Imidazolium-based chiral ionic liquids: Synthesis and application

Article abstract of DOI:10.1016/j.tet.2013.09.017

Synthesis of chiral ionic liquids containing an imidazole nucleus and chiral centers on N-substituents is reported. [(2S,3S)-2,3-Dihydroxybutane-1,4- bis(3-butylimidazolium)]-[bis(trifluoromethanesulfonyl)amide]₂ and [(4S,5S)-2-phenyl-1,3-dioxo

Full text of DOI:10.1016/j.tet.2013.09.017

Tetrahedron 69 (2013) 9690e9700
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Imidazolium-based chiral ionic liquids: synthesis and application
,
b
b
b
Yumiko Suzuki a , Junichiro Wakatsuki , Mariko Tsubaki , Masayuki Sato
*
a Department of Materials & Life Sciences, Faculty of Science & Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan
b School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 August 2013
Received in revised form 4 September 2013
Accepted 5 September 2013
Available online 13 September 2013
Synthesis of chiral ionic liquids containing an imidazole nucleus and chiral centers on N-substituents is
reported. [(2S,3S)-2,3-Dihydroxybutane-1,4-bis(3-butylimidazolium)]-[bis(trifluoromethanesulfonyl)am-
ide]2 and [(4S,5S)-2-phenyl-1,3-dioxolane-4,5-bis(1-methylimidazolium)]-[bis(trifluoromethanesulfonyl)
amide]2 induced enantioselectivity in the Michael addition of malonic esters to chalcones.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Chiral ionic liquid
Chiral solvent
Imidazolium salt
Michael addition
1. Introduction
can be viable chiral solvents for effectively transferring their
chiralities to reaction products. In fact, several examples of
Ionic liquids (ILs) are molten salts with melting points be-
low 100 ꢀC. The most common ILs are N,N-dialkylimidazolium,
N-alkylpyridinium, and alkylammonium salts. In the last two
decades, ILs have attracted considerable attention from various
disciplines because of their unique and diverse properties,
such as tunable miscibility, thermal stability, and high con-
ductivity.1,2 Since the report of Wilkes and co-workers on air-
and water-stable molten imidazolium salts,2 studies on syn-
theses, properties, and applications of ILs have increased
substantially, and the use of ILs in organic synthesis has be-
come widespread.
asymmetric induction by CILs have been reported in the liter-
ature.5,6 This growing interest in the use of CILs as solvents for
chiral induction has prompted us to commence the present
study on the synthesis and application of chiral molten imida-
zolium salts.
Herein, we describe the synthesis of novel imidazolium-based
CILs, and their application as chiral solvents in Michael addition.
The synthetic routes for the CILs are straightforward and all ster-
eogenic centers in the newly-synthesized CILs were derived from
those of ‘chiral pool’ precursors or commonly used chiral building
blocks.
There are many reports of successful applications of ILs as
solvents in asymmetric reactions. In most of these studies,
chiral substrates, reagents, or both, or immobilized chiral cat-
alysts were used as chiral sources.3 Enantioselective synthesis
may also be carried out by the use of chiral ionic liquids (CILs)
as chiral sources. To date, successful syntheses through asym-
metric induction by chiral solvents are rare.4 The use of chiral
solvents has been precluded because of their high cost and
difficulties in their synthesis. However, because of their recy-
clability, ease of synthesis, and high degree of organization, CILs
2. Results and discussion
We synthesized the following structural types of CILs:
molecular structure with one imidazole nucleus bearing
an asymmetric carbon atom
a N-substituent (A); molecular structure with one imidazole
nucleus bearing an asymmetric carbon atom to the nitrogen
atom on a N-substituent (B); C2-symmetric bisimidazolium
salts bearing asymmetric carbon atoms to the nitrogen atom
of imidazoles (C); and C2-symmetric bisimidazolium salts
a to the nitrogen atom on
b
a
bearing asymmetric carbon atoms
imidazoles (D).
b to the nitrogen atom of
* Corresponding author. Tel./fax: þ81 332383089; e-mail address: yumiko_su-
zuki@sophia.ac.jp (Y. Suzuki).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.017

Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
9691
the imidazole of 6 has a shift of 9.37 ppm, whereas that of 5 has
a shift of 10.97 ppm. The lower chemical shifts of 6 were also ob-
served in the 13C NMR spectrum. It can be considered that the
imidazole rings and the planar trifluoromethanesulfonate ions in-
teract, and that electrons of oxygen atoms of triflate ions shield the
imidazoles.
Reaction of 5 with lithium bis(trifluoromethanesulfonyl)imide
produced CIL 7. The 19F NMR signal of 7 was observed at ꢁ78.9 ppm,
and a peak at 280 m/z in the negative ion mode of the mass spec-
trum was assigned to the anion.
CIL 10 was synthesized from (R)-(ꢁ)-1-cyclohexylethylamine 8
in two steps (Scheme 2). First, the imidazole nucleus was con-
structed in the reaction of 8 with formaldehyde, glyoxal, and am-
monium acetate, and then the resulting imidazole
9 was
quaternized using dimethyl sulfonate to afford 10 as an oil.
2.1. Synthesis of CIL A
AcONH4
(CHO)2
The chiral imidazolium tetrafluoroborate 1 is a solid at room
temperature, and its melting point is 90 ꢀC.7 Conversion of the
counter anion of 1 to anions, such as trifluoromethanesulfonates,
bis(trifluoromethanesulfonyl)amide, and methyl sulfonates, as well
as the longer N-alkyl substituents was anticipated to lower the
melting points of 1-(1-phenylethyl)imidazolium salts.
Me
NH2
Me
N
N
HCHO
AcOH
MeOH, H2O
70 °C, overnight
23%
Cy
Cy
8
9
(MeO)2SO2
Me
N
N
Me
MeOSO3
10
Me
N
N
Et
BF4
MeCN
60 °C, 1.5 h
quant.
Cy
Ph
1
Scheme 2.
Imidazole 2 was prepared from (R)-(þ)-1-phenylethylamine by
reaction with glyoxal and formaldehyde.7 The reaction of 2 with
2-bromoethyl ethyl ether 3 and n-butylbromide in toluene heated
at reflux afforded CILs 4 and 5, respectively (Scheme 1). The anion
exchanges of 5 were carried out according to a method in the lit-
erature.8 Treatment of 5 with potassium trifluoromethanesulfonate
in water at 25 ꢀC afforded CIL 6. The anion exchange was confirmed
by mass spectrometry and 19F NMR spectroscopy. The signal for
trifluoromethanesulfonate was observed at 149 m/z in the negative
ion mode, and no peak for bromide was seen in FABMS. The
chemical shift of trifluoromethanesulfonate was observed at
ꢁ79.0 ppm in the 19F NMR spectrum.
2.2. Synthesis of CIL B
Bao’s research group reported asymmetric Michael addition
reaction using CIL 11 as a solvent and a chiral source (Scheme 3).6b
They synthesized 11 by the reaction of 1-methylimidazole with 14,
which was prepared from (
with 1,2-dimethylimidazole (12) and 1-butylimidazole (13) affor-
ded imidazolium salt 15 (a solid) and 16 (a liquid).
L
)-(ꢁ)-ethyl lactate. The reaction of 14
OBn
N
N
Br
Me
Me
O
Me
11 Br
Me
3
Me
N
N
N
N
Me
O
toluene
Br
Ph
Ph
OBn
Br
14
reflux, overnight
quant.
2
4
OBn
Me
N
N
N
N
R1
R1
n-BuBr
toluene
reflux,
Me
R2
R2
toluene, reflux
overnight
quant.
Br
1
2
1
2
overnight
99%
12
15
; R = Me, R = Me
; R = Me, R = Me
KOTf
Me
Me
N
N
Bu
Bu
13; R1 = Bu, R2 = H
16; R1 = Bu, R2 = H
H2O, rt, 3 h
76%
Ph
Ph
TfO
Scheme 3.
6
Me
N
N
Bu
In an attempt to convert it into a liquid, 15 was treated with
potassium trifluoromethanesulfonate in water (Scheme 4). The
product 17, however, was also a solid. The 1H NMR frequency of 17
is also shifted upfield compared with that of 15, as in the case of 5
and 6. In particular, the signals of the 4,5-protons of the imidazole
ring are shifted to 7.07e7.09 ppm from 7.54 to 7.71 ppm. The other
anion exchange reactions of 15 were successfully carried out using
lithium bis(trifluoromethanesulfonyl)imide and sodium tetra-
fluoroborate to afford CILs 18 and 19, respectively. The isolated yield
of 18 was low, presumably because of its high solubility in water
Br
Ph
LiNTf2
N
N
5
H2O, 70 °C
overnight
66%
Tf2N
7
Scheme 1.
Compared with that of 5, the 1H NMR frequency of 6 is shifted
upfield. In particular, the signal of the proton at the 2-position of

9692
Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
and the low efficiency of extraction with dichloromethane. Anion
exchange of 16 was also performed to afford triflate 20, bis(tri-
fluoromethanesulfonyl)imide 21, and tetrafluoroborate 22 in ex-
cellent yields (Scheme 4). All of the butylimidazolium salts 20e22
were obtained as oils. The anions of 17e22 were detected and
confirmed by 1H NMR and 19F NMR spectroscopy, as well as by mass
spectrometry.
imidazole
NaH
Me
OMs
Me
MsO
N
N
DMF, 80 °C
overnight
64%
N
N
Me
Me
23
24
Me
Br
n-BuBr
N
N
Bu
Bu
N
N
toluene
reflux
Br
Me
OBn
KOTf, H2O
rt, 5 h, 96%
25
overnight
99%
N
N
N
Me
Me
Me
Me
Me OTf
17
OBn
OBn
LiNTf2, H2O
rt, 5 h, 95%
Me
I
MeI
toluene
rt, 3 h
93%
N
Me
N
N
N
N
24
Me
Br
Me
N
N
Me
Me
NTf2
Me
I
Me
18 Me
OBn
15
26
NaBF4, H2O
rt, 5 h, 36%
N
N
Me
Me
Cl
AgCl
N
Me
N
BF4
Me
19
Me
N
N
MeOH
rt, overnight
quant.
Cl
Me
27
OBn
OBn
OBn
KOTf, H2O
rt, 5 h, 96%
OTf
Bu
N
N
Scheme 5.
Me
Me
Me
20
OBn
LiNTf2, H2O
rt, 5 h, 91%
OTs
OTs
Me
N
N
NTf2
Bu
Me
N
N
N
N
Bu
Me
N
N
N
21
Br
16
NaBF4, H2O
rt, 5 h, quant.
O
O
BF4
Bu
N
Me Me
28
22
Scheme 4.
TsO
OTs
OTs
N
OTs
N
Bu
Bu
N
13
N
O
O
toluene, reflux
overnight
quant.
O
O
Me Me
29
2.3. Synthesis of CIL C
Me Me
30
Dicationic ILs including bisimidazolium salts were first reported
by Armstrong and his co-workers.9 Their studies showed that this
type of ILs have thermal stabilities greater than that of mono-
cationic ILs. The C2-symmetric CILs 25 and 27, which are chiral
bisimidazolium salts, were prepared as follows (Scheme 5). The
reaction of mesylate 2310 with imidazole in the presence of NaH in
DMF produced diimidazolylhexane 24, which subsequently un-
derwent quaternization by reaction with 1-bromobutane to afford
bisimidazolium bromide 25 as an oil in excellent yield. On the other
hand, treatment of 24 with iodomethane produced 26 as a solid,
which was then quantitatively converted to an oily chloride 27
using AgCl. The anion exchange was confirmed by mass spectros-
copy. Only a peak for chloride was observed at 35 m/z in the neg-
ative ion mode, and no peak for iodide was seen.
NTf2
NTf2
Bu
N
Bu
LiNTf2
N
N
N
H2O
rt, overnight
42%
O
O
Me Me
31
Scheme 6.
The CILs with benzylidene acetal moiety were synthesized from
dibutyl-(
)-(þ)-tartrate 32 (Schemes 7e9). After the formation of
L
the acetal, dibutyl esters were reduced into hydroxyl groups, which
were then converted into bromo groups to afford 35 (Scheme 7).
The amorphous bromide 36 was obtained by the reaction of 35 with
13. The anion exchange reactions of 36 were carried out to afford
the triflate 37 and the bis(trifluoromethanesulfonyl)imide 38 as oils
and tetrafluoroborate 39 as a solid (Scheme 8). The reaction of the
bromide 35 with 1-metylimidazole afforded the amorphous imi-
dazolium bromide 40, which was then converted to the oily bis(-
trifluoromethanesulfonyl)imide 41 (Scheme 9). The anions of
37e39, 41 were detected and confirmed by 1H NMR, 19F NMR, and
mass spectra.
2.4. Synthesis of CIL D
The synthesis of chiral imidazolium salt 28 from 29 was re-
ported by Dorta’s group (Scheme 6).11 Although 28 is solid, it was
anticipated that the conversion of the counter anion and N-sub-
stituents would afford CILs having the chiral dioxolane (dimethy-
lacetal) structures. The reaction of 29 with 1-butylimidazole
produced the amorphous product 30, which was then treated with
lithium bis(trifluoromethanesulfonyl)imide in water to afford 31 as
an oil (Scheme 6).

Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
9693
Br
N
Br
N
Me
BuO2C
CO2Bu
Br
Me
Br
N
N
PhCHO
TsOH
N
N
BuO2C
HO
CO2Bu
OH
Me
O
O
O
O
O
N
O
toluene
benzene
reflux, overnight
Ph
33
reflux, overnight
72%
Ph
35
40
Ph
32
HO
OH
Br
Br
Me
NTf2
NTf2
Me
N
N
N
PPh3, CBr4
LiNTf2
LiAlH4
O
O
O
O
ether, rt, 2 h
84% (2 steps)
O
O
CH2Cl2, rt, 3 h
H2O
rt, 4 h
77%
Ph
34
Ph
35
87%
Ph 41
Scheme 9.
Br
N
Br
N
Bu
Bu
N
N
13
Br
Br
OH
O
O
H2, Pd/C, HCl
toluene
reflux, overnight
73%
Br
O
O
Br
MeOH
rt, 5 h
62%
Ph
36
OH
Ph
35
42
Scheme 7.
Br
OH
13
toluene
OTf
N
OTf
N
Bu
Bu
N
Bu
N
N
KOTf, H2O
N
N
N
Bu
Bu
N
rt, overnight
86%
reflux, overnight
54%
OH
43
Br
O
O
Ph
37
NTf2
OH
LiNTf2
Bu
N
Bu
N
NTf2
N
NTf2
N
Bu
Bu
LiNTf2, H2O
rt, overnight
quant.
N
N
N
H2O
rt, 10 h
86%
N
OH
44
NTf2
36
O
O
Scheme 10.
Ph
38
BF4
BF4
N
Bu
N
carbonate was used as base. When the monoimidazolium-type
CILs A and B (5 and 11, respectively) were used, the reaction
showed no enantioselectivity (entries 1, 2). On the other hand, the
bisimidazolium-type CILs C and D (27, 41, and 44) induced
enantioselectivity to give 49a,b12 in 2e5% ee (entries 3e6). The
enantiomeric excess was analyzed by HPLC using a Daicel CHIR-
ALPAK AD or AD-H column (hexane/2-propanol¼9/1). When CIL
41 was used, the enantiomer that was produced in excess was
eluted faster. On the other hand, in the case of CIL 44, the en-
antiomer that was obtained in excess was eluted later except for
entries 12, and 16. (The absolute configurations of each enantio-
mer are unknown.) The use of chalcone derivatives 46,13 47,14 and
4814, which have the bulkier aromatic substituents 1-naphthyl, 2-
naphthyl, and 9-anthryl increased the enantioselectivities as
a whole (3e14% ee, entries 7e12). In the case of the substrate 47
and 48, however, the reaction rates were significantly decreased.
The use of di-tert-butyl malonate 49b and a cyclic ester Mel-
drum’s acid 49c as Michael addition donors also decreased the
reaction rates (entries 13e20). In the reaction of 45, the use of 49c
resulted in higher selectivities (12e13% ee, entries 15, 16) com-
pared with that achieved with diethyl malonate 49a (4% ee, en-
tries 4, 6).
NaBF4, H2O
rt, overnight
57%
N
O
O
Ph
39
Scheme 8.
The C2-symmetric CIL 44 was also synthesized from 35
(Scheme 10). After the benzylidene acetal of 35 was deprotected,
the resulting 42 was subjected to a reaction with 13. The product 43
was obtained as an amorphous solid. The anion of 43 was ex-
changed to bis(trifluoromethanesulfonyl)imide to afford 44 as an
oil.
2.5. Michael addition in CIL AeD
Michael addition11 of diethyl malonate 49a to the chalcone 45
was examined (Table 1, entries 1e6). CILs were diluted with the
co-solvent toluene to reduce their viscosity,6b and potassium

9694
Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
Table 1
Michael addition of malonate esters to chalcone derivatives in CILs
45, 50: Ar1 = Ar2 = Ph
CO2R
O
RO2C
Ar1
1
2
46 51
,
: Ar = 1-naphthyl, Ar = Ph
O
CIL
47, 52: Ar1 = 1-naphthyl, Ar2 = 2-naphthyl
CO2R
CO2R
K2CO3
Ar1
1
2
Ar2
48 53
, : Ar = 9-anthryl, Ar = Ph
H2C
+
toluene
Ar2
Me
Me
a: R = Et; b: R = t-Bu; c: R =
45 48
49a c
50 53
Entry
Ar1
Ar2
R
CIL
Conditionsa
Yield %
ee %b
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
5
11
27
41
41
44
41
44
41
44
41
44
41
44
41
rt, overnight
rt, overnight
rt, overnight
rt, overnight
74
100c
90
81
33
100
82
82
17
34
10
4
0
0c
2
4
5
4
7
10
14
3
2
11
3
4
12
0
ꢀC, 2 days
rt, overnight
rt, overnight
rt, overnight
rt, 1 day
rt, 1 day
rt, 1 day
1-Naphthyl
1-Naphthyl
1-Naphthyl
1-Naphthyl
9-Anthryl
9-Anthryl
Ph
9
2-Naphtyl
2-Naphtyl
10
11
12
13
14
15
Ph
Ph
Ph
Ph
Ph
rt, 1 day
t-Bu
t-Bu
rt, overnight
rt, overnight
rt, 1 day
13
35
55
Ph
Ph
16
17
18
19
Ph
Ph
44
41
44
41
44
rt, 1 day
rt, 3 days
rt, 3 days
rt, 3 days
rt, 3 days
28
40
8
13
8d
11d
6
1-Naphthyl
1-Naphthyl
1-Naphthyl
1-Naphthyl
Ph
Ph
2-Naphtyl
2-Naphtyl
27
12
20
8
a
The reaction was conducted with chalcone derivatives (0.1 mmol), malonate esters (0.12 mmol), and K2CO3 (0.3 mmol), in CILs (1.0 mmol) and toluene (0.1 mL).
b
c
Determined by HPLC.
96% yield, 25% ee, as reported.6b
d
HPLC analysis was performed after conversion of 50c to dimethyl 2-[1-(naphthalen-1-yl)-3-oxo-3-phenylpropyl]malonate.
3. Conclusion
4.2. Synthesis of CIL A
We have shown the syntheses and spectroscopic characteristics
of four structural types of CILs: monoimidazolium salts bearing an
4.2.1. (R)-1-(1-Phenylethyl)-1H-imidazole (2).7 (R)-1-Phenylethyl-
amine (2.6 mL, 20 mmol) and aqueous ammonia (2.8 mL,
40 mmol) were added to a mixture of formaldehyde (1.5 mL,
20 mmol) and glyoxal (2.3 mL, 20 mmol). The mixture was stirred
at a reflux temperature overnight, and then the product was
extracted with dichloromethane. The organic layer was washed
with brine, dried over MgSO4, and filtered. The solvent was
evaporated in vacuo to give the crude product, which was purified
by silica gel chromatography (8% MeOH/CH2Cl2) to give 2 (1.6 g,
asymmetric carbon atom
(A); monoimidazolium salts bearing an asymmetric carbon atom
to the nitrogen atom on a N-substituent (B); C2-symmetric bisi-
midazolium salts bearing asymmetric carbon atoms to the ni-
trogen atoms of imidazoles (C); and C2-symmetric bisimidazolium
salts bearing asymmetric carbon atoms to the nitrogen atoms of
a to the nitrogen atom on a N-substituent
b
a
b
imidazoles (D). We also performed Michael addition using CILs
AeD as solvents in order to evaluate their chiral-inducing abilities.
The bisimidazolium-type CILs C and D were observed to have subtle
but steady inducing effects. Notably, CILs 41 and 44 induce opposite
selectivities, although both CILs come from the same chiral starting
material 32 and have stereogenic centers with the same configu-
rations. At present, the mechanism of the selectivity remains un-
clear and it is still quite a challenge to achieve high selectivity using
chiral solvents. However, our result indicates that more efficient
chiral solvents can be developed by designing CIL structures based
on bis- or polyimidazolium salts, and that chiral ionic liquids can be
used in asymmetric synthesis as green solvents/or catalysts. We
believe that asymmetric induction by recyclable chiral solvents is
the final frontier in asymmetric organic synthesis.
47%) as a brown oil; 1H NMR (500 MHz, CDCl3)
d: 1.86 (3H, d,
J¼6.9 Hz, CH3), 5.34 (1H, q, J¼6.9 Hz, CH), 6.92 (1H, t, J¼1.4 Hz,
imidazole), 7.09 (1H, t, J¼1.4 Hz, imidazole), 7.14 (2H, q, J¼2.9 Hz,
phenyl), 7.28e7.36 (3H, m, phenyl), 7.66 (1H, s, imidazole); 13C
NMR (126 MHz, CDCl3) d: 22.1, 56.7, 118.1, 126.1, 128.2, 129.0, 129.5,
136.2, 141.7; HRMS (FAB) m/z: MHþ, found 173.1094. C11H13N2 re-
quires 173.1079.
4.2.2. (R)-1-(2-Ethoxyethyl)-3-(1-phenylethyl)imidazolium bromide
(4). 2-Bromoethylethylether (3) (0.14 mL, 3.2 mmol) was drop-
wisely added to a solution of imidazole 2 (0.37 g, 2.2 mmol) in
toluene (3 mL). The mixture was stirred at a reflux temperature
overnight to give the oily product insoluble to toluene. After de-
cantation of the supernatant, the crude product was washed with
toluene several times, and then the remaining solvent was
evaporated in vacuo to give 4 (0.70 g, quant.) as a brown oil; 1H
4. Experimental section
4.1. General
NMR (500 MHz, CDCl3)
d
: 1.53 (3H, t, J¼7.5 Hz, CH3CH2), 2.05 (3H,
d, J¼7.3 Hz, CH3CH), 3.52 (2H, q, J¼7.5 Hz, CH3CH2), 3.84 (2H, t,
J¼4.5 Hz, CH2N), 4.66 (2H, t, J¼4.5 Hz, CH2O), 5.82 (1H, q,
J¼7.3 Hz, CH), 7.04 (1H, t, J¼1.8 Hz, imidazole), 7.40e7.42 (6H, m,
All of the chiral starting materials were used without purifica-
tion.15 The enantiomeric purities of CILs were not determined.

Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
9695
imidazole, phenyl), 10.86 (1H, s, imidazole); 13C NMR (126 MHz,
CDCl3) : 15.1, 21.4, 50.1, 60.0, 66.8, 68.3, 120.4, 123.5, 127.0, 129.5,
cyclohexylethylamine (1) (1.0 mL, 6.7 mmol) were added to a mix-
ture of formaldehyde (0.72 mL, 9.7 mmol) in acetic acid (2.5 mL).
The mixture was stirred overnight at 70 ꢀC. After being cooled, the
mixture was neutralized by adding a NaHCO3 solution, and then the
product was extracted with dichloromethane. The organic layer
was washed with brine, dried over MgSO4, and filtered. The solvent
was evaporated in vacuo to give the crude product, which was
purified by silica gel chromatography (2% MeOH/CH2Cl2) to give 9
d
136.3, 138.0; IR (neat) cmꢁ1: 1557, 1454, 1155, 1113; HRMS (FAB)
m/z: Mþ, found 245.1638. C15H21N2O requires 245.1654; ½a D21
ꢂ
þ1.45 (c 1.0, CHCl3).
4.2.3. (R)-1-Butyl-3-(1-phenylethyl)imidazolium bromide (5). 1-Bro-
mobutane (1.6 mL, 14.2 mmol) was dropwisely added to a solu-
tion of imidazole 2 (1.6 g, 9.5 mmol) in toluene (6 mL). The
mixture was stirred at a reflux temperature overnight to give the
oily product insoluble to toluene. After decantation of the su-
pernatant, the crude product was washed with toluene several
times, and then the remaining solvent was evaporated in vacuo to
(0.28 g, 23%) as a pale brown oil; 1H NMR (500 MHz, CDCl3)
d:
0.70e0.80 (1H, m, cyclohexyl), 0.90e1.00 (1H, m, cyclohexyl),
1.07e1.28 (3H, m, cyclohexyl), 1.30e1.36 (1H, m, cyclohexyl), 1.45
(3H, d, J¼6.9 Hz, CH3), 1.48e1.55 (1H, m, cyclohexyl),1.60e1.70 (2H,
m), 1.73e1.80 (2H, m, cyclohexyl), 3.83 (1H, quint, J¼6.9 Hz, CH),
6.88 (1H, t, J¼1.1 Hz, imidazole), 7.06 (1H, t, J¼1.1 Hz, imidazole),
give 5 (0.70 g, quant.) as a brown oil; 1H NMR (500 MHz, CDCl3)
d:
0.95 (3H, t, J¼7.4 Hz, CH3CH2CH2CH2), 1.39 (2H, sext, J¼7.4 Hz,
CH3CH2CH2CH2), 1.85 (2H, quint, J¼7.4 Hz, CH3CH2CH2CH2), 2.03
(3H, d, J¼6.9 Hz, CH3CH), 4.38 (2H, t, J¼7.4 Hz, CH3CH2CH2CH2),
5.99 (1H, q, J¼6.9 Hz, CH), 7.13 (1H, t, J¼1.7 Hz, imidazole), 7.23
(1H, t, J¼1.7 Hz, imidazole), 7.32e7.45 (5H, m, phenyl), 10.97 (1H,
7.40 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d: 19.0, 25.9,
26.0, 26.2, 29.5, 29.9, 44.5, 58.9,117.2,129.0,136.4; HRMS (FAB) m/z:
MHþ, found 179.1569. C11H19N2 requires179.1548; ½a D23
ꢁ17.01 (c
ꢂ
1.0, CHCl3).
s, imidazole); 13C NMR (126 MHz, CDCl3)
d
: 13.6, 19.6, 21.4, 32.2,
4.2.7. (R)-3-(1-Cyclohexylethyl)-1-methylimidazolium methylsulfonate
(10). A solution of 9 (0.54 g, 3.0 mmol) and dimethyl sulfonate
(0.29 mL, 3.0 mmol) in acetonitrile (6 mL) was stirred at 70 ꢀC for
1.5 h. The solvent was evaporated off. The oily residue was
washed with diethyl ether and dried in vacuo to give 10 (0.97 g,
50.0, 59.8, 120.8, 122.3, 127.0, 129.4, 129.5, 136.4, 138.1; IR (neat)
cmꢁ1: 3408, 2961, 1553, 1456, 1155; HRMS (FAB) m/z: Mþ, found
229.1680.
CHCl3).
C
15H21N2O requires 229.1705;
½
a 2D5
ꢂ
þ18.33 (c 0.9,
quant.) as a yellow oil; 1H NMR (500 MHz, CDCl3)
d: 0.88e1.02
4.2.4. (R)-1-Butyl-3-(1-phenylethyl)imidazolium trifluoromethane-
sulfonate (6). A solution of 5 (0.31 g, 1.0 mmol) and potassium
trifluoromethanesulfonate (0.29 g, 1.5 mmol) in water (2 mL) was
stirred at room temperature overnight. The product was extracted
with chloroform. The organic layer was dried over MgSO4, and
filtered. The solvent was evaporated in vacuo to give 6 (0.29 g,
(2H, m, cyclohexyl), 1.08e1.33 (4H, m, cyclohexyl), 1.55 (3H, d,
J¼6.9 Hz, CH3CH), 1.59e1.78 (5H, m, cyclohexyl), 3.74 (3H, s,
CH3O), 4.04 (3H, s, CH3N), 4.28 (1H, quint, J¼6.9 Hz, CH), 7.19 (1H,
t, J¼1.7 Hz, imidazole), 7.35 (1H, t, J¼1.7 Hz, imidazole), 9.56 (1H,
s, imidazole); 13C NMR (126 MHz, CDCl3)
d: 18.1, 25.6, 25.7, 25.8,
29.1, 29.2, 36.5, 43.4, 54.5, 62.3, 120.4, 124.0, 136.8; IR (neat)
76%) as a brown oil; 1H NMR (500 MHz, CDCl3)
d
: 0.93 (3H, t,
cmꢁ1: 2928, 1557, 1450, 1165, 1043, 843; HRMS (FAB) m/z: Mþ,
J¼7.4 Hz, CH3CH2CH2CH2), 1.34 (2H, sext, J¼7.4 Hz,
CH3CH2CH2CH2), 1.85 (2H, quint, J¼7.4 Hz, CH3CH2CH2CH2), 1.96
(3H, d, J¼6.9 Hz, CH3CH), 4.23 (2H, t, J¼7.4 Hz, CH3CH2CH2CH2),
5.70 (1H, q, J¼6.9 Hz, CH), 7.20 (1H, t, J¼1.7 Hz, imidazole), 7.30
(1H, t, J¼1.7 Hz, imidazole), 7.35e7.41 (5H, m, phenyl), 9.37 (1H, s,
found 193.1715. C12H21N2 requires 193.1705; ½a D25
ꢁ2.99 (c 0.8,
ꢂ
CH3OH).
4.3. Synthesis of CIL B
imidazole); 13C NMR (126 MHz, CDCl3)
d: 13.4, 19.5, 20.9, 32.1,
50.1, 60.3, 120.8 (q, J¼1300 Hz), 120.8, 122.2, 122.2, 126.9, 129.6,
4.3.1. Ethyl (S)-2-(benzyloxy)propionate.6b Sodium hydride (60% in
oil, 3.8 g, 94.4 mmol) and (
135.7, 137.8; 19F NMR (470 MHz, CDCl3)
d
: ꢁ79.0; IR (neat) cmꢁ1
:
L)-(ꢁ)-ethyl lactate (1) (10.0 mL,
1555, 1458, 1348, 1179, 1132, 1051; HRMS (FAB) m/z: Mþ, found
85.8 mmol) were added to a solution of benzyl bromide (12.5 mL,
103 mmol) in THF/DMF (50 mL/50 mL). The mixture was stirred at
70 ꢀC for 3 h. The product was extracted with ethyl acetate. The
organic layer was washed with brine, dried over MgSO4, filtered,
and concentrated. The residue was purified by silica gel chroma-
tography (30% AcOEt/hexane) to give the product (16.2 g, 91%) as
229.1687. C15H21N2 requires 229.1705; MS (FABꢁ) m/z: 149; ½a D26
ꢂ
þ10.16 (c 1.2, CHCl3).
4.2.5. (R)-1-Butyl-3-(1-phenylethyl)imidazolium bis(trifluoromethane-
sulfonyl)amide (7). A solution of 5 (0.31 g, 1.0 mmol) and lithium
bis(trifluoromethanesulfonyl)imide (0.29 g, 1.0 mmol) in water
(2 mL) was stirred overnight at 70 ꢀC. The product was extracted
with chloroform. The organic layer was washed with brine, dried
over NaSO4, and filtered. The solvent was evaporated in vacuo to
a colorless oil; 1H NMR (500 MHz, CDCl3)
d
: 1.28 (3H, t, J¼7.4 Hz,
CH3CH2), 1.43 (3H, d, J¼6.9 Hz, CH3CH), 4.04 (1H, q, J¼6.9 Hz, CH),
4.16e4.25 (2H, m, CH3CH2), 4.44 (1H, d, J¼12.0 Hz, PhCH2), 4.69
(1H, d, J¼12.0 Hz, PhCH2), 7.27e7.37 (5H, m, phenyl); 13C NMR
give 6 (0.33 g, 66%) as a yellow oil; 1H NMR (500 MHz, CDCl3)
d: 0.97
(126 MHz, CDCl3)
137.7, 173.3.
d: 14.3, 18.8, 60.9, 72.1, 74.1, 127.9, 128.1, 128.5,
(3H, t, J¼7.4 Hz, CH3CH2CH2CH2), 1.38 (2H, sext, J¼7.4 Hz,
CH3CH2CH2CH2), 1.87 (2H, quint, J¼7.4 Hz, CH3CH2CH2CH2), 1.97 (3H,
d, J¼6.9 Hz, CH3CH), 4.22 (2H, t, J¼7.4 Hz, CH3CH2CH2CH2), 5.70 (1H,
d, J¼6.9 Hz, CH), 7.12 (1H, t, J¼1.7 Hz, imidazole), 7.19 (1H, t,
J¼1.7 Hz, imidazole), 7.32e7.35 (2H, m, phenyl), 7.41e7.45 (3H, m,
4.3.2. (S)-2-Benzyloxypropan-1-ol.6b Ethyl (S)-2-(benzyloxy)pro-
pionate (16.2 g, 77.8 mmol) was added dropwisely to a suspen-
sion of LiAlH4 (3.2 g, 77.8 mmol) in dry diethyl ether (200 mL)
with ice-cooling. The mixture was stirred at room temperature for
2 h, neutralized with saturated ammonium chloride solution, and
then filtered. The filtrate was extracted with ethyl acetate. The
organic layer was washed with brine, dried over MgSO4, filtered,
and concentrated. The residue was purified by silica gel chro-
matography (AcOEt/hexane: 1/8) to give the product (3.7 g,
phenyl), 9.01 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d: 13.3,
19.4, 20.8, 32.0, 50.1, 60.3, 119.9 (q, J¼1250 Hz), 121.2, 122.6, 126.9,
129.7, 129.7, 134.5, 137.6; 19F NMR (470 MHz, CDCl3)
d
: ꢁ78.9; IR
(neat) cmꢁ1: 1557, 1456, 1252, 1152, 1028; HRMS (FAB) m/z: Mþ,
found 229.1717. C15H21N2 requires 229.1705; MS (FABꢁ) m/z: 280;
½
a 2D6
ꢂ
þ12.84 (c 1.0, CHCl3).
quant.) as a colorless oil; 1H NMR (500 MHz, CDCl3)
d: 1.19 (3H, d,
4.2.6. (R)-1-(1-Cyclohexylethyl)-1H-imidazole (9). Glyoxal (0.72 mL,
9.7 mmol), an aqueous solution (1 mL) of ammonium acetate
(0.75 g, 9.7 mmol), and a methanol (1 mL) solution of (R)-(ꢁ)-1-
J¼6.7 Hz, CH3), 2.04 (1H, t, J¼3.7 Hz, OH), 3.48e3.53 (1H, m, CH),
3.60e3.72 (2H, m, CH2OH), 4.49 (1H, d, J¼11.6 Hz, PhCH2), 4.66
(1H, d, J¼11.6 Hz, PhCH2), 7.27e7.37 (5H, m, phenyl); 13C NMR

9696
Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
(126 MHz, CDCl3)
138.7.
d
: 16.3, 66.1, 70.9, 75.8, 127.7, 127.9, 127.9, 128.5,
1456, 1261, 1148, 1028; HRMS (FAB) m/z: Mþ, found 245.1630.
C
15H21N2O requires 245.1648; MS (FABꢁ) m/z: 149; ½a D26
þ36.80 (c
ꢂ
1.0, CHCl3).
4.3.3. (S)-Benzyl 1-bromo-2-propyl ether (14).6b Triphenylphosphine
(49.1 g, 182 mmol) and NBS (33.0 g, 182 mmol) were added to
a solution of (S)-2-benzyloxypropan-1-ol (15.1 g, 90.8 mmol) in
dichloromethane (200 mL) with ice-cooling. The mixture was stir-
red at room temperature overnight, and poured into water. The
organic layer was washed with brine, dried over MgSO4, filtered, and
concentrated. The residue was purified by silica gel chromatography
(20% AcOEt/hexane) to give 14 (17.7 g, 85%) as a colorless oil; 1H
4.3.7. (S)-1-(2-Benzyloxypropyl)-2,3-dimethylimidazolium bis(tri-
fluoromethanesulfonyl)amide (18). A solution of 15 (1.3 g, 4.2 mmol)
and lithium bis(trifluoromethanesulfonyl)imide (1.8 g, 6.3 mmol) in
water (10 mL) was stirred at room temperature for 5 h. The product
was extracted with chloroform. The organic layer was washed with
brine, dried over NaSO4, and filtered. The solvent was evaporated in
vacuo to give 18 (2.1 g, 95%) as a yellow oil; 1H NMR (500 MHz,
NMR (500 MHz, CDCl3)
d
: 1.33 (3H, d, J¼6.7 Hz, CH3), 3.39 (1H, dd,
CDCl3)
d
: 1.30 (3H, d, J¼5.7 Hz, CH3CH), 2.47 (3H, s, 2-CH3), 3.75 (3H,
J¼4.9,10.4 Hz, CH2Br), 3.46 (1H, dd, J¼4.9,10.4 Hz, CH2Br), 3.73e3.76
s, CH3N), 3.85e3.89 (1H, m, CH), 3.98 (1H, dd, J¼9.2, 14.3 Hz,
CH2CH), 4.20 (1H, d, J¼12.0 Hz, PhCH2), 4.32 (1H, dd, J¼2.9, 14.3 Hz,
CH2CH), 4.55 (1H, d, J¼12.0 Hz, PhCH2), 7.07e7.10 (2H, m, phenyl),
7.27e7.30 (2H, m, phenyl), 7.32 (1H, d, J¼1.7 Hz, imidazole), 7.39
(1H, m, CH), 4.59 (2H, s, PhCH2), 7.27e7.38 (5H, m, phenyl); 13C NMR
(126 MHz, CDCl3) d: 19.2, 36.8, 71.2, 74.3, 127.9, 128.6, 138.4.
4.3.4. (S)-1-(2-Benzyloxypropyl)-2,3-dimethylimidazolium bromide
(15). 1,2-Dimethylimidazole (12) (0.14 mL, 1.38 mmol) was added
dropwisely to a solution of 14 (0.21 g, 0.92 mmol) in toluene (5 mL).
The mixture was stirred at reflux temperature overnight. The crude
product was washed with toluene, and the remaining solvent and
the starting materials were distilled off using a glass tube oven to
give 15 (0.29 g, quant.) as a colorless solid; 1H NMR (500 MHz,
(1H, d, J¼1.7 Hz, imidazole); 13C NMR (126 MHz, CDCl3)
d: 9.8, 16.7,
35.1, 53.6, 71.1, 73.2, 119.9 (q, J¼1278 Hz), 121.2, 121.9, 122.0, 128.1,
128.5, 137.6, 144.7; 19F NMR (470 MHz, CDCl3)
d: ꢁ79.4; IR (neat)
cmꢁ1: 1564, 1454, 1049, 1026; HRMS (FAB) m/z: Mþ, found
245.1637. C15H21N2O requires 245.1648; MS (FABꢁ) m/z: 280; ½a D26
ꢂ
þ26.48 (c 1.0, CHCl3).
CDCl3)
d
: 1.35 (3H, d, J¼6.1 Hz, CH3CH), 2.61 (3H, s, 2-CH3), 3.88 (3H,
4.3.8. (S)-1-(2-Benzyloxypropyl)-2,3-dimethylimidazolium tetrafluoro-
borate (19). A solution of 15 (0.31 g, 1.0 mmol) and sodium tetra-
fluoroborate (0.17 g, 1.5 mmol) in water (2 mL) was stirred at room
temperature for 5 h. The product was extracted with chloroform.
The organic layer was washed with brine, dried over NaSO4, and
filtered. The solvent was evaporated in vacuo to give 19 (0.12 g, 36%)
s, CH3N), 3.95e3.97 (1H, m, CH), 4.06 (1H, dd, J¼14.0, 9.1 Hz,
CH2CH), 4.25 (1H, d, J¼14.0 Hz, PhCH2), 4.58e4.60 (2H, m, CH2CH,
PhCH2), 7.10 (2H, dd, J¼1.8, 6.7 Hz, phenyl), 7.27e7.31 (3H, m,
phenyl), 7.54 (1H, d, J¼1.8 Hz, imidazole), 7.71 (1H, d, J¼1.8 Hz,
imidazole); 13C NMR (126 MHz, CDCl3)
d: 10.9, 17.0, 35.9, 53.7, 71.0,
73.6, 122.3, 122.4, 127.9, 128.0, 128.5, 137.6, 144.7; IR (neat) cmꢁ1
:
as a yellow oil; 1H NMR (500 MHz, CDCl3)
d: 1.28 (3H, d, J¼6.3 Hz,
1533, 1454, 1024; HRMS (FAB) m/z: Mþ, found 245.1637 C15H21N2O
CH3CH), 2.41 (3H, s, 2-CH3), 3.68 (3H, s, CH3N), 3.79e3.84 (1H, m,
CH), 3.93 (1H, dd, J¼14.3, 9.2 Hz, CH2CH), 4.14 (1H, dd, J¼2.3,
14.3 Hz, CH2CH), 4.20 (1H, d, J¼11.5 Hz, PhCH2), 4.55 (1H, d,
J¼11.5 Hz, PhCH2), 7.07e7.09 (3H, m, phenyl), 7.16 (1H, d, J¼2.3 Hz,
imidazole), 7.27e7.29 (3H, m, phenyl, imidazole); 13C NMR
requires 245.1648; MS (FABꢁ) m/z: 79, 81; ½a D25
ꢂ
þ35.24 (c 1.0,
CHCl3).
4.3.5. (S)-1-(2-Benzyloxypropyl)-3-butylimidazolium
bromide
(16). 1-Butylimidazole (13) (2.6 g, 21.0 mmol) was added drop-
wisely to a solution of 14 (3.2 g, 14.0 mmol) in toluene (15 mL). The
mixture was stirred at reflux temperature overnight. The crude
product was washed with toluene, and the remaining solvent was
evaporated in vacuo to give 16 (4.8 g, quant.) as a yellow oil; 1H
(126 MHz, CDCl3) d: 10.0, 16.8, 35.2, 53.4, 71.0, 73.6, 122.0, 122.2,
127.9, 128.0, 128.5, 137.7, 144.8; 19F NMR (470 MHz, CDCl3)
d:
ꢁ152.9; IR (neat) cmꢁ1: 1564, 1454, 1049, 1026; HRMS (FAB) m/z:
Mþ, found 245.1679. C15H21N2O requires 245.1648; MS (FABꢁ) m/z:
87; ½a 2D5
þ41.47 (c 1.0, CHCl3).
ꢂ
NMR (500 MHz, CDCl3)
d
: 0.97 (3H, t, J¼7.3 Hz, CH3CH2CH2CH2),
1.32 (3H, d, J¼6.1 Hz, CH3CH), 1.36e1.39 (2H, sext, J¼7.3 Hz,
CH3CH2CH2CH2), 1.88 (2H, quint, J¼7.9, CH3CH2CH2CH2), 4.03e4.06
(1H, m, CH), 4.22e4.29 (4H, m, CH3CH2CH2CH2, CH2CH), 4.36 (1H, d,
J¼11.6 Hz, PhCH2), 4.63 (1H, d, J¼11.6 Hz, PhCH2), 4.78 (1H, dd,
J¼2.4, 14.0 Hz, CH2CH), 7.10 (1H, s, imidazole), 7.14e7.34 (5H, m,
phenyl), 7.37 (1H, s, imidazole), 10.62 (1H, s, imidazole); 13C NMR
4.3.9. (S)-1-(2-Benzyloxypropyl)-3-butylimidazolium
trifluoro-
methanesulfonate (20). A solution of 16 (0.38 g, 1.1 mmol) and
potassium trifluoromethanesulfonate (0.20 g, 1.7 mmol) in water
(2 mL) was stirred at room temperature for 5 h. The product was
extracted with chloroform. The organic layer was washed with
brine, dried over MgSO4, and filtered. The solvent was evaporated
in vacuo to give 20 (0.43 g, 96%) as a yellow oil; 1H NMR (500 MHz,
(126 MHz, CDCl3) d: 13.5, 16.7, 19.4, 32.1, 49.8, 54.4, 70.8, 73.2, 121.6,
123.6, 127.8, 127.9, 128.5, 136.9, 137.6; IR (neat) cmꢁ1: 1533, 1454,
CDCl3)
d
: 0.95 (3H, t, J¼7.4 Hz, CH3CH2CH2CH2), 1.28 (3H, d,
1024; HRMS (FAB) m/z: Mþ, found 273.1967. C16H23N2O requires
J¼6.3 Hz, CH3CH), 1.33 (2H, sext, J¼7.4 Hz, CH3CH2CH2CH2), 1.83
(2H, quint, J¼7.4 Hz, CH3CH2CH2CH2), 3.94e3.97 (1H, m, CH),
4.14e4.17 (3H, m, CH3CH2CH2CH2, CH2CH), 4.33 (1H, d, J¼12.0,
PhCH2), 4.53 (1H, dd, J¼2.9, 14.3 Hz, CH2CH), 4.62 (1H, d, J¼12.0 Hz,
PhCH2), 7.13 (1H, t, J¼1.7 Hz, imidazole), 7.20 (2H, d, J¼7.4 Hz,
phenyl), 7.30e7.32 (3H, m, phenyl), 7.35 (1H, t, J¼1.7 Hz, imidaz-
273.1961; MS (FABꢁ) m/z: 79, 81; ½a D26
þ41.48 (c 1.1, CHCl3).
ꢂ
4.3.6. (S)-1-(2-Benzyloxypropyl)-2,3-dimethylimidazolium trifluoro-
methanesulfonate (17). A solution of 15 (0.46 g, 1.5 mmol) and po-
tassium trifluoromethanesulfonate (0.58 g, 3.0 mmol) in water
(5 mL) was stirred at room temperature overnight. The product was
extracted with chloroform. The organic layer was dried over
MgSO4, and filtered. The solvent was evaporated in vacuo to give 17
ole), 9.47 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d
: 13.3,
16.5, 19.3, 31.9, 49.7, 54.3, 70.7, 73.0, 120.7 (q, J¼1273 Hz), 121.9,
123.5, 127.8, 127.9, 128.5, 136.4, 137.6; 19F NMR (470 MHz, CDCl3)
d:
(0.29 g, 76%) as a yellow solid; 1H NMR (500 MHz, CDCl3)
d: 1.29
ꢁ79.0; IR (neat) cmꢁ1: 1564, 1454, 1256, 1223, 1155, 1028; HRMS
(3H, d, J¼6.3 Hz, CH3CH), 2.45 (3H, s, 2-CH3), 3.72 (3H, s, CH3N),
3.83e3.88 (1H, m, CH), 3.97 (1H, dd, J¼9.2, 11.5 Hz, CH2CH), 4.21
(1H, d, J¼11.5 Hz, PhCH2), 4.24 (1H, dd, J¼2.9, 11.5 Hz, CH2CH), 4.55
(1H, d, J¼11.5 Hz, PhCH2), 7.07e7.09 (2H, m, imidazole), 7.28e7.30
(FAB) m/z: Mþ, found 273.1951. C16H23N2O requires 273.1961; MS
(FABꢁ) m/z: 149; ½a 2D7
þ37.17 (c 1.1, CHCl3).
ꢂ
4.3.10. (S)-1-(2-Benzyloxypropyl)-3-butylimidazolium bis(trifluoro-
methanesulfonyl)amide (21). A solution of 16 (0.38 g, 1.1 mmol) and
lithium bis(trifluoromethanesulfonyl)imide (0.49 g, 1.7 mmol) in
water (2 mL) was stirred at room temperature for 5 h. The product
(5H, m, phenyl); 13C NMR (126 MHz, CDCl3)
d: 10.0, 16.8, 35.3, 53.5,
71.1, 73.5, 102.8 (q, J¼1273 Hz), 122.1, 128.0, 128.1, 128.5, 137.6,
144.8; 19F NMR (470 MHz, CDCl3)
d
: ꢁ79.0; IR (neat) cmꢁ1: 1541,

Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
9697
was extracted with chloroform. The organic layer was washed with
brine, dried over NaSO4, and filtered. The solvent was evaporated in
vacuo to give 21 (0.54 g, 91%) as a yellow oil; 1H NMR (500 MHz,
z: MHþ, found 219.1608. C12H19N4 requires 219.1610; MS (FABꢁ)
m/z: 87; ½a 2D5
ꢁ22.59 (c 1.0, CHCl3).
ꢂ
CDCl3)
d
: 0.95 (3H, t, J¼7.4 Hz, CH3CH2CH2CH2), 1.26 (3H, d,
4.4.3. [(2S,5S)-Hexane-2,5-bis(3-butylimidazolium)][bromide]2
(25). n-Butylbromide (14 l, 0.013 mmol) was added dropwisely
to a solution of 24 (11 mg, 0.05 mmol) in toluene (2 mL). The
mixture was stirred at reflux temperature overnight. The crude
product was washed with toluene, and the remaining solvent was
evaporated in vacuo to give 25 (24 mg, 99%) as a yellow oil; 1H
J¼6.3 Hz, CH3CH), 1.33 (2H, sext, J¼7.4 Hz CH3CH2CH2CH2), 1.80 (2H,
quint, J¼7.4 Hz, CH3CH2CH2CH2), 3.88e3.95 (1H, m, CH), 4.06 (1H,
dd, J¼7.9, 14.0 Hz, CH2CH), 4.13 (3H, m, CH3CH2CH2CH2, CH2CH),
4.31 (1H, d, J¼12.0 Hz, PhCH2), 4.38 (1H, dd, J¼2.9, 14.3 Hz, CH2CH),
4.62 (1H, d, J¼12.0 Hz, PhCH2), 7.15 (1H, t, J¼1.7 Hz, imidazole), 7.19
(2H, dd, J¼2.3, 8.0 Hz, phenyl), 7.30e7.32 (4H, m, phenyl, imidaz-
m
NMR (500 MHz, CDCl3)
d
: 0.98 (6H, t, J¼7.3 Hz, CH3CH2CH2CH2),
ole), 8.76 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d
: 13.3, 16.4,
1.39 (4H, sext, J¼7.3 Hz, CH3CH2CH2CH2), 1.60 (6H, d, J¼6.7 Hz,
CH3C), 1.90 (4H, quint, J¼6.7 Hz, CH3CH2CH2CH2), 2.08e2.14 (4H,
m, CH2CH), 4.26e4.35 (4H, m, CH3CH2CH2CH2), 5.04e5.06 (2H, m,
CH), 7.26 (2H, t, J¼1.8 Hz, imidazole), 8.03 (2H, t, J¼1.8 Hz, imid-
19.3, 31.9, 49.9, 54.6, 70.8, 72.9, 119.9 (q, J¼1273 Hz), 121.8, 123.7,
127.9, 128.1, 128.6, 135.7, 137.5; 19F NMR (470 MHz, CDCl3)
d: ꢁ79.4;
IR (neat) cmꢁ1: 1564, 1454, 1348, 1182, 1134, 1051; HRMS (FAB) m/z:
Mþ, found 273.1954. C16H23N2O requires 273.1961; MS (FABꢁ) m/z:
azole), 10.19 (2H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d: 13.5,
280; ½a 2D6
ꢂ
þ29.16 (c 1.4, CHCl3).
19.6, 21.8, 32.1, 32.8, 50.0, 57.0, 121.5, 122.1, 135.7; IR (neat) cmꢁ1
:
3397, 1557, 1456, 1163; HRMS (FAB) m/z: Mþ, found 332.2913.
4.3.11. (S)-1-(2-Benzyloxypropyl)-3-butylimidazolium tetrafluoro-
borate (22). A solution of 16 (0.91 g, 2.7 mmol) and sodium tet-
rafluoroborate (0.46 g, 4.1 mmol) in water (10 mL) was stirred at
room temperature for 5 h. The product was extracted with chlo-
roform. The organic layer was washed with brine, dried over
NaSO4, and filtered. The solvent was evaporated in vacuo to give 22
C
20H36N4 requires 332.2940; MS (FABꢁ) m/z: 79, 81; ½a D24
ꢁ10.77
ꢂ
(c 1.0, CHCl3).
4.4.4. [(2S,5S)-Hexane-2,5-bis(3-metylimidazolium)][iodide]2
(26). Methyl iodide (1.44 mL, 21.6 mmol) was added dropwisely
to a solution of 24 (0.59 g, 2.7 mmol) in toluene (10 mL) with
ice-cooling. The mixture was stirred at 80 ꢀC for 3 h. The crude
product was washed with toluene, and the remaining solvent
was evaporated in vacuo to give 26 (1.26 g, 93%) as a yellow
(1.0 g, quant.) as a yellow oil; 1H NMR (500 MHz, CDCl3)
d: 0.94
(3H, t, J¼7.4 Hz, CH3CH2CH2CH2), 1.28 (3H, d, J¼6.3 Hz, CH3CH),1.34
(2H, sext, J¼8.0 Hz, CH3CH2CH2CH2), 1.84 (2H, quint, J¼8.0 Hz,
CH3CH2CH2CH2), 3.95e4.01 (1H, m, CH), 4.15e4.21 (3H, m,
CH3CH2CH2CH2, CH2CH), 4.33 (1H, d, J¼11.5 Hz, PhCH2), 4.58e4.62
(2H, m, PhCH2, CH2CH), 7.14 (1H, t, J¼1.7 Hz, imidazole), 7.20 (2H, d,
J¼8.0 Hz, phenyl), 7.26e7.33 (3H, m, phenyl), 7.36 (1H, t, J¼1.7 Hz,
solid; 1H NMR (500 MHz, CDCl3)
d
: 1.60 (6H, d, J¼6.9 Hz, CH3CH),
2.15 (4H, dd, J¼2.3, 4.6 Hz, CH2), 4.02 (6H, s, CH3N), 4.88e4.95
(2H, m, CH), 7.18 (2H, t, J¼1.7 Hz, imidazole), 7.78 (2H, t,
J¼1.7 Hz, imidazole), 9.85 (2H, s, imidazole); 13C NMR (126 MHz,
imidazole), 9.79 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d
:
CDCl3) d :
: 18.8, 31.2, 34.4, 55.5, 119.1, 122.6, 134.3; IR (neat) cmꢁ1
13.4, 16.6, 19.4, 32.0, 49.8, 54.4, 70.8, 73.2, 121.6, 123.6, 127.8, 127.9,
3393, 3082, 1553, 1456, 1165; HRMS (FAB) m/z: [MI]þ, found
128.5, 136.7, 137.6; 19F NMR (470 MHz, CDCl3)
d
: ꢁ151.9; IR (neat)
375.1042. C14H24N4I requires 375.1046; MS (FABꢁ) m/z: 127; ½a D26
ꢂ
cmꢁ1: 1539, 1454, 1364, 1179, 1134, 1051; HRMS (FAB) m/z: Mþ,
þ4.09 (c 1.0, CH3OH).
found 273.1962. C16H23N2O requires 273.1961; MS (FABꢁ) m/z: 87;
½
a 2D5
ꢂ
þ39.95 (c 1.0, CHCl3).
4.4.5. [(2S,5S)-Hexane-2,5-bis(3-metylimidazolium)][chloride]2
(27). Silver chloride (1.4 g, 9.6 mmol) was added dropwisely to
a solution of 26 (0.81 g,1.6 mmol) in methanol (10 mL). The mixture
was stirred room temperature overnight. The resulting AgI was
filtered off and the filtrate was evaporated in vacuo to give 27
4.4. Synthesis of CIL C
4.4.1. (2R,5R)-Hexanediol dimethanesulfonate (23).10 Triethylamine
(12.4 mL, 87.9 mmol) and mesyl chloride (4.9 mL, 62.8 mmol) were
added to a solution of (2R,5R)-2,5-hexanediol (3.0 mL, 25.1 mmol)
in dichloromethane (75 mL) with ice-cooling. The mixture was
stirred at room temperature for 4 h, and then neutralized by ad-
dition of hydrochloric acid. The product was extracted with
dichloromethane. The organic layer was washed with brine, dried
over MgSO4, filtered, and concentrated. The residue was purified by
silica gel chromatography (2% MeOH/CH2CL2) to give 23 (6.9 g,
(0.51 g, quant.) as a yellow oil; 1H NMR (500 MHz, CDCl3)
d: 1.55
(6H, d, J¼6.9 Hz, CH3CH), 1.69e1.94 (4H, m, CH2), 3.92 (6H, s, CH3N),
4.56 (2H, sext, J¼6.9 Hz, CH), 7.58 (2H, t, J¼1.7 Hz, imidazole), 7.70
(2H, t, J¼1.7 Hz, imidazole), 9.07 (2H, s, imidazole); 13C NMR
(126 MHz, CDCl3) d: 20.8, 32.1, 36.0, 56.2, 120.6, 123.8, 136.5; IR
(neat) cmꢁ1: 3366, 1668, 1558, 1167; HRMS (FAB) m/z: [MCl]þ,
found 283.1692. C14H24N4Cl requires 283.1684; MS (FABꢁ) m/z: 35;
½
a 2D6
ꢂ
þ4.09 (c 1.0, CH3OH).
quant.) as a colorless oil; 1H NMR (500 MHz, CDCl3)
d: 1.42 (6H, d,
4.4.6. [(4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-bis(1-methylene-3-
J¼6.1 Hz, CH3CH), 1.75e1.86 (4H, m, CH2), 3.02 (6H, s, CH3S),
butylimidazolium)][p-toluenesulfonate]2
(30). 1-Butylimidazole
4.86e4.89 (2H, m, CH).
(0.37 g, 3.0 mmol) was added dropwisely to a solution of 2811
(0.50 g, 1.0 mmol) in toluene (5 mL). The mixture was stirred
at reflux temperature overnight. The crude product was washed
with toluene, and the remaining solvent was evaporated in
vacuo to give 30 (0.72 g, quant.) as a brown amorphous solid;
4.4.2. (2S,5S)-2,5-Di(1-imidazolyl)hexane (24). Imidazole (1.4 g,
21.0 mmol) and sodium hydride (0.84 g, 21.0 mmol) were added to
a solution of 23 (1.9 g, 6.9 mmol) in DMF (20 mL) with ice-cooling.
The mixture was stirred at 80 ꢀC overnight, and then poured into
water. The product was extracted with dichloromethane. The or-
ganic layer was washed with brine, dried over MgSO4, filtered, and
concentrated. The residue was purified by silica gel chromatogra-
phy (2% MeOH/CH2CL2) to give 24 (0.97 g, 64%) as a yellow solid; 1H
NMR 1.41e1.50 (8H, m, CH3, CH2), 1.60e1.68 (2H, m, CH2), 4.07e4.12
(2H, m, CH), 6.81 (2H, t, J¼1.2 Hz, imidazole), 7.07 (2H, t, J¼1.2 Hz,
1H NMR (500 MHz, CDCl3)
d
:
0.85 (6H, t, J¼7.3 Hz,
CH3CH2CH2CH2), 1.23 (4H, sext, J¼7.3 Hz, CH3CH2CH2CH2), 1.31
(6H, s, CH3), 1.72 (4H, quint, J¼7.3 Hz, CH3CH2CH2CH2), 2.32 (6H,
s, tosyl), 4.11 (4H, m, CH3CH2CH2CH2), 4.26 (2H, dt, J¼14.3,
2.3 Hz, CH), 4.62 (2H, dd, J¼14.3, 2.3 Hz, CH2), 4.94 (2H, d,
J¼14.3 Hz, CH2), 7.24 (2H, s, imidazole), 7.63 (2H, s, 8.0 Hz,
imidazole), 9.64 (2H, s, imidazole); 13C NMR (126 MHz, CDCl3)
imidazole), 7.45 (2H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d:
d: 13.4, 19.5, 21.4, 27.0, 31.9, 49.9, 50.3, 75.9, 111.4, 121.6, 123.9,
13.4, 16.6, 19.4, 32.0, 49.8, 54.4, 70.8, 73.2, 121.6, 123.6, 127.8, 127.9,
125.9, 128.8, 137.8, 139.5, 143.6; IR (neat) cmꢁ1: 1564, 1456,
128.5, 136.7, 137.6; IR (neat) cmꢁ1: 1497, 1223, 1078; HRMS (FAB) m/
1186, 1119, 1032, 1011; HRMS (FAB) m/z: [MTsO]þ, found

9698
Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
547.2964. C28H43N4O5S requires 547.2943; MS (FABꢁ) m/z: 171;
a 2D2
ꢁ27.03 (c 0.3, CH3OH).
toluene, and the remaining solvent was evaporated in vacuo to give
½
ꢂ
36 (1.8 mg, 73%) as a brown amorphous solid; 1H NMR (500 MHz,
CDCl3) d: 0.56e0.62 (6H, m, CH3CH2CH2CH2), 0.98e1.01 (4H, m,
4.4.7. [(4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-bis(1-methylene-3-
butylimidazolium)][ bis(trifluoromethanesulfonyl)amide]2 (31). A
solution of 30 (0.71 g, 0.99 mmol) and lithium bis(tri-
fluoromethanesulfonyl)imide (0.86 g, 3.0 mmol) in water (3 mL)
was stirred at room temperature overnight. The product was
extracted with chloroform. The organic layer was washed with
brine, dried over NaSO4, and filtered. The solvent was evaporated in
vacuo to give 31 (0.39 g, 42%) as a yellow oil; 1H NMR (500 MHz,
CH3CH2CH2CH2),1.47e1.55 (4H, m, CH3CH2CH2CH2), 3.91e4.00 (4H,
m, CH3CH2CH2CH2), 4.35 (2H, d, J¼38.9 Hz, CH), 4.73e4.88 (4H, m,
CH2CH), 6.09 (1H, s, PhCH), 7.02e7.04 (3H, m, phenyl), 7.09e7.10
(2H, m, phenyl), 7.29 (1H, s, imidazole), 7.34 (1H, s, imidazole), 7.68
(1H, s, imidazole), 7.95 (1H, s, imidazole), 9.54 (1H, s, imidazole),
9.80 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d: 13.3, 19.2, 31.7,
49.7, 76.4, 103.1, 121.8, 123.6, 124.0, 126.7, 128.3, 129.7, 135.2, 136.6,
136.8; IR (neat) cmꢁ1: 3401, 2959, 1560, 1458, 1163, 1072; HRMS
(FAB) m/z: [MBr79]þ, found 503.2003. C25H36N4O2Br79 requires
503.2016. [MBr81]þ, found 505.1980. C25H36N4O2Br81 requires
CDCl3)
d
: 0.94 (6H, t, J¼7.4 Hz, CH3CH2CH2CH2), 1.27e1.41 (10H, m,
CH3CH2CH2CH2, CH3), 1.85 (4H, quint, J¼7.4 Hz, CH3CH2CH2CH2),
4.17e4.18 (2H, m, CH), 4.22 (4H, t, J¼7.4 Hz, CH3CH2CH2CH2), 4.41
(2H, dd, J¼14.3, 6.9 Hz, CH2), 4.64 (2H, d, J¼14.3 Hz, CH2), 7.59 (4H,
d, J¼1.7 Hz, imidazole), 8.85 (2H, s, imidazole); 13C NMR (126 MHz,
505.2005; MS (FABꢁ) m/z: 79, 81; ½a D24
ꢁ55.65 (c 1.0, CH3OH).
ꢂ
4.4.11. [(4S,5S)-2-Phenyl-1,3-dioxolane-4,5-bis(1-methylene-3-
butylimidazolium)][trifluoromethanesulfonate]2 (37). A solution of
16 (0.60 g, 1.0 mmol) and potassium trifluoromethanesulfonate
(0.36 g, 3.0 mmol) in water (3 mL) was stirred at room temperature
overnight. The product was extracted with chloroform. The organic
layer was washed with brine, dried over NaSO4, and filtered. The
solvent was evaporated in vacuo to give 20 (0.62 g, 86%) as a brown
CDCl3) d: 12.4, 19.0, 25.9, 31.7, 49.6, 50.4, 75.8, 111.6, 119.8 (q,
J¼1278 Hz), 122.4, 123.3, 136.4; 19F NMR (470 MHz, CDCl3)
: ꢁ79.5;
d
IR (neat) cmꢁ1: 1562, 1464, 1346, 1179, 1132, 1051; HRMS (FAB) m/z:
Mþ, found 375.2761. C21H36N4O2 requires 375.2838. [MNTf2]þ,
found 656.2005. C23H36N5O6S2F6 requires 656.2011; MS (FABꢁ) m/
a 25
z: 280; ½ ꢂD ꢁ18.50 (c 0.9, CHCl3).
oil; 1H NMR (500 MHz, CDCl3)
d:
0.89e0.93 (6H, m,
4.4.8. (4S,5S)-1,3-Dioxolane-2-phenyl-4,5-dimethanol
(34). Benzaldehyde (81.2 mL, 800 mmol) and p-toluenesulfonic
acid (1.9 mL, 10 mmol) were added to a solution of dibutyl-(L)-
CH3CH2CH2CH2), 1.32e1.39 (4H, m, CH3CH2CH2CH2), 1.82e1.87 (4H,
m, CH3CH2CH2CH2), 4.14e4.18 (4H, m, CH3CH2CH2CH2), 4.47 (2H,
td, J¼7.3, 1.8 Hz, CH), 4.62 (1H, dd, J¼14.6, 5.5 Hz, CH2CH), 4.79 (1H,
dd, J¼14.6, 1.8 Hz, CH2CH), 4.89 (1H, q, J¼7.3 Hz, CH2CH), 5.05 (1H,
dd, J¼14.6, 1.8 Hz, CH2CH), 6.11 (1H, s, PhCH), 7.17 (2H, d, J¼1.8 Hz,
imidazole), 7.37e7.44 (5H, m, phenyl), 7.54 (1H, s, imidazole), 7.74
(1H, s, imidazole), 9.33 (1H, s, imidazole), 9.46 (1H, s, imidazole);
(þ)-tartrate 31 in benzene (100 mL). The reaction flask was fitted
with a DeaneStark water separator and the mixture was stirred at
reflux temperature overnight. After the neutralization with satu-
rated NaHCO3 solution, the solvent was evaporated off. The product
was extracted with diethyl ether and the organic layer was dried
over MgSO4, filtered, and concentrated. The remaining benzalde-
hyde was distilled off in vacuo to give crude 32 (46g) as a yellow oil.
The crude 33 (46 g) was added dropwisely to a suspension of
LiAlH4 (12.4 g, 300 mmol) in dry diethyl ether (200 mL) with ice-
cooling. The mixture was stirred at room temperature for 2 h,
neutralized with saturated ammonium chloride solution, and then
filtered. The filtrate was extracted with ethyl acetate. The organic
layer was washed with brine, dried over MgSO4, filtered, and con-
centrated. The residue was purified by silica gel chromatography
(20% AcOEt/hexane) to give 34 (17.6 g, 84% in 2 steps) as a yellow
13C NMR (126 MHz, CDCl3)
50.4, 77.0, 103.7, 120.6 (q, J¼1250 Hz), 122.3, 122.5, 123.2, 123.4,
d: 12.5, 19.0, 31.6, 31.6, 49.5, 49.5, 49.9,
126.7, 128.2, 129.7, 135.9, 136.6, 136.8; 19F NMR (470 MHz, CDCl3)
d:
ꢁ79.0; IR (neat) cmꢁ1: 1560, 1460, 1252, 1223, 1157, 1028; HRMS
(FAB) m/z: Mþ, found 573.2336. C26H36F3N4O5S requires 573.2353;
MS (FABꢁ) m/z: 149; ½a 2D7
ꢁ45.59 (c 1.0, CH3OH).
ꢂ
4.4.12. [(4S,5S)-2-Phenyl-1,3-dioxolane-4,5-bis(1-methylene-3-
butylimidazolium)][bis(trifluoromethanesulfonyl)amide]2
(38). A solution of 36 (0.60 g, 1.0 mmol) and lithium bis(tri-
fluoromethanesulfonyl)imide (0.86 g, 3.0 mmol) in water (3 mL)
was stirred at room temperature overnight. The product was
extracted with chloroform. The organic layer was washed with
brine, dried over NaSO4, and filtered. The solvent was evaporated in
vacuo to give 38 (0.98 g, quant.) as a yellow oil; 1H NMR (500 MHz,
oil; 1H NMR (500 MHz, CDCl3)
d: 2.13e2.18 (2H, m, OH), 3.75e3.90
(4H, m, CH2), 4.18 (2H, td, J¼4.9, 1.8 Hz, CH), 5.98 (1H, s, PhCH),
7.39e7.40 (3H, m, phenyl), 7.48 (2H, dd, J¼2.4, 6.7 Hz, phenyl); 13
C
NMR (126 MHz, CDCl3)
129.8, 137.2.
d: 62.3, 62.4, 78.7, 79.6, 103.9, 126.8, 128.6,
CDCl3) d: 0.79e0.84 (6H, m, CH3CH2CH2CH2), 1.19e1.24 (4H, m,
CH3CH2CH2CH2), 1.64e1.77 (4H, m, CH3CH2CH2CH2), 3.98e4.07
(4H, m, CH3CH2CH2CH2), 4.28e4.40 (3H, m, CH2, CH), 4.49e4.52
(2H, m, CH2), 4.68 (1H, d, J¼13.7 Hz, CH), 6.02 (1H, s, PhCH),
7.25e7.38 (8H, m, phenyl, imidazole), 7.47 (1H, s, imidazole), 8.48
(1H, s, imidazole), 8.66 (1H, s, imidazole); 13C NMR (126 MHz,
4.4.9. (4R,5R)-4,5-Bis(bromomethyl)-2-phenyl-1,3-dioxolane
(34). Triphenylphosphine (3.1 g, 11.5 mmol) and tetrabromo-
methane (4.9 g, 14.4 mmol) were added to a solution of 33 (1.0 g,
4.8 mmol) in dichloromethane (30 mL) with ice-cooling. The mix-
ture was stirred at room temperature for 3 h, and neutralized with
saturated NaHCO3 solution. The product was extracted with
dichloromethane. The organic layer was washed with brine, dried
over MgSO4, filtered, and concentrated. The residue was purified by
silica gel chromatography (AcOEt/hexane: 1:8) to give 35 (1.4 g,
CDCl3) d: 12.3, 19.1, 31.6, 31.7, 50.8, 50.8, 51.3, 51.9, 77.0, 103.8, 119.9
(q, J¼1273 Hz), 122.4, 122.6, 123.1, 126.6, 128.2, 129.7, 135.8, 136.5,
136.6; 19F NMR (470 MHz, CDCl3)
d
: ꢁ79.4; IR (neat) cmꢁ1: 1562,
1464, 1346, 1182, 1132, 1053; HRMS (FAB) m/z: [MNTf2]þ, found
704.2000. C27H36F6N5O6S2 requires 704.2011; MS (FABꢁ) m/z: 280;
87%) as a colorless oil; 1H NMR (500 MHz, CDCl3)
d: 3.58e3.65 (4H,
½
a 2D5
ꢂ
ꢁ37.44 (c 1.3, CH3OH).
m, CH2), 4.36e4.41 (2H, m, CH), 6.07 (1H, s, PhCH), 7.39e7.40 (3H,
m, phenyl), 7.50e7.52 (2H, m, phenyl); 13C NMR (126 MHz, CDCl3)
d:
4.4.13. [(4S,5S)-2-Phenyl-1,3-dioxolane-4,5-bis(1-methylene-3-
butylimidazolium)][tetrafluoroborate]2 (39). A solution of 36 (0.60 g,
1.0 mmol) and sodium tetrafluoroborate (0.34 g, 3.0 mmol) in water
(3 mL) was stirred at room temperature overnight. The product was
extracted with chloroform. The organic layer was washed with
brine, dried over NaSO4, and filtered. The solvent was evaporated in
vacuo to give 39 (0.34 g, 57%) as a yellow oil; 1H NMR (500 MHz,
32.3, 32.8, 79.1, 80.1, 104.4, 127.0, 128.7, 130.0, 136.6.
4.4.10. [(4S,5S)-2-Phenyl-1,3-dioxolane-4,5-bis(1-methylene-3-
butylimidazolium)][bromide]2 (36). 1-Butylimidazole (1.6 g,
12.6 mmol) was added dropwisely to a solution of 35 (1.4 g,
4.2 mmol) in toluene (20 mL). The mixture was stirred at reflux
temperature overnight. The crude product was washed with
CDCl3) d: 0.88e0.92 (6H, m, CH3CH2CH2CH2), 1.24e1.35 (4H, m,

Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
9699
CH3CH2CH2CH2), 1.74e1.86 (4H, m, CH3CH2CH2CH2), 4.10e4.25 (4H,
m, CH3CH2CH2CH2), 4.47e4.84 (6H, m, CH2, CH), 6.09 (1H, s, PhCH),
7.34e7.44 (5H, m, phenyl), 7.62 (2H, s, imidazole), 7.64 (1H, s, im-
idazole), 7.67 (1H, s, imidazole), 7.76 (1H, s, imidazole), 8.95 (1H, s,
product was washed with toluene, and the remaining solvent was
evaporated off. The residue was purified by silica gel chromatog-
raphy (4% methanol/dichloromethane) to give 43 (1.6 mg, 66%) as
a brown solid; 1H NMR (500 MHz, CDCl3)
d: 0.90e0.94 (6H, m,
imidazole), 9.07 (1H, s, imidazole); 13C NMR (126 MHz, CDCl3)
d:
CH3CH2CH2CH2),1.31e1.42 (4H, m, CH3CH2CH2CH2),1.87 (4H, quint,
J¼7.4, CH3CH2CH2CH2), 4.24 (4H, t, J¼7.4 Hz, CH3CH2CH2CH2),
4.31e4.35 (2H, m, CH), 4.52 (2H, dd, J¼14.3, 8.6 Hz, CH2CH), 4.65
(2H, dd, J¼14.3, 2.9 Hz, CH2CH), 5.08 (2H, d, J¼5.7, OH), 7.33 (2H, s,
imidazole), 7.89 (2H, s, imidazole), 9.59 (2H, s, imidazole); 13C NMR
12.5, 19.1, 31.7, 49.4, 49.4, 49.9, 50.3, 76.9, 103.6, 122.3, 122.5, 123.2,
123.5, 126.7, 128.2, 129.7, 135.9, 136.6, 136.8; 19F NMR (470 MHz,
CDCl3)
d
: ꢁ150.9; IR (neat) cmꢁ1: 2961, 1562, 1462, 1167, 1049;
HRMS (FAB) m/z: [MBF4]þ, found 511.2844. C25H36BF4N4O2 requires
511.2862; MS (FABꢁ) m/z: 87; ½a D23
ꢂ
ꢁ60.26 (c 1.2, CH3OH).
(126 MHz, CDCl3) d: 13.6, 19.6, 31.9, 49.9, 52.9, 69.9, 121.5, 124.1,
136.8; IR (neat) cmꢁ1: 3088, 1562, 1456, 1161, 1120, 1070; HRMS
(FAB) m/z: [M]þ, found 335.2448. C18H32N4O2 requires 335.2447.
[MBr79]þ, found 415.1684. C18H32N4O2Br79 requires 415.1703.
[MBr81]þ, found 417.1675. C18H32N4O2Br81 requires 417.1690;
4.4.14. (S)-1-(2-Benzyloxypropyl)-2,3-dimethylimidazolium bromide
(40). 1-Methylimidazole (1.9 mL, 24.6 mmol) was added drop-
wisely to a solution of 35 (2.7 g, 8.2 mmol) in toluene (20 mL). The
mixture was stirred at reflux temperature overnight. The crude
product was washed with toluene, and the remaining solvent and
the starting materials were distilled off using a glass tube oven to
give 40 (3.0 g, 72%) as a brown amorphous solid; 1H NMR (500 MHz,
½
a 2D6
ꢂ
ꢁ11.41 (c 1.0, CH3OH).
4.4.18. [(2S,3S)-2,3-Dihydroxybutane-1,4-bis(3-butylimidazolium)]
[bis(trifluoromethanesulfonyl)amide]2 (44). A solution of 43 (1.5 g,
1.6 mmol) and lithium bis(trifluoromethanesulfonyl)imide (1.4 g,
4.9 mmol) in water (5 mL) was stirred at room temperature for 6 h.
The product was extracted with chloroform. The organic layer was
washed with brine, dried over NaSO4, and filtered. The filtrate was
concentrated and purified by silica gel chromatography (4% meth-
anol/dichloromethane) to give 44 (1.5 g, quant.) as a yellow oil; 1H
CDCl3) d: 3.88 (3H, s, CH3), 3.94 (3H, s, CH3), 4.40e4.45 (2H, m, CH2),
4.55e4.63 (3H, m, CH2, CH), 4.70 (1H, dd, J¼2.3, 14.3 Hz, CH), 5.95
(1H, s, PhCH), 7.30e7.41 (5H, m, phenyl), 7.70e7.72 (2H, m, imid-
azole), 7.80 (1H, t, J¼1.7 Hz, imidazole), 7.84 (1H, t, J¼1.7 Hz, im-
idazole), 9.15 (1H, s, imidazole), 9.19 (1H, s, imidazole); 13C NMR
(126 MHz, CDCl3) d: 35.7, 50.0, 50.4, 77.0, 103.8, 123.2, 123.4, 123.5,
123.6, 126.9, 128.3, 129.8, 136.0, 137.3, 137.6; IR (neat) cmꢁ1: 3401,
NMR (500 MHz, CDCl3)
d
: 0.96 (6H, t, J¼7.4 Hz, CH3CH2CH2CH2),
3065, 1562, 1456, 1169, 1072; HRMS (FAB) m/z: Mþ, found 339.1818.
1.36 (4H, sext, J¼7.4 Hz, CH3CH2CH2CH2), 1.86 (4H, quint, J¼7.4 Hz,
CH3CH2CH2CH2), 3.95 (2H, dd, J¼2.9, 9.2 Hz, CH), 4.22 (4H, t,
J¼7.4 Hz, CH3CH2CH2CH2), 4.29 (2H, dd, J¼9.2, 14.3 Hz, CH2), 4.37
(2H, dd, J¼2.9, 14.3 Hz, CH2), 7.58 (2H, t, J¼1.7 Hz, imidazole), 7.61
(2H, t, J¼1.7 Hz, imidazole), 8.87 (2H, s, imidazole); 13C NMR
C
C
C
19H24N4O2 requires 339.1899. [MBr79]þ, found 419.1072.
19H24N4O2Br79 requires 419.1077. [MBr81]þ, found 421.1050.
19H24N4O2Br81 requires 421.1064; ½a 2D5
ꢁ62.29 (c 1.2, CH3OH).
ꢂ
4.4.15. [(4S,5S)-2-Phenyl-1,3-dioxolane-4,5-bis(1-methylene-3-
methylimidazolium)][bis(trifluoromethanesulfonyl)amide]2 (41). A
solution of 40 (2.9 g, 5.8 mmol) and lithium bis(trifluoro-
methanesulfonyl)imide (5.0 g, 17.4 mmol) in water (20 mL) was
stirred at room temperature for 4 h. The product was extracted with
chloroform. The organic layer was washed with brine, dried over
NaSO4, and filtered. The solvent was evaporated in vacuo to give 37
(126 MHz, CDCl3) d: 13.6, 19.6, 31.9, 49.9, 52.9, 69.9, 119.8 (q,
J¼1273 Hz), 122.3, 123.1, 136.8; 19F NMR (470 MHz, CDCl3)
: ꢁ79.9;
d
IR (neat) cmꢁ1: 3501, 1564, 1464, 1346, 1180, 1130, 1051; HRMS
(FAB) m/z: [MNTf2]þ, found 616.1675. C20H32N5O6S2 requires
616.1693; MS (FABꢁ) m/z: 280; ½a D27
ꢁ7.71 (c 1.3, CH3OH).
ꢂ
4.5. General procedure for Michael addition in CIL
(4.0 g, 77%) as a brown oil; 1H NMR (500 MHz, CDCl3)
d: 3.82 (3H, s,
CH3), 3.85 (3H, s, CH3), 4.39 (2H, d, J¼6.9 Hz, CH2), 4.50 (2H, dd,
J¼14.3, 6.9 Hz, CH2), 4.58 (1H, dd, J¼14.3, 12.0 Hz, CH), 4.66 (1H, d,
J¼12.0 Hz, CH), 5.94 (1H, s, PhCH), 7.32e7.40 (5H, m, phenyl),
7.69e7.70 (2H, m, phenyl), 7.72 (1H, t, J¼1.7 Hz, imidazole), 7.74 (1H,
t, J¼1.7 Hz, imidazole), 9.05 (1H, s, imidazole), 9.08 (1H, s, imid-
Chalcone (0.1 mmol), malonate esters (0.12 mmol), and K2CO3
(0.3 mmol) were added to a mixture of CIL (1.1 mmol) and toluene
(0.1 mL). The mixture was stirred at room temperature, and then
the crude product was extracted by washing the CIL layer with
diethyl ether several times. The extracts were combined and con-
centrated. The residue was purified by silica gel chromatography
(20% ethyl acetate/hexane) to obtain Michael adducts.
azole); 13C NMR (126 MHz, CDCl3)
d: 133.8, 33.9, 48.4, 49.0, 75.5,
75.5, 102.5, 118.3 (q, J¼1273 Hz), 119.6, 121.5, 121.7, 122.1, 122.2,
125.2, 126.8, 128.3, 134.4, 137.1, 137.3; 19F NMR (470 MHz, CDCl3)
d:
ꢁ80.1; IR (neat) cmꢁ1: 1562, 1456, 1346, 1173, 1132, 1049; HRMS
(FAB) m/z: Mþ, found 339.1836. C19H24N4O2 requires 339.1899.
[MNTf2]þ, found 620.1075. C21H24N5O6S2F6 requires 620.1072; MS
4.5.1. Diethyl 2-(3-oxo-1,3-diphenylpropyl)malonate (50a).12 1H
NMR (500 MHz, CDCl3)
d
: 0.99 (3H, t, J¼7.2 Hz, CH3CH2), 1.23 (3H, t,
J¼7.2 Hz, CH3CH2), 3.45 (1H, q, J¼9.2 Hz, CH3CH2), 3.54 (1H, dd,
J¼16.0, 4.6 Hz, CH3CH2), 3.82 (1H, d, J¼9.2 Hz, EtO2CCH), 3.94 (2H, q,
J¼7.1 Hz, CH3CH2), 4.17e4.20 (3H, m, PhCH, PhCOCH2), 7.14e7.17
(1H, m, phenyl), 7.21e7.27 (4H, m, phenyl), 7.41 (2H, t, J¼7.7 Hz,
phenyl), 7.51 (1H, t, J¼7.7 Hz, phenyl), 7.89 (2H, d, J¼6.9 Hz, phenyl);
(FABꢁ) m/z: 280; ½a 2D5
ꢁ39.73 (c 1.2, CH3OH).
ꢂ
4.4.16. (2R,3R)-1,4-Dibromobutane-2,3-diol (42). Palladium carbon
(5%, 60 mg) and several drops of hydrochloric acid were added to
a solution of 35 (1.0 g, 4.8 mmol) in methanol (50 mL). The mixture
was stirred at room temperature for 3 h under H2 atmosphere and
filtered. The filtrate was concentrated. Then the residue was puri-
fied by silica gel chromatography (AcOEt/hexane: 1:2) to give 42
13C NMR (126 MHz, CDCl3)
d: 13.9, 14.1, 40.9, 42.7, 57.7, 61.5, 61.8,
127.2, 128.2, 128.3, 128.5, 128.6, 133.2, 136.9, 140.5, 167.9, 168.5,
197.6; Analytical chiral HPLC: Daicel CHIRALPAK AD column,
0.46ꢃ25 cm, hexane/2-propanol¼9/1, 1.0 mL minꢁ1, 19.9 min,
33.0 min.
(0.26 g, 62%) as a colorless solid; 1H NMR (500 MHz, CDCl3)
d: 2.56
(2H, d, J¼5.2 Hz, OH), 3.50 (2H, dd, J¼10.3, 5.2 Hz, CH2), 3.55 (2H,
dd, J¼10.3, 5.2 Hz, CH2), 3.99 (2H, dt, J¼5.2, 5.2 Hz, CH).; 13C NMR
4.5.2. Diethyl 2-[1-(naphthalen-1-yl)-3-oxo-3-phenylpropyl]malo-
(126 MHz, CDCl3)
d
: 34.7, 71.5.
nate (51a). 1H NMR (500 MHz, CDCl3)
d
: 0.88 (3H, t, J¼7.3 Hz,
CH3CH2), 1.19 (3H, t, J¼7.3 Hz, CH3CH2), 3.73 (2H, q, J¼6.9 Hz,
CH3CH2), 3.87 (2H, q, J¼6.9 Hz, CH3CH2), 4.03 (1H, d, J¼8.5,
EtO2CCH), 4.10e4.23 (2H, m, PhCOCH2), 5.14e5.16 (1H, m, NaphCH),
7.35e7.54 (7H, m, aromatic), 7.70 (1H, d, J¼8.5 Hz, aromatic), 7.81
(1H, d, J¼8.5 Hz, aromatic), 7.88 (2H, dd, J¼8.5, 1.8 Hz, aromatic),
4.4.17. [(2S,3S)-2,3-Dihydroxybutane-1,4-bis(3-butylimidazolium)]
[bromide]2 (43). 1-Butylimidazole (1.8 g, 12.6 mmol) was added
dropwisely to a solution of 42 (1.2 g, 4.8 mmol) in toluene (20 mL).
The mixture was stirred at reflux temperature overnight. The crude

9700
Y. Suzuki et al. / Tetrahedron 69 (2013) 9690e9700
8.30 (1H, d, J¼8.5 Hz, aromatic); 13C NMR (126 MHz, CDCl3)
d
: 13.7,
J¼8.5 Hz, aromatic), 7.88 (1H, d, J¼7.5, aromatic), 7.98 (2H, d,
J¼7.0 Hz, aromatic), 8.29 (1H, d, J¼8.5 Hz, aromatic); 13C NMR
14.1, 38.8, 42.4, 57.2, 61.5, 61.7, 123.5, 125.2, 125.7, 126.4, 128.2,
128.6, 128.9, 133.0, 131.6, 132.5, 133.1, 136.8, 168.0, 168.7, 197.7;
HRMS (FAB) m/z: Mþ, found 418.1767. C26H26O5 requires 418.1780;
Analytical chiral HPLC: Daicel CHIRALPAK AD column, 0.46ꢃ25 cm,
hexane/2-propanol¼9/1, 1.0 mL minꢁ1, 22.1 min, 34.9 min.
(126 MHz, CDCl3) d: 27.6, 28.3, 33.7, 39.9, 49.4, 105.3, 122.7, 125.3,
125.6, 126.0, 127.1, 128.2, 128.3, 128.7, 129.3, 131.1, 133.6, 134.2,
136.6, 137.4, 164.8, 166.2, 199.2; HRMS (FAB) m/z: Mþ, found
402.1460. C25H22O5 requires 402.1467.
The obtained 50c was converted to dimethyl 2-[1-(naphthalen-
1-yl)-3-oxo-3-phenylpropyl]malonate for HPLC analysis as follows:
Ring-opening reaction with methanol in refluxing toluene to
4.5.3. Diethyl 2-[1-(naphthalen-1-yl)-3-(naphthalen-2-yl)-3-
oxopropyl]malonate (52a). 1H NMR (500 MHz, CDCl3)
d: 0.90 (3H,
t, J¼7.4 Hz, CH3CH2), 1.20 (3H, t, J¼7.4 Hz, CH3CH2), 3.88e3.91 (4H,
m, CH3CH2), 4.08e4.23 (3H, m, EtO2CCH, 2-NaphCH2), 5.22e5.24
(1H, m, 1-NaphCH), 7.37 (1H, t, J¼7.4 Hz, aromatic), 7.47 (2H, t,
J¼6.8 Hz, aromatic), 7.69 (1H, d, J¼7.9 Hz, aromatic), 7.81e7.93 (8H,
m, aromatic), 8.08 (1H, dt, J¼12.7, 5.2 Hz, aromatic), 8.33 (1H, d,
J¼8.5 Hz, aromatic); Analytical chiral HPLC: Daicel CHIRALPAK AD
a carboxylic acid (monoester) and esterification with diazo-
methane; Analytical chiral HPLC: Daicel CHIRALPAK AD-H column,
0.46ꢃ15 cm, hexane/2-propanol¼9/1, 1.0 mL minꢁ1, 31.6 min,
34.1 min.
4.5.8. 2,2-Dimethyl-5-(1-(naphthalen-1-yl)-3-(naphthalen-2-yl)-3-
column, 0.46ꢃ25 cm, hexane/2-propanol¼9/1, 0.8 mL minꢁ1
,
oxopropyl)-1,3-dioxane-4,6-dione (52c). 1H NMR (500 MHz, CDCl3)
40.5 min, 52.3 min.
d
: 1.64 (3H, s, CH3), 1.69 (3H, s, CH3), 3.97 (1H, dd, J¼18.0, 5.5 Hz, 2-
NaphCOCH2), 4.16e4.21 (2H, m, CH, 2-NaphCOCH2), 5.45e5.48
(1H, m, 1-NaphCH), 7.47e7.62 (5H, m, aromatic), 7.77 (1H, d,
J¼7.5 Hz, aromatic), 7.81 (1H, d, J¼8.5 Hz, aromatic), 7.89e7.92 (4H,
m, aromatic), 8.03 (1H, dd, J¼8.5, 2.0 Hz, aromatic), 8.32 (1H, d,
J¼8.5 Hz, aromatic), 8.52 (1H, s, aromatic); 13C NMR (126 MHz,
4.5.4. Diethyl 2-(1-(anthracen-9-yl)-3-oxo-3-phenylpropyl)malonate
(53a). 1H NMR (500 MHz, CDCl3)
d: 1.18e1.21 (6H, m, CH3CH2),
3.36e3.47 (2H, m, CH3CH2), 3.79 (1H, dd, J¼17.5, 6.1 Hz, PhCOCH2),
3.98 (1H, dd, J¼17.5, 4.9 Hz, PhCOCH2), 4.13e4.18 (2H, m, CH3CH2),
4.59 (1H, d, J¼11.6 Hz, EtO2CCH), 6.03e6.07 (1H, m, ArCH), 7.28 (2H,
t, J¼8.0 Hz, aromatic), 7.34e7.52 (5H, m, aromatic), 7.77 (2H, d,
J¼8.0 Hz, aromatic), 7.85 (1H, d, J¼7.9 Hz, aromatic), 7.95 (1H, d,
J¼8.0 Hz, aromatic), 8.29e8.31 (2H, m, aromatic), 8.76 (1H, d,
J¼9.2 Hz, aromatic); HRMS (FAB) m/z: Mþ, found 468.1922.
CDCl3) d: 27.6, 28.4, 34.0, 39.9, 49.5, 105.3, 122.7, 123.9, 125.3, 125.6,
126.0, 126.9, 127.1, 127.9, 128.3, 128.6, 128.7, 129.3, 129.8, 130.2,
131.1, 132.5, 133.9, 134.2, 135.8, 137.4, 164.8, 166.2, 199.3; HRMS
(FAB) m/z: Mþ, found 452.1614. C29H29O5 requires 452.1624; An-
alytical chiral HPLC: Daicel CHIRALPAK AD-H column, 0.46ꢃ15 cm,
hexane/2-propanol¼9/1, 1.0 mL minꢁ1, 27.8 min, 41.6 min.
C
30H28O5 requires 468.1937; Analytical chiral HPLC: Daicel CHIR-
ALPAK AD column, 0.46ꢃ25 cm, hexane/2-propanol¼9/1,
1.0 mL minꢁ1, 32.7 min, 42.5 min.
References and notes
4.5.5. Di-tert-butyl 2-(3-oxo-1,3-diphenylpropyl)malonate (50b). 1H
NMR (500 MHz, CDCl3) d: 1.18 (9H, s, CH3C), 1.46 (9H, s, CH3C), 3.39
1. (a) Welton, T. Chem. Rev. 1999, 99, 2071e2083; (b) Rogers, R. D.; Voth, G. A. Acc.
Chem. Res. 2007, 40, 1077e1078; (c) Han, X.; Armstrong, D. W. Acc. Chem. Res.
2007, 40, 1079e1086; (d) Giernoth, R. Angew. Chem., Int. Ed. 2010, 49,
5608e5609.
2. Wilkes, J. S.; Zaworotko, M. J. J. Chem. Soc., Chem. Commun. 1992, 965e967.
3. Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard, D.; Gaumont, A.-C.; Plaquevent,
J.-C. Tetrahedron: Asymmetry 2003, 14, 3081e3093.
(1H, dd, J¼15.5, 9.7 Hz, CH2), 3.50 (1H, dd, J¼15.5, 4.0 Hz, CH2), 3.63
(1H, d, J¼9.7 Hz, CH), 4.06 (1H, td, J¼15.5, 4.0 Hz, CH), 7.12-7.15 (1H,
m, phenyl), 7.19-7.25 (4H, m, phenyl), 7.40 (2H, t, J¼7.4 Hz, phenyl),
7.51 (1H, t, J¼7.4 Hz, phenyl), 7.88 (2H, dd, J¼8.0, 1.1 Hz, phenyl); 13
C
4. (a) Seebach, D.; Oei, H. A. Angew. Chem., Int. Ed. Engl. 1975, 14, 634e636; (b)
NMR (126 MHz, CDCl3) d: 27.6, 28.0, 40.9, 43.4, 59.4, 81.6, 82.1,127.0,
Laarhoven, W. H.; Cuppen, T. J. M. J. Chem. Soc., Chem. Commun. 1977, 47ae47a;
ꢀ
128.2, 128.3, 128.6, 128.6, 133.0, 137.0, 140.8, 167.1, 167.9, 197.9;
Analytical chiral HPLC: Daicel CHIRALPAK AD column, 0.46ꢃ25 cm,
hexane/2-propanol¼9/1, 1.0 mL minꢁ1, 22.7 min, 36.9 min.
(c) Ulbert, O.; Szarka, A.; Halasi, S.; Somogyi, B.; Belafi-Bako, K.; Gubicza, L.
Biotechnol. Tech. 1999, 13, 299e302; (d) Verbit, L.; Halvert, T. R.; Patterson, R. B.
J. Org. Chem. 1975, 40, 1649e1650.
5. For reviews see: (a) Baudequin, C.; Bregeon, D. J.; Levillain, J.; Guillen, F.;
Plaquevent, J.-C.; Gaumont, A.-C. Tetrahedron: Asymmetry 2005, 16, 3921e3945;
(b) Ding, J.; Armstrong, D. W. Chirality 2005, 17, 281e292; (c) Chen, X.; Li, X.;
Hu, A.; Wang, F. Tetrahedron: Asymmetry 2008, 19, 1e14; (d) Payagala, T.;
Armstrong, D. W. Chirality 2012, 24, 17e25.
4.5.6. 2,2-Dimethyl-5-(3-oxo-1,3-diphenylpropyl)-1,3-dioxane-4,6-
dione (50c).16 1H NMR (500 MHz, CDCl3)
d: 1.35 (3H, s, CH3), 1.68
(3H, s, CH3), 3.60 (1H, dd, J¼19.0, 5.0 Hz, PhCOCH2), 4.29 (1H, dd,
J¼19.0,10.5 Hz, PhCOCH2), 4.34 (1H, d, J¼3.5 Hz, CH), 4.47e4.51 (1H,
m, Ph CH), 7.25e7.28 (1H, m, phenyl), 7.32 (2H, t, J¼8.5 Hz, phenyl),
7.42 (2H, d, J¼7.5 Hz, phenyl), 7.47 (2H, t, J¼8.5 Hz, phenyl),
7.56e7.59 (2H, t, J¼7.5 Hz, phenyl), 8.00 (2H, d, J¼8.5 Hz, phenyl);
6. (a) Pegot, B.; Vo-Thanh, G.; Gori, D.; loupy, A. Tetrahedron Lett. 2004, 45,
6425e6428; (b) Wang, Z.; Wang, Q.; Zhang, Y.; Bao, W. Tetrahedron Lett.
2005, 46, 4657e4660; (c) Ding, J.; Desikan, V.; Han, X.; Xiao, T. L.; Ding, R.;
Jenks, W. S.; Armstrong, D. W. Org. Lett. 2005, 7, 335e337; (d) Schulz, P. S.;
Muller, N.; Bosmann, A.; Wasserscheid, P. Angew. Chem., Int. Ed. 2007, 46,
1293e1295.
€
€
13C NMR (126 MHz, CDCl3)
d: 28.0, 28.2, 40.0, 40.9, 49.4, 105.4,
7. Bao, W.; Wang, Z.; Li, Y. J. Org. Chem. 2003, 68, 591e593.
8. Singh, R. P.; Manandhar, S.; Shreeve, J. M. Synthesis 2003, 1579e1585.
9. (a) Anderson, J. L.; Ding, R.; Ellern, A.; Armstrong, D. W. J. Am. Chem. Soc. 2005,
127, 593e604; (b) Han, X.; Armstrong, D. W. Org. Lett. 2005, 7, 4205e4208.
10. Meca, L.; Cisarova, I.; Dvorak, D. Organometallics 2003, 22, 3703e3709.
11. For selected examples of Michael addition using ionic liquids as catalysts or
solvents see: (a) Luo, S.; Mi, X.; Zhang, L.; Liu, S.; Xu, H.; Cheng, J.-P. Angew.
Chem., Int. Ed. 2006, 45, 3093e3097; (b) Ni, B.; Zhang, Q.; Headley, A. D. Green
127.9, 128.2, 128.8, 128.9, 129.0, 133.6, 136.7, 140.1, 165.4, 165.6,
199.2; HRMS (FAB) m/z: Mþ, found 353.1414. C21H21O5 requires
353.1389; Analytical chiral HPLC: Daicel CHIRALPAK AD-H column,
0.46ꢃ15 cm, hexane/2-propanol¼9/1, 0.8 mL minꢁ1, 20.1 min,
29.6 min.
ꢁ
ꢀ
Chem. 2007, 9, 737e739; (c) Meciarova, M.; Toma, S. Chem.dEur. J. 2007, 13,
1268e1272.
4.5.7. 2,2-Dimethyl-5-[1-(naphthalen-1-yl)-3-oxo-3-phenylpropyl]-
12. Machado, M. Y.; Dorta, R. Synthesis 2005, 2473e2475.
13. Chong, J. M.; Shen, L.; Taylor, N. J. J. Am. Chem. Soc. 2000, 122, 1822e1823.
14. Robinson, T. P.; Hubbard, R. B., IV; Ehlers, T. J.; Arbiser, J. L.; Goldsmith, D. J.;
Bowen, J. P. Bioorg. Med. Chem. 2005, 13, 4007e4013.
15. Huang, K.; Breitbach, Z. S.; Armstrong, D. W. Tetrahedron: Asymmetry 2006, 17,
2821e2832.
1,3-dioxane-4,6-dione (51c). 1H NMR (500 MHz, CDCl3)
d: 1.62 (3H,
s, CH3),1.68 (3H, s, CH3), 3.82 (1H, dd, J¼18.0, 6.0 Hz, PhCOCH2), 4.06
(1H, dd, J¼18.0, 9.5 Hz, PhCOCH2), 4.16 (1H, d, J¼2.5 Hz, CH),
5.39e5.43 (1H, m, ArCH), 7.43e7.48 (3H, m, aromatic), 7.51e7.62
(3H, m, aromatic), 7.71 (1H, d, J¼7.5 Hz, aromatic), 7.79 (1H, d,
16. Mizukami, S.; Kihara, N.; Endo, T. Tetrahedron Lett. 1993, 34, 7437e7440.