of Dd X at X = 0.5, which means that com-
pound 4 forms a 1:1 instantaneous complex with L-11 or D-11 un-
der these experimental conditions (see Fig. 9).
In order to evaluate further the discriminating abilities of 2 and
4, we performed the titration curves of 2 and 4 with -11 or -11.
The association constants of 2 and 4 with -11 or -11 were deter-
L-11 or D-11 were illustrated in Figure 9,
L
D
riched Ts-serine (L:D = 3:1) as the analyte and aquired its NMR
L
D
spectrum under the same experimental conditions but using CDCl3
(containing 4% acetone-d6) as a solvent. As expected, the amide
mined from the titration curves by the non-linear least-squares
fitting method (Table 3).52 From Table 3, it was noticed that
proton signal of the
L-enantiomer resonated at a higher field and
the
D-enantiomer was more strongly bound to 2 or 4 than the
the separation was up to 64.6 Hz. The same trend occurred with
L-enantiomer. In order to investigate the intrinsic chemical shift

W. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 1193–1199
1197
Figure 9. Job plots for the complexation of compound 4 with L-11 and D-11. (X =
[4]/([11] + [4]); Dd = variation of the chemical shift of the observed proton).
Table 3
Association constants Ka (mol/l)ꢀ1 of the host–guest complexes of hosts 2 and 4 with
L-11 or D-11 in CDCl3
Entry
CSAs
Guests
-11
-11
-11
-11
Ka (mol/l)ꢀ1
Ka(D)/Ka(L)
Figure 10. Partial 1H NMR (500 MHz) spectra of 8 with various enantiomeric
purities (4 mM) in the presence of an equimolar amount of compound 4.
1
2
3
4
2
2
4
4
D
(1.9 0.6) ꢁ 104
(1.2 0.3) ꢁ 104
(2.3 0.5) ꢁ 104
(2.0 0.2) ꢁ 104
1.58
1.13
L
D
L
4. Experimental
4.1. General methods
non-equivalences of the two diastereoisomeric instantaneous
complexes, we performed the NOESY spectra of the complexes
IR spectra were obtained on a Nicolet 360 Avatar IR spectro-
meter as KBr pellets. NMR spectra were recorded on Avance 500
Bruker spectrometer (1H at 500 MHz and 13C at 125 MHz). Mass
spectra were recorded on Trace MS 2000-Mass Spectrometer using
the EI technique. The 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.
The solvents (dichloromethane, ethanol and THF) were analyti-
cal and thoroughly dried. 2-(N,N-Dimethylamino)-5-bromo-benz-
aldehyde 6 (DMABB) was prepared according to the literature
method.53 Intermediate 7 [2-(dimethylamino)-5-methylphenyl]-
(1-naphthyl) methanol was synthesized according to the literature
method.17
formed from 4 with an equimolar amount of L-11 or D-11, but no
intermolecular NOE phenomena were observed. The incorporation
of anisotropic group into compound 2 may play an important role
for the excellent chiral recognition abilities by the combination of
steric and electrical factors.
Finally, we attempted to demonstrate the accuracy of this enan-
tiomeric excess determination method. With this aim, we prepared
six samples containing different proportions of both enantiomers
of 8, and analyzed their enantiomeric compositions in the presence
of compound 4 by using 1H NMR method (see Fig. 10). The results,
which were calculated based on the integrations of the corre-
sponding CH3(Ts) proton signals, are within 1% of the actual enan-
tiopurity of these samples and thus, demonstrate the high accuracy
of this method.
4.2. Preparation of compounds 4 and 5
3. Conclusion
4.2.1. Preparation of (S)-2-(5-bromo-2-dimethylamino-
In conclusion, several chiral amino alcohols were screened for
their enantiodiscriminating abilities for carboxylic acids, and chiral
amino alcohols 2 and 4 were discovered to exhibit good chiral rec-
ognition abilities towards carboxylic acids. The two new diastereo-
isomeric chiral amino alcohols 5a and 5b were also synthesized
conveniently and effectively, which proved to be less effective than
compound 2 and compound 4 in enantiodiscriminating chiral car-
boxylic acids. In particular, for the Ts-derivatives of amino acids
studied herein, 4 could be used for the assignment of the absolute
configurations of the Ts-derivatives of amino acids with neutral
side chains through the chemical shift non-equivalences of their
NH (Ts) protons with certain confidence.
benzylamino)-1,1,3-triphenyl-propan1-1-ol 4
To a mixture of chiral amino alcohol 2 (0.303 g, 1 mmol) and
anhydrous sodium sulfonate (0.284 g, 2 mmol) in CH2Cl2 (10 mL),
a solution of aldehyde 6 (0.31 g, 0.0015 mol) in dry CH2Cl2
(10 mL) was added at room temperature. The mixture was stirred
at room temperature for 5 h. CH2Cl2 was evaporated, and the mix-
ture was dissolved in anhydrous ethanol (10 mL). Then portions of
NaBH4 (0.076 g, 2 mmol) were added slowly at 0 °C, after 10 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 chromatography (petro-
leum ether/acetyl acetate = 15:1) to give a white solid 4 (0.44 g,

1198
W. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 1193–1199
20
85%). Compound 4. Mp 60–61 °C; ½aꢂD ¼ ꢀ41:6 (c 0.44, CHCl3); 1H
NMR (500 MHz, CDCl3, ppm): d = 7.79–6.65 (m, 18H, 18ArH), 4.06
(dd, 1H, J = 10.7 Hz, J = 2.7 Hz, CHNH), 3.20–2.96 (m, 3H, ArCH2NH
and PhCHA), 2.41 (dd, 1H, J = 10.8 Hz, J = 14.8 Hz, PhCHB), 2.25 (s,
6H, 2NCH3); 13C NMR (125 MHz, CDCl3, ppm): d = 151.6, 147.7,
145.1, 139.4, 136.4, 132.6, 130.5, 128.9, 128.6, 128.2, 126.6,
126.5, 126.4, 126.1, 125.7, 121.0, 115.8, 78.3, 66.2, 50.3, 44.4,
37.6; MS: m/z 515 (M+); Anal. Calcd for C30H31N2OBr: C, 69.90; N,
5.43; H, 6.06. Found: C, 70.38; N, 5.22; H, 6.29; IR (KBr): 3480,
induced shifts (Dd) were multiplied by X and plotted against X itself
to afford a 1:1 (host to guest) binding model.
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 contain-
ing a solution of the corresponding
L-11 or D-11 also in CDCl3. The
final concentration of -11 or -11 in all tubes was adjusted to be
L
D
3037, 2859, 2823, 2780, 1597, 1496, 1452, 1160, 776 cmꢀ1
.
2 mM while the guest concentrations varied from 0 to 8 mM. The
1H NMR spectrum of each sample was recorded on a 500 MHz
spectrometer. 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.
4.2.2. Preparation of (S,S)-2-{[(2-dimethylamino-5-
methylphenyl)-naphthalen-1-yl-methyl]amino}-1,1,3-
triphenyl-propan-1-ol 5a and (S,R)-2-{[(2-Dimethylamino-5-
methylphenyl)-naphthalen-1-yl-methyl]amino}-1,1,3-
triphenyl-propan-1-ol 5b
4.6. Evaluation of the accuracy of this determining method
To a mixture of compound 7 (0.291 g, 1 mmol) and triethyl-
amine (0.303 g, 3 mmol) in CH2Cl2 (10 mL), a solution of (CF3CO)2O
(0.31 g, 1.5 mmol) in dry CH2Cl2 (10 mL) was added at 0 °C. The
mixture was stirred at 0 °C for 1 h. A solution of chiral amino alco-
hol 2 (0.303 g, 1 m mol) in dry CH2Cl2 (10 mL) was added at 0 °C.
After 24 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 chroma-
tography (petroleum ether/acetyl acetate = 40:1) to give a white
solid 5a (0.16 g, 28 %) and a white solid 5 b (0.26 g, 45%),
respectively.
To demonstrate the accuracy of our method for the determina-
tion of the enantiomeric excess of carboxylic acids, we prepared
seven samples containing compound 8 with 0, 20, 40, 60, 80, 90
and 95% ee, respectively. All samples were prepared by adding
1 equiv of compound 4 into solutions of compound 8 (4 mM in
CDCl3) and their enantiomeric compositions were determined in
the presence of compound 4 by using 1H NMR method. The results,
which were calculated based on the integrations of the CH3Ts
protons signals, are shown in Figure 10.
20
Compound 5a. Mp 198–199 °C; ½aꢂD ¼ þ42:8 (c 0.50, CHCl3); 1H
Acknowledgement
NMR (500 MHz, CDCl3, ppm): d = 7.76–6.34 (m, 25H, 25ArH), 5.74
(s, 1H, ArCH), 4.15–4.14 (m, 1H, CHNH), 2.69–2.67 (m, 1H, PhCHA),
2.63 (s, 6H, 2NCH3), 2.47 (dd, 1H, J = 10.0 Hz, J = 13.5 Hz, PhCHB),
2.06 (s, 3H, ArCH3); 13C NMR (125 MHz, CDCl3, ppm): d = 148.0,
146.4, 140.1, 137.6, 134.3, 133.7, 129.7, 129.1, 128.6, 128.5,
128.0, 126.0, 124.3, 121.6, 77.9, 61.4, 53.8, 46.8, 37.9, 21.0; MS:
m/z 577 (M++1); Anal. Calcd for C41H40N2O: C, 85.38; N, 4.86; H,
6.99. Found: C, 85.19; N, 4.69; H, 7.32; IR (KBr): 3480, 3037,
The authors thank the National Natural Science Foundation of
China (No. 201720080) for supporting this work.
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