Imidazolinium sulfonate and sulfamate zwitterions as chiral solvating agents for enantiomeric excess calculations

Article abstract of DOI:10.1016/j.tetasy.2011.09.018

The synthesis of enantiopure unsymmetrical N-heterocyclic based zwitterions incorporating imidazolinium and alkylsulfonate or sulfamate groups is described. The desired compounds were prepared in good yields from 1,3-propanesultone or cyclic sulfamidates

Full text of DOI:10.1016/j.tetasy.2011.09.018

Tetrahedron: Asymmetry 22 (2011) 1632–1639
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Tetrahedron: Asymmetry
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Imidazolinium sulfonate and sulfamate zwitterions as chiral solvating
agents for enantiomeric excess calculations
Sobia Tabassum a, , Mazhar Amjad Gilani a,à, René Wilhelm b,
⇑
a Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
b University of Paderborn, Department of Chemistry, Warburgerstrasse 100, 33098 Paderborn, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 July 2011
Accepted 29 September 2011
Available online 1 November 2011
The synthesis of enantiopure unsymmetrical N-heterocyclic based zwitterions incorporating imidazolin-
ium and alkylsulfonate or sulfamate groups is described. The desired compounds were prepared in good
yields from 1,3-propanesultone or cyclic sulfamidates and imidazolines. The imidazolinium based zwit-
terions proved to be versatile chiral solvating agents for Mosher’s acid, alcohols, cyanohydrins, amino
alcohols, nitro alcohols, thiols, and carboxylic acids with very high shifts in the 1H and 19F NMR.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
substituent. Davis and co-workers used them as dual solvent
catalysts in the Fischer esterification. Later in 2004, Ohno12
NMR spectroscopy is a very powerful technique used in differ-
entiating diastereomeric entities. Chiral shift reagents or chiral sol-
vating agents interact with racemic compounds and both
enantiomers can be recognized by NMR spectroscopy. This helps
determine the relative ratio of the two enantiomers (enantiomeric
excess) formed during a reaction and can sometimes also be used
to determine an absolute configuration.1,2 Different chiral shift re-
agents such as the metal complexes of porphyrins,3 cyclodextrins,4
lanthanide complexes,5 and crown ethers6 have also been
exploited.
In recent years, chiral ionic liquids have also been used as chiral
solvating agents.7 Mainly chiral cations have been used in these
experiments7 and recently we were able to show that ionic liquids
with chiral sulfonate and sulfate anions can be applied as chiral
solvating agents.7i,j In order to investigate the potential of
chiral anions further and to combine this with the influence of a
chiral cationic moiety close to the chiral anionic group, it was
decided to prepare zwitterions incorporating imidazolinium and
sulfonate or sulfamate groups. The results are described herein.
To date there have been only a few reports of imidazolium salts
incorporating an anionic substituent, such as a carboxylate,8 sulfo-
nate,9 or amide group.10 Imidazolinium zwitterions containing sul-
fonate or sulfamate groups in the side chain are also known.
In 2002 Davis and co-workers11 reported novel Brønsted acid
ionic liquids based on an imidazolium salt with an alkylsulfonate
reported 1-(1-butyl-l-3-imidazolio) propane-3-sulfonate and
HTFSI (bis(trifluoromethylsulfonyl)amide) as an anhydrous proton
transporter with an ionic conductivity of approximately
10ꢀ2 S cmꢀ1 at 150 °C. Recently, Funabiki et al.13 reported acidic io-
nic liquids for the direct benzylation, allylation, and propargylation
of 1,3-diketones with various alcohols with up to 98% yield.
Cheng and co-workers14 used chiral sulfate and sulfamate imid-
azole zwitterions as precursors for the synthesis of Brønsted acidic
and Brønsted basic chiral ionic liquids (CILs).
In 2006, Shaughnessy8 reported alkylsulfonate imidazolium sil-
ver and palladium imidazol-2-ylidene complexes. Later, in 2007
Hoveyda and co-workers9a reported a chiral imidazolium sulfonate
salt as a bidentate ligand for the synthesis of an NHC–sulfonate sil-
ver complex while very recently Nozaki9b reported a NHC–sulfo-
nate palladium complex.
2. Results and discussion
New enantiopure unsymmetrical imidazolinium zwitterions
bearing alkylsulfonate or sulfamate substituents were prepared
by two main steps (Scheme 1).
Enantiomerically pure (1R,2R)-1,2-diphenylethane-1,2-diamine
1 was treated with 1 equiv of mesitylaldehyde in order to obtain a
mono-substituted diamine. The reaction gave in water the corre-
sponding imine in 99% yield. The NMR spectrum of the imine
showed a mixture of the cis- and trans-isomers of the imine. The
compound was used in the next step with sodium borohydride,
which gave the desired diamine 3 in quantitative yield.
⇑
Corresponding author. Tel.: +49 5251 605766; fax: +49 5251 603245.
E-mail address: rene.wilhelm@uni-paderborn.de (R. Wilhelm).
Current address: Interdisciplinary Research Center in Biomedical Materials,
COMSATS Institute of Information Technology, Defence Road, Off Raiwind Road,
Lahore, Pakistan.
It is well established that diamines undergo facile ring closure
to imidazolines via reaction with an electrophile such as an ortho-
ester.15 A method reported by Genisson16 was followed. Diamine 3
was treated with trimethylorthoformate in the presence of an
à
Current address: Department of Chemical Engineering, COMSATS Institute of
Information Technology, Defence Road, Off Raiwind Road, Lahore, Pakistan.
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.09.018

S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
1633
1. ArCHO, H2O, rt, 16h
2. NaBH4, MeOH, rt, 16h
AcOH, (MeO)3CH
R1
R1
R1
R1
reflux, 1 h, CH3CN
R1
R1
or
or
H2N
NH2
H2N
HN R2
N
N
R2
ArBr, Pd(OAc)2
BINAP, NaOtBu
(MeO)2CHNMe2
120 °C, 1 h
1
1
2
96% 3 R1 = Ph, R2 = CH2Mes
91% 4 R1 = H, R2 = CH2Mes
R = Ph
6
80%
R
1 = Ph, R2 = CH2Mes
R1= H
91% 7 R1 = H, R2 = CH2Mes
R
1 = Ph, R2 = o-Tol
96%
R
1 = Ph, R2 = o-Tol
5
8
80%
Ph
O2S
CH2Cl2, rt, 7 d
O
N
MeN
O
9
S
11
10
O2S
O
O2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
O3S
N
N
Mes
N
N
Mes
Ph
Ph
N
N
Mes
Mes
N
SO3
NMeSO3
81% 12
99% 14
55% 17
Ph
Ph
Ph
N
N
O3S
N
N
N
N
Mes
Mes
N
SO3
NMeSO3
99% 15
81% 13
90% 18
Ph
Ph
N
N
N
SO3
Ph
N
N
95% 16
NMeSO3
53% 19
Scheme 1.
equimolar amount of acetic acid. The product 6 was isolated in 80%
yield. Similarly ent-6 was also synthesized by using the opposite
(1S,2S)-enantiomer of diamine 1 as the starting material.
Monoalkylated diamine 4 was synthesized in one step. The 1,2-
diaminoethane 2 was reacted with mesitylaldehyde in methanol
for 24 h and the imine was reduced in situ by the addition of so-
dium borohydride.17 Monoalkylated diamine 4 was obtained in
91% yield as an oil.
For the cyclization of 4, neat reaction conditions were applied.
Diamine 4 was treated with trimethylorthoformate at 80 °C for
2 h, but there was no desired imidazoline 7 formed. We next
decided to perform the reaction at a higher temperature. For this
purpose dimethoxy-N,N-dimethylformamide was used instead of
trimethylorthoformate Ethylenediamine 4 was heated with dime-
thoxy-N,N-dimethylformamide at 95 °C for 2 h. In order to remove
MeOH and HNMe2, generated as a side product during the reaction,
the temperature was raised to 120 °C for 1 h. Next, a high vacuum
was applied to remove the rest of the MeOH and HNMe2. The
remaining yellow viscous crude product was distilled and product
7 was obtained as a colorless thick liquid in 90% yield, which solid-
ified upon standing.18
atom. The o-substituted aryl ring provides steric bulk for stereo-
control and decreases the electronic character of 8, which was syn-
thesized in two steps as shown in Scheme 1. The monoalkylation of
the diamine was performed by a modified procedure reported by
Grubbs.19 Diamine 1 was heated with palladium acetate, sodium
tert-butoxide, BINAP, and bromotoluene in toluene to form the de-
sired product 5 in 96% yield. The monoalkylated diamine 5 was cy-
clized to product 8 by treatment with trimethylorthoformate.
The imidazolines were quaternized with 1,3-propanesultone 9
and with inexpensive cyclic sulphamidates 10 and 11. The 1,3-pro-
panesultone 9 is commercially available, while 10 and 11 were
synthesized by the following procedure.
The chiral cyclic sulphamidates were synthesized from readily
available cheap chiral pseudoephedrine and prolinol. For the syn-
thesis of 10 and 11, the reported procedure of Cheng and co-work-
ers was used.14 The chiral amino alcohol pseudoephedrine was
treated with thionyl chloride (SOCl2). In the next step the interme-
diate was oxidized with RuCl3/NaIO4 and converted into the de-
sired product 11. However, only trace amounts of product 11
were obtained. Therefore, a procedure as reported by Avenoza20
in 2007 was followed.
Imidazoline 8 is different from the aforementioned imidazo-
lines as now an aromatic ring is directly attached to the nitrogen
Sulfuryl chloride and triethylamine were reacted with prolinol
at low temperature to give sulphamidate 10. The reaction was very

1634
S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
much dependent on the purity of the sulfuryl chloride. The desired
product 10 was obtained in 66% yield, when 1.5 equiv of sulfuryl
chloride were used in the presence of 4 equiv triethylamine at
ꢀ20 to 0 °C for 4 h. Pseudoephedrine based chiral cyclic sulpham-
idate 11 was also synthesized by applying the same conditions
with 66% yield.
Imidazolinium zwitterions bearing sulfonate or sulfamate
groups were synthesized by ring-opening reactions of the cyclic
sulfates and sulfamidates. Imidazolinium zwitterions 12 and 14,
bearing sulfonate or sulfamidate groups, were synthesized from
6. Imidazolinium zwitterion 12 contains its chirality only in the
backbone, while 14 and 17, prepared from ent-6, have stereogenic
centers both in the backbone as well as in the side arm. Imidazo-
quaternization reaction was performed in CH2Cl2 and in acetone
at rt. An excellent yield of 99% was obtained, when 6 was quatern-
ized with chiral cyclic sulphamidate 10 (Scheme 1).
The imidazolinium zwitterion 15 was prepared by the reaction
of ent-6 (4S,5S-4,5-diphenyl-1-(2,4,6-trimethylbenzyl)-1H-imidaz-
oline) with 10 in 99% yield. It was synthesized to explore matched/
mismatched influences. The depicted inner salt 15 is a diastereo-
mer of 14.
Chiral imidazolinium zwitterions 16 and 18 were synthesized
by the reaction of achiral imidazoline and chiral cyclic sulphami-
dates with excellent yields of 95% and 90%, respectively (Scheme 1).
The aryl substituted zwitterion 13 was prepared by reacting 1-ary-
limidazoline 8 with 9 in 81% yield, while 19 was isolated from 8
and cyclic sulphamidate 11 in CH2Cl2 in 53% yield.
line
6 was stirred with a cyclic sulfonate or sulphamidate.
Zwitterion 12 was isolated in 81% yield in acetone with 2 equiv
of 1,3-propane sultone, while for the synthesis of imidazolinium
zwitterions 14 and 17, 1.5 equiv of reactants were used. The
The newly synthesized zwitterions were evaluated as chiral sol-
vating agents. The zwitterions were mixed with
a-(trifluoro-
methyl)benzyl alcohol 20 in a 1:1 ratio and a splitting of the CF3
Table 1
19F-Chemical shifts d of 2,2,2-trifluoro-1-phenyl ethanol 20 in ppm and resolution
D
d values in Hz (378 MHz 19F NMR)
Entry
1
Zwitterion
—
Solvent
CDCl3
d (ppm)
ꢀ78.88
19F
D
d (Hz)
0
Ph
N
N
Mes
2
CDCl3
ꢀ78.55/ꢀ78.52
11.3
NMeSO3
18
N
N
Mes
N
3
4
CDCl3
CDCl3
ꢀ78.49/ꢀ78.46
ꢀ78.48/ꢀ78.52
11.3
17
SO3
16
Ph
Ph
N
N
Mes
Mes
N
SO3
15
C7D8
CDCl3
CD2Cl2
CD3CN
CD3OD
ꢀ77.61/ꢀ77.53
ꢀ78.50/ꢀ78.54
30
15
5.7
0
Ph
Ph
ꢀ78.21/ꢀ78.23
ꢀ77.38/ꢀ77.38
ꢀ77.96/ꢀ77.96
5
6
N
N
N
SO3
0
14
C7D8
CDCl3
ꢀ77.54/ꢀ77.52
ꢀ78.49/ꢀ78.51
0
7.6
Ph
Ph
N
O3S
N
Mes
12
Ph
Ph
N
O3S
N
7
8
CDCl3
ꢀ78.54/ꢀ78.53
3.8
13
C7D8
CDCl3
ꢀ77.54/ꢀ77.53
ꢀ78.57/ꢀ78.53
5.7
15
Ph
Ph
Ph
Ph
N
N
Mes
NMeSO3
17
CDCl3
CD2Cl2
CD3CN
CD3OD
ꢀ78.72/ꢀ78.66
ꢀ78.42/ꢀ78.39
20.1
11
0
0
Ph
Ph
ꢀ77.46/ꢀ77.46
ꢀ77.96/ꢀ77.96
N
N
9
NMeSO3
19

S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
1635
group in the 19F spectra was observed. The results are summarized
in Table 1.
cyanohydrin had a split with a value of 40 Hz (Table 2, entry 3).
Norephedrine was also tested and its methyl group was split with
a value of 4 Hz while the proton of the carbon bearing a hydroxyl
The 19F spectra were recorded for the mixtures of alcohol and
zwitterions 14 and 19 in different solvents. Compound 14 showed
the highest splitting of 30 Hz in toluene. No stereodiscrimination
for the CF3 group was observed in CD3CN and CD3OD solvents from
either zwitterion. In CDCl3, zwitterion 14 showed a splitting of
15 Hz, while 19 showed a splitting of 22 Hz. It was not possible
to measure the splitting of 19 in toluene due to its insolubility.
The results obtained from screening different solvents show, that
the more polar the solvents, the weaker the hydrogen bonds be-
tween the host and guest molecules were. For further experiments,
CDCl3 was chosen as the solvent (Fig. 1).
Table 2
1H NMR (400 MHz) of racemic compounds in the presence of enantiopure zwitterion
19 in CDCl3
Entry
1
Compounds
d (ppm)
d (ppm) with 19
1H
Dd (Hz)
H
Ph
CF3
5.02
5.02/4.89
52 (CH)
OH
20
The maximum splitting displayed by the zwitterions 18 and 16,
with stereogenic centers at the side arms, was 11 Hz (Table 1, en-
tries 2 and 3). Sulfonate based zwitterions 12 and 13 showed a
poor stereodiscrimination (Table 1, entries 6 and 7).
H
OH
OH
2
8.00
8.03/8.01
8.0 (CH)
Zwitterion 19 was also mixed with Mosher’s acid 26 and the
chemical shift difference of the CF3 group was 26 Hz in CDCl3.
The CF3 peak of the acid split from ꢀ71.62 to ꢀ72.43/ꢀ72.36.
H
Zwitterion 19 gave the best results with
a-(trifluoro-
21
methyl)benzyl alcohol 20. Therefore, this was selected for further
investigation.
H
Ph
CN
Due to the importance of enantioenriched compounds such as
alcohols, cyanohydrins, amino alcohols, nitro compounds, carbox-
ylic acids and so on, there is a constant need to examine their enan-
tiomeric excess after asymmetric synthesis. The racemic
compounds were mixed with 19 and the chemical shift differences
in the 1H NMR were recorded. The results obtained were satisfac-
tory and are summarized in Table 2.
3
4
5.39
5.72/5.62
40 (CH)
OH
22
4.46
0.90
4.48/4.46
0.90/0.89
8 (CH)
4 (CH3)
HO
H
CH3
Ph
NH2
The methine proton of
a splitting of 52 Hz. BINOL interacted with 19 and the aromatic –
a-trifluoromethyl benzyl alcohol showed
23
4.72
1.50
4.69/4.53
1.51/1.49
64 (CH)
8 (CH3)
H
CH showed
a
baseline separation of 8 Hz. The a-proton of
H3C
OH
5
6
NO2
24
mg474d.019.esp
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
H
Ph
Ph
3.23
3.23/3.20
12 (CH)
H
COOH
CF
3
OH
25
COOH
20
F3C OCH3
7
8
3.56
5.35
3.42/3.33
5.21/5.09
36 (CH3)
48 (CH)
26
H
Ph
Ph
Ph
COOH
Br
-78.45
-78.50
-78.55
-78.60
-78.65
-78.70
-78.75
-78.80
-78.85
-78.90
-78.95
-79.00
-79.05
Chemical Shift (ppm)
st111.019.esp
27
H
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
COOH
Ph
Ph
H
9
5.19
4.06
5.00/4.85
3.98/3.93
60 (CH)
20 (CH)
CF3
OH
N+
OH
28
H
N
O-
N
S
O
O
COOH
OH
19
20
10
11
29
H
2.28
1.56
2.06/2.00
1.40/1.31
24 (SH)
36 (CH3)
H3C
COOH
-78.20
-78.25
-78.30
-78.35
-78.40
-78.45
-78.50
-78.55
-78.60
-78.65
-78.70
-78.75 -78.80
SH
Chemical Shift (ppm)
30
Figure 1. 19F-Spectra of 20 in the presence of 19 in CDCl3.

1636
S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
group was split to 8 Hz. The methine proton of a nitroalcohol
exhibited a chiral shift non-equivalence of 68 Hz. The methyl
group of a nitroalcohol also showed a chiral discrimination with
a magnitude of 8 Hz.
and 26 Hz of the CF3 group were observed, respectively. In addi-
tion, the chemical shift differences of the protons of several com-
pounds were at an excellent level.
A series of racemic carboxylic acids was screened for observing
the baseline separation of characteristic protons, thus differentiat-
ing the two enantiomers. The proton, attached to the stereogenic
4. Experimental
4.1. General remarks
center of
a-cyclohexylphenyl acetic acid showed a splitting of
12 Hz, -bromophenyl acetic acid of 48 Hz and
a
a
-hydroxy phenyl
Compounds 1, ent-1, 2, and 9 were purchased from commercial
sources. Melting points are uncorrected. Infrared spectra were re-
corded on a Bruker Vektor 22 FTIR spectrometer. With KBr pellets
in case of solid compounds and as thin films between NaCl plates
in cases of oils and liquids. 1H NMR spectra were acquired at ambi-
ent temperature on a Bruker AMX 400 (400 MHz) and a Bruker AC
200F (200 MHz) in deuterated solvents as stated. 13C NMR spectra
were recorded at ambient temperature on a Bruker AMX 400
(100 MHz) and a Bruker AC 200F (50 MHz) in deuterated solvents.
19F NMR spectra were recorded at ambient temperature on a Bru-
ker AMX 400 (378 MHz). Mass spectra (EI) were recorded with a
Hewlett Packard 5989B at 70 eV. Mass spectra (ESI) were recorded
on Hewlett Packard MS LC/MSD Series 1100 MSD. High resolution
mass spectra were measured on a Bruker Daltonik Tesla-Fourier
Transform-Ion Cyclotron Resonance-Masspectrometer with Elec-
trospray-Ionization by Dr. Dräger at the Institute of Organic Chem-
istry, University of Hanover. Elemental analyses were carried out
by the Microanalytical Laboratory of the Institut fur
Pharmazeutische Chemie der Technische Universitat
Braunschweig on ‘‘Elemental Analyzer’’ Model 1106 from the ‘Carlo
Erba Instrumentazione’ company. Flash column chromatography21
was performed on Sorbisil C-60. Reactions were monitored by TLC
with Merck Silica gel 60 F254 plates. THF and diethyl ether were
distilled from sodium benzophenone ketyl. Toluene was distilled
from sodium. CH2Cl2 and acetonitrile were distilled from calcium
hydride.
acetic acid of 60 Hz. The splitting was lowered to 20 Hz, when a hy-
droxyl group was at the b-carbon. The baseline separation was
clear enough to differentiate between both enantiomers. The
methyl group of the Mosher acid also showed a strong interaction
and the diastereomeric methoxy groups were spaced apart with a
splitting value of 36 Hz. Another member of the carboxylic acid
series that contains a thiol group at the b-carbon can also be differ-
entiated as the proton of the SH group split to 24 Hz and the
methyl to 36 Hz (Table 2, entry 11).
The mode of interaction of the zwitterions with different guest
molecules is via the formation of hydrogen bonds. It is assumed
that the negative part of the zwitterion forms a hydrogen bond
with the acidic portion of the guest molecules. Due to the differ-
ences in pKa, it is unlikely that in case of the carboxylic acids, a
complete proton transfer to the zwitterions occurs (Fig. 2).
3. Conclusion
Newly synthesized zwitterions incorporating an imidazolinium
unit and a sulfonate or sulfamate unit have been screened for their
ability to resolve spectroscopically different racemic compounds
such as alcohols, cyanohydrins or carboxylic acids. The zwitterion
19 proved to be a versatile chiral discriminating agent for different
types of racemic compounds. It interacted with
methyl)benzyl alcohol and Mosher acid and splittings of 22 Hz
a-(trifluoro-
mg-500b.010.esp
0.25
4.2. (S)-Tetrahydro-3H-pyrrolo[1,2-c][1,2,3]oxathiazolea1,1-
dioxide 10
COOH
H
0.20
0.15
0.10
0.05
0
Prepared from
a mixture of (S)-(+)-2-pyrrolidinemethanol
(104 mg, 1.04 mmol, 1 equiv), triethylamine (0.575 mL, 4.13 mmol,
4 equiv), and sulphuryl chloride (0.125 mL, 1.55 mmol, 1.5 equiv)
at ꢀ20 to 0 °C in 4 h. The solvent was removed and the residue
was purified by FCC on silica gel (ethyl acetate/petrol ether
25
40:60) to afford sulfamidate 10 as
a white solid (102 mg,
0.62 mmol, 66% yield). Spectroscopic data were consistent with
the literature values.14
1.00
3.20
4.3. (4R,5R)-3,4-Dimethyl-5-phenyl-1,2,3-oxathiazolidine-2,2-
3.80
3.75
3.70
3.65
3.60
3.55
3.50
3.45
3.40
3.35
3.30
3.25
3.15
3.10
3.05 3.00
dioxide 11
Chemical Shift (ppm)
mg-501b.010.esp
0.15
0.10
0.05
0
Prepared
0.61 mmol, 1 equiv), triethylamine (0.340 mL, 2.44 mmol, 4 equiv),
and sulphuryl chloride (74
in 4 h. The solvent was removed and the residue was purified by
FCC on silica gel (ethyl acetate/petrol ether 40:60) to afford sulfam-
idate 11 as a white solid (92 mg, 0.402 mmol, 66% yield). Spectro-
scopic data were consistent with the literature values.22
from
(1R,2R)-(ꢀ)-pseudoephedrine
(100 mg,
Ph
Ph
COOH
H
+
N
N
N
l
L, 0.91 mmol, 1.5 equiv) at ꢀ20 to 0 °C
-
O
S
O
O
19
25
4.4. (4R,5R)-4,5-Diphenyl-1-(2,4,6-trimethylbenzyl)-1H-
imidazoline 6
4.4.1. (1R,2R)-1,2-Diphenyl-N1-(2,4,6-trimethylbenzylidene)-
ethane-1,2-diamine
0.99
3.240
1.00
3.215
3.245
3.235
3.230
Chemical Shift (ppm)
3.225
3.220
3.210
3.205
2,4,6-Trimethylbenzylaldyde (0.58 mL, 3.96 mmol, 1 equiv) and
Figure 2. 1H-Spectra of 25 in the presence of 19 in CDCl3.
(+)-(1R,2R)-1,2-diphenyl-1,2-ethylenediamine
1
(841 mg,

S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
1637
3.969 mmol, 1 equiv) were stirred in water (15 mL) overnight. The
mixture was extracted three times with CH2Cl2 and the solvent
was removed to afford the product as a cis/trans mixture of a yel-
low semisolid (1.35 g, 3.96 mmol, 99% yield). The product was used
in the next step without purification.
120 °C for 1 h. The volatiles were removed under vacuum and the
remaining yellow viscous liquid was distilled under vacuum (108–
109 °C/0.01 mmHg) to give a colorless liquid, which solidified upon
standing as a white solid (3.2 g 15.87 mmol, 90% yield). The spectro-
scopic data were consistent with the literature values.23
4.4.2. (1R,2R)-1,2-Diphenyl-N1-(2,4,6-trimethylbenzyl)ethane-
1,2-diamine 3
4.6. (1R,2R)-1,2-Diphenyl-N1-(o-tolyl)ethane-1,2-diamine 5
(1R,2R)-1,2-Diphenyl-N1-(2,4,6-trimethylbenzylidene)ethane-
1,2-diamine (1.24 g, 3.6 mmol, 1 equiv) was dissolved in dry meth-
anol (60 mL) under a stream of nitrogen and NaBH4 (112 mg,
10.8 mmol, 3 equiv) was added slowly. After stirring at rt over-
night, water was carefully added and the methanol was removed
under reduced pressure. Ethyl acetate was added and the organic
layer was washed three times with a solution of 1 M HCl. The aque-
ous layer was then basified with pellets of NaOH and extracted
three times with CH2Cl2. The combined organic layers were dried
(Na2SO4) and the solvent was removed to give a yellow oil (1.2 g,
3.49 mmol, 97% yield). The product was used in the next step with-
out purification.
Under an inert atmosphere, palladium acetate (0.526 mg,
0.235 mmol, 5 mol %), BINAP (293 mg, 0.47 mmol, 10 mol %), and
sodium t-butoxide (1.36 g, 14.13 mmol) were added to toluene
and stirred for 20 min. (R,R)-Diphenylethylenediamine (1.00 g,
4.71 mmol, 1 equiv) and 2-bromotoluene (805 mg, 4,71 mmol,
1 equiv) were then added and the solution was heated to 100 °C
for 16 h. The solution was cooled to ambient temperature, diluted
with hexane. (75 mL) and filtered through a plug of silica. The silica
was washed with a CH2Cl2/MeOH mixture to elute the crude prod-
uct. The filtrate was concentrated and dissolved in CH2Cl2. Next,
12 M HCl was added and the organic layer was separated. The
water layer was washed (2 ꢂ CH2Cl2) and the organic layer was
discarded. After that, the water layer was cooled with an ice bath
and carefully basified by the dropwise addition of concentrated
NaOH until it became strongly basic (pH 14), followed by extrac-
tion with CH2Cl2. The desired product was obtained after removing
the solvent as a white solid (1.37 g, 4.5 mmol, 96% yield). mp:
4.4.3. (4R,5R)-4,5-Diphenyl-1-(2,4,6-trimethylbenzyl)-1H-
imidazoline 6
Prepared from diamine 3 (1.00 g, 2.9 mmol, 1 equiv), trimethyl
orthoformate (0.3 mL, 3.1 mmol, 1.06 equiv), and acetic acid
(0.176 mL, 3.1 mmol, 1.06 equiv) in CH3CN by refluxing for 1 h un-
der an inert atmosphere. Dihydroimidazole 6 was purified with
94 °C, ½a 2D2
ꢁ
¼ þ93:4 (c 1, CH2Cl2); 1H NMR (CDCl3, 200 MHz):
d = 7.40–7.03 (m, 10H), 6.89 (dd, J = 7.3, 0.6 Hz, 1H), 6.81–6.65
(m, 1H), 6.49–6.33 (m, 1H), 6.14–5.98 (m, 1H), 4.41 (d, J = 4.3 Hz,
1H), 4.25 (d, J = 4.3 Hz, 1H)), 2.15 (s, 3H), 1.65 (br s, 2H); 13C
NMR (CDCl3, 50 MHz): d = 145.3, 142.8, 141.6, 129.8, 128.64,
128.4, 127.5, 127.3, 126.9, 126.8, 122.3, 116.4, 110.9, 63.3, 61.3,
17.7. IR (KBr): 3438, 3387, 3384, 3024, 2909, 2859, 2738, 1909,
1777, 1606, 1512, 1449, 1351, 1319, 1209, 1124, 1048, 1025,
926, 902, 844, 789, 767, 744, 574, 531, 479, 443 cmꢀ1; MS (EI):
m/z 261 (M++H, 10%), 229 (15), 203 (25), 144 (25), 130 (100),
100 (50), 86 (50), 74 (40), 57 (45); HRMS (ESI): Calcd for
FCC (MeOH/CH2Cl2 5:95) as
a light yellow solid (712 mg,
2.03 mmol, 70% yield). mp: 112 °C; ½a D22
ꢁ
¼ þ17:8 (c 1, CH2Cl2); 1H
NMR (CDCl3, 200 MHz): d = 7.29–7.18 (m, 10H), 6.89 (d,
J = 1.6 Hz, 1H), 6.77 (s, 2H), 4.92 (dd, J = 9.5, 1.6 Hz, 1H), 4.03 (dt,
J = 21.7, 11.2 Hz, 3H), 2.18 (s, 3H), 2.10 (s, 6H); 13C NMR (CDCl3,
50 MHz): d = 155.1, 143.3, 140.7, 137.8, 137.5, 129.3, 128.9,
128.5, 128.48, 128.0, 127.2, 126.6, 80.1, 74.4, 44.6, 20.9, 19.7; IR
(KBr) 3426, 3085, 3032, 2974, 2944, 2919, 2860 2800, 1950,
1880, 1880, 1748, 1668, 1597, 1452, 1396, 1303, 1245, 1219,
1153, 1074, 1029, 1219, 993, 904, 858, 797, 772, 751, 699, 626,
562, 499, 447 cmꢀ1; MS (EI): m/z 354 (M+, 50%), 238 (2), 221
(75), 133 (40), 117 (15), 91 (100), 77 (5), 51 (2); HRMS (ESI): Calcd
for C25H27N2: 355.2174. Found: 355.2170.
C14H33N2O2: 261.2542. Found: 261.2546.
4.7. (4R,5R)-4,5-Diphenyl-1-o-tolyl-1H-imidazoline 8
Prepared from diamine 5 (362 mg, 1.2 mmol, 1 equiv), trimethyl
4.5. 1-(2,4,6-Trimethylbenzyl)-1H-imidazoline 7
orthoformate (0.140 mL, 1.27 mmol, 1.06 equiv) and acetic acid
(0.72 lL, 1.27 mmol, 1.06 equiv) in CH3CN by refluxing for 1 h under
4.5.1. N1-(2,4,6-Trimethylbenzyl)ethane-1,2-diamine 4
an inert atmosphere. The dihydroimidazole 8 was obtained as a light
yellow solid (300 mg, 0.96 mmol, 80% yield) after FCC (MeOH/
CH2Cl2, 5:95). 1H NMR (CDCl3, 200 MHz): d = 7.36 (d, J = 1.8 Hz, 1H,
ArH), 7.34–7.11 (m, 10H), 7.10–7.01 (m, 1H), 6.99–6.90 (m, 2H),
6.84 (dd, J = 5.3, 4.0 Hz, 1H), 5.13 (dd, J = 9.1, 1.8 Hz, 1H), 4.82 (d,
J = 9.1 Hz, 1H), 2.24 (s, 3H); 13C NMR (CDCl3, 50 MHz): d = 161.6,
144.7, 139.5, 137.8, 130.1, 128.8, 128.3, 128.2, 127.6, 127.5, 127.3,
126.9, 122.6, 117.3, 110.9, 63.3, 57.9, 17.7; MS (EI): m/z 312 (M+,
20%), 196 (100), 118 (25), 104 (6), 91 (40), 77 (25), 65 (25), 51 (10);
HRMS (ESI): Calcd for C22H21N2: 313.1705. Found: 313.1694.
A round-bottom flask was charged with absolute methanol and
ethylenediamine (10 mL, 150 mmol, 2 equiv), and then cooled in
an ice bath. A solution of 2,4,6-trimethylbenzylaldyde (11.0 mL,
75 mmol, 1 equiv) in absolute methanol (l20 mL) was added via a
dropping funnel. The resulting solution was stirred for 24 h at rt
and then the solution was cooled again in an ice bath and solid so-
dium borohydride (5.6 g, 150 mmol) was added in 5–7 portions
over 20 min. The reaction was allowed to warm to rt and stirred
for an additional 24 h. Next, water was added carefully and the
methanol was removed under reduced pressure. The aqueous layer
was then basified with pellets of NaOH and extracted three times
with CH2Cl2. The combined organic layers were dried (Na2SO4)
and the solvent was removed to give a yellow oil. The excess of
ethylenediamine was removed at low pressure and the desired
product was obtained in 91% as an oil. Spectroscopic data were
consistent with the literature values.23
4.8. General procedure for the quaternization of imidazoline
A solution of imidazoline (1 equiv) in CH2Cl2 or acetone was
treated with sulfonate or sulphamidate (1.5–2 equiv) for 5–7 d at
rt. Nextm the solvent was removed under reduced pressure and
the imidazolinium zwitterion was purified by FCC and obtained
as a white solid.
4.5.2. 1-(2,4,6-Trimethylbenzyl)-1H-imidazoline 7
N-(2,4,6-Trimethylbenzyl)ethylenediamine
4
(3.40 g, 17.64
4.8.1. 3-((4R,5R)-4,5-Diphenyl-1-(2,4,6-trimethylbenzyl)-4,5-
dihydro-1H-imidazol-3-ium-3-yl)propane-1-sulfonate 12
Prepared from (4R,5R)-4,5-diphenyl-1-(2,4,6-trimethylbenzyl)-
1H-imidazoline 3 (532 mg, 1.5 mmol, 1 equiv) and cyclic sulfonate
mmol, 1 equiv) and N,N-dimethylformamide dimethylacetal
(2.6 mL, 19.4 mmol, 1.1 equiv) were heated at 95 °C for 2 h. In order
to remove MeOH and HNMe2, the residue was further heated to

1638
S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
esters 1,3-propane sultone 9 (367 mg, 3.0 mmol, 2 equiv) in ace-
tone for 5 d. The residue was purified by FCC (MeOH/CH2Cl2
10:90) to afford the imidazolinium zwitterion 12 as a white solid
the imidazolinium zwitterion 15 as a white solid (1.15 g,
2.23 mmol, 99% yield); mp: 296 °C, ½a D22
ꢁ
¼ ꢀ13:5 (c 1, CH2Cl2); 1H
NMR (CDCl3, 200 MHz): d = 9.47 (s, 1H), 7.41–7.29 (m, 5H), 7.22–
7.14 (m, 2H), 7.09 (td, J = 3.2, 5.9 Hz, 3H), 6.76 (s, 2H), 5.54–5.46
(m, 1H), 5.43 (d, J = 8.3 Hz, 1H), 4.37–4.22 (m, 2H), 4.14–3.97 (m,
1H,), 3.80–3.37 (m, 3H), 3.03–2.83 (m, 1H), 2.24 (s, 3H), 2.14–
2.01 (m, 1H), 2.01–1.93 (m, 1H), 1.87 (s, 6H), 1.80–1.67 (m, 1H),
1.32–1.20 (m, 1H); 13C NMR (CDCl3, 50 MHz): d = 160.2, 138.5,
138.2, 134.4, 133.8, 129.6, 129.5, 129.3, 129.2, 127.5, 124.8, 73.0,
72.8, 55.3, 51.5, 50.5, 44.8), 29.8, 24.9, 20.8, 19.8; IR (KBr): 3452,
2963, 1634, 1496, 1457, 1379, 1197, 1109, 1037, 977, 852, 757,
702, 634, 554 cmꢀ1; MS (ESI): m/z = 540.8 [M++Na]; HRMS (ESI):
Calcd for C30H35N3O3NaS: 540.2306. Found: 540.2297.
(579 mg, 1.21 mmol, 81% yield). mp: >350 °C; ½a D22
¼ þ105:6 (c 1,
ꢁ
CH2Cl2); 1H NMR (CDCl3, 200 MHz): d = 9.55 (s, 1H), 7.45–6.99
(m, 12H), 6.69 (s, 2H), 5.00 (dd, J = 25.3, 11.9 Hz, 2H), 4.41 (dd,
J = 19.8, 11.8 Hz, 2H), 3.45–3.20 (m, 1H), 3.08 (dd, J = 8.6, 6.1 Hz,
1H), 2.92 (t, J = 6.8 Hz, 2H), 2.14 (s, 3H), 2.10–1.96 (m, 2H), 1.90
(s, 6H); 13C NMR (CDCl3, 50 MHz): d = 159.9, 158.1, 138.9, 138.4,
135.22, 134.9, 130.2, 130.1, 130.1, 129.8, 127.8, 127.2, 124.8,
73.5, 72.5, 53.8, 48.3, 45.6, 22.6, 21.1, 19.8. IR (KBr): 3442, 3034,
2923, 1638, 1496, 1457, 1207, 1039, 758, 701, 621, 523 cmꢀ1
;
(ESI): m/z = 499.2031 [M++Na]; HRMS (ESI): Calcd for C28H33N2O2S:
477.2212. Found: 477.2201.
4.8.5. (S)-2-((1-(2,4,6-Trimethylbenzyl)-4,5-dihydro-1H-
imidazol-3-ium-3-yl)ethyl)pyrrolidine-1-sulfonate 16
4.8.2. (S)-2-((4R,5R)-4,5-Diphenyl-1-(2,4,6-trimethylbenzyl)-4,
5-dihydro-1H-imidazol-3-ium-3-yl)methyl)pyrrolidine-1-
sulfonate 14
Prepared from imidazoline 3 (714 mg, 1.5 mmol, 1 equiv) and
sulphamidate 10 (367 mg, 2.4 mmol, 1.6 equiv) in CH2Cl2 for 7 d.
The residue was purified by FCC (MeOH/CH2Cl2 10:90) to afford
Prepared from imidazoline 7 (413 mg, 2.04 mmol, 1 equiv) and
sulphamidate 10 (500 mg, 3.06 mmol, 1.5 equiv) in CH2Cl2 for 7 d.
The residue was purified by FCC (MeOH/CH2Cl2 15:85) to afford the
imidazolinium zwitterion 16 as a white solid (709 mg, 1.39 mmol,
95% yield). mp: >350 °C, ½a D22
ꢁ
¼ þ40:3 (c 1, CH2Cl2); 1H NMR
the imidazolinium zwitterion 14 as
a
white solid (765 mg,
¼ þ129:7 (c 1, CH2Cl2);
(CDCl3, 200 MHz): d = 8.31 (s, 1H), 6.74 (s, 2H), 4.60 (q,
J = 14.6 Hz, 2H), 4.04 (dd, J = 20.0, 9.6 Hz, 1H), 3.96–3.73 (m, 2H),
3.72–3.50 (m, 2H), 3.48–3.29 (m, 2H)), 3.27–3.07 (m, 2H)), 2.21
(s, 6H)), 2.13 (s, 3H), 2.07–1.83 (m, 1H)), 1.83–1.67 (m, 1H)), 1.63
(dd, J = 13.3, 6.3 Hz, 1H)), 1.49–1.25 (m, 1H)); 13C NMR (CDCl3,
50 MHz): d = 157.9, 138.6, 137.9, 129.6, 125.7, 56.9, 52.4, 50.1,
49.5, 48.0, 45.8, 29.3, 24.6, 20.8, 19.7; IR (KBr) 3455, 2964, 1651,
1449, 1278, 1190, 1124, 1039, 981, 853, 730, 689, 633, 581,
471 cmꢀ1; MS (ESI): m/z = 388 [M++Na]; HRMS (ESI): Calcd for
1.48 mmol, 99% yield). mp: 295 °C; ½a D22
ꢁ
1H NMR (CDCl3, 400 MHz): d = 9.85 (s, 1H), 7.42–7.32 (m, 5H),
7.29–7.25 (m, 3H), 7.17–7.11 (m, 2H), 6.71 (s, 2H), 5.44 (d,
J = 10.8 Hz, 1H), 5.26 (d, J = 14.9 Hz, 1H), 4.58 (d, J = 14.7 Hz, 1H),
4.41–4.35 (m, 1H), 4.33 (d, J = 10.8 Hz, 1H) 3.87 (dd, J = 4.0,
14.2 Hz, 1H), 3.61 (td, J = 7.5, 10.7 Hz, 1H), 3.24 (ddd, J = 5.0, 6.4,
11.0 Hz, 1H), 2.77 (dd, J = 9.1, 14.2 Hz, 1H), 2.20 (s, 3H), 2.12–
2.03 (m, 1H), 2.02–1.92 (m, 1H), 1.89 (s, 6H), 1.61–1.48 (m, 1H),
1.42–1.32 (m, 1H); 13C NMR (CDCl3, 100 MHz): d = 161.4, 138.5,
138.2, 135.5, 134.9, 129.7, 129.6, 129.5, 129.5, 128.6, 127.5,
125.1, 76.6, 72.5, 59.8, 50.3, 50.2, 45.17, 29.9, 24.8, 20.9, 19.7. IR
(KBr): 3449, 3035, 2960, 2870, 1735, 16370, 1497, 1457, 1372,
1198, 1112, 852, 759, 703, 636, 581, 553 cmꢀ1; MS (ESI): m/
z = 540 [M++Na]; HRMS (ESI): Calcd for C30H35N3O3S: 518.2477.
Found: 518.2474, Calcd for C30H35N3O3NaS: 540.2297. Found:
540.2290.
C18H28N3O3S: 366.1815. Found: 366.1838, Calcd for C18H27N3O3-
NaS: 388.1671. Found: 388.1664.
4.8.6. Methyl((1R,2R)-1-phenyl-1-(1-(2,4,6-trimethylbenzyl)-
4,5-dihydro-1H-imidazol-3-ium-3-yl)propan-2-yl)sulfonate 18
Prepared from imidazoline 7 (297 mg, 1.46 mmol, 1 equiv) and
sulphamidate 11 (500 mg, 2.2 mmol, 1.5 equiv) in CH2Cl2 for 7 d.
The residue was purified by FCC (MeOH/CH2Cl2 10:90) to afford
the imidazolinium zwitterion 18 as
a white solid (596 mg,
4.8.3. ((1R,2R)-1-((4S,5S)-4,5-Diphenyl-1-(2,4,6-
1.38 mmol, 95% yield). mp: 299 °C; ½a D22
ꢁ
¼ þ35:5 (c 1, CH2Cl2); 1H
trimethylbenzyl)-4,5-dihydro-1H-imidazol-3-ium-3-yl)-1-
phenylpropan-2-yl)(methyl)sulfamate 17
NMR (CDCl3, 200 MHz): d = 10.16 (s, 1H), 7.20–7.46 (m, 5H), 6.87
(s, 2H)), 4.70–4.98 (m, 3H), 4.55 (d, J = 4.22 Hz, 1H), 3.34–3.90
(m, 4H), 2.36 (s, 6H), 2.25 (s, 3H), 2.18 (s, 3H), 1.38 (d,
J = 6.91 Hz, 3H); 13C NMR (CDCl3, 50 MHz): d = 158.9, 138.8,
137.9, 133.8, 129.7, 128.7, 128.6, 125.8, 66.9, 53.7, 48.4, 46.3,
31.8, 20.9, 20.0, 14.1. IR (KBr): 3457, 2969, 2236, 1641, 1456,
1379, 1197, 1097, 1036, 943, 923, 876, 747, 591 cmꢀ1; MS (ESI):
m/z = 451.7 [M++Na]; HRMS (ESI): Calcd for C23H32N3O3S:
430.2164. Found: 430.2147, Calcd for C23H31N3O3NaS: 452.1984.
Found: 452.1976.
Prepared from imidazoline ent-6 (825 mg, 2.33 mmol, 1 equiv)
and sulphamidate 11 (846 mg, 3.72 mmol, 1.6 equiv) in CH2Cl2
for 7 d. The residue was purified by FCC (MeOH/CH2Cl2 10:90) to
afford the imidazolinium zwitterion 18 as a white solid (745 mg,
1.28 mmol, 55% yield). mp: >450 °C; ½a D22
¼ ꢀ117:8 (c 1, CH2Cl2);
ꢁ
1H NMR (CDCl3, 200 MHz): d = 11.14 (s, 1H), 7.48–7.33 (m, 9H),
7.29–7.20 (m, 2H), 7.02–6.86 (m, 4H), 6.75 (s, 2H), 5.15 (d,
J = 14.8 Hz, 1Hr), 4.95 (tt, J = 6.9, 3.3 Hz, 1H), 4.65 (d, J = 14.7 Hz,
1H), 4.37 (dd, J = 19.6, 8.4 Hz, 2H), 3.81 (d, J = 2.3 Hz, 1H), 2.21 (s,
3H), 2.11 (s, 3H)), 1.94 (s, 6H), 1.25 (d, J = 7.0 Hz, 3H). 13C NMR
(CDCl3, 50 MHz): d = 159.6, 138.9, 138.1, 135.4, 134.9, 132.2,
130.1, 130.0, 129.8, 129.7, 129.3, 128.9, 128.5, 126.8, 126.7,
124.1, 73.6, 70.1, 65.4, 54.5, 45.8, 32.0, 20.8, 19.6, 14.5; IR (KBr):
34540, 2922, 1628, 1456, 1203, 1036, 862, 756, 700, 669,
595 cmꢀ1; MS (ESI): m/z = 604 [M++Na]. HRMS (ESI): Calcd for
4.8.7. 3-((4R,5R)-4,5-Diphenyl-1-(o-tolyl)-4,5-dihydro-1H-
imidazol-3-ium-3-yl)propane-1-sulfonate 13
Prepared from imidazoline 8 (500 mg, 1.6 mmol, 1 equiv) and
sulphamidate 9 (489 mg, 4.0 mmol, 2.5 equiv) in acetone for 5 d.
The residue was purified by FCC (MeOH/CH2Cl2 10:90) to afford
the imidazolinium zwitterion 13 as
a white solid (565 mg,
C35H40N3O3S: 582.2790. Found: 582.2790, Calcd for C35H40N3O3-
1.3 mmol, 81% yield). mp: 297 °C, ½a D22
ꢁ
¼ þ262:2 (c 1, CH2Cl2); 1H
NaS: 604.2610. Found: 604.2605.
NMR (CDCl3, 400 MHz): d = 9.33 (s, 1H), 7.50 (d, J = 7.3 Hz, 3H),
7.44–7.36 (m, 4H), 7.35–7.27 (m, 4H), 7.19–7.09 (m, 2H), 7.09–
7.02 (m, 1H), 5.47 (d, J = 9.3 Hz, 1H), 5.34 (d, J = 9.3 Hz, 1H), 4.21
(td, J = 7.2, 14.2 Hz, 1H), 3.52 (td, J = 6.1, 14.0 Hz, 1H), 3.03–2.90
(m, 2H), 2.37 (s, 3H), 2.23 (tt, J = 7.3, 14.4 Hz, 1H), 2.06–1.97 (m,
1H); 13C NMR (CDCl3, 100 MHz) d = 159.5, 134.6, 134.2, 133.8,
133.2, 131.6, 130.1, 130.0, 129.9, 129.5), 129.4, 128.1, 127.5,
127.3, 127.2, 76.1, 72.7, 48.2, 45.7, 22.5, 18.4. IR (KBr): 34310,
4.8.4. (S)-2-(((4S,5S)-4,5-Diphenyl-1-(2,4,6-trimethylbenzyl)-4,5-
dihydro-1H-imidazol-3-ium-3-yl)methyl)pyrrolidine-1-
sulfonate 15
Prepared from ent-6 (800 mg, 2.26 mmol, 1 equiv) and sulp-
hamidate 10 (553 mg, 3.38 mmol, 1.5 equiv) in CH2Cl2 for 7 d.
The residue was purified by FCC (MeOH/CH2Cl2 10:90) to afford

S. Tabassum et al. / Tetrahedron: Asymmetry 22 (2011) 1632–1639
1639
Cavalluzzi, M. M.; Bruno, C.; Lentini, G.; Lovece, A.; Catalano, A.; Carocci, A.;
Franchini, C. Tetrahedron: Asymmetry 1984, 2009, 20; (l) Altava, B.; Burguete, M.
I.; Carbó, N.; Escorihuela, J.; Luis, S. V. Tetrahedron: Asymmetry 2010, 21, 98; (m)
Moon, L. S.; Pal, M.; Kasetti, Y.; Bharatam, P. V.; Jolly, R. S. J. Org. Chem. 2010, 75,
5487; (n) Nazirogul, H. N.; Durmatz, M.; Bozkurt, S.; Sirit, A. Chirality 2011, 23,
463; (o) Ucello-Barretta, G.; Vanni, L.; Berni, M. G.; Balzano, F. Chirality 2011,
23, 417; (p) Tanaka, K.; Nakai, Y.; Takahashi, H. Tetrahedron: Asymmetry 2011,
22, 178; (q) Pham, N. H.; Wenzel, T. J. J. Org. Chem. 2011, 76, 986; (r) Bozkurt, S.;
Durmaz, M.; Naziroglu, H. N.; Yilmaz, M.; Sirit, A. Tetrahedron: Asymmetry 2011,
22, 541.
3034, 2932, 1715, 1631, 1498, 1456, 1216, 1039, 759, 702,
524 cmꢀ1; MS (ESI): m/z = 457 [M+ +Na]; HRMS (ESI): Calcd for
C25H27N2O3S: 435.1728. Found: 435.1742, Calcd for C25H27N2O3-
NaS: 457.1562. Found: 457.1552.
4.8.8. ((1R,2R)-1-((4R,5R)-4,5-Diphenyl-1-(o-tolyl)-4,5-dihydro-
1H-imidazol-3-ium-3-yl)-1-phenylpropan-2-
yl)(methyl)sulfamate 19
2. For a review see: (a) Parker, D. Chem. Rev. 1991, 91, 1441; (b) Wenzel, T. J.;
Chisholm, C. D. Chirality 2011, 23, 190.
Prepared from imidazoline 8 (520 mg, 1.1 mmol, 1 equiv) and
sulphamidate 11 (376 mg, 1.65 mmol, 1.5 equiv) in CH2Cl2 for
6 d. The residue was purified by FCC (MeOH/ethylacetate/CH2Cl2
70:20:10) to afford the imidazolinium zwitterion 19 as a white so-
3. (a) Simonato, J.-P.; Chappellet, S.; Pecaut, J.; Baret, P.; Marchon, J.-C. New J.
Chem. 2001, 25, 714; (b) Claeys-Bruno, M.; Toronto, D.; Pecaut, J.; Bardet, M.;
Marchon, J.-C. J. Am. Chem. Soc. 2001, 123, 11067; (c) Schwenninger, R.; Schlögl,
J.; Maynollo, J.; Gruber, K.; Ochsenbein, P.; Bürgi, H.-B.; Konrat, R.; Kräutler, B.
Chem. Eur. J. 2001, 7, 2676; (d) Ema, T.; Ouchi, N.; Doi, T.; Korenga, T.; Sakai, T.
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lid (314 mg, 0.58 mmol, 53% yield). mp: >400 °C, ½a D22
¼ þ183 (c
ꢁ
0.5, CH2Cl2); IR (KBr): 3443, 3062, 2983, 1616, 1497, 1456, 1233,
1107, 1035, 862, 759, 701, 667, 632, 596; 1H NMR (CDCl3,
400 MHz): d = 9.45 (s, 1H), 8.02 (dd, J = 1.3, 7.7 Hz, 1H), 7.54 (dd,
J = 1.9, 7.5 Hz, 2H), 7.43–7.29 (m, 9H), 7.26–7.16 (m, 2H), 7.15–
7.04 (m, 5H), 5.64 (d, J = 10.8 Hz, 1H), 5.28 (d, J = 8.0 Hz, 1H), 4.88
(dq, J = 2.9, 7.2 Hz, 1H), 3.97 (d, J = 2.9 Hz, 1H), 2.47 (s, 3H), 2.29 (s,
3H), 1.08 (d, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d = 156.6,
134.4, 134.3, 133.5, 133.4, 132.7, 131.1, 130.1, 129.9, 129.7, 129.6,
129.6, 129.3, 128.9, 128.9, 128.8, 128.4, 128.1, 127.7, 77.5, 74.8,
66.5, 53.4, 32.7, 18.6, 14.6. MS (ESI): m/z = 562 [M+Na]; HRMS
(ESI): Calcd for C32H34N3O3S: 540.2321. Found: 540.2316, Calcd
for C32H33N3O3NaS: 562.2214. Found: 562.2214.
4. Wenzel, T. J.; Amonoo, E. P.; Shariff, S. S.; Aniagyei, S. E. Tetrahedron: Asymmetry
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4.9. NMR Experiments with the racemic compounds
The racemic compound (1 equiv) and the corresponding zwit-
terion (1 equiv) were dissolved in a deuterated organic solvent
and the 1H NMR and 19F NMR spectra were recorded at rt. For re-
sults see Table 1 and 2.
Acknowledgments
S.T. gratefully acknowledges a fellowship from the DAAD/HEC.
In addition the authors would like to thank Dr. Dräger from the
University of Hanover for HRMS measurements.
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