Easily accessible chiral imidazolinium salts bearing two hydroxy-containing substituents as shift reagents and carbene precursors

Article abstract of DOI:10.1002/ejoc.200600584

The behavior of new enantiopure imidazolinium salts bearing two hydroxy-containing substituents as chiral shift reagents and as carbene precursors for diethylzinc addition to aldehydes is presented. The new hydroxy-containing imidazolinium salts can be prepared in a few steps from amino alcohols and qualify as new tridentate ligands and ionic liquids. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200600584

FULL PAPER
DOI: 10.1002/ejoc.200600584
Easily Accessible Chiral Imidazolinium Salts Bearing Two Hydroxy-
Containing Substituents as Shift Reagents and Carbene Precursors
[a]
[a]
[a]
Václav Jur cˇ ík, Mazhar Gilani, and René Wilhelm*
Keywords: Carbenes / Shift reagents / Ionic liquids / Imidazolinium salts
The behavior of new enantiopure imidazolinium salts bear-
ing two hydroxy-containing substituents as chiral shift rea-
gents and as carbene precursors for diethylzinc addition to
aldehydes is presented. The new hydroxy-containing imid-
azolinium salts can be prepared in a few steps from amino
alcohols and qualify as new tridentate ligands and ionic li-
quids.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
II
Introduction
bene precursors in the Cu -catalyzed addition of dieth-
ylzinc to cyclohexenone, with ees of up to 93% being
achieved. Moreover, the groups of Mauduit and Alexakis
have used salts of type 4 together with other chiral imid-
azolinium salts in copper-catalyzed conjugated Grignard
additions to 3-substituted cyclohexenones in order to create
N-Heterocyclic carbenes (NHCs) have found an impor-
tant role as ligands in various applications in organometal-
[1–3]
lic chemistry in recent years.
In addition, various carb-
enes themselves can be used as organocatalysts.[
4–6]
The pre-
cursors of the corresponding carbenes are salts, some of
which have been found to be ionic liquids, and recently a
quaternary chiral centers, and have achieved ees of up to
[17]
96%.
few examples of chiral ionic liquids based on chiral imid-
azolinium cations have been reported.[
7,8]
The examples of
this class of chiral ionic liquids remain few in number in
relation to other types of chiral ionic liquids.[
9–11]
Examples of chiral imidazolinium and imidazolium salts
incorporating substituents bearing hydroxy groups are
rather rare. These salts act as precursors for bidentate li-
gands and can also be used as ionic liquids.[ An interesting
bidentate hydroxy-carbene ligand based on salt 1 was re-
cently described by Hoveyda et al.[ and applied with ru-
thenium in an asymmetric olefin metathesis, giving ees of
up to 96%. In addition, the carbene ligand was also investi-
gated in a copper-catalyzed allylic alkylation, which gave
the desired product in up to 98% ee. Furthermore, Arnold’s
7]
12]
I
group has synthesized salt 2, a Cu complex with this car-
bene ligand having been isolated[
13,14]
Because of our interest in imidazolinium salts as ionic
and used as a catalyst
[
18]
[19–21]
liquids and catalysts
we were keen to synthesize and
in a diethylzinc conjugated addition to cyclohexenone, re-
sulting in ees of up to 51%. Very recently, Mauduit’s group
has reported the synthesis of salt 3 and has shown it to be
possible to use this as a shift reagent for potassium Mosh-
investigate chiral imidazolinium salts incorporating two hy-
droxy groups on their substituents. These salts can be pre-
pared by the route shown in Scheme 1, and their behavior
as shift reagents and carbene ligands is presented here.
1
er’s salt, with splittings of 60 Hz in H NMR and 63 Hz in
1
9
[7]
F NMR spectroscopy. Furthermore, the same group has
also prepared salt 4 and various analogues based on dif-
Results and Discussion
ferent amino alcohols.[
15,16]
These salts were used as car-
The appropriate bis(amino alcohol)s were first prepared
[
a] Institute of Organic Chemistry, Clausthal University of Tech- from amino alcohols and 1,2-dibromoethane by a literature
nology,
[22]
procedure, as shown in Scheme 1. Bis(amino alcohol) 5,
Leibnizstrasse 6, 38678 Clausthal-Zellerfeld, Germany
Fax: +49-5323-722834
derived from (–)-norephedrine, was isolated in 79% yield,
E-mail: rene.wilhelm@tu-clausthal.de
while ent-5 was prepared from (+)-norephedrine in the same
Eur. J. Org. Chem. 2006, 5103–5109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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V. Ju r cˇ ík, M. Gilani, R. Wilhelm
FULL PAPER
Table 1. In some cases anion exchange with LiNTf was
2
performed, although only moderate yields were achieved
here (Table 1, Entries 5 and 7). Salts 12B, 13A, 13C, and
1
4A could qualify as ionic liquids, since their melting points
[
24]
are below 100 °C,
while salts 10B, 10C, 11A, 11B, and
1
2A could qualify as room-temperature ionic liquids.
[25]
In view of previous reports of the use of thiazolinium-,
[
7]
[26]
imidazolinium-,
or ammonium-based
chiral ionic
liquids as chiral shift reagents, and also of our investi-
gations with chiral bis(imidazolinium)-based salts,[
19]
se-
veral of the prepared salts were tested for their ability to
interact with Mosher’s carboxylate, by examination of dif-
ferences in the chemical shifts of the OMe group and the
CF group in the two enantiomers of Mosher’s carboxylate.
3
For these experiments, enantioenriched (12% ee, in order
to permit the assignment of signals to the corresponding
enantiomers) potassium Mosher’s carboxylate 15 was mixed
Scheme 1.
with the chiral imidazolinium salts in different ratios (the
1
mixtures were dissolved in [D ]acetone) and H NMR and
6
19
F NMR spectra were recorded. The results are summa-
yield. The bis(amino alcohol) 6 was obtained in 77% yield rized in Table 2.
from -valinol in 77% yield, while 7 was isolated in 91%
When enantiopure salt 10A with a BF – counteranion
4
yield after treatment of -tert-leucinol with dibromoethane. was used in combination with Mosher’s carboxylate
Finally, bis(amino alcohol) 8 was isolated in 75% yield by (Table 2, Entry 2), no signal splitting was seen either in the
1
19
starting from (–)-(1R,2R)-2-amino-1-phenylpropane-1,3-
H NMR or in the F NMR spectra. On changing the
–
diol. The bis(amino alcohol) 9 was prepared from (1R,2R)- counteranion to NTf , a significant increase in the split-
trans-diaminocyclohexane and cyclohexene oxide as de- ting, to 12 Hz in the H NMR and 118 Hz in the F NMR,
2
1
19
scribed in the literature.[
23]
was observed (Table 2, Entry 3). A picture of these spectra
The imidazolinium salts were prepared by direct treat- is shown in Figure 1. This splitting could not be improved
ment of the bis(amino alcohol)s with triethyl orthoformate by use of an excess of the imidazolinium salt (Table 2, En-
in the presence of NH BF as shown in Scheme 1. Op- try 4), but the splitting was increased further, to 24 in the
4
4
1
19
tionally, more lipophilic anions could be introduced by
counteranion exchange in a mixture of chloroform and change in the counteranion to B[C H (CF ) ] (Table 2,
H NMR and 151 Hz in the F NMR spectra, with a
–
6
3
3 2 4
water. The reaction proceeded in high yields, as shown in Entry 5). To the best of our knowledge this is the largest
Table 1. Preparation of imidazolinium salts containing hydroxylated substituents.
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Chiral Imidazolinium Salts as Shift Reagents and Carbene Precursors
FULL PAPER
Table 2. Chemical shifts δ of Mosher’s carboxylate in ppm and ∆δ values in Hz (400 MHz NMR spectroscopy).
1
19
1
19
Entry
Salt
Ratio
δ( H)
δ( F)
∆δ( H)
∆δ( F)
(S)
(R)
(S)
(R)
1
2
3
4
5
6
7
8
9
–
N/A
1:1
1:1
3:1
1:1
1:1
1:1
1:1
1:1
3.54
3.54
3.55
3.55
3.50
3.590
3.58
3.55
3.60
3.54
3.54
3.52
3.52
3.56
3.587
3.58
3.55
3.60
–71.59
–71.59
–70.90
–70.90
–71.39
–71.65
–71.63
–71.52
–71.32
–71.59
–71.59
–71.22
–71.22
–70.99
–71.70
–71.60
–71.50
–71.41
0
0
12
12
24
1.2
0
0
0
10A
10B
10B
10C
11A
11B
13C
14A
118
118
151
18
15
7
0
0
32
Figure 1. NMR spectra of salt 10B with potassium Mosher’s carboxylate (15).
reported 19F NMR signal splitting obtained with an imid- ferent solvents being tested. The results are summarized in
azolinium salt.
Salt 11A showed a poor splitting, 1.2 Hz in the H NMR
Table 3.
1
1
9
and 18 Hz in the F NMR (Table 2, Entry 6), while a
–
change in the counteranion to NTf2 did not in this case
result in any improved splitting (Table 2, Entry 7). Salt 13C,
–
with a B[C H (CF ) ] moiety, showed no splitting in its
6
3
3 2 4
1
19
H NMR spectrum and a poor splitting of 7 Hz in its
F
–
Scheme 2.
NMR spectrum (Table 2, Entry 9), while the BF salt 14A
4
displayed a splitting of 32 Hz in its 19F NMR signal. An
1
upfield shift of the signal in the H NMR indicated interac-
In order to generate the carbene, imidazolinium salt 14A
tions between the imidazolinium cation and the Mosher’s was deprotonated with tBuOK in a PhMe solution. After
salt, but no stereodiscrimination was observed (Table 2, En- 5 min of stirring, Et Zn (1.1 equiv.) was added, followed by
2
try 9).
benzaldehyde (1 equiv.). After 30 h of stirring at room temp.
In order to demonstrate that the new imidazolinium salts and quenching of the reaction mixture with HCl (1 ), the
bearing two hydroxy-containing substituents are potential product was isolated in 67% yield and showing 66% ee
new carbene ligands, they were tested in diethylzinc ad- (Table 3, Entry 2). When no base was present, no reaction
dition to aldehydes. This enantioselective C–C bond forma- occurred, indicating that the carbene generation is essential
tion for the preparation of optically active secondary for the reaction to proceed (Table 3, Entry 1). The mecha-
alcohols has been intensely studied with various catalytic nism of the reaction has been thoroughly examined in the
[
27–29]
[30,31]
systems.
The salts were first tested in the addition of case of β-amino alcohol ligands.
In the present case,
diethylzinc to benzaldehyde (16), as shown in Scheme 2, the the carbene unit is probably taking over the role of the
reactions being performed at room temperature and dif- amine substituent of a β-amino alcohol.
Eur. J. Org. Chem. 2006, 5103–5109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5105

V. Ju r cˇ ík, M. Gilani, R. Wilhelm
FULL PAPER
2
Table 3. Addition of Et Zn to benzaldehyde (16).
Entry
Catalyst
Solvent
Base
Yield [%]
ee [%]
Configuration
1
2
3
4
5
6
7
8
14A
14A
PhMe
PhMe
THF
DME
dioxane
PhMe
PhMe
PhMe
–
0
67
traces
0
0
57
–
66
–
–
–
40
35
8
–
(R)
–
–
–
(S)
(R)
(R)
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
10A
10A
10A
ent-10A
11A
12A
38
70
Table 4. Addition of Et
2
Zn to 1-naphthaldehyde (18).
Entry
Catalyst
Base
T [°C]
Yield [%]
ee [%]
Configuration
1
2
3
4
5
6
7
8
9
10A
10A
10A
10A
10A
10A
10A
10A
13A
14A
tBuOK (0.1 equiv.)
KHMDS (0.1 equiv.)
KHMDS (0.2 equiv.)
KHMDS (0.3 equiv.)
KHMDS (0.1 equiv.)
KHMDS (0.1 equiv.)
NaHMDS (0.1 equiv.)
LiHMDS (0.1 equiv.)
KHMDS (0.1 equiv.)
KHMDS (0.1 equiv.)
room temp.
room temp.
room temp.
room temp.
–5
61
92
84
78
85
traces
80
76
60
58
60
45
45
31
55
–
47
36
33
25
(R)
(R)
(R)
(R)
(R)
–
(R)
(R)
(R)
(R)
–78
room temp.
room temp.
room temp.
–25
10
Next, salt 13A was tested in various solvents. In DME sulted in yields of 80 and 76% and ees of 47 and 33%
and dioxane the reaction did not give any product, while (Table 4, Entries 7 and 8), showing that potassium is the
a reaction in THF gave only traces (Table 3, Entries 3–5). best countercation for this type of reaction.
Finally, the reaction in PhMe gave the corresponding prod-
uct in 57% yield and with 40% ee (Table 3, Entry 6). The under the optimized conditions, salt 10A was dissolved in
-valinol-based compound 11A gave the alcohol 17 in 38% toluene. After the addition of tBuOK, diethylzinc was
In order to show that the formed carbenes were stable

yield and with 35% ee (Table 3, Entry 7). Changing the iPr added and the solution was stirred overnight. After aque-
groups to tBu groups in catalyst 12A resulted in an increase ous workup and extraction, salt 10A was recovered and
1
of the yield to 70% but an ee of only 8% was detected identified by H NMR spectroscopy.
(Table 3, Entry 8).
1-Naphthaldehyde (18) was also used, as shown in
Scheme 3, and the influence of different bases was investi- Conclusion
gated. The results are presented in Table 4.
We have presented the preparation of a series of new,
enantiopure imidazolinium salts bearing two hydroxylated
substituents, which were shown to be efficient and reusable
shift reagents for Mosher’s carboxylate. In addition, they
can be used as carbene ligands for the enantioselective ad-
dition of Et Zn to aldehydes and also qualify as new chiral
2
Scheme 3.
ionic ligands. Further applications of this new class of po-
tential tridentate ligands are currently being investigated in
our group, and these will be reported soon.
When the reaction was conducted with catalyst 10A in
the presence of tBuOK as a base, the corresponding alcohol
9 was isolated in 61% yield and with 60% ee (Table 4, En-
1
try 1). Changing the base to KHMDS resulted in a dra-
matic increase in the yield to 92%, but the ee decreased to
Experimental Section
General Experimental: Flash column chromatography[32] was per-
formed on Sorbisil C-60. Reactions were monitored by TLC on
Merck silica gel 60 F254 plates. Elemental analysis were carried
out by the Microanalytical Laboratory of the Institut für Pharma-
zeutische Chemie der Technische Universität Braunschweig with an
Elemental Analyzer Model 1106 from Carlo Erba Instru-
mentazione. Infrared spectra were recorded with a Bruker Vek-
tor 22 FTIR spectrometer, as KBr pellets in cases of solid com-
4
5% (Table 4, Entry 2). Use of 2 and 3 equiv. of the base
resulted in decreases in the yield to 84 and 78%, respec-
tively, while in the case of 3 equiv. the ee dropped to 31%
(Table 4, Entries 3 and 4). If the reaction temperature was
decreased to –5 °C, the yield decreased slightly to 85%, but
the ee increased to 55% (Table 4, Entry 5). After a further
reduction in temperature to –78 °C, only traces of com-
pound 19 were isolated (Table 4, Entry 6). Performing the pounds and as thin films between NaCl plates in cases of oils and
1
reaction with use of different hexamethyldisilazane salts re- liquids. H NMR spectra were recorded at ambient temperature
5106
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Eur. J. Org. Chem. 2006, 5103–5109

Chiral Imidazolinium Salts as Shift Reagents and Carbene Precursors
FULL PAPER
with Bruker AMX 400 (400 MHz) and AC 200F (200 MHz) instru-
ments with tetramethylsilane as internal standard. 13C NMR spec-
tra were recorded at ambient temperature with Bruker AMX 400
ppm. 13C NMR (100 MHz, CDCl
3
): δ = 67.9, 62.9, 49.7, 34.4,
27.2 ppm. IR (KBr): ν˜ = 3314 s, 2958 s, 2873 s, 1467 s, 1052 s, 452
–
1
+
s cm . MS (EI): m/z (%) = 261 (10) [M + H] , 229 (15), 203 (25),
19
(100 MHz) and AC 200F (50 MHz) instruments and F NMR
144 (25), 130 (100), 100 (50), 86 (50), 74 (40), 57 (45). HRMS (ESI):
spectra were recorded at ambient temperature with a Bruker
AMX 400 (378 MHz) instrument. Mass spectra (ESI) were re-
corded with a Hewlett–Packard MS LC/MSD Series 1100 MSD
instrument, while high-resolution mass spectra were measured with
a Bruker Daltonik Tesla–Fourier Transform-Ion Cyclotron Reso-
nance Mass Spectrometer. Melting points were taken with a
Dr. Tottoli apparatus and are uncorrected. Reactions were per-
formed under nitrogen. All solvents were dried by standard pro-
33 2 2 32 2 2
calcd. for C14H N O 261.2542; found 261.2546. C14H N O
(260.4): C 64.57, H 12.39, N 10.76; found C 64.44, H 12.54, N
10.88.
(
1R,1ЈR,2R,2ЈR)-2,2Ј-[Ethane-1,2-diylbis(azanediyl)]bis(1-phenyl-
propane-1,3-diol) (8): This compound was prepared from (–)-
1R,2R)-2-amino-1-phenylpropane-1,3-diol (1.15 g, 6.89 mmol)
and dibromoethane (296 µL, 3.45 mmol) as a yellow oil (930 mg,
(
22
1
75%). [α]
D
= –78.2 (c = 0.28, CHCl
3
). H NMR (400 MHz,
[33]
[34]
cedures before used in the reactions. -Valinol, -tert-leucinol,
CDCl
3
): δ = 7.45–7.30 (m, 10 H), 4.60 (d, J = 7.6 Hz, 2 H), 3.65–
sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate,[
35]
(1R,2S)-
13
3.55 (m, 2 H), 3.35–3.25 (m, 2 H), 2.80–2.60 (m, 4 H) ppm.
C
2
-({2-[(1S,2R)-2-hydroxy-1-methyl-2-phenylethylamino]ethyl}-
NMR (100 MHz, CDCl
3
): δ = 142.0, 128.5, 127.8, 126.7, 73.8, 64.8,
[22]
[23]
amino)-1-phenylpropan-1-ol (5)
and compound 9
were pre-
6
0.2, 46.8 ppm. IR (neat): ν˜ = 3356 vs, 2882 s, 1454 s, 1027 s, 759
pared according to literature procedures. (–)-Norephedrine, (+)-no-
rephedrine, (–)-(1R,2R)-amino-1-phenylpropane-1,3-diol, alde-
hydes, potassium tert-butoxide, lithium bis(trifluoromethylsulf-
onyl)imide, and diethylzinc were purchased from Aldrich. Mosher’s
reagent was purchased from Lancaster.
–1
+
vs, 702 vs cm . MS (ESI = 0 V): m/z (%) = 361.0 (70) [M + H] .
HRMS (ESI): calcd. for C20 361.2127; found 361.2122.
29 2 4
H N O
General Procedure for Preparation of Imidazolium Tetrafluroborate
Salts: A bis(amino alcohol) (1.00 mmol) was placed in a flask, and
the counteranion source (typically NH BF , 1.00 mmol) and either
4 4
triethyl orthoformate (148 mg, 165 µL, 1.00 mmol) or triethyl or-
thoacetate (127 µL 97%, 0.66 mmol) was added. The reaction ves-
sel was flushed with nitrogen and sealed, and the mixture was
heated to 120 °C for 2 h. After cooling, the mixture was dried under
vacuum, in order to remove ethanol, formed during the reaction,
to give the crude salt in high purity. Optionally, the product was
crystallized from absolute ethanol.
Preparation of Diamines
General Procedure for the Preparation of Diamines by Alkylation
[
22]
with BrCH
2
CH
2
Br:
An amino alcohol (1.00 mmol) and dibro-
moethane (87 µL, 0.50 mmol) were placed in a pressure vessel,
which was flushed with nitrogen and sealed. The reaction mixture
was heated at 100 °C for 10 h, during which the reaction mixture
solidified. After the system had cooled to room temp., the solid
was dissolved in water (10 mL) and the aqueous phase was washed
General Procedure for the Counteranion Exchange with Lithium Bis-
with CHCl
NaOH (40 mg, 1 equiv.) and the precipitated free base was ex-
tracted with CHCl (3×5 mL). The combined organic fractions
were dried (Na SO ) and the solvent was removed under reduced
pressure to give the pure bis(amino alcohol).
3
(3 × 3 mL). The aqueous phase was basified with
(
trifluoromethylsulfonyl)imide: An imidazolinium tetrafluoroborate
salt (1.00 mmol) was dissolved in CH Cl (3 mL) and the mixture
was vigorously stirred with a solution of LiNTf (1.00 mmol) in
2
2
3
2
2
4
water (3 mL) for 3 h. The organic phase was separated, washed
with water (3×3 mL), and dried with molecular sieves (3 Å). The
solvent was evaporated and the product was further dried under
vacuum to give the corresponding imidazolinium bis(trifluoro-
methylsulfonyl)imide salt.
(
1S,2R)-2-[(2-{[(1R,2S)-2-Hydroxy-1-methyl-2-phenylethyl]amino}-
ethyl)amino]-1-phenylpropan-1-ol (ent-5): This compound was pre-
pared from (+)-norephedrine (5.01 g, 33.00 mmol) and dibromo-
ethane (1.42 mL, 16.50 mmol), after basification with NaOH (2 ,
General Procedure for the Counteranion Exchange with Sodium Tet-
rakis[3,5-bis(trifluoromethyl)phenyl]borate: An imidazolinium tetra-
1
4.00 mL, 28.00 mmol), as a yellow oil (4.15 g, 79%). Spectral data
[36]
are consistent with literature values.
fluroborate (1.00 mmol) was dissolved in CH
2 2
Cl (3 mL), and
(
S)-2-[(2-{[(S)-1-(Hydroxymethyl)-2-methylpropyl]amino}ethyl)-
NaB[C (CF (1.00 mmol, 1 equiv.) and water (3 mL) were
6
H
3
3 2 4
) ]
amino]-3-methylbutan-1-ol (6): This compound was prepared from
added sequentially. The reaction mixture was then vigorously
stirred for 3 h. The organic phase was separated (centrifugation was
used to improve separation if separation did not occur), washed
with water (3×3 mL), and dried with molecular sieves (3 Å). The

5
1
-valinol (1.23 g, 11.90 mmol) and dibromoethane (513 µL,
.95 mmol), after basification with NaOH (2 , 5.10 mL,
22
0.20 mmol), as a yellow oil (1.06 g, 77%). [α]
D
= +14.3 (c = 0.65,
1
CHCl
3
1
3
). H NMR (200 MHz, CDCl
.42–3.33 (m, 2 H), 2.90–2.50 (m, 4 H), 2.40–2.25 (m, 2 H), 1.90–
.70 (m, 2 H), 1.01–0.85 (m, 12 H) ppm. 13C NMR (50 MHz, methyl)phenyl]borate salt.
): δ = 65.2, 62.0, 47.4, 29.4, 20.1, 18.7 ppm. IR (neat): ν˜ =
3
): δ = 3.67–3.59 (m, 2 H), solvent was evaporated and the product was further dried in vacuo
to give the corresponding imidazolinium tetrakis[3,5-bis(trifluoro-
CDCl
314 s, 2958 s, 2873 s, 1467 s, 1052 s, 452 s cm . MS (ESI = 0 V):
3
1
,3-Bis[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]imidazolinium
Tetrafluoroborate (10A): This compound was prepared from 5
657 mg, 2.00 mmol), NH BF (216 mg, 2.00 mmol), and
CH(OEt) (326 µL, 2.00 mmol) as described in the General Pro-
–1
3
+
m/z (%) = 233.3 (100) [M + H] . The preparation of this compound
by the reduction of a bis(amide) had previously been reported,[37]
but no spectroscopic data were provided.
(
4
4
3
cedure. The reaction mixture was heated to 120 °C in a sealed vessel
(
S)-2-[(2-{[(S)-1-(Hydroxymethyl)-2-methylpropyl]amino}ethyl)-
for 8 h, giving the title compound as a yellow solid (743 mg, 87%);
2
2
1
amino]-3-methylbutan-1-ol (7): This compound was prepared from
m.p. 162 °C. [α]
[D ]DMSO): δ = 8.32 (s, 1 H), 7.50–7.20 (m, 10 H), 5.95 (br. s, 2
H), 4.81 (d, J = 4.0 Hz, 2 H), 4.00–3.70 (m, 6 H), 1.08 (d, J =
D
= +17.9 (c = 1.2, MeOH). H NMR (200 MHz,

8
1
-tert-leucinol (2.00 g, 17.10 mmol) and dibromoethane (740 µL,
.55 mmol), after basification with NaOH (2 , 8.55 mL,
7.10 mmol), as a white solid (2.01 g, 91%). For elemental analysis
6
1
3
6
6.9 Hz) ppm. C NMR (50 MHz, [D ]DMSO): δ = 156.2, 141.4,
2
2
the diamine was crystallized from EtOH; m.p. 53 °C. [α]
D
= +53.8
128.1, 127.4, 126.1, 72.7, 58.6, 47.0, 12.1 ppm. IR (KBr): ν˜ = 3273
1
–1
(c = 0.34, CHCl
3
). H NMR (400 MHz, CDCl
3
): δ = 3.71 (dd, J =
s, 1652 vs, 1265 s, 1139 s, 1070 vs, 1015 s, 988 s, 704 s cm . MS
+
3
(
.52, 10.6 Hz, 2 H), 3.55–3.42 (m, 2 H), 3.08 (d, J = 8.6 Hz), 2.73 (ESI = 0 V): m/z (%) = 339 (100) [M] . HRMS (ESI): calcd for
d, J = 8.6 Hz), 2.34 (dd, J = 3.52, 10.6 Hz, 2 H), 0.97 (s, 18 H)
+
21 27 2 2
C H N O 339.2073; found 339.2074.
Eur. J. Org. Chem. 2006, 5103–5109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5107

V. Ju r cˇ ík, M. Gilani, R. Wilhelm
FULL PAPER
1
,3-Bis[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]imidazolinium
for 8 h and standard workup gave the title compound as a colorless
2
2
1
Tetrafluoroborate (ent-10A): This compound was prepared in the
same manner, from ent-5.
oil (1.30 g, 88%). [α]
(400 MHz, CDCl ): δ = 8.15 (s, 1 H), 4.20–4.10 (m, 2 H), 4.10–
.00 (m, 2 H), 3.95 (dd, J = 3.7, 12.3 Hz, 2 H), 3.82 (t, J = 10.8 Hz,
D 3
= +24.4 (c = 0.46, CHCl ). H NMR
3
4
2
1
,3-Bis[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]imidazolinium
Bis(trifluoro-methylsulfonyl)imide (10B): This compound was pre-
pared from 10A (300 mg, 0.70 mmol) and LiNTf (208 mg, 97%,
.70 mmol) in a mixture of dichloromethane (DCM) (5 mL) and
1
3
H), 3.60 (dd, J = 3.7, 12.3 Hz), 1.04 (s, 18 H) ppm. C NMR
): δ = 160.2, 69.9, 57.8, 49.7, 33.8, 27.3 ppm. IR
neat): ν˜ = 3541 s, 2967 vs, 1699 m, 1639 vs, 1479 s, 1409 m, 1373
(100 MHz, CDCl
3
2
(
0
–
1
s, 1283 s, 1237 m, 1058 vs, 451 s, 415 m, 406 m cm . MS (ESI =
0
C
22
water (5 mL), as a yellow oil (404 mg, 93%). [α]
MeOH). H NMR (200 MHz, CDCl
D
= +20.8 (c = 0.9,
+
V): m/z = 271.3 [M(cation)] . HRMS (ESI): calcd. for
1
3
): δ = 7.78 (s, 1 H), 7.37–7.20
+
15 31 2 2
H N O 271.2386; found 271.2396.
(m, 10 H), 4.96 (d, J = 3.2 Hz, 2 H), 4.00–3.70 (m, 4 H), 3.16 (br. s,
2
=
H), 1.17 (d, J = 7.0 Hz, 6 H) ppm. 13C NMR (50 MHz, CDCl
155.6, 139.2, 128.7, 128.3, 125.9, 73.6, 59.5, 47.6, 12.2 ppm. IR
3
): δ 1,3-Bis[(S)-1-hydroxy-3,3-dimethylbut-2-yl]imidazolinium Bis(tri-
fluoromethylsulfonyl)imide (12B): This compound was prepared
(
neat): ν˜ = 3523 s, 1642 vs, 1352 vs, 1197 vs, 1137 vs, 1057 vs, 706
from 12A (294 mg, 0.86 mmol) and LiNTf
1 equiv.) in a mixture of DCM (5 mL) and water (5 mL), as a white
2
(246 mg, 0.86 mmol,
–
1
s, 617 s, 442 vs cm . MS (ESI = 0 V): m/z (%) = 339.2 (100)
+
+
22
[
M] . HRMS (ESI): calcd. for C21
H
27
N
2
O
2
339.2073; found
solid (277 mg, 59%); m.p. 98 °C. [α]
H NMR (200 MHz, [D
6
D
= +19.7 (c = 0.36, CHCl
]acetone): δ = 8.36 (s, 1 H), 4.25–4.05 (m,
H), 4.00–3.80 (m, 4 H), 3.60–3.45 (m, J = 10.8 Hz, 2 H), 0.93 (s,
3
).
1
3
39.2073.
4
1
1
,3-Bis[(1S,2R)-2-hydroxy-1-methyl-2-phenylethyl]imidazolinium
1
3
6
8 H) ppm. C NMR (50 MHz, [D ]acetone): δ = 161.7, 121.0 (q,
Bis(trifluoro-methylsulfonyl)imide (ent-10B): This compound was
prepared in the same manner, from ent-10A.
J = 319.5 Hz), 70.9, 57.9, 48.8, 34.4, 27.5 ppm. IR (KBr): ν˜ = 3423
–
1
+
s, 1637 s, 1194 s, 1057 s cm . MS (ESI = 0 V): m/z = 271.3 [M] .
1
,3-Bis[(1R,2S)-1-hydroxy-1-phenylpropan-2-yl]imidazolinium Tet-
rakis[3,5-bis(trifluoromethyl)phenyl]borate (10C): This compound
was prepared from 10A (200 mg, 0.47 mmol) and NaB[C
CF (416 mg, 0.47 mmol) in a mixture of DCM (5 mL) and
water (5 mL), as a brown oil (477 mg, 84%). [α]
HRMS (ESI): calcd for C H N O 271.2386; found 271.2381.
1
5
31
2
2
1
,3-Bis[(1R,2R)-1,3-dihydroxy-1-phenylprop-2-yl]imidazolinium Tet-
rafluoroborate (13A): This compound was prepared from 8
320 mg, 0.89 mmol), NH BF (93 mg, 0.89 mmol), and
CH(OEt) (146 µL, 0.89 mmol) as described in the General Pro-
cedure. The mixture was heated at 120 °C for 16 h to give the title
6
3
H -
(
3 2 4
) ]
(
4
4
2
2
D
= –53.2 (c = 0.5,
]acetone): δ = 8.33 (s, 1 H), 7.08
br. s, 8 H), 7.69 (br. s, 4 H), 7.50–7.30 (m, 10 H), 5.20–5.05 (m, 2
H), 4.25–4.05 (m, 6 H), 2.88 (br. s, 2 H), 1.29 (d, J = 8.1 Hz, 6 H)
ppm. 13C NMR (100 MHz, [D
]acetone): δ = 161.7 (q, J =
9.5 Hz), 156.4, 140.9, 134.6, 129.3 (q, J = 28.4 Hz), 128.4, 127.9,
1
3
3 6
CHCl ). H NMR (400 MHz, [D
(
2
2
compound as a yellow solid (400 mg, 99%); m.p. 80–85 °C. [α]
D
1
=
=
4
–116.2 (c = 0.37, acetone). H NMR (200 MHz, [D
6
]acetone): δ
6
8.27 (s, 1 H), 7.40–7.05 (m, 10 H), 4.92 (d, J = 6.3 Hz, 2 H),
.10–3.40 (m, 10 H) ppm. C NMR (50 MHz, [D
4
1
1
1
3
6
]acetone): δ =
26.2 124.5 (q, J = 269.8 Hz), 117.6, 73.8, 59.6, 52.5, 47.8, 47.6,
2.1 ppm. IR (KBr): ν˜ = 1641 m, 1356 s, 1279 vs, 1124 vs, 682 m
1
60.1, 142.4, 129.4, 128.8, 127.3, 71.4, 67.2, 60.3, 48.4 ppm. IR
–
1
(
KBr): ν˜ = 3386 m, 1641 vs, 1063 vs, 704 s cm . MS (ESI = 0 V):
–1
+
cm . MS (ESI = 0 V): m/z (%) = 339.2 (100) [M] . HRMS (ESI):
+
+
27 2 4
m/z (%) = 371 (100) [M] . HRMS (ESI): calcd. for C21H N O
+
calcd. for C21
,3-Bis[(S)-1-(hydroxymethyl)-2-methylpropyl]-4,5-imidazolinium
Tetrafluoroborate (11A): This compound was prepared from 6
27 2 2
H N O 339.2073; found 339.2079.
371.1971; found 371.1980.
1
1,3-Bis[(1R,2R)-1,3-dihydroxy-1-phenylprop-2-yl]imidazolinium Tet-
rakis[3,5-bis(trifluoromethyl)phenyl]borate (13C): This compound
was prepared from 13A (100 mg, 0.22 mmol) and NaB[C
CF (193 mg, 0.22 mmol) in a mixture of DCM (3 mL) and
water (3 mL), as a yellow solid (215 mg, 80%); m.p. 50 °C. [α]
(
12 mg, 1.34 mmol), NH
4 4
BF (141 mg, 1.34 mmol), and CH-
6
3
H -
(OEt) (220 µL, 1.34 mmol) as described in the General Procedure,
3
(
3 2 4
) ]
22
1
as a yellow oil (418 mg, 94%). [α]
NMR (200 MHz, [D ]acetone): δ = 8.20 (s, 1 H), 4.07 (br. s, 2 H),
.00–3.85 (m, 4 H), 3.75–3.25 (m, 6 H), 2.00–1.70 (m, 2 H), 0.91
d, J = 6.5 Hz, 12 H) ppm. 13C NMR (50 MHz, [D
]acetone): δ =
60.1, 67.5, 59.8, 46.2, 27.9, 20.1, 19.4 ppm. IR (neat): ν˜ = 3548 s,
D
= –10.6 (c = 0.68, acetone). H
2
2
D
= –
]acetone): δ = 8.32
s, 1 H), 7.70 (br. s, 8 H), 7.55 (br. s, 4 H), 7.40–7.00 (m, 10 H),
6
1
4
(
5
2.5 (c = 4.7, acetone). H NMR (200 MHz, [D
6
4
(
1
2
6
1
3
.10–4.90 (m, 2 H), 4.30–3.60 (m, 10 H) ppm. C NMR (50 MHz,
]acetone): δ = 161.6 (q, J = 49.5 Hz), 160.1, 142.4, 135.5, 120.0
q, J = 28.4 Hz), 129.4, 128.9, 127.2, 125.3 (q, J = 269.8 Hz), 118.4,
[D
6
–
1
968 s, 2881 s, 1644 vs, 1472 s, 1394 s, 1254 s, 1074 vs, 446 s cm .
(
MS (ESI = 0 V): m/z = 243.2 [cation]. HRMS (ESI): calcd. for
C H N O 243.2073; found 243.2073.
13 27 2 2
7
1
1.6, 67.2, 60.4, 48.5 ppm. IR (KBr): ν˜ = 1640 w, 1357 s, 1279 vs,
+
–
1
+
124 s cm . MS (ESI = 0 V): m/z (%) = 371 (100) [M] . HRMS
+
1
,3-Bis[(S)-1-(hydroxymethyl)-2-methylpropyl]-4,5-imidazolinium (ESI): calcd. for C H N O 371.1971; found 371.1974.
21 27 2 4
Bis(trifluoromethylsulfonyl)imide (11B): This compound was pre-
(
3aS,7aS)-1,3-Bis[(1R,2R)-2-hydroxycyclohexyl]-3a,4,5,6,7,7a-hexa-
hydro-3H-benzo[d]imidazol-1-ium Tetrafluoroborate (14A): This
compound was prepared from 9 (310 mg, 1.00 mmol), NH BF
113 mg, 1.00 mmol), and CH(OEt) (163 µL, 1.00 mmol) as de-
scribed in the General Procedure, as a yellow solid (380 mg, 93%);
pared from 11A (235 mg, 0.71 mmol) and LiNTf
2
(204 mg,
0
.71 mmol, 1 equiv.) in a mixture of DCM (5 mL) and water
22
4
4
(5 mL), as a yellow oil (197 mg, 52%). [α]
D
= –18.9 (c = 0.28,
): δ = 8.16 (s, 1 H), 4.00–3.80
(
3
1
CHCl
3
). H NMR (200 MHz, CDCl
3
(
m, 4 H), 3.70–3.30 (m, 4 H), 3.09 (br. s, 2 H), 2.00–1.75 (m, 2 H),
2
2
1
m.p. 56 °C. [α]
D 3
= +7.1 (c = 0.1, CHCl ). H NMR (200 MHz,
0
1
2
.99 (d, J = 6.7 Hz, 12 H) ppm. 13C NMR (50 MHz, CDCl
59.2, 66.9, 59.4, 45.3, 27.6, 19.7, 18.9 ppm. IR (neat): ν˜ = 3537 m,
3
): δ =
CDCl ): δ = 8.33 (s, 1 H), 4.23 (br. s, 2 H), 3.90–3.30 (m, 6 H),
2
7
=
cm . MS (ESI = 0 V): m/z (%) = 321 (100) [M] . HRMS (ESI):
33 2 2
calcd. for C19H N O 321.2542; found 321.2540.Experiment for
the Stereodiscrimination of Potassium Mosher’s Carboxylate (15):
Mosher’s salt (12 % ee, 0.50 mmol) and the corresponding imid-
azolinium salt (0.50 mmol, 1 equiv.) were dissolved in [D ]acetone
6
3
1
3
.50–0.80 (m, 24 H) ppm. C NMR (50 MHz, CDCl
2.0, 68.9, 63.7, 34.6, 30.3, 28.5, 24.6, 24.0, 23.9 ppm. IR (KBr): ν˜
3528 s, 2940 vs, 2865 s, 1607 vs, 1453 s, 1226 s, 1074 vs, 530 m
3
): δ = 158.8,
–
1
971 s, 1644 vs, 1352 vs, 120 vs, 1137 vs, 1058 vs, 617 vs cm . MS
+
(
ESI = 0 V): m/z = 243.3 [M] . HRMS (ESI): calcd. for
+
C
13
H
27
N
2
O
2
243.2073; found 243.2077.
,3-Bis[(S)-1-hydroxy-3,3-dimethylbut-2-yl]imidazolinium Tetrafluo-
roborate (12A): This compound was prepared from 7 (1.00 g,
.85 mmol), NH BF (615 mg, 3.85 mmol), and CH(OEt)
633 µL, 3.85 mmol). The reaction mixture was heated at 120 °C
–
1
+
+
1
3
(
4
4
3
5108
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5103–5109

Chiral Imidazolinium Salts as Shift Reagents and Carbene Precursors
and the H NMR and 19F NMR spectra were recorded at room
FULL PAPER
[6] D. Enders, T. Balensiefer, Acc. Chem. Res. 2004, 37, 534.
7] H. Clavier, L. Boulanger, N. Audic, L. Toupet, M. Mauduit,
J. C. Guillemin, Chem. Commun. 2004, 1224.
8] Y. Génisson, N. Lauth-de Viguerie, C. André, M. Baltas, L.
1
[
temp. For chemical shifts and stereodiscrimination see Table 2.
Regeneration of the Salt: Regeneration of imidazolinium salt 10A.
[
[D
6
]Acetone was removed under reduced pressure and the remain-
Gorrichon, Tetrahedron: Asymmetry 2005, 16, 1017.
ing residue was dissolved in CHCl (2 mL). The organic phase was
3
[9] C. Baudequin, J. Baudoux, J. Levillain, D. Cahard, A. C. Gau-
washed with water (4×3 mL), dried with molecular sieves (3 Å),
and concentrated, giving the pure imidazolinium salt 10A.
mont, J. C. Plaquevent, Tetrahedron: Asymmetry 2003, 14,
3081.
[
[
10] J. Ding, D. W. Armstrong, Chirality 2005, 17, 281.
11] C. Baudequin, D. Bregeon, J. Levillain, F. Guillen, J. C. Pla-
quevent, A. C. Gaumont, Tetrahedron: Asymmetry 2005, 16,
3921.
General Procedure for Carbene-Catalyzed Et
hydes: An imidazolinium salt (0.04 mmol) and tBuOK (4.5 mg,
.04 mmol) were placed in a dry Schlenk flask and dissolved in dry
toluene (1 mL). After the mixture had been stirred for 5 min, Et Zn
0.5 mL of a 1  solution in hexane) was added, and after another
2
Zn Addition to Alde-
0
[12] A. O. Larsen, W. Leu, C. N. Oberhuber, J. E. Campbell, A. H.
2
Hoveyda, J. Am. Chem. Soc. 2004, 126, 11130.
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Commun. 2001, 2340.
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Blake, C. Wilson, Chem. Commun. 2004, 1612.
15] H. Clavier, L. Coutable, L. Toupet, J.-C. Guillemin, M. Maud-
uit, J. Organomet. Chem. 2005, 690, 5237.
(
[
[
[
5
min, an aldehyde (0.40 mmol) was added. The mixture was stirred
at room temp. for 30 h (for differences in reaction times and tem-
peratures see Tables 3 and 4), quenched by the addition of HCl
(1 , 0.5 mL), and extracted with Et
2
O (3×5 mL). The combined
organic phases were dried (Na SO ) and the solvent was removed
2
4
under reduced pressure to give the crude product, which was puri-
fied by flash column chromatography (petroleum ether/ethyl ace-
tate, 9:1) to give the corresponding alcohol.
[16] H. Clavier, L. Coutable, J.-C. Guillemin, M. Mauduit, Tetrahe-
dron: Asymmetry 2005, 16, 921.
[17] D. Martin, S. Kehrli, M. d’Augustin, H. Clarvier, M. Mauduit,
A. Alexakis, J. Am. Chem. Soc. 2006, 128, 8416.
1
-Phenylpropan-1-ol (17): This compound was prepared as a color-
less oil from benzaldehyde (16, 40 µL, 0.40 mmol) and Et Zn
0.50 mL, 1  solution in hexane) in PhMe (1 mL) and the carbene
generated from an imidazolinium salt (0.04 mmol) and tBuOK
4.5 mg, 0.04 mmol). For catalysts and yields, see Table 3. Spectral
[
[
18] V. Jurcik, R. Wilhelm, Green Chem. 2005, 7, 844.
2
19] V. Jurcik, R. Wilhelm, Tetrahedron: Asymmetry 2006, 17, 801.
(
[20] V. Jurcík, R. Wilhelm, Org. Biomol. Chem. 2005, 3, 239.
[21] A. Blanrue, R. Wilhelm, Synlett 2004, 2621.
[22] V. Santes, E. Gomez, R. Santiallan, N. Farfan, Synthesis 2001,
235.
(
[38]
data are consistent with literature values. The enantiomeric ratio
[
[
23] A. J. A. Cobb, C. M. Marson, Tetrahedron 2005, 61, 1269.
24] P. Wasserscheid, T. Welton, Ionic Liquids in Synthesis, Wiley-
VCH, Weinheim, 2003.
was determined by HPLC [OD-H; iPrOH/hexane, 10:90;
–1
0
.2 mLmin ; t
1 2
(R) = 32.6 min, t (S) = 38.8 min].
1-(Naphth-1-yl)propan-1-ol (19): This compound was prepared as a
[25] J. Levillain, G. Dubant, I. Abrunhosa, M. Gulea, A.-C. Gau-
mont, Chem. Commun. 2003, 2914.
colorless oil from 1-naphthaldehyde (18) (56 µL, 0.40 mmol) and
Et Zn (0.5 mL 1  solution in hexane) in PhMe (1 mL) and the
carbene generated from an imidazolinium carbene precursor
0.04 mmol) and a base. For catalysts, bases, and yields, see Table 4.
[
[
26] P. Wasserscheid, A. Bösmann, C. Bolm, Chem. Commun. 2002,
2
200.
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(
Chem. Int. Ed. Engl. 1991, 30, 49.
[39]
Spectral data are consistent with literature values. The enantio-
[
[
28] K. Soai, S. Niwa, Chem. Rev. 1992, 92, 833.
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R. E. Ziegert, Synlett 2004, 2647.
meric ratio was determined by HPLC [OD-H; iPrOH/hexane, 5:95;
–1
0
1 2
.4 mLmin ; t (S) = 28.4 min, t (R) = 55.4 min].
[
30] M. Kitamura, S. Okada, S. Suga, R. Noyori, J. Am. Chem. Soc.
1
989, 111, 4028.
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Acknowledgments
4
Financial support by the Fonds der Chemischen Industrie and the
DFG is gratefully acknowledged. M. G. gratefully acknowledges a
scholarship from the Higher Education Commission of Pakistan.
[
33] L. A. Bromley, S. G. Davies, C. L. Goodfellow, Tetrahedron:
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[
[
[
[
[
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Published Online: September 18, 2006
Eur. J. Org. Chem. 2006, 5103–5109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5109