Synthesis and preliminary use of novel acrylic ester-derived task-specific ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2003.10.198

Novel electrophilic alkenes bearing an ionic liquid-type appendage have been prepared and used in Diels-Alder cycloadditions, 1,4-additions, Heck couplings and Stetter reactions; this new type of support allows easy monitoring of the reactions by NMR and MS as well as simple and efficient work-up and isolation procedures.

Full text of DOI:10.1016/j.tetlet.2003.10.198

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 569–571
Synthesis and preliminary use of novel acrylic ester-derived
task-specific ionic liquids
a
Siddam Anjaiah, Srivari Chandrasekhar and Rene Gree
b
a,
*
ꢀ
ꢀ
aEcole Nationale Supeꢀrieure de Chimie de Rennes, Laboratoire de Synthꢁeses et Activations de Biomoleꢀcules, CNRS UMR 6052,
Avenue du Geꢀneꢀral Leclerc, 35700 Rennes, France
bIndian Institute of Chemical Technology, Hyderabad 500007, India
Received 27 September 2003; revised 21 October 2003; accepted 30 October 2003
Abstract—Novel electrophilic alkenes bearing an ionic liquid-type appendage have been prepared and used in Diels–Alder cyclo-
additions, 1,4-additions, Heck couplings and Stetter reactions; this new type of support allows easy monitoring of the reactions by
NMR and MS as well as simple and efficient work-up and isolation procedures.
ꢀ 2003 Elsevier Ltd. All rights reserved.
Room temperature ionic liquids (RTILs) are the subject
of current interest as novel reaction media.1 This is
mainly due to their unique physical properties, which
makes them attractive solvents for organic synthesis,2
organometallic catalysis3 as well as for biotransforma-
tions.4 In parallel to these uses a new class of reagents
designed as task-specific ionic liquids (TSILs) have been
developed: such derivatives combine an ionic liquid-type
part (in order to maintain the corresponding physical
properties) with an attached extra function designed for
the specific property.1;5 Excellent representative examples
include co-ordination and extraction of metal ions,6 CO2
capture7 and transition metal catalysts supported on
ionic liquids.8 Very recently a polymerizable ionic liquid
has been used to increase the hardness of materials.9
reagents at each step of the synthesis, (ii) these deriva-
tives are low molecular weight supports and therefore
they should maintain good mobility at the attached
function making their reactivity very close to solution
chemistry and (iii) last, but not the least, this should
greatly assist the spectral analysis of such small mole-
cules for instance by NMR and MS. The first examples
validating this concept have been reported recently in
the cases of the Knoevenagel condensation and 1,3-
dipolar cycloadditions, as well as for the preparation
of a small library of thiazolidinones.11
As an extension of our programme dealing with chem-
istry on soluble supports,12 we have selected as the first
model the structures of type 1 and 2 with an imidazo-
lium core in order to be as close as possible to classic
RTILs and retain the corresponding physical properties
(Fig. 1). A Wang-type linker was chosen since it is also
Another very attractive possibility is to develop such
TSILs as alternatives to classical solid and soluble
polymeric supports used in parallel, as well as for multi-
step synthesis. The general principle is similar to those
used in such methods with the RTILs replacing the
polymeric support.10 The main potential advantages of
such derivatives are the following: (i) due to the insol-
ubility properties induced by the RTIL part of the
molecule, it is anticipated that simple washing with the
appropriate solvents should remove the excess of
O
R
N
O
R
_
X
N
O
O
O
1a R=H, X=BF4, 2a R=Me, X=BF4
1b R=H, X=NTf2, 2b R=Me, X=NTf2
Keywords: Ionic liquids; Chemistry on support; Task-specific ionic
liquids.
* Corresponding author. Tel.: +33-2-23-23-80-70; fax: +33-2-23-23-81-
08; e-mail: rene.gree@ensc-rennes.fr
Figure 1. New task-specific ionic liquids.
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.198

570
S. Anjaiah et al. / Tetrahedron Letters 45 (2004) 569–571
O
OH
(i)
R1
(ii)
3 : R1 = CH2CH2OH
4 : R1 = CH2CH2Cl
5 : R1 = CH2CH2Im
MeO
N
MeO
(ii)
(i)
O
(iii)
O
1a
O
MeO2C
MeO2C
O
O
10
O
O
N
(v)
8
(iv)
_
N
R2
N
R2
I
7
6
O
(iii)
R2= CH2OH
(ii)
1a
O
R
N
(vi)
O
11
9
X-
(vii)
N
O
Scheme 2. Reagents and conditions: (i) 2,3-dimethylbutadiene
(50 equiv), 70 ꢁC, 72 h, 95%; (ii) NaOMe, THF, MeOH, reflux, 4 h,
75%; (iii) cyclopentadiene (3 equiv), 120 ꢁC, 4 h, 90%.
1, 2
Scheme 1. Reagents and conditions: (i) 2-Chloroethanol (2 equiv),
KOH (2 equiv), [Bmim][PF6], 80 ꢁC, 12 h, 87%; (ii) SOCl2 (2 equiv), Py
(2 equiv), reflux, 3 h, 80%; (iii) NaH (1.2 equiv), Im., DMF, 100 ꢁC,
16 h, 60%; (iv) LAH (1.2 equiv), THF, reflux, 17 h, 88%; (v) MeI
(2 equiv), CH2Cl2, reflux, 24 h, 90%; (vi) NH4BF4 (1.2 equiv), CH3CN,
60 ꢁC, 24 h, 95% or LiNTf2 (1.2 equiv), CH3CN, 60 ꢁC, 24 h, 92%; (vii)
acryloyl chloride (2 equiv), DIEA (2 equiv), CH3CN, rt, 20 h, 1a 85%,
1b 90% or methacryloyl chloride (2 equiv), DIEA (2 equiv), CH3CN,
rt, 20 h, 2a 92%, 2b 90%.
as previously described. In the same way transesterifi-
cation led to compounds 14–150 (Scheme 3).
The Heck reaction has become a very important method
for C–C bond formation14 therefore it was logical to
extend our study to such Pd-catalyzed reactions. The
acrylate 1b underwent a smooth coupling with PhI to
give, as expected, compound 16 (Scheme 4).
versatile in combinatorial chemistry with flexible labil-
ity. Finally electrophilic alkenes have been selected as
functional groups since they offer a wide range of pos-
sible reactions such as cycloadditions, nucleophilic
additions or transition metal-catalyzed reactions.
R
1b
or
2b
(i)
O
Nu
The purpose of this communication is to report an
efficient synthesis of the new TSILs 1 and 2 and describe
preliminary results of their use in different types of
organic reactions. These compounds 1 and 2 have been
prepared from commercially available methyl 4-
hydroxybenzoate as shown in Scheme 1. A classical
sequence afforded in four steps and 30% overall yield the
imidazole bearing the Wang-type linker 6. Alkylation
followed by ion exchange gave the corresponding salts,
and final esterification steps using the corresponding
acid chloride in the presence of HunigÕs base gave the
key intermediates 1 and 2. It should be noted that, while
intermediates before quaternization were purified by
classical chromatography, compounds 1 and 2 were
isolated in pure form by simple extraction and washing
procedures.13
or (ii)
O
12 (R=H, Nu=pyrr) 12' (R=Me, Nu=pyrr)
13 (R=H, Nu=PhS) 13' (R=Me, Nu=PhS)
(iii)
R
14 (R=H, Nu=pyrr)
14' (R=Me, Nu=pyrr)
15 (R=H, Nu=PhS)
15' (R=Me, Nu=PhS)
Nu
MeO
O
Scheme 3. Reagents and conditions: (i) pyrrolidine (1.5 equiv), 24 h, rt,
90%; (ii) PhSH (1.5 equiv), TEA, 20 h, rt, 96%; (iii) NaOMe, THF,
MeOH, reflux, 70%.
A Diels–Alder cycloaddition was chosen as the first
model reaction, wherein addition of 2,3-dimethylbu-
tadiene to 1a gave quantitatively the adduct 8; similarly
cyclopentadiene afforded the compound 9.
(i)
O
Ph
O
O
O
16
1b
After removal of excess reagents under vacuum and
washing with ether, the products were obtained in pure
form and fully characterized by NMR and MS (Scheme
2). Furthermore transesterification of adducts 8 or 9
gave respectively the cyclohexene derivatives 10 and 11,
which were identical to authentic samples.
O
O
(ii)
(iii)
O
(iv)
O
MeO
O
Ph
Ph
O
O
_+
(
)
18
+
_
(
)
17
Scheme 4. Reagents and conditions: (i) PhI (1.5 equiv), cat. Pd(OAc)2,
TPP (0.2 equiv), TEA (2 equiv), 120 ꢁC, 1 h, 75%; (ii) cat. OsO4, NMO
(1.2 equiv), acetone, water, rt 12 h, 87%; (iii) 2,2-dimethoxypropane
(10 equiv), cat. PPTS, reflux, 97%; (iv) NaOMe, THF, MeOH reflux,
60%.
Nucleophilic additions were next studied and pyrroli-
dine and thiophenol were selected as models. In both
cases the reaction afforded quantitatively the desired
products 12–130, which were purified and characterized

S. Anjaiah et al. / Tetrahedron Letters 45 (2004) 569–571
571
6. Visser, A. E.; Swatloski, R. P.; Reichert, M. W.; Mayton,
R.; Sheff, S.; Wierzbicki, A.; Davis, J. H.; Rogers, R. D.
Chem. Commun. 2001, 135.
O
O
(i)
N
1b
7. Bates, E. D.; Mayton, R. D.; Ntai, I.; Davis, J. H. J. Am.
Chem. Soc. 2002, 124, 926.
O
19
8. (a) Kottsieper, K. W.; Stelzer, O.; Wasserscheid, P. J. Mol.
Cat. A 2001, 175, 285; (b) Audic, N.; Clavier, H.;
Mauduit, M.; Guillemin, J. C. J. Am. Chem. Soc. 2003,
125, 9248.
9. Takanori, F.; Takuzo, A. Science 2003, 300, 2072.
10. Tzschucke, C. C.; Market, C.; Bannwarth, W.; Roller, S.;
Hebel, A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41,
3964.
N
(ii)
O
O
20
Scheme 5. Reagents and conditions: (i) pyridine-2-carboxaldehyde
(2 equiv), 80 ꢁC, 12 h, 87%; (ii) NaBH4, MeOH, rt, 50%.
11. (a) Fraga-Dubreuil, J.; Bazureau, J. P. Tetrahedron Lett.
2001, 42, 6097; (b) Fraga-Dubreuil, J.; Bazureau, J. P.
Tetrahedron 2003, 59, 6121.
Dihydroxylation of the latter derivative using OsO4 was
also uneventful affording, after acetonide formation,
compound 17. Transesterification afforded the desired
product 18 in 35% overall yield from 1b.
12. Chandrasekhar, S.; Schameem, S.; Narshimulu, C.;
ꢀ
Yadav, J. S.; Gree, R.; Guillemin, J. C. Tetrahedron Lett.
2002, 43, 8335.
13. All new compounds have spectral (NMR and MS) data in
full agreement with the indicated structures. All molecules
having the ionic liquid-type appendage are viscous oils.
1a,b and 2a,b were found to be soluble in CH2Cl2,
CH3CN, THF and insoluble in water and ether. The
nature of the counter anion Xꢀ was established by LSIMS/
MS through the presence of the [2Cþ, Xꢀ] anion.
Representative procedure for 1a: To a stirred solution of 7
(1.00 g, 2.77 mmol) in acetonitrile (10 mL) was added
NH4BF4 (0.395 g, 3.32 mmol) in one portion. The reaction
mixture was heated under stirring at 60 ꢁC for 24 h. After
cooling to room temperature it was filtered through Celite
and the solvent removed under vacuum. The crude
product was used directly for the next step: after dissolu-
tion in acetonitrile (10 mL) were added HunigÕs base
(0.81 g, 6.28 mmol) and acryloyl chloride (0.56 g,
6.28 mmol) at 0 ꢁC. The reaction mixture was stirred for
20 h at room temperature then diluted with water and
extracted with CH2Cl2 (2 · 50 mL), dried and concentrated
under vacuum to give 1a (0.828 g, 80% yield).
The Stetter reaction is also a very useful method for the
preparation of 1,4-dicarbonyl compounds.15 Reaction of
1b with pyridine-2-carboxaldehyde led to compound 19,
which after reaction with NaBH4 afforded lactone 20 in a
process equivalent to the cyclorelease strategy (Scheme 5).
In conclusion, these preliminary results clearly demon-
strate that new families of TSILs with electrophilic
alkene-type appendages are easily prepared and used in
synthesis. Their development in asymmetric synthesis, as
well as in multistep and/or parallel synthesis, is under
active study in our laboratories.
Acknowledgements
We thank P. Guenot (CRMPO Rennes) for the mass
spectral analysis. This work was supported by the
1a: 1H NMR (400 MHz, CDCl3): 3.99 (s, 3H), 4.35 (t,
J ¼ 4:8 Hz, 2H), 4.74 (t, J ¼ 4:8 Hz, 2H), 5.09 (s, 2H), 5.82
(dd, J ¼ 10:4 Hz, J ¼ 1:2 Hz, 1H), 6.14 (dd, J ¼ 17:2 Hz,
J ¼ 10:4 Hz, 1H), 6.38 (dd, J ¼ 17:2 Hz, J ¼ 1:2 Hz, 1H),
6.98 (m, 2H), 7.27 (m, 2H), 7.4 (m, 1H), 7.62 (m, 1H), 9.35
(s, N–CH–N). 13C NMR (100 MHz, CDCl3): 36.24, 42.27,
48.94, 54.01, 65.28, 65.52, 114.02, 122.70, 122.78, 127.65,
128.69, 129.53, 130.69, 136.38, 156.90, 165.48. HRMS/
LSIMS; Cþ calcd for C16H19N2O3: 287.1396, found:
287.1391; [2Cþ, BF4ꢀ]þ calcd for C32H38N4O6F411B:
661.2821, found: 661.2830.
2b: 1H NMR (400 MHz, CDCl3): 1.92 (s, 3H), 3.91 (s, 3H),
4.57 (t, J ¼ 5:0 Hz, 2H), 4.60 (t, J ¼ 5:0 Hz, 2H), 5.09 (s,
2H), 5.55 (m, 1H), 6.10 (m, 1H), 6. 87 (m, 2H), 7.26–7.35
(m, 3H), 7.5 (m, 1H), 8.81 (1H, N–CH–N). 13C NMR,
(100 MHz, CDCl3): 18.67, 36.75, 49.84, 66.24, 66.29,
114.83, 118.57, 121.77, 122.70, 122.78, 127.83, 130.33,
130.69, 136.57, 136.95, 157.70, 167.69. HRMS/ESIMS; Cþ
calcd for C17H21N2O3: 301.1552, found: 301.1550; [2Cþ,
NTf2]þ: 882.
ꢁ
ꢁ
Ministere des Affaires Etrangeres (fellowship to S.A.) as
part of CEFISO/IFCOS. S.C. thanks the CEFIPRA/
IFCPAR (2305-1) for supporting the visits to Rennes.
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