Chirality sensing of tertiary alcohols by a novel strong hydrogen-bonding donor-selenourea

Article abstract of DOI:10.1039/c5sc03780h

Chemical sensors are powerful for the fast recognition of chiral compounds. However, the established sensing systems are less effective for chiral tertiary alcohols. The chiral tertiary alcohol group is an important structural unit in natural products and drug molecules, and its enantioselective recognition represents a significant and challenging task. In this paper, a novel type of chiral bisselenourea sensor was first synthesized and used as a strong hydrogen-bonding donor for highly efficient chiral recognition of a diverse range of tertiary alcohols. The obtained sharply split NMR signals are well-distinguishable with a large (up to 0.415 ppm) chemical shift nonequivalence. The NMR signal of the hydroxyl hydrogen atom was first employed for enantiomeric excess determination of tertiary alcohols, giving accurate results with <2% absolute errors. The 2D NOESY spectra and computational studies suggest that the geometrical differentiation of the formed diastereomeric complexes between the sensor and tertiary alcohols enables the chiral discrimination of the hydroxyl hydrogen signals of the tertiary alcohol in the ¹H NMR spectrum.

Full text of DOI:10.1039/c5sc03780h

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Chirality sensing of tertiary alcohols by a novel
strong hydrogen-bonding donor – selenourea†
Cite this: DOI: 10.1039/c5sc03780h
a
a
a
a
a
*
Guangling Bian, Shiwei Yang, Huayin Huang, Hua Zong, Ling Song,
b
c
*
*
Hongjun Fan and Xiaoqiang Sun
Chemical sensors are powerful for the fast recognition of chiral compounds. However, the established
sensing systems are less effective for chiral tertiary alcohols. The chiral tertiary alcohol group is an
important structural unit in natural products and drug molecules, and its enantioselective recognition
represents a significant and challenging task. In this paper, a novel type of chiral bisselenourea sensor
was first synthesized and used as a strong hydrogen-bonding donor for highly efficient chiral recognition
of a diverse range of tertiary alcohols. The obtained sharply split NMR signals are well-distinguishable
with a large (up to 0.415 ppm) chemical shift nonequivalence. The NMR signal of the hydroxyl hydrogen
atom was first employed for enantiomeric excess determination of tertiary alcohols, giving accurate
results with <2% absolute errors. The 2D NOESY spectra and computational studies suggest that the
geometrical differentiation of the formed diastereomeric complexes between the sensor and tertiary
alcohols enables the chiral discrimination of the hydroxyl hydrogen signals of the tertiary alcohol in the
1H NMR spectrum.
Received 5th October 2015
Accepted 20th October 2015
DOI: 10.1039/c5sc03780h
www.rsc.org/chemicalscience
tertiary centers and can be found in many well-known
compounds, for example linalool, bedaquiline, camptothecin,
escitalopram, efavirenz, etc.11 Chiral recognition of tertiary
Introduction
Chirality plays a key role in modern science and technology.
Therefore, the recognition of chirality and enantiomeric excess
determination of chiral compounds are intensive areas of
research.1 Furthermore, the exponentially growing detection
demand in modern asymmetric synthesis and drug discovery
drives the development of fast, accurate and convenient systems
for chiral recognition. Compared with chiral chromatography
and X-ray crystallography, sensing systems using chiral chem-
ical sensors are appropriate for this purpose.2 So far, a lot of
chiral sensors have emerged employing CD,1b,3 UV-vis,4 uo-
rescence2b,5 or NMR spectroscopy6–9 for enantiomeric excess (ee)
determination of various types of guests. However, there is one
kind of guest, chiral tertiary alcohols, whose enantioselective
discrimination has been very challenging until now because of
their large steric hindrance, weak coordination ability, and
complex stereoelectronic effect.10 The chiral tertiary alcohol
group is an important substructure with fully substituted
alcohols is mainly dependent on using time-consuming and
expensive chiral chromatography.12 Only very few chiral
lanthanide shi reagents13 and chiral solvating agents (CSA)8h–j
have been reported as NMR sensors for chiral tertiary alcohols,
and the resolved effects were less than satisfactory because of
either inherent line broadening6a,8a,14 or a small signal split.
Therefore, an accurate and highly efficient chemical sensing
system for chiral tertiary alcohols is still highly desirable.
To address this problem, we targeted a chirality sensing
system with NMR sensors, employing the proton signal of the
hydroxyl group (O–H) attached to the quaternary stereogenic
center of a tertiary alcohol. Since the O–H group is involved in
intermolecular interactions with CSA via hydrogen bonds, the
aThe Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian
Institute of Research on the Structure of Matter, Chinese Academy of Sciences,
Fuzhou, Fujian 350002, P. R. China. E-mail: songling@irsm.ac.cn
bThe State Key Lab of Molecular Reaction Dynamics, Dalian Institute of Chemical
Physics (iCheM), Chinese Academy of Sciences, Dalian, Liaoning, 116023, P. R.
China. E-mail: fanhj@dicp.ac.cn
cSchool of Petrochemical Engineering, Changzhou University, Changzhou, Jiangsu,
213164, P. R. China. E-mail: xqsun@cczu.edu.cn
† Electronic supplementary information (ESI) available: Original NMR spectra
and the results of the computational modeling. See DOI: 10.1039/c5sc03780h
Fig. 1 Structures of bisthiourea and bisselenourea.
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Table 1 The N–H pKa values of (thio)urea and selenourea
O–H signal is more easily split. Herein, we report a novel type of
sensor, bisselenourea (S,S)-CSA-2 (Fig. 1, right), which could
give well-resolved and sharp O–H signals for the enantiodis-
crimination of structurally diverse tertiary alcohols using 1H
NMR technology.
Compound
pKDa MSO (exptl)
pKDa MSO (calcd)a
18.7 (ref. 18)
18.5
Results and discussion
13.4 (ref. 18)
13.8
Molecular design
A large number of studies has shown that the urea (thiourea)
groups of chemical molecules are important recognition sites
because they are involved in intermolecular interactions with
other molecules via hydrogen bonds.15 In the recognition of
chiral compounds, the urea (thiourea) groups primarily act as
hydrogen bond donors, and their ability to provide a hydrogen
bond is an important factor for the success or failure of the
recognition. In general, a urea (thiourea) with a stronger N–H
acidity is a better hydrogen bond donor, which is helpful for
improving chiral recognition. Accordingly, we developed a CF3-
substituted bisthiourea with a strong N–H acidity (Fig. 1, le,
(S,S)-CSA-1), which showed excellent enantiodiscrimination for
a series of a-carboxylic acids based on split a-H NMR signals.16
However, when used to discriminate several tertiary alcohols,
(S,S)-CSA-1 gave much smaller splits of the proton signals due to
weak intermolecular interactions. To improve the chiral
discrimination of chiral alcohols, we conceived that a stronger
hydrogen bond donor than (S,S)-CSA-1 should facilitate the
hydrogen-bonding interactions between CSA and tertiary
alcohols.
In order to achieve an outstanding performance for the
chiral recognition of tertiary alcohols, selenourea attracted our
attention. Selenium has similar properties to sulfur with
a larger atomic radius. The larger atomic radius makes sele-
nium able to accommodate more negative charge than sulfur,
which could induce a stronger N–H acidity of selenoureas.17
Therefore, selenourea should be a stronger hydrogen-bonding
donor than thiourea. However, the study of selenourea as
a proton donor is limited and data on the N–H acidity of sele-
nourea is not available in literature. Using diphenyl urea,
diphenyl thiourea and diphenyl selenourea as model molecules,
we found that the N–H pKaDMSO values decrease in the order of
diphenyl urea, diphenyl thiourea and diphenyl selenourea, as
shown in Table 1 by theoretical calculations. This suggests that
selenourea is a stronger hydrogen-bonding donor than thio-
urea. This result encouraged us to employ selenourea
compounds for the chiral recognition of tertiary alcohols. So, we
designed and synthesized (S,S)-CSA-2, which is an analog of
(S,S)-CSA-1 (Scheme 1). The calculated pKDa MSO value of (S,S)-
CSA-2 is signicantly less than that of (S,S)-CSA-1 (Table 1).
(S,S)-CSA-2 was expected to give a better performance in the
chiral recognition of tertiary alcohols than (S,S)-CSA-1.
—
11.8
(S,S)-CSA-1
(S,S)-CSA-2
—
—
9.9b
7.5c
a
Calculated pKDa MSO values with the use of the relative determination
method. 4-Nitrophenol (10.8) was chosen as the reference acid. N–H
of 3,5-bistriuormethyl aniline of (S,S)-CSA-1.
bistriuormethyl aniline of (S,S)-CSA-2.
b
c
N–H of 3,5-
mM racemic guest and 10 mM host in CDCl3) (Table 2). As
shown in Table 2, (S,S)-CSA-2 does have a better recognition
effect than (S,S)-CSA-1, in line with our expectation. This result
conrms that replacing S with Se does effectively enhance the
acidity of N–H to facilitate the hydrogen-bonding interactions of
the alcohols with (S,S)-CSA-2 and improve the chiral recogni-
tion. Then, we chose guest A as a model molecule to optimize
the discriminating conditions (Table 3). By changing the
solvent, a larger (up to 0.052 ppm) DDd value was obtained with
deuterated benzene, implying that a tighter diastereomeric
complex could be formed in a more nonpolar solvent, resulting
in a better resolution (Table 3, entries 1–4). Increasing the
concentrations of guest A and (S,S)-CSA-2 caused the resolution
effect to signicantly improve because the equilibrium of the
diastereomeric complex formation was driven to the right with
higher concentrations (Table 3, entries 4–7). The best result was
obtained with 30 mM of guest A and 90 mM of (S,S)-CSA-2
(Table 3, entry 9). The corresponding DDd value is 0.137 ppm,
Test discriminating ability
With (S,S)-CSA-2 in hand, we rst compared its enantiomeric
discriminating ability with that of (S,S)-CSA-1 by testing several
tertiary alcohols under the same experimental conditions (10 Scheme 1 Synthesis of bisselenourea (S,S)-CSA-2.
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Table 2 Comparison of the discriminating ability of (S,S)-CSA-2 and Table 4 Measurements of NMR DDd of racemic guests in the pres-
(S,S)-CSA-1a
ence of (S,S)-CSA-2a
Entry Guest
Spectrumb
DDdc (ppm)
Entry
1
Guest19
Spectrumb
DDd (ppm)
0.137c
1
2
0.027 (blue), 0.020 (red)
0.043 (blue), 0.028 (red)
0.022 (blue), 0.012 (red)
2
3
0.328c
0.415c
3
a
All samples were prepared by mixing 1 : 1 of CSAs and guests in NMR
b
tubes (10 mM in CDCl3). Red spectra were obtained with (S,S)-CSA-1,
and blue spectra were obtained with (S,S)-CSA-2 by 1H NMR (400
c
4
5
0.105c
0.320c
MHz) at 25 ꢀC. Chemical shi non equivalences (DDd) of the O–Hs
of guests, red values were obtained with (S,S)-CSA-1, and blue values
were obtained with (S,S)-CSA-2.
Table 3 Optimization of the discriminating conditions for 2-phenyl-
2-butanol (guest A) by (S,S)-CSA-2a
C (mM)
6
7
0.144c
0.111c
Entry
Solvent
Guest A
(S,S)-CSA-2
DDdb (ppm)
1
2
3
4
5
6
7
8
9
CDCl3
DMSO
10
10
10
10
20
30
40
30
30
10
10
10
10
20
30
40
60
90
0.027
0
0
0.052
0.074
0.097
0.108
0.125
0.137
CD3COCD3
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
8
0.315c
a
Guest A and (S,S)-CSA-2 were mixed in the specied solvent (0.6 mL)
and the 1H NMR data were collected on a Bruker Avance 400 MHz
spectrometer at 25 ꢀC. b DDd of the O–H group of guest A.
9
0.144c
0.062c
which shows enantiodifferentiation of the enantiomers of the
racemic guest A clearly. Therefore, the optimized conditions for
our further investigations were chosen as follows: C6D6 as the
solvent with 30 mM of the tertiary alcohol guests and 90 mM of
bisselenourea (S,S)-CSA-2.
10
The applicability of these conditions for racemic alcohols
with various structures is demonstrated by the data displayed in
Table 4. The DDd values of the O–H groups are large enough to
give a baseline resolution for all the tested tertiary alcohols
ranging from simple to multifunctional ones on a 400 MHz
11
0.029d
ꢀ
NMR instrument at 25 C (Table 4, entries 1–7). Guest C con-
taining a tetrahydronaphthyl group gave well-distinguishable
proton signals with a large (up to 0.415 ppm) DDd value.
Racemic axially chiral BINOL (guest H), containing sp2 C–OH
and being structurally similar to tertiary alcohols, could also be
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Table 4 (Contd.)
Entry
Guest19
Spectrumb
DDd (ppm)
12
0.046d
a
All samples were prepared by mixing (S,S)-CSA-2 and the guests in
NMR tubes (30 mM of the guest and 90 mM of (S,S)-CSA-2 in 0.6 mL
of C6D6). 1H NMR and 19F NMR data were collected on a Bruker
b
Avance 400 MHz spectrometer at 25 ꢀC. The O–H signals of guests
A–J and the uorine signals of guests K and L; the conguration was
Fig. 2 Selected regions of the 1H NMR spectra of nonracemic guest F
(various ee values) with (S,S)-CSA-2 and the linear correlation between
the ee values determined by HPLC and NMR (ee values are defined in
terms of (S)-F).
determined by comparing with the spectra of nonracemic samples of
c
d
known congurations. DDd of the O–H of guests A–J. DDd of the
uorine atoms of guests K and L.
the host–guest in the complex by Job plots (see the ESI†). The
Job plots exhibit a maximum at X ¼ 0.5, indicating 1 : 1
complexation of the host–guest. Then, the binding constants of
the (R)-A/(S,S)-CSA-2 complex and (S)-A/(S,S)-CSA-2 complex
were determined by the nonlinear least-squares method (see the
ESI†). The larger binding constant of (S)-A/(S,S)-CSA-2 suggests
that it is a more stable complex than (R)-A/(S,S)-CSA-2 (Table 5).
2D NOESY experiments for the mixture of racemic guest A
and (S,S)-CSA-2 show a strong correlation between guest A and
(S,S)-CSA-2 (Fig. 3), indicating that the intermolecular non-
covalent interactions present in the complexes result in
a closeness of multiple hydrogen atoms (Hk, Hl, Hm, HR or HS)
of guest A to (S,S)-CSA-2 (Ha and Hd) in space. Among them, Ha
of (S,S)-CSA-2 shows strong NOESY correlated signals with guest
A. In addition, its chemical shi dramatically moves downeld
(see the ESI†). These results suggest that Ha is more likely to be
the intermolecular interaction site.
Computational modeling studies20 show that both (S)-A/
(S,S)-CSA-2 and (R)-A/(S,S)-CSA-2 complexes have hydrogen-
bonding and pi–pi interactions. As shown in Fig. 4 and Table 6,
(S)-A/(S,S)-CSA-2 has a relatively shorter hydrogen bond length,
a larger calculated binding energy DG and a larger calculated
chemical shi of O–H compared to (R)-A/(S,S)-CSA-2, which also
indicates that (S)-A/(S,S)-CSA-2 is more stable. We propose that
the preference of (S)-A/(S,S)-CSA-2 is due to a weaker steric
repulsion between (S)-A and (S,S)-CSA-2. As shown by the opti-
mized structures, in (S)-A/(S,S)-CSA-2, the CH3 group is situated
in the bimolecular interacting region, while the larger C2H5
group is far away. By contrast, in (R)-A/(S,S)-CSA-2, the larger
C2H5 group is situated in the bimolecular interacting region,
effectively enantiodiscriminated by (S,S)-CSA-2 (Table 4, entry
8). Compared with A, although secondary alcohol I lacks one
electron-donating ethyl group, its smaller steric hindrance
facilitates the intermolecular noncovalent interactions with
(S,S)-CSA-2 resulting in a similar DDd value to A (Table 4, entry
9). Compared with the 0.062 ppm DDd value of aliphatic
secondary alcohol J, the much larger DDd value (0.144 ppm) of I
indicates that pi–pi interactions between the aromatic rings of I
and (S,S)-CSA-2 contribute to the chiral discrimination (Table 4
entries 9–10). In addition, (S,S)-CSA-2 has no proton signals in
the middle and high elds of its 1H NMR spectrum (see the
ESI†), and so it does not interfere with the O–H signals of the
1
guests. Besides H NMR spectroscopy, (S,S)-CSA-2 could chiral
discriminate tertiary alcohols by other heteronuclear NMR
spectroscopy methods. For instance, guests K and L could be
clearly resolved by (S,S)-CSA-2 using 19F NMR spectroscopy
(guest L is a precursor of efavirenz, an important chiral drug
used against HIV) (Table 4, entries 11–12).
We further investigated the inuences of time and temper-
ature on the chiral discrimination of alcohols using guest I as
an example. The results show that time has no inuence on the
chiral discrimination. Lowering the temperature increases the
DDd value but has no effect on the ee value (see the ESI†).
To verify the accuracy of the ee determination method for
tertiary alcohols using (S,S)-CSA-2, the ee values of several
nonracemic samples of guest F were determined by integration
of the O–H signals of guest F. Fig. 2 shows that (S,S)-CSA-2
maintains analytical resolution for the tertiary alcohol F
samples over a wide range of ee values. The linear relationship
between the NMR determined values (based on the O–H signals)
and the HPLC determined values is excellent. The absolute
errors in the ee measurements by NMR and HPLC integrations
are within 2%.
Table 5 Binding constants between (S,S)-CSA-2 and guest A
Host
Guest
Kaa (Mꢁ1
)
Molecular recognition modes
(S,S)-CSA-2
(S,S)-CSA-2
(R)-A
(S)-A
12.4
26.8
To understand the nature of the chiral recognition of (S,S)-CSA-
2 for tertiary alcohols, the recognition modes of (S,S)-CSA-2 to
guest A were studied. We rst investigated the stoichiometry of
a
The Ka values were calculated by the nonlinear least-squares method.
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which could result in stronger steric repulsion. Therefore, (S)-A/
(S,S)-CSA-2 is a sterically preferred complex compared to (R)-A/
(S,S)-CSA-2.
On the basis of the above experimental investigations, the
mechanism of the chiral discrimination of tertiary alcohol A
with (S,S)-CSA-2 was proposed. Each enantiomer of racemic
guest A interacts with chiral (S,S)-CSA-2 to form a 1 : 1 diaste-
reomeric complex via noncovalent interactions. The spatial
differentiations of the two O–H groups in the formed diaste-
reomeric complexes cause a split of the O–H signals of the two
enantiomers of racemic guest A. (S)-A combines with (S,S)-CSA-2
more tightly than (R)-A, which causes the chemical shi of O–H
of (S)-A to be moved more downeld with a larger d value.
Experimental
Materials and methods
Diphenyl urea (TCI Co. Ltd.), diphenyl thiourea (TCI Co. Ltd.),
BINOL (TCI Co. Ltd.), 1-phenylethanol (TCI Co. Ltd.),
(1R,2R,5R)-(+)-2-hydroxy-3-pinanone (TCI Co. Ltd.), (1S,2S,5S)-
(ꢁ)-2-hydroxy-3-pinanone (TCI Co. Ltd.), (1S,2R,5S)-(+)-menthol
(Adamas-beta®), (1R,2S,5R)-(ꢁ)-menthol (Adamas-beta®), 3,5-
di(triuoromethyl)aniline (Adamas-beta®), and (S,S)-1,2-
diphenylethane-1,2-diamine (TCI Co. Ltd.) were used as
received. Other tertiary alcohols and isoselenocyanate were
synthesized by following the literature procedure.21
Fig. 3 A portion of the 500 MHz 2D NOESY spectrum of a solution of
racemic guest A (100 mM)/(S,S)-CSA-2 (100 mM) in C6D6 at 25 ꢀC
(intermolecular correlations of guest A to (S,S)-CSA-2 are circled in
red).
Theoretical calculations
All electronic structure calculations were performed with the
Gaussian09 program.20 The pKDa MSO values were calculated with
the use of the relative determination method, and 4-nitro-
phenol (10.8) was chosen as the reference.18 The gas-phase
acidities of all compounds were calculated using the M06-2X/cc-
pVTZ method, the solvent effects were evaluated with the
IEFPCM model, and the pKa values of all compounds in DMSO
were calculated by DpKa ¼ DG/RT (DpKa and DG are the pKa and
free energy differences between the given compound and the
reference molecule). Computational modeling studies were
performed with the Gaussian09 program.20 The geometries of
the ternary complexes were optimized using the molecular
mechanics method initially and then the DFT method at the
M06-2X/cc-pVTZ level of theory. All geometry optimizations
were carried out in the gas phase. Binding energies and NMR
chemical shis were calculated at the M06-2X/cc-pVTZ level of
theory in benzene solvent with the GIAO method (solvent effects
were evaluated with the IEFPCM model).
Fig. 4 Space-filling representations of the complexes.
Table 6 Calculated d values of guest A and binding energies between
(S,S)-CSA-2 and guest A
General procedure for the synthesis of (S,S)-CSA-2
3,5-Bis(triuoromethyl)aniline (10 g, 43.6 mmol) and anhy-
drous ZnCl2 (1.186 g, 8.7 mmol) were taken in a 50 mL round
bottomed ask. To the mixture, formic acid (10 mL, 267 mmol)
was added drop-wise with constant stirring for 10 min. This
mixture was heated at 70 ꢀC for 5 h and the progress of the
reaction was monitored by TLC. When the reaction was
completed, the mixture was cooled to room temperature and
diluted with ethyl acetate (40 mL). The organic layer was washed
ꢁDG
Guest
d (calcd)a (ppm)
(kcal molꢁ1
)
(R)-A
(S)-A
2.17
2.54
15.8
18.0
a
The chemical shi of O–H of guest A in the guest A/(S,S)-CSA-2
complex.
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with water and brine, and dried over anhydrous Na2SO4. The tertiary alcohols. So, it is especially suitable for chiral discrim-
solvent was removed under reduced pressure and the resulting ination and ee determination of tertiary alcohols.
crude product was puried by recrystallization (in ethanol) to
obtain the corresponding N-formyl derivative (10.66 g, 95%, mp
121–122 ꢀC, lit.22 124–125 ꢀC). A solution of triphosgene (692
Acknowledgements
mg, 2.33 mmol) in dry dichloromethane (5 mL) was added The authors gratefully acknowledge the nancial support from
dropwise under Ar over a period of 1 hour to a reuxing mixture The Key Laboratory of Coal to Ethylene Glycol and Its Related
of formamide (1 g, 3.89 mmol), TEA (2.25 mL, 15.56 mmol), and Technology, National Natural Science Foundation of China (No.
4 A molecular sieves (2 g) in dry dichloromethane (10 mL). Aer 21173212, 21207131), and Fujian Institute of Research on the
the addition, the resulting mixture was reuxed for 4 hours and Structure of Matter, Chinese Academy of Sciences.
then black selenium powder (768 mg, 9.72 mmol) was added
and the mixture was reuxed overnight in the dark. Then, the
mixture was cooled to room temperature and ltered. The
Notes and references
ltrate was collected and concentrated to give a residue, which
was puried by column chromatography (eluting with dry
hexane) to afford isoselenocyanate (0.49 g, 40%). Caution, this
isoselenocyanate is best used directly aer separation because it
is not very stable and must be stored in the dark.
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3,5-Bis(triuoromethyl)phenyl isoselenocyanate (0.64 g, 2
mmol) was added to a solution of (S,S)-1,2-diphenylethane-1,2-
diamine (0.21 g, 1 mmol) in dry dichloromethane (15 mL). The
solution was stirred overnight at room temperature in the dark.
Aer completion, dry hexane (100 mL) was added dropwise. The
solution was stirred for another 3 hours at room temperature
and this produced a lot of white solid, which was ltered off,
washed with hexane and dried under vacuum to afford (S,S)-CSA-
D
2 (0.81 g, 95%). Mp 165–166 ꢀC; ½aꢂ30 ¼ 31.8 g per 100 mL (c ¼ 1.0
1
in CHCl3). H NMR (400 MHz, CDCl3): d ¼ 8.84 (br s, 2H), 7.95
(br s, 2H), 7.73–7.67 (m, 6H), 7.40–7.20 (m, 10H), 6.17 (s, 2H)
ppm; 13C NMR (100 MHz, CDCl3): d ¼ 179.9, 138.1, 136.4, 133.9,
133.6, 133.2, 132.9, 129.3, 128.9, 127.8, 126.8, 124.8, 124.1, 121.4,
120.7, 118.7, 67.6 ppm; 77Se NMR (95 MHz, CDCl3): d ¼ 247 ppm;
ESI-MS: calcd for C32H22F12N4Se2 + H 851.0062, found 851.0073.
General spectroscopic methods for the chiral discrimination
of guests
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18 mmol of the guests and 54 mmol of (S,S)-CSA-2 were mixed in
0.6 mL of C6D6, and the 1H NMR dataꢀwere collected on a Bruker
Avance 400 MHz spectrometer at 25 C.
Conclusions
A chiral bisselenourea was rationally designed and synthesized
to serve as a highly efficient NMR sensor for the enantiodiscri-
mination of various tertiary alcohols. The method employed the
sharply split NMR signals of the hydroxyl hydrogen atoms for ee
determination, giving accurate results with <2% absolute
errors. The study of the chiral resolution mechanism suggests
that the geometrical differentiation of the formed diastereo-
meric complexes enables chiral discrimination of the hydroxyl
1
hydrogen signals of tertiary alcohols in H NMR spectra. This
method can give well-resolved and sharp signals of the hydroxyl
hydrogen atoms of tertiary alcohols with a large chemical shi
nonequivalence. Due to the lack of proton signals of this bis-
1
selenourea in the middle and high elds of the H NMR spec-
trum, it does not interfere with the hydroxyl hydrogen signals of
Chem. Sci.
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