Asymmetric Diels-Alder reactions in ionic liquids

Article abstract of DOI:10.1016/S0040-4039(03)01590-9

Recent interest in ionic liquids has developed various uses for them, including some applications by synthetic chemists. Ionic liquids have joined the potential list of non-traditional solvents for Diels-Alder reactions. We report here our own efforts to

Full text of DOI:10.1016/S0040-4039(03)01590-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6465–6468
Asymmetric Diels–Alder reactions in ionic liquids
Ildiko Meracz and Taeboem Oh*
Department of Chemistry, California State University, Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8262, USA
Received 28 April 2003; revised 23 June 2003; accepted 23 June 2003
Abstract—Recent interest in ionic liquids has developed various uses for them, including some applications by synthetic chemists.
Ionic liquids have joined the potential list of non-traditional solvents for Diels–Alder reactions. We report here our own efforts
to examine the rates and selectivities of carbon Diels–Alder reactions. Our investigations show that excellent diastereoselective and
enantioselective carbon Diels–Alder reactions can be achieved in imidazolium ionic solvents at room temperature.
© 2003 Elsevier Ltd. All rights reserved.
and 1,3-dibutylimidazolium tetrafluoroborate (DiBuIm)
(Fig. 1).12 These ionic solvents were chosen because they
were known to catalyze Diels–Alder reactions.11a The
protonated HBuIm were also looked at for the potential
increase in reactivity of the system. The Diels–Alder
substrates were substituted oxazolidinones and cyclopen-
tadiene (Eq. (1)). The reactions proceeded well in HBuIm
with excellent endo-exo ratios for the acryloyl oxazolidi-
none (entry a, Table 1). However, for the crotonyl
oxazolidinone, use of HBuIm or DiBuIm gave low yields
but high endo-exo selectivities (entries b and c). Addition
of ZnCl2 to the ionic liquids gave mixed results. The
presence of 1% ZnCl2 in DiBuIm increased the rate of
reaction to give a 68% yield of the cycloadduct in 92:8
endo-exo ratio (entry d). However, ZnCl2 in HBuIm gave
no product (entry e). These Diels–Alder reactions were
The variety of applications for which ionic liquids can
be used has sparked an increasing interest in these
compounds.1,2 Ionic liquids have potential as environ-
mentally friendly solvents for synthesis.3 The solvent
effect of ionic liquids is being investigated using transi-
tion metal mediated reactions, such as palladium,4 ruthe-
nium,5 and nickel,6 as well as enzymatic7 and other
reactions.8 Ionic liquids also appear to have potential as
extraction solvents.9 Previously, solvents such as water
and 5 M lithium perchlorate in ether have been explored
as non-traditional solvents for Diels–Alder reactions;10
ionic liquids have now joined this list of potential
non-traditional solvents as they have been tested in
simple Diels–Alder reactions.11 To our knowledge, the
present communication reports for the first time, the high
stereoselectivities for substrate and reagent controlled
asymmetric Diels–Alder reactions in ionic liquids. These
investigations indicate excellent diastereoselective and
enantioselective Diels–Alder reactions. The selectivities
in room temperature ionic liquid rival the reaction in
conventional solvents at −78°C.
Figure
1. Hydrogenbutylimidazolium
tetrafluoroborate
The ionic solvents chosen for initial investigation were
hydrogen butylimidazolium tetrafluoroborate (HBuIm)
(HBuIm) and 1,3-dibutylimidazolium tetrafluoroborate
(DiBuIm).
(1)
* Corresponding author. E-mail: taeboem.oh@csun.edu
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01590-9

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I. Meracz, T. Oh / Tetrahedron Letters 44 (2003) 6465–6468
Table 1. Reactions of oxazolidinones 3 or 6 with cyclopentadiene (Eq. (1)).
Entry
R
Rxn conditions
Diene (equiv.)
Ma
Time
Yieldb (%)
endo:exoc
a
b
c
d
e
f
H
HBuIm
DiBuIm
HBuIm
1% ZnCl2/DiBuIm
1% ZnCl2/HBuIm
1% Zn(OAc)2/CH2Cl2
1% ZnCl2/ether
3.0
7.0
6.4
3.0
3.0
2.4d
2.5d
0.5
1.0
1.0
2.0
1.7
1.3
1.0
3 h
48 h
48 h
40 min
45 min
12 h
65
11
7
68
0
100:0e
87:13
100:0e
92:8
CH3
CH3
CH3
CH3
CH3
CH3
0
2
13
87:13
95:5
g
12 h
a Molarity of 3 or 6.
b Isolated yield except entries f and g, which are percent conversion as determined by NMR.
c Determined by 1H NMR spectra of the crude material.
d Diene added in two equal portions 2 h apart.
e Within the detection limits of a 200 MHz 1H NMR spectrometer.
Table 2. Reactions of chiral oxazolidinones with cyclopentadiene (Eq. (2))
Entry
Substrate
Rxn conditions
T (h)
10:11b
endo:exob,d
Yield (%)
a
b
c
d
e
f
g
h
9a
9a
9a
9b
9c
9d
9d
9d
1% ZnCl2/DiBuIm
1% Zn(OAc)2/CH2Cl2
1% ZnCl2/ether
13
12
12
3.25
12
12
12
12
79:21
–
–
100:0c
100:0c
–
67
Traces
0
55
97
55
62
Traces
1% ZnCl2/DiBuIm
1% ZnCl2/DiBuIm
1% ZnCl2/DiBuIm
0:100b
10:90
5:95
48:52
–
100:0c
90:10
100:0c
80:20
-
a
Et2AlCl/CH2Cl2
1% ZnCl2/ether
a 1.4 equiv. Et2AlCl relative to 9c.
b Determined by 1H NMR.
c Within the detection limits of a 200 MHz 1H NMR spectrometer.
d endo-exo Ratios of the major isomer 10 or 11.
also carried out in more typical solvents: Zn(OAc)2 or
ZnCl2 in CH2Cl2 or Et2O gave low reaction yields even
with additional diene (entries f and g). GC analysis of
the reactions showed a marked increase in the dimeriza-
tion of cyclopentadiene in the ionic liquids. In the case
of 1% ZnCl2 in HBuIm, the dimerization was very
rapid. The ionic solvent increases the rates of both the
Diels–Alder reaction and the dimerization of cyclopen-
tadiene.
Next, the stereoselectivity of the cycloaddition using
chiral oxazolidinones 9a–d (Eq. (2)) was examined.13
Use of 1% ZnCl2 in DiBuIm at room temperature
resulted in 55–97% yields and high endo-exo selectivities
for the cycloadducts of the chiral dienophiles (Table 2).
As previously noted, the use of Lewis acids in CH2Cl2
or Et2O still gave trace amounts or no product, how-
ever, use of 1.4 equiv. of Et2AlCl in CH2Cl2 gave 62%
cycloadduct (entries b, c, g, and h). The reactions that
used 1% ZnCl2 in DiBuIm at room temperature gave
very high diastereoselectivities that arose from the chi-
ral center on the oxazolidinones. The lowest
diastereoselectivity of 79:21 was obtained for 9a (entry
a). For 9b, only one isomer was detected (entry d). For
9c and 9d, 10:90 and 5:95 ratios were detected (entries
e and f). For comparison purposes, the reaction of 9d
was repeated in Et2AlCl/CH2Cl2 at room temperature,
from which a ratio of 48:52 was obtained.
(2)
Figure 2. Copper bisoxazoline based chiral Lewis acid.

I. Meracz, T. Oh / Tetrahedron Letters 44 (2003) 6465–6468
6467
Enantioselective reactions of dienophile 6 with chiral
catalyst 12 were also attempted (Fig. 2, and Eq. (3)).14
The catalytic activity of the reaction in DiBuIm was
compared to its activity in CH2Cl2 at room tempera-
ture, and a much faster reaction was observed in the
ionic liquid. The reaction in DiBuIm gave a 65% yield
compared to a 4% yield for the reaction in CH2Cl2. The
endo-exo ratios were also higher: 93:7 for the ionic
liquid versus 79:21 for CH2Cl2. The enantioselectivity in
DiBuIm gave 96:4, whereas the reaction in CH2Cl2 gave
an enantioselectivity of 76:24.
combined organic layers were dried over Mg2SO4, con-
centrated, and flash column chromatographed (2:1 hex-
anes:EtOAc) to yield 0.1310 g (65%) of 7 and 13.15 The
endo:exo ratios were analyzed by measuring the inte-
1
grals of the vinyl peaks on the H NMR spectrum. The
enantiomeric excess of the endo-isomers were deter-
mined using an HPLC column (Chiralcel OD-H) and a
mobile phase of 95% hexanes, 2% 2-propanol, and 3%
EtOAc at a flow rate of 0.95 mL/min (681 psi), and the
retention time of each enantiomer was: tR (7)=17.74
min, tR (13)=19.43 min.
(3)
In summary, ionic solvents gave unusually high
stereoselectivities for the present substrates in the
Diels–Alder reactions at room temperature, as opposed
to the necessarily low temperatures required of these
reactions to effect good stereoselectivities in the tradi-
tional solvents. Although, the results show that ionic
solvents increases the rate of reaction, the mechanism
which gives the Diels–Alder reactions such high
diastereoselectivities or enantioselectivities at room
temperature is unclear at this time. We have initiated
mechanistic investigations to elucidate the interaction
between the ionic liquid and the substrates that can
account for the high selectivities.
Acknowledgements
This work was supported in part by the College of
Science and Mathematics and Graduate Studies of
California State University Northridge.
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